TheGALE
ENCYCLOPEDIA
ofMEDICINE
SECOND EDITION
JACQUELINE L. LONGE, EDITOR
DEIRDRE S. BLANCHFIELD, ASSOCIATE EDITOR
VOLUME
A-B1

STAFF
Jacqueline L. Longe, Project Editor
Deirdre S. Blanchfield, Associate Editor
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Multimedia Content
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of MEDICINE
SECOND EDITIONSince this page cannot legibly accommodate all copyright notices, the
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ISBN 0-7876-5489-2 (set)
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Printed in the United States of America
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Library of Congress Cataloging-in-Publication Data
Gale encyclopedia of medicine / Jacqueline L. Longe, editor;

Deirdre S. Blanchfield, associate editor — 2nd ed.
p. cm.
Includes bibliographical references and index.
Contents: V ol. 1. A-B — v. 2. C-F — v. 3.G-M — v. 4. N-S — v. 5. T-Z.
ISBN 0-7876-5489-2 (set: hardcover) — ISBN 0-7876-5490-6
(vol. 1) — ISBN 0-7876-5491-4 (vol. 2) — ISBN 0-7876-5492-2(vol. 3) — ISBN 0-7876-5493-0 (vol. 4) — ISBN 0-7876-5494-9(vol. 5)
1. Internal medicine—Encyclopedias. I. Longe, Jacqueline L. 
II. Blanchfield, Deirdre S. III. Gale Research Company.
RC41.G35 2001

Introduction .................................................... ix
Advisory Board .............................................. xi
Contributors ................................................. xiii
Entries
Volume 1: A-B .............................................. 1
Volume 2: C-F .......................................... 625
Volume 3: G-M ....................................... 1375
Volume 4: N-S ........................................ 2307

Volume 5: T-Z ........................................ 3237
Organizations ............................................ 3603
General Index ............................................ 3625
GALE ENCYCLOPEDIA OF MEDICINE 2 VCONTENTS

erence product designed to inform and educate readersabout a wide variety of disorders, conditions, treatments,and diagnostic tests. The Gale Group believes the productto be comprehensive, but not necessarily definitive. It isintended to supplement, not replace, consultation with aphysician or other healthcare practitioner. While the GaleGroup has made substantial efforts to provide informationthat is accurate, comprehensive, and up-to-date, the GaleGroup makes no representations or warranties

GaleGroup makes no representations or warranties of anykind, including without limitation, warranties of mer-

chantability or fitness for a particular purpose, nor does itguarantee the accuracy, comprehensiveness, or timelinessof the information contained in this product. Readersshould be aware that the universe of medical knowledgeis constantly growing and changing, and that differencesof medical opinion exist among authorities. Readers arealso advised to seek professional diagnosis and treatmentfor any medical condition, and to discuss informationobtained from this book with their health care

GALE ENCYCLOPEDIA OF MEDICINE 2 VIIPLEASE READ—IMPORTANT INFORMATION

The Gale Encyclopedia of Medicine 2 (GEM2) is a
one-stop source for medical information on nearly 1,700common medical disorders, conditions, tests, and treat-ments, including high-profile diseases such as AIDS,Alzheimer’s disease, cancer, and heart attack. This ency-clopedia avoids medical jargon and uses language thatlaypersons can understand, while still providing thor-ough coverage of each topic. The Gale Encyclopedia of
Medicine 2 fills a gap between basic consumer health

resources, such as single-volume family medical guides,and highly technical professional materials.
SCOPE
Almost 1,700 full-length articles are included in the
Gale Encyclopedia of Medicine 2 , including disorders/
conditions, tests/procedures, and treatments/therapies.Many common drugs are also covered, with generic drugnames appearing first and brand names following inparentheses, eg. acetaminophen (Tylenol). Throughoutthe Gale Encyclopedia of Medicine 2 , many prominent

individuals are highlighted as sidebar biographies thataccompany the main topical essays. Articles follow astandardized format that provides information at aglance. Rubrics include:
Disorders/Conditions Tests/Treatments
Definition Definition
Description Purpose
Causes and symptoms Precautions
Diagnosis DescriptionTreatment Preparation
Alternative treatment Aftercare
Prognosis Risks
Prevention Normal/Abnormal results
Resources ResourcesKey terms Key terms

In recent years there has been a resurgence of interest
in holistic medicine that emphasizes the connectionbetween mind and body. Aimed at achieving and main-taining good health rather than just eliminating disease,this approach has come to be known as alternative medi-
cine. The Gale Encyclopedia of Medicine 2 includes a

number of essays on alternative therapies, ranging fromtraditional Chinese medicine to homeopathy and frommeditation to aromatherapy. In addition to full essays onalternative therapies, the encyclopedia features specificAlternative treatment sections for diseases and condi-
tions that may be helped by complementary therapies.
INCLUSION CRITERIA
A preliminary list of diseases, disorders, tests and treat-

ments was compiled from a wide variety of sources,including professional medical guides and textbooks aswell as consumer guides and encyclopedias. The generaladvisory board, made up of public librarians, medicallibrarians and consumer health experts, evaluated the top-ics and made suggestions for inclusion. The list was sortedby category and sent to GEM2 medical advisors, certified

physicians with various medical specialities, for review.Final selection of topics to include was made by the med-ical advisors in conjunction with the Gale Group editor.
ABOUT THE CONTRIBUTORS
The essays were compiled by experienced medical
writers, including physicians, pharmacists, nurses, andother health care professionals. GEM2 medical advisors
reviewed the completed essays to insure that they areappropriate, up-to-date, and medically accurate.
HOW TO USE THIS BOOK

The Gale Encyclopedia of Medicine 2 has been
designed with ready reference in mind.
• Straight alphabetical arrangement allows users to
locate information quickly.
• Bold-faced terms function as print hyperlinks that
point the reader to related entries in the encyclopedia.
GALE ENCYCLOPEDIA OF MEDICINE 2 IXINTRODUCTION

•Cross-references placed throughout the encyclopedia
direct readers to where information on subjects with-out entries can be found. Synonyms are also cross-ref-erenced.
• A list of key terms are provided where appropriate to
define unfamiliar terms or concepts.
• Valuable contact information for organizations and
support groups is included with each entry. Theappendix contains an extensive list of organizationsarranged in alphabetical order.•Resources section directs users to additional sources

of medical information on a topic.
• A comprehensive general index allows users to easily
target detailed aspects of any topic, including Latinnames.
GRAPHICS
The Gale Encyclopedia of Medicine 2 is enhanced
with over 675 color images, including photos, charts,tables, and customized line drawings.
GALE ENCYCLOPEDIA OF MEDICINE 2 XIntroduction

MEDICAL ADVISORS
A. Richard Adrouny, M.D.,
F.A.C.P.
Clinical Assistant Professor of
Medicine
Division of OncologyStanford UniversityDirector of Medical OncologyCommunity Hospital of Los Gatos-
Saratoga
Los Gatos, CA
Laurie Barclay, M.D.
Neurological Consulting ServicesTampa, FL
Kenneth J. Berniker, M.D.
Attending PhysicianEmergency DepartmentKaiser Permanente Medical CenterVallejo, CA
Rosalyn Carson-DeWitt, M.D.
Durham, NC
Robin Dipasquale, N.D.
Clinical FacultyBastyr UniversitySeattle, WA

Faye Fishman, D.O.
Randolph, NJ
J. Gary Grant, M.D.
Pacific Grove, CA
Laith F. Gulli, M.D.
M.Sc., M.Sc.(MedSci), MSA,
Msc.Psych., MRSNZ
FRSH, FRIPHH, FAIC, FZSDAPA, DABFC, DABCIConsultant Psychotherapist in
Private Practice
Lathrup Village, MI
L. Anne Hirschel, D.D.S.
Southfield, MI
Larry I. Lutwick M.D., F.A.C.P.
Director, Infectious DiseasesV A Medical CenterBrooklyn, NY
Ira Michelson, M.D., M.B.A.,
F.A.C.O.G.

Physician and Clinical InstructorUniversity of MichiganAnn Arbor, MI
Susan Mockus, M.D.
Scientific ConsultantSeattle, WA
Ralph M. Myerson, M.D.,
F.A.C.P.
Clinical Professor of MedicineMedical College of Pennsylvania–
Hahnemann University
Philadelphia, PA
Ronald Pies, M.D.
Clinical Professor of PsychiatryTufts UniversitySchool of MedicineBoston, MA
Lecturer on Psychiatry
Harvard Medical SchoolCambridge, MA
Lee A. Shratter, M.D.

Staff RadiologistThe Permanente Medical Group
Richmond, CA
Amy B. Tuteur, M.D.
Sharon, MA
LIBRARIAN ADVISORS
Maureen O. Carleton, MLISMedical Reference SpecialistKing County Library SystemBellevue, WA
Elizabeth Clewis Crim, MLS
Collection SpecialistPrince William Public Library, V A
Valerie J. Lawrence, MLS
Assistant LibrarianWestern States Chiropractic
College
Portland, OR
Barbara J. O’Hara, MLS
Adult Services LibrarianFree Library of Philadelphia, PA
Alan M. Rees, MLS

Professor EmeritusCase Western Reserve UniversityCleveland, OH
GALE ENCYCLOPEDIA OF MEDICINE 2 XIADVISORY BOARD
A number of experts in the library and medical communities provided invaluable assistance in the formulation of this ency-
clopedia. Our advisory board performed a myriad of duties, from defining the scope of coverage to reviewing individualentries for accuracy and accessibility. The editor would like to express her appreciation to them.

Margaret Alic, Ph.D.
Science WriterEastsound, WA
Janet Byron Anderson
Linguist/Language ConsultantRocky River, OH
Lisa Andres, M.S., C.G.C.
Certified Genetic Counselor and
Medical Writer
San Jose, CA
Greg Annussek
Medical Writer/EditorNew York, NY
Bill Asenjo, M.S., C.R.C.
Science WriterIowa City, IA
Sharon A. Aufox, M.S., C.G.C.
Genetic CounselorRockford Memorial HospitalRockford, IL
Sandra Bain Cushman
Massage Therapist, Alexander
Technique Practitioner
Charlottesville, V A
Howard Baker

Medical WriterNorth York, Ontario
Neurological Consulting Services
Tampa, FL
Jeanine Barone
Nutritionist, Exercise PhysiologistNew York, NY
Julia R. Barrett
Science WriterMadison, WIDonald G. Barstow, R.N.
Clincal Nurse SpecialistOklahoma City, OK
Carin Lea Beltz, M.S.
Genetic Counselor and Program
Director
The Center for Genetic CounselingIndianapolis, IN
Linda K. Bennington, C.N.S.
Science WriterVirginia Beach, V A
Issac R. Berniker

Medical WriterVallejo, CA
Kathleen Berrisford, M.S.V .
Science Writer
Bethanne Black
Medical WriterAtlanta, GA
Jennifer Bowjanowski, M.S.,
C.G.C.
Genetic CounselorChildren’s Hospital OaklandOakland, CA
Michelle Q. Bosworth, M.S., C.G.C.
Genetic CounselorEugene, OR
Barbara Boughton
Health and Medical WriterEl Cerrito, CA
Cheryl Branche, M.D.
Retired General PractitionerJackson, MS
Michelle Lee Brandt
Medical WriterSan Francisco, CAMaury M. Breecher, Ph.D.

Health Communicator/JournalistNorthport, AL
Ruthan Brodsky
Medical WriterBloomfield Hills, MI
Tom Brody, Ph.D.
Science WriterBerkeley, CA
Leonard C. Bruno, Ph.D.
Medical WriterChevy Chase, MD
Diane Calbrese
Medical Sciences and Technology
Writer
Silver Spring, Maryland
Richard H. Camer
EditorInternational Medical News GroupSilver Spring, MD
Medical WriterDurham, NC
Lata Cherath, Ph.D.
Science Writing InternCancer Research InstituteNew York, NY
Linda Chrisman

Massage Therapist and EducatorOakland, CA
Lisa Christenson, Ph.D.
Science WriterHamden, CT
Geoffrey N. Clark, D.V .M.
EditorCanine Sports Medicine UpdateNewmarket, NH
GALE ENCYCLOPEDIA OF MEDICINE 2 XIIICONTRIBUTORS

Rhonda Cloos, R.N.
Medical WriterAustin, TX
Gloria Cooksey, C.N.E
Medical WriterSacramento, CA
Amy Cooper, M.A., M.S.I.
Medical WriterVermillion, SD
David A. Cramer, M.D.
Medical WriterChicago, IL
Esther Csapo Rastega, R.N., B.S.N.
Medical WriterHolbrook, MA
Arnold Cua, M.D.
PhysicianBrooklyn, NY
Tish Davidson, A.M.
Medical WriterFremont, California
Dominic De Bellis, Ph.D.
Medical Writer/EditorMahopac, NY
Lori De Milto
Medical WriterSicklerville, NJ
Robert S. Dinsmoor

Medical WriterSouth Hamilton, MA
Stephanie Dionne, B.S.
Medical WriterAnn Arbor, MI
Martin W. Dodge, Ph.D.
Technical Writer/EditorCentinela Hospital and Medical
Center
Inglewood, CA
David Doermann
Medical WriterSalt Lake City, UT
Stefanie B. N. Dugan, M.S.
Genetic CounselorMilwaukee, WI
Doug Dupler, M.A.
Science WriterBoulder, COJulie A. Gelderloos
Biomedical WriterPlaya del Rey, CA
Gary Gilles, M.A.
Medical WriterWauconda, IL
Harry W. Golden

Medical WriterShoreline Medical WritersOld Lyme, CT
Debra Gordon
Medical WriterNazareth, PA
Megan Gourley
WriterGermantown, MD
Jill Granger, M.S.
Senior Research AssociateUniversity of MichiganAnn Arbor, MI
Alison Grant
Medical WriterAverill Park, NY
Elliot Greene, M.A.
former president, American
Massage Therapy Association
Massage TherapistSilver Spring, MD
Peter Gregutt
WriterAsheville, NC
M.Sc., M.Sc.(MedSci), M.S.A.,

Msc.Psych, MRSNZ
Kapil Gupta, M.D.
Medical WriterWinston-Salem, NC
Maureen Haggerty
Medical WriterAmbler, PA
Clare Hanrahan
Medical WriterAsheville, NCThomas Scott Eagan
Student ResearcherUniversity of ArizonaTucson, AZ
Altha Roberts Edgren
Medical WriterMedical InkSt. Paul, MN
Karen Ericson, R.N.
Medical WriterEstes Park, CO
L. Fleming Fallon Jr., M.D.,

Dr.PH
Associate Professor of Public
Health
Bowling Green State UniversityBowling Green, OH
PhysicianRandolph, NJ
Janis Flores
Medical WriterLexikon CommunicationsSebastopol, CA
Risa Flynn
Medical WriterCulver City, CA
Paula Ford-Martin
Medical WriterChaplin, MN
Janie F. Franz
WriterGrand Forks, ND
Sallie Freeman, Ph.D., B.S.N.
Rebecca J. Frey, Ph.D.
Research and Administrative
Associate
East Rock InstituteNew Haven, CT

Associate
Cynthia L. Frozena, R.N.
Nurse, Medical WriterManitowoc, WI
Ron Gasbarro, Pharm.D.
Medical WriterNew Milford, PA
GALE ENCYCLOPEDIA OF MEDICINE 2 XIVContributors

Ann M. Haren
Science WriterMadison, CT
Judy C. Hawkins, M.S.
Genetic CounselorThe University of Texas Medical
Branch
Galveston, TX
Caroline Helwick
Medical WriterNew Orleans, LA
David Helwig
Medical WriterLondon, Ontario
Lisette Hilton
Medical WriterBoca Raton, FL
Katherine S. Hunt, M.S.
Genetic CounselorUniversity of New Mexico Health
Sciences Center
Albuquerque, NM
Kevin Hwang, M.D.
Medical WriterMorristown, NJ
Holly Ann Ishmael, M.S., C.G.C.

Genetic CounselorThe Children’s Mercy HospitalKansas City, MO
Dawn A. Jacob, M.S.
Genetic CounselorObstetrix Medical Group of TexasFort Worth, TX
Sally J. Jacobs, Ed.D.
Medical WriterLos Angeles, CA
Michelle L. Johnson, M.S., J.D.
Patent Attorney and Medical WriterPortland, OR
Paul A. Johnson, Ed.M.
Medical WriterSan Diego, CA
Cindy L. A. Jones, Ph.D.
Biomedical WriterSagescript CommunicationsLakewood, CO
David Kaminstein, M.D.
Medical WriterJohn T. Lohr, Ph.D.

Assistant Director, Biotechnology
Center
Utah State UniversityLogan, UT
Larry Lutwick, M.D., F.A.C.P.
Suzanne M. Lutwick
Medical WriterBrooklyn, NY
Nicole Mallory, M.S.
Medical StudentWayne State UniversityDetroit, MI
Warren Maltzman, Ph.D.
Consultant, Molecular PathologyDemarest, NJ
Adrienne Massel, R.N.
Medical WriterBeloit, WI
Ruth E. Mawyer, R.N.
Medical WriterCharlottesville, V A

Richard A. McCartney M.D.
Fellow, American College of
Surgeons
Diplomat American Board of
Surgery
Richland, WA
Bonny McClain, Ph.D.
Medical WriterGreensboro, NC
Sally C. McFarlane-Parrott
Mercedes McLaughlin
Medical WriterPhoenixville, CA
Alison McTavish, M.Sc.
Medical Writer and EditorMontreal, Quebec
Liz Meszaros
Medical WriterLakewood, OHWest Chester, PA
Beth A. Kapes
Medical WriterBay Village, OH
Christine Kuehn Kelly

Medical WriterHavertown, PA
Bob Kirsch
Medical WriterOssining, NY
Joseph Knight, P.A.
Medical WriterWinton, CA
Melissa Knopper
Karen Krajewski, M.S., C.G.C.
Genetic CounselorAssistant Professor of NeurologyWayne State UniversityDetroit, MI
Jeanne Krob, M.D., F.A.C.S.
Physician, writerPittsburgh, PA
Jennifer Lamb
Medical WriterSpokane, WA
Richard H. Lampert
Senior Medical EditorW.B. Saunders Co.Philadelphia, PA
Jeffrey P. Larson, R.P.T.

Physical TherapistSabin, MN
Jill Lasker
Medical WriterMidlothian, V A
Kristy Layman
Music TherapistEast Lansing, MI
Victor Leipzig, Ph.D.
Biological ConsultantHuntington Beach, CA
Lorraine Lica, Ph.D.
GALE ENCYCLOPEDIA OF MEDICINE 2 XVContributors

Betty Mishkin
Medical WriterSkokie, IL
Barbara J. Mitchell
Medical WriterHallstead, PA
Mark A. Mitchell, M.D.
Medical WriterSeattle, WA
Susan J. Montgomery
Medical WriterMilwaukee, WI
Louann W. Murray, PhD
Medical WriterHuntington Beach, CA
Bilal Nasser, M.Sc.
Senior Medical StudentUniversidad IberoamericanaSanto Domingo, Domincan 
Republic
Laura Ninger
Medical WriterWeehawken, NJ
Nancy J. Nordenson
Medical WriterMinneapolis, MN
Teresa Norris, R.N.
Medical WriterUte Park, NM
Lisa Papp, R.N.

Medical WriterCherry Hill, NJ
Patience Paradox
Medical WriterBainbridge Island, WA
Barbara J. Pettersen
Genetic CounselorGenetic Counseling of Central
Oregon
Bend, OR
Genevieve Pham-Kanter, M.S.
Collette Placek
Medical WriterWheaton, ILBelinda Rowland, Ph.D.
Medical WriterV oorheesville, NY
Andrea Ruskin, M.D.
Whittingham Cancer CenterNorwalk, CT
Laura Ruth, Ph.D.
Medical, Science, & Technology
Writer
Los Angeles, CA

Writer
Karen Sandrick
Kausalya Santhanam, Ph.D.
Technical WriterBranford, CT
Jason S. Schliesser, D.C.
ChiropractorHolland Chiropractic, Inc.Holland, OH
Joan Schonbeck
Medical WriterNursingMassachusetts Department of
Mental Health
Marlborough, MA
Laurie Heron Seaver, M.D.
Clinical GeneticistGreenwood Genetic CenterGreenwood, SC
Catherine Seeley
Kristen Mahoney Shannon, M.S.,
C.G.C.

C.G.C.
Genetic CounselorCenter for Cancer Risk AnalysisMassachusetts General HospitalBoston, MA
Kim A. Sharp, M.Ln.
WriterRichmond, TX
Judith Sims, M.S.
Medical WriterLogan, UT
Joyce S. Siok, R.N.
Medical WriterSouth Windsor, CTJ. Ricker Polsdorfer, M.D.
Medical WriterPhoenix, AZ
Scott Polzin, M.S., C.G.C.
Medical WriterBuffalo Grove, IL
Elizabeth J. Pulcini, M.S.
Medical WriterPhoenix, Arizona
Nada Quercia, M.S., C.C.G.C.

Genetic CounselorDivision of Clinical and Metabolic
Genetics
The Hospital for Sick ChildrenToronto, ON, Canada
Ann Quigley
Medical WriterNew York, NY
Robert Ramirez, B.S.
Medical StudentUniversity of Medicine & Dentistry
of New Jersey
Stratford, NJ
Kulbir Rangi, D.O.
Medical Doctor and WriterNew York, NY
Esther Csapo Rastegari, Ed.M.,
R.N./B.S.N.
Registered Nurse, Medical WriterHolbrook, MA
Toni Rizzo
Martha Robbins

Medical WriterEvanston, IL
Richard Robinson
Medical WriterTucson, AZ
Nancy Ross-Flanigan
Science WriterBelleville, MI
Anna Rovid Spickler, D.V .M.,
Ph.D.
Medical WriterMoorehead, KY
GALE ENCYCLOPEDIA OF MEDICINE 2 XVIContributors

Jennifer Sisk
Patricia Skinner
Medical WriterAmman, Jordan
Genevieve Slomski, Ph.D.
Medical WriterNew Britain, CT
Stephanie Slon
Medical WriterPortland, OR
Linda Wasmer Smith
Medical WriterAlbuquerque, NM
Java O. Solis, M.S.
Medical WriterDecatur, GA
Elaine Souder, PhD
Medical WriterLittle Rock, AR
Jane E. Spehar
Medical WriterCanton, OH
Lorraine Steefel, R.N.
Medical WriterMorganville, NJ
Kurt Sternlof
Science WriterNew Rochelle, NY
Roger E. Stevenson, M.D.

DirectorGreenwood Genetic CenterGreenwood, SC
Dorothy Stonely
Medical WriterLos Gatos, CAAmy Vance, M.S., C.G.C.
Genetic CounselorGeneSage, Inc.San Francisco, CA
Michael Sherwin Walston
Ronald Watson, Ph.D.
Science WriterTucson, AZ
Ellen S. Weber, M.S.N.
Medical WriterFort Wayne, IN
Ken R. Wells
Freelance WriterLaguna Hills, CA
Jennifer F. Wilson, M.S.
Science WriterHaddonfield, NJ
Kathleen D. Wright, R.N.

Medical WriterDelmar, DE
Jennifer Wurges
Medical WriterRochester Hills, MI
Mary Zoll, Ph.D.
Science WriterNewton Center, MA
Jon Zonderman
Medical WriterOrange, CA
Michael V . Zuck, Ph.D.
Medical WriterBoulder, COLiz Swain
Deanna M. Swartout-Corbeil,
R.N.
Medical WriterThompsons Station, TN
Keith Tatarelli, J.D.
Mary Jane Tenerelli, M.S.
Medical WriterEast Northport, NY
Catherine L. Tesla, M.S., C.G.C.

Senior Associate, FacultyDept. of Pediatrics, Division of
Medical Genetics
Emory University School of
Medicine
Atlanta, GA
Bethany Thivierge
Biotechnical Writer/EditorTechnicality ResourcesRockland, ME
Mai Tran, Pharm.D.
Medical WriterTroy, MI
Carol Turkington
Medical WriterLancaster, PA
Judith Turner, B.S.
Medical WriterSandy, UT
Medical AdvisorSharon, MA
Samuel Uretsky, Pharm.D.
Medical WriterWantagh, NY

GALE ENCYCLOPEDIA OF MEDICINE 2 XVIIContributors

Abdominal aorta ultrasound seeAbdominal
ultrasound
Abdominal aortic aneurysm seeAortic
aneurysm
Abdominal hernia seeHernia
Abdominal thrust seeHeimlich maneuver
Abdominal ultrasound
Definition
Ultrasound technology allows doctors to “see”

inside a patient without resorting to surgery. A transmit-ter sends high frequency sound waves into the body,where they bounce off the different tissues and organs toproduce a distinctive pattern of echoes. A receiver“hears” the returning echo pattern and forwards it to acomputer, which translates the data into an image on atelevision screen. Because ultrasound can distinguishsubtle variations between soft, fluid-filled tissues, it isparticularly useful in providing diagnostic images of

useful in providing diagnostic images of theabdomen. Ultrasound can also be used in treatment.

were first recognized in the 1940s as an outgrowth of thesonar technology developed to detect submarines duringWorld War II. The first useful medical images were pro-duced in the early 1950s, and, by 1965, ultrasound quali-ty had improved to the point that it came into generalmedical use. Improvements in the technology, applica-tion, and interpretation of ultrasound continue. Its lowcost, versatility, safety and speed have brought it into thetop drawer of medical imaging techniques.While pelvic

drawer of medical imaging techniques.While pelvic ultrasound is widely known and com-

monly used for fetal monitoring during pregnancy ,
ultrasound is also routinely used for general abdominalimaging. It has great advantage over x-ray imaging tech-nologies in that it does not damage tissues with ionizingradiation. Ultrasound is also generally far better thanplain x rays at distinguishing the subtle variations of softtissue structures, and can be used in any of severalmodes, depending on the need at hand.
As an imaging tool, abdominal ultrasound generally

is warranted for patients afflicted with: chronic or acuteabdominal pain ; abdominal trauma; an obvious or sus-
pected abdominal mass; symptoms of liver disease, pan-creatic disease, gallstones , spleen disease, kidney dis-
ease and urinary blockage; or symptoms of an abdominalaortic aneurysm . Specifically:
• Abdominal pain. Whether acute or chronic, pain can

signal a serious problem—from organ malfunction orinjury to the presence of malignant growths. Ultrasoundscanning can help doctors quickly sort through poten-tial causes when presented with general or ambiguoussymptoms. All of the major abdominal organs can bestudied for signs of disease that appear as changes insize, shape and internal structure.
• Abdominal trauma. After a serious accident, such as a

car crash or a fall, internal bleeding from injuredabdominal organs is often the most serious threat tosurvival. Neither the injuries nor the bleeding areimmediately apparent. Ultrasound is very useful as aninitial scan when abdominal trauma is suspected, and itcan be used to pinpoint the location, cause, and severityof hemorrhaging. In the case of puncture wounds ,f r o m

a bullet for example, ultrasound can locate the foreignobject and provide a preliminary survey of the damage.The easy portability and versatility of ultrasound tech-nology has brought it into common emergency roomuse, and even into limited ambulance service.
• Abdominal mass. Abnormal growths—tumors, cysts,
abscesses, scar tissue and accessory organs—can beA
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located and tentatively identified with ultrasound. In
particular, potentially malignant solid tumors can bedistinguished from benign fluid-filled cysts andabscesses. Masses and malformations in any organ orpart of the abdomen can be found.
• Liver disease. The types and underlying causes of liver
disease are numerous, though jaundice tends to be a

general symptom. Ultrasound can differentiate betweenmany of the types and causes of liver malfunction, andis particularly good at identifying obstruction of thebile ducts and cirrhosis , which is characterized by
abnormal fibrous growths and reduced blood flow.
• Pancreatic disease. Inflammation and malformation of
the pancreas are readily identified by ultrasound, as arepancreatic stones (calculi), which can disrupt properfunctioning.
• Gallstones. Gallstones cause more hospital admissions

than any other digestive malady. These calculi cancause painful inflammation of the gallbladder and alsoobstruct the bile ducts that carry digestive enzymesfrom the gallbladder and liver to the intestines. Gall-stones are readily identifiable with ultrasound.
• Spleen disease. The spleen is particularly prone to
injury during abdominal trauma. It may also becomepainfully inflamed when beset with infection orcancer . These conditions also lend themselves well to

ultrasonic inspection and diagnosis.
• Kidney disease. The kidneys are also prone to traumatic
injury and are the organs most likely to form calculi,which can block the flow of urine and cause blood poi-
soning (uremia). A variety of diseases causing distinct
changes in kidney morphology can also lead to com-plete kidney failure. Ultrasound imaging has provenextremely useful in diagnosing kidney disorders.
• Abdominal aortic aneurysm. This is a bulging weak

spot in the abdominal aorta, which supplies blooddirectly from the heart to the entire lower body. Theseaneurysms are relatively common and increase inprevalence with age. A burst aortic aneurysm is immi-nently life-threatening. However, they can be readilyidentified and monitored with ultrasound before acutecomplications result.
Ultrasound technology can also be used for treat-

ment purposes, most frequently as a visual aid duringsurgical procedures—such as guiding needle placementto drain fluid from a cyst, or to extract tumor cells forbiopsy. Increasingly, direct therapeutic applications forultrasound are being developed.
The direct therapeutic value of ultrasonic waves lies

in their mechanical nature. They are shock waves, just likeaudible sound, and vibrate the materials through whichthey pass. These vibrations are mild, virtually unnotice-
able at the frequencies and intensities used for imaging.Properly focused however, high-intensity ultrasound canbe used to heat and physically agitate targeted tissues.
High-intensity ultrasound is used routinely to treat

soft tissue injuries, such as strains, tears and associatedscarring. The heating and agitation are believed to pro-mote rapid healing through increased circulation. Strong-ly focused, high-intensity, high-frequency ultrasound canalso be used to physically destroy certain types oftumors, as well as gallstones and other types of calculi.Developing new treatment applications for ultrasound isan active area of medical research.
Precautions
Properly performed, ultrasound imaging is virtually

without risk or side effects. Some patients report feelinga slight tingling and/or warmth while being scanned, butmost feel nothing at all. Ultrasound waves of appropriatefrequency and intensity are not known to cause or aggra-vate any medical condition, though any woman whothinks she might be pregnant should raise the issue withher doctor before undergoing an abdominal ultrasound.
The value of ultrasound imaging as a medical tool,

however, depends greatly on the quality of the equipmentused and the skill of the medical personnel operating it.Improperly performed and/or interpreted, ultrasound canbe worse than useless if it indicates that a problem existswhere there is none, or fails to detect a significant condi-tion. Basic ultrasound equipment is relatively inexpen-sive to obtain, and any doctor with the equipment canperform the procedure whether qualified or not. Patientsshould not hesitate to verify the credentials of

not hesitate to verify the credentials of techni-cians and doctors performing ultrasounds, as well as thequality of the equipment used and the benefits of the pro-posed procedure.

In cases where ultrasound is used as a treatment tool,
patients should educate themselves about the proposedprocedure with the help of their doctors—as is appropri-ate before any surgical procedure. Also, any abdominalultrasound procedure, diagnostic or therapeutic, may behampered by a patient’s body type or other factors, suchas the presence of excessive bowel gas (which is opaqueto ultrasound). In particular, very obese people are oftennot good candidates for abdominal ultrasound.
Description

Ultrasound includes all sound waves above the fre-
quency of human hearing—about 20 thousand hertz, orcycles per second. Medical ultrasound generally uses fre-quencies between one and 10 million hertz (1-10 MHz).
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KEY TERMS
Accessory organ —A lump of tissue adjacent to an
organ that is similar to it, but which serves noimportant purpose, if functional at all. While notnecessarily harmful, such organs can cause prob-lems if they grow too large or become cancerous. Inany case, their presence points to an underlyingabnormality in the parent organ.
Benign —In medical usage, benign is the opposite of
malignant. It describes an abnormal growth that isstable, treatable and generally not life-threatening.

Biopsy —The surgical removal and analysis of a tis-
sue sample for diagnostic purposes. Usually, theterm refers to the collection and analysis of tissuefrom a suspected tumor to establish malignancy.
Calculus —Any type of hard concretion (stone) in

the body, but usually found in the gallbladder, pan-creas and kidneys. They are formed by the accumu-lation of excess mineral salts and other organicmaterial such as blood or mucous. Calculi (pl.) cancause problems by lodging in and obstructing theproper flow of fluids, such as bile to the intestines orurine to the bladder.
Cirrhosis —A chronic liver disease characterized by

the invasion of connective tissue and the degenera-tion of proper functioning—jaundice is often anaccompanying symptom. Causes of cirrhosis includealcoholism, metabolic diseases, syphilis and conges-tive heart disease.
Common bile duct —The branching passage
through which bile—a necessary digestiveenzyme—travels from the liver and gallbladder intothe small intestine. Digestive enzymes from thepancreas also enter the intestines through the com-mon bile duct.

Computed tomography scan (CT scan) —A special-
ized type of x-ray imaging that uses highly focusedand relatively low energy radiation to producedetailed two-dimensional images of soft tissuestructures, particularly the brain. CT scans are thechief competitor to ultrasound and can yield higherquality images not disrupted by bone or gas. Theyare, however, more cumbersome, time consumingand expensive to perform, and they use ionizing
electromagnetic radiation.

Doppler —The Doppler effect refers to the apparent
change in frequency of sound wave echoes returningto a stationary source from a moving target. If theobject is moving toward the source, the frequencyincreases; if the object is moving away, the frequen-cy decreases. The size of this frequency shift can beused to compute the object’s speed—be it a car onthe road or blood in an artery. The Doppler effectholds true for all types of radiation, not just sound.

Frequency —Sound, whether traveling through air
or the human body, produces vibrations—mole-cules bouncing into each other—as the shock wavetravels along. The frequency of a sound is the num-ber of vibrations per second. Within the audiblerange, frequency means pitch—the higher the fre-quency, the higher a sound’s pitch.
Ionizing radiation —Radiation that can damage liv-

ing tissue by disrupting and destroying individualcells at the molecular level. All types of nuclearradiation—x rays, gamma rays and beta rays—arepotentially ionizing. Sound waves physically vibratethe material through which they pass, but do notionize it.
Jaundice —A condition that results in a yellow tint

to the skin, eyes and body fluids. Bile retention inthe liver, gallbladder and pancreas is the immediatecause, but the underlying cause could be as simpleas obstruction of the common bile duct by a gall-stone or as serious as pancreatic cancer. Ultrasoundcan distinguish between these conditions.
Malignant —The term literally means growing worse
and resisting treatment. It is used as a synonym forcancerous and connotes a harmful condition thatgenerally is life-threatening.

Morphology —Literally, the study of form. In medi-
cine, morphology refers to the size, shape andstructure rather than the function of a given organ.As a diagnostic imaging technique, ultrasound facil-itates the recognition of abnormal morphologies assymptoms of underlying conditions.
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Higher frequency ultrasound waves produce more
detailed images, but are also more readily absorbed andso cannot penetrate as deeply into the body. Abdominalultrasound imaging is generally performed at frequenciesbetween 2-5 MHz.
An ultrasound machine consists of two parts: the

transducer and the analyzer. The transducer both producesthe sound waves that penetrate the body and receives thereflected echoes. Transducers are built around piezoelec-tric ceramic chips. (Piezoelectric refers to electricity thatis produced when you put pressure on certain crystalssuch as quartz). These ceramic chips react to electric puls-es by producing sound waves ( they are transmittingwaves) and react to sound waves by producing electricpulses (receiving). Bursts of high frequency

(receiving). Bursts of high frequency electric puls-es supplied to the transducer causes it to produce thescanning sound waves. The transducer then receives thereturning echoes, translates them back into electric pulsesand sends them to the analyzer—a computer that orga-nizes the data into an image on a television screen.

tissues at nearly the same speed—about 3,400 miles perhour—the microseconds it takes for each echo to bereceived can be plotted on the screen as a distance into thebody. The relative strength of each echo, a function of thespecific tissue or organ boundary that produced it, can beplotted as a point of varying brightness. In this way, theechoes are translated into a picture. Tissues surroundedby bone or filled with gas (the stomach, intestines andbowel) cannot be imaged using ultrasound, because

cannot be imaged using ultrasound, because thewaves are blocked or become randomly scattered.

Four different modes of ultrasound are used in med-
ical imaging:
• A-mode. This is the simplest type of ultrasound in
which a single transducer scans a line through the bodywith the echoes plotted on screen as a function ofdepth. This method is used to measure distances withinthe body and the size of internal organs. Therapeuticultrasound aimed at a specific tumor or calculus is alsoA-mode, to allow for pinpoint accurate focus of thedestructive wave energy.

• B-mode. In B-mode ultrasound, a linear array of trans-
ducers simultaneously scans a plane through the bodythat can be viewed as a two-dimensional image onscreen. Ultrasound probes containing more than 100transducers in sequence form the basis for these mostcommonly used scanners, which cost about $50,000.
• M-Mode. The M stands for motion. A rapid sequence

of B-mode scans whose images follow each other insequence on screen enables doctors to see and mea-sure range of motion, as the organ boundaries thatproduce reflections move relative to the probe. M-mode ultrasound has been put to particular use in
studying heart motion.
• Doppler mode. Doppler ultrasonography includes the

capability of accurately measuring velocities of movingmaterial, such as blood in arteries and veins. The prin-ciple is the same as that used in radar guns that measurethe speed of a car on the highway. Doppler capability ismost often combined with B-mode scanning to produceimages of blood vessels from which blood flow can bedirectly measured. This technique is used extensively toinvestigate valve defects, arteriosclerosis and hyper-
tension , particularly in the heart, but also in the abdom-

inal aorta and the portal vein of the liver. Thesemachines cost about $250,000.
The actual procedure for a patient undergoing an
abdominal ultrasound is relatively simple, regardless ofthe type of scan or its purpose. Fasting for at least eight

hours prior to the procedure ensures that the stomach isempty and as small as possible, and that the intestinesand bowels are relatively inactive. Fasting also allows thegall bladder to be seen, as it contracts after eating andmay not be seen if the stomach is full. In some cases, afull bladder helps to push intestinal folds out of the wayso that the gas they contain does not disrupt the image.The patient’s abdomen is then greased with a special gelthat allows the ultrasound probe to glide

gelthat allows the ultrasound probe to glide easily across theskin while transmitting and receiving ultrasonic pulses.

This procedure is conducted by a doctor with the
assistance of a technologist skilled in operating theequipment. The probe is moved around the abdomen toobtain different views of the target areas. The patient willlikely be asked to change positions from side to side andto hold their breath as necessary to obtain the desiredviews. Discomfort during the procedure is minimal.
The many types and uses of ultrasound technology

makes it difficult to generalize about the time and costsinvolved. Relatively simple imaging—scanning a suspi-cious abdominal mass or a suspected abdominal aorticaneurysm—will take about half an hour to perform andwill cost a few hundred dollars or more, depending onthe quality of the equipment, the operator and other fac-tors. More involved techniques such as multiple M-modeand Doppler-enhanced scans, or cases where the targetsnot well defined in advance, generally take more timeand are more

Regardless of the type of scan used and the potential
difficulties encountered, ultrasound remains faster andless expensive than computed tomography scans (CT),
its primary rival in abdominal imaging. Furthermore, asabdominal ultrasounds are generally undertaken as“medically necessary” procedures designed to detect thepresence of suspected abnormalities, they are covered
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under most types of major medical insurance. As always,
though, the patient would be wise to confirm that theircoverage extends to the specific procedure proposed. Fornonemergency situations, most underwriters stipulateprior approval as a condition of coverage.
Specific conditions for which ultrasound may be
selected as a treatment option—certain types of tumors,lesions, kidney stones and other calculi, muscle and lig-

ament injuries, etc.—are described in detail under theappropriate entries in this encyclopedia.
Preparation
A patient undergoing abdominal ultrasound will be
advised by their physician about what to expect and howto prepare. As mentioned above, preparations generallyinclude fasting and arriving for the procedure with a fullbladder, if necessary. This preparation is particularly use-ful if the gallbladder, ovaries or veins are to be examined.
Aftercare

Aftercare
In general, no aftercare related to the abdominal
ultrasound procedure itself is required.
Risks
Abdominal ultrasound carries with it no recognized
risks or side effects, if properly performed using appropri-ate frequency and intensity ranges. Sensitive tissues, par-ticularly those of the reproductive organs, could possiblysustain damage if violently vibrated by overly intenseultrasound waves. In general though, such damage wouldonly result from improper use of the equipment.

Any woman who thinks she might be pregnant
should raise this issue with her doctor before undergoingan abdominal ultrasound, as a fetus in the early stages ofdevelopment could be injured by ultrasound meant toprobe deeply recessed abdominal organs.
Normal results
As a diagnostic imaging technique, a normal abdom-
inal ultrasound is one that indicates the absence of thesuspected condition that prompted the scan. For example,symptoms such as a persistent cough , labored breathing,

and upper abdominal pain suggest the possibility of,among other things, an abdominal aortic aneurysm. Anultrasound scan that indicates the absence of an aneurysmwould rule out this life-threatening condition and point toother, less serious causes.
Abnormal results
Because abdominal ultrasound imaging is generally
undertaken to confirm a suspected condition, the resultsof a scan often will prove abnormal—that is they will

confirm the diagnosis, be it kidney stones, cirrhosis ofthe liver or an aortic aneurysm. At that point, appropriatemedical treatment as prescribed by a patient’s doctor is inorder. See the relevant disease and disorder entries in thisencyclopedia for more information.
Resources
BOOKS
Hall, Rebecca. The Ultrasonic Handbook: Clinical, Etiologic
and Pathologic Implications of Sonographic Findings.Philadelphia: Lippincott, 1993.
Kevles, Bettyann Holtzmann. Naked to the Bone: Medical

Imaging in the Twentieth Century. New Brunswick, NJ:
Rutgers University Press, 1997.
Kremkau, Frederick W. Diagnostic Ultrasound: Principles and
Instruments. Philadelphia: W. B. Saunders Co., 1993.
Shtasel, Philip. Medical Tests and Diagnostic Procedures: A
Patient’s Guide to Just What the Doctor Ordered. New
York: Harper & Row, 1991.
Tempkin, Betty Bates. Ultrasound Scanning: Principles and
Protocols. Philadelphia: W. B. Saunders Co., 1993.

The Patient’s Guide to Medical Tests. Ed. Barry L. Zaret, et al.
Boston: Houghton Mifflin, 1997.
PERIODICALS
“Ultrasound Detects Stomach Problems.” USA Today Maga-
zine (October 1992): 5.
Freundlich, Naomi. “Ultrasound: What’s Wrong with this Pic-
ture?” Business Week (15 September 1997): 84-5.
McDonagh, D. Brian. “Ultrasound: Unsung Medical Hero.”
USA Today Magazine (September 1996): 66-7.
Murray, Maxine. “Basics of Ultrasonography.” Student British
Medical Journal (August 1996): 269-72.

Tait, N., and J. M. Little. “The Treatment of Gallstones.”
British Medical Journal (8 July 1995): 99-105.
ORGANIZATIONS
American College of Gastroenterology. 4900 B South 31st St.,
Arlington, V A 22206-1656. (703) 820-7400. <http://www.acg.gi.org>.
American Institute of Ultrasound in Medicine. 14750 Sweitzer
Lane, Suite 100, Laurel, MD 20707-5906. (800) 638-5352. <http://www.aium.org>.
American Society of Radiologic Technologists. 15000 Central

Ave., SE, Albuquerque, NM 87123-3917. (505) 298-4500.<http://www.asrt.org>.
Kurt Richard Sternlof
Abdominal wall defects
Abdominal wall defects are birth (congenital)
defects that allow the stomach or intestines to protrude.
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Many unexpected and fascinating events occur dur-
ing the development of a fetus inside the womb. Thestomach and intestines begin development outside thebaby’s abdomen and only later does the abdominal wallenclose them. Occasionally, either the umbilical openingis too large, or it develops improperly, allowing the bow-els or stomach to remain outside or squeeze through theabdominal wall.
Causes and symptoms
There are many causes for birth defects that still

remain unclear. Presently, the cause(s) of abdominal walldefects is unknown, and any symptoms the mother mayhave to indicate that the defects are present in the fetusare nondescript.
Diagnosis
At birth, the problem is obvious, because the base of

the umbilical cord at the navel will bulge or, in worsecases, contain viscera (internal organs). Before birth, anultrasound examination may detect the problem. It isalways necessary in children with one birth defect to lookfor others, because birth defects are usually multiple.
Treatment
Abdominal wall defects are effectively treated with

surgical repair. Unless there are accompanying anom-alies, the surgical procedure is not overly complicated.The organs are normal, just misplaced. However, if thedefect is large, it may be difficult to fit all the viscera intothe small abdominal cavity.
Prognosis
If there are no other defects, the prognosis after sur-
gical repair of this condition is relatively good. However,KEY TERMS
Hernia —Movement of a structure into a place it
does not belong.
Umbilical —Referring to the opening in the

abdominal wall where the blood vessels from theplacenta enter.
Viscera —Any of the body’s organs located in the
chest or abdomen.10% of those with more severe or additional abnormali-
ties die from it. The organs themselves are fully function-al; the difficulty lies in fitting them inside the abdomen.The condition is, in fact, a hernia requiring only replace-

ment and strengthening of the passageway throughwhich it occurred. After surgery, increased pressure inthe stretched abdomen can compromise the function ofthe organs inside.
Prevention
Some, but by no means all, birth defects are pre-
ventable by early and attentive prenatal care, good nutri-
tion, supplemental vitamins , diligent avoidance of all
unnecessary drugs and chemicals—especially tobacco—and other elements of a healthy lifestyle.
Resources

Resources
Dunn, J. C., and E. W. Fonkalsrud. “Improved Survival of
Infants with Omphalocele.” American Journal of Surgery
173 (April 1997): 284-7.
Langer, J. C. “Gastroschisis and Omphalocele.” Seminars in
Pediatric Surgery 5 (May 1996): 124-8.
J. Ricker Polsdorfer, MD
Abnormal heart rhythms seeArrhythmias
ABO blood typing seeBlood typing and
crossmatching
ABO incompatibility seeErythroblastosis
fetalis
Abortion, habitual seeRecurrent
miscarriage
Abortion, partial birth

Partial birth abortion is a method of late-term abor-
tion that terminates a pregnancy and results in the death
and intact removal of a fetus. This procedure is mostcommonly referred to as intact dilatation and extraction(D & X).
Purpose
Partial birth abortion, or D&X, is performed to end a
pregnancy and results in the death of a fetus, typically in

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the late second or third trimester. Although D&X is high-
ly controversial, some physicians argue that it has advan-tages that make it a preferable procedure in some circum-stances. One perceived advantage is that the fetus isremoved largely intact, allowing for better evaluation andautopsy of the fetus in cases of known fetal anomalies.

Intact removal of the fetus may also confer a lower riskof puncturing the uterus or damaging the cervix. Anotherperceived advantage is that D&X ends the pregnancywithout requiring the woman to go through labor, whichmay be less emotionally traumatic than other methods oflate-term abortion. In addition, D&X may offer a lowercost and shorter procedure time.
Women considering D&X should be aware of the

highly controversial nature of this procedure. A contro-versy common to all late-term abortions is whether thefetus is viable, or able to survive outside of the woman’sbody. A specific area of controversy with D&X is thatfetal death does not occur until after most of the fetalbody has exited the uterus. Several states have takenlegal action to limit or ban D&X and many physicianswho perform abortions do not perform D&X. This mayrestrict the availability of this procedure to women seek-ing

availability of this procedure to women seek-ing late-term abortion.

Intact D&X, or partial birth abortion first involves

administration of medications to cause the cervix todilate, usually over the course of several days. Next, thephysician rotates the fetus to a footling breech position.The body of the fetus is then drawn out of the uterus feetfirst, until only the head remains inside the uterus. Then,the physician uses an instrument to puncture the base ofthe skull, which collapses the fetal head. Typically, thecontents of the fetal head are then partially suctioned out,which results in the death of the fetus,

out,which results in the death of the fetus, and reduces thesizes of the fetal head enough to allow it to pass throughthe cervix. The dead and otherwise intact fetus is thenremoved from the woman’s body.

Medical preparation for D&X involves an outpatient
visit to administer medications, such as laminaria ,t o
cause the cervix to begin dilating.
In addition, preparation may involve fulfilling local
legal requirements, such as a mandatory waiting period,counseling, or an informed consent procedure reviewingstages of fetal development, childbirth , alternative abor-
tion methods, and adoption.KEY TERMS
Cervix —The narrow outer end of the uterus that

separates the uterus from the vaginal canal.
Footling breech —A position of the fetus while in
the uterus where the feet of the fetus are nearestthe cervix would be the first part of the fetus to exitthe uterus, with the head of the fetus being the lastpart to exit the uterus.
Laminaria —A medical product made from a cer-
tain type of seaweed that is physically placed nearthe cervix to cause it to dilate.
Aftercare

Aftercare
D&X typically does not require an overnight hospi-
tal stay, so a follow up appointment may be scheduled tomonitor the woman for any complications.
Risks
With all abortion, the later in pregnancy an abortion

is performed, the more complicated the procedure andthe greater the risk of injury to the woman. In addition toassociated emotion reactions, D&X carries the risk ofinjury to the woman, including heavy bleeding, bloodclots, damage to the cervix or uterus, pelvic infection,and anesthesia-related complications. There is also a riskof incomplete abortion, meaning that the fetus is notdead when removed from the woman’s body. Possiblelong-term risks include difficulty becoming pregnant orcarrying a

include difficulty becoming pregnant orcarrying a future pregnancy to term.

The expected outcome of D&X is the termination of
a pregnancy with removal of a dead fetus from thewoman’s body.
Resources
Epner, Janet E., et al. “Late-term Abortion.” JAMA 280, no. 8
(26 August 1998): 724-729.
Sprang, M. LeRoy, and Neerhof, Mark G. “Rationale for Ban-
ning Abortions Late in Pregnancy.” JAMA (26 August
1998): 744-747.
Swomley, John M. “The ‘Partial-birth’ Debate in 1998.”
Humanist (March/April 1998): 5-7.

Grimes, David A. “The Continuing Need for Late Abortion.”
JAMA (26 August 1998): 747-750.
GALE ENCYCLOPEDIA OF MEDICINE 2 7Abortion, partial birthGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 7

Planned Parenthood Federation of America. 810 Seventh Ave.,
New York, NY 10019. (212) 541-7800. FAX: (212) 245-1845.
OTHER
Status of partial-birth abortion laws in the states. Othmer Insti-
tute at Planned Parenthood of NYC. 2000.
Abortion, selective
Selective abortion, also known as selective reduc-
tion, refers to choosing to abort a fetus, typically in amulti-fetal pregnancy , to decrease the health risks to the

mother in carrying and giving birth to more than one ortwo babies, and also to decrease the risk of complicationsto the remaining fetus(es). The term selective abortionalso refers to choosing to abort a fetus for reasons such asthe woman is carrying a fetus which likely will be bornwith some birth defect or impairment, or because the sexof the fetus is not preferred by the individual.
Purpose
A woman may decide to abort for health reasons, for

example, she is at higher risk for complications during preg-nancy because of a disorder or disease such as diabetes.
However, selective reduction is recommended often in
cases of multi-fetal pregnancy, or the presence of more thanone fetus, typically, at least three or more fetuses. In thegeneral population, multi-fetal pregnancy happens in onlyabout 1-2% of pregnant women. But multi-fetal pregnan-cies occur far more often in women using fertility drugs.

Because women or couples who use fertility drugs
have made an extra effort to become pregnant, it is possi-ble that the individuals may be unwilling or uncomfort-able with the decision to abort a fetus in cases of multi-fetal pregnancy. Individuals engaging in fertility treat-ment should be made aware of the risk of multi-fetalpregnancy and consider the prospect of recommendedreduction before undergoing fertility treatment.

Selective reduction is usually performed between
nine and 12 weeks of pregnancy and is most successfulwhen performed in early pregnancy. It is a simple proce-dure and can be performed on an outpatient basis. A nee-dle is inserted into the woman’s stomach or vagina andpotassium chloride is injected into the fetus.
Individuals who have chosen selective reduction to

safeguard the remaining fetuses should be counseledprior to the procedure. Individuals should receive infor-mation regarding the risks of a multi-fetal pregnancy toboth the fetuses and the mother compared with the risksafter the reduction.
Individuals seeking an abortion for any reason
should consider the ethical implications whether it bebecause the fetus is not the preferred sex or because thefetus would be born with a severe birth defect.
Aftercare

Aftercare
Counseling should continue after the abortion
because it is a traumatic event. Individuals may feelguilty about choosing one fetus over another. Mentalhealth professionals should be consulted throughout theprocess.
Risks
About 75% of women who undergo selective reduc-
tion will go into premature labor . About 4-5% of
women undergoing selective reduction also miscarry oneor more of the remaining fetuses. The risks associatedwith multi-fetal pregnancy is considered higher.

In cases where a multi-fetal pregnancy, three or
more fetuses, is reduced to two, the twin fetuses typicallydevelop as they would as if they were conceived as twins.
Resources
BOOKS
Knobil, Ernst and Jimmy D. Neill, editors. “Abortion.” In
Encyclopedia of Reproduction. San Diego: Adademic
Press, 1998, pp.1-5.
Scott, James R., editor. “Induced Abortion.” In Danforth’s
Obstetrics and Gynecology. Philadelphia: Lippincott
Williams & Wilkins, 1999, pp.567-578.

Author unspecified. “Multiple Pregnancy Associated With
Infertility Therapy.” American Society for Reproductive
Medicine, A Practice Committee Report (November
2000): 1-8.
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The American Society for Reproductive Medicine. 1209 Mont-
gomery Highway, Birmingham, AL 35216-2809. (205)978-5000. <http://www.asrm.org>.
The Alan Guttmacher Institute. 120 Wall Street, New York, NY
10005. (212) 248-1111. <http://www.agi-usa.org>.
Meghan M. Gourley
Abortion, spontaneous seeMiscarriage
Abortion, therapeutic
Therapeutic abortion is the intentional termination
of a pregnancy before the fetus can live independently.

Abortion has been a legal procedure in the United Statessince 1973.
Purpose
An abortion may be performed whenever there is
some compelling reason to end a pregnancy. Womenhave abortions because continuing the pregnancy wouldcause them hardship, endanger their life or health, orbecause prenatal testing has shown that the fetus will beborn with severe abnormalities.
Abortions are safest when performed within the first

six to 10 weeks after the last menstrual period. The cal-culation of this date is referred to as the gestational ageand is used in determining the stage of pregnancy. Forexample, a woman who is two weeks late having herperiod is said to be six weeks pregnant, because it is sixweeks since she last menstruated.
About 90% of women who have abortions do so
before 13 weeks and experience few complications.Abortions performed between 13-24 weeks have a higherKEY TERMS

Multi-fetal pregnancy —A pregnancy of two or
more fetuses.
Selective reduction —Typically referred to in cases
of multifetal pregnancy, when one or more fetusesare aborted to preserve the viability of the remain-ing fetuses and decrease health risks to the mother.rate of complications. Abortions after 24 weeks are
extremely rare and are usually limited to situations wherethe life of the mother is in danger.
Most women are able to have abortions at clinics or

outpatient facilities if the procedure is performed early inpregnancy. Women who have stable diabetes, controlledepilepsy, mild to moderate high blood pressure, or whoare HIV positive can often have abortions as outpatientsif precautions are taken. Women with heart disease, pre-vious endocarditis ,asthma , lupus erythematosus, uter-

ine fibroid tumors, blood clotting disorders, poorly con-trolled epilepsy, or some psychological disorders usuallyneed to be hospitalized in order to receive special moni-toring and medications during the procedure.
V ery early abortions
Between five and seven weeks, a pregnancy can be

ended by a procedure called menstrual extraction. Thisprocedure is also sometimes called menstrual regulation,mini-suction, or preemptive abortion. The contents of theuterus are suctioned out through a thin (3-4 mm) plastictube that is inserted through the undilated cervix. Suctionis applied either by a bulb syringe or a small pump.
Another method is called the “morning after” pill, or
emergency contraception . Basically, it involves taking

high doses of birth control pills within 24 to 48 hours ofhaving unprotected sex. The high doses of hormonescauses the uterine lining to change so that it will not sup-port a pregnancy. Thus, if the egg has been fertilized, it issimply expelled from the body.
There are two types of emergency contraception.

One type is identical to ordinary birth control pills, anduses the hormones estrogen and progestin). This type isavailable with a prescription under the brand name Pre-ven. But women can even use their regular birth controlpills for emergency contraception, after they check withtheir doctor about the proper dose. About half of womenwho use birth control pills for emergency contraceptionget nauseated and 20 percent vomit. This method cuts therisk of pregnancy 75 percent.

The other type of morning-after pill contains only
one hormone: progestin, and is available under the brandname Plan B. It is more effective than the first type witha lower risk of nausea and vomiting . It reduces the risk
of pregnancy 89 percent.
Women should check with their physicians regard-
ing the proper dose of pills to take, as it depends on the
GALE ENCYCLOPEDIA OF MEDICINE 2 9Abortion, therapeuticGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 9

brand of birth control pill. Not all birth control pills will
work for emergency contraception.
Menstrual extractions are safe, but because the
amount of fetal material is so small at this stage of devel-opment, it is easy to miss. This results in an incompleteabortion that means the pregnancy continues.
First trimester abortions
The first trimester of pregnancy includes the first 13

weeks after the last menstrual period. In the UnitedStates, about 90% of abortions are performed during thisperiod. It is the safest time in which to have an abortion,and the time in which women have the most choice ofhow the procedure is performed.
MEDICAL ABORTIONS. Medical abortions are brought
about by taking medications that end the pregnancy. Theadvantages of a first trimester medical abortion are:
• The procedure is non-invasive; no surgical instruments
are used.

are used.
• Anesthesia is not required.• Drugs are administered either orally or by injection.• The procedure resembles a natural miscarriage .
Disadvantages of a medical abortion are:
• The effectiveness decreases after the seventh week.• The procedure may require multiple visits to the doctor.
• Bleeding after the abortion lasts longer than after a sur-
gical abortion.
• The woman may see the contents of her womb as it is
expelled.
Two different medications can be used to bring about

an abortion. Methotrexate (Rheumatrex) works by stop-ping fetal cells from dividing which causes the fetus to die.
On the first visit to the doctor, the woman receives

an injection of methotrexate. On the second visit, abouta week later, she is given misoprostol (Cytotec), anoxygenated unsaturated cyclic fatty acid responsible forvarious hormonal reactions such as muscle contraction(prostaglandin), that stimulates contractions of theuterus. Within two weeks, the woman will expel thecontents of her uterus, ending the pregnancy. A follow-up visit to the doctor is necessary to assure that theabortion is complete.
With this procedure, a woman will feel cramping

and may feel nauseated from the misoprostol. Thiscombination of drugs is 90-96% effective in endingpregnancy.
Mifepristone (RU-486), which goes by the brand

name Mifeprex, works by blocking the action of prog-esterone, a hormone needed for pregnancy to continue,then stimulates uterine contractions thus ending thepregnancy. It can be taken a much as 49 days after thefirst day of a woman’s last period. On the first visit tothe doctor, a woman takes a mifepristone pill. Two dayslater she returns and, if the miscarriage has notoccurred, takes two misoprostol pills, which causes theuterus to contract. Five percent of women won’t need totake misoprostol.

percent of women won’t need totake misoprostol. After an observation period, shereturns home.

Within four days, 90% of women have expelled the
contents of their uterus and completed the abortion.Within 14 days, 95-97% of women have completed theabortion. A third follow-up visit to the doctor is neces-sary to confirm through observation or ultrasound thatthe procedure is complete. In the event that it is not, asurgical abortion is performed. Studies show that 4.5 to 8percent of women need surgery or a blood transfusion

after taking mifepristone, and the pregnancy persists inabout 1 percent of women. In this case, surgical abortionis recommended because the fetus may be damanged.Side effects include nausea, vaginal bleeding and heavycramping. The bleeding is typically heavier than a nor-mal period and may last up to 16 days.
Mifepristone is not recommended for women with
ectopic pregnancy , an IUD, who have been taking long-
GALE ENCYCLOPEDIA OF MEDICINE 2 10Abortion, therapeuticUterus
Embryonic

Embryonic
tissueVaginaVulsellum
CervixSpeculum
Extraction tube
Between 5 and 7 weeks, a pregnancy can be ended by a pro-
cedure called menstrual extraction.The contents of theuterus are suctioned out through a thin extraction tube thatis inserted through the undilated cervix. (Illustration by Elec-
tronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 10

term steroidal therapy, have bleeding abnormalities or on
blood-thinners such as Coumadin.
Surgical abortions
First trimester surgical abortions are performed
using vacuum aspiration. The procedure is also calleddilation and evacuation (D & E), suction dilation, vacu-um curettage, or suction curettage.
Advantages of a vacuum aspiration abortion are:
• It is usually done as a one-day outpatient procedure.• The procedure takes only 10-15 minutes.

• Bleeding after the abortion lasts five days or less.
• The woman does not see the products of her womb
being removed.
Disadvantages include:
• The procedure is invasive; surgical instruments are used.• Infection may occur.
During a vacuum aspiration, the woman’s cervix is

gradually dilated by expanding rods inserted into thecervical opening. Once dilated, a tube attached to a suc-tion pump is inserted through the cervix and the con-tents of the uterus are suctioned out. The procedure is97-99% effective. The amount of discomfort a womanfeels varies considerably. Local anesthesia is oftengiven to numb the cervix, but it does not mask uterinecramping. After a few hours of rest, the woman mayreturn home.

Second trimester abortions
Although it is better to have an abortion during the
first trimester, some second trimester abortions may beinevitable. The results of genetic testing are often not
available until 16 weeks. In addition, women, especiallyteens, may not have recognized the pregnancy or come toterms with it emotionally soon enough to have a firsttrimester abortion. Teens make up the largest group hav-ing second trimester abortions.
Some second trimester abortions are performed as a

D & E. The procedures are similar to those used in thefirst trimester, but a larger suction tube must be usedbecause more material must be removed. This increasesthe amount of cervical dilation necessary and increasesthe risk of the procedure. Many physicians are reluctantto perform a D & E this late in pregnancy, and for somewomen is it not a medically safe option.
The alternative to a D & E in the second trimester is

an abortion by induced labor. Induced labor may requirean overnight stay in a hospital. The day before the proce-dure, the woman visits the doctor for tests, and to eitherKEY TERMS
Endocarditis —An infection of the inner mem-
brane lining of the heart.
Fibroid tumors —Fibroid tumors are non-cancer-
ous (benign) growths in the uterus. They occur in30-40% of women over age 40, and do not needto be removed unless they are causing symptomsthat interfere with a woman’s normal activities.

Lupus erythematosus —A chronic inflammatory
disease in which inappropriate immune systemreactions cause abnormalities in the blood vesselsand connective tissue.
Prostaglandin —Oxygenated unsaturated cyclic
fatty acids responsible for various hormonal reac-tions such as muscle contraction.
Rh negative —Lacking the Rh factor, genetically

determined antigens in red blood cells that pro-duce immune responses. If an Rh negative womanis pregnant with an Rh positive fetus, her body willproduce antibodies against the fetus’s blood, caus-ing a disease known as Rh disease. Sensitization tothe disease occurs when the women’s blood isexposed to the fetus’s blood. Rh immune globulin(RhoGAM) is a vaccine that must be given to awoman after an abortion, miscarriage, or prenataltests in order to prevent sensitization to Rh disease.

have rods inserted in her cervix to help dilate it or to
receive medication that will soften the cervix and speedup labor.
On the day of the abortion, drugs, usually prosta-
glandins to induce contractions, and a salt water solution,are injected into the uterus. Contractions begin, and with-in eight to 72 hours the woman delivers the fetus.
Side effects of this procedure include nausea, vomit-
ing, and diarrhea from the prostaglandins, and pain

from uterine cramps. Anesthesia of the sort used inchildbirth can be given to mask the pain. Many women
are able to go home a few hours after the procedure.
Very early abortions cost between $200-$400. Later

abortions cost more. The cost increases about $100 perweek between the thirteenth and sixteenth week. Secondtrimester abortions are much more costly because theyoften involve more risk, more services, anesthesia, andsometimes a hospital stay. Insurance carriers and HMOsmay or may not cover the procedure. Federal law pro-
GALE ENCYCLOPEDIA OF MEDICINE 2 11Abortion, therapeuticGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 11

hibits federal funds including Medicaid funds, from
being used to pay for an elective abortion.
The doctor must know accurately the stage of a
woman’s pregnancy before an abortion is performed. Thedoctor will ask the woman questions about her menstrualcycle and also do a physical examination to confirm the

stage of pregnancy. This may be done at an office visitbefore the abortion or on the day of the abortion. Somestates require a waiting period before an abortion can beperformed. Others require parental or court consent for achild under age 18 to receive an abortion.
Despite the fact that almost half of all women in the

United States have had at least one abortion by the timethey reach age 45, abortion is surrounded by controversy.Women often find themselves in emotional turmoil whendeciding if an abortion is a procedure they wish to under-go. Pre-abortion counseling is important in helping awoman resolve any questions she may have about havingthe procedure.
Aftercare
Regardless of the method used to perform the abor-

tion, a woman will be observed for a period of time tomake sure her blood pressure is stable and that bleedingis controlled. The doctor may prescribe antibiotics to

reduce the chance of infection. Women who are Rh nega-tive (lacking genetically determined antigens in their redblood cells that produce immune responses) should begiven a human Rh immune globulin (RhoGAM) after theprocedure unless the father of the fetus is also Rh nega-tive. This prevents blood incompatibility complicationsin future pregnancies.
Bleeding will continue for about five days in a surgical

abortion and longer in a medical abortion. To decrease therisk of infection, a woman should avoid intercourse and notuse tampons and douches for two weeks after the abortion.
A follow-up visit is a necessary part of the woman’s
aftercare. Contraception will be offered to women whowish to avoid future pregnancies, because menstrualperiods normally resume within a few weeks.
Risks
Serious complications resulting from abortions per-

formed before 13 weeks are rare. Of the 90% of womenwho have abortions in this time period, 2.5% have minorcomplications that can be handled without hospitaliza-tion. Less than 0.5% have complications that require ahospital stay. The rate of complications increases as thepregnancy progresses.Complications from abortions can include:
• uncontrolled bleeding
• infection• blood clots accumulating in the uterus
• a tear in the cervix or uterus

• missed abortion where the pregnancy continues• incomplete abortion where some material from the
pregnancy remains in the uterus
Women who experience any of the following symp-
toms of post-abortion complications should call the clin-ic or doctor who performed the abortion immediately.
• severe pain
• fever over 100.4°F (38.2°C)• heavy bleeding that soaks through more than one sani-
tary pad per hour
• foul-smelling discharge from the vagina

• continuing symptoms of pregnancy
Usually the pregnancy is ended without complica-
tion and without altering future fertility.
Resources
BOOKS
Carlson, Karen J., Stephanie A. Eisenstat, and Terra Ziporyn.
“Abortion.” In The Harvard Guide to Women’s Health.
Cambridge, MA: Harvard University Press, 1996.
DeCherney, Alan H., and Martin L. Peroll. “Contraception and
Family Planning.” In Current Obstetric and Gynecologic

Diagnosis and Treatment. Norwalk, CT: Appleton &
Lange, 1994.
ORGANIZATION
National Abortion Federation. (800) 772-9100. <http://www.
prochoice.org>.
Abrasions seeWounds
Abruptio placentae seePlacental abruption
Abscess
An abscess is an enclosed collection of liquefied tis-
sue, known as pus, somewhere in the body. It is the resultof the body’s defensive reaction to foreign material.

GALE ENCYCLOPEDIA OF MEDICINE 2 12AbcessGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 12

There are two types of abscesses, septic and sterile.

Most abscesses are septic, which means that they are theresult of an infection. Septic abscesses can occur any-where in the body. Only a germ and the body’s immuneresponse are required. In response to the invading germ,white blood cells gather at the infected site and beginproducing chemicals called enzymes that attack the germby digesting it. These enzymes act like acid, killing thegerms and breaking them down into small pieces that canbe picked up by the circulation and eliminated from

picked up by the circulation and eliminated from thebody. Unfortunately, these chemicals also digest bodytissues. In most cases, the germ produces similar chemi-cals. The result is a thick, yellow liquid—pus—contain-ing digested germs, digested tissue, white blood cells,and enzymes.

An abscess is the last stage of a tissue infection that
begins with a process called inflammation. Initially, asthe invading germ activates the body’s immune system,several events occur:
• Blood flow to the area increases.• The temperature of the area increases due to the
increased blood supply.
• The area swells due to the accumulation of water, blood,
and other liquids.
• It turns red.• It hurts, because of the irritation from the swelling and
the chemical activity.

These four signs—heat, swelling, redness, and pain—
characterize inflammation.
As the process progresses, the tissue begins to turn

to liquid, and an abscess forms. It is the nature of anabscess to spread as the chemical digestion liquefiesmore and more tissue. Furthermore, the spreading fol-lows the path of least resistance—the tissues most easilydigested. A good example is an abscess just beneath theskin. It most easily continues along beneath the skinrather than working its way through the skin where itcould drain its toxic contents. The contents of the abscessalso leak into the general circulation and produce symp-toms

the general circulation and produce symp-toms just like any other infection. These include chills,fever , aching, and general discomfort.

Sterile abscesses are sometimes a milder form of the
same process caused not by germs but by non-living irri-tants such as drugs. If an injected drug like penicillin isnot absorbed, it stays where it was injected and maycause enough irritation to generate a sterile abscess—sterile because there is no infection involved. Sterileabscesses are quite likely to turn into hard, solid lumps asthey scar, rather than remaining pockets of pus.Causes and symptoms

Many different agents cause abscesses. The most
common are the pus-forming (pyogenic) bacteria likeStaphylococcus aureus , which is nearly always the cause

of abscesses under the skin. Abscesses near the largebowel, particularly around the anus, may be caused byany of the numerous bacteria found within the largebowel. Brain abscesses and liver abscesses can be causedby any organism that can travel there through the circula-tion. Bacteria, amoeba, and certain fungi can travel inthis fashion. Abscesses in other parts of the body arecaused by organisms that normally inhabit nearby struc-tures or that infect them. Some common causes of specif-ic

that infect them. Some common causes of specif-ic abscesses are:

• skin abscesses by normal skin flora• dental and throat abscesses by mouth flora• lung abscesses by normal airway flora, pneumonia
germs, or tuberculosis
• abdominal and anal abscesses by normal bowel flora
Specific types of abscesses
Listed below are some of the more common and
important abscesses.
• Carbuncles and other boils . Skin oil glands (sebaceous

glands) on the back or the back of the neck are the onesusually infected. The most common germ involved isStaphylococcus aureus . Acne is a similar condition of
sebaceous glands on the face and back.
• Pilonidal abscess. Many people have as a birth defect a
tiny opening in the skin just above the anus. Fecal bac-teria can enter this opening, causing an infection andsubsequent abscess.
GALE ENCYCLOPEDIA OF MEDICINE 2 13Abcess
An amoebic abscess caused by Entameoba histolytica.

(Phototake NYC. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 13

• Retropharyngeal, parapharyngeal, peritonsillar abscess.
As a result of throat infections like strep throat and
tonsillitis , bacteria can invade the deeper tissues of the
throat and cause an abscess. These abscesses can com-promise swallowing and even breathing.
• Lung abscess. During or after pneumonia, whether it’s
due to bacteria [common pneumonia], tuberculosis,fungi, parasites, or other germs, abscesses can developas a complication.
• Liver abscess. Bacteria or amoeba from the intestines

can spread through the blood to the liver and causeabscesses.
• Psoas abscess. Deep in the back of the abdomen on
either side of the lumbar spine lie the psoas muscles.They flex the hips. An abscess can develop in one ofthese muscles, usually when it spreads from the appen-dix, the large bowel, or the fallopian tubes.
Diagnosis
The common findings of inflammation—heat, red-

ness, swelling, and pain—easily identify superficialabscesses. Abscesses in other places may produce onlygeneralized symptoms such as fever and discomfort. Ifthe patient’s symptoms and physical examination do not
help, a physician may have to resort to a battery of tests toKEY TERMS
Cellulitis —Inflammation of tissue due to infection.
Enzyme —Any of a number of protein chemicals
that can change other chemicals.

Fallopian tubes —Part of the internal female anato-
my that carries eggs from the ovaries to the uterus.
Flora —Living inhabitants of a region or area.
Pyogenic —Capable of generating pus. Streptococ-
cus, Staphocococcus , and bowel bacteria are the
primary pyogenic organisms.
Sebaceous glands —Tiny structures in the skin that
produce oil (sebum). If they become plugged,sebum collects inside and forms a nurturing placefor germs to grow.

Septicemia —The spread of an infectious agent
throughout the body by means of the bloodstream.
Sinus —A tubular channel connecting one body
part with another or with the outside.locate the site of an abscess, but usually something in the
initial evaluation directs the search. Recent or chronic dis-ease in an organ suggests it may be the site of an abscess.Dysfunction of an organ or system—for instance, seizuresor altered bowel function—may provide the clue. Pain

and tenderness on physical examination are commonfindings. Sometimes a deep abscess will eat a small chan-nel (sinus) to the surface and begin leaking pus. A sterileabscess may cause only a painful lump deep in the but-tock where a shot was given.
Treatment
Since skin is very resistant to the spread of infection,

it acts as a barrier, often keeping the toxic chemicals ofan abscess from escaping the body on their own. Thus,the pus must be drained from the abscess by a physician.The surgeon determines when the abscess is ready fordrainage and opens a path to the outside, allowing thepus to escape. Ordinarily, the body handles the remaininginfection, sometimes with the help of antibiotics or other

drugs. The surgeon may leave a drain (a piece of cloth orrubber) in the abscess cavity to prevent it from closingbefore all the pus has drained out.
Alternative treatment
If an abscess is directly beneath the skin, it will be

slowly working its way through the skin as it is morerapidly working its way elsewhere. Since chemicalswork faster at higher temperatures, applications of hotcompresses to the skin over the abscess will hasten thedigestion of the skin and eventually result in its breakingdown, releasing the pus spontaneously. This treatment isbest reserved for smaller abscesses in relatively less dan-gerous areas of the body—limbs, trunk, back of the neck.It is also useful for all superficial abscesses in their

useful for all superficial abscesses in their veryearly stages. It will “ripen” them.

Contrast hydrotherapy , alternating hot and cold
compresses, can also help assist the body in resorption ofthe abscess. There are two homeopathic remedies thatwork to rebalance the body in relation to abscess forma-tion, Silica and Hepar sulphuris . In cases of septic
abscesses, bentonite clay packs (bentonite clay and asmall amount of Hydrastis powder) can be used to draw
the infection from the area.
Prognosis
Once the abscess is properly drained, the prognosis

is excellent for the condition itself. The reason for theabscess (other diseases the patient has) will determinethe overall outcome. If, on the other hand, the abscessruptures into neighboring areas or permits the infectious
GALE ENCYCLOPEDIA OF MEDICINE 2 14AbcessGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 14

agent to spill into the bloodstream, serious or fatal conse-
quences are likely. Abscesses in and around the nasalsinuses, face, ears, and scalp may work their way into thebrain. Abscesses within an abdominal organ such as theliver may rupture into the abdominal cavity. In eithercase, the result is life threatening. Blood poisoning is a

term commonly used to describe an infection that hasspilled into the blood stream and spread throughout thebody from a localized origin. Blood poisoning, known tophysicians as septicemia, is also life threatening.
Of special note, abscesses in the hand are more seri-
ous than they might appear. Due to the intricate structureand the overriding importance of the hand, any handinfection must be treated promptly and competently.
Infections that are treated early with heat (if superfi-

cial) or antibiotics will often resolve without the forma-tion of an abscess. It is even better to avoid infectionsaltogether by taking prompt care of open injuries, partic-ularly puncture wounds . Bites are the most dangerous of
all, even more so because they often occur on the hand.
Resources
BOOKS
Bennett, J. Claude, and Fred Plum, eds. Cecil Textbook of Med-
icine. Philadelphia: W. B. Saunders Co., 1996.
Current Medical Diagnosis and Treatment, 1996. 35th ed. Ed.

Stephen McPhee, et al. Stamford: Appleton & Lange, 1995.
Harrison’s Principles of Internal Medicine. Ed. Anthony S.
Fauci, et al. New York: McGraw-Hill, 1997.
Abscess drainage seeAbscess incision and
drainage
Abscess incision & drainage
An infected skin nodule that contains pus may need to
be drained via a cut if it does not respond to antibiotics .
This allows the pus to escape, and the infection to heal.
Purpose

bacterial infection. The pus is made up of both live anddead organisms and destroyed tissue from the whiteblood cells that were carried to the area to fight the infec-tion. Abscesses are often found in the soft tissue underthe skin, such as the armpit or the groin. However, theymay develop in any organ, and are commonly found inthe breast and gums. Abscesses are far more serious andcall for more specific treatment if they are located indeep organs such as the lung, liver or brain.

Because the lining of the abscess cavity tends to
interfere with the amount of the drug that can penetratethe source of infection from the blood, the cavity itselfmay require draining. Once an abscess has fully formed,it often does not respond to antibiotics. Even if theantibiotic does penetrate into the abscess, it doesn’t func-tion as well in that environment.
An abscess can usually be diagnosed visually, al-

though an imaging technique such as a computed tomog-raphy scan may be used to confirm the extent of theabscess before drainage. Such procedures may also beneeded to localize internal abscesses, such as those in theabdominal cavity or brain.
GALE ENCYCLOPEDIA OF MEDICINE 2 15Abcess incision & drainage
Liver
StomachSpleen
ColonCommon sites of abscess 
above and below the liver
Although abscesses are often found in the soft tissue under

the skin, such as the armpit or the groin, they may developin any organ, such as the liver. (Illustration by Electronic Illus-
trators Group.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 15

A doctor will cut into the lining of the abscess, allow-
ing the pus to escape either through a drainage tube or byleaving the cavity open to the skin. How big the incisionis depends on how quickly the pus is encountered.
Once the abscess is opened, the doctor will clean
and irrigate the wound thoroughly with saline. If it is nottoo large or deep, the doctor may simply pack theabscess wound with gauze for 24–48 hours to absorb thepus and discharge.

If it is a deeper abscess, the doctor may insert a
drainage tube after cleaning out the wound. Once the tube isin place, the surgeon closes the incision with simple stitch-es, and applies a sterile dressing. Drainage is maintained forseveral days to help prevent the abscess from reforming.
The skin over the abscess will be cleansed by swab-
bing gently with an antiseptic solution.
Aftercare
Much of the pain around the abscess will be gone

after the surgery. Healing is usually very fast. After thetube is taken out, antibiotics may be continued for sever-al days. Applying heat and keeping the affected area ele-vated may help relieve inflammation.
Risks
If there is any scarring, it is likely to become much

less noticeable as time goes on, and eventually almostinvisible. Occasionally, an abscess within a vital organ(such as the brain) damages enough surrounding tissuethat there is some permanent loss of normal function.
Most abscesses heal after drainage alone; others
require drainage and antibiotic drug treatment.
Resources
BOOKS
Turkington, Carol A., and Jeffrey S. Dover. Skin Deep. New
York: Facts on File, 1998.KEY TERMS
White blood cells —Cells that protect the body

against infection.ORGANIZATIONS
National Institute of Arthritis and Musculoskeletal and Skin
Diseases. 9000 Rockville Pike, Bldg. 31, Rm 9A04,Bethesda, MD 20892.
Carol A. Turkington
Abuse
Abuse is defined as any thing that is harmful, injuri-

ous, or offensive. Abuse also includes excessive andwrongful misuse of anything. There are several major typesof abuse: physical and sexual abuse of a child or an adult,substance abuse, elderly abuse, and emotional abuse.
Physical abuse of a child is the infliction of injury by

an other person. The injuries can include punching, kick-ing, biting, burning, beating, or pulling the victim’s hair.The physical abuse inflicted on a child can result inbruises ,burns ,poisoning , broken bones, and internal
hemorrhages. Physical assault against an adult primarilyoccurs with women, usually in the form of domestic vio-lence. It is estimated that approximately three millionchildren witness domestic violence every year.
Sexual abuse of a child refers to sexual behavior

between an adult and child or between two children, oneof whom is dominant or significantly older. The sexualbehaviors can include touching breasts, genitals, and but-tocks; either dressed or undressed. The behavior can alsoinclude exhibitionism, cunnilingus, fellatio, or penetra-tion of the vagina or anus with sexual organs or objects.
Pornographic photography is also used in sexual

abuse with children. Reported sex offenders are 97%male. Females are more often perpetrators in child-caresettings, since children may confuse sexual abuse by afemale with normal hygiene care. Sexual abuse by step-fathers is five times more common than with biologicalfathers. Sexual abuse of daughters by stepfathers orfathers is the most common form of incest.
Sexual abuse can also take the form of rape. The

legal definition of rape includes only slight penile pene-tration in the victim’s outer vulva area. Complete erec-tion and ejaculation are not necessary. Rape is the perpe-tration of an act of sexual intercourse whether:
• will is overcome by force or fear (from threats or by use
of drugs).
GALE ENCYCLOPEDIA OF MEDICINE 2 16AbuseGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 16

• mental impairment renders the victim incapable of
rational judgment.
• if the victim is below the legal age established for con-
sent.
Substance abuse is an abnormal pattern of substance
usage leading to significant distress or impairment. Thecriteria include one or more of the following occurringwithin a 12-month period:
• recurrent substance use resulting in failure to fulfill
obligations at home, work, or school.
• using substance in situations that are physically danger-

ous (i.e., while driving).
• recurrent substance-related legal problems.
• continued usage despite recurrent social and interper-
sonal problems (i.e., arguments and fights with signifi-cant other).
Abuse in the elderly is common and occurs mostly

as a result of caretaker burnout, due to the high level ofdependency frail, elderly patients usually require. Abusecan be manifested by physical signs, fear, and delayingor not reporting the need for advanced medical care.Elderly patients may also exhibit financial abuse (moneyor possessions taken away) and abandonment.
Emotional abuse generally continues even after phys-

ical assaults have stopped. In most cases it is a personallytailored form of verbal or gesture abuse expressed to illic-it a provoked response.
Children who have been abused usually have a variety
of symptoms that encompass behavioral, emotional, andpsychosomatic problems. Children who have been physi-cally abused tend to be more aggressive, angry, hostile,depressed, and have low self-esteem. Additionally, theyexhibit fear, anxiety , and nightmares. Severe psychological

problems may result in suicidal behavior or posttraumaticstress disorder. Physically abused children may complain
of physical illness even in the absence of a cause. Theymay also suffer from eating disorders and encopresis. Chil-dren who are sexually abused may exhibit abnormal sexualbehavior in the form of aggressiveness and hyperarousal.Adolescents may display promiscuity, sexual acting out,and—in some situations—homosexual contact.
Physical abuse directed towards adults can ultimately

lead to death . Approximately 50% of women murdered
in the United States were killed by a former or currentmale partner. Approximately one-third of emergencyroom consultations by women were prompted due todomestic violence. Female victims who are married alsohave a higher rate of internal injuries and unconscious-KEY TERMS
Encopresis —Abnormalities relating to bowel move-
ments that can occur as a result of stress or fear.
ness than victims of stranger assault (mugging, robbery).

Physical abuse or rape can also occur between marriedpersons and persons of the same gender. Perpetrators usu-ally sexually assault their victims to dominate, hurt, anddebase them. It is common for physical and sexual vio-lence to occur at the same time. A large percentage of sex-ually assaulted persons were also physically abused in theform of punching, beating, or threatening the victim witha weapon such as a gun or knife. Usually males who arehurt and humiliated tend to physical assault

arehurt and humiliated tend to physical assault personswhom they are intimately involved with, such as spousesand/or children. Males who assault a female tend to haveexperienced or witnessed violence during childhood.They also tend to abuse alcohol, to be sexually assaultive,and are at increased risk for assaultive behavior directedagainst children. Jealous males tend to monitor thewomen’s movements and whereabouts and to isolateother sources of protection and support. They interprettheir

of protection and support. They interprettheir behavior as betrayal of trust and this causes resent-ment and explosive anger outbursts during periods of los-ing control. Males may also use aggression againstfemales in an effort to control and intimidate partners.

Abuse in the elderly usually occurs in the frail, elderly
community. The caretaker is usually the perpetrator. Care-taker abuse can be suspected if there is evidence suggest-ing behavioral changes in the elderly person when thecaretaker is present. Additionally, elderly abuse can bepossible if there are delays between injuries and treatment,inconsistencies between injury and explanations, lack ofhygiene or clothing, and prescriptions no being filled.
Diagnosis

Diagnosis
Children who are victims of domestic violence are
frequently injured attempting to protect their motherfrom an abusive partner. Injuries are visible by inspectionor self-report. Physical abuse of an adult may be also beevident by inspection with visible cuts and/or bruises orself report.
Sexual abuse of both a child and an adult can be

diagnosed with a history from the victim. Victims can beassessed for ejaculatory evidence from the perpetrator.Ejaculatory specimens can be retrieved from the mouth,rectum, and clothing. Tests for sexually transmitted dis-
eases may be performed.
GALE ENCYCLOPEDIA OF MEDICINE 2 17AbuseGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 17

Elderly abuse can be suspected if the elderly patient
demonstrates a fear from the caretaker. Additionally,elderly abuse can be suspected if there are signs indicat-ing intentional delay of required medical care or achange in medical status.
Substance abuse can be suspected in a person who

continues to indulge in their drug of choice despite recur-rent negative consequences. The diagnosis can be madeafter administration of a comprehensive bio-psycho-social exam and standardized chemical abuse assess-ments by a therapist.
Treatment
Children who are victims of physical or sexual abuse

typically require psychological support and medical atten-tion. A complaint may be filed with the local family socialservices that will initiate investigations. The authoritieswill usually follow up the allegation or offense. Childrenmay also be referred for psychological evaluation and/ortreatment. The victim may be placed in foster care pendingthe investigation outcome. The police may also investigatephysical and sexual abuse of an adult. The victim mayrequire immediate medical care and

The victim mayrequire immediate medical care and long-term psychologi-cal treatment. It is common for children to be adverselyaffected by domestic violence situations and the local fam-ily services agency may be involved.

Substance abusers should elect treatment, either inpa-
tient or outpatient, depending on severity of addiction .
Long term treatment and/or medications may be utilized toassist in abstinence. The patient should be encouraged toparticipate in community centered support groups.
Prognosis
The prognosis depends on the diagnosis. Usually

victims of physical and sexual abuse require therapy todeal with emotional distress associated with the incident.Perpetrators require further psychological evaluation andtreatment. Victims of abuse may have a variety of emo-tional problems including depression, acts of suicide, oranxiety. Children of sexual abuse may as adults enterabusive relationships or have problems with intimacy.The substance abuser may experience relapses, since thecardinal feature of all addictive disorders is a tendency

feature of all addictive disorders is a tendency toreturn to symptoms. Elderly patients may suffer fromfurther medical problems and/or anxiety, and in somecases neglect may precipitate death.

Prevention programs are geared to education and
awareness. Detection of initial symptoms or characteris-tic behaviors may assist in some situations. In some
cases treatment may be sought before incident. The pro-fessional treating the abused persons must develop aclear sense of the relationship dynamics and the chancesfor continued harm.
Resources
BOOKS
Behrman, Richard E., et al, eds. Nelson Textbook of Pediatrics.
16th ed. W. B. Saunders Company, 2000.

Duthie, Edmund H., et al, eds. Practice of Geriatrics. 3rd ed.
W. B. Saunders Company, 1998.
Rosen, Peter. Emergency Medicine: Concepts and Clinical
Practice. 4th ed. Mosby-Year Book, Inc., 1998.
Narendra, K., and S. Lazoritz. “Physical Assessment: Evalua-
tion for Possible Physical and Sexual Abuse.” Pediatric
Clinics of North America 45 (Feb. 1998).
Stringham, P. “Mental Health: Domestic Violence.” Primary

Care; Clinics in Office Practice 26 (June 1999).
National Clearinghouse on Child Abuse and Neglect Informa-
tion. 330 C Street SW, Washington, DC 20447. (800) 392-3366.
OTHER
Elder Abuse Prevention. <http://www.oaktrees.org/elder>.National Institute on Drug Abuse. <http://www.nida.nih.gov>.
Laith Farid Gulli, M.D.
Acceleration-deceleration cervical injury
seeWhiplash
ACE inhibitors seeAngiotensin-converting
enzyme inhibitors
Acetaminophen

Acetaminophen is a medicine used to relieve pain
and reduce fever .
Purpose
Acetaminophen is used to relieve many kinds of
minor aches and pains—headaches, muscle aches, back-aches, toothaches, menstrual cramps, arthritis, and theaches and pains that often accompany colds.
GALE ENCYCLOPEDIA OF MEDICINE 2 18AcetaminophenGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 18

This drug is available without a prescription. Aceta-
minophen—or APAP—is sold under various brandnames, including Tylenol, Panadol, Aspirin Free Anacin,
and Bayer Select Maximum Strength Headache Pain
Relief Formula. Many multi-symptom cold, flu, andsinus medicines also contain acetaminophen. Check theingredients listed on the container to see if aceta-minophen is included in the product.
Studies have shown that acetaminophen relieves pain

and reduces fever about as well as aspirin. But differencesbetween these two common drugs exist. Acetaminophenis less likely than aspirin to irritate the stomach. However,unlike aspirin, acetaminophen does not reduce the red-ness, stiffness, or swelling that accompany arthritis.
Recommended dosage
The usual dosage for adults and children age 12 and

over is 325-650 mg every 4- 6 hours as needed. No morethan 4 grams (4000 mg) should be taken in 24 hours.Because the drug can potentially harm the liver, peoplewho drink alcohol in large quantities should take consid-erably less acetaminophen and possibly should avoid thedrug completely.
For children ages 6-11 years, the usual dose is 150-
300 mg, three to four times a day. Check with a physicianfor dosages for children under age 6 years.

Never take more than the recommended dosage of
acetaminophen unless told to do so by a physician ordentist.
Patients should not use acetaminophen for more than

10 days to relieve pain (5 days for children) or for morethan 3 days to reduce fever, unless directed to do so by aphysician. If symptoms do not go away—or if they getworse—contact a physician. Anyone who drinks three ormore alcoholic beverages a day should check with aphysician before using this drug and should never takemore than the recommended dosage. A risk of liver dam-age exists from combining large amounts of alcohol andacetaminophen. People who already have kidney or liverdisease or

People who already have kidney or liverdisease or liver infections should also consult with aphysician before using the drug. So should women whoare pregnant or breastfeeding.

Smoking cigarettes may interfere with the effective-
ness of acetaminophen. Smokers may need to take higherdoses of the medicine, but should not take more than therecommended daily dosage unless told by a physician todo so.KEY TERMS
Arthritis —Inflammation of the joints. The condi-
tion causes pain and swelling.
Fatigue —Physical or mental weariness.
Inflammation —A response to irritation, infection,
or injury, resulting in pain, redness, and swelling.

Many drugs can interact with one another. Consult
a physician or pharmacist before combining aceta-minophen with any other medicine. Do not use twodifferent acetaminophen-containing products at thesame time.
Acetaminophen interferes with the results of some
medical tests. Before having medical tests done, check tosee whether taking acetaminophen will affect the results.Avoiding the drug for a few days before the tests may benecessary.
Side effects
Acetaminophen causes few side effects. The most

common one is lightheadedness. Some people mayexperience trembling and pain in the side or the lowerback. Allergic reactions do occur in some people, butthey are rare. Anyone who develops symptoms such asa rash, swelling, or difficulty breathing after takingacetaminophen should stop taking the drug and getimmediate medical attention. Other rare side effectsinclude yellow skin or eyes, unusual bleeding or bruis-ing, weakness, fatigue , bloody or black stools, bloody

or cloudy urine, and a sudden decrease in the amountof urine.
Overdoses of acetaminophen may cause nausea,
vomiting, sweating, and exhaustion. Very large overdosescan cause liver damage. In case of an overdose, getimmediate medical attention.
Interactions
Acetaminophen may interact with a variety of other

medicines. When this happens, the effects of one or bothof the drugs may change or the risk of side effects maybe greater. Among the drugs that may interact withacetaminophen are alcohol, nonsteroidal anti-inflam-
matory drugs (NSAIDs) such as Motrin, oral contra-
ceptives , the antiseizure drug phenytoin (Dilantin), the
blood-thinning drug warfarin (Coumadin), the choles-terol-lowering drug cholestyramine (Questran), theantibiotic Isoniazid, and zidovudine (Retrovir, AZT).

GALE ENCYCLOPEDIA OF MEDICINE 2 19AcetaminophenGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 19

Check with a physician or pharmacist before combining
acetaminophen with any other prescription or nonpre-scription (over-the-counter) medicine.
Acetylsalicylic acid seeAspirin
Achalasia
Achalasia is a disorder of the esophagus that pre-
vents normal swallowing.
Achalasia affects the esophagus, the tube that carries

swallowed food from the back of the throat down into thestomach. A ring of muscle called the lower esophagealsphincter encircles the esophagus just above the entrance tothe stomach. This sphincter muscle is normally contractedto close the esophagus. When the sphincter is closed, thecontents of the stomach cannot flow back into the esopha-gus. Backward flow of stomach contents (reflux) can irri-tate and inflame the esophagus, causing symptoms such asheartburn . The act of swallowing causes a

esophageal contraction called peristalsis. Peristalsis pushesfood along the esophagus. Normally, peristalsis causes theesophageal sphincter to relax and allow food into the stom-ach. In achalasia, which means “failure to relax,” theesophageal sphincter remains contracted. Normal peristal-sis is interrupted and food cannot enter the stomach.
Causes
Achalasia is caused by degeneration of the nerve

cells that normally signal the brain to relax theesophageal sphincter. The ultimate cause of this degener-ation is unknown. Autoimmune disease or hidden infec-tion is suspected.
Symptoms
Dysphagia, or difficulty swallowing, is the most com-

mon symptom of achalasia. The person with achalasia usu-ally has trouble swallowing both liquid and solid foods,often feeling that food “gets stuck” on the way down. Theperson has chest pain that is often mistaken for angina
pectoris (cardiac pain). Heartburn and difficulty belchingare common. Symptoms usually get steadily worse. Othersymptoms may include nighttime cough or recurrent
pneumonia caused by food passing into the lower airways.
Diagnosis

Diagnosis
Diagnosis of achalasia begins with a careful medical
history. The history should focus on the timing of symp-toms and on eliminating other medical conditions thatmay cause similar symptoms. Tests used to diagnoseachalasia include:
• Esophageal manometry. In this test, a thin tube is
passed into the esophagus to measure the pressureexerted by the esophageal sphincter.
• X ray of the esophagus. Barium may be swallowed to

act as a contrast agent. Barium reveals the outlines ofthe esophagus in greater detail and makes it easier tosee its constriction at the sphincter.
• Endoscopy. In this test, a tube containing a lens and a
light source is passed into the esophagus. Endoscopy isused to look directly at the surface of the esophagus.This test can also detect tumors that cause symptomslike those of achalasia. Cancer of the esophagus occurs
as a complication of achalasia in 2-7% of patients.
Treatment

Treatment
The first-line treatment for achalasia is balloon dila-
tion. In this procedure, an inflatable membrane or bal-loon is passed down the esophagus to the sphincter andinflated to force the sphincter open. Dilation is effectivein about 70% of patients.
Three other treatments are used for achalasia when
balloon dilation is inappropriate or unacceptable.
• Botulinum toxin injection. Injected into the sphincter,

botulinum toxin paralyzes the muscle and allows it torelax. Symptoms usually return within one to two years.
• Esophagomyotomy. This surgical procedure cuts the
sphincter muscle to allow the esophagus to open.Esophagomyotomy is becoming more popular with thedevelopment of techniques allowing very small abdom-inal incisions.
• Drug therapy. Nifedipine, a calcium-channel blocker,

reduces muscle contraction. Taken daily, this drug pro-vides relief for about two-thirds of patients for as longas two years.
Prognosis
Most patients with achalasia can be treated effective-
ly. Achalasia does not reduce life expectancy unlessesophageal carcinoma develops.
GALE ENCYCLOPEDIA OF MEDICINE 2 20AchalasiaGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 20

There is no known way to prevent achalasia.
Resources
BOOKS
Grendell, James H., Kenneth R. McQuaid, and Scott L. Fried-
man, eds. Current Diagnosis and Treatment in Gastroen-
terology. Stamford: Appleton & Lange, 1996.
Achondroplasia
Achondroplasia is the most common cause of
dwarfism, or significantly abnormal short stature.KEY TERMS
Botulinum toxin —Any of a group of potent bacte-

rial toxins or poisons produced by different strainsof the bacterium Clostridium botulinum . The tox-
ins cause muscle paralysis.
Dysphagia —Difficulty in swallowing.
Endoscopy —A test in which a viewing device and
a light source are introduced into the esophagus bymeans of a flexible tube. Endoscopy permits visualinspection of the esophagus for abnormalities.
Esophageal manometry —A test in which a thin

tube is passed into the esophagus to measure thedegree of pressure exerted by the muscles of theesophageal wall.
Esophageal sphincter —A circular band of muscle
that closes the last few centimeters of the esopha-gus and prevents the backward flow of stomachcontents.
Esophagomyotomy —A surgical incision through
the muscular tissue of the esophagus.
Esophagus —The muscular tube that leads from the
back of the throat to the entrance of the stomach.

Peristalsis —The coordinated, rhythmic wave of
smooth muscle contraction that forces foodthrough the digestive tract.
Reflux —An abnormal backward or return flow of
a fluid.Description
Achondroplasia is one of a number of chondodystro-
phies, in which the development of cartilage, and there-fore, bone is disturbed. The disorder appears in approxi-mately one in every 10,000 births. Achondroplasia isusually diagnosed at birth, owing to the characteristicappearance of the newborn.

cartilage (a fibrous connective tissue). Over time, calci-um is deposited within the cartilage, causing it to hard-en and become bone. In achondroplasia, abnormalitiesof this process prevent the bones (especially those inthe limbs) from growing as long as they normallyshould, at the same time allowing the bones to becomeabnormally thickened. The bones in the trunk of thebody and the skull are mostly not affected, although theopening from the skull through which the spinal cordpasses (foramen

through which the spinal cordpasses (foramen magnum) is often narrower than nor-mal, and the opening (spinal canal) through which thespinal cord runs in the back bones (vertebrae) becomesincreasingly and abnormally small down the length ofthe spine.

Achondroplasia is caused by a genetic defect. It is a
dominant trait, meaning that anybody with the geneticdefect will display all the symptoms of the disorder. Aparent with the disorder has a 50% chance of passing it
GALE ENCYCLOPEDIA OF MEDICINE 2 21Achondroplasia
An x-ray image of an achondroplastic person’s head and
chest. (Custom Medical Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 21

on to the offspring. Although achondroplasia can be
passed on to subsequent offspring, the majority of casesoccur due to a new mutation (change) in a gene. Interest-ingly enough, the defect seen in achondroplasia is one ofonly a few defects known to increase in frequency withincreasing age of the father (many genetic defects arelinked to increased age of the mother).
People with achondroplasia have abnormally short

arms and legs. Their trunk is usually of normal size, as istheir head. The appearance of short limbs and normalhead size actually makes the head appear to be oversized.The bridge of the nose often has a scooped out appear-ance termed “saddle nose.” The lower back has an abnor-mal curvature, or sway back. The face often displays anoverly prominent forehead, and a relative lack of devel-opment of the face in the area of the upper jaw. Becausethe foramen magnum and spinal canal are

Becausethe foramen magnum and spinal canal are abnormallynarrowed, nerve damage may occur if the spinal cord ornerves become compressed. The narrowed foramen mag-num may disrupt the normal flow of fluid between thebrain and the spinal cord, resulting in the accumulationof too much fluid in the brain ( hydrocephalus ). Children

with achondroplasia have a very high risk of serious andrepeated middle ear infections, which can result in hear-
ing loss . The disease does not affect either mental capac-
ity, or reproductive ability.KEY TERMS
Cartilage —A flexible, fibrous type of connective tis-
sue which serves as a base on which bone is built.
Foramen magnum —The opening at the base of the
skull, through which the spinal cord and the brain-stem pass.
Hydrocephalus —An abnormal accumulation of

fluid within the brain. This accumulation can bedestructive by pressing on brain structures, anddamaging them.
Mutation —A new, permanent change in the struc-
ture of a gene, which can result in abnormal struc-ture or function somewhere in the body.
Spinal canal —The opening that runs through the
center of the column of spinal bones (vertebrae),and through which the spinal cord passes.
Vertebrae —The individual bones of the spinal col-

umn which are stacked on top of each other. Thereis a hole in the center of each bone, throughwhich the spinal cord passes.Diagnosis
Diagnosis is often made at birth due to the characteris-
tically short limbs, and the appearance of a large head. X-ray examination will reveal a characteristic appearance tothe bones, with the bones of the limbs appearing short inlength, yet broad in width. A number of measurements ofthe bones in x-ray images will reveal abnormal proportions.
Treatment

Treatment
No treatment will reverse the defect present in achon-
droplasia. All patients with the disease will be short, withabnormally proportioned limbs, trunk, and head. Treat-ment of achondroplasia primarily addresses some of thecomplications of the disorder, including problems due tonerve compression, hydrocephalus, bowed legs, andabnormal curves in the spine. Children with achondropla-sia who develop middle ear infections (acute otitis

media ) will require quick treatment with antibiotics and
careful monitoring in order to avoid hearing loss.
Prognosis
Achondroplasia is a disease which causes consider-
able deformity. However, with careful attention paid tothe development of dangerous complications (nervecompression, hydrocephalus), most people are in goodhealth, and can live a normal lifespan.
The only form of prevention is through genetic
counseling , which could help parents assess their risk of

having a child with achondroplasia.
Resources
BOOKS
Hall, Bryan D. “Achondroplasia.” In Nelson Textbook of Pedi-
atrics , ed. Richard E. Behrman. Philadelphia: W. B. Saun-
ders Co., 1996.
Horton, W. A., and J. T. Hecht. “The Chondrodysplasias.” In
Connective Tissue and Its Heritable Disorders , ed. R. M.
Royce and B. Steinmann. Somerset, NJ: Wiley-Liss, 1993.
Krane, Stephen M., and Alan L. Schiller. “Achondroplasia.” In
Harrison’s Principles of Internal Medicine , ed. Anthony

S. Fauci, et al. New York: McGraw-Hill, 1997.
Whyte, Michael, P. “Achondroplasia.” In Cecil Textbook of
Medicine , ed. J. Claude Bennett and Fred Plum. Philadel-
phia: W. B. Saunders Co., 1996.
Little People of America, c/o Mary Carten. 7238 Piedmont
Drive, Dallas, TX 75227-9324. (800) 243-9273.
Rosalyn Carson-DeWitt, MD
GALE ENCYCLOPEDIA OF MEDICINE 2 22AchondroplasiaGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 22

Achromatopsia seeColor blindness
Acid indigestion seeHeartburn
Acid phosphatase test
Acid phosphatase is an enzyme found throughout
the body, but primarily in the prostate gland. Like allenzymes, it is needed to trigger specific chemical reac-tions. Acid phosphatase testing is done to diagnosewhether prostate cancer has spread to other parts of the

body (metastasized), and to check the effectiveness oftreatment. The test has been largely supplanted by theprostate specific antigen test (PSA).
Purpose
The male prostate gland has 100 times more acid
phosphatase than any other body tissue. When prostatecancer spreads to other parts of the body, acid phos-

phatase levels rise, particularly if the cancer spreads tothe bone. One-half to three-fourths of persons who havemetastasized prostate cancer have high acid phosphataselevels. Levels fall after the tumor is removed or reducedthrough treatment.
Tissues other than prostate have small amounts of
acid phosphatase, including bone, liver, spleen, kidney,and red blood cells and platelets. Damage to these tissuescauses a moderate increase in acid phosphatase levels.

Acid phosphatase is very concentrated in semen.
Rape investigations will often include testing for thepresence of acid phosphatase in vaginal fluid.
This is not a screening test for prostate cancer. Acid
phosphatase levels rise only after prostate cancer hasmetastasized.
Laboratory testing measures the amount of acid

phosphatase in a person’s blood, and can determine fromwhat tissue the enzyme is coming. For example, it isimportant to know if the increased acid phosphatase isfrom the prostate or red blood cells. Acid phosphatasefrom the prostate, called prostatic acid phosphatase(PAP), is the most medically significant type of acidphosphatase.KEY TERMS
Enzyme —A substance needed to trigger specific
chemical reactions.

Metastasize —Spread to other parts of the body;
usually refers to cancer.
Prostate gland —A gland of the male reproductive
system.
Subtle differences between prostatic acid phos-

phatase and acid phosphatases from other tissues causethem to react differently in the laboratory when mixedwith certain chemicals. For example, adding the chemi-cal tartrate to the test mixture inhibits the activity of pro-static acid phosphatase but not red blood cell acid phos-phatase. Laboratory test methods based on these differ-ences reveal how much of a person’s total acid phos-phatase is derived from the prostate. Results are usuallyavailable the next day.

This test requires drawing about 5-10 mL of blood.
The patient should not have a rectal exam or prostatemassage for two to three days prior to the test.
Aftercare
Discomfort or bruising may occur at the puncture
site, and the person may feel dizzy or faint. Applyingpressure to the puncture site until the bleeding stops willreduce bruising. Warm packs to the puncture site willrelieve discomfort.
Normal results vary based on the laboratory and the
method used.

The highest levels of acid phosphatase are found in
metastasized prostate cancer. Diseases of the bone, suchas Paget’s disease or hyperparathyroidism ; diseases of
blood cells, such as sickle cell disease or multiple
myeloma ; or lysosomal disorders, such as Gaucher’s dis-
ease, will show moderately increased levels.
Certain medications can cause temporary increases

or decreases in acid phosphatase levels. Manipulation ofthe prostate gland through massage, biopsy, or rectalexam before a test can increase the level.
GALE ENCYCLOPEDIA OF MEDICINE 2 23Acid phosphatase testGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 23

Resources
BOOKS
A Manual of Laboratory and Diagnostic Tests. 5th ed. Ed.
Francis Fishback. Philadelphia: Lippincott, 1996.
Garza, Diana, and Kathleen Becan-McBride. Phlebotomy
Handbook. 4th ed. Stamford: Appleton & Lange, 1996.
Moul, Judd W., et al. “The Contemporary Value of Pretreat-
ment Prostatic Acid Phosphatase to Predict PathologicalStage and Recurrence in Radical Prostatectomy Cases.”Journal of Urology (Mar. 1998): 935-940.
Acid reflux seeHeartburn

Acidosis seeRespiratory acidosis; Renal
tubular acidosis; Metabolic acidosis
Acne
Acne is a common skin disease characterized by
pimples on the face, chest, and back. It occurs when thepores of the skin become clogged with oil, dead skincells, and bacteria.
Acne vulgaris, the medical term for common acne, is

the most common skin disease. It affects nearly 17 millionpeople in the United States. While acne can arise at anyage, it usually begins at puberty and worsens during ado-
lescence. Nearly 85% of people develop acne at some timebetween the ages of 12-25 years. Up to 20% of womendevelop mild acne. It is also found in some newborns.
The sebaceous glands lie just beneath the skin’s sur-

face. They produce an oil called sebum, the skin’s naturalmoisturizer. These glands and the hair follicles withinwhich they are found are called sebaceous follicles.These follicles open onto the skin through pores. Atpuberty, increased levels of androgens (male hormones)cause the glands to produce too much sebum. Whenexcess sebum combines with dead, sticky skin cells, ahard plug, or comedo, forms that blocks the pore. Mildnoninflammatory acne consists of the two types of come-dones, whiteheads

Moderate and severe inflammatory types of acne
result after the plugged follicle is invaded by Propioni-
bacterium acnes , a bacteria that normally lives on theskin. A pimple forms when the damaged follicle weakens

and bursts open, releasing sebum, bacteria, and skin andwhite blood cells into the surrounding tissues. Inflamedpimples near the skin’s surface are called papules; whendeeper, they are called pustules. The most severe type ofacne consists of cysts (closed sacs) and nodules (hardswellings). Scarring occurs when new skin cells are laiddown to replace damaged cells.
The most common sites of acne are the face, chest,

shoulders, and back since these are the parts of the bodywhere the most sebaceous follicles are found.
The exact cause of acne is unknown. Several risk
factors have been identified:
• Age. Due to the hormonal changes they experience,
teenagers are more likely to develop acne.
• Gender. Boys have more severe acne and develop it
more often than girls.
• Disease. Hormonal disorders can complicate acne in
girls.
• Heredity. Individuals with a family history of acne have

greater susceptibility to the disease.
• Hormonal changes. Acne can flare up before menstrua-
tion, during pregnancy , and menopause .
• Diet. No foods cause acne, but certain foods may cause
flare-ups.
• Drugs. Acne can be a side effect of drugs including
tranquilizers, antidepressants, antibiotics ,oral contra-
ceptives , and anabolic steroids.
• Personal hygiene. Abrasive soaps, hard scrubbing, or
picking at pimples will make them worse.
• Cosmetics. Oil-based makeup and hair sprays worsen

acne.
• Environment. Exposure to oils and greases, polluted air,
and sweating in hot weather aggravate acne.
•Stress . Emotional stress may contribute to acne.
Acne is usually not conspicuous, although inflamed
lesions may cause pain , tenderness, itching , or swelling.

The most troubling aspects of these lesions are the nega-tive cosmetic effects and potential for scarring. Somepeople, especially teenagers, become emotionally upsetabout their condition, and have problems forming rela-tionships or keeping jobs.
Diagnosis
Acne patients are often treated by family doctors.
Complicated cases are referred to a dermatologist, a skin
GALE ENCYCLOPEDIA OF MEDICINE 2 24AcneGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 24

disease specialist, or an endocrinologist, a specialist who
treats diseases of the body’s endocrine (hormones andglands) system.
Acne has a characteristic appearance and is not diffi-
cult to diagnose. The doctor takes a complete medicalhistory, including questions about skin care, diet, factorscausing flare-ups, medication use, and prior treatment.Physical examination includes the face, upper neck,

chest, shoulders, back, and other affected areas. Undergood lighting, the doctor determines what types and howmany blemishes are present, whether they are inflamed,whether they are deep or superficial, and whether there isscarring or skin discoloration.
In teenagers, acne is often found on the forehead,

nose, and chin. As people get older, acne tends to appeartowards the outer part of the face. Adult women mayhave acne on their chins and around their mouths. Theelderly may develop whiteheads and blackheads on theupper cheeks and skin around the eyes.
Laboratory tests are not done unless the patient
appears to have a hormonal disorder or other medicalproblem. In this case, blood analyses or other tests maybe ordered. Most insurance plans cover the costs of diag-nosing and treating acne.

Treatment
Acne treatment consists of reducing sebum produc-
tion, removing dead skin cells, and killing bacteria withtopical drugs and oral medications. Treatment choicedepends upon whether the acne is mild, moderate, orsevere.
Drugs
TOPICAL DRUGS. Treatment for mild noninflamma-

tory acne consists of reducing the formation of newcomedones with topical tretinoin, benzoyl peroxide, ada-palene, or salicylic acid. Tretinoin is especially effectivebecause it increases turnover ( death and replacement) of
skin cells. When complicated by inflammation, topicalantibiotics may be added to the treatment regimen.Improvement is usually seen in two to four weeks.
Topical medications are available as cream, gel,

lotion, or pad preparations of varying strengths. Theyinclude antibiotics (agents that kill bacteria), such as ery-thromycin, clindamycin (Cleocin-T), and meclocycline(Meclan); comedolytics (agents that loosen hard plugsand open pores) such as the vitamin A acid tretinoin(Retin-A), salicylic acid, adapalene (Differin), resorci-nol, and sulfur. Drugs that act as both comedolytics andantibiotics, such as benzoyl peroxide, azelaic acid(Azelex), or benzoyl peroxide plus erythromycin (Benza-mycin),

benzoyl peroxide plus erythromycin (Benza-mycin), are also used. These drugs may be used for

months to years to achieve disease control.
After washing with mild soap, the drugs are applied
alone or in combination, once or twice a day over theentire affected area of skin. Possible side effects includemild redness, peeling, irritation, dryness, and an increasedsensitivity to sunlight that requires use of a sunscreen.
ORAL DRUGS. Oral antibiotics are taken daily for

two to four months. The drugs used include tetracycline,erythromycin, minocycline (Minocin), doxycycline, clin-damycin (Cleocin), and trimethoprim- sulfamethoxazole(Bactrim, Septra). Possible side effects include allergicreactions, stomach upset, vaginal yeast infections, dizzi-
ness, and tooth discoloration.
The goal of treating moderate acne is to decrease

inflammation and prevent new comedone formation. Oneeffective treatment is topical tretinoin along with a topical
GALE ENCYCLOPEDIA OF MEDICINE 2 25Acne
Acne vulgaris affecting a woman’s face. Acne is the general
name given to a skin disorder in which the sebaceousglands become inflamed. (Photograph by Biophoto Associ-
ates, Photo Researchers, Inc. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 25

or oral antibiotic. A combination of topical benzoyl per-
oxide and erythromycin is also very effective. Improve-ment is normally seen within four to six weeks, but treat-ment is maintained for at least two to four months.
A drug reserved for the treatment of severe acne, oral

isotretinoin (Accutane), reduces sebum production andcell stickiness. It is the treatment of choice for severe acnewith cysts and nodules, and is used with or without topicalor oral antibiotics. Taken for four to five months, it pro-vides long-term disease control in up to 60% of patients. Ifthe acne reappears, another course of isotretinoin may beneeded by about 20% of patients, while another 20% maydo well with topical drugs or oral antibiotics. Side effectsinclude temporary worsening of the

Side effectsinclude temporary worsening of the acne, dry skin, nose-bleeds, vision disorders, and elevated liver enzymes, bloodfats and cholesterol. This drug must not be taken duringpregnancy since it causes birth defects .

Anti-androgens, drugs that inhibit androgen produc-
tion, are used to treat women who are unresponsive toother therapies. Certain types of oral contraceptives (forKEY TERMS
Androgens —Male sex hormones that are linked
with the development of acne.
Antiandrogens —Drugs that inhibit the production
of androgens.
Antibiotics —Medicines that kill bacteria.
Comedo —A hard plug composed of sebum and
dead skin cells. The mildest type of acne.
Comedolytic —Drugs that break up comedones

and open clogged pores.
Corticosteroids —A group of hormones produced
by the adrenal glands with different functions,including regulation of fluid balance, androgenactivity, and reaction to inflammation.
Estrogens —Hormones produced by the ovaries,
the female sex glands.
Isotretinoin —A drug that decreases sebum pro-
duction and dries up acne pimples.
Sebaceous follicles —A structure found within the

skin that houses the oil-producing glands and hairfollicles, where pimples form.
Sebum —An oily skin moisturizer produced by
sebaceous glands.
Tretinoin —A drug that works by increasing the
turnover (death and replacement) of skin cells.example, Ortho-Tri-Cyclen) and female sex hormones
(estrogens) reduce hormone activity in the ovaries. Otherdrugs, for example, spironolactone and corticosteroids ,

reduce hormone activity in the adrenal glands. Improve-ment may take up to four months.
Oral corticosteroids, or anti-inflammatory drugs, are
the treatment of choice for an extremely severe, but raretype of destructive inflammatory acne called acne fulmi-nans, found mostly in adolescent males. Acne congloba-ta, a more common form of severe inflammation, is char-acterized by numerous, deep, inflammatory nodules thatheal with scarring. It is treated with oral isotretinoin andcorticosteroids.

Other treatments
Several surgical or medical treatments are available
to alleviate acne or the resulting scars:
• Comedone extraction. The comedo is removed from the
pore with a special tool.
• Chemical peels. Glycolic acid is applied to peel off the
top layer of skin to reduce scarring.
• Dermabrasion. The affected skin is frozen with a chem-
ical spray, and removed by brushing or planing.
• Punch grafting. Deep scars are excised and the area
repaired with small skin grafts.

• Intralesional injection. Corticosteroids are injected
directly into inflamed pimples.
• Collagen injection. Shallow scars are elevated by colla-
gen (protein) injections.
Alternative treatments for acne focus on proper
cleansing to keep the skin oil-free; eating a well-bal-anced diet high in fiber, zinc, and raw foods; and avoid-ing alcohol, dairy products, smoking ,caffeine ,

sugar,processed foods, and foods high in iodine, such assalt. Supplementation with herbs such as burdock root(Arctium lappa ), red clover ( Trifolium pratense ), and
milk thistle ( Silybum marianum ), and with nutrients such
as essential fatty acids, vitamin B complex, zinc, vitaminA, and chromium is also recommended. Chinese herbalremedies used for acne include cnidium seed ( Cnidium
monnieri ) and honeysuckle flower ( Lonicera japonica ).

Wholistic physicians or nutritionists can recommend theproper amounts of these herbs.
Prognosis
Acne is not curable, although long-term control is
achieved in up to 60% of patients treated with
GALE ENCYCLOPEDIA OF MEDICINE 2 26AcneGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 26

isotretinoin. It can be controlled by proper treatment,
with improvement taking two or more months. Acnetends to reappear when treatment stops, but spontaneous-ly improves over time. Inflammatory acne may leavescars that require further treatment.
There are no sure ways to prevent acne, but the fol-
lowing steps may be taken to minimize flare-ups:
• gentle washing of affected areas once or twice every day
• avoid abrasive cleansers
• use noncomedogenic makeup and moisturizers

• shampoo often and wear hair off face
• eat a well-balanced diet, avoiding foods that trigger
flare-ups
• unless told otherwise, give dry pimples a limited
amount of sun exposur
• do not pick or squeeze blemishes
• reduce stress
Resources
BOOKS
Balch, James F., and Phyllis A. Balch. “The Disorders: Acne.”
In Prescription for Nutritional Healing , ed. Amy C. Teck-
lenburg, et al. New York: Avery Publishing Group, 1997.

Bark, Joseph P. Your Skin: An Owner’s Guide. Englewood
Cliffs, NJ: Prentice Hall, 1995.
Goldstein, Sanford M., and Richard B. Odom. “Skin &
Appendages: Pustular Disorders.” In Current Medical
Diagnosis and Treatment, 1996. 35th ed. Ed. Stephen
McPhee, et al. Stamford: Appleton & Lange, 1995.
Kaptchuk, Ted J., Z’ev Rosenberg, and K’an Herb Co., Inc.
K’an Herbals: Formulas by Ted Kaptchuk, O.M.D. San
Francisco: Andrew Miller, 1996.

“Adult Acne.” Harvard Women’s Health Watch (Mar. 1995): 4-
5.
Bergfeld, Wilma F. “The Evaluation and Management of Acne:
Economic Considerations.” Journal of the American
Academy of Dermatology 32 (1995): S52-6.
Billings, Laura. “Getting Clear.” Health Magazine , Apr. 1997,
48-52.
Christiano, Donna. “Acne Treatment Meant for Grown- Ups.”
American Health (Oct. 1994): 23-4.
“Clearly Better New Treatments Help Adult Acne.” Prevention

Magazine , Aug. 1997, 50-51.
Leyden, James J. “Therapy For Acne Vulgaris.” New England
Journal of Medicine 17 (Apr. 1997): 1156-1162.
Nguyen, Quan H., Y . Alyssa Kim, and Robert A. Schwartz.
“Management of Acne Vulgaris.” American Family Physi-
cian (July 1994): 89-96.
“Pimple Control Pill?” Prevention Magazine , May 1997, 132.ORGANIZATIONS
American Academy of Dermatology. 930 N. Meacham Road,
P.O. Box 4014, Schaumburg, IL 60168-4014. (847) 330-0230. <http://www.aad.org>.

Acne rosacea seeRosacea
Acoustic neurinoma seeAcoustic neuroma
Acoustic neuroma
An acoustic neuroma is a benign tumor involving
cells of the myelin sheath that surrounds the vestibulo-cochlear nerve (eighth cranial nerve).
The vestibulocochlear nerve extends from the inner

ear to the brain and is made up of a vestibular branch,often called the vestibular nerve, and a cochlear branch,called the cochlear nerve. The vestibular and cochlearnerves lie next to one another. They also run along sideother cranial nerves. People possess two of each type ofvestibulocochlear nerve, one that extends from the leftear and one that extends from the right ear.
The vestibular nerve transmits information concern-

ing balance from the inner ear to the brain and the cochlearnerve transmits information about hearing. The vestibularnerve, like many nerves, is surrounded by a cover called amyelin sheath. A tumor, called a schwannoma, can some-times develop from the cells of the myelin sheath. A tumoris an abnormal growth of tissue that results from theuncontrolled growth of cells. Acoustic neuromas are oftencalled vestibular schwannomas because they are tumorsthat arise from the myelin sheath that surrounds

arise from the myelin sheath that surrounds thevestibular nerve. Acoustic neuromas are consideredbenign (non-cancerous) tumors since they do not spread toother parts of the body. They can occur anywhere alongthe vestibular nerve but are most likely to occur where thevestibulocochlear nerve passes through the tiny bony canalthat connects the brain and the inner ear.

An acoustic neuroma can arise from the left vestibu-
lar nerve or the right vestibular nerve. A unilateral tumoris a tumor arising from one nerve and a bilateral tumorarises from both vestibular nerves. Unilateral acousticneuromas usually occur spontaneously (by chance). Bilat-eral acoustic neuromas occur as part of a hereditary con-
GALE ENCYCLOPEDIA OF MEDICINE 2 27Acoustic neuromaGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 27

dition called Neurofibromatosis Type 2 (NF2). A person
with NF2 has inherited a predisposition for developingacoustic neuromas and other tumors of the nerve cells.
Acoustic neuromas usually grow slowly and can

take years to develop. Some acoustic neuromas remainso small that they do not cause any symptoms. As theacoustic neuroma grows it can interfere with the func-tioning of the vestibular nerve and can cause vertigo andbalance difficulties. If the acoustic nerve grows largeenough to press against the cochlear nerve, then hearing
lossand a ringing ( tinnitus ) in the affected ear will usu-

ally occur. If untreated and the acoustic neuroma contin-ues to grow it can press against other nerves in the regionand cause other symptoms. This tumor can be life threat-ening if it becomes large enough to press against andinterfere with the functioning of the brain.
Causes
An acoustic neuroma is caused by a change or

absence of both of the NF2 tumor suppressor genes in anerve cell. Every person possesses a pair of NF2 genes inevery cell of their body including their nerve cells. OneNF2 gene is inherited from the egg cell of the mother andone NF2 gene is inherited from the sperm cell of thefather. The NF2 gene is responsible for helping to pre-vent the formation of tumors in the nerve cells. In partic-ular the NF2 gene helps to prevent acoustic neuromas.

necessary to prevent the formation of an acoustic neuro-ma. If both NF2 genes become changed or missing inone of the myelin sheath cells of the vestibular nervethen an acoustic neuroma will usually develop. Most uni-lateral acoustic neuromas result when the NF2 genesbecome spontaneously changed or missing. Someonewith a unilateral acoustic neuroma that has developedspontaneously is not at increased risk for having childrenwith an acoustic neuroma. Some unilateral acoustic neu-romas result from

Some unilateral acoustic neu-romas result from the hereditary condition NF2. It is alsopossible that some unilateral acoustic neuromas may becaused by changes in other genes responsible for pre-venting the formation of tumors.

affected with the hereditary condition NF2. A person withNF2 is typically born with one unchanged and onechanged or missing NF2 gene in every cell of their body.Sometimes they inherit this change from their mother orfather. Sometimes the change occurs spontaneously whenthe egg and sperm come together to form the first cell ofthe baby. The children of a person with NF2 have a 50%chance of inheriting the changed or missing NF2 gene.A person with NF2 will develop an acoustic neuro-

ma if the remaining unchanged NF2 gene becomes spon-taneously changed or missing in one of the myelin sheathcells of their vestibular nerve. People with NF2 oftendevelop acoustic neuromas at a younger age. The meanage of onset of acoustic neuroma in NF2 is 31 years ofage versus 50 years of age for sporadic acoustic neuro-mas. Not all people with NF2, however, develop acousticneuromas. People with NF2 are at increased risk fordeveloping cataracts and tumors in other nerve cells.

not affected with NF2. Some people with NF2, however,only develop a tumor in one of the vestibulocochlearnerves. Others may initially be diagnosed with a unilater-al tumor but may develop a tumor in the other nerve anumber of years later. NF2 should be considered in some-one under the age of 40 who has a unilateral acoustic neu-roma. Someone with a unilateral acoustic neuroma andother family members diagnosed with NF2 probably isaffected with NF2. Someone with a unilateral acousticneuroma and

Someone with a unilateral acousticneuroma and other symptoms of NF2 such as cataractsand other tumors may also be affected with NF2. On theother hand, someone over the age of 50 with a unilateralacoustic neuroma, no other tumors and no family historyof NF2 is very unlikely to be affected with NF2.

the functioning of the vestibulocochlear nerve. The mostcommon first symptom of an acoustic neuroma is hearingloss, which is often accompanied by a ringing sound (tin-nitis). People with acoustic neuromas sometimes reportdifficulties in using the phone and difficulties in perceivingthe tone of a musical instrument or sound even when theirhearing appears to be otherwise normal. In most cases thehearing loss is initially subtle and worsens gradually overtime until deafness occurs in the affected

overtime until deafness occurs in the affected ear. In approxi-mately 10% of cases the hearing loss is sudden and severe.

Acoustic neuromas can also affect the functioning of
the vestibular branch of the vestibulocochlear nerve andvan cause vertigo and dysequilibrium. Twenty percent ofsmall tumors are associated with periodic vertigo, whichis characterized by dizziness or a whirling sensation.

Larger acoustic neuromas are less likely to cause vertigobut more likely to cause dysequilibrium. Dysequilibrium,which is characterized by minor clumsiness and a gener-al feeling of instability, occurs in nearly 50% of peoplewith an acoustic neuroma.
As the tumor grows larger it can press on the surround-
ing cranial nerves. Compression of the fifth cranial nervecan result in facial pain and or numbness. Compression of
the seventh cranial nerve can cause spasms, weakness or

GALE ENCYCLOPEDIA OF MEDICINE 2 28Acoustic neuromaGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 28

paralysis of the facial muscles. Double vision is a rare
symptom but can result when the 6th cranial nerve is affect-ed. Swallowing and/or speaking difficulties can occur if thetumor presses against the 9th, 10th, or 12th cranial nerves.
If left untreated, the tumor can become large enough

to press against and affect the functioning of the brainstem. The brain stem is the stalk like portion of the brainthat joins the spinal cord to the cerebrum, the thinking andreasoning part of the brain. Different parts of the brain-stem have different functions such as the control of breath-ing and muscle coordination. Large tumors that impact thebrain stem can result in headaches, walking difficulties(gait ataxia) and involuntary shaking movements of themuscles ( tremors ). In rare cases when

of themuscles ( tremors ). In rare cases when an acoustic neuro-

ma remains undiagnosed and untreated it can cause nau-sea, vomiting, lethargy and eventually coma , respiratory
difficulties and death . In the vast majority of cases, how-
ever, the tumor is discovered and treated long before it islarge enough to cause such serious manifestations.
Diagnosis
Anyone with symptoms of hearing loss should under-
go hearing evaluations. Pure tone and speech audiometryKEY TERMS
Benign tumor —A localized overgrowth of cells that

does not spread to other parts of the body.
Chromosome —A microscopic structure, made of a
complex of proteins and DNA, that is found withineach cell of the body.
Computed tomography (CT) —An examination that
uses a computer to compile and analyze the imagesproduced by x rays projected at a particular part ofthe body.
Cranial nerves —The set of twelve nerves found on

each side of the head and neck that control the sen-sory and muscle functions of a number of organssuch as the eyes, nose, tongue face and throat.
DNA testing —Testing for a change or changes in a
gene or genes.
Gene —A building block of inheritance, made up of
a compound called DNA (deoxyribonucleic acid)and containing the instructions for the productionof a particular protein. Each gene is found on a spe-cific location on a chromosome.

Magnetic resonance imaging (MRI) —A test whichuses an external magnetic field instead of x rays to
visualize different tissues of the body.
Myelin sheath —The cover that surrounds many
nerve cells and helps to increase the speed bywhich information travels along the nerve.
Neurofibromatosis type 2 (NF2) —A hereditary
condition associated with an increased risk of bilat-eral acoustic neuromas, other nerve cell tumors andcataracts.
Protein —A substance produced by a gene that is

involved in creating the traits of the human bodysuch as hair and eye color or is involved in control-ling the basic functions of the human body.
Schwannoma —A tumor derived from the cells of
the myelin sheath that surrounds many nerve cells.
Tinnitus —A ringing sound or other noise in the ear.
Vertigo —A feeling of spinning or whirling.
Vestibulocochlear nerve (Eighth cranial nerve) —

Nerve that transmits information, about hearing andbalance from the ear to the brain.
are two screening tests that are often used to evaluate hear-

ing. Pure tone audiometry tests to see how well someonecan hear tones of different volume and pitch and speechaudiometry tests to see how well someone can hear andrecognize speech. An acoustic neuroma is suspected insomeone with unilateral hearing loss or hearing loss that isless severe in one ear than the other ear(asymmetrical).
Sometimes an auditory brainstem response (ABR,

BAER) test is performed to help establish whethersomeone is likely to have an acoustic neuroma. Duringthe ABR examination, a harmless electrical impulse ispassed from the inner ear to the brainstem. An acousticneuroma can interfere with the passage of this electri-cal impulse and this interference can, sometimes beidentified through the ABR evaluation. A normal ABRexamination does not rule out the possibility of anacoustic neuroma. An abnormal ABR examinationincreases the likelihood that an

ABR examinationincreases the likelihood that an acoustic neuroma ispresent but other tests are necessary to confirm thepresence of a tumor.

If an acoustic neuroma is strongly suspected then
magnetic resonance imaging (MRI) is usually per-
formed. The MRI is a very accurate evaluation that is
GALE ENCYCLOPEDIA OF MEDICINE 2 29Acoustic neuromaGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 29

able to detect nearly 100% of acoustic neuromas. Com-
puterized tomography (CT scan, CAT scan)is unable toidentify smaller tumors; but it can be used when anacoustic neuroma is suspected and an MRI evaluationcannot be performed.
Once an acoustic neuroma is diagnosed, an evalua-

tion by genetic specialists such as a geneticist and genet-ic counselor may be recommended. The purpose of thisevaluation is to obtain a detailed family history andcheck for signs of NF2. If NF2 is strongly suspectedthen DNA testing may be recommended. DNA testinginvolves checking the blood cells obtained from a rou-tine blood draw for the common gene changes associat-ed with NF2.
Treatment
The three treatment options for acoustic neuroma

are surgery, radiation, and observation. The physicianand patient should discuss the pros and cons of the differ-ent options prior to making a decision about treatment.The patient’s, physical health, age, symptoms, tumorsize, and tumor location should be considered.
Microsurgery
The surgical removal of the tumor or tumors is the

most common treatment for acoustic neuroma. In mostcases the entire tumor is removed during the surgery. Ifthe tumor is large and causing significant symptoms, yetthere is a need to preserve hearing in that ear, then onlypart of the tumor may be removed. During the procedurethe tumor is removed under microscopic guidance andgeneral anesthetic. Monitoring of the neighboring cranialnerves is done during the procedure so that damage tothese nerves can be prevented. If preservation of hearingis a

can be prevented. If preservation of hearingis a possibility, then monitoring of hearing will also takeplace during the surgery.

Most people stay in the hospital four to seven days
following the surgery. Total recovery usually takes fourto six weeks. Most people experience fatigue and head

discomfort following the surgery. Problems with balanceand head and neck stiffness are also common. The mor-tality rate of this type of surgery is less than 2% at mostmajor centers. Approximately 20% of patients experi-ence some degree of post-surgical complications. In mostcases these complications can be managed successfullyand do not result in long term medical problems. Surgerybrings with it a risk of stroke , damage to the brain stem,

infection, leakage of spinal fluid and damage to the cra-nial nerves. Hearing loss and/or tinnitis often result fromthe surgery. A follow-up MRI is recommended one tofive years following the surgery because of possibleregrowth of the tumor.Stereotactic Radiation therapy
During stereotactic radiation therapy , also called

radiosurgery or radiotherapy, many small beams of radia-tion are aimed directly at the acoustic neuroma. The radi-ation is administered in a single large dose, under localanesthetic and is performed on an outpatient basis. Thisresults in a high dose of radiation to the tumor but littleradiation exposure to the surrounding area. This treat-ment approach is limited to small or medium tumors.The goal of the surgery is to cause tumor shrinkage or atleast limit the growth of the tumor. The long term

limit the growth of the tumor. The long term effica-cy and risks of this treatment approach are not known.Periodic MRI monitoring throughout the life of thepatient is therefore recommended.

sometimes occurs even years later. Radiation therapy canalso cause damage to neighboring cranial nerves, whichcan result in symptoms such as numbness, pain or paralysisof the facial muscles. In many cases these symptoms aretemporary. Radiation treatment can also induce the forma-tion of other benign or malignant schwannomas. This typeof treatment may therefore be contraindicated in the treat-ment of acoustic neuromas in those with NF2 who are pre-disposed to developing schwannomas and other

some cases they will stop growing and even becomesmaller or disappear entirely. It may therefore be appro-priate in some cases to hold off on treatment and to peri-odically monitor the tumor through MRI evaluations.Long-term observation may be appropriate for examplein an elderly person with a small acoustic neuroma andfew symptoms. Periodic observation may also be indicat-ed for someone with a small and asymptomatic acousticneuroma that was detected through an evaluation foranother medical

detected through an evaluation foranother medical problem. Observation may also be sug-gested for someone with an acoustic neuroma in the onlyhearing ear or in the ear that has better hearing. The dan-ger of an observational approach is that as the tumorgrows larger it can become more difficult to treat.

neuroma is usually quite good provided the tumor is diag-nosed early and appropriate treatment is instituted. Longterm hearing loss and tinnitis in the affected ear are com-mon, even if appropriate treatment is provided. Regrowth ofthe tumor is also a possibility following surgery or radiationtherapy and repeat treatment may be necessary. The progno-sis can be poorer for those with NF2 who have an increasedrisk of bilateral acoustic neuromas and other tumors.

GALE ENCYCLOPEDIA OF MEDICINE 2 30Acoustic neuromaGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 30

Resources
BOOKS
Filipo, R., and Barbara Maurizio Acoustic neuroma: trends and
controversies: proceedings of the Symposium AcousticNeuroma: Trends and Controversies, Rome, Italy, Novem-ber 13–15, 1997. The Hague, Netherlands: Kugler,1999.
Malis, Leonard Acoustic Neuroma New York: Elsevier, 1998.
Roland, Peter, and Bradley Marple. Diagnosis and Manage-
ment of Acoustic Neuroma (Sipac). Alexandria, V A:
American Academy of Otolaryngology—Head and NeckSurvey Foundation, 1998.

Broad, R. W. “Management of Acoustic Neuroma.” In New
England Journal of Medicine. 340(14) (8 April
1999):1119.
Lederman G, E. Arbit, and J. Lowry. “Management of Acoustic
Neuroma.” New England Journal of Medicine. 340(14) (8
April 1999):1119–1120.
Levo H., I. Pyykko, and G. Blomstedt. “Non-surgical Treat-
ment of Vestibular Schwannoma Patients.” Acta Oto-
Laryngologica 529 (1997): 56–8.
O’Donoghue G.M., T. Nikolopoulos and J. Thomsen. “Man-

agement of Acoustic Neuroma.” In New England Journal
of Medicine 340(14) (8 April 1999):1120–1121.
Rigby, P. L., et al. “Acoustic Neuroma Surgery: Outcome
Analysis of Patient-Perceived Disability.” In American
Journal of Otology 18 (July 1997): 427–35.
van Roijen, L., et al. “Costs and Effects of Microsurgery versus
Radiosurgery in Treating Acoustic Neuroma.” In Acta
Neurochirurgica 139 (1997): 942–48.
Acoustic Neuroma Association. 600 Peachtree Pkwy, Suite

108, Cumming, GA 30041-6899. Phone:(770) 205-8211.Fax: (770) 205-0239. ANAusa@aol.com <http://anausa.org>. 28 June 2001.
Acoustic Neuroma Association of Canada Box 369, Edmonton,
AB T5J 2J6. 1-800-561-ANAC(2622). (780)428-3384.anac@compusmart.ab.ca. <http://www.anac.ca>. 28 June2001.
British Acoustic Neuroma Association. Oak House, Ransom

Wood Business Park, Southwell Road West, Mansfield,Nottingham, NG21 0HJ. Tel: 01623 632143. Fax: 01623635313. bana@btclick.com. <http://www.ukan.co.uk/bana>. 28 June 2001.
Seattle Acoustic Neuroma Group. Emcityland@aol.com
<http://acousticneuromaseattle.org/entryenglish.html>. 28June 2001.
OTHER
National Institute of Health Consensus Statement Online.
Acoustic Neuroma 9(4)(11-13 December 1991). <http://
text.nlm.nih.gov/nih/cdc/www/87txt.html>. (28 June 2001).

University of California at San Francisco (UCSF). Information
on Acoustic Neuromas (28 June 2001). <http://itsa.ucsf.
edu/~rkj/IndexAN. html>.
Lisa Andres, M.S., CGCAcquired hypogammaglobulinemia see
Common variable immunodeficiency
Acquired immunodeficiency syndrome see
AIDS
Acrocyanosis
Acrocyanosis is a decrease in the amount of oxygen

delivered to the extremities. The hands and feet turn bluebecause of the lack of oxygen. Decreased blood supplyto the affected areas is caused by constriction or spasm ofsmall blood vessels.
Acrocyanosis is a painless disorder caused by constric-

tion or narrowing of small blood vessels in the skin of affect-ed patients. The spasm of the blood vessels decreases theamount of blood that passes through them, resulting in lessblood being delivered to the hands and feet. The hands maybe the main area affected. The affected areas turn blue andbecome cold and sweaty. Localized swelling may also occur.Emotion and cold temperatures can worsen the symptoms,while warmth can decrease symptoms. The disease is seenmainly in women and the effect of

disease is seenmainly in women and the effect of the disorder is mainlycosmetic. People with the disease tend to be uncomfortable,with sweaty, cold, bluish colored hands and feet.

The sympathetic nerves cause constriction or spasms

in the peripheral blood vessels that supply blood to theextremities. The spasms are a contraction of the musclesin the walls of the blood vessels. The contractiondecreases the internal diameter of the blood vessels,thereby decreasing the amount of blood flow through theaffected area. The spasms occur on a persistent basis,resulting in long term reduction of blood supply to thehands and feet. Sufficient blood still passes through theblood vessels so that the tissue in the affected areas doesnot

so that the tissue in the affected areas doesnot starve for oxygen or die. Mainly, blood vessels nearthe surface of the skin are affected.

Diagnosis
Diagnosis is made by observation of the main clini-
cal symptoms, including persistently blue and sweatyhands and/or feet and a lack of pain . Cooling the hands
increases the blueness, while warming the hands decreas-
GALE ENCYCLOPEDIA OF MEDICINE 2 31AcrocyanosisGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 31

es the blue color. The acrocyanosis patient’s pulse is nor-
mal, which rules out obstructive diseases. Raynaud’s dis-
ease differs from acrocyanosis in that it causes white and
red skin coloration phases, not just bluish discoloration.
Treatment
Acrocyanosis usually isn’t treated. Drugs that block
the uptake of calcium ( calcium channel blockers ) and

alpha-one antagonists reduce the symptoms in mostcases. Drugs that dilate blood vessels are only effectivesome of the time. Sweating from the affected areas canbe profuse and require treatment. Surgery to cut the sym-pathetic nerves is performed rarely.
Prognosis
Acrocyanosis is a benign and persistent disease. The
main concern of patients is cosmetic. Left untreated, thedisease does not worsen.
Resources
BOOKS
Alexander, R. W., R. C. Schlant, and V . Fuster, eds. The Heart.

9th ed. New York: McGraw-Hill, 1998.
Berkow, Robert, ed. Merck Manual of Medical Information.
Whitehouse Station, NJ: Merck Research Laboratories,1997.
Larsen, D. E., ed. Mayo Clinic Family Health Book. New York:
William Morrow and Co., Inc., 1996.
John T. Lohr, PhD
Acromegaly and gigantism
Acromegaly is a disorder in which the abnormal

release of a particular chemical from the pituitary glandin the brain causes increased growth in bone and soft tis-sue, as well as a variety of other disturbances throughoutthe body. This chemical released from the pituitary glandis called growth hormone (GH). The body’s ability toKEY TERMS
Sympathetic nerve —A nerve of the autonomic

nervous system that regulates involuntary andautomatic reactions, especially to stress.process and use nutrients like fats and sugars is also

altered. In children whose bony growth plates have notclosed, the chemical changes of acromegaly result inexceptional growth of long bones. This variant is calledgigantism, with the additional bone growth causingunusual height. When the abnormality occurs after bonegrowth stops, the disorder is called acromegaly.
Acromegaly is a relatively rare disorder, occurring in

approximately 50 out of every one million people (50/1,000,000). Both men and women are affected. Becausethe symptoms of acromegaly occur so gradually, diagno-sis is often delayed. The majority of patients are notidentified until they are middle aged.
The pituitary is a small gland located at the base of

the brain. A gland is a collection of cells that releasescertain chemicals, or hormones, which are important tothe functioning of other organs or body systems. Thepituitary hormones travel throughout the body and areinvolved in a large number of activities, including theregulation of growth and reproductive functions. Thecause of acromegaly can be traced to the pituitary’s pro-duction of GH.
Under normal conditions, the pituitary receives input

from another brain structure, the hypothalamus, locatedat the base of the brain. This input from the hypothala-mus regulates the pituitary’s release of hormones. Forexample, the hypothalamus produces growth hormone-releasing hormone (GHRH), which directs the pituitaryto release GH. Input from the hypothalamus should alsodirect the pituitary to stop releasing hormones.
In acromegaly, the pituitary continues to release GH

and ignores signals from the hypothalamus. In the liver,GH causes production of a hormone called insulin-likegrowth factor 1 (IGF-1), which is responsible for growththroughout the body. When the pituitary refuses to stopproducing GH, the levels of IGF-1 also reach abnormalpeaks. Bones, soft tissue, and organs throughout the bodybegin to enlarge, and the body changes its ability toprocess and use nutrients like sugars and fats.
In acromegaly, an individual’s hands and feet begin

to grow, becoming thick and doughy. The jaw line, nose,and forehead also grow, and facial features are describedas “coarsening”. The tongue grows larger, and becausethe jaw is larger, the teeth become more widely spaced.Due to swelling within the structures of the throat andsinuses, the voice becomes deeper and sounds more hol-low, and patients may develop loud snoring . Various hor-
monal changes cause symptoms such as:

GALE ENCYCLOPEDIA OF MEDICINE 2 32Acromegaly and gigantismGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 32

• heavy sweating
• oily skin
• increased coarse body hair
• improper processing of sugars in the diet (and some-
times actual diabetes)
• high blood pressure
• increased calcium in the urine (sometimes leading to
kidney stones)
• increased risk of gallstones ; and
• swelling of the thyroid gland
People with acromegaly have more skin tags, or out-

growths of tissue, than normal. This increase in skin tagsis also associated with the development of growths,called polyps, within the large intestine that may eventu-ally become cancerous. Patients with acromegaly oftensuffer from headaches and arthritis. The variousswellings and enlargements throughout the body maypress on nerves, causing sensations of local tingling orburning, and sometimes result in muscle weakness.
The most common cause of this disorder (in 90% of

patients) is the development of a noncancerous tumor with-in the pituitary, called a pituitary adenoma. These tumorsare the source of the abnormal release of GH. As thesetumors grow, they may press on nearby structures within thebrain, causing headaches and changes in vision. As the ade-noma grows, it may disrupt other pituitary tissue, interferingwith the release of other hormones. These disruptions maybe responsible for changes in the menstrual cycle ofwomen, decreases in the sexual drive in

cycle ofwomen, decreases in the sexual drive in men and women,and the abnormal production of breast milk in women. Inrare cases, acromegaly is caused by the abnormal produc-tion of GHRH, which leads to the increased production ofGH. Certain tumors in the pancreas, lungs, adrenal glands,thyroid, and intestine produce GHRH, which in turn triggersproduction of an abnormal quantity of GH.

time, diagnosis is often significantly delayed. In fact, thecharacteristic coarsening of the facial features is oftennot recognized by family members, friends, or long-timefamily physicians. Often, the diagnosis is suspected by anew physician who sees the patient for the first time andis struck by the patient’s characteristic facial appearance.Comparing old photographs from a number of differenttime periods will often increase suspicion of the disease.

Because the quantity of GH produced varies widely
under normal conditions, demonstrating high levels ofGH in the blood is not sufficient to merit a diagnosis ofacromegaly. Instead, laboratory tests measuring anincrease of IGF-1 (3-10 times above the normal level) are
useful. These results, however, must be carefully inter-preted because normal laboratory values for IGF-1 varywhen the patient is pregnant, undergoing puberty , elder-

ly, or severely malnourished. Normal patients will show adecrease in GH production when given a large dose ofsugar (glucose). Patients with acromegaly will not showthis decrease, and will often show an increase in GH pro-duction. Magnetic resonance imaging (MRI) is useful
for viewing the pituitary, and for identifying and locatingan adenoma. When no adenoma can be located, the searchfor a GHRH-producing tumor in another location begins.
Treatment

Treatment
The first step in treatment of acromegaly is removal of
all or part of the pituitary adenoma. Removal requiressurgery, usually performed by entering the skull throughthe nose. While this surgery can cause rapid improvementof many acromegaly symptoms, most patients will also
GALE ENCYCLOPEDIA OF MEDICINE 2 33Acromegaly and gigantism
Enlarged feet is one deformity caused by acromegaly. (Cus-

tom Medical Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 33

KEY TERMS
Adenoma —A type of noncancerous (benign)
tumor that often involves the overgrowth of certaincells found in glands.
Gland —A collection of cells that releases certain
chemicals, or hormones, that are important to thefunctioning of other organs or body systems.
Hormone —A chemical produced in one part of
the body that travels to another part of the body inorder to exert an effect.
Hypothalamus —A structure within the brain

responsible for a large number of normal functionsthroughout the body, including regulating sleep,temperature, eating, and sexual development. Thehypothalamus also regulates the functions of thepituitary gland by directing the pituitary to stop orstart production of its hormones.
Pituitary —A gland located at the base of the brain

that produces a number of hormones, includingthose that regulate growth and reproductive func-tions. Overproduction of the pituitary hormonecalled growth hormone (GH) is responsible for thecondition known as acromegaly.require additional treatment with medication. Bromocrip-

tine (Parlodel) is a medication that can be taken by mouth,while octreotide (Sandostatin) must be injected every eighthours. Both of these medications are helpful in reducingGH production, but must often be taken for life and pro-duce their own unique side effects. Some patients who can-not undergo surgery are treated with radiation therapy to

the pituitary in an attempt to shrink the adenoma. Radiatingthe pituitary may take up to 10 years, however, and mayalso injure/destroy other normal parts of the pituitary.
Prognosis
Without treatment, patients with acromegaly will
most likely die early because of the disease’s effects on theheart, lungs, brain, or due to the development of cancer in
the large intestine. With treatment, however, a patient withacromegaly may be able to live a normal lifespan.
Resources
BOOKS

Resources
BOOKS
Biller, Beverly M. K., and Gilbert H. Daniels. “Growth Hor-
mone Excess: Acromegaly and Gigantism.” In Harrison’s
Principles of Internal Medicine , ed. Anthony S. Fauci, et
al. New York: McGraw-Hill, 1997.
Jameson, J. Larry. “Growth Hormone Excess: Acromegaly and
Gigantism.” In Cecil Textbook of Medicine , ed. J. Claude
Bennett and Fred Plum. Philadelphia: W. B. Saunders Co.,1996.
Jaffe, C. A. “Acromegaly: Recognition and Treatment.” Drugs
47, no. 3 (1994): 425+.

Krishna, A. Y . “Management of Acromegaly: A Review.” Ameri-
can Journal of Medical Science 308, no. 6 (1994): 370+.
Maugans, Todd, and Michael L. Coates. “Diagnosis and Treat-
ment of Acromegaly.” American Family Physician 52, no.
1 (July 1995): 207+.ORGANIZATIONS
Pituitary Tumor Network Association. 16350 Ventura Blvd.,
#231, Encino, CA 91436. (805) 499-9973.
ACT seeAlanine aminotransferase test
ACTH test seeAdrenocorticotropic
hormone test

Actinomyces israelii infection see
Actinomycosis
Actinomycosis is an infection primarily caused by
the bacterium Actinomyces israelii . Infection most often
occurs in the face and neck region and is characterizedby the presence of a slowly enlarging, hard, red lump.
GALE ENCYCLOPEDIA OF MEDICINE 2 34Actinomycosis
A comparison of the right hand of a person afflicted with

acromegaly (left) and the hand of a normal sized person.(Custom Medical Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 34

Actinomycosis is a relatively rare infection occurring

in one out of 300,000(1/300,000) people per year. It ischaracterized by the presence of a lump or mass that oftenforms, draining sinus tracts to the skin surface. Fifty per-cent of actinomycosis cases are of the head and neck region(also called “lumpy jaw” and “cervicofacial actinomyco-sis”), 15% are in the chest, 20% are in the abdomen, andthe rest are in the pelvis, heart, and brain. Men are threetimes more likely to develop actinomycosis than women.

Actinomycosis is usually caused by the bacterium
Actinomyces israelii . This bacterium is normally present
in the mouth but can cause disease if it enters tissues fol-lowing an injury. Actinomyces israelii is an anaerobic
bacterium which means it dislikes oxygen but grows verywell in deep tissues where oxygen levels are low. Tooth
extraction , tooth disease, root canal treatment ,j a w
surgery, or poor dental hygiene can allow Actinomyces

israelii to cause an infection in the head and neck region.
The main symptom of cervicofacial actinomycosis is
the presence of a hard lump on the face or neck. The lumpmay or may not be red. Fever occurs in some cases.
Diagnosis
Cervicofacial actinomycosis can be diagnosed by a fam-

ily doctor or dentist and the patient may be referred to an oralsurgeon or infectious disease specialist. The diagnosis ofactinomycosis is based upon several things. The presence of ared lump with draining sinuses on the head or neck is stronglysuggestive of cervicofacial actinomycosis. A recent history oftooth extraction or signs of tooth decay or poor dental

hygiene aid in the diagnosis. Microscopic examination of thefluid draining from the sinuses shows the characteristic “sul-fur granules” (small yellow colored material in the fluid) pro-duced by Actinomyces israelii . A biopsy may be performed to
remove a sample of the infected tissue. This procedure can beperformed under local anesthesia in the doctor’s office. Occa-sionally the bacteria can be cultured from the sinus tract fluidor from samples of the infected tissue.

Actinomycosis in the lungs, abdomen, pelvis, or
brain can be very hard to diagnose since the symptomsoften mimic those of other diseases. Actinomycosis ofthe lungs or abdomen can resemble tuberculosis or can-
cer. x-ray results, the presence of draining sinus tracts,
and microscopic analysis and culturing of infected tissueassist in the diagnosis.
Treatment
Actinomycosis is difficult to treat because of its
dense tissue location. Surgery is often required to drainKEY TERMS

Biopsy —The process which removes a sample of
tissue for microscopic examination to aid in thediagnosis of a disease.
Sinus tract —A narrow, elongated channel in the
body which allows the escape of fluid.
the lesion and/or to remove the site of infection. To kill

the bacteria, large doses of penicillin are given through avein daily for two to six weeks followed by six to twelvemonths of penicillin taken by mouth. Tetracycline, clin-damycin, or erythromycin may be used instead of peni-cillin. The antibiotic therapy must be completed to insurethat the infection does not return. Hyperbaric oxygen(oxygen under high pressure) therapy in combinationwith the antibiotic therapy has been successful.
Prognosis
Complete recovery is achieved following treatment.

If left untreated, the infection may cause localized bonedestruction.
The best prevention is to maintain good dental hy-
giene.
Resources
OTHER
“Actinomycosis.” HealthAnswers.com. 6 Feb. 1998. <http://
www.healthanswers.com/database/ami/converted/000599.html>.
Belinda Rowland, PhD
Activated charcoal seeCharcoal, activated
Activated partial thromboplastin time see
Partial thromboplastin time
Acupressure
Acupressure is a form of touch therapy that utilizes

the principles of acupuncture and Chinese medicine. In
acupressure, the same points on the body are used as inacupuncture, but are stimulated with finger pressure
GALE ENCYCLOPEDIA OF MEDICINE 2 35AcupressureGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 35

instead of with the insertion of needles. Acupressure is
used to relieve a variety of symptoms and pain .
Purpose
Acupressure massage performed by a therapist can be
very effective both as prevention and as a treatment for manyhealth conditions, including headaches, general aches andpains, colds and flu, arthritis, allergies ,asthma , nervous ten-
sion, menstrual cramps, sinus problems, sprains, tennis
elbow , and toothaches, among others. Unlike acupuncture

which requires a visit to a professional, acupressure can beperformed by a layperson. Acupressure techniques are fairlyeasy to learn, and have been used to provide quick, cost-free,and effective relief from many symptoms. Acupressurepoints can also be stimulated to increase energy and feelingsof well-being, reduce stress , stimulate the immune system,
and alleviate sexual dysfunction .
Origins
One of the oldest text of Chinese medicine is the

Huang Di , The Yellow Emperor’s Classic of InternalMedicine, which may be at least 2,000 years old. Chi-
nese medicine has developed acupuncture, acupressure,herbal remedies, diet, exercise , lifestyle changes, and
other remedies as part of its healing methods. Nearly allof the forms of Oriental medicine that are used in theWest today, including acupuncture, acupressure, shiatsu ,

and Chinese herbal medicine, have their roots in Chinesemedicine. One legend has it that acupuncture and acu-pressure evolved as early Chinese healers studied thepuncture wounds of Chinese warriors, noting that certain
points on the body created interesting results when stim-ulated. The oldest known text specifically on acupunc-ture points, the Systematic Classic of Acupuncture , dates
back to 282 
A.D. Acupressure is the non-invasive form of

acupuncture, as Chinese physicians determined thatstimulating points on the body with massage and pres-sure could be effective for treating certain problems.
Outside of Asian-American communities, Chinese

medicine remained virtually unknown in the UnitedStates until the 1970s, when Richard Nixon became thefirst U.S. president to visit China. On Nixon’s trip, jour-nalists were amazed to observe major operations beingperformed on patients without the use of anesthetics.Instead, wide-awake patients were being operated on,
GALE ENCYCLOPEDIA OF MEDICINE 2 36Acupressure

Therapist working acupressure points on a woman’s shoulder. (Photo Researchers, Inc. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 36

with only acupuncture needles inserted into them to con-
trol pain. At that time, a famous columnist for the New
York Times , James Reston, had to undergo surgery and

elected to use acupuncture for anesthesia. Later, he wrotesome convincing stories on its effectiveness. Despitebeing neglected by mainstream medicine and the Ameri-can Medical Association (AMA), acupuncture and Chi-nese medicine became a central to alternative medicinepractitioners in the United States. Today, there are mil-lions of patients who attest to its effectiveness, and near-ly 9,000 practitioners in all 50 states.
Acupressure is practiced as a treatment by Chinese

medicine practitioners and acupuncturists, as well as bymassage therapists. Most massage schools in Americaninclude acupressure techniques as part of their bodyworkprograms. Shiatsu massage is very closely related to acu-pressure, working with the same points on the body andthe same general principles, although it was developedover centuries in Japan rather than in China. Reflexology

is a form of bodywork based on acupressure concepts.Jin Shin Do is a bodywork technique with an increasingnumber of practitioners in America that combines acu-pressure and shiatsu principles with qigong , Reichian
theory, and meditation .
Acupressure and Chinese medicine
Chinese medicine views the body as a small part of

the universe, subject to laws and principles of harmonyand balance. Chinese medicine does not make as sharp adestinction as Western medicine does between mind andbody. The Chinese system believes that emotions andmental states are every bit as influential on disease aspurely physical mechanisms, and considers factors likework, environment, and relationships as fundamental to apatient’s health. Chinese medicine also uses very differentsymbols and ideas to discuss the body and health.

and ideas to discuss the body and health. WhileWestern medicine typically describes health as mainlyphysical processes composed of chemical equations andreactions, the Chinese use ideas like yin and yang, chi,and the organ system to describe health and the body.

Everything in the universe has properties of yin and
yang. Yin is associated with cold, female, passive, down-ward, inward, dark, wet. Yang can be described as hot,male, active, upward, outward, light, dry, and so on.Nothing is either completely yin or yang. These two prin-ciples always interact and affect each other, although thebody and its organs can become imbalanced by havingeither too much or too little of either.
Chi (pronounced chee, also spelled qior kiin Japan-

ese shiatsu) is the fundamental life energy. It is found infood, air, water, and sunlight, and it travels through thebody in channels called meridians . There are 12 major
GALE ENCYCLOPEDIA OF MEDICINE 2 37Acupressure
/K47/K6F/K76/K65/K72/K6E/K69/K6E/K67 /K76/K65/K73/K73/K65/K6C /K32/K34/K2E/K35
/K4C/K75/K6E/K67 /K31/K30
/K53/K74/K6F/K6D/K61/K63/K68 /K33/K36
Acupressure points to relieve hay fever, sore throat, and

heartburn. (Illustration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 37

meridians in the body that transport chi, corresponding to
the 12 main organs categorized by Chinese medicine.
Disease is viewed as an imbalance of the organs and

chi in the body. Chinese medicine has developed intri-cate systems of how organs are related to physical andmental symptoms, and it has devised correspondingtreatments using the meridian and pressure point net-works that are classified and numbered. The goal of acu-pressure, and acupuncture, is to stimulate and unblockthe circulation of chi, by activating very specific points,called pressure points or acupoints . Acupressure seeks

to stimulate the points on the chi meridians that passclose to the skin, as these are easiest to unblock andmanipulate with finger pressure.
Acupressure can be used as part of a Chinese
physician’s prescription, as a session of massage ther-
apy, or as a self-treatment for common aches and ill-

nesses. A Chinese medicine practitioner examines apatient very thoroughly, looking at physical, mental andemotional activity, taking the pulse usually at thewrists, examining the tongue and complexion, andobserving the patient’s demeanor and attitude, to get acomplete diagnosis of which organs and meridianpoints are out of balance. When the imbalance is locat-ed, the physician will recommend specific pressurepoints for acupuncture or acupressure. If acupressure isrecommended, the patient might

If acupressure isrecommended, the patient might opt for a series oftreatments from a massage therapist.

In massage therapy, acupressurists will evaluate a
patient’s symptoms and overall health, but a massagetherapist’s diagnostic training isn’t as extensive as aChinese physician’s. In a massage therapy treatment, aperson usually lies down on a table or mat, with thinclothing on. The acupressurist will gently feel and pal-pate the abdomen and other parts of the body to deter-KEY TERMS
Acupoint —A pressure point stimulated in acu-
pressure.
Chi—Basic life energy.

pressure.
Meridian —A channel through which chi travels in
the body.
Moxibustion —An acupuncture technique that
burns the herb moxa or mugwort.
Shiatsu —Japanese form of acupressure massage.
Yin/yang —Universal characteristics used to des-
cribe aspects of the natural world.mine energy imbalances. Then, the therapist will work

with different meridians throughout the body, depend-ing on which organs are imbalanced in the abdomen.The therapist will use different types of finger move-ments and pressure on different acupoints, dependingon whether the chi needs to be increased or dispersed atdifferent points. The therapist observes and guides theenergy flow through the patient’s body throughout thesession. Sometimes, special herbs ( Artemesia vulgaris

or moxa) may be placed on a point to warm it, a processcalled moxibustion . A session of acupressure is general-
ly a very pleasant experience, and some people experi-ence great benefit immediately. For more chronic con-ditions, several sessions may be necessary to relieveand improve conditions.
Acupressure massage usually costs from $30–70 per

hour session. A visit to a Chinese medicine physician oracupuncturist can be more expensive, comparable to avisit to an allopathic physician if the practitioner is anMD. Insurance reimbursement varies widely, and con-sumers should be aware if their policies cover alternativetreatment, acupuncture, or massage therapy.
Self-treatment
Acupressure is easy to learn, and there are many

good books that illustrate the position of acupoints andmeridians on the body. It is also very versatile, as it canbe done anywhere, and it’s a good form of treatment forspouses and partners to give to each other and for parentsto perform on children for minor conditions.
While giving self-treatment or performing acupressure

on another, a mental attitude of calmness and attention isimportant, as one person’s energy can be used to helpanother’s. Loose, thin clothing is recommended. There arethree general techniques for stimulating a pressure point.
• Tonifying is meant to strengthen weak chi, and is done
by pressing the thumb or finger into an acupoint with afirm, steady pressure, holding it for up to two minutes.
• Dispersing is meant to move stagnant or blocked chi,

and the finger or thumb is moved in a circular motion orslightly in and out of the point for two minutes.
• Calming the chi in a pressure point utilizes the palm to
cover the point and gently stroke the area for about twominutes.
There are many pressure points that are easily found
and memorized to treat common ailments from headachesto colds.
• For headaches, toothaches, sinus problems, and pain in

the upper body, the “LI4” point is recommended. It islocated in the web between the thumb and index finger,on the back of the hand. Using the thumb and index fin-ger of the other hand, apply a pinching pressure until
GALE ENCYCLOPEDIA OF MEDICINE 2 38AcupressureGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 38

the point is felt, and hold it for two minutes. Pregnant
women should never press this point.
• To calm the nerves and stimulate digestion, find the
“CV12” point that is four thumb widths above the navelin the center of the abdomen. Calm the point with thepalm, using gentle stroking for several minutes.
• To stimulate the immune system, find the “TH5” point

on the back of the forearm two thumb widths above thewrist. Use a dispersing technique, or circular pressurewith the thumb or finger, for two minutes on each arm.
• For headaches, sinus congestion, and tension, locate the

“GB20” points at the base of the skull in the back of thehead, just behind the bones in back of the ears. Dispersethese points for two minutes with the fingers or thumbs.Also find the “yintang” point, which is in the middle ofthe forehead between the eyebrows. Disperse it withgentle pressure for two minutes to clear the mind and torelieve headaches.
Acupressure is a safe technique, but it is not meant to

replace professional health care. A physician shouldalways be consulted when there are doubts about medicalconditions. If a condition is chronic, a professional shouldbe consulted; purely symptomatic treatment can exacer-bate chronic conditions. Acupressure should not beapplied to open wounds, or where there is swelling andinflammation. Areas of scar tissue, blisters, boils ,rashes ,
or varicose veins should be avoided. Finally, certain acu-

pressure points should not be stimulated on people withhigh or low blood pressure and on pregnant women.
Research and general acceptance
In general, Chinese medicine has been slow to gain

acceptance in the West, mainly because it rests on ideasvery foreign to the scientific model. For instance, West-ern scientists have trouble with the idea of chi, the invisi-ble energy of the body, and the idea that pressing on cer-tain points can alleviate certain conditions seems some-times too simple for scientists to believe.
Western scientists, in trying to account for the action

of acupressure, have theorized that chi is actually part ofthe neuroendocrine system of the body. Celebrated ortho-pedic surgeon Robert O. Becker, who was twice nominatedfor the Nobel Prize, wrote a book on the subject calledCross Currents: The Promise of Electromedicine; The Per-ils of Electropollution . By using precise electrical measur-

ing devices, Becker and his colleagues showed that thebody has a complex web of electromagnetic energy, andthat traditional acupressure meridians and points containedamounts of energy that non-acupressure points did not.The mechanisms of acupuncture and acupressure

remain difficult to document in terms of the biochemicalprocesses involved; numerous testimonials are the prima-ry evidence backing up the effectiveness of acupressureand acupuncture. However, a body of research is growingthat verifies the effectiveness in acupressure andacupuncture techniques in treating many problems and incontrolling pain.
Resources
BOOKS
Jarmey, Chris and John Tindall. Acupressure for Common Ail-
ments. London: Gaia, 1991.

Kakptchuk, Ted. The Web That Has No Weaver: Understanding
Chinese Medicine. New York: Congdon and Weed, 1983.
Warren, Frank Z., MD. Freedom From Pain Through Acupres-
sure. New York: Fell, 1976.
Massage Therapy Journal. 820 Davis Street, Suite 100,
Evanston, IL 60201-4444.
OTHER
American Association of Oriental Medicine. <http://www.
aaom.org/> (December 28, 2000).
National Acupuncture and Oriental Medicine Alliance. <http://

www.acuall.org/> (December 28, 2000).
Douglas Dupler
Acupressure, foot seeReflexology
Acupuncture
Acupuncture is one of the main forms of treatment in
traditional Chinese medicine . It involves the use of
sharp, thin needles that are inserted in the body at veryspecific points. This process is believed to adjust and alterthe body’s energy flow into healthier patterns, and is usedto treat a wide variety of illnesses and health conditions.
Purpose

Purpose
The World Health Organization (WHO) recommends
acupuncture as an effective treatment for over forty med-ical problems, including allergies , respiratory conditions,
gastrointestinal disorders, gynecological problems, ner-vous conditions, and disorders of the eyes, nose andthroat, and childhood illnesses, among others. Acupunc-ture has been used in the treatment of alcoholism and
substance abuse. It is an effective and low-cost treatment

GALE ENCYCLOPEDIA OF MEDICINE 2 39AcupunctureGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 39

for headaches and chronic pain, associated with problems
like back injuries and arthritis. It has also been used tosupplement invasive Western treatments like chemother-
apyand surgery. Acupuncture is generally most effective
when used as prevention or before a health conditionbecomes acute, but it has been used to help patients suf-fering from cancer and AIDS . Acupuncture is limited in
treating conditions or traumas that require surgery oremergency care (such as for broken bones).

Origins
The original text of Chinese medicine is the Nei
Ching, The Yellow Emperor’s Classic of Internal Medi-cine, which is estimated to be at least 2,500 years old.
Thousands of books since then have been written on thesubject of Chinese healing, and its basic philosophiesspread long ago to other Asian civilizations. Nearly all ofthe forms of Oriental medicine which are used in the Westtoday, including acupuncture, shiatsu ,acupressure mas-

sage, and macrobiotics, are part of or have their roots inChinese medicine. Legend has it that acupuncture devel-oped when early Chinese physicians observed unpredict-ed effects of puncture wounds in Chinese warriors. The
oldest known text on acupuncture, the Systematic Classic
of Acupuncture , dates back to 282 
A.D. Although acupunc-
ture is its best known technique, Chinese medicine tradi-tionally utilizes herbal remedies, dietary therapy, lifestylechanges and other means to treat patients.

who had visited China were fascinated by acupuncture,but outside of Asian-American communities it remainedvirtually unknown until the 1970s, when Richard Nixonbecame the first U.S. president to visit China. On Nixon’strip, journalists were amazed to observe major operationsbeing performed on patients without the use of anesthetics.Instead, wide-awake patients were being operated on withonly acupuncture needles inserted into them to controlpain. During that time, a famous columnist for the New

elected to use acupuncture instead of pain medication, andhe wrote some convincing stories on its effectiveness.
Today acupuncture is being practiced in all 50 states
by over 9,000 practitioners, with over 4,000 MDs includ-ing it in their practices. Acupuncture has shown notablesuccess in treating many conditions, and over 15 millionAmericans have used it as a therapy. Acupuncture, how-
GALE ENCYCLOPEDIA OF MEDICINE 2 40Acupuncture

Woman undergoing facial acupuncture. (Photograph by Y oav Levy. Phototake NYC. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 40

ever, remains largely unsupported by the medical estab-
lishment. The American Medical Association has beenresistant to researching it, as it is based on concepts verydifferent from the Western scientific model.
Several forms of acupuncture are being used today in

America. Japanese acupuncture uses extremely thin nee-dles and does not incorporate herbal medicine in its prac-tice. Auricular acupuncture uses acupuncture points onlyon the ear, which are believed to stimulate and balanceinternal organs. In France, where acupuncture is very pop-ular and more accepted by the medical establishment, neu-rologist Paul Nogier developed a system of acupuncturebased on neuroendocrine theory rather than on traditionalChinese concepts, which is gaining some use in

Basic ideas of Chinese medicine
the universe, and subject to universal laws and principlesof harmony and balance. Chinese medicine does notdraw a sharp line, as Western medicine does, betweenmind and body. The Chinese system believes that emo-tions and mental states are every bit as influential on dis-ease as purely physical mechanisms, and considers fac-tors like work, environment, lifestyle and relationships as

fundamental to the overall picture of a patient’s health.Chinese medicine also uses very different symbols andideas to discuss the body and health. While Western med-icine typically describes health in terms of measurablephysical processes made up of chemical reactions, theChinese use ideas like yin and yang, chi, the organ sys-tem, and the five elements to describe health and thebody. To understand the ideas behind acupuncture, it isworthwhile to introduce some of these basic terms.

the universe and the body can be described by two sepa-rate but complementary principles, that of yin and yang.For example, in temperature, yin is cold and yang is hot.In gender, yin is female and yang is male. In activity, yinis passive and yang is active. In light, yin is dark andyang is bright; in direction yin is inward and downwardand yang is outward and up, and so on. Nothing is evercompletely yin or yang, but a combination of the two.These two principles are always interacting,

two.These two principles are always interacting, opposing,and influencing each other. The goal of Chinese medi-cine is not to eliminate either yin or yang, but to allowthe two to balance each other and exist harmoniouslytogether. For instance, if a person suffers from symptoms

GALE ENCYCLOPEDIA OF MEDICINE 2 41Acupuncture
Conception vessel
Stomach meridian
Large intestine meridian
Gallbladder meridianGovernor vessel
Bladder meridian
Triple burner meridian
Small intestine meridian
Acupuncture sites and meridians on the face and neck. (Illustration by Hans & Cassady.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 41

of high blood pressure, the Chinese system would say
that the heart organ might have too much yang, andwould recommend methods either to reduce the yang orto increase the yin of the heart, depending on the othersymptoms and organs in the body. Thus, acupuncturetherapies seek to either increase or reduce yang, orincrease or reduce yin in particular regions of the body.
CHI. Another fundamental concept of Chinese med-
icine is that of chi (pronounced chee, also spelled qi). Chi

is the fundamental life energy of the universe. It is invisi-ble and is found in the environment in the air, water, foodand sunlight. In the body, it is the invisible vital forcethat creates and animates life. We are all born with inher-ited amounts of chi, and we also get acquired chi fromthe food we eat and the air we breathe. The level andquality of a person’s chi also depends on the state ofphysical, mental and emotional balance. Chi travelsthrough the body along channels called meridians .

are twelve main organs: the lung, large intestine, stom-ach, spleen, heart, small intestine, urinary bladder, kid-ney, liver, gallbladder, pericardium, and the “triplewarmer,” which represents the entire torso region. Eachorgan has chi energy associated with it, and each organinteracts with particular emotions on the mental level. Asthere are twelve organs, there are twelve types of chiwhich can move through the body, and these movethrough twelve main channels or meridians. Chinesedoctors

twelve main channels or meridians. Chinesedoctors connect symptoms to organs. That is, symptomsare caused by yin/yang imbalances in one or moreorgans, or by an unhealthy flow of chi to or from oneKEY TERMS

Acupressure —Form of massage using acupunc-
ture points.
Auricular acupuncture —Acupuncture using only
points found on the ears.
Meridian —Channel through which chi travels in
the body.
Moxibustion —Acupuncture technique which
Tonification —Acupuncture technique for strength-
ening the body.
Yin/Yang —Universal characteristics used to des-
cribe aspects of the natural world.organ to another. Each organ has a different profile of

symptoms it can manifest.
THE FIVE ELEMENTS. Another basis of Chinese theo-

ry is that the world and body are made up of five mainelements: wood, fire, earth, metal, and water. These ele-ments are all interconnected, and each element eithergenerates or controls another element. For instance,water controls fire and earth generates metal. Each organis associated with one of the five elements. The Chinesesystem uses elements and organs to describe and treatconditions. For instance, the kidney is associated withwater and the heart is associated with fire, and the twoorgans

heart is associated with fire, and the twoorgans are related as water and fire are related. If the kid-ney is weak, then there might be a corresponding fireproblem in the heart, so treatment might be made byacupuncture or herbs to cool the heart system and/orincrease energy in the kidney system.

The Chinese have developed an intricate system of
how organs and elements are related to physical andmental symptoms, and the above example is a very sim-ple one. Although this system sounds suspect to Westernscientists, some interesting parallels have been observed.For instance, Western medicine has observed that withsevere heart problems, kidney failure often follows, but itstill does not know exactly why. In Chinese medicine,this connection between the two organs has long beenestablished.

nese medicine, disease as seen as imbalances in the organsystem or chi meridians, and the goal of any remedy ortreatment is to assist the body in reestablishing its innateharmony. Disease can be caused by internal factors likeemotions, external factors like the environment andweather, and other factors like injuries, trauma, diet, andgerms. However, infection is seen not as primarily aproblem with germs and viruses, but as a weakness in theenergy of the body which is allowing a sickness to

of the body which is allowing a sickness to occur.In Chinese medicine, no two illnesses are ever the same,as each body has its own characteristics of symptoms andbalance. Acupuncture is used to open or adjust the flowof chi throughout the organ system, which will strength-en the body and prompt it to heal itself.

acupuncturist will do is get a thorough idea of a patient’smedical history and symptoms, both physical and emo-tional. This is done with a long questionnaire and inter-view. Then the acupuncturist will examine the patient tofind further symptoms, looking closely at the tongue, thepulse at various points in the body, the complexion, gen-eral behavior, and other signs like coughs or pains. Fromthis, the practitioner will be able to determine patterns ofsymptoms which indicate which organs and

GALE ENCYCLOPEDIA OF MEDICINE 2 42AcupunctureGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 42

imbalanced. Depending on the problem, the acupunctur-
ist will insert needles to manipulate chi on one or moreof the twelve organ meridians. On these twelve meridi-ans, there are nearly 2,000 points which can be used inacupuncture, with around 200 points being most fre-quently used by traditional acupuncturists. During anindividual treatment, one to twenty needles may be used,depending on which meridian points are chosen.
Acupuncture needles are always sterilized and

acupuncture is a very safe procedure. The depth of inser-tion of needles varies, depending on which chi channels arebeing treated. Some points barely go beyond superficiallayers of skin, while some acupuncture points require adepth of 1-3 in (2.5-7.5 cm) of needle. The needles general-ly do not cause pain. Patients sometimes report pinchingsensations and often pleasant sensations, as the body expe-riences healing. Depending on the problem, the acupunc-turist might spin or move the needles, or

acupunc-turist might spin or move the needles, or even pass a slightelectrical current through some of them. Moxibustion may

be sometimes used, in which an herbal mixture (moxa ormugwort) is either burned like incense on the acupuncturepoint or on the end of the needle, which is believed to stim-ulate chi in a particular way. Also, acupuncturists some-times use cupping , during which small suction cups are
placed on meridian points to stimulate them.
How long the needles are inserted also varies. Some
patients only require a quick in and out insertion to clearproblems and provide tonification (strengthening of

health), while some other conditions might require nee-dles inserted up to an hour or more. The average visit toan acupuncturist takes about thirty minutes. The numberof visits to the acupuncturist varies as well, with someconditions improved in one or two sessions and othersrequiring a series of six or more visits over the course ofweeks or months.
Costs for acupuncture can vary, depending on whether

the practitioner is an MD. Initial visits with non-MDacupuncturists can run from $50-$100, with follow-up vis-its usually costing less. Insurance reimbursement alsovaries widely, depending on the company and state. Regu-lations have been changing often. Some states authorizeMedicaid to cover acupuncture for certain conditions, andsome states have mandated that general coverage pay foracupuncture. Consumers should be aware of the provisionsfor acupuncture in their individual policies.

Acupuncture is generally a very safe procedure. If a
patient is in doubt about a medical condition, more thanone physician should be consulted. Also, a patient shouldalways feel comfortable and confident that theiracupuncturist is knowledgable and properly trained.Research and general acceptance
Mainstream medicine has been slow to accept acupunc-

ture; although more MDs are using it, the American MedicalAssociation does not recognize it as a specialty. The reasonfor this is that the mechanism of acupuncture is difficult toscientifically understand or measure, such as the invisibleenergy of chi in the body. Western medicine, admitting thatacupuncture works in many cases, has theorized that theenergy meridians are actually part of the nervous system andthat acupuncture relieves pain by releasing endorphins, ornatural pain killers, into

endorphins, ornatural pain killers, into the bloodstream. Despite the ambi-guity in the biochemistry involved, acupuncture continues toshow effectiveness in clinical tests, from reducing pain toalleviating the symptoms of chronic illnesses, and researchin acupuncture is currently growing. The Office of Alterna-tive Medicine of the National Institute of Health is currentlyfunding research in the use of acupuncture for treatingdepression and attention-deficit disorder.

Resources
BOOKS
Fleischman, Dr. Gary F. Acupuncture: Everything You Ever
Wanted To Know. New York: Barrytown, 1998.
Requena, Yves, MD. Terrains and Pathology in Acupuncture.
Massachusetts: Paradigm, 1986.
American Journal of Acupuncture. 1840 41st Ave., Suite 102,
P.O. Box 610, Capitola, CA 95010.
OTHER

North American Society of Acupuncture and Alternative Medi-
cine. <http://www.nasa-altmed.com/> (December 28, 2000).
Acute glomerulonephritis seeAcute
poststreptococcal glomerulonephritis
Acute homeopathic remedies see
Homeopathic remedies, acuteprescribing
Acute kidney failure
Acute kidney failure occurs when illness, infection,
or injury damages the kidneys. Temporarily, the kidneys

GALE ENCYCLOPEDIA OF MEDICINE 2 43Acute kidney failureGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 43

cannot adequately remove fluids and wastes from the
body or maintain the proper level of certain kidney-regu-lated chemicals in the bloodstream.
The kidneys are the body’s natural filtration system.

They perform the critical task of processing approximate-ly 200 quarts of fluid in the bloodstream every 24 hours.Waste products like urea and toxins, along with excessfluids, are removed from the bloodstream in the form ofurine. Kidney (or renal) failure occurs when kidney func-tioning becomes impaired. Fluids and toxins begin toaccumulate in the bloodstream. As fluids build up in thebloodstream, the patient with acute kidney failure maybecome puffy and swollen (edematous) in the face,

puffy and swollen (edematous) in the face, hands,and feet. Their blood pressure typically begins to rise, andthey may experience fatigue and nausea.

Unlike chronic kidney failure , which is long term
and irreversible, acute kidney failure is a temporary con-dition. With proper and timely treatment, it can typicallybe reversed. Often there is no permanent damage to thekidneys. Acute kidney failure appears most frequently asa complication of serious illness, like heart failure ,l i v e r
failure, dehydration , severe burns , and excessive bleed-

ing (hemorrhage). It may also be caused by an obstruc-tion to the urinary tract or as a direct result of kidney dis-ease, injury, or an adverse reaction to a medicine.
Acute kidney failure can be caused by many differ-
ent illnesses, injuries, and infections. These conditionsfall into three main categories: prerenal ,postrenal , and
intrarenal conditions.
Prerenal conditions do not damage the kidney, but

can cause diminished kidney function. They are the mostcommon cause of acute renal failure, and include:
• dehydration
• hemorrhage• septicemia, or sepsis
• heart failure
• liver failure• burns
Postrenal conditions cause kidney failure by obstruct-
ing the urinary tract. These conditions include:
• inflammation of the prostate gland in men (prostatitis)
• enlargement of the prostate gland (benign prostatic
hypertrophy)
• bladder or pelvic tumors

•kidney stones (calculi)Intrarenal conditions involve kidney disease or
direct injury to the kidneys. These conditions include:
• lack of blood supply to the kidneys (ischemia)
• use of radiocontrast agents in patients with kidney
problems
• drug abuse or overdose• long-term use of nephrotoxic medications, like certain
pain medicines
• acute inflammation of the glomeruli, or filters, of the
kidney ( glomerulonephritis )

• kidney infections (pyelitis or pyelonephritis)
Common symptoms of acute kidney failure include:
• anemia. The kidneys are responsible for producing ery-
thropoietin (EPO), a hormone that stimulates red bloodcell production. If kidney disease causes shrinking ofthe kidney, red blood cell production is reduced, lead-ing to anemia.
• bad breath or bad taste in mouth. Urea in the saliva may
cause an ammonia-like taste in the mouth.

• bone and joint problems. The kidneys produce vitamin
D, which helps the body absorb calcium and keepsbones strong. For patients with kidney failure, bonesmay become brittle. In children, normal growth may bestunted. Joint pain may also occur as a result of highphosphate levels in the blood. Retention of uric acidmay cause gout .
• edema. Puffiness or swelling in the arms, hands, feet,
and around the eyes.
• frequent urination.

• foamy or bloody urine. Protein in the urine may cause it
to foam significantly. Blood in the urine may indicatebleeding from diseased or obstructed kidneys, bladder,or ureters.
• headaches. High blood pressure may trigger headaches.
• hypertension, or high blood pressure. The retention of
fluids and wastes causes blood volume to increase. Thismakes blood pressure rise.
• increased fatigue. Toxic substances in the blood and the

presence of anemia may cause the patient to feelexhausted.
• itching. Phosphorus, normally eliminated in the urine,
accumulates in the blood of patients with kidney failure.An increased phosphorus level may cause the skin to itch.
• lower back pain. Patients suffering from certain kidney
problems (like kidney stones and other obstructions)may have pain where the kidneys are located, in thesmall of the back below the ribs.
• nausea. Urea in the gastric juices may cause upset
stomach.

stomach.
GALE ENCYCLOPEDIA OF MEDICINE 2 44Acute kidney failureGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 44

gist, a doctor that specializes in the kidney, may be con-sulted to confirm the diagnosis and recommend treat-ment options. The patient that is suspected of havingacute kidney failure will have blood and urine tests todetermine the level of kidney function. A blood test willassess the levels of creatinine, blood urea nitrogen(BUN), uric acid, phosphate, sodium, and potassium.The kidney regulates these agents in the blood. Urinesamples will also be collected, usually over a 24-hourperiod, to

be collected, usually over a 24-hourperiod, to assess protein loss and/or creatinine clearance.

Determining the cause of kidney failure is critical to
proper treatment. A full assessment of the kidneys is neces-sary to determine if the underlying disease is treatable and ifthe kidney failure is chronic or acute. X rays, magnetic res-
onance imaging (MRI), computed tomography scan (CT),

ultrasound, renal biopsy, and/or arteriogram of the kidneysmay be used to determine the cause of kidney failure andlevel of remaining kidney function. X rays and ultrasoundof the bladder and/or ureters may also be needed.
Treatment
Treatment for acute kidney failure varies. Treatment

is directed to the underlying, primary medical conditionthat has triggered kidney failure. Prerenal conditions maybe treated with replacement fluids given through a vein,diuretics , blood transfusion , or medications. Postrenal
conditions and intrarenal conditions may require surgeryand/or medication.
Frequently, patients in acute kidney failure require
hemodialysis ,hemofiltration , or peritoneal dialysis to fil-

ter fluids and wastes from the bloodstream until the pri-mary medical condition can be controlled.
Hemodialysis
Hemodialysis involves circulating the patient’s

blood outside of the body through an extracorporeal cir-cuit (ECC), or dialysis circuit. The ECC is made up ofplastic blood tubing, a filter known as a dialyzer (or arti-ficial kidney), and a dialysis machine that monitors andmaintains blood flow and administers dialysate.Dialysate is a sterile chemical solution that is used todraw waste products out of the blood. The patient’s bloodleaves the body through the vein and travels through theECC and the dialyzer, where fluid removal takes place.

During dialysis, waste products in the bloodstream
are carried out of the body. At the same time, electrolytesand other chemicals are added to the blood. The purified,chemically-balanced blood is then returned to the body.KEY TERMS
Blood urea nitrogen (BUN) —A waste product that
is formed in the liver and collects in the blood-stream; patients with kidney failure have highBUN levels.
Creatinine —A protein produced by muscle that
healthy kidneys filter out.

Extracorporeal —Outside of, or unrelated to, the
body.
Ischemia —A lack of blood supply to an organ or
tissue.
Nephrotoxic —Toxic, or damaging, to the kidney.
Radiocontrast agents —Dyes administered to a
patient for the purposes of a radiologic study.
Sepsis —A bacterial infection of the bloodstream.
Vasopressors —Medications that constrict the blood
vessels.
A dialysis “run” typically lasts three to four hours,

depending on the type of dialyzer used and the physicalcondition of the patient. Dialysis is used several times aweek until acute kidney failure is reversed.
Blood pressure changes associated with hemodialy-
sis may pose a risk for patients with heart problems. Peri-toneal dialysis may be the preferred treatment option inthese cases.
Hemofiltration
Hemofiltration, also called continuous renal replace-

ment therapy (CRRT), is a slow, continuous blood filtra-tion therapy used to control acute kidney failure in criti-cally ill patients. These patients are typically very sickand may have heart problems or circulatory problems.They cannot handle the rapid filtration rates of hemodial-ysis. They also frequently need antibiotics ,nutrition ,

vasopressors, and other fluids given through a vein totreat their primary condition. Because hemofiltration iscontinuous, prescription fluids can be given to patients inkidney failure without the risk of fluid overload.
Like hemodialysis, hemofiltration uses an ECC. A

hollow fiber hemofilter is used instead of a dialyzer toremove fluids and toxins. Instead of a dialysis machine, ablood pump makes the blood flow through the ECC. Thevolume of blood circulating through the ECC in hemofil-tration is less than that in hemodialysis. Filtration ratesare slower and gentler on the circulatory system.
GALE ENCYCLOPEDIA OF MEDICINE 2 45Acute kidney failureGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 45

Hemofiltration treatment will generally be used until kid-
ney failure is reversed.
Peritoneal dialysis
Peritoneal dialysis may be used if an acute kidney

failure patient is stable and not in immediate crisis. Inperitoneal dialysis (PD), the lining of the patient’sabdomen, the peritoneum, acts as a blood filter. A flexibletube-like instrument (catheter) is surgically inserted intothe patient’s abdomen. During treatment, the catheter isused to fill the abdominal cavity with dialysate. Wasteproducts and excess fluids move from the patient’s blood-stream into the dialysate solution. After a certain timeperiod, the waste-filled dialysate is drained

timeperiod, the waste-filled dialysate is drained from theabdomen, and replaced with clean dialysate. There arethree type of peritoneal dialysis, which vary according totreatment time and administration method.

Peritoneal dialysis is often the best treatment option
for infants and children. Their small size can make veinaccess difficult to maintain. It is not recommended forpatients with abdominal adhesions or other abdominaldefects (like a hernia ) that might reduce the efficiency of
the treatment. It is also not recommended for patientswho suffer frequent bouts of an inflammation of thesmall pouches in the intestinal tract (diverticulitis).
Prognosis
Because many of the illnesses and underlying con-

ditions that often trigger acute kidney failure are critical,the prognosis for these patients many times is not good.Studies have estimated overall death rates for acute kid-

ney failure at 42-88%. Many people, however, diebecause of the primary disease that has caused the kid-ney failure. These figures may also be misleadingbecause patients who experience kidney failure as aresult of less serious illnesses (like kidney stones ordehydration) have an excellent chance of completerecovery. Early recognition and prompt, appropriatetreatment are key to patient recovery.
Up to 10% of patients who experience acute kidney

failure will suffer irreversible kidney damage. They willeventually go on to develop chronic kidney failure orend-stage renal disease. These patients will require long-term dialysis or kidney transplantation to replace their
lost renal functioning.
Since acute kidney failure can be caused by many

things, prevention is difficult. Medications that mayimpair kidney function should be given cautiously.Patients with pre-existing kidney conditions who arehospitalized for other illnesses or injuries should be care-
fully monitored for kidney failure complications. Treat-ments and procedures that may put them at risk for kid-ney failure (like diagnostic tests requiring radiocontrastagents or dyes) should be used with extreme caution.
Resources

Resources
BOOKS
Bock, G. H., E. J. Ruley, and M. P. Moore. A Parent’s Guide to
Kidney Disorders. Minneapolis: University of Minnesota
Press, 1993.
Brenner, Barry M., and Floyd C. Rector Jr., eds. The Kidney.
Philadelphia: W. B. Saunders Co., 1991.
Cameron, J. Stewart. Kidney Failure: The Facts. New York:
Oxford University Press, 1996.
Ross, Linda M., ed. Kidney and Urinary Tract Diseases and
Disorders Sourcebook. V ol. 21. Detroit: Omnigraphics,
Inc., 1997.

Stark, June. “Dialysis Choices: Turning the Tide in Acute
Renal Failure.” Nursing 27, no. 2 (Feb. 1997): 41-8.
National Institute of Diabetes and Digestive and Kidney Dis-
eases (NIDDK). Building 31, Room 9A04, 31 CenterDrive, MSC 2560, Bethesda, MD 208792-2560. (301)496-3583. <http://www.niddk.nih.gov>.
National Kidney Foundation. 30 East 33rd St., New York, NY
10016. (800) 622-9010. <http://www.kidney.org>.
Paula Anne Ford-Martin

Acute leukemias seeLeukemias, acute
Acute lymphangitis
Acute lymphangitis is a bacterial infection in the
lymphatic vessels which is characterized by painful, redstreaks below the skin surface. This is a potentially seri-ous infection which can rapidly spread to the blood-stream and be fatal.
Acute lymphangitis affects a critical member of the

immune system—the lymphatic system. Waste materialsfrom nearly every organ in the body drain into the lym-phatic vessels and are filtered in small organs calledlymph nodes. Foreign bodies, such as bacteria or viruses,are processed in the lymph nodes to generate an immuneresponse to fight an infection.
GALE ENCYCLOPEDIA OF MEDICINE 2 46Acute lymphangitisGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 46

In acute lymphangitis, bacteria enter the body
through a cut, scratch, insect bite, surgical wound, orother skin injury. Once the bacteria enter the lymphaticsystem, they multiply rapidly and follow the lymphaticvessel like a highway. The infected lymphatic vesselbecomes inflamed, causing red streaks that are visiblebelow the skin surface. The growth of the bacteria occursso rapidly that the immune system does not respond fastenough to stop the infection.

If left untreated, the bacteria can cause tissue
destruction in the area of the infection. A pus-filled,painful lump called an abscess may be formed in the
infected area. Cellulitis , a generalized infection of the
lower skin layers, may also occur. In addition, the bacte-ria may invade the bloodstream and cause septicemia.Lay people, for that reason, often call the red streaks seenin the skin “blood poisoning.” Septicemia is a very seri-ous illness and may be fatal.

Acute lymphangitis is most often caused by the bac-
terium Streptococcus pyogenes . This potentially danger-
ous bacterium also causes strep throat , infections of the
heart, spinal cord, and lungs, and in the 1990s has beencalled the “flesh-eating bacterium.” Staphylococci bacte-ria may also cause lymphangitis.
Although anyone can develop lymphangitis, some
people are more at risk. People who have had radical mas-
tectomy (removal of a breast and nearby lymph nodes), a

leg vein removed for coronary bypass surgery, or recurrentlymphangitis caused by tinea pedis (a fungal infection onthe foot) are at an increased risk for lymphangitis.
The characteristic symptoms of acute lymphangitis
are the wide, red streaks which travel from the site ofinfection to the armpit or groin. The affected areas are red,swollen, and painful. Blistering of the affected skin mayoccur. The bacterial infection causes a fever of 100-104°F

(38°–40°C). In addition, a general ill feeling, muscleaches, headache , chills, and loss of appetite may be felt.
Diagnosis
If lymphangitis is suspected, the person should call

his or her doctor immediately or go to an emergencyroom. Acute lymphangitis could be diagnosed by thefamily doctor, infectious disease specialist, or an emer-gency room doctor. The painful, red streaks just belowthe skin surface and the high fever are diagnostic of acutelymphangitis. A sample of blood would be taken for cul-ture to determine whether the bacteria have entered thebloodstream. A biopsy (removal of a piece of infectedtissue) sample may be taken for culture to identify whichKEY

diseased or infected tissue for microscopic exami-nation to aid in diagnosis.
Lymphatic system —A component of the immune
system consisting of vessels and nodes. Wastematerials from organs drain into the lymphaticvessels and are filtered by the lymph nodes.
Septicemia —Disease caused by the presence and
growth of bacteria in the bloodstream.
type of bacteria is causing the infection. Diagnosis is

immediate because it is based primarily on the symp-toms. Most insurance policies should cover the expensesfor the diagnosis and treatment of acute lymphangitis.
Treatment
Because of the serious nature of this infection, treat-

ment would begin immediately even before the bacterialculture results were available. The only treatment foracute lymphangitis is to give very large doses of anantibiotic, usually penicillin, through the vein. Growingstreptococcal bacteria are usually eliminated rapidly andeasily by penicillin. The antibiotic clindamycin may beincluded in the treatment to kill any streptococci whichare not growing and are in a resting state. Alternatively, a“broad spectrum” antibiotic may be used which

a“broad spectrum” antibiotic may be used which wouldkill many different kinds of bacteria.

Aspirin or other medications which reduce the pain
and the fever may also be given. Medications whichreduce any inflammation of the infected region may alsobe provided. The patient is likely to be hospitalized toadminister the antibiotic and other medications and toclosely monitor his or her condition. Surgical drainage ofan abscess may be necessary.
Prognosis
Complete recovery is expected if antibiotic treatment

is begun at an early stage of the infection. However, ifuntreated, acute lymphangitis can be a very serious andeven deadly disease. Acute lymphangitis that goes untreat-ed can spread, causing tissue damage. Extensive tissuedamage would need to be repaired by plastic surgery.Spread of the infection into the bloodstream could be fatal.
Although acute lymphangitis can occur in anyone, good
hygiene and general health may help to prevent infections.

GALE ENCYCLOPEDIA OF MEDICINE 2 47Acute lymphangitisGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 47

KEY TERMS
Streptococcus —A gram-positive, round or oval
bacteria in the genus Streptococcus . Group A
streptococci cause a number of human diseasesincluding strep throat, impetigo, and ASPGN.Resources
Dajer, Tony. “A Lethal Scratch.” Discover (Feb. 1998): 34-7.
Acute pericarditis seePericarditis
Acute poststreptococcal
glomerulonephritis
Acute poststreptococcal glomerulonephritis

(APSGN) is an inflammation of the kidney tubules(glomeruli) that filter waste products from the blood, fol-lowing a streptococcal infection such as strep throat .
APSGN is also called postinfectious glomerulonephritis.
APSGN develops after certain streptococcal bacteria

(group A beta-hemolytic streptococci) have infected theskin or throat. Antigens from the dead streptococciclump together with the antibodies that killed them.These clumps are trapped in the kidney tubules, cause thetubules to become inflamed, and impair that organs’ abil-ity to filter and eliminate body wastes. The onset ofAPSGN usually occurs one to six weeks (average twoweeks) after the streptococcal infection.
APSGN is a relatively uncommon disease affecting

about one of every 10,000 people, although four or fivetimes that many may actually be affected by it but showno symptoms. APSGN is most prevalent among boysbetween the ages of 3 and 7, but it can occur at any age.
Frequent sore throats and a history of streptococcal
infection increase the risk of acquiring APSGN. Symp-toms of APSGN include:
• fluid accumulation and tissue swelling ( edema ) initial-

ly in the face and around the eyes, later in the legs
• low urine output (oliguria)• blood in the urine (hematuria)
• protein in the urine (proteinuria)
• high blood pressure• joint pain or stiffnessDiagnosis
Diagnosis of APSGN is made by taking the patient’s
history, assessing his/her symptoms, and performing cer-tain laboratory tests. Urinalysis usually shows blood and

protein in the urine. Concentrations of urea and creati-nine (two waste products normally filtered out of theblood by the kidneys) in the blood are often high, indi-cating impaired kidney function. A reliable, inexpensiveblood test called the anti-streptolysin-O test can confirmthat a patient has or has had a streptococcal infection. Athroat culture may also show the presence of group A
beta-hemolytic streptococci.
Treatment
Treatment of ASPGN is designed to relieve the

symptoms and prevent complications. Some patients areadvised to stay in bed until they feel better and to restrictfluid and salt intake. Antibiotics may be prescribed to
kill any lingering streptococcal bacteria, if their presenceis confirmed. Antihypertensives may be given to helpcontrol high blood pressure and diuretics may be used to
reduce fluid retention and swelling. Kidney dialysis is
rarely needed.
Prognosis

Prognosis
Most children (up to 95%) fully recover from
APSGN in a matter of weeks or months. Most adults (upto 70%) also recover fully. In those who do not recoverfully, chronic or progressive problems of kidney functionmay occur. Kidney failure may result in some patients.
Receiving prompt treatment for streptococcal infec-
tions may prevent APSGN.
Resources
BOOKS

Professional Guide to Diseases. 5th ed. Springhouse, PA:
Springhouse Corporation, 1995.
GALE ENCYCLOPEDIA OF MEDICINE 2 48Acute poststreptococcal glomerulonephritisGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 48

American Kidney Fund. 6110 Executive Boulevard, Rockville,
MD 20852. (800) 638-8299. <http://216.248.130.102/Default.htm>.
Acute respiratory distress syndrome see
Adult respiratory distress syndrome
Acute stress disorder
Acute stress disorder (ASD) is an anxiety disorder

characterized by a cluster of dissociative and anxietysymptoms occurring within one month of a traumaticevent. (Dissociation is a psychological reaction to traumain which the mind tries to cope by “sealing off” somefeatures of the trauma from conscious awareness).
Acute stress disorder is a new diagnostic category
that was introduced in 1994 to differentiate time-limitedreactions to trauma from post-traumatic stress disorder
(PTSD).

(PTSD).
Acute stress disorder is caused by exposure to trau-
ma, which is defined as a stressor that causes intense fearand, usually, involves threats to life or serious injury tooneself or others. Examples are rape, mugging, combat,natural disasters, etc.
The symptoms of stress disorder include a combining

of one or more dissociative and anxiety symptoms withthe avoidance of reminders of the traumatic event. Disso-ciative symptoms include emotional detachment, tempo-rary loss of memory, depersonalization, and derealization.
Anxiety symptoms connected with acute stress disor-
der include irritability, physical restlessness, sleep prob-lems, inability to concentrate, and being easily startled.
Diagnosis
Diagnosis of acute stress disorder is based on a com-

bination of the patient’s history and a physical examina-
tion to rule out diseases that can cause anxiety. TheKEY TERMS
Depersonalization —A dissociative symptom in
which the patient feels that his or her body is unre-al, is changing, or is dissolving.
Derealization —A dissociative symptom in which
the external environment is perceived as unreal.
Dissociation —A reaction to trauma in which the

mind splits off certain aspects of the trauma fromconscious awareness. Dissociation can affect thepatient’s memory, sense of reality, and sense ofidentity.
Trauma —In the context of ASD, a disastrous or
life-threatening event.
essential feature is a traumatic event within one month of
the onset of symptoms. Other diagnostic criteria include:
• The symptoms significantly interfere with normal
social or vocational functioning

• The symptoms last between two days and four weeks.
Treatment
Treatment for acute stress disorder usually includes
a combination of antidepressant medications and short-term psychotherapy.
Acupuncture has been recommended as a treatment
for acute stress disorder. Some other alternativeapproaches, including meditation , breathing exercises,
and yoga , may be helpful when combined with short-

term psychotherapy. Homeopathic treatment and the useof herbal medicine and flower essences also can help theperson with acute stress disorder rebalance on the physi-cal, mental, and emotional levels.
Prognosis
The prognosis for recovery is influenced by the sever-

ity and duration of the trauma, the patient’s closeness to it,and the patient’s previous level of functioning. Favorablesigns include a short time period between the trauma andonset of symptoms, immediate treatment, and appropriatesocial support. If the patient’s symptoms are severeenough to interfere with normal life and have lasted longerthan one month, the diagnosis may be changed to PTSD.If the symptoms have lasted longer than one month but are

GALE ENCYCLOPEDIA OF MEDICINE 2 49Acute stress disorderGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 49

not severe enough to meet the definition of PTSD, the
diagnosis may be changed to adjustment disorder.
Patients who do not receive treatment for acute
stress disorder are at increased risk for substance abuseor major depressive disorders .
Traumatic events cannot usually be foreseen and,

thus, cannot be prevented. However, in theory, profession-al intervention soon after a major trauma might reduce thelikelihood or severity of ASD. In addition, some symp-toms of acute stress disorder result from biochemicalchanges in the central nervous system, muscles, anddigestive tract that are not subject to conscious control.
Resources
BOOKS
“Acute Stress Disorder.” In Diagnostic and Statistical Manual

of Mental Disorders. 4th ed. Washington, DC: American
Psychiatric Association, 1994.
Corbman, Gene R. “Anxiety Disorders.” In Current Diagnosis.
V ol. 9. Ed. Rex B. Conn, et al. Philadelphia: W. B. Saun-ders Co., 1997.
Eisendrath, Stuart J. “Psychiatric Disorders.” In Current Med-
ical Diagnosis and Treatment, 1998. 37th ed. Ed. Stephen
McPhee, et al. Stamford: Appleton & Lange, 1997.
Kabat-Zinn, Jon. Full Catastrophe Living: Using the Wisdom

of Your Body and Mind to Face Stress, Pain, and Illness.New York: Bantam Doubleday Dell Publishing Group,Inc., 1990.
“On-Call Problems: Insomnia.” In Surgery On Call ,e d .
Leonard G. Gomella and Alan T. Lefor. Stamford: Apple-ton & Lange, 1996.
Rebecca J. Frey
Acute stress gastritis seeGastritis
Acute transverse myelitis seeTransverse
myelitis
Acyclovir seeAntiviral drugs
Addiction
Addiction is a dependence on a behavior or sub-

stance that a person is powerless to stop. The term hasbeen partially replaced by the word dependence for sub-
stance abuse. Addiction has been extended, however, toinclude mood-altering behaviors or activities. Someresearchers speak of two types of addictions: substanceaddictions (for example, alcoholism , drug abuse, and
smoking ); and process addictions (for example, gam-

bling, spending, shopping, eating, and sexual activity).There is a growing recognition that many addicts, such aspolydrug abusers, are addicted to more than one sub-stance or process.
Addiction is one of the most costly public health

problems in the United States. It is a progressive syn-drome, which means that it increases in severity overtime unless it is treated. Substance abuse is characterizedby frequent relapse, or return to the abused substance.Substance abusers often make repeated attempts to quitbefore they are successful.
In 1995 the economic cost of substance abuse in the

United States exceeded $414 billion, with health carecosts attributed to substance abuse estimated at morethan $114 billion.
By eighth grade, 52% of adolescents have consumed

alcohol, 41% have smoked tobacco, and 20% havesmoked marijuana. Compared to females, males arealmost four times as likely to be heavy drinkers, nearlyone and a half more likely to smoke a pack or more ofcigarettes daily, and twice as likely to smoke marijuanaweekly. However, among adolescents these gender dif-ferences are decreasing. Although frequent use of tobac-co,cocaine and heavy drinking appears to have remained

stable in the 1990s, marijuana use increased.
In 1999, an estimated four million Americans over the
age of 12 used prescription pain relievers, sedatives, and
stimulants for “nonmedical” reasons during one month.
In the United States, 25% of the population regularly

uses tobacco. Tobacco use reportedly kills 2.5 times asmany people each year as alcohol and drug abuse com-bined. According to 1998 data from the World HealthOrganization, there were 1.1 billion smokers worldwideand 10,000 tobacco-related deaths per day. Furthermore,in the United States, 43% of children aged 2-11 years areexposed to environmental tobacco smoke, which hasbeen implicated in sudden infant death syndrome ,l o w
birth weight, asthma , middle ear disease, pneumonia ,

cough , and upper respiratory infection.
Eating disorders, such as anorexia nervosa ,bulim-
ia nervosa , and binge eating, affect over five million
American women and men. Fifteen percent of youngwomen have substantially disordered attitudes towardeating and eating behaviors. More than 1,000 women dieeach year from anorexia nervosa.
GALE ENCYCLOPEDIA OF MEDICINE 2 50AddictionGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 50

A 1997 Harvard study found that an estimated 15.4
million Americans suffered from a gambling addiction.Over half that number (7.9 million) were adolescents.
Addiction to substances results from the interaction
of several factors:
Drug chemistry
Some substances are more addictive than others,
either because they produce a rapid and intense change inmood; or because they produce painful withdrawalsymptoms when stopped suddenly.
Genetic factor

Some people appear to be more vulnerable to addic-
tion because their body chemistry increases their sensi-tivity to drugs. Some forms of substance abuse and
dependence seem to run in families; and this may be the
result of a genetic predisposition, environmental influ-ences, or a combination of both.
Brain structure and function
Using drugs repeatedly over time changes brain

structure and function in fundamental and long-lastingways. Addiction comes about through an array ofchanges in the brain and the strengthening of new memo-ry connections. Evidence suggests that those long-lastingbrain changes are responsible for the distortions of cog-nitive and emotional functioning that characterizeaddicts, particularly the compulsion to use drugs.Although the causes of addiction remain the subject ofongoing debate and research, many experts now consideraddiction to be a

many experts now consideraddiction to be a brain disease: a condition caused bypersistent changes in brain structure and function. How-ever, having this brain disease does not absolve theaddict of responsibility for his or her behavior, but it doesexplain why many addicts cannot stop using drugs bysheer force of will alone.

Social learning
Social learning is considered the most important sin-
gle factor. It includes patterns of use in the addict’s fami-ly or subculture, peer pressure, and advertising or mediainfluence.
Availability
Inexpensive or readily available tobacco, alcohol, or
drugs produce marked increases in rates of addiction.Individual development
Before the 1980s, the so-called addictive personality

was used to explain the development of addiction. Theaddictive personality was described as escapist, impul-sive, dependent, devious, manipulative, and self-cen-tered. Many doctors now believe that these charactertraits develop in addicts as a result of the addiction,rather than the traits being a cause of the addiction.
Diagnosis
In addition to a preoccupation with using and
acquiring the abused substance, the diagnosis of addic-tion is based on five criteria:
• loss of willpower

• harmful consequences
• unmanageable lifestyle• tolerance or escalation of use• withdrawal symptoms upon quitting
GALE ENCYCLOPEDIA OF MEDICINE 2 51Addiction
Crack users. Crack, a form of cocaine, is one of the most
addictive drugs. (Photograph by Roy Marsch, The Stock Mar-
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KEY TERMS
Addiction —Dependence on a habit-forming sub-
stance or behavior that the person is powerless tostop.
Addictive personality —A concept that was for-
merly used to explain addiction as the result ofpre-existing character defects in individuals.
Process addiction —Addiction to certain mood-
altering behaviors, such as eating disorders, gam-bling, sexual activity, overwork, and shopping.
Tolerance —A condition in which an addict needs

higher doses of a substance to achieve the sameeffect previously achieved with a lower dose.
Withdrawal —The unpleasant, sometimes life-
threatening physiological changes that occur, dueto the discontinuation of use of some drugs afterprolonged, regular use.Treatment
Treatment requires both medical and social

approaches. Substance addicts may need hospital treat-ment to manage withdrawal symptoms. Individual orgroup psychotherapy is often helpful, but only after sub-stance use has stopped. Anti-addiction medications, suchas methadone and naltrexone, are also commonly used.
The most frequently recommended social form of

outpatient treatment is the twelve-step program. Suchprograms are also frequently combined with psychother-apy. According to a recent study reported by the Ameri-can Psychological Association (APA), anyone, regardlessof his or her religious beliefs or lack of religious beliefs,can benefit from participation in 12-step programs suchas Alcoholics Anonymous (AA) or Narcotics Anony-mous (NA). The number of visits to 12-step self-helpgroups exceeds the number of visits to all mental

exceeds the number of visits to all mental healthprofessionals combined. There are twelve-step groupsfor all major substance and process addictions.

The Twelve Steps are:
• Admit powerlessness over the addiction.• Believe that a Power greater than oneself could restore
sanity.
• Make a decision to turn your will and your life over to
the care of God, as you understand him.
• Make a searching and fearless moral inventory of self.
• Admit to God, yourself, and another human being the
exact nature of your wrongs.
• Become willing to have God remove all these defects
from your character.

• Humbly ask God to remove shortcomings.• Make a list of all persons harmed by your wrongs and
become willing to make amends to them all.
• Make direct amends to such people, whenever possible
except when to do so would injure them or others.
• Continue to take personal inventory and promptly
admit any future wrongdoings.
• Seek to improve contact with a God of the individual’s
understanding through meditation and prayer.

• Carry the message of spiritual awakening to others and
practice these principles in all your affairs.
Acupuncture and homeopathy have been used to
treat withdrawal symptoms. Meditation, yoga , and reiki
healing have been recommended for process addictions,however, the success of these programs has not been welldocumented through controlled studies.Prognosis
The prognosis for recovery from any addiction

depends on the substance or process, the individual’s cir-cumstances, and underlying personality structure. Poly-drug users have the worst prognosis for recovery.
The most effective form of prevention appears to be
a stable family that models responsible attitudes towardmood-altering substances and behaviors. Prevention edu-cation programs are also widely used to inform the pub-lic of the harmfulness of substance abuse.
Resources
BOOKS

Resources
BOOKS
“Psychiatric Disorders: Drug Dependence.” In The Merck Man-
ual of Diagnosis and Therapy. V ol. 1. Ed. Robert Berkow,
et al. Rahway, N.J.: Merck Research Laboratories, 1992.
Robert Wood Johnson Foundation. Substance Abuse: The
Nation’s #1 Problem. Princeton, N.J., 2001.
Kalivas, Peter. “Drug Addiction: To the Cortex..and beyond”
The American Journal of Psychiatry volume 158, issue 3,
(March 2001).
Kelly, Timothy. “Addiction: A Booming $800 Billion Industry.

The World and I (July 1, 2000).
Leshner, Alan. “Addiction is a Brain Disease” Issues in Science
and Technology volume 17, issue 3, (April 1, 2001).
Mattas-Curry, L. “12-step self-help programs proved success-
ful regardless of participants’ religious background, study
GALE ENCYCLOPEDIA OF MEDICINE 2 52AddictionGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 52

suggests.” APA Monitor Online. volume 30, number 11,
(December 1999). <http://www.apa.org/monitor/>.
Al-Anon Family Groups. Box 182, Madison Square Station,
New York, NY 10159. <http://www.Al-Anon Alateen.org>.
Alcoholics Anonymous World Services, Inc. Box 459, Grand
Central Station, New York, NY 10163. <http://www.alcoholics-anonymous.org>.
American Anorexia Bulimina Association. <http://www.aab
ainc.org/>.

American Psychiatric Association. <http://www.pscyh.org>.Center for On-Line Addiction. <http://www.netaddiction.com/>.eGambling: Electronic Joural of Gambling Issues. <http://
www.camh.net/egambling/main.html>.
National Center on Addiction and Substance Abuse at Colum-
bia University. <http://www.casacolumbia.org/>.
National Alliance on Alcoholism and Drug Dependence, Inc.
12 West 21st St., New York, NY 10010. (212)206-6770.
National Clearinghouse for Alcohol and Drug Information.

<http://www.health.org>.
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
6000 Executive Boulevard, Bethesda, Maryland 20892-7003. <http://www.niaaa.nih.gov>.
Bill Asenjo, MS, CRC
Addison’s disease
Addison’s disease is a disorder involving disrupted
functioning of the part of the adrenal gland called thecortex. This results in decreased production of twoimportant chemicals (hormones) normally released bythe adrenal cortex: cortisol and aldosterone.

The adrenals are two glands, each perched on the
upper part of the two kidneys. The outer part of the glandis known as the cortex; the inner part is known as themedulla. Each of these parts of the adrenal gland isresponsible for producing different types of hormones.
Cortisol is a very potent hormone produced by the

adrenal cortex. It is involved in regulating the functioningof nearly every type of organ and tissue throughout thebody, and is considered to be one of the few hormonesabsolutely necessary for life. Cortisol is involved in:
• the very complex processing and utilization of many nutri-
ents, including sugars (carbohydrates), fats, and proteins
• the normal functioning of the circulatory system and
the heartKEY TERMS

Gland —A collection of cells whose function is to
release certain chemicals, or hormones, which areimportant to the functioning of other, sometimesdistantly located, organs or body systems.
the body, which travels to another part of the bodyin order to exert its effect.
• the functioning of muscles
• normal kidney function
• production of blood cells• the normal processes involved in maintaining the skele-
tal system

tal system
• proper functioning of the brain and nerves
• the normal responses of the immune system
Aldosterone, also produced by the adrenal cortex,
plays a central role in maintaining the appropriate pro-portions of water and salts in the body. When this bal-ance is upset, the volume of blood circulating throughoutthe body will fall dangerously low, accompanied by adrop in blood pressure.
Addison’s disease is also called primary adrenocorti-

cal insufficiency. In other words, some process interferesdirectly with the ability of the adrenal cortex to produceits hormones. Levels of both cortisol and aldosteronedrop, and numerous functions throughout the body aredisrupted.
Addison’s disease occurs in about four in every
100,000 people. It strikes both men and women of all ages.
The most common cause of Addison’s disease is the

destruction and/or shrinking (atrophy) of the adrenalcortex. In about 70% of all cases, this atrophy isbelieved to occur due to an autoimmune disorder. In anautoimmune disorder, the immune system of the body,responsible for identifying foreign invaders such asviruses or bacteria and killing them, accidentally beginsto identify the cells of the adrenal cortex as foreign, anddestroy them. In about 20% of all cases, destruction ofthe adrenal cortex is caused by tuberculosis . The

remaining cases of Addison’s disease may be caused byfungal infections, such as histoplasmosis , coccidiomy-
cosis, and cryptococcosis , which affect the adrenal
gland by producing destructive, tumor-like masses
GALE ENCYCLOPEDIA OF MEDICINE 2 53Addison’s diseaseGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 53

called granulomas; a disease called amyloidosis ,i n
which a starchy substance called amyloid is deposited inabnormal places throughout the body, interfering withthe function of whatever structure it is present within; orinvasion of the adrenal glands by cancer .
In about 75% of all patients, Addison’s disease

tends to be a very gradual, slowly developing disease.Significant symptoms are not noted until about 90% ofthe adrenal cortex has been destroyed. The most com-mon symptoms include fatigue and loss of energy,
decreased appetite, nausea, vomiting, diarrhea ,
abdominal pain , weight loss, muscle weakness, dizzi-
ness when standing, dehydration , unusual areas of

darkened (pigmented) skin, and dark freckling. As thedisease progresses, the patient may appear to have verytanned, or bronzed skin, with darkening of the lining ofthe mouth, vagina, and rectum, and dark pigmentationof the area around the nipples (aereola). As dehydrationbecomes more severe, the blood pressure will continueto drop and the patient will feel increasingly weak andlight-headed. Some patients have psychiatric symp-toms, including depression and irritability. Women losepubic and

depression and irritability. Women losepubic and underarm hair, and stop having normal men-strual periods.

When a patient becomes ill with an infection, or
stressed by an injury, the disease may suddenly andrapidly progress, becoming life-threatening. Symptomsof this “Addisonian crisis” include abnormal heartrhythms, severe pain in the back and abdomen, uncon-trollable nausea and vomiting , a drastic drop in blood
pressure, kidney failure, and unconsciousness. About25% of all Addison’s disease patients are identified dueto the development of Addisonian crisis.
Diagnosis

sion of symptoms and the disease is ultimately identifiedwhen a physician notices the areas of increased pigmen-tation of the skin. Once suspected, a number of bloodtests can lead to the diagnosis of Addison’s disease. It isnot sufficient to demonstrate low blood cortisol levels,as normal levels of cortisol vary quite widely. Instead,patients are given a testing dose of another hormonecalled corticotropin (ACTH). ACTH is produced in thebody by the pituitary gland, and normally acts by

by the pituitary gland, and normally acts by pro-moting growth within the adrenal cortex and stimulatingthe production and release of cortisol. In Addison’s dis-ease, even a dose of synthetic ACTH does not increasecortisol levels.

To distinguish between primary adrenocortical
insufficiency (Addison’s disease) and secondaryadrenocortical insufficiency (caused by failure of thepituitary to produce enough ACTH), levels of ACTH in
the blood are examined. Normal or high levels ofACTH indicate that the pituitary is working properly,but the adrenal cortex is not responding normally to thepresence of ACTH. This confirms the diagnosis ofAddison’s disease.
Treatment
Treatment of Addison’s disease involves replacing

the missing or low levels of cortisol. In the case of Addis-onian crisis, this will be achieved by injecting a potentform of steroid preparation through a needle placed in avein (intravenous or IV). Dehydration and salt loss willalso be treated by administering carefully balanced solu-tions through the IV . Dangerously low blood pressuremay require special medications to safely elevate it untilthe steroids take effect.

Patients with Addison’s disease will need to take a
steroid preparation (hydrocortisone) and a replacementfor aldosterone (fludrocortisone) by mouth for the rest oftheir lives. When a patient has an illness which causesnausea and vomiting (such that they cannot hold downtheir medications), he or she will need to enter a medicalfacility where IV medications can be administered.When a patient has any kind of infection or injury, thenormal dose of hydrocortisone will need to be doubled.
Prognosis

Prognosis
Prognosis for patients appropriately treated with
hydrocortisone and aldosterone is excellent. Thesepatients can expect to enjoy a normal lifespan. Withouttreatment, or with substandard treatment, patients arealways at risk of developing Addisonian crisis.
Resources
BOOKS
Williams, Gordon H., and Robert G. Dluhy. “Hypofunction of
the Adrenal Cortex.” In Harrison’s Principles of Internal
Medicine , ed. Anthony S. Fauci, et al. New York:
McGraw-Hill, 1997.

Brosnan, C. M., and N. F. C. Gowing. “Addison’s Disease.”
British Medical Journal 312, no. 7038 (27 Apr. 1996):
1085+.
Oelkers, Wolfgang. “Adrenal Insufficiency.” New England
Journal of Medicine 335, no. 16 (17 Oct. 1996): 1206+.
National Adrenal Disease Foundation. 505 Northern Boule-
vard, Suite 200, Great Neck, NY 11021. (516) 487-4992.

GALE ENCYCLOPEDIA OF MEDICINE 2 54Addison’s diseaseGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 54

Adenoid hyperplasia
Adenoid hyperplasia is the overenlargement of the
lymph glands located above the back of the mouth.
Located at the back of the mouth above and below

the soft palate are two pairs of lymph glands. The tonsilsbelow are clearly visible behind the back teeth; the ade-noids lie just above them and are hidden from view by thepalate. Together these four arsenals of immune defenseguard the major entrance to the body from foreigninvaders—the germs we breathe and eat. In contrast to therest of the body’s tissues, lymphoid tissue reaches itsgreatest size in mid-childhood and recedes thereafter. Inthis way children are best able to develop the

Inthis way children are best able to develop the immunitiesthey need to survive in a world full of infectious diseases.

Beyond its normal growth pattern, lymphoid tissue
grows excessively (hypertrophies) during an acute infec-tion, as it suddenly increases its immune activity to fightoff the invaders. Often it does not completely return to itsformer size. Each subsequent infection leaves behind alarger set of tonsils and adenoids. To make mattersworse, the sponge-like structure of these hypertrophiedglands can produce safe havens for germs where thebody cannot reach and eliminate them. Before antibi-

otics and the reduction in infectious childhood diseases
over the past few generations, tonsils and adenoidscaused greater health problems.
Most tonsil and adenoid hypertrophy is simply
caused by the normal growth pattern for that type of tis-sue. Less often, the hypertrophy is due to repeated throatinfections by cold viruses, strep throat , mononucleosis,
and in times gone by, diphtheria . The acute infections
are usually referred to as tonsillitis , the adenoids getting

little recognition because they cannot be seen withoutspecial instruments. Symptoms include painful, brightred, often ulcerated tonsils, enlargement of lymph nodes(glands) beneath the jaw, fever , and general discomfort.
After the acute infection subsides, symptoms are gen-

erated simply by the size of the glands. Extremely largetonsils can impair breathing and swallowing, although thatis quite rare. Large adenoids can impair nose breathingand require a child to breathe through the mouth. Becausethey encircle the only connection between the middle earand the eustachian tube, hypertrophied adenoids can alsoobstruct it and cause middle ear infections.KEY TERMS
Eustacian tube —A tube connecting the middle ear

with the back of the nose, allowing air pressure toequalize within the ear whenever it opens, such aswith yawning.
Hyperplastic —Overgrown.
Hypertrophy —Overgrowth.
Strep throat —An infection of the throat caused by
bacteria of the Streptococcus family, which causes
tonsillitis.
Ulcerated —Damaged so that the surface tissue is
lost and/or necrotic (dead).
Diagnosis
A simple tongue blade depressing the tongue allows

an adequate view of the tonsils. Enlarged tonsils mayhave deep pockets (crypts) containing dead tissue(necrotic debris). Viewing adenoids requires a small mir-ror or fiberoptic scope. A child with recurring middle earinfections may well have large adenoids. A throat cul-
ture or mononucleosis test will usually reveal the identi-
ty of the germ.
Treatment
It used to be standard practice to remove tonsils

and/or adenoids after a few episodes of acute throat or earinfection. The surgery is called tonsillectomy and ade-
noidectomy (T and A). Opinion changed as it was realized
that this tissue is beneficial to the development of immuni-ty. For instance, children without tonsils and adenoids pro-duce only half the immunity to oral polio vaccine. In addi-

tion, treatment of ear and throat infections with antibioticsand of recurring ear infections with surgical drainagethrough the ear drum (tympanostomy) has greatly reducedthe incidence of surgical removal of these lymph glands.
There are many botanical/herbal remedies that can

be used alone or in formulas to locally assist the tonsilsand adenoids in their immune function at the opening ofthe oral cavity and to tone these glands. Keeping theEustachian tubes open is an important contribution tooptimal function in the tonsils and adenoids. Food aller-
gies are often the culprits for recurring ear infections, as

well as tonsilitis and adenoiditis. Identification andremoval of the allergic food(s) can greatly assist in alle-
GALE ENCYCLOPEDIA OF MEDICINE 2 55Adenoid hyperplasiaGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 55

viating the cause of the problem. Acute tonsillitis also
benefits from warm saline gargles.
Prognosis
Hypertrophied adenoids are a normal part of grow-
ing up and should be respected for their important role inthe development of immunity. Only when their size caus-es problems by obstructing breathing or middle eardrainage do they demand intervention.
Prevention can be directed toward prompt evaluation

and appropriate treatment of sore throats to prevent over-growth of adenoid tissue. Avoiding other children withacute respiratory illness will also reduce the spread ofthese common illnesses.
Resources
BOOKS
Ballenger, John Jacob. Disorders of the Nose, Throat, Ear,
Head, and Neck. Philadelphia: Lea & Febiger, 1991.
“Otitis Media with Effusion.” In Nelson Textbook of Pediatrics ,
ed. Richard E. Behrman. Philadelphia: W. B. SaundersCo., 1996.

“Tonsils and Adenoids.” In Nelson Textbook of Pediatrics ,e d .
Richard E. Behrman. Philadelphia: W. B. Saunders Co.,1996.
Weil, Andrew. Natural Health, Natural Medicine. Boston:
Houghton Mifflin Co., 1995.
Laliberte, Richard. “The Tonsils Controversy.” Parents Maga-
zine, (Dec. 1995): 38.
Adenoid hypertrophy seeAdenoid
hyperplasia
Adenoid removal seeTonsillectomy and
adenoidectomy
Adenoidectomy seeTonsillectomy and
Adenovirus infections

Adenoviruses are DNA viruses (small infectious
agents) that cause upper respiratory tract infections, con-
junctivitis , and other infections in humans.Description
Adenoviruses were discovered in 1953. About 47 dif-

ferent types have been identified since then, and abouthalf of them are believed to cause human diseases. Infantsand children are most commonly affected by adenovirus-es. Adenovirus infections can occur throughout the year,but seem to be most common from fall to spring.
Adenoviruses are responsible for 3-5% of acute res-

piratory infections in children and 2% of respiratory ill-nesses in civilian adults. They are more apt to causeinfection among military recruits and other young peoplewho live in institutional environments. Outbreaks amongchildren are frequently reported at boarding schools andsummer camps.
Acquired immunity
Most children have been infected by at least one

adenovirus by the time they reach school age. Mostadults have acquired immunity to multiple adenovirustypes due to infections they had as children.
In one mode of adenovirus infection (called lytic

infection because it destroys large numbers of cells), ade-noviruses kill healthy cells and replicate up to one mil-lion new viruses per cell killed (of which 1-5% are infec-tious). People with this kind of infection feel sick. Inchronic or latent infection, a much smaller number ofviruses are released and healthy cells can multiply morerapidly than they are destroyed. People who have thiskind of infection don’t seem to be sick. This is probablywhy many adults have immunity to adenoviruses

many adults have immunity to adenoviruses withoutrealizing they have been infected.

Childhood infections
In children, adenoviruses most often cause acute
upper respiratory infections with fever and runny nose.
Adenovirus types 1, 2, 3,5, and 6 are responsible formost of these infections. Occasionally more seriouslower respiratory diseases, such as pneumonia , may
occur.
Adenoviruses also cause acute pharyngoconjunctival
fever in children. This disease is most often caused bytypes 3 and 7. Symptoms, which appear suddenly andusually disappear in less than a week, include:

• inflammation of the lining of the eyelid (conjunctivitis)
•f e v e r
•sore throat (pharyngitis)
• runny nose
• inflammation of lymph glands in the neck (cervical
adenitis)
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Adenoviruses also cause acute diarrhea in young
children, characterized by fever and watery stools. Thiscondition is caused by adenovirus types 40 and 41 andcan last as long as two weeks.
As much as 51% of all hemorrhagic cystitis (inflam-

mation of the bladder and of the tubes that carry urine tothe bladder from the kidneys) in American and Japanesechildren can be attributed to adenovirus infection. Achild who has hemorrhagic cystitis has bloody urine forabout three days, and invisible traces of blood can befound in the urine a few days longer. The child will feelthe urge to urinate frequently—but find it difficult to doso—for about the same length of time.
Adult infections
In adults, the most frequently reported adenovirus

infection is acute respiratory disease (ARD, caused bytypes 4 and 7) in military recruits. Influenza-like symp-toms including fever, sore throat, runny nose, and cough
are almost always present; weakness, chills, headache ,
and swollen lymph glands in the neck may also occur.The symptoms typically last three to five days.
Epidemic keratoconjunctivitis (EKC, caused by ade-

novirus types 8, 19, and 37) was first seen in shipyardworkers whose eyes had been slightly injured by chips ofrust or paint. This inflammation of tissues lining the eye-lid and covering the front of the eyeball can also becaused by using contaminated contact lens solutions orby drying the hands or face with a towel used by some-one who has this infection.
The inflamed, sticky eyelids characteristic of con-

junctivitis develop 4-24 days after exposure and lastbetween one and four weeks. Only 5-8% of patients withepidemic keratoconjunctivitis experience respiratorysymptoms. One or both eyes may be affected. As symp-toms of conjunctivitis subside, eye pain and watering
and blurred vision develop. These symptoms of keratitis
may last for several months, and about 10% of theseinfections spread to at least one other member of thepatient’s household.
Other illnesses associated with adenovirus include:

• encephalitis (inflammation of the brain) and other
infections of the central nervous system (CNS)
• gastroenteritis (inflammation of the stomach and intes-
tines)
• acute mesenteric lymphadenitis (inflammation of
lymph glands in the abdomen)
• chronic interstitial fibrosis (abnormal growth of con-
nective tissue between cells)
• intussusception (a type of intestinal obstruction)KEY TERMS
Conjunctivitis —Inflammation of the conjunctiva,

the mucous membrane lining the inner surfaces ofthe eyelid and the front of the eyeball.
Virus —A small infectious agent consisting of a
core of genetic material (DNA or RNA) surround-ed by a shell of protein.
• pneumonia that doesn’t respond to antibiotic therapy
•whooping cough syndrome when Bordetella pertussis
(the bacterium that causes classic whooping cough) isnot found

Specific adenovirus infections can be traced to par-
ticular sources and produce distinctive symptoms. Ingeneral, however, adenovirus infection is caused by:
• inhaling airborne viruses• getting the virus in the eyes by swimming in contami-
nated water, using contaminated eye solutions or instru-ments, wiping the eyes with contaminated towels, orrubbing the eyes with contaminated fingers.
• not washing the hands after using the bathroom, and
then touching the mouth or eyes

Symptoms common to most types of adenovirus
infections include:
• cough•f e v e r• runny nose• sore throat• watery eyes
Diagnosis
Although symptoms may suggest the presence of
adenovirus, distinguishing these infections from otherviruses can be difficult. A definitive diagnosis is based onculture or detection of the virus in eye secretions, spu-tum, urine, or stool.
The extent of infection can be estimated from the

results of blood tests that measure increases in the quan-tity of antibodies the immune system produces to fight it.Antibody levels begin to rise about a week after infectionoccurs and remain elevated for about a year.
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Treatment
Treatment of adenovirus infections is usually sup-
portive and aimed at relieving symptoms of the illness.Bed rest may be recommended along with medications toreduce fever and/or pain. ( Aspirin should not be given to
children because of concerns about Reye’s syndrome.)Eye infections may benefit from topical corticosteroids

to relieve symptoms and shorten the course of the dis-ease. Hospitalization is usually required for severe pneu-monia in infants and for EKC (to prevent blindness). Noeffective antiviral drugs have been developed.
Prognosis
Adenovirus infections are rarely fatal. Most patients
recover fully.
Practicing good personal hygiene and avoiding peo-

ple with infectious illnesses can reduce the risk of devel-oping adenovirus infection. Proper handwashing can pre-vent the spread of the virus by oral-fecal transmission.Sterilization of instruments and solutions used in the eyecan prevent the spread of EKC, as can adequate chlorina-tion of swimming pools.
A vaccine containing live adenovirus types 4 and 7

is used to control disease in military recruits, but it is notrecommended or available for civilian use. Vaccines pre-pared from purified subunits of adenovirus are underinvestigation.
Resources
BOOKS
Mandell, Gerald L., ed., et al. Principles and Practices of Infec-
tious Diseases. New York: Churchill Livingstone, 1995.

Adjustment disorders
An adjustment disorder is a debilitating reaction,
usually lasting less than six months, to a stressful eventor situation. It is not the same thing as post-traumatic
stress disorder (PTSD), which usually occurs in reac-
tion to a life-threatening event and can be longer lasting.Description
An adjustment disorder usually begins within three

months of a stressful event, and ends within six monthsafter the stressor stops. There are many different sub-types of adjustment disorders, including adjustment dis-order with:
• depression•anxiety
• mixed anxiety and depression• conduct disturbances• mixed disturbance of emotions and conduct• unspecified
Adjustment disorders are very common and can

affect anyone, regardless of gender, age, race, or lifestyle.By definition, an adjustment disorder is short-lived,unless a person is faced with a chronic recurring crisis(such as a child who is repeatedly abused). In such cases,the adjustment disorder may last more than six months.
An adjustment disorder occurs when a person can’t

cope with a stressful event and develops emotional orbehavioral symptoms. The stressful event can be anything:it might be just one isolated incident, or a string of prob-lems that wears the person down. The stress might be any-
thing from a car accident or illness, to a divorce, or even acertain time of year (such as Christmas or summer).
People with adjustment disorder may have a wide

variety of symptoms. How those symptoms combinedepend on the particular subtype of adjustment disorderand on the individual’s personality and psychologicaldefenses. Symptoms normally include some (but not all)of the following:
• hopelessness
• sadness• crying• anxiety• worry
• headaches or stomachaches
• withdrawal• inhibition• truancy• vandalism• reckless driving• fighting• other destructive acts

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Diagnosis
It is extremely important that a thorough evaluation
rule out other more serious mental disorders, since thetreatment for adjustment disorder may be very differentthan for other mental problems.
In order to be diagnosed as a true adjustment disor-

der, the level of distress must be more severe than whatwould normally be expected in response to the stressor,or the symptoms must significantly interfere with a per-son’s social, job, or school functioning. Normal expres-sion of grief, in bereavement for instance, is not consid-ered an adjustment disorder.
Treatment
Psychotherapy (counseling) is the treatment of

choice for adjustment disorders, since the symptoms arean understandable reaction to a specific stress. The typeof therapy depends on the mental health expert, but itusually is short-term treatment that focuses on resolvingthe immediate problem.
Therapy usually will help clients:
• develop coping skills
• understand how the stressor has affected their lives
• develop alternate social or recreational activities

Family or couples therapy may be helpful in some
cases. Medications are not usually used to treat adjust-ment disorders, although sometimes a few days or weeksof an anti-anxiety drug can control anxiety or sleepingproblems.
Self-help groups aimed at a specific problem (such
as recovering from divorce or job loss) can be extremelyhelpful to people suffering from an adjustment disorder.Social support, which is usually an important part of self-help groups, can lead to a quicker recovery.

Prognosis
Most people recover completely from adjustment
disorders, especially if they had no previous history ofmental problems, and have a stable home life with strongsocial support. People with progressive or cyclic disor-ders (such as multiple sclerosis ) may experience an
adjustment disorder with each exacerbation period.
Resources
BOOKS
Horowitz, Mardi J. Stress Response Syndromes: PTSD, Grief and
Adjustment Disorders. Northvale, NJ: Jason Aronson, 1997.

Luther, Suniya G., Jacob A. Burack, and Dante Cicchetti. Develop-
mental Psychopathology: Perspectives on Adjustment, Risk,and Disorder. London: Cambridge University Press, 1997.KEY TERMS
Multiple sclerosis —A progressive disorder of the
central nervous system in which scattered patchesof the protective sheath covering the nerves isdestroyed. The disease, which causes progressiveparalysis, is marked by periods of exacerbationand remission. There is no cure.

Post-traumatic stress disorder (PTSD) —A specific
form of anxiety that begins after a life-threateningevent, such as rape, a natural disaster, or combat-related trauma.
Newcorn, Jeffrey H., and James Strain. “Adjustment Disorder
in Children and Adolescents.” Journal of the American
Academy of Child and Adolescent Psychiatry 31 (Mar.
1992): 318-27.
Adrenal gland cancer
Adrenal gland cancers are rare cancers occuring in

the endocrine tissue of the adrenals. They are character-ized by overproduction of adrenal gland hormones.
Cancers of the adrenal gland are very rare. The
adrenal gland is a hormone producing endocrine glandwith two main parts, the cortex and the medulla. Themain hormone of the adrenal cortex is cortisol and themain hormone of the adrenal medulla is epinephrine.When tumors develop in the adrenal gland, they secreteexcess amounts of these hormones. A cancer that arises

in the adrenal cortex is called an adrenocortical carcino-ma and can produce high blood pressure, weight gain,excess body hair, weakening of the bones and diabetes. Acancer in the adrenal medulla is called a pheochromocy-
toma and can cause high blood pressure, headache ,pal-
pitations , and excessive perspiration. Although these can-
cers can happen at any age, most occur in young adults.
It is not known what causes adrenal gland cancer,

but some cases are associated with hereditary diseases.
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Symptoms of adrenal cancer are related to the specific
hormones produced by that tumor. An adrenocortical car-cinoma typically secretes high amounts of cortisol, pro-ducing Cushing’s Syndrome . This syndrome produces
progressive weight gain, rounding of the face, andincreased blood pressure. Women can experience men-strual cycle alterations and men can experience feminiza-tion. The symptoms for pheochromocytoma includehypertension , acidosis, unexplained fever and weight

loss. Because of the hormones produced by this type oftumor, anxiety is often a feature also.
Diagnosis
Diagnosis for adrenal cancer usually begins with
blood tests to evaluate the hormone levels. These hor-mones include epinephrine, cortisol, and testosterone. Italso includes magnetic resonance imaging , and com-
puted tomography scans to determine the extent of the
disease. Urine and blood tests can be done to detect thehigh levels of hormone secreted by the tumor.
Treatment

Treatment
Treatment is aimed at removing the tumor by
surgery. In some cases, this can be done by laparoscopy .
Surgery is sometimes followed by chemotherapy and/or
radiation therapy . Because the surgery removes the
source of many important hormones, hormones must besupplemented following surgery. If adrenocortical cancerrecurs or has spread to other parts of the body (metasta-sized), additional surgery may be done followed bychemotherapy using the drug mitotane.KEY TERMS

Cortisol —A hormone produced by the adrenal
cortex. It is partially responsible for regulatingblood sugar levels.
Diabetes —A disease characterized by low blood
sugar.
Epinephrine —A hormone produced by the adren-
al medulla. It is important in the response to stressand partially regulates heart rate and metabolism.It is also called adrenaline.
Laparoscopy —The insertion of a tube through the

abdominal wall. It can be used to visualize theinside of the abdomen and for surgical procedures.Alternative treatment
As with any form of cancer, all conventional treat-
ment options should be considered and applied as appro-priate. Nutritional support, as well as supporting the func-tioning of the entire person diagnosed with adrenal glandcancer through homeopathic medicine, acupuncture , vit-

amin and mineral supplementation, and herbal medicine,can benefit recovery and enhance quality of life.
Prognosis
The prognosis for adrenal gland cancer is variable.
For localized pheochromocytomas the 5-year survival rateis 95%. This rate decreases with aggressive tumors thathave metastasized. The prognosis for adrenal cortical can-cer is not as good with a 5-year survival rate of 10-35%.
Since so little is known about the cause of adrenal

gland cancer, it is not known if it can be prevented.
Resources
BOOKS
Norton, J. A. “Adrenal Tumors.” In Cancer, Principles and
Practice of Oncology. Ed. V . T. DeVita, S. Hellman, and
S. A. Rosenberg. Philadelphia: Lippincott-Raven, 1997.
OTHER
Endocrine Web. <http://www.endocrineweb.com>.
Cindy L. A. Jones, PhD
Adrenal gland removal seeAdrenalectomy
Adrenal gland scan
The adrenal gland scan is a nuclear medicine evalua-
tion of the medulla (inner tissue) of the adrenal gland.

Purpose
The adrenal glands are a pair of small organs located
just above the kidney, which contain two types of tissue.The adrenal cortex produces hormones that affect waterbalance and metabolism in the body. The adrenal medul-la produces adrenaline and noradrenaline (also calledepinepherine and norepinepherine).
An adrenal gland scan is done when too much
adrenaline and noradrenaline is produced in the body and

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a tumor in the adrenal gland is suspected. One such situa-
tion in which a tumor might be suspected is when highblood pressure ( hypertension ) does not respond to med-
ication. Tumors that secrete adrenaline and noradrenalinecan also be found outside the adrenal gland. An adrenalgland scan usually covers the abdomen, chest, and head.
Adrenal gland scans are not recommended for preg-

nant women because of the potential harm to the devel-oping fetus. A pregnant woman should discuss with herdoctor the risks of the procedure against the benefits ofthe information it can provide in evaluating her individ-ual medical situation.
People who have recently undergone tests that use
barium must wait until the barium has been eliminatedfrom their system in order to obtain accurate results fromthe adrenal gland scan.

The adrenal gland scan takes several days. On the
first day, a radiopharmaceutical is injected intravenouslyinto the patient. On the second, third, and fourth day thepatient is positioned under the camera for imaging. Thescanning time each day takes approximately 30 minutes.It is essential that the patient remain still during imaging.
Occasionally, the scanning process may involve

fewer than three days, or it may continue several dayslonger. The area scanned extends from the pelvis andlower abdomen to the lower chest. Sometimes the upperlegs, thighs, and head are also included.
For two days before and ten days after the injection
of the radiopharmaceutical, patients are given eitherLugol’s solution or potassium iodine. This prevents thethyroid from taking up radioactive iodine and interferingwith the scan.

Aftercare
The patient should not feel any adverse effects of the
test and can resume normal activity immediately. Follow-up tests that might be ordered include a nuclear scan ofthe bones or kidney, a computed tomography scan (CT)of the adrenals, or an ultrasound of the pelvic area.
Risks
The main risk associated with this test is to the fetus
of a pregnant woman.KEY TERMS
Adrenal cortex —The outer tissue of the adrenal

gland. It produces a group of chemically relatedhormones called corticosteroids that control min-eral and water balance in the body and includealdosterone and cortisol.
Adrenal medulla —The inner tissue of the adrenal
gland. It produces the hormones adrenaline andnoradrenaline.
Lugol’s solution —A strong iodine solution.
Normal results will show no unusual areas of hor-
mone secretion and no tumors.

Abnormal results will show evidence of a tumor
where there is excessive secretion of adrenaline or nora-drenaline. Over 90% of these tumors are in the abdomen.
Resources
BOOKS
Tish Davidson
Adrenal hypofunction seeAddison’s disease
Adrenal insufficiency seeAddison’s disease
Adrenal virilism

Adrenal virilism is the development or premature
development of male secondary sexual characteristicscaused by male sex hormones (androgens) excessivelyproduced by the adrenal gland. This disorder can occurbefore birth and can lead to sexual abnormalities in new-borns. It can also occur in girls and women later in life.
In the normal human body, there are two adrenal
glands. They are small structures that lie on top of the

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kidneys. The adrenal glands produce many hormones
that regulate body functions. These hormones includeandrogens, or male hormones. Androgens are producedin normal girls and women. Sometimes, one or both ofthe adrenal glands becomes enlarged or overactive, pro-ducing more than the usual amount of androgens. Theexcess androgens create masculine characteristics.
In infants and children, adrenal virilism is usually

the result of adrenal gland enlargement that is present atbirth. This is called congenital adrenal hyperplasia .
The cause is usually a genetic problem that leads tosevere enzyme deficiencies. In rare cases, adrenal viril-ism is caused by an adrenal gland tumor. The tumor canbe benign (adrenal adenoma) or cancerous (adrenal car-cinoma). Sometimes virilism is caused by a type oftumor on a woman’s ovary (arrhenoblastoma).
Newborn girls with adrenal virilism have external

sex organs that seem to be a mixture of male and femaleorgans (called female pseudohermaphrodism). Newbornboys with the disorder have enlarged external sex organs,and these organs develop at an abnormally rapid pace.
Children with congenital adrenal hyperplasia begin
growing abnormally fast, but they stop growing earlierthan normal. Later in childhood, they are typically short-er than normal but have well-developed trunks.

Women with adrenal virilization may develop facial
hair. Typically, their menstrual cycles are infrequent orabsent. They may also develop a deeper voice, a moreprominent Adam’s apple, and other masculine signs.
Diagnosis
Endocrinologists, doctors who specialize in the
diagnosis and treatment of glandular disorders, have themost expertise to deal with adrenal virilization. SomeKEY TERMS
Glucocorticoid —A hormone produced by the

adrenal gland; this hormone leads to an increasein blood sugar and creation of sugar molecules bythe liver.
Hydrocortisone —A hormone in the group of glu-
cocorticoid hormones.
Prednisone —A drug that functions as a glucocorti-
coid hormone.doctors who treat disorders of the internal organs
(internists) and doctors who specialize in treating thereproductive system of women (gynecologists) may alsobe able to help patients with this disorder.

tests on blood samples from the patient. These tests mea-sure the concentration of different hormones. Differentabnormalities of the adrenal gland produce a differentpattern of hormonal abnormalities. These tests can alsohelp determine if the problem is adrenal or ovarian. If atumor is suspected, special x rays may be done to visual-ize the tumor in the body. Final diagnosis may depend onobtaining a tissue sample from the tumor (biopsy), andexamining it under a microscope in order to verify

treated with daily doses of a glucocorticoid. Usuallyprednisone is the drug of choice, but in infants hydrocor-tisone is usually given. Laboratory tests are usually need-ed from time to time to adjust the dosage. Girls withpseudohermaphrodism may require surgery to make theirexternal sex organs appear more normal. If a tumor iscausing the disorder, the treatment will depend on thetype and location of the tumor. Information about thetumor cell type and the spread of the tumor is used todecide

type and the spread of the tumor is used todecide the best kind of treatment for a particular patient.If the tumor is cancerous, the patient will require specialtreatment depending on how far the cancer has

advanced. Treatment can be a combination of surgery,medications used to kill cancer cells ( chemotherapy ),
and x rays or other high energy rays used to kill cancercells ( radiation therapy ). Sometimes the doctor must
remove the adrenal gland and the surrounding tissues. Ifthe tumor is benign, then surgically removing the tumormay be the best option.
Prognosis
Ongoing glucocorticoid treatment usually controls

adrenal virilism in cases of adrenal hyperplasia, but thereis no cure. If a cancerous tumor has caused the disorder,patients have a better prognosis if they have an early stageof cancer that is diagnosed quickly and has not spread.
Resources
BOOKS
Little, M., and D. C. Garrell. Encyclopedia of Health; The

Endocrine System: The Healthy Body. Chelsea House,
1990.
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Willensy, D. “The Endocrine System.” American Health (Apr.
1996): 92-3.
Adrenalectomy
Adrenalectomy is the surgical removal of one or

both of the adrenal glands. The adrenal glands are pairedendocrine glands, one located above each kidney, thatproduce hormones such as epinephrine, norepinephrine,androgens, estrogens, aldosterone, and cortisol. Adrena-lectomy is usually performed by conventional (open)surgery, but in selected patients surgeons may uselaparoscopy . With laparoscopy, adrenalectomy can be
accomplished through four very small incisions.
Purpose

Purpose
Adrenalectomy is usually advised for patients with
tumors of the adrenal glands. Adrenal gland tumors maybe malignant or benign, but all typically excrete excessiveamounts of one or more hormones. A successful proce-dure will aid in correcting hormone imbalances, and mayalso remove cancerous tumors that can invade other partsof the body. Occasionally, adrenalectomy may be recom-mended when hormones produced by the adrenal glandsaggravate another condition such as breast cancer .

The adrenal glands are fed by numerous blood ves-
sels, so surgeons need to be alert to extensive bleedingduring surgery. In addition, the adrenal glands lie close toone of the body’s major blood vessels (the vena cava),and to the spleen and the pancreas. The surgeon needs toremove the gland(s) without damaging any of theseimportant and delicate organs.
Open adrenalectomy
The surgeon may operate from any of four direc-

tions, depending on the exact problem and the patient’sbody type.
In the anterior approach, the surgeon cuts into the

abdominal wall. Usually the incision will be horizontal,just under the rib cage. If the surgeon intends to operateon only one of the adrenal glands, the incision will rununder just the right or the left side of the rib cage. Some-times a vertical incision in the middle of the abdomenprovides a better approach, especially if both adrenalglands are involved.
In the posterior approach, the surgeon cuts into the

back, just beneath the rib cage. If both glands are to beremoved, an incision is made on each side of the body.This approach is the most direct route to the adrenalglands, but it does not provide quite as clear a view of thesurrounding structures as the anterior approach.
In the flank approach, the surgeon cuts into the

patient’s side. This is particularly useful in massively obesepatients. If both glands need to be removed, the surgeonmust remove one gland, repair the surgical wound, turn thepatient onto the other side, and repeat the entire process.
The last approach involves an incision into the chest

cavity, either with or without part of the incision into theabdominal cavity. It is used when the surgeon anticipatesa very large tumor, or if the surgeon needs to examine orremove nearby structures as well.
Laparoscopic adrenalectomy
This technique does not require the surgeon to open

the body cavity. Instead, four small incisions (about 1/2in diameter each) are made into a patient’s flank, justunder the rib cage. A laparoscope, which enables the sur-geon to visualize the inside of the abdominal cavity on atelevision monitor, is placed through one of the incisions.The other incisions are for tubes that carry miniaturizedversions of surgical tools. These tools are designed to beoperated by manipulations that the surgeon makes out-side the body.

Most aspects of preparation are the same as in other
major operations. In addition, hormone imbalances areoften a major challenge. Whenever possible, physicianswill try to correct hormone imbalances through medica-tion in the days or weeks before surgery. Adrenal tumorsmay cause other problems such as hypertension or inad-

equate potassium in the blood, and these problems alsoshould be resolved if possible before surgery is per-formed. Therefore, a patient may take specific medicinesfor days or weeks before surgery.
Most adrenal tumors can be imaged very well with a

CT scan or MRI, and benign tumors tend to look differ-ent on these tests than do cancerous tumors. Surgeonsmay order a CT scan, MRI, or scintigraphy (viewing ofthe location of a tiny amount of radioactive agent) to helplocate exactly where the tumor is.
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The day before surgery, patients will probably have
an enema to clear the bowels. In patients with lung prob-lems or clotting problems, physicians may advise specialpreparations.
Aftercare
Patients stay in the hospital for various lengths of
time after adrenalectomy. The longest hospital stays arerequired for open surgery using an anterior approach;hospital stays of about three days are indicated for opensurgery using the posterior approach or for laparoscopicadrenalectomy.

The special concern after adrenalectomy is the
patient’s hormone balance. There may be several sets oflab tests to define hormone problems and monitor theresults of drug treatment. In addition, blood pressureproblems and infections are more common after removalof certain types of adrenal tumors.
As with most open surgery, surgeons are also con-

cerned about blood clots forming in the legs and travel-ing to the lungs (venous thromboembolism), bowel prob-lems, and postoperative pain . With laparoscopic adrena-
lectomy, these problems are somewhat less difficult, butthey are still present.
Risks
The special risks of adrenalectomy involve major
hormone imbalances, caused by the underlying disease,KEY TERMS
Laparoscope —An instrument that enables the sur-

geon to see inside the abdominal cavity by meansof a thin tube that carries an image to a televisionmonitor.
Pancreas —An organ that secretes a number of
digestive hormones and also secretes insulin toregulate blood sugar.
Pheochromocytoma —A tumor of specialized cells
of the adrenal gland.
Spleen —An organ that traps and breaks down red
blood cells at the end of their useful life and man-ufactures some key substances used by theimmune system.

Vena cava —The large vein that drains directly into
the heart after gathering incoming blood from theentire body.the surgery, or both.These can include problems with
wound healing itself, blood pressure fluctuations, andother metabolic problems.
Other risks are typical of many operations.These
include:
• bleeding• damage to adjacent organs (spleen, pancreas)• loss of bowel function• blood clots in the lungs• lung problems• surgical infections• pain• extensive scarring
Resources
BOOKS

Resources
BOOKS
Bradley, Edward L., III. The Patient’s Guide to Surgery.
Philadelphia: University of Pennsylvania Press, 1994.
Little, M., and D. C. Garrell. The Endocrine System: The
Healthy Body. Chelsea House, 1990.
Janis O. Flores
Adrenocortical insufficiency seeAddison’s
disease
Adrenocorticotropic hormone
test

test
Adrenocorticotropic hormone test (also known as an
ACTH test or a corticotropin test) measures pituitarygland function.
Purpose
The pituitary gland produces the hormone ACTH,

which stimulates the outer layer of the adrenal gland (theadrenal cortex). ACTH causes the release of the hormoneshydrocortisone (cortisol), aldosterone, and androgen. Themost important of these hormones released is cortisol.The ACTH test is used to determine if too much cortisolis being produced ( Cushing’s syndrome ) or if not
enough cortisol is being produced ( Addison’s disease ).

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ACTH has diurnal variation, meaning that the levels
of this hormone vary according to the time of day. Thehighest levels occur in the morning hours. Testing fornormal secretion, as well as for Cushing’s disease, mayrequire multiple samples. For sequential follow-up, ablood sample analyzed for ACTH should always bedrawn at the same time each day.
ACTH can be directly measured by an analyzing

method (immunoassay) in many large laboratories. How-ever, smaller laboratories are usually not equipped to per-form this test and they may need to send the blood sam-ple to a larger laboratory. Because of this delay, resultsmay take several days to obtain.
ACTH production is partly controlled by an area in

the center of the brain (the hypothalamus) and partlycontrolled by the level of cortisol in the blood. WhenACTH levels are too high, cortisol production increasesto suppress ACTH release from the pituitary gland. IfACTH levels are too low, the hypothalamus producescorticotropin-releasing hormone (CRH) to stimulate thepituitary gland to make more ACTH. ACTH levels rise inresponse to stress , emotions, injury, infection, burns ,
surgery, and decreased blood pressure.
Cushing’s syndrome

Cushing’s syndrome is caused by an abnormally high
level of circulating hydrocortisone. The high level may bethe result of an adrenal gland tumor or enlargement ofboth adrenal glands due to a pituitary tumor. The highlevel of hydrocortisone may be the result of taking corti-costeroid drugs for a long time. Corticosteroid drugs arewidely used for inflammation in disorders like rheuma-
toid arthritis , inflammatory bowel disease, and asthma .

symptoms are caused by a deficiency of hydrocorti-sone and aldosterone. The most common cause of thisdisease is an autoimmune disorder. The immune sys-tem normally fights foreign invaders in the body likebacteria. In an autoimmune disorder, the immune sys-tems attacks the body. In this case, the immune systemproduces antibodies that attack the adrenal glands.Addison’s disease generally progresses slowly, withsymptoms developing gradually over months or years.However, acute episodes, called

months or years.However, acute episodes, called Addisonian crises, arebrought on by infection, injury, or other stresses. Diag-nosis is generally made if the patient fails to respond toKEY TERMS

Adrenal glands —A pair of endocrine glands that
lie on top of the kidneys.
Pituitary gland —The most important of the
endocrine glands, glands that release hormonesdirectly into the bloodstream; sometimes calledthe master gland.
an injection of ACTH, which normally stimulates the
secretion of hydrocortisone.
A person’s ACTH level is determined from a blood

sample. The patient must fast from midnight until the testthe next morning. This means that the patient cannot eator drink anything after midnight except water. The patientmust also avoid radioisotope scanning tests or recentlyadministered radioisotopes prior to the blood test.
Risks
The risks associated with this test are minimal. They

may include slight bleeding from the location where theblood was drawn. The patient may feel faint or lighthead-ed after the blood is drawn. Sometimes the patient mayhave an accumulation of blood under the puncture site(hematoma) after the test.
Each laboratory will have its own set of normal val-
ues for this test. The normal values can range from:Morning (4-8 
A.M.) 8-100 pg/mL or 10-80 ng/L (SI units)
Evening (8-10 P.M.) less than 50 pg/mL or less than 50
ng/L (SI units)

In Cushing’s syndrome, high levels of ACTH may
be caused by ACTH-producing tumors. These tumorsmay be either in the pituitary or in another area (liketumors from lung cancer or ovarian cancer ). Low
ACTH levels may be caused by adrenal enlargement dueto high levels of cortisol and feedback to the pituitary.
In Addison’s disease, high levels of ACTH may be

caused by adrenal gland diseases. These diseases decreaseadrenal hormones and the pituitary attempts to increasefunctioning. Low levels of ACTH may occur because ofdecreased pituitary function.
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KEY TERMS
Amniocentesis —The collection of amniotic fluid
through a needle inserted through the abdomen.Used to collect fetal cells for genetic analysis.
Ataxia —Loss of coordination of muscular move-
ment.
Hypertonia —Having excessive muscular tone.
Myelin —A layer that encloses nerve cells and
some axons and is made largely of lipids andlipoproteins.
Neuropathy —A disease or abnormality of the
peripheral nerves.Resources
BOOKS
Jacobs, David S., et al. Laboratory Test Handbook. 4th ed. New

York: Lexi-Comp Inc., 1996.
Pagana, Kathleen Deska. Mosby’s Manual of Diagnostic and
Laboratory Tests. St. Louis: Mosby, Inc., 1998.
Adrenogenital syndrome seeAdrenal virilism
Adrenoleukodystrophy
Adrenoleukodystrophy is a rare genetic disease
characterized by a loss of myelin surrounding nerve cellsin the brain and progressive adrenal gland dysfunction.
Adrenoleukodystrophy (ALD) is a member of a

group of diseases, leukodystrophies, that cause damageto the myelin sheath of nerve cells. Approximately one in100,000 people is affected by ALD. There are three basicforms of ALD: childhood, adult-onset, and neonatal. Thechildhood form of the disease is the classical form and isthe most severe. Childhood ALD is progressive and usu-ally leads to total disability or death . It affects only boys

because the genetic defect is sex-linked (carried on the Xchromosome). Onset usually occurs between ages fourand ten and can include many different symptoms, not allof which appear together. The most common symptomsare behavioral problems and poor memory. Other symp-toms frequently seen are loss of vision, seizures, poorlyarticulated speech, difficulty swallowing, deafness, prob-lems with gait and coordination, fatigue , increased skin
pigmentation, and progressive dementia .

The adult-onset form of the disease, also called
adrenomyeloneuropathy, is milder, progresses slowly, isusually associated with a normal life span, and usuallyappears between ages 21-35. Symptoms may includeprogressive stiffness, weakness, or paralysis of the lower

limbs and loss of coordination. Brain function deteriora-tion may also been seen. Women who are carriers of thedisease occasionally experience the same symptoms, aswell as others, including ataxia, hypertonia (excessivemuscle tone), mild peripheral neuropathy , and urinary
problems. The neonatal form affects both male andfemale infants and may produce mental retardation ,

facial abnormalities, seizures, retinal degeneration, poormuscle tone, enlarged liver, and adrenal dysfunction.Neonatal ALD usually progresses rapidly.
The genetic defect in ALD causes a decrease in the

ability to degrade very long chain fatty acids. These buildup in the adrenal glands, brain, plasma, and fibroblasts.The build-up of very long chain fatty acids interfereswith the ability of the adrenal gland to convert choles-terol into steroids and causes demyelination of nerves inthe white matter of the brain. Demyelinated nerve cellsare unable to function properly.
Diagnosis
Diagnosis is made based on observed symptoms, a

biochemical test, and a family history. The biochemicaltest detects elevated levels of very long chain fatty acidsin samples from amniocentesis , chorionic villi, plasma,
red blood cells, or fibroblasts. A family history may indi-cate the likelihood of ALD because the disease is carriedon the X-chromosome by the female lineage of families.
Treatment
Treatment for all forms of ALD consists of treating

the symptoms and supporting the patient with physicaltherapy, psychological counseling, and special educationin some cases. There is no cure for this disease, and thereare no drugs that can reverse demyelination of nerve andbrain cells. Dietary measures consist of reducing theintake of foods high in fat, which are a source of verylong chain fatty acids. A mixture called Lorenzo’s Oilhas been shown to reduce the level of long chain fattyacids if used long term; however, the rate of myelin loss

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is unaffected. Experimental bone marrow transplanta-
tion has not been very effective.
Prognosis
Prognosis for childhood and neonatal ALD patients
is poor because of the progressive myelin degeneration.Death usually occurs between one and ten years afteronset of symptoms.
Since ALD is a genetic disease, prevention is largely
limited to genetic counseling and fetal monitoring
through amniocentesis or chorionic villus sampling .
Resources
BOOKS

Resources
BOOKS
Berkow, Robert. Merck Manual of Medical Information. White-
house Station, NJ: Merck Research Laboratories, 1997.
Adrenomyeloneuropathy seeAdrenoleuko-
dystrophy
Adult respiratory distress
syndrome
Adult respiratory distress syndrome (ARDS), also

called acute respiratory distress syndrome, is a type oflung (pulmonary) failure that may result from any dis-ease that causes large amounts of fluid to collect in thelungs. ARDS is not itself a specific disease, but a syn-drome, a group of symptoms and signs that make up oneof the most important forms of lung or respiratory fail-
ure. It can develop quite suddenly in persons whose

lungs have been perfectly normal. Very often ARDS is atrue medical emergency. The basic fault is a breakdownof the barrier, or membrane, that normally keeps fluidfrom leaking out of the small blood vessels of the lunginto the breathing sacs (the alveoli).
Another name for ARDS is shock lung. Its formal

name is misleading, because children, as well as adults,may be affected. In the lungs the smallest blood vessels,or capillaries, make contact with the alveoli, tiny air sacsat the tips of the smallest breathing tubes (the bronchi).This is the all-important site where oxygen passes fromair that is inhaled to the blood, which carries it to all partsof the body. Any form of lung injury that damages thispoint of contact, called the alveolo-capillary junction,will allow blood and tissue fluid to

junction,will allow blood and tissue fluid to leak into the alveoli,eventually filling them so that air cannot enter. The resultis the type of breathing distress called ARDS. ARDS isone of the major causes of excess fluid in the lungs, theother being heart failure .

inflamed cells in the lungs. There also is debris left overfrom damaged lung cells, and fibrin, a semi-solid materi-al derived from blood in the tissues. Typically thesematerials join together with large molecules in the blood(proteins), to form hyaline membranes. (These mem-branes are very prominent in premature infants whodevelop respiratory distress syndrome; it is often calledhyaline membrane disease.) If ARDS is very severe orlasts a long time, the lungs do not heal, but rather

a long time, the lungs do not heal, but rather becomescarred, a process known as fibrosis. The lack of a nor-mal amount of oxygen causes the blood vessels of thelung to become narrower, and in time they, too, maybecome scarred and filled with clotted blood. The lungsas a whole become very “stiff,” and it becomes muchharder for the patient to breathe.

A very wide range of diseases or toxic substances,
including some drugs, can cause ARDS. They include:
• Breathing in (aspiration) of the stomach contents when
regurgitated, or salt water or fresh water from nearlydrowning.
• Inhaling smoke, as in a fire; toxic materials in the air,
such as ammonia or hydrocarbons; or too much oxy-gen, which itself can injure the lungs.
• Infection by a virus or bacterium, or sepsis , a wide-
spread infection that gets into the blood.

• Massive trauma, with severe injury to any part of the
body.
• Shock with persistently low blood pressure may not in
itself cause ARDS, but it can be an important factor.
• A blood clotting disorder called disseminated intravas-
cular coagulation, in which blood clots form in vesselsthroughout the body, including the lungs.
• A large amount of fat entering the circulation and trav-

eling to the lungs, where it lodges in small blood ves-sels, injuring the cells lining the vessel walls.
• An overdose of a narcotic drug, a sedative, or, rarely,
aspirin .
GALE ENCYCLOPEDIA OF MEDICINE 2 67Adult respiratory distress syndromeGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 67

• Inflammation of the pancreas ( pancreatitis ), when
blood proteins, called enzymes, pass to the lungs andinjure lung cells.
• Severe burn injury.
• Injury of the brain, or bleeding into the brain, from any
cause may be a factor in ARDS for reasons that are notclear. Convulsions also may cause some cases.
Usually ARDS develops within one to two days of the

original illness or injury. The person begins to take rapidbut shallow breaths. The doctor who listens to the patient’schest with a stethoscope may hear “crackling” or wheez-
ingsounds. The low blood oxygen content may cause the
skin to appear mottled or even blue. As fluid continues tofill the breathing sacs, the patient may have great troublebreathing, take very rapid breaths, and gasp for air.
Diagnosis
A simple test using a device applied to the ear will

show whether the blood is carrying too little oxygen, andthis can be confirmed by analyzing blood taken from anartery. The chest x ray may be normal in the early stages,
but, in a short time, fluid will be seen where it does notbelong. The two lungs are about equally affected. A heartof normal size indicates that the problem actually is ARDSand not heart failure. Another way a physician can distin-guish between these two possibilities is to place a catheterKEY TERMS

Alveoli —The tiny air sacs at the ends of the breath-
ing tubes of the lung where oxygen normally istaken up by the capillaries to enter the circulation.
Aspiration —The process in which solid food, liq-
uids, or secretions that normally are swallowedare, instead, breathed into the lungs.
Capillaries —The smallest arteries which, in the
lung, are located next to the alveoli so that theycan pick up oxygen from inhaled air.
Face mask —The simplest way of delivering a high

level of oxygen to patients with ARDS or otherlow-oxygen conditions.
Steroids —A class of drugs resembling normal
body substances that often help control inflamma-tion in the body tissues.
Ventilator —A mechanical device that can take
over the work of breathing for a patient whoselungs are injured or are starting to heal.into a vein and advance it into the main artery of the lung.

In this way, the pressure within the pulmonary capillariescan be measured. Pressure within the pulmonary capillar-ies is elevated in heart failure, but normal in ARDS.
Treatment
The three main goals in treating patients with ARDS
are:
• To treat whatever injury or disease has caused ARDS.
Examples are: to treat septic infection with the properantibiotics , and to reduce the level of oxygen therapy if
ARDS has resulted from a toxic level of oxygen.

• To control the process in the lungs that allows fluid to
leak out of the blood vessels. At present there is no cer-tain way to achieve this. Certain steroid hormones havebeen tried because they can combat inflammation, butthe actual results have been disappointing.
• To make sure the patient gets enough oxygen until the

lung injury has had time to heal. If oxygen delivered bya face mask is not enough, the patient is placed on aventilator, which takes over breathing, and, through atube placed in the nose or mouth (or an incision in thewindpipe), forces oxygen into the lungs. This treatmentmust be closely supervised, and the pressure adjustedso that too much oxygen is not delivered.
Patients with ARDS should be cared for in an inten-

sive care unit, where experienced staff and all neededequipment are available. Enough fluid must be provided,by vein if necessary, to prevent dehydration . Also, the
patient’s nutritional state must be maintained, again byvein, if oral intake is not sufficient.
Prognosis
If the patient’s lung injury does not soon begin to
heal, the lack of sufficient oxygen can injure other organs,such as the kidneys. There always is a risk that bacterialpneumonia will develop at some point. Without prompt

treatment, as many as 90% of patients with ARDS can beexpected to die. With modern treatment, however, abouthalf of all patients will survive. Those who do live usuallyrecover completely, with little or no long-term breathingdifficulty. Lung scarring is a risk after a long period on aventilator, but it may improve in the months after thepatient is taken off ventilation. Whether a particularpatient will recover depends to a great extent on whetherthe primary disease that caused ARDS to develop

primary disease that caused ARDS to develop in thefirst place can be effectively treated.

The only way to prevent ARDS is to avoid those dis-
eases and harmful conditions that damage the lung. For
GALE ENCYCLOPEDIA OF MEDICINE 2 68Adult respiratory distress syndromeGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 68

instance, the danger of aspirating stomach contents into
the lungs can be avoided by making sure a patient does noteat shortly before receiving general anesthesia. If a patientneeds oxygen therapy, as low a level as possible should begiven. Any form of lung infection, or infection anywherein the body that gets into the blood, must be treatedpromptly to avoid the lung injury that causes ARDS.
Resources
BOOKS
Smolley, Lawrence A., and Debra F. Bryse. Breathe Right

Now: A Comprehensive Guide to Understanding andTreating the Most Common Breathing Disorders. New
York: W. W. Norton & Co., 1998.
National Heart, Lung and Blood Institute. P.O. Box 30105,
Bethesda, MD 20824-0105. (301) 251-1222. <http://www.nhlbi.nih.gov>.
National Respiratory Distress Syndrome Foundation. P.O. Box
723, Montgomeryville, PA 18936.
OTHER
“Pulmonary Medicine.” HealthWeb.com. 5 Jan. 1998. <http://
healthweb.org>.
David A. Cramer, MD
AFP test seeAlpha-fetoprotein test

African American health seeMinority
health
African sleeping sickness seeSleeping
sickness
African trypanosomiasis seeSleeping
sickness
Agammaglobulinemia seeCommon
variable immunodeficiency
Aggression seeConduct disorder
Aging
Starting at what is commonly called middle age, oper-

ations of the human body begin to be more vulnerable todaily wear and tear; there is a general decline in physical,and possibly mental, functioning. In the Western countries,the length of life is often into the 70s. The upward limit ofthe life span, however, can be as high as 120 years. Duringthe latter half of life, an individual is more prone to haveproblems with the various functions of the body and todevelop any number of chronic or fatal diseases. The car-diovascular, digestive, excretory,

The car-diovascular, digestive, excretory, nervous, reproductiveand urinary systems are particularly affected. The mostcommon diseases of aging include Alzheimer’s, arthritis,cancer , diabetes, depression, and heart disease.

Human beings reach a peak of growth and develop-
ment around the time of their mid 20s. Aging is the normaltransition time after that flurry of activity. Although thereare quite a few age-related changes that tax the body, dis-ability is not necessarily a part of aging. Health andlifestyle factors together with the genetic makeup of theindividual, and determines the response to these changes.Body functions that are most often affected by age include:

• Hearing, which declines especially in relation to the
highest pitched tones.
• The proportion of fat to muscle, which may increase by
as much as 30%. Typically, the total padding of bodyfat directly under the skin thins out and accumulatesaround the stomach. The ability to excrete fats isimpaired, and therefore the storage of fats increases,including cholesterol and fat-soluble nutrients.
• The amount of water in the body decreases, which there-

fore decreases the absorption of water-soluble nutrients.Also, there is less saliva and other lubricating fluids.
• The liver and the kidneys cannot function as efficiently,
thus affecting the elimination of wastes.
• A decrease in the ease of digestion, with a decrease in
stomach acid production.
• A loss of muscle strength and coordination, with an
accompanying loss of mobility, agility, and flexibility.
• A decline in sexual hormones and sexual functioning.

• A decrease in the sensations of taste and smell.• Changes in the cardiovascular and respiratory systems,
leading to decreased oxygen and nutrients throughoutthe body.
• Decreased functioning of the nervous system so that
nerve impulses are not transmitted as efficiently, reflex-es are not as sharp, and memory and learning arediminished.
• A decrease in bone strength and density.
• Hormone levels, which gradually decline. The thyroid
and sexual hormones are particularly affected.

• Declining visual abilities. Age-related changes may
lead to diseases such as macular degeneration .
GALE ENCYCLOPEDIA OF MEDICINE 2 69AgingGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 69

• A compromised ability to produce vitamin D from sun-
light.
• A reduction in protein formation leading to shrinkage
in muscle mass and decreased bone formation, possiblyleading to osteoporosis.
There are several theories as to why the aging body
loses functioning. It may be that several factors worktogether or that one particular factor is at work more thanothers in a given individual.
• Programmed senescence, or aging clock, theory. The

aging of the cells of each individual is programmed intothe genes, and there is a preset number of possible reju-venations in the life of a given cell. When cells die at arate faster than they are replaced, organs do not func-tion properly, and they are soon unable to maintain thefunctions necessary for life.
• Genetic theory. Human cells maintain their own seed of
destruction at the level of the chromosomes.
• Connective tissue, or cross-linking theory. Changes in

the make-up of the connective tissue alter the stabilityof body structures, causing a loss of elasticity and func-tioning, and leading to symptoms of aging.
• Free-radical theory. The most commonly held theory of

aging, it is based on the fact that ongoing chemicalreactions of the cells produce free radicals. In the pres-ence of oxygen, these free radicals cause the cells of thebody to break down. As time goes on, more cells die orlose the ability to function, and the body soon ceases tofunction as a whole.
• Immunological theory. There are changes in the immune

system as it begins to wear out, and the body is moreprone to infections and tissue damage, which may finallycause death . Also, as the system breaks down, the body
is more apt to have autoimmune reactions, in which thebody’s own cells are mistaken for foreign material andare destroyed or damaged by the immune system.
Diagnosis
Many problems can arise due to age-related changes

in the body. Although there is no one test to be given, athorough physical exam and a basic blood screening andblood chemistry panel can point to areas in need of fur-ther attention. When older people become ill, the firstsigns of disease are often nonspecific. Further examsshould be conducted if any of the following occur:
• diminished or lack of desire for food
• increasing confusion• failure to thrive
• urinary incontinence• dizziness• weight loss• falling
Treatment

Treatment
For the most part, doctors prescribe medications to
control the symptoms and diseases of aging. In the Unit-ed States, about two-thirds of people 65 and over takemedications for various complaints. More women thanmen use these medications. The most common drugsused by the elderly are painkillers, diuretics or water
pills, sedatives, cardiac drugs, antibiotics , and mental
health drugs.
Estrogen replacement therapy (ERT) is commonly

prescribed to postmenopausal women for symptoms ofaging. It is often used in conjunction with progesterone.ERT functions to help keep bones strong, reduce risk ofheart disease, restore vaginal lubrication, and to improveskin elasticity. Evidence suggests that it may also helpmaintain mental functions.
Expected results
Aging is unavoidable, but major physical impair-

ment is not. People can lead a healthy, disability-free lifewell through their later years. A well established supportsystem of family, friends, and health care providers,together with focus on good nutrition and lifestyle
habits and good stress management, can prevent disease
and lessen the impact of chronic conditions.
Nutritional supplements
Consumption of a high–quality multivitamin is rec-

ommended. Common nutritional deficiencies connectedwith aging include B vitamins , vitamins A and C, folic
acid, calcium, magnesium, zinc, iron, chromium, and
trace minerals . Since stomach acids may be decreased, it
is suggested that the use of a powdered multivitamin for-mula in gelatin capsules be used, as this form is the easi-est to digest. Such formulas may also contain enzymesfor further help with digestion.
Antioxidants can help to neutralize damage by the

free radical actions thought to contribute to problems ofaging. They are also helpful in preventing and treatingcancer and in treating cataracts and glaucoma . Supple-
ments that serve as antioxidants include:
GALE ENCYCLOPEDIA OF MEDICINE 2 70AgingGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 70

• Vitamin E, 400–1,000 IUs daily. Protects cell mem-
branes against damage. It shows promise in preventionagainst heart disease, and Alzheimer’s and Parkinson’sdiseases.
• Selenium, 50 mg taken twice daily. Research suggests
that selenium may play a role in reducing the risk ofcancer.
• Beta-carotene, 25,000–40,000 IUs daily. May help in
treating cancer, colds and flu, arthritis, and immunesupport.
• Vitamin C, 1,000–2,000 mg per day. It may cause diar-

rhea in large doses. If this occurs, however, all that is
needed is a decrease in the dosage.
Other supplements that are helpful in treating age-
related problems including:
•B
12/B-complex vitamins, studies show that B12may help
reduce mental symptoms, such as confusion, memoryloss, and depression.
• Coenzyme Q10 may be helpful in treating heart dis-
ease, as up to three-quarters cardiac patients have beenfound to be lacking in this heart enzyme.
Hormones

Hormones
The following hormone supplements may be taken
to prevent or to treat various age-related problems. How-ever, caution should be taken before beginning treatment,and the patient should consult his or her health care pro-fessional.
DHEA improves brain functioning and serves as a
building block for many other important hormones in thebody. It may be helpful in restoring declining hormonelevels and in building up muscle mass, strengthening thebones, and maintaining a healthy heart.

Melatonin may be helpful for insomnia . It has also
been used to help fight viruses and bacterial infections,reduce the risk of heart disease, improve sexual function-ing, and to protect against cancer.
Human growth hormone (hGH) has been shown to
regulate blood sugar levels and to stimulate bone, carti-lage, and muscle growth while reducing fat.
Herbs
Garlic ( Allium sativa ) is helpful in preventing heart

disease, as well as improving the tone and texture ofskin. Garlic stimulates liver and digestive system func-tions, and also helps in dealing with heart disease andhigh blood pressure.
Siberian ginseng ( Eleutherococcus senticosus ) sup-
ports the adrenal glands and immune functions. It isKEY TERMS
Antioxidants —Substances that reduce the damage
of the highly reactive free radicals that are thebyproducts of the cells.
Alzheimer’s disease —A condition causing a

decline in brain function that interferes with theability to reason and to perform daily activities.
Senescence —Aging.
Vata—One of the three main constitutional types
found under Ayurvedic principles. Keeping one’sparticular constitution in balance is consideredimportant in maintaining health.
believed to be helpful in treating problems related to

stress. Siberian ginseng also increases mental and physi-cal performance, and may be useful in treating memoryloss, chronic fatigue , and immune dysfunction.
Ginkgo biloba works particularly well on the brain
and nervous system. It is effective in reducing the symp-toms of conditions, such as Alzheimer’s, depression,visual problems, and problems of blood circulation. Itmay also help treat heart disease, strokes, dementia ,
Raynaud’s disease , head injuries, leg cramps, macular

degeneration, tinnitus ,impotence due to poor blood
flow, and diabetes-related nerve damage.
Proanthocyanidins, or PCO, are Pycnogenol, derived
from grape seeds and skin, and from pine tree bark, andmay help in the prevention of cancer and poor vision.
In Ayurvedic medicine , aging is described as a

process of increased vata, in which there is a tendency tobecome thinner, drier, more nervous, more restless, andmore fearful, while having a loss of appetite as well assleep. Bananas, almonds, avocados, and coconuts aresome of the foods used in correcting such conditions.One of the main herbs used for such conditions is gotukola ( Centella asiatica ), which is used to revitalize the

nervous system and brain cells and to fortify the immunesystem. Gotu kola is also used to treat memory loss, anx-
iety, and insomnia.
In Chinese medicine, most symptoms of aging are

regarded as symptoms of a yin deficiency. Moisteningfoods such as millet, barley soup, tofu, mung beans,wheat germ, spirulina, potatoes, black sesame seeds,walnuts, and flax seeds are recommended. Jing tonicsmay also be used. These include deer antler, dodderseeds, processed rehmannia, longevity soup, mussels,and chicken.
GALE ENCYCLOPEDIA OF MEDICINE 2 71AgingGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 71

Preventive health practices such as healthy diet,
daily exercise , stress management, and control of
lifestyle habits such as smoking and drinking, can
lengthen the life span and improve the quality of life aspeople age. Exercise can improve the appetite, the healthof the bones, the emotional and mental outlook, and thedigestion and circulation.
Drinking plenty of fluids aids in maintaining healthy

skin, good digestion, and proper elimination of wastes.Up to eight glasses of water should be consumed daily,along with plenty of herbal teas, diluted fruit and veg-etable juices, and fresh fruits and vegetables with highwater content.
Because of a decrease in the sense of taste, older
people often increase their intake of salt, which can con-tribute to high blood pressure and nutrient loss. Use ofsugar is also increased. Seaweeds and small amounts ofhoney can be used as replacements.

Alcohol, nicotine, and caffeine all have potential
damaging effects, and should be limited or completelyeliminated from consumption.
A diet high in fiber and low in fat is recommended.
Processed foods should be replaced by complex carbohy-drates, such as whole grains. If chewing becomes a prob-lem, there should be an increased intake of protein drinks,freshly juiced fruits and vegetables, and creamed cereals.
Resources
BOOKS
Darden Ph.D., Ellington. Living Longer Stronger. New York: A

Perigee Book, The Berkeley Publishing Group, 1995.
Pitchford, Paul. Healing with Whole Foods. Berkeley, CA:
North Atlantic Books, 1993.
OTHER
“Anti-Aging-Nutritional Program.” <http://www.healthy.net/
hwlibrarybooks/haas/perform/antiagin.htm/> (December28, 2000).
“Effects of Hormone in the Body.” <http://www.anti-aging.org/
Effects_hGH.html/> (December 28, 2000).
“The Elderly-Nutritional Programs.”
<http://www.healthy.net/hwlibrarybooks/haas/lifestage/elderly.htm/> (December 28, 2000).

“Evaluating the Elderly Patient: the Case for Assessment Tech-
nology.” <http://text.nlm.nih.gov/nih/ta/www/01.html/>(December 28, 2000).
“Herbal Phytotherapy and the Elderly.” <http://www.healthy.
net/hwlibrarybooks/hoffman/elders/elders.htm/> (Decem-ber 28, 2000).
“Pharmacokinetics.” Merck & Co., Inc. (1995-2000). <http://
www.merck.com/pubs/mmanual/section22/chapter304/304a.htm/> (December 28, 2000).“To a Long and Healthy Life.” <http://www.healthy.net/

hwlibraryarticles/aesoph/longandhealthy.htm/> (Decem-ber 28, 2000).
Agoraphobia
The word agoraphobia is derived from Greek words
literally meaning “fear of the marketplace.” The term isused to describe an irrational and often disabling fear ofbeing out in public.
Agoraphobia is just one type of phobia, or irrational
fear. People with phobias feel dread or panic when they

face certain objects, situations, or activities. People withagoraphobia frequently also experience panic attacks, butpanic attacks, or panic disorder , are not a requirement
for a diagnosis of agoraphobia. The defining feature ofagoraphobia is anxiety about being in places from which
escape might be embarrasing or difficult, or in whichhelp might be unavailable. The person suffering fromagoraphobia usually avoids the anxiety-provoking situa-tion and may become totally housebound.

Agoraphobia is the most common type of phobia, and
it is estimated to affect between 5-12% of Americans withintheir lifetime. Agoraphobia is twice as common in womenas in men and usually strikes between the ages of 15-35.
The symptoms of the panic attacks which may
accompany agoraphobia vary from person to person, andmay include trembling, sweating, heart palpitations (a

feeling of the heart pounding against the chest), jitters,fatigue , tingling in the hands and feet, nausea, a rapid
pulse or breathing rate, and a sense of impending doom.
Agoraphobia and other phobias are thought to be the

result of a number of physical and environmental factors.For instance, they have been associated with biochemicalimbalances, especially related to certain neurotransmit-ters (chemical nerve messengers) in the brain. Peoplewho have a panic attack in a given situation (e.g., a shop-ping mall) may begin to associate the panic with that sit-uation and learn to avoid it. According to some theories,irrational anxiety results from unresolved emotional con-flicts. All of these factors may play a role

con-flicts. All of these factors may play a role to varyingextents in different cases of agoraphobia.

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Diagnosis
People who suffer from panic attacks should discuss
the problem with a physician. The doctor can diagnosethe underlying panic or anxiety disorder and make surethe symptoms aren’t related to some other underlyingmedical condition.
The doctor makes the diagnosis of agoraphobia

based primarily on the patient’s description of his or hersymptoms. The person with agoraphobia experiencesanxiety in situations where escape is difficult or help isunavailable—or in certain situations, such as being alone.While many people are somewhat apprehensive in thesesituations, the hallmark of agoraphobia is that a person’sactive avoidance of the feared situation impairs his or herability to work, socialize, or otherwise function.
Treatment

Treatment
Treatment for agoraphobia usually consists of both
medication and psychotherapy. Usually, patients canbenefit from certain antidepressants, such as amitripty-line (Elavil), or selective serotonin reuptake inhibitors ,
such as paroxetine (Paxil), fluoxetine (Prozac), or sertra-line (Zoloft). In addition, patients may manage panicattacks in progress with certain tranquilizers called ben-
zodiazepines , such as alprazolam (Xanax) or clon-
azepam (Klonipin).

The mainstay of treatment for agoraphobia and other

phobias is cognitive behavioral therapy. A specific tech-nique that is often employed is called desensitization.The patient is gradually exposed to the situation that usu-ally triggers fear and avoidance, and, with the help ofbreathing or relaxation techniques, learns to cope withthe situation. This helps break the mental connectionbetween the situation and the fear, anxiety, or panic.Patients may also benefit from psychodynamically ori-ented psychotherapy, discussing underlying

ori-ented psychotherapy, discussing underlying emotionalconflicts with a therapist or support group.

Prognosis
With proper medication and psychotherapy, 90% of
patients will find significant improvement in their symp-toms.
Resources
BOOKS
Hallowell, Edward M. Worry: Controlling It and Using It Wise-
ly.New York: Pantheon Books, 1997.
Forsyth, Sondra. “I Panic When I’m Alone.” Mademoiselle ,
Apr. 1998, 119-24.
Hale, Anthony S. “ABC of Mental Health: Anxiety.” British
Medical Journal 314 (28 June 1997): 1886-9.KEY TERMS
Benzodiazepines —A group of tranquilizers often

used to treat anxiety.
Desensitization —A treatment for phobias which
involves exposing the phobic person to the fearedsituation. It is often used in conjunction withrelaxation techniques.
Phobia —An intense and irrational fear of a specif-
ic object, activity, or situation.
“Panic Disorder—Panic Attacks and Agoraphobia.” American
Family Physician 52, no. 7 (15 Nov. 1995): 2067-8.

American Psychiatric Association. 1400 K Street NW, Washing-
ton DC 20005. (888) 357-7924. <http://www.psych.org>.
Anxiety Disorders Association of America. 11900 Park Lawn
Drive, Ste. 100, Rockville, MD 20852. (800) 545-7367.<http://www.adaa.org>.
National Institute of Mental Health. Mental Health Public
Inquiries, 5600 Fishers Lane, Room 15C-05, Rockville,MD 20857. (888) 826-9438. <http://www.nimh.nih.gov>.
Robert Scott Dinsmoor
Agranulocytosis seeNeutropenia
AIDS

AIDS
Acquired immune deficiency syndrome (AIDS) is an
infectious disease caused by the human immunodeficien-
cyvirus (HIV). It was first recognized in the United States

in 1981. AIDS is the advanced form of infection with theHIV virus, which may not cause recognizable disease for along period after the initial exposure (latency). No vaccineis currently available to prevent HIV infection. At present,all forms of AIDS therapy are focused on improving thequality and length of life for AIDS patients by slowing orhalting the replication of the virus and treating or prevent-ing infections and cancers that take advantage of a per-son’s weakened immune system.

AIDS is considered one of the most devastating public
health problems in recent history. In June 2000, the Centers
GALE ENCYCLOPEDIA OF MEDICINE 2 73AIDSGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 73

120,223 (includes only those cases in areas that have confi-dential HIV reporting) in the United States are HIV-posi-tive, and 311,701 are living with AIDS (includes only thosecases where vital status is known). Of these patients, 44%are gay or bisexual men, 20% are heterosexual intravenousdrug users, and 17% are women. In addition, approximate-ly 1,000-2,000 children are born each year with HIV infec-tion. The World Health Organization (WHO) estimates that33 million adults and 1.3 million

estimates that33 million adults and 1.3 million children worldwide wereliving with HIV/AIDS as of 1999 with 5.4 million beingnewly infected that year. Most of these cases are in thedeveloping countries of Asia and Africa.

Risk factors
AIDS can be transmitted in several ways. The risk
factors for HIV transmission vary according to category:
• Sexual contact. Persons at greatest risk are those who
do not practice safe sex, those who are not monoga-mous, those who participate in anal intercourse, andthose who have sex with a partner with symptoms ofadvanced HIV infection and/or other sexually trans-
mitted diseases (STDs). In the United States and

Europe, most cases of sexually transmitted HIV infec-tion have resulted from homosexual contact, whereas inAfrica, the disease is spread primarily through sexualintercourse among heterosexuals.
• Transmission in pregnancy . High-risk mothers include
women married to bisexual men or men who have anabnormal blood condition called hemophilia and

require blood transfusions, intravenous drug users, andwomen living in neighborhoods with a high rate of HIVinfection among heterosexuals. The chances of trans-
mitting the disease to the child are higher in women inadvanced stages of the disease. Breast feeding increasesthe risk of transmission by 10-20%. The use of zidovu-dine (AZT) during pregnancy, however, can decreasethe risk of transmission to the baby.
• Exposure to contaminated blood or blood products.

With the introduction of blood product screening in themid-1980s, the incidence of HIV transmission in bloodtransfusions has dropped to one in every 100,000 trans-fused. With respect to HIV transmission among drugabusers, risk increases with the duration of using injec-tions, the frequency of needle sharing, the number ofpersons who share a needle, and the number of AIDScases in the local population.
• Needle sticks among health care professionals. Present

studies indicate that the risk of HIV transmission by a nee-dle stick is about one in 250. This rate can be decreased ifthe injured worker is given AZT, an anti-retroviral medica-tion, in combination with other medication.
HIV is not transmitted by handshakes or other casu-
al non-sexual contact, coughing or sneezing, or by blood-sucking insects such as mosquitoes.
AIDS in women
AIDS in women is a serious public health concern.

Women exposed to HIV infection through heterosexualcontact are the most rapidly growing risk group in theUnited States population. The percentage of AIDS casesdiagnosed in women has risen from 7% in 1985 to 23% in1999. Women diagnosed with AIDS may not live as longas men, although the reasons for this finding are unclear.
GALE ENCYCLOPEDIA OF MEDICINE 2 74AIDSRisk of acquiring HIV infection by entry site

Entry site Risk virus reaches entry site Risk virus enters Risk inoculated
Conjuntiva Moderate Moderate Very low
Oral mucosa Moderate Moderate LowNasal mucosa Low Low Very lowLower respiratory Very low Very low Very lowAnus Very high Very high Very highSkin, intact Very low Very low Very lowSkin, broken Low High High
Sexual:
Vagina Low High High
Penis Low Low HighUlcers (STD) Medium Low Very high
Blood:
Products High High Low

Blood:
Shared needles High High HighAccidental needle High Very High LowTraumatic wound Modest High HighPerinatal High High HighGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 74

AIDS in children
Since AIDS can be transmitted from an infected moth-
er to the child during pregnancy, during the birth process, orthrough breast milk, all infants born to HIV-positive moth-ers are a high-risk group. As of 2000, it was estimated that87% of HIV-positive women are of childbearing age; 41%of them are drug abusers. Between 15-30% of children bornto HIV-positive women will be infected with the virus.
AIDS is one of the 10 leading causes of death in chil-

dren between one and four years of age. The intervalbetween exposure to HIV and the development of AIDS isshorter in children than in adults. Infants infected with HIVhave a 20-30% chance of developing AIDS within a yearand dying before age three. In the remainder, AIDS pro-gresses more slowly; the average child patient survives toseven years of age. Some survive into early adolescence.
Because HIV destroys immune system cells, AIDS

is a disease that can affect any of the body’s major organsystems. HIV attacks the body through three diseaseprocesses: immunodeficiency, autoimmunity, and ner-
vous system dysfunction.
Immunodeficiency describes the condition in which

the body’s immune response is damaged, weakened, or isnot functioning properly. In AIDS, immunodeficiencyresults from the way that the virus binds to a protein calledCD4, which is primarily found on the surface of certainsubtypes of white blood cells called helper T cells or CD4cells. After the virus has attached to the CD4 receptor, thevirus-CD4 complex refolds to uncover another receptorcalled a chemokine receptor that helps to mediate entry ofthe virus into the cell. One chemokine receptor

ofthe virus into the cell. One chemokine receptor in particu-lar, CCR5, has gotten recent attention after studies showedthat defects in its structure (caused by genetic mutations)cause the progression of AIDS to be prevented or slowed.Scientists hope that this discovery will lead to the develop-ment of drugs that trigger an artificial mutation of theCCR5 gene or target the CCR5 receptor.

Once HIV has entered the cell, it can replicate intra-
cellularly and kill the cell in ways that are still not com-pletely understood. In addition to killing some lympho-cytes directly, the AIDS virus disrupts the functioning of
GALE ENCYCLOPEDIA OF MEDICINE 2 75AIDS
Mature HIV-1 viruses (above) and the lymphocyte from which they emerged (below).Two immature viruses can be seen bud-

ding on the surface of the lymphocyte (right of center). (Photograph by Scott Camazir, Photo Researchers, Inc. Reproduced by
permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 75

the remaining CD4 cells. Because the immune system
cells are destroyed, many different types of infectionsand cancers that take advantage of a person’s weakenedimmune system (opportunistic) can develop.
Autoimmunity is a condition in which the body’s

immune system produces antibodies that work against itsown cells. Antibodies are specific proteins produced inresponse to exposure to a specific, usually foreign, proteinor particle called an antigen. In this case, the body pro-duces antibodies that bind to blood platelets that are nec-essary for proper blood clotting and tissue repair. Oncebound, the antibodies mark the platelets for removal fromthe body, and they are filtered out by the spleen. SomeAIDS patients develop a disorder, called

SomeAIDS patients develop a disorder, called immune-relatedthrombocytopenia purpura (ITP), in which the number

of blood platelets drops to abnormally low levels.
As of 2000, researchers do not know precisely how
HIV attacks the nervous system since the virus can causedamage without infecting nerve cells directly. One theoryis that, once infected with HIV , one type of immune sys-tem cell, called a macrophage, begins to release a toxinthat harms the nervous system.
The course of AIDS generally progresses through
three stages, although not all patients will follow thisprogression precisely:

Acute retroviral syndrome
Acute retroviral syndrome is a term used to describe
a group of symptoms that can resemble mononucleosisand that may be the first sign of HIV infection in 50-70%of all patients and 45-90% of women. Most patients arenot recognized as infected during this phase and may notseek medical attention. The symptoms may includefever ,fatigue , muscle aches, loss of appetite, digestive
disturbances, weight loss, skin rashes ,headache , and

chronically swollen lymph nodes (lymphadenopathy).Approximately 25-33% of patients will experience aform of meningitis during this phase in which the mem-
branes that cover the brain and spinal cord becomeinflamed. Acute retroviral syndrome develops betweenone and six weeks after infection and lasts for two tothree weeks. Blood tests during this period will indicatethe presence of virus (viremia) and the appearance of theviral p24 antigen in the blood.
Latency period

After the HIV virus enters a patient’s lymph nodes
during the acute retroviral syndrome stage, the diseasebecomes latent for as many as 10 years or more beforesymptoms of advanced disease develop. During latency,the virus continues to replicate in the lymph nodes, whereit may cause one or more of the following conditions:PERSISTENT GENERALIZED LYMPHADENOPATHY (PGL).

Persistent generalized lymphadenopathy, or PGL, is a con-dition in which HIV continues to produce chronic painlessswellings in the lymph nodes during the latency period.The lymph nodes that are most frequently affected by PGLare those in the areas of the neck, jaw, groin, and armpits.PGL affects between 50-70% of patients during latency.
CONSTITUTIONAL SYMPTOMS. Many patients will

develop low-grade fevers, chronic fatigue, and generalweakness. HIV may also cause a combination of foodmalabsorption, loss of appetite, and increased metabo-lism that contribute to the so-called AIDS wasting orwasting syndrome.
OTHER ORGAN SYSTEMS. At any time during the
course of HIV infection, patients may suffer from a yeastinfection in the mouth called thrush, open sores or ulcers,or other infections of the mouth; diarrhea and other gas-

trointestinal symptoms that cause malnutrition and
weight loss; diseases of the lungs and kidneys; anddegeneration of the nerve fibers in the arms and legs.HIV infection of the nervous system leads to general lossof strength, loss of reflexes, and feelings of numbness orburning sensations in the feet or lower legs.
Late-stage disease (AIDS)
AIDS is usually marked by a very low number of

CD4+ lymphocytes, followed by a rise in the frequencyof opportunistic infections and cancers. Doctors monitorthe number and proportion of CD4+ lymphocytes in thepatient’s blood in order to assess the progression of thedisease and the effectiveness of different medications.About 10% of infected individuals never progress to thisovert stage of the disease and are referred to as nonpro-gressors.
OPPORTUNISTIC INFECTIONS. Once the patient’s

CD4+ lymphocyte count falls below 200 cells/mm3, he or
she is at risk for a variety of opportunistic infections. Theinfectious organisms may include the following:
• Fungi. The most common fungal disease associated
with AIDS is Pneumocystis carinii pneumonia (PCP).

PCP is the immediate cause of death in 15-20% ofAIDS patients. It is an important measure of a patient’sprognosis. Other fungal infections include a yeastinfection of the mouth ( candidiasis or thrush) and
cryptococcal meningitis.
• Protozoa. Toxoplasmosis is a common opportunistic
infection in AIDS patients that is caused by a proto-zoan. Other diseases in this category include isoporiasisand cryptosporidiosis.
• Mycobacteria. AIDS patients may develop tuberculo-

sisor MAC infections. MAC infections are caused by
GALE ENCYCLOPEDIA OF MEDICINE 2 76AIDSGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 76

Mycobacterium avium-intracellulare , and occur in
about 40% of AIDS patients. It is rare until CD4+counts falls below 50 cells/mm
3.
• Bacteria. AIDS patients are likely to develop bacterial
infections of the skin and digestive tract.
• Viruses. AIDS patients are highly vulnerable to

cytomegalovirus (CMV), herpes simplex virus (HSV),varicella zoster virus (VZV), and Epstein-Barr virus(EBV) infections. Another virus, JC virus, causes pro-gressive destruction of brain tissue in the brain stem, cere-brum, and cerebellum (multifocal leukoencephalopathyor PML), which is regarded as an AIDS-defining illnessby the Centers for Disease Control and Prevention.
AIDS DEMENTIA COMPLEX AND NEUROLOGIC COM-

PLICATIONS. AIDS dementia complex is usually a late
complication of the disease. It is unclear whether it iscaused by the direct effects of the virus on the brain or byintermediate causes. AIDS dementia complex is marked

by loss of reasoning ability, loss of memory, inability toconcentrate, apathy and loss of initiative, and unsteadi-ness or weakness in walking. Some patients also developseizures. There are no specific treatments for AIDSdementia complex.
MUSCULOSKELETAL COMPLICATIONS. Patients in
late-stage AIDS may develop inflammations of the mus-cles, particularly in the hip area, and may have arthritis-like pains in the joints.
ORAL SYMPTOMS. In addition to thrush and painful

ulcers in the mouth, patients may develop a conditioncalled hairy leukoplakia of the tongue. This condition isalso regarded by the CDC as an indicator of AIDS. Hairyleukoplakia is a white area of diseased tissue on thetongue that may be flat or slightly raised. It is caused bythe Epstein-Barr virus.
GALE ENCYCLOPEDIA OF MEDICINE 2 77AIDS
CENTRAL NERVOUS SYSTEM
MUCOCUTANEOUS
PNEUMONIAL YMPHOPROLIFERATIVE DISEASE
SKIN
DIARRHEA

SKIN
DIARRHEA 
OPPORTUNISTIC INFECTIONS CAUSED BY AIDS
Because the immune system cells are destroyed by the AIDS virus, many different types of infections and cancers can devel-
op, taking advantage of a person’s weakened immune system. (Illustration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 77

AIDS-RELATED CANCERS. Patients with late-stage
AIDS may develop Kaposi’s sarcoma (KS), a skin
tumor that primarily affects homosexual men. KS is themost common AIDS-related malignancy. It is character-ized by reddish-purple blotches or patches (brownish inAfrican-Americans) on the skin or in the mouth. About40% of patients with KS develop symptoms in the diges-tive tract or lungs. KS may be caused by a herpes virus-like sexually transmitted disease agent rather than HIV .

The second most common form of cancer in AIDS
patients is a tumor of the lymphatic system (lymphoma).AIDS-related lymphomas often affect the central nervoussystem and develop very aggressively.KEY TERMS
Acute retroviral syndrome —A group of symptoms
resembling mononucleosis that often are the firstsign of HIV infection in 50-70% of all patients and45-90% of women.
AIDS dementia complex —A type of brain dysfunc-

tion caused by HIV infection that causes difficultythinking, confusion, and loss of muscular coordi-nation.
Antibody —A specific protein produced by the
immune system in response to a specific foreignprotein or particle called an antigen.
Antigen —Any substance that stimulates the body to
produce antibody.
Autoimmunity —A condition in which the body’s

immune system produces antibodies in response toits own tissues or blood components instead of for-eign particles or microorganisms.
CCR5 —A chemokine receptor; defects in its struc-
ture caused by genetic mutation cause the progres-sion of AIDS to be prevented or slowed.
CD4—A type of protein molecule in human blood,

sometimes called the T4 antigen, that is present onthe surface of 65% of immune cells. The HIV virusinfects cells with CD4 surface proteins, and as aresult, depletes the number of T cells, B cells, natur-al killer cells, and monocytes in the patient’s blood.Most of the damage to an AIDS patient’s immunesystem is done by the virus’ destruction of CD4+lymphocytes.
Chemokine receptor —A receptor on the surface of

some types of immune cells that helps to mediateentry of HIV into the cell.Hairy leukoplakia of the tongue —A white area of
diseased tissue on the tongue that may be flat orslightly raised. It is caused by the Epstein-Barr virusand is an important diagnostic sign of AIDS.
Hemophilia —Any of several hereditary blood coag-

ulation disorders occurring almost exclusively inmales. Because blood does not clot properly, evenminor injuries can cause significant blood loss thatmay require a blood transfusion, with its associatedminor risk of infection.
Human immunodeficiency virus (HIV) —A transmis-

sible retrovirus that causes AIDS in humans. Twoforms of HIV are now recognized: HIV-1, which caus-es most cases of AIDS in Europe, North and SouthAmerica, and most parts of Africa; and HIV-2, whichis chiefly found in West African patients. HIV-2, dis-covered in 1986, appears to be less virulent than HIV-1 and may also have a longer latency period.
Immunodeficient —A condition in which the body’s

immune response is damaged, weakened, or is notfunctioning properly.
Kaposi’s sarcoma —A cancer of the connective tis-
sue that produces painless purplish red (in peoplewith light skin) or brown (in people with dark skin)blotches on the skin. It is a major diagnostic markerof AIDS.
Latent period —Also called incubation period, the
time between infection with a disease-causingagent and the development of disease.

Lymphocyte —A type of white blood cell that is
important in the formation of antibodies and thatcan be used to monitor the health of AIDS patients.
Invasive cancer of the cervix (related to certain types
of human papilloma virus [HPV]) is an important diag-nostic marker of AIDS in women.
Diagnosis
Because HIV infection produces such a wide range

of symptoms, the CDC has drawn up a list of 34 condi-tions regarded as defining AIDS. The physician will usethe CDC list to decide whether the patient falls into oneof these three groups:
• definitive diagnoses with or without laboratory evi-
dence of HIV infection
GALE ENCYCLOPEDIA OF MEDICINE 2 78AIDSGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 78

• definitive diagnoses with laboratory evidence of HIV
infection
• presumptive diagnoses with laboratory evidence of
HIV infection
Physical findings
Almost all the symptoms of AIDS can occur with
other diseases. The general physical examination may
range from normal findings to symptoms that are closelyassociated with AIDS. These symptoms are hairy leuko-plakia of the tongue and Kaposi’s sarcoma. When theKEY TERMS
Lymphoma —A cancerous tumor in the lymphatic

system that is associated with a poor prognosis inAIDS patients.
Macrophage —A large white blood cell, found pri-
marily in the bloodstream and connective tissue,that helps the body fight off infections by ingestingthe disease-causing organism. HIV can infect andkill macrophages.
Monocyte —A large white blood cell that is formed
in the bone marrow and spleen. About 4% of thewhite blood cells in normal adults are monocytes.

Mycobacterium avium (MAC) infection —A type of
opportunistic infection that occurs in about 40% ofAIDS patients and is regarded as an AIDS-definingdisease.
Non-nucleoside reverse transcriptase inhibitors —
The newest class of antiretroviral drugs that work byinhibiting the reverse transcriptase enzyme neces-sary for HIV replication.
Nucleoside analogues —The first group of effective
anti-retroviral medications. They work by interferingwith the AIDS virus’ synthesis of DNA.

Opportunistic infection —An infection by organ-
isms that usually don’t cause infection in peoplewhose immune systems are working normally.
Persistent generalized lymphadenopathy (PGL) —A
condition in which HIV continues to producechronic painless swellings in the lymph nodes dur-ing the latency period.Pneumocystis carinii pneumonia (PCP) —An oppor-
tunistic infection caused by a fungus that is a majorcause of death in patients with late-stage AIDS.
Progressive multifocal leukoencephalopathy

(PML) —A disease caused by a virus that destroys
white matter in localized areas of the brain. It isregarded as an AIDS-defining illness.
Protease inhibitors —The second major category of
drug used to treat AIDS that works by suppressingthe replication of the HIV virus.
Protozoan —A single-celled, usually microscopic
organism that is eukaryotic and, therefore, differentfrom bacteria (prokaryotic).
Retrovirus —A virus that contains a unique enzyme

called reverse transcriptase that allows it to repli-cate within new host cells.
T cells —Lymphocytes that originate in the thymus
gland. T cells regulate the immune system’sresponse to infections, including HIV. CD4 lympho-cytes are a subset of T lymphocytes.
Thrush —A yeast infection of the mouth character-
ized by white patches on the inside of the mouthand cheeks.
Viremia —The measurable presence of virus in the

bloodstream that is a characteristic of acute retrovi-ral syndrome.
Wasting syndrome —A progressive loss of weight
and muscle tissue caused by the AIDS virus.
doctor examines the patient, he or she will look for the
overall pattern of symptoms rather than any one finding.
Laboratory tests for HIV infection
BLOOD TESTS (SEROLOGY). The first blood test for

AIDS was developed in 1985. At present, patients whoare being tested for HIV infection are usually given anenzyme-linked immunosorbent assay (ELISA) test for thepresence of HIV antibody in their blood. Positive ELISAresults are then tested with a Western blot or immunofluo-rescence (IFA) assay for confirmation. The combinationof the ELISA and Western blot tests is more than 99.9%

GALE ENCYCLOPEDIA OF MEDICINE 2 79AIDSGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 79

accurate in detecting HIV infection within four to eight
weeks following exposure. The polymerase chain reac-tion (PCR) test can be used to detect the presence of viralnucleic acids in the very small number of HIV patientswho have false-negative results on the ELISA and West-ern blot tests. These tests are also used to detect virusesand bacterium other than HIV and AIDS.
OTHER LABORATORY TESTS. In addition to diagnos-

tic blood tests, there are other blood tests that are used totrack the course of AIDS in patients that have alreadybeen diagnosed. These include blood counts, viral loadtests, p24 antigen assays, and measurements of /H9252
2-
microglobulin ( /H92522M).
Doctors will use a wide variety of tests to diagnose the

presence of opportunistic infections, cancers, or other dis-ease conditions in AIDS patients. Tissue biopsies, samples ofcerebrospinal fluid, and sophisticated imaging techniques,such as magnetic resonance imaging (MRI) and computed
tomography scans (CT) are used to diagnose AIDS-related

cancers, some opportunistic infections, damage to the centralnervous system, and wasting of the muscles. Urine and stoolsamples are used to diagnose infections caused by parasites.AIDS patients are also given blood tests for syphilis and
other sexually transmitted diseases.
Diagnosis in children
Diagnostic blood testing in children older than 18

months is similar to adult testing, with ELISA screeningconfirmed by Western blot. Younger infants can be diag-nosed by direct culture of the HIV virus, PCR testing,and p24 antigen testing.
In terms of symptoms, children are less likely than

adults to have an early acute syndrome. They are, howev-er, likely to have delayed growth, a history of frequentillness, recurrent ear infections, a low blood cell count,failure to gain weight, and unexplained fevers. Childrenwith AIDS are more likely to develop bacterial infec-tions, inflammation of the lungs, and AIDS-related braindisorders than are HIV-positive adults.
Treatment
Treatment for AIDS covers four considerations:
TREATMENT OF OPPORTUNISTIC INFECTIONS AND

MALIGNANCIES. Most AIDS patients require complex
long-term treatment with medications for infectious dis-eases. This treatment is often complicated by the devel-opment of resistance in the disease organisms. AIDS-related malignancies in the central nervous system areusually treated with radiation therapy . Cancers else-
where in the body are treated with chemotherapy .PROPHYLACTIC TREATMENT FOR OPPORTUNISTIC

INFECTIONS. Prophylactic treatment is treatment that is
given to prevent disease. AIDS patients with a history ofPneumocystis pneumonia; with CD4+ counts below 200
cells/mm
3or 14% of lymphocytes; weight loss; or thrush
should be given prophylactic medications. The threedrugs given are trimethoprim-sulfamethoxazole, dap-sone, or pentamidine in aerosol form.
ANTI-RETROVIRAL TREATMENT. In recent years

researchers have developed drugs that suppress HIVreplication, as distinct from treating its effects on thebody. These drugs fall into three classes:
• Nucleoside analogues. These drugs work by interfering

with the action of HIV reverse transcriptase inside infect-ed cells, thus ending the virus’ replication process. Thesedrugs include zidovudine (sometimes called azidothymi-dine or AZT), didanosine (ddI), zalcitabine (ddC), stavu-dine (d4T), lamivudine (3TC), and abacavir (ABC).
•Protease inhibitors . Protease inhibitors can be effective

against HIV strains that have developed resistance tonucleoside analogues, and are often used in combinationwith them. These compounds include saquinavir, riton-avir, indinavir, nelfinavir, amprenavir, and lopinavir.
• Non-nucleoside reverse transcriptase inhibitors. This is
a new class of antiretroviral agents. Three are available,nevirapine, which was approved first, delavirdine andefavirin.
Treatment guidelines for these agents are in constant

change as new medications are developed and intro-duced. Two principles currently guide doctors in workingout drug regimens for AIDS patients: using combinationsof drugs rather than one medication alone; and basingtreatment decisions on the results of the patient’s viralload tests.
STIMULATION OF BLOOD CELL PRODUCTION.

Because many patients with AIDS suffer from abnormal-ly low levels of both red and white blood cells, they maybe given medications to stimulate blood cell production.Epoetin alfa (erythropoietin) may be given to anemicpatients. Patients with low white blood cell counts maybe given filgrastim or sargramostim.
Treatment in women
Treatment of pregnant women with HIV is particu-

larly important in that anti-retroviral therapy has beenshown to reduce transmission to the infant by 65%.
Alternative treatments for AIDS can be grouped into
two categories: those intended to help the immune sys-
GALE ENCYCLOPEDIA OF MEDICINE 2 80AIDSGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 80

tem and those aimed at pain control. Treatments that
may enhance the function of the immune system includeChinese herbal medicine and western herbal medicine,macrobiotic and other special diets ,guided imagery and
creative visualization, homeopathy , and vitamin therapy.
Pain control therapies include hydrotherapy ,reiki ,
acupuncture ,meditation ,chiropractic treatments, and

therapeutic massage. Alternative therapies can also beused to help with side effects of the medications used inthe treatment of AIDS.
Prognosis
At the present time, there is no cure for AIDS.
Treatment stresses aggressive combination drug

therapy for those patients with access to the expensivemedications and who tolerate them adequately. The useof these multi-drug therapies has significantly reducedthe numbers of deaths, in this country, resulting fromAIDS. The data is still inconclusive, but the potentialexists to possibly prolong life indefinitely using theseand other drug therapies to boost the immune system,keep the virus from replicating, and ward off opportunis-tic infections and malignancies.

Prognosis after the latency period depends on the
patient’s specific symptoms and the organ systemsaffected by the disease. Patients with AIDS-related lym-phomas of the central nervous system die within two tothree months of diagnosis; those with systemic lym-phomas may survive for eight to ten months.
As of 2001, there is no vaccine effective against

AIDS. Several vaccines are currently being investigated,however, both to prevent initial HIV infection and as atherapeutic treatment to prevent HIV from progressing tofull-blown AIDS.
In the meantime, there are many things that can be
done to prevent the spread of AIDS:
• Be monogamous and practice safe sex. Individuals

must be instructed in the proper use of condoms andurged to practice safe sex. Besides avoiding the risk ofHIV infection, condoms are successful in preventingother sexually transmitted diseases and unwanted preg-nancies. Before engaging in a sexual relationship withsomeone, get tested for HIV infection.
• Avoid needle sharing among intravenous drug users.
• Although blood and blood products are carefully moni-

tored, those individuals who are planning to undergomajor surgery may wish to donate blood ahead of timeto prevent a risk of infection from a blood transfusion .• Healthcare professionals must taken all necessary pre-
cautions by wearing gloves and masks when handlingbody fluids and preventing needle-stick injuries.
• If you suspect that you may have become infected, get

tested for HIV infection. If treated aggressively earlyon, the development of AIDS may be postponed indefi-nitely. If HIV infection is confirmed, it is also vital tolet your sexual partners know so that they can be testedand, if necessary, receive medical attention.
Resources
BOOKS
Early HIV Infection Guideline Panel. Evaluation and Manage-
ment of Early HIV Infection. Rockville, MD: U.S. Depart-
ment of Health and Human Services, Agency for HealthCare Policy and Research, 1994.

Huber, Jeffrey T. Dictionary of AIDS-Related Terminology. New
York and London: Neal-Schuman Publishers, Inc., 1993.
“Infectious Diseases: Human Immunodeficiency Virus (HIV).”
In Neonatology: Management, Procedures, On-Call Prob-
lems, Diseases and Drugs. Ed. Tricia Lacy Gomella, et al.
Norwalk, CT: Appleton & Lange, 1994.
Katz, Mitchell H., and Harry Hollander. “HIV Infection.” In
Current Medical Diagnosis & Treatment. Ed. Lawrence M.
Tierney Jr., et al. Stamford, CT: Appleton & Lange, 1998.

McFarland, Elizabeth J. “Human Immunodeficiency Virus
(HIV) Infections: Acquired Immunodeficiency Syndrome(AIDS).” In Current Pediatric Diagnosis & Treatment. Ed.
William W. Hay Jr., et al. Stamford, CT: Appleton &Lange, 1997.
So, Peter, and Livette Johnson. “Acquired Immune Deficiency
Syndrome (AIDS).” In Conn’s Current Therapy. Ed. Robert
E. Rakel. Philadelphia: W. B. Saunders Company, 1997.
Xiao, X., L. Wu, T. S. Stantchev, Y . R. Feng, S. Ugolini, H.

Chen, Z. Shen, J. L. Riley, C. C. Broder, Q. J. Sattentau,and D. S. Dimitrov. “Constitutive cell surface associationbetween CD4 and CCR5.” Proceedings of the National
Academy of Sciences of the United States of America.(June 1999): 7496-7501.
Gay Men’s Health Crisis, Inc., 129 West 20th Street, New York,
NY 10011-0022. (212) 807-6655.
National AIDS Hot Line. (800) 342-AIDS (English). (800) 344-
SIDA (Spanish). (800) AIDS-TTY (hearing-impaired).
OTHER

OTHER
“FDA Approved Drugs for HIV Infection and AIDS-Related
Conditions.” HIV/AIDS Treatment Information Service
website. January 2001. <http://hivatis.org>.
AIDS serology seeAIDS tests
GALE ENCYCLOPEDIA OF MEDICINE 2 81AIDSGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 81

AIDS tests
AIDS tests, short for acquired immunodeficiency

syndrome tests, cover a number of different proceduresused in the diagnosis and treatment of HIV patients. Thesetests are sometimes called AIDS serology tests. Serologyis the branch of immunology that deals with the contentsand characteristics of blood serum. Serum is the clear lightyellow part of blood that remains liquid when blood cellsform a clot. AIDS serology evaluates the presence ofhuman immunodeficiency virus (HIV) infection in bloodserum and its effects on each patient’s immune

Purpose
AIDS serology serves several different purposes.
Some AIDS tests are used to diagnose patients or con-firm a diagnosis; others are used to measure the progres-sion of the disease or the effectiveness of specific treat-ment regimens. Some AIDS tests can also be used toscreen blood donations for safe use in transfusions.
In order to understand the different purposes of the

blood tests used with AIDS patients, it is helpful tounderstand how HIV infection affects human blood andthe immune system. HIV is a retrovirus that enters theblood stream of a new host in the following ways:
• by sexual contact
• by contact with infected body fluids (such as blood and
urine)
• by transmission during pregnancy ,o r
• through transfusion of infected blood products
A retrovirus is a virus that contains a unique enzyme

called reverse transcriptase that allows it to replicate with-in new host cells. The virus binds to a protein called CD4,which is found on the surface of certain subtypes of whiteblood cells, including helper T cells, macrophages, andmonocytes. Once HIV enters the cell, it can replicate andkill the cell in ways that are still not completely under-stood. In addition to killing some lymphocytes directly, theAIDS virus disrupts the functioning of the remaining CD4cells. CD4 cells ordinarily

of the remaining CD4cells. CD4 cells ordinarily produce a substance calledinterleukin-2 (IL-2), which stimulates other cells (T cellsand B cells) in the human immune system to respond toinfections. Without the IL-2, T cells do not reproduce asthey normally would in response to the HIV virus, and Bcells are not stimulated to respond to the infection.

In some states such as New York, a signed consent
form is needed in order to administer an AIDS test. Aswith all blood tests, healthcare professionals shouldalways wear latex gloves and to avoid being pricked bythe needle used in drawing blood for the tests. Also, itmay be difficult to get blood from a habitual intravenousdrug user due to collapsed veins.
Diagnostic tests
Diagnostic blood tests for AIDS are usually given to

persons in high-risk populations who may have beenexposed to HIV or who have the early symptoms ofAIDS. Most persons infected with HIV will develop adetectable level of antibody within three months of infec-tion. The condition of testing positive for HIV antibodyin the blood is called seroconversion, and persons whohave become HIV-positive are called seroconverters.
It is possible to diagnose HIV infection by isolating

the virus itself from a blood sample or by demonstratingthe presence of HIV antigen in the blood. Viral culture,however, is expensive, not widely available, and slow—ittakes 28 days to complete the viral culture test. Morecommon are blood tests that work by detecting the pres-ence of antibodies to the HIV virus. These tests are inex-pensive, widely available, and accurate in detecting99.9% of AIDS infections when used in combination toscreen patients and confirm diagnoses.

This type of blood test is used to screen blood for trans-fusions as well as diagnose patients. An ELISA test forHIV works by attaching HIV antigens to a plastic well orbeads. A sample of the patient’s blood serum is added,and excess proteins are removed. A second antibody cou-pled to an enzyme is added, followed by addition of asubstance that will cause the enzyme to react by forminga color. An instrument called a spectrophotometer canmeasure the color. The name of the test is derived fromthe

color. The name of the test is derived fromthe use of the enzyme that is coupled or linked to the sec-ond antibody.

The latest generation of ELISA tests are 99.5% sen-
sitive to HIV . Occasionally, the ELISA test will be posi-tive for a patient without symptoms of AIDS from a low-risk group. Because this result is likely to be a false-posi-tive, the ELISA must be repeated on the same sample of
the patient’s blood . If the second ELISA is positive, the
result should be confirmed by the Western blot test.
WESTERN BLOT (IMMUNOBLOT). The Western blot

or immunoblot test is used as a reference procedure toconfirm the diagnosis of AIDS. In Western blot testing,HIV antigen is purified by electrophoresis (large proteinmolecules are suspended in a gel and separated from oneanother by running an electric current through the gel).
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The HIV antigens are attached by blotting to a nylon or
nitrocellulose filter. The patient’s serum is reacted againstthe filter, followed by treatment with developing chemi-cals that allow HIV antibody to show up as a coloredpatch or blot. A commercially produced Western blot testfor HIV-1 is now available. It consists of a prefabricatedstrip that is incubated with a sample of the patient’s bloodserum and the developing chemicals. About nine differentHIV-1 proteins can be detected in the blots.

When used in combination with ELISA testing,
Western blot testing is 99.9% specific. It can, however,yield false negatives in patients with very early HIVinfection and in those infected by HIV-2. In somepatients the Western blot yields indeterminate results.
IMMUNOFLUORESCENCE ASSAY (IFA). This method

is sometimes used to confirm ELISA results instead ofWestern blotting. An IFA test detects the presence ofHIV antibody in a sample of the patient’s serum by mix-ing HIV antigen with a fluorescent chemical, adding theblood sample, and observing the reaction under a micro-scope with ultraviolet light.
POLYMERASE CHAIN REACTION (PCR). This test is

used to evaluate the very small number of AIDS patientswith false-negative ELISA and Western blot tests. Thesepatients are sometimes called antibody-negative asympto-matic (without symptoms) carriers, because they do nothave any symptoms of AIDS and there is no detectablequantity of antibody in the blood serum. Antibody-nega-tive asymptomatic carriers may be responsible for thevery low ongoing risk of HIV infection transmitted byblood transfusions. It is estimated that the risk is between1 in

It is estimated that the risk is between1 in 10,000 and 1 in 100,000 units of transfused blood.

sure the presence of viral nucleic acids in the patient’sblood even when there is no detectable antibody to HIV .This test works by amplifying the presence of HIV nucle-ic acids in a blood sample. Numerous copies of a gene aremade by separating the two strands of DNA containingthe gene segment, marking its location, using DNA poly-merase to make a copy, and then continuously replicatingthe copies. It is questionable whether PCR will replaceWestern blotting as the method of confirming AIDS

blotting as the method of confirming AIDS diag-noses. Although PCR can detect the low number of per-sons (1%) with HIV infections that have not yet generatedan antibody response to the virus, the overwhelmingmajority of infected persons will be detected by ELISAscreening within one to three months of infection. Inaddition, PCR testing is based on present knowledge ofthe genetic sequences in HIV . Since the virus is continual-ly generating new variants, PCR testing could yield afalse negative in

PCR testing could yield afalse negative in patients with these new variants.In 1999, the U.S. Food and Drug Administration

(FDA) approved an HIV home testing kit. The kit containsmultiple components, including material for specimen col-lection, a mailing envelope to send the specimen to a labo-ratory for analysis, and provides pre- and post-test coun-seling. It uses a finger prick process for blood collection.The results are obtained by the purchaser through a tollfree telephone number using a personal identificationnumber (PIN). Post test counseling is provided over thetelephone by a licensed counselor. The only

thetelephone by a licensed counselor. The only kit approvedby the FDA as of 2001 was the Home Access test system.

Prognostic tests
Blood tests to evaluate patients already diagnosed
with HIV infection are as important as the diagnostictests. Because AIDS has a long latency period, some per-sons may be infected with the virus for 10 years or longerbefore they develop symptoms of AIDS. These patientsare sometimes called antibody-positive asymptomaticcarriers. Prognostic tests also help drug researchers eval-uate the usefulness of new medications in treating AIDS.
BLOOD CELL COUNTS. Doctors can measure the

number or proportion of certain types of cells in an AIDSpatient’s blood to see whether and how rapidly the dis-ease is progressing, or whether certain treatments arehelping the patient. These cell count tests include:
• Complete blood count (CBC). A CBC is a routine analy-
sis performed on a sample of blood taken from thepatient’s vein with a needle and vacuum tube. The mea-
GALE ENCYCLOPEDIA OF MEDICINE 2 83AIDS tests

A three-dimensional model of the HIV virus. (Corbis Corpora-
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surements taken in a CBC include a white blood cell count
(WBC), a red blood cell count (RBC), the red cell distribu-tion width, the hematocrit (ratio of the volume of the red

blood cells to the blood volume), and the amount of hemo-globin (the blood protein that carries oxygen). AlthoughCBCs are used on more than just AIDS patients, they canhelp the doctor determine if an AIDS patient has anadvanced form of the disease. Specific AIDS-related signsin a CBC include a low hematocrit, a sharp decrease in thenumber of blood platelets, and a low level of a certain typeof white blood cell called neutrophils.
• Absolute CD4+ lymphocytes. A lymphocyte is a type

of white blood cell that is important in the formationKEY TERMS
Antibody —A protein in the blood that identifies
and helps remove disease organisms or their toxins.Antibodies are secreted by B cells. AIDS diagnostictests work by demonstrating the presence of HIVantibody in the patient’s blood.
produce antibodies.
B cell —A type of white blood cell derived from

bone marrow. B cells are sometimes called B lym-phocytes. They secrete antibody and have a numberof other complex functions within the humanimmune system.
CD4—A type of protein molecule in human blood

that is present on the surface of 65% of human Tcells. CD4 is a receptor for the HIV virus. When theHIV virus infects cells with CD4 surface proteins, itdepletes the number of T cells, B cells, natural killercells, and monocytes in the patient’s blood. Most ofthe damage to an AIDS patient’s immune system isdone by the virus’ destruction of CD4+ lympho-cytes. CD4 is sometimes called the T4 antigen.
Complete blood count (CBC) —A routine analysis

performed on a sample of blood taken from thepatient’s vein with a needle and vacuum tube. Themeasurements taken in a CBC include a white bloodcell count, a red blood cell count, the red cell distri-bution width, the hematocrit (ratio of the volume ofthe red blood cells to the blood volume), and theamount of hemoglobin (the blood protein that car-ries oxygen). CBCs are a routine blood test used formany medical reasons and are not used only forAIDS patients. They can help the doctor determine if

a patient is in advanced stages of the disease.
Electrophoresis —A method of separating complex
protein molecules suspended in a gel by running anelectric current through the gel.
Enzyme-linked immunosorbent assay (ELISA) —A

diagnostic blood test used to screen patients forAIDS or other viruses. The patient’s blood is mixedwith antigen attached to a plastic tube or bead sur-face. A sample of the patient’s blood serum isadded, and excess proteins are removed. A secondantibody coupled to an enzyme is added, followedby a chemical that will cause a color reaction thatcan be measured by a special instrument.

sible retrovirus that causes AIDS in humans. Twoforms of HIV are now recognized: HIV-1, which caus-es most cases of AIDS in Europe, North and SouthAmerica, and most parts of Africa; and HIV-2, whichis chiefly found in West African patients. HIV-2, dis-covered in 1986, appears to be less virulent than HIV-1, but may also have a longer latency period.
Immunofluorescent assay (IFA) —A blood test

sometimes used to confirm ELISA results instead ofusing the Western blotting. In an IFA test, HIV anti-gen is mixed with a fluorescent compound and thenwith a sample of the patient’s blood. If HIV antibodyis present, the mixture will fluoresce when exam-ined under ultraviolet light.
important in the formation of antibodies. Doctors
of an immune response. Because HIV targets CD4+

lymphocytes, their number in the patient’s blood canbe used to track the course of the infection. This bloodcell count is considered the most accurate indicatorfor the presence of an opportunistic infection in anAIDS patient. The absolute CD4+ lymphocyte countis obtained by multiplying the patient’s white bloodcell count (WBC) by the percentage of lymphocytesamong the white blood cells, and multiplying theresult by the percentage of lymphocytes bearing theCD4+ marker. An absolute count below

bearing theCD4+ marker. An absolute count below 200-300CD+4 lymphocytes in 1 cubic millimeter (mm

3) of
blood indicates that the patient is vulnerable to someopportunistic infections.
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• CD4+ lymphocyte percentage. Some doctors think that
this is a more accurate test than the absolute countbecause the percentage does not depend on a manualcalculation of the number of types of different whiteblood cells. A white blood cell count that is brokendown into categories in this way is called a WBC dif-ferential.
It is important for doctors treating AIDS patients to

measure the lymphocyte count on a regular basis.Experts consulted by the United States Public HealthService recommend the following frequency of serumtesting based on the patient’s CD4+ level:
• CD4+ count more than 600 cells/mm
3: Every six months.KEY TERMS
can monitor the health of AIDS patients by measur-
ing the number or proportion of certain types oflymphocytes in the patient’s blood.

marily in the bloodstream and connective tissue,that helps the body fight off infections by ingestingthe disease organism. HIV can infect and killmacrophages.
Opportunistic infection —An infection that devel-
ops only when a person’s immune system is weak-ened, as happens to AIDS patients.

Polymerase chain reaction (PCR) —A test performed
to evaluate false-negative results to the ELISA andWestern blot tests. In PCR testing, numerous copiesof a gene are made by separating the two strands ofDNA containing the gene segment, marking itslocation, using DNA polymerase to make a copy,and then continuously replicating the copies. Theamplification of gene sequences that are associatedwith HIV allows for detection of the virus by thismethod.

Seroconversion —The change from HIV- negative to
HIV-positive status during blood testing. Personswho are HIV-positive are called seroconverters.Serology —The analysis of the contents and proper-
ties of blood serum.
Serum —The part of human blood that remains liq-
uid when blood cells form a clot. Human bloodserum is clear light yellow in color.

Viral load test —A new blood test for monitoring the
speed of HIV replication in AIDS patients. The viralload test is based on PCR techniques and supple-ments the CD4+ cell count tests.
Western blot —A technique developed in 1979 that

is used to confirm ELISA results. HIV antigen is puri-fied by electrophoresis and attached by blotting to anylon or nitrocellulose filter. The patient’s serum isreacted against the filter, followed by treatment withdeveloping chemicals that allow HIV antibody toshow up as a colored patch or blot. If the patient isHIV-positive, there will be stripes at specific loca-tions for two or more viral proteins. A negativeresult is blank.

WBC differential —A white blood cell count in
which the technician classifies the different whiteblood cells by type as well as calculating the num-ber of each type. A WBC differential is necessary tocalculate the absolute CD4+ lymphocyte count.
• CD4+ count between 200-600 cells/mm
3: Every three
months.
• CD4+ count less than 200 cells/mm3: Every three months.
When the CD4+ count falls below 200 cells/mm3,

the doctor will put the patient on a medication regimen toprotect him or her against opportunistic infections.
HIV VIRAL LOAD TESTS. Another type of blood test
for monitoring AIDS patients is the viral load test. It sup-plements the CD4+ count, which can tell the doctor theextent of the patient’s loss of immune function, but notthe speed of HIV replication in the body. The viral loadtest is based on PCR techniques and can measure the

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number of copies of HIV nucleic acids. Successive test
results for a given patient’s viral load are calculated on abase 10 logarithmic scale.
BETA2-MICROGLOBULIN ( /H92522M).Beta2-microglobulin
is a protein found on the surface of all human cells witha nucleus. It is released into the blood when a cell dies.Although rising blood levels of /H9252
2M are found in
patients with cancer and other serious diseases, a rising
/H92522M blood level can be used to measure the progression
of AIDS.

of AIDS.
P24 ANTIGEN CAPTURE ASSAY. Found in the viral
core of HIV , p24 is a protein that can be measured bythe ELISA technique. Doctors can use p24 assays tomeasure the antiviral activity of the patient’s medica-tions. In addition, the p24 assay is sometimes useful indetecting HIV infection before seroconversion. Howev-er, p24 is consistently present in only 25% of personsinfected with HIV .
GENOTYPIC DRUG RESISTANCE TEST. Genotypic

testing can help determine whether specific gene muta-tions, common in people with HIV , are causing drugresistance and drug failure. The test looks for specificgenetic mutations of within the virus that are known tocause resistance to certain drugs used in HIV treatment.For example the drug 3TC, also known as lamivudine(Epivir), is not effective against strains of HIV that havea mutation at a particular position on the reverse tran-scriptase protein—amino acid 184—known as M184V(M/L50478V ,

protein—amino acid 184—known as M184V(M/L50478V , methionine to valine). So if the genotypic resis-

tance test shows a mutation at position M184V , it is like-ly that person is resistant to 3TC and not likely torespond to 3TC treatment. Genotypic tests are onlyeffective if the person is already taking antiviral medica-tion and if the viral load is greater than 1,000 copies permilliliter (mL) of blood. The cost of the test, usuallybetween $300 and $500, is usually now covered bymany insurance plans.
PHENOTYPIC DRUG RESISTANCE TESTING. Pheno-

typic testing directly measures the sensitivity of apatient’s HIV to particular drugs and drug combinations.To do this, it measures the concentration of a drugrequired to inhibit viral replication in the test tube. Thisis the same method used by researchers to determinewhether a drug might be effective against HIV beforeusing it in human clinical trials. Phenotypic testing is amore direct measurement of resistance than genotypictesting. Also, unlike genotypic testing, phenotypic test-ing does

genotypic testing, phenotypic test-ing does not require a high viral load but it is recom-mended that persons already be taking antiretroviral

drugs . The cost is between $700 and $900 and is now
covered by many insurance plans.AIDS serology in children
Children born to HIV-infected mothers may acquire

the infection through the mother’s placenta or during thebirth process. Public health experts recommend the test-ing and monitoring of all children born to mothers withHIV . Diagnostic testing in children older than 18 monthsis similar to adult testing, with ELISA screening con-firmed by Western blot. Younger infants can be diagnosedby direct culture of the HIV virus, PCR testing, and p24antigen testing. These techniques allow a pediatrician toidentify 50% of infected children at or near birth,

50% of infected children at or near birth, and95% of cases in infants three to six months of age.

Preparation and aftercare are important parts of AIDS

diagnostic testing. Doctors are now advised to take thepatient’s emotional, social, economic, and other circum-stances into account and to provide counseling before andafter testing. Patients are generally better able to cope withthe results if the doctor has spent some time with thembefore the blood test explaining the basic facts about HIVinfection and testing. Many doctors now offer this type ofinformational counseling before performing the tests.
Aftercare

Aftercare
If the test results indicate that the patient is HIV- pos-
itive, he or she will need counseling, information, referralfor treatment, and support. Doctors can either counsel thepatient themselves or invite an experienced HIV coun-selor to discuss the results of the blood tests with thepatient. They will also assess the patient’s emotional andpsychological status, including the possibility of violentbehavior and the availability of a support network.
Risks

Risks
The risks of AIDS testing are primarily related to
disclosure of the patient’s HIV status rather than to anyphysical risks connected with blood testing. Somepatients are better prepared to cope with a positive diag-nosis than others, depending on their age, sex, health,resources, belief system, and similar factors.
Normal results for ELISA, Western blot, IFA, and
PCR testing are negative for HIV antibody.
Normal results for blood cell counts:

• WBC differential: Total lymphocytes 24-44% of the
white blood cells.
• Hematocrit: 40-54% in men; 37-47% in women.
GALE ENCYCLOPEDIA OF MEDICINE 2 86AIDS testsGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 86

• T cell lymphocytes: 644-2200/mm3, 60-88% of all lym-
phocytes.
• B cell lymphocytes: 82-392/mm3, 3-20% of all lympho-
cytes.
• CD4+ lymphocytes: 500-1200/mm3, 34-67% of all
lymphocytes.
The following results in AIDS tests indicate progres-
sion of the disease:
• Percentage of CD4+ lymphocytes: less than 20% of all
• CD4+ lymphocyte count: less than 200 cells/mm3.

• Viral load test: Levels more than 5000 copies/mL.•/H9252-2-microglobulin: Levels more than 3.5 mg/dL.
• P24 antigen: Measurable amounts in blood serum.
Resources
BOOKS
Avrameas, Stratis, and Therese Ternynck. “Enzyme Linked
Immunosorbent Assay (ELISA).” In Encyclopedia of
Immunology. V ol. 1. Ed. Ivan M. Roitt and Peter J. Delves.
London: Academic Press, 1992.
Bennett, Rebecca, and Erin, Charles A. (Editors). HIV and

AIDS Testing, Screening, and Confidentiality: Ethics, Law,and Social Policy. Oxford, England: Oxford University
Press, 2001.
Huber, Jeffrey T. Dictionary of AIDS- Related Terminology.
New York: Neal-Schuman Publishers, Inc., 1993.

lems, Diseases and Drugs. Ed. Tricia Lacy Gomella et al.
Current Medical Diagnosis & Treatment. Ed. Lawrence
M. Tierney et al. Stamford, CT: Appleton & Lange, 1998.
McClure, Myra. “Human Immunodeficiency Viruses.” In Ency-
clopedia of Immunology. V ol. 2. Ed. by Ivan M. Roitt and
Peter J. Delves. London: Academic Press, 1992.

William W. Hay et al. Stamford, CT: Appleton & Lange,1997.
Syndrome (AIDS).” In Conn’s Current Therapy. Ed.
Robert E. Rakel. Philadelphia: W. B. Saunders Company,1997.Springhouse Publishing. Handbook of Diagnostic Tests.

Springhouse, PA: Springhouse Publishing Co., 1999.
Towbin, Harry. “Western Blotting.” In Encyclopedia of
Immunology. V ol. 3. Ed. Ivan M. Roitt and Peter J. Delves.
Freedberg, Kenneth A., and Samet, Jeffrey H. “Think HIV
(HIV Testing).” Archives of Internal Medicine (September
27, 1999): 1994
Kaplan, Edward H., and Satten, Glen A. “Repeat Screening for
HIV: When to Test and Why.” The Journal of the Ameri-
can Medical Association. (July 19, 2000): 285.

Sieff, Elaine M., et al. “Anticipated Versus Actual Reaction to
HIV Test Results.” American Journal of Psychology.
(Summer 1999): 297-298.
Weinhardt, Lance S., et al. “Human Immunodeficiency Virus
Testing and Behavior Change.” Archives of Internal Medi-
cine. (May 22, 2000): 1538.
Woehrle, Theresa A., and Branson, Bernard. “New Tests for
Detecting HIV Infection.” The Western Journal of Medi-
cine. (December 1998): 371-372.

National Association of People with Aids. 1413 K St.N.W.,
Washington, DC 20005-3442. (202) 898-0414.
National Institute of Health. Office of Aids Research. (301)
496-0357. <http://www.nih.gov/od/oar/index.htm>.
Centers for Disease Control and Prevention (CDC). 1600
Clifton Rd., Atlanta, GA 30337. (404) 639-3311. <http://www.cdc.gov>.
OTHER
Food and Drug Administration (FDA). “Testing Yourself for

HIV-1, the Virus that Causes AIDS.” 1999. Available atFDA Website: <http://www.fda.gov>. or by calling (301)827-4460.
Air embolism seeGas embolism
Alanine aminotransferase test
The alanine aminotransferase test, also known as
ALT, is one of a group of tests known as liver function
tests (or LFTs) and is used to monitor damage to the liver.
Purpose
ALT levels are used to detect liver abnormalities.

Since the alanine aminotransferase enzyme is also foundin muscle, tests indicating elevated AST levels might alsoindicate muscle damage. However, other tests, such as
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the levels of the MB fraction of creatine kinase should
indicate whether the abnormal test levels are because ofmuscle or liver damage.
The alanine aminotransferase test (ALT) can reveal

liver damage. It is probably the most specific test forliver damage. However, the severity of the liver damageis not necessarily shown by the ALT test, since theamount of dead liver tissue does not correspond to higherALT levels. Also, patients with normal, or declining,ALT levels may experience serious liver damage withoutan increase in ALT.
Nevertheless, ALT is widely used, and useful,

because ALT levels are elevated in most patients withliver disease. Although ALT levels do not necessarilyindicate the severity of the damage to the liver, they mayindicate how much of the liver has been damaged. ALTlevels, when compared to the levels of a similar enzyme,aspartate aminotransferase (AST), may provide impor-tant clues to the nature of the liver disease. For example,within a certain range of values, a ratio of 2:1 or greaterfor AST: ALT might indicate that a patient suffers

AST: ALT might indicate that a patient suffers fromalcoholic liver disease. Other diagnostic data may begleaned from ALT tests to indicate abnormal results.

No special preparations are necessary for this test.
Aftercare
This test involves blood being drawn, probably from
a vein in the patient’s elbow. The patient should keep thewound from the needle puncture covered (with a ban-dage) until the bleeding stops. Patients should report anyunusual symptoms to their physician.
Normal values vary from laboratory to laboratory,

and should be available to your physician at the time ofthe test. An informal survey of some laboratories indi-cates many laboratories find values from approximatelyseven to 50 IU/L to be normal.
Low levels of ALT (generally below 300 IU/L) may

indicate any kind of liver disease. Levels above 1,000IU/L generally indicate extensive liver damage from tox-ins or drugs, viral hepatitis, or a lack of oxygen (usuallyresulting from very low blood pressure or a heart
attack ). A briefly elevated ALT above 1,000 IU/L thatresolves in 24-48 hours may indicate a blockage of the
bile duct. More moderate levels of ALT (300-1,000IU/L)may support a diagnosis of acute or chronic hepatitis.

It is important to note that persons with normal liv-
ers may have slightly elevated levels of ALT. This is anormal finding.
Michael V . Zuck, PhD
Alanine aminotransferase test seeLiver
function tests
Albers-Schönberg disease see
Osteopetroses
Albinism
Albinism is an inherited condition present at birth,

characterized by a lack of pigment that normally givescolor to the skin, hair, and eyes. Many types of albinismexist, all of which involve lack of pigment in varyingdegrees. The condition, which is found in all races, maybe accompanied by eye problems and may lead to skincancer later in life.
Albinism is a rare disorder found in fewer than five

people per 100,000 in the United States and Europe.Other parts of the world have a much higher rate; forexample, albinism is found in about 20 out of every100,000 people in southern Nigeria.
There are 10 types of the most common form of the

condition, known as “oculocutaneous albinism,” whichaffects the eyes, hair, and skin. In its most severe form,hair and skin remain pure white throughout life. Peoplewith a less severe form are born with white hair andskin, which turn slightly darker as they age. Everyonewith oculocutaneous albinism experiences abnormalflickering eye movements ( nystagmus ) and sensitivity

to bright light. There may be other eye problems aswell, including poor vision and crossed or “lazy” eyes(strabismus ).
The second most common type of the condition is
known as “ocular” albinism, in which only the eyes lackcolor; skin and hair are normal. There are five forms ofocular albinism; some types cause more problems—especially eye problems—than others.
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Every cell in the body contains a matched pair of
genes, one inherited from each parent. These genes act as asort of “blueprint” that guides the development of a fetus.
Albinism is an inherited problem caused by a flaw in
one or more of the genes that are responsible for direct-ing the eyes and skin to make melanin (pigment). As aresult, little or no pigment is made, and the child’s skin,eyes and hair may be colorless.
In most types of albinism, a recessive trait, the child

inherits flawed genes for making melanin from both par-ents. Because the task of making melanin is complex,there are many different types of albinism, involving anumber of different genes.
It’s also possible to inherit one normal gene and one

albinism gene. In this case, the one normal gene providesenough information in its cellular blueprint to makesome pigment, and the child will have normal skin andeye color. They “carry” one gene for albinism. About onein 70 people are albinism carriers, with one flawed genebut no symptoms; they have a 50% chance of passing thealbinism gene to their child. However, if both parents areKEY TERMS
Amino acids —Natural substances that are the

building blocks of protein. The body breaks downthe protein in food into amino acids, and then usesthese amino acids to create other proteins. The bodyalso changes amino acids into melanin pigment.
Astigmatism —An eye condition in which the lens
doesn’t focus light evenly on the retina, leading toproblems with visual sharpness.
Carrier —A person with one normal gene and one

faulty gene, who can pass on a condition to otherswithout actually having symptoms.
DNA —The abbreviation for “deoxyribonucleic
acid,” the primary carrier of genetic informationfound in the chromosomes of almost all organisms.The entwined double structure allows the chromo-somes to be copied exactly during cell division.
DOPA —The common name for a natural chemical
(3,4-dihydroxyphenylalanine) made by the bodyduring the process of making melanin.

Enzyme —A protein that helps the body convert one
chemical substance to another.Gene —The basic unit of genetic material carried in
a particular place on a chromosome. Genes arepassed on from parents to child when the spermand egg unite during conception.
Hairbulb —The root of a strand of hair from which
the color develops.
Hermansky-Pudlak Syndrome (HPS) —A rare type
of albinism characterized by a problem with bloodclotting and a buildup of waxy material in lungsand intestines.

Melanin —Pigment made in the hair, skin and eyes.
Nystagmus —An involuntary back-and-forth move-
ment of the eyes that is often found in albinism.
Strabismus —Crossed or “lazy” eyes, often found in
albinism.
Tyrosine —A protein building block found in a wide
variety of foods that is used by the body to makemelanin.
Tyrosinase —An enzyme in a pigment cell which
helps change tyrosine to DOPA during the processof making melanin.
carriers with one flawed gene each, they have a 1 in 4

chance of passing on both copies of the flawed gene tothe child, who will have albinism. (There is also a type ofocular albinism that is carried on the X chromosome andoccurs almost exclusively in males because they haveonly one X chromosome and, therefore, no other gene forthe trait to override the flawed one.)
Symptoms of albinism can involve the skin, hair,
and eyes. The skin, because it contains little pigment,appears very light, as does the hair.

ety of eye problems, one of the myths about albinism is thatit causes people to have pink or red eyes. In fact, peoplewith albinism can have irises varying from light gray orblue to brown. (The iris is the colored portion of the eyethat controls the size of the pupil, the opening that lets lightinto the eye.) If people with albinism seem to have reddisheyes, it’s because light is being reflected from the back ofthe eye (retina) in much the same way as happens whenpeople are photographed with an

as happens whenpeople are photographed with an electronic flash.

People with albinism may have one or more of the
following eye problems:
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• They may be very far-sighted or near-sighted, and may
have other defects in the curvature of the lens of the eye(astigmatism ) that cause images to appear unfocused.
• They may have a constant, involuntary movement of
the eyeball called nystagmus.
• They may have problems in coordinating the eyes in fix-

ing and tracking objects (strabismus), which may lead toan appearance of having “crossed eyes” at times. Stra-bismus may cause some problems with depth percep-tion, especially at close distances.
• They may be very sensitive to light (photophobia)
because their irises allow “stray” light to enter their eyes.It’s a common misconception that people with albinismshouldn’t go out on sunny days, but wearing sunglassescan make it possible to go outside quite comfortably.

In addition to the characteristically light skin and
eye problems, people with a rare form of albinism calledHermansky-Pudlak Syndrome (HPS) also have a greatertendency to have bleeding disorders, inflammation of thelarge bowel (colitis), lung (pulmonary) disease, and kid-ney (renal) problems.Diagnosis
It’s not always easy to diagnose the exact type of

albinism a person has; there are two tests available thatcan identify only two types of the condition. Recently, ablood test has been developed that can identify carriersof the gene for some types of albinism; a similar test dur-ing amniocentesis can diagnose some types of albinism
in an unborn child. A chorionic villus sampling test dur-
ing the fifth week of pregnancy may also reveal some
types of albinism.
The specific type of albinism a person has can be

determined by taking a good family history and examin-ing the patient and several close relatives.
The “hairbulb pigmentation test” is used to identify

carriers by incubating a piece of the person’s hair in asolution of tyrosine, a substance in food which the bodyuses to make melanin. If the hair turns dark, it means thehair is making melanin (a “positive” test); light hairmeans there is no melanin. This test is the source of thenames of two types of albinism: “ty-pos” and “ty-neg.”
The tyrosinase test is more precise than the hairbulb
pigmentation test. It measures the rate at which hair con-
GALE ENCYCLOPEDIA OF MEDICINE 2 90Albinism

A man with albinism stands with his normally pigmented father. (Photograph by Norman Lightfoot, Photo Researchers, Inc.
Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 90

verts tyrosine into another chemical (DOPA), which is
then made into pigment. The hair converts tyrosine withthe help of a substance called “tyrosinase.” In some typesof albinism, tyrosinase doesn’t do its job, and melaninproduction breaks down.
Treatment
There is no treatment that can replace the lack of

melanin that causes the symptoms of albinism. Doctorscan only treat, not cure, the eye problems that oftenaccompany the lack of skin color. Glasses are usuallyneeded and can be tinted to ease pain from too much
sunlight. There is no cure for involuntary eye movements(nystagmus), and treatments for focusing problems(surgery or contact lenses) are not effective in all cases.
Crossed eyes (strabismus) can be treated during

infancy, using eye patches, surgery or medicine injec-tions. Treatment may improve the appearance of theeye, but it can do nothing to cure the underlying con-dition.
Patients with albinism should avoid excessive expo-
sure to the sun, especially between 10 
A.M. and 2 P.M.I f

exposure can’t be avoided, they should use UV A-UVBsunblocks with an SPF of at least 20. Taking beta-carotene may help provide some skin color, although itdoesn’t protect against sun exposure.
Prognosis
In the United States, people with this condition

can expect to have a normal lifespan. People withalbinism may experience some social problemsbecause of a lack of understanding on the part of oth-ers. When a member of a normally dark-skinned ethnicgroup has albinism, he or she may face some verycomplex social challenges.
One of the greatest health hazards for people with

albinism is excessive exposure to sun without protec-tion, which could lead to skin cancer. Wearing opaqueclothes and sunscreen rated SPF 20, people withalbinism can safely work and play outdoors safely evenduring the summer.
Genetic counseling is very important to prevent fur-
ther occurrences of the condition.
Resources
BOOKS
National Association for the Visually Handicapped. Larry: A
Book for Children with Albinism Going to School. New

York: National Association for the Visually Handicapped.Witkop Jr., C. J., W. C. Quevedo Jr., T. B. Fitzpatrick, and R. A
King. “Albinism.” In The Metabolic Basis of Inherited
Disease. 6th ed. Ed. C. R. Scriver, et al. New York:
McGraw-Hill, 1989.
Campbell, Maude. “Gene Found for Albinism, Other Pigment
Disorders.” Dermatology Times (1 Apr. 1995): 1.
Siegel-Itzkovich, Judy. “Early-warning Test for Albinism.”
Jerusalem Post (4 Dec. 1994).

Albinism World Alliance. <http://www.albinism.org/awa.html>.
American Foundation for the Blind. 15 W. 16th St., New York,
NY 10011. (800) AFB-LIND.
Hermansky-Pudlak Syndrome Network, Inc. One South Road,
Oyster Bay, NY 11771-1905. (800) 789-9477. <appell@theonramp.net>.
National Organization for Albinism and Hypopigmentation
(NOAH). 1530 Locust St., #29, Philadelphia, PA 19102-4415. (800) 473-2310. <http://www.albinism.org>.

Albuterol seeBronchodilators
Alcohol-related 
neurologic disease
Alcohol, or ethanol, is a poison with direct toxic

effects on nerve and muscle cells. Depending on whichnerve and muscle pathways are involved, alcohol canhave far-reaching effects on different parts of the brain,peripheral nerves, and muscles, with symptoms of mem-ory loss, incoordination, seizures, weakness, and senso-ry deficits. These different effects can be grouped inthree main categories: (1) intoxication due to the acuteeffects of ethanol, (2) withdrawal syndrome from sud-denly stopping drinking, and (3) disorders related tolong-term or

and (3) disorders related tolong-term or chronic alcohol abuse. Alcohol-relatedneurologic disease includes Wernicke-Korsakoff dis-ease, alcoholic cerebellar degeneration, alcoholicmyopathy, alcoholic neuropathy, alcohol withdrawalsyndrome with seizures and delirium tremens, and fetal

alcohol syndrome .
Acute excess intake of alcohol can cause drunken-
ness (intoxication) or even death , and chronic or long-
term abuse leads to potentially irreversible damage tovirtually any level of the nervous system. Any given
GALE ENCYCLOPEDIA OF MEDICINE 2 91AlbinismGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 91

patient with long-term alcohol abuse may have no neu-
rologic complications, a single alcohol-related disease,or multiple conditions, depending on the genes theyhave inherited, how well nourished they are, and otherenvironmental factors, such as exposure to other drugsor toxins.
Neurologic complications of alcohol abuse may also
result from nutritional deficiency, because alcoholicstend to eat poorly and may become depleted of thiamineor other vitamins important for nervous system function.

Persons who are intoxicated are also at higher risk forhead injury or for compression injuries of the peripheral
nerves. Sudden changes in blood chemistry, especiallysodium, related to alcohol abuse may cause central pon-tine myelinolysis, a condition of the brainstem in whichnerves lose their myelin coating. Liver disease compli-cating alcoholic cirrhosis may cause dementia , deliri-
um, and movement disorder.
When a person drinks alcohol, it is absorbed by

blood vessels in the stomach lining and flows rapidlythroughout the body and brain, as ethanol freely crossesthe blood-brain barrier that ordinarily keeps large mole-cules from escaping from the blood vessel to the braintissue. Drunkenness, or intoxication, may occur at bloodethanol concentrations of as low as 50-150 mg per dL inpeople who don’t drink. Sleepiness, stupor, coma ,o r

even death from respiratory depression and low bloodpressure occur at progressively higher concentrations.
Although alcohol is broken down by the liver, the

toxic effects from a high dose of alcohol are most likely adirect result of alcohol itself rather than of its breakdownproducts. The fatal dose varies widely because peoplewho drink heavily develop a tolerance to the effects ofalcohol with repeated use. In addition, alcohol toleranceresults in the need for higher levels of blood alcohol toachieve intoxicating effects, which increases the likeli-hood that habitual drinkers will be exposed to high andpotentially toxic levels of ethanol. This is

andpotentially toxic levels of ethanol. This is particularlytrue when binge drinkers fail to eat, because fasting

decreases the rate of alcohol clearance and causes evenhigher blood alcohol levels.
When a chronic alcoholic suddenly stops drinking,
withdrawal of alcohol leads to a syndrome of increasedexcitability of the central nervous system, called deliri-um tremens or “DTs.” Symptoms begin six to eighthours after abstinence, and are most pronounced 24-72hours after abstinence. They include body shaking(tremulousness), insomnia , agitation, confusion, hear-

ing voices or seeing images that are not really there(such as crawling bugs), seizures, rapid heart beat, pro-fuse sweating, high blood pressure, and fever . Alcohol-
related seizures may also occur without withdrawal,such as during active heavy drinking or after more than aweek without alcohol.
Wernicke-Korsakoff syndrome is caused by defi-

ciency of the B-vitamin thiamine, and can also be seen inpeople who don’t drink but have some other cause of thi-amine deficiency, such as chronic vomiting that preventsthe absorption of this vitamin. Patients with this condi-tion have the sudden onset of Wernicke encephalopathy;the symptoms include marked confusion, delirium, dis-orientation, inattention, memory loss, and drowsiness.Examination reveals abnormalities of eye movement,including jerking of the eyes ( nystagmus ) and double

vision. Problems with balance make walking difficult.People may have trouble coordinating their leg move-ments, but usually not their arms. If thiamine is not givenpromptly, Wernicke encephalopathy may progress to stu-por, coma, and death.
If thiamine is given and death averted, Korsakoff’s
syndrome may develop in some patients, who suffer

from memory impairment that leaves them unable toremember events for a period of a few years before theonset of illness (retrograde amnesia ) and unable to learn
new information (anterograde amnesia). Most patientshave very limited insight into their memory dysfunctionand have a tendency to make up explanations for eventsthey have forgotten (confabulation).
Severe alcoholism can cause cerebellar degenera-

tion, a slowly progressive condition affecting portions ofthe brain called the anterior and superior cerebellar ver-mis, causing a wide-based gait, leg incoordination, andan inability to walk heel-to-toe in tightrope fashion. Thegait disturbance usually develops over several weeks, butmay be relatively mild for some time, and then suddenlyworsen after binge drinking or an unrelated illness.
Fetal alcohol syndrome occurs in infants born to

alcoholic mothers when prenatal exposure to ethanolretards fetal growth and development. Affected infantsoften have a distinctive appearance with a thin upper lip,flat nose and mid-face, short stature and small head size.Almost half are mentally retarded, and most others aremildly impaired intellectually or have problems withspeech, learning, and behavior.
Alcoholic myopathy, or weakness secondary to

breakdown of muscle tissue, is also known as alcoholicrhabdomyolysis or alcoholic myoglobinuria. Males areaffected by acute (sudden onset) alcoholic myopathyfour times as often as females. Breakdown of muscle tis-sue (myonecrosis), can come on suddenly during bingedrinking or in the first days of alcohol withdrawal. In itsmildest form, this breakdown may cause no noticeable

GALE ENCYCLOPEDIA OF MEDICINE 2 92Alcohol-related neurologic diseaseGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 92

symptoms, but may be detected by a temporary elevation
in blood levels of an enzyme found predominantly inmuscle, the MM fraction of creatine kinase.
The severe form of acute alcoholic myopathy is
associated with the sudden onset of muscle pain ,

swelling, and weakness; a reddish tinge in the urinecaused by myoglobin, a breakdown product of muscleexcreted in the urine; and a rapid rise in muscle enzymesin the blood. Symptoms usually worsen over hours to afew days, and then improve over the next week to 10days as the patient is withdrawn from alcohol. Musclesymptoms are usually generalized, but pain and swellingmay selectively involve the calves or other musclegroups. The muscle breakdown of acute alcoholicmyopathy may be worsened by

of acute alcoholicmyopathy may be worsened by crush injuries, whichmay occur when people drink so much that they com-press a muscle group with their body weight for a longtime without moving, or by withdrawal seizures withgeneralized muscle activity.

chronic alcoholic myopathy may develop. Males andfemales are equally affected. Symptoms include pain-less weakness of the limb muscles closest to the trunkand the girdle muscles, including the thighs, hips,shoulders, and upper arms. This weakness developsgradually, over weeks or months, without symptoms ofacute muscle injury. Muscle atrophy, or decreased bulk,may be striking. The nerves of the extremities may alsobegin to break down, a condition known as alcoholicperipheral neuropathy , which

known as alcoholicperipheral neuropathy , which can add to the person’s

difficulty in moving.
The way in which alcohol destroys muscle tissue is
still not well understood. Proposed mechanisms includemuscle membrane changes affecting the transport of cal-cium, potassium, or other minerals ; impaired muscle

energy metabolism; and impaired protein synthesis.Alcohol is metabolized or broken down primarily by theliver, with a series of chemical reactions in which ethanolis converted to acetate. Acetate is metabolized by skeletalmuscle, and alcohol-related changes in liver functionmay affect skeletal muscle metabolism, decreasing theamount of blood sugar available to muscles during pro-longed activity. Because not enough sugar is available tosupply needed energy, muscle protein may be brokendown as an

energy, muscle protein may be brokendown as an alternate energy source. However, toxiceffects on muscle may be a direct result of alcohol itselfrather than of its breakdown products.

Although alcoholic peripheral neuropathy may con-
tribute to muscle weakness and atrophy by injuring themotor nerves controlling muscle movement, alcoholicneuropathy more commonly affects sensory fibers.Injury to these fibers can cause tingling or burning painin the feet, which may be severe enough to interfere with
walking. As the condition worsens, pain decreases butnumbness increases.
Diagnosis
The diagnosis of alcohol-related neurologic disease

depends largely on finding characteristic symptoms andsigns in patients who abuse alcohol. Other possiblecauses should be excluded by the appropriate tests,which may include blood chemistry, thyroid function
tests , brain MRI ( magnetic resonance imaging ) or CT
(computed tomography scan), and/or cerebrospinalfluid analysis.
Acute alcoholic myopathy can be diagnosed by

finding myoglobin in the urine and increased creatinekinase and other blood enzymes released from injuredmuscle. The surgical removal of a small piece of musclefor microscopic analysis (muscle biopsy) shows thescattered breakdown and repair of muscle fibers. Doc-tors must rule out other acquired causes of musclebreakdown, which include the abuse of drugs such asheroin, cocaine , or amphetamines; trauma with crush

injury; the depletion of phosphate or potassium; or anunderlying defect in the metabolism of carbohydrates orlipids. In chronic alcoholic myopathy, serum creatinekinase often is normal, and muscle biopsy shows atro-phy, or loss of muscle fibers. Electromyography
(EMG) may show features characteristic of alcoholicmyopathy or neuropathy.
Treatment
Acute management of alcohol intoxication, delirium

tremens, and withdrawal is primarily supportive, to mon-itor and treat any cardiovascular or respiratory failure
that may develop. In delirium tremens, fever and sweat-ing may necessitate treatment of fluid loss and secondarylow blood pressure. Agitation may be treated with ben-
zodiazepines such as chlordiazepoxide, beta-adrenergic

antagonists such as atenolol, or alpha 2-adrenergic ago-nists such as clonidine. Because Wernicke’s syndrome israpidly reversible with thiamine, and because death mayintervene if thiamine is not given promptly, all patientsadmitted for acute complications of alcohol, as well asall patients with unexplained encephalopathy, should begiven intravenous thiamine.
Withdrawal seizures typically resolve without spe-

cific anti-epileptic drug treatment, although status epilep-ticus (continual seizures occurring without interruption)should be treated vigorously. Acute alcoholic myopathywith myoglobinuria requires monitoring and mainte-nance of kidney function, and correction of imbalances
GALE ENCYCLOPEDIA OF MEDICINE 2 93Alcohol-related neurologic diseaseGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 93

in blood chemistry including potassium, phosphate, and
magnesium levels.
Chronic alcoholic myopathy and other chronic con-
ditions are treated by correcting associated nutritionaldeficiencies and maintaining a diet adequate in proteinand carbohydrate. The key to treating any alcohol-relateddisease is helping the patient overcome alcohol addic-
tion. Behavioral measures and social supports may be

needed in patients who develop broad problems in theirthinking abilities (dementia) or remain in a state of con-fusion and disorientation (delirium). People with walk-ing disturbances may benefit from physical therapy andassistive devices. Doctors may also prescribe drugs totreat the pain associated with peripheral neuropathy.
Prognosis
Complete recovery from Wernicke’s syndrome may

follow prompt administration of thiamine. However,repeated episodes of encephalopathy or prolonged alco-hol abuse may cause persistent dementia or Korsakoffpsychosis . Most patients recover fully from acute alco-
holic myopathy within days to weeks, but severe casesmay be fatal from acute kidney failure and disturbances
in heart rhythm secondary to increased potassium levels.Recovery from chronic alcoholic myopathy may occurKEY TERMS

Abstinence —Refraining from the use of alcoholic
beverages.
Atrophy —A wasting or decrease in size of a muscle
or other tissue.
Cerebellum —The part of the brain involved in coor-
dination of movement, walking, and balance.
Degeneration —Gradual, progressive loss of nerve
cells.
Delirium —Sudden confusion with decreased or
fluctuating level of consciousness.
Delirium tremens —A complication that may

accompany alcohol withdrawal. The symptomsinclude body shaking (tremulousness), insomnia,agitation, confusion, hearing voices or seeingimages that are not really there (hallucinations),seizures, rapid heart beat, profuse sweating, highblood pressure, and fever.
Dementia —Loss of memory and other higher func-
tions, such as thinking or speech, lasting six monthsor more.Myoglobinuria —Reddish urine caused by excretion

of myoglobin, a breakdown product of muscle.
Myopathy —A disorder that causes weakening of
muscles.
Neuropathy —A condition affecting the nerves sup-
plying the arms and legs. Typically, the feet andhands are involved first. If sensory nerves areinvolved, numbness, tingling, and pain are promi-nent, and if motor nerves are involved, the patientexperiences weakness.
Thiamine —A B vitamin essential for the body to

process carbohydrates and fats. Alcoholics may suf-fer complications (including Wernike-Korsakoff syn-drome) from a deficiency of this vitamin.
Wernicke-Korsakoff syndrome —A combination of
symptoms, including eye-movement problems,tremors, and confusion, that is caused by a lack ofthe B vitamin thiamine and may be seen in alco-holics.
over weeks to months of abstinence from alcohol and
correction of malnutrition . Cerebellar degeneration and

alcoholic neuropathy may also improve to some extentwith abstinence and balanced diet, depending on theseverity and duration of the condition.
Prevention requires abstinence from alcohol. Per-
sons who consume small or moderate amounts of alcoholmight theoretically help prevent nutritional complica-tions of alcohol use with dietary supplements includingB vitamins. However, proper nutrition cannot protect

against the direct toxic effect of alcohol or of its break-down products. Patients with any alcohol-related symp-toms or conditions, pregnant women, and patients withliver or neurologic disease should abstain completely.Persons with family history of alcoholism or alcohol-related conditions may also be at increased risk for neu-rologic complications of alcohol use.
Resources
Diamond, I., and R. O. Messing. “Neurologic Effects of Alco-

holism.” Western Journal of Medicine 161 (1994): 279-87.
GALE ENCYCLOPEDIA OF MEDICINE 2 94Alcohol-related neurologic diseaseGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 94

Neiman, J., et al. “Movement Disorders in Alcoholism: A
Review.” Neurology 40 (1990): 741-6.
Saitz, R. “Individualized Treatment for Alcohol Withdrawal. A
Randomized Double-Blind Controlled Trial.” Journal of
the American Medical Association 272 (1994): 557-8.
Victor, M. “Alcoholic Dementia.” Candian Journal of Neuro-
logical Science 21 (1994): 88-99.
National Institute on Alcohol Abuse and Alcoholism. 6000

Executive Boulevard, Willco Building, Bethesda, MD20892-7003. <http://silk.nih.gov/silk/niaaa1>.
Laurie Barclay, MD
Alcohol abuse seeAlcoholism
Alcohol dependence seeAlcoholism
Alcohol withdrawal seeWithdrawal
syndromes
Alcoholic cerebellar disease seeAlcohol-
related neurologic disease
Alcoholic hepatitis seeHepatitis, alcoholic
Alcoholic rose gardener’s disease see
Sporotrichosis
Alcoholism
The essential feature of alcohol abuse is the mal-

adaptive use of alcohol with recurrent and significantadverse consequences related to its repeated use. Alco-holism is the popular term for two disorders, alcoholabuse and alcohol dependence. The hallmarks of boththese disorders involve repeated life problems that can bedirectly attributed to the use of alcohol. Both these disor-ders can have serious consequences, affecting an individ-ual’s health and personal life, as well as having an impacton society at large.

The effects of alcoholism are quite far-reaching.
Alcohol affects every body system, causing a wide rangeof health problems. Some such problems include poornutrition , memory disorders, difficulty with balance and
walking, liver disease (including cirrhosis and hepatitis),

high blood pressure, muscle weakness (including theheart), heart rhythm disturbances, anemia, clotting disor-ders, decreased immunity to infections, gastrointestinalinflammation and irritation, acute and chronic problemswith the pancreas, low blood sugar, high blood fat con-tent, interference with reproductive fertility, and weak-ened bones.
On a personal level, alcoholism results in marital

and other relationship difficulties, depression, unemploy-ment, child abuse , and general family dysfunction.
Alcoholism causes or contributes to a variety of

severe social problems including homelessness, murder,suicide, injury, and violent crime. Alcohol is a contribut-ing factor in at least 50% of all deaths from motor vehi-cle accidents. In fact, about 100,000 deaths occur eachyear due to the effects of alcohol, of which 50% are dueto injuries of some sort. According to a recent specialreport prepared for the U.S. Congress by the NationalInstitute on Alcohol Abuse and Alcoholism, the impactof alcohol on society, including violence, traffic

alcohol on society, including violence, traffic acci-dents, lost work productivity, and premature death , costs

our nation an estimated $185 billion annually. In addi-tion, it is estimated that approximately one in four chil-dren (19 million children or 29 percent of children up to17 years of age) is exposed at some time to familial alco-hol abuse, alcohol dependence, or both. Furthermore, ithas been estimated that approximately 18 percent ofadults experience an episode of alcohol abuse or depen-dence a some time during their lives.
There are probably a number of factors that work

together to cause a person to become an alcoholic.Recent genetic studies have demonstrated that close rel-atives of an alcoholic are four times more likely tobecome alcoholics themselves. Furthermore, this riskholds true even for children who were adopted awayfrom their biological families at birth and raised in anon-alcoholic adoptive family, with no knowledge oftheir biological family’s difficulties with alcohol. Moreresearch is being conducted to determine if genetic fac-tors could account

to determine if genetic fac-tors could account for differences in alcohol metabo-lism that may increase the risk of an individual becom-ing an alcoholic.

The symptoms of alcoholism can be broken down
into two major categories: symptoms of acute alcoholuse and symptoms of long-term alcohol use.
Immediate (acute) effects of alcohol use
Alcohol exerts a depressive effect on the brain. The

blood-brain barrier does not prevent alcohol from enter-ing the brain, so the brain alcohol level will quicklybecome equivalent to the blood alcohol level. Alcohol’sdepressive effects result in difficulty walking, poor bal-ance, slurring of speech, and generally poor coordination
GALE ENCYCLOPEDIA OF MEDICINE 2 95AlcoholismGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 95

(accounting in part for the increased likelihood of
injury). The affected person may also have impairment ofperiperal vision. At higher alcohol levels, a person’sbreathing and heart rates will be slowed, and vomitingmay occur (with a high risk of the vomit being breathedinto the lungs, resulting in severe problems, including thepossibility of pneumonia ). Still higher alcohol levels
may result in coma and death.
Effects of long-term (chronic) alcoholism

Long-term use of alcohol affects virtually every
organ system of the body:
• Nervous system. An estimated 30-40% of all men in
their teens and twenties have experienced alcoholicblackout, which occurs when drinking a large quantityof alcohol results in the loss of memory of the timesurrounding the episode of drinking. Alcohol is well-known to cause sleep disturbances, so that overallsleep quality is affected. Numbness and tingling may

occur in the arms and legs. Two syndromes, which canoccur together or separately, are known as Wernicke’sand Korsakoff’s syndromes. Both are due to the lowthiamine (a form of vitamin B complex) levels foundin alcoholics. Wernicke’s syndrome results in disor-dered eye movements, very poor balance and difficultywalking, while Korsakoff’s syndrome severely
affects one’s memory, preventing new learning fromtaking place.
• Gastrointestinal system. Alcohol causes loosening of

the muscular ring that prevents the stomach’s contentsfrom re-entering the esophagus. Therefore, the acidfrom the stomach flows backwards into the esopha-gus, burning those tissues, and causing pain and

bleeding. Inflammation of the stomach can also resultin bleeding and pain, and decreased desire to eat. Amajor cause of severe, uncontrollable bleeding (hem-orrhage) in an alcoholic is the development ofenlarged (dilated) blood vessels within the esophagus,which are called esophageal varices. These varices areactually developed in response to liver disease, andare extremely prone to bursting and hemorrhaging.Diarrhea is a common symptom, due to alcohol’s

effect on the pancreas. In addition, inflammation ofthe pancreas ( pancreatitis ) is a serious and painful

problem in alcoholics. Throughout the intestinal tract,alcohol interferes with the absorption of nutrients,creating a malnourished state. Because alcohol is bro-ken down (metabolized) within the liver, that organ isseverely affected by constant levels of alcohol. Alco-hol interferes with a number of important chemicalprocesses that also occur in the liver. The liver beginsto enlarge and fill with fat ( fatty liver ), fibrous scartissue interferes with the liver’s normal structure and

function (cirrhosis), and the liver may becomeinflamed (hepatitis).
• Blood. Alcohol can cause changes to all the types of
blood cells. Red blood cells become abnormallylarge. White blood cells (important for fighting infec-tions) decrease in number, resulting in a weakenedimmune system. This places alcoholics at increasedrisk for infections, and is thought to account in partfor the increased risk of cancer faced by alcoholics

(ten times increased over normal). Platelets and bloodclotting factors are affected, causing an increased riskof bleeding.
• Heart. Small amounts of alcohol cause a drop in blood

pressure, but with increased use, alcohol begins toincrease blood pressure into a dangerous range. Highlevels of fats circulating in the bloodstream increase therisk of heart disease. Heavy drinking results in anincrease in heart size, weakening of the heart muscle,abnormal heart rhythms, a risk of blood clots formingwithin the chambers of the heart, and a greatlyincreased risk of stroke (due to a blood clot from the

heart entering the circulatory system, going to thebrain, and blocking a brain blood vessel).
• Reproductive system. Heavy drinking has a negative
effect on fertility in both men and women, by decreas-ing testicle and ovary size, and interfering with bothsperm and egg production. When pregnancy is
achieved in an alcoholic woman, the baby has a greatrisk of being born with fetal alcohol syndrome , which
causes distinctive facial defects, lowered IQ, andbehavioral problems.
Diagnosis

Diagnosis
Two different types of alcohol-related difficulties
have been identified. The first is called alcohol depen-
dence , which refers to a person who literally depends on
the use of alcohol. Three of the following traits must bepresent to diagnose alcohol dependence:
• tolerance, meaning that a person becomes accustomed
to a particular dose of alcohol, and must increase thedose in order to obtain the desired effect
• withdrawal, meaning that a person experiences

unpleasant physical and psychological symptoms whenhe or she does not drink alcohol
• the tendency to drink more alcohol than one intends
(once an alcoholic starts to drink, he or she finds it dif-ficult to stop)
• being unable to avoid drinking or stop drinking once
started
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• having large blocks of time taken up by alcohol use
• choosing to drink at the expense of other important
tasks or activities
• drinking despite evidence of negative effects on one’s
health, relationships, education, or job
Alcohol abuse requires that one of the following four
criteria is met. Because of drinking, a person repeatedly:
• fails to live up to his or her most important responsibili-
ties
• physically endangers him or herself, or others (for
example, by drinking when driving)

• gets into trouble with the law• experiences difficulties in relationships or jobs
Diagnosis is sometimes brought about when family
members call an alcoholic’s difficulties to the attentionof a physician. A clinician may begin to be suspiciouswhen a patient suffers repeated injuries or begins toexperience medical problems related to the use of alco-hol. In fact, some estimates suggest that about 20% of aphysician’s patients will be alcoholics.

logical assessments that try to determine what aspects ofa person’s life may be affected by his or her use of alco-hol. Determining the exact quantity of alcohol that a per-son drinks is of much less importance than determininghow his or her drinking affects relationships, jobs, educa-tional goals, and family life. In fact, because the metabo-lism of alcohol (how the body breaks down and process-es alcohol) is so individual, the quantity of alcohol con-sumed is not part of the criteria list for

con-sumed is not part of the criteria list for diagnosing eitheralcohol dependence or alcohol abuse.

One very simple tool for beginning the diagnosis of
alcoholism is called the CAGE questionnaire. It consistsof four questions, with the first letters of each key wordspelling out the word CAGE:
• Have you ever tried to Cutdown on your drinking?
• Have you ever been Annoyed by anyone’s comments
about your drinking?
• Have you ever felt Guilty about your drinking?• Do you ever need an Eye-opener (a morning drink of
alcohol) to start the day)?
Other, longer lists of questions exist to help deter-

mine the severity and effects of a person’s alcohol use.Given the recent research pointing to a genetic basisfor alcoholism, it is important to ascertain whetheranyone else in the person’s family has ever sufferedfrom alcoholism.
Physical examination may reveal signs suggestive
of alcoholism: evidence of old injuries; a visible networkof enlarged veins just under the skin around the navel(called caput medusae); fluid in the abdomen ( ascites );

yellowish-tone to the skin; decreased testicular size inmen; and poor nutritional status. Lab work may reveal anincrease in the size of the red blood cells; abnormalitiesin the white blood cells (cells responsible for fightinginfection) and platelets (particles responsible for clot-ting); and an increase in certain liver enzymes.
Treatment
Treatment of alcoholism has two parts. The first step
in the treatment of alcoholism, called detoxification ,

involves helping the person stop drinking and ridding hisor her body of the harmful (toxic) effects of alcohol.Because the person’s body has become accustomed toalcohol, the person will need to be supported throughwithdrawal. Withdrawal will be different for differentpatients, depending on the severity of the alcoholism, asmeasured by the quantity of alcohol ingested daily and thelength of time the patient has been an alcoholic. With-drawal symptoms can range from mild to life-threatening.Mild

can range from mild to life-threatening.Mild withdrawal symptoms include nausea, achiness, diar-rhea, difficulty sleeping, sweatiness, anxiety , and trem-

bling. This phase is usually over in about three to fivedays. More severe effects of withdrawal can include hallu-
cinations (in which a patient sees, hears, or feels some-
thing that is not actually real), seizures, an unbearablecraving for more alcohol, confusion, fever , fast heart rate,
high blood pressure, and delirium (a fluctuating level of

consciousness). Patients at highest risk for the most severesymptoms of withdrawal (referred to as delirium tremens)are those with other medical problems, including malnu-
trition , liver disease, or Wernicke’s syndrome. Delirium
GALE ENCYCLOPEDIA OF MEDICINE 2 97Alcoholism
Symptoms Of Co-Alcohol Dependence
Psychological distress manifested in symptoms such as anxiety, aggression, anorexia nervosa, bulimia, depression, insomnia, hyp eractivity, and suicidal tendency

Psychosomatic illness (ailments that have no biological basis and clear up after the co-alcoholism clears up)Family violence or neglectAlcoholism or other drug abuseGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 97

tremens usually begin about three to five days after the
patient’s last drink, progressing from the more mild symp-toms to the more severe, and may last a number of days.
Patients going through only mild withdrawal are sim-

ply monitored carefully to make sure that more severesymptoms do not develop. No medications are necessary,however. Treatment of a patient suffering the more severeeffects of withdrawal may require the use of sedative med-ications to relieve the discomfort of withdrawal and toavoid the potentially life-threatening complications of highblood pressure, fast heart rate, and seizures. Drugs calledbenzodiazapines are helpful in those patients sufferingfrom hallucinations. Because of the patient’s

hallucinations. Because of the patient’s nausea, fluidsmay need to be given through a vein (intravenously), alongwith some necessary sugars and salts. It is crucial that thi-amine be included in the fluids, because thiamine is usuallyquite low in alcoholic patients, and deficiency of thiamineis responsible for the Wernicke-Korsakoff syndrome.

After cessation of drinking has been accomplished,
the next steps involve helping the patient avoid ever tak-ing another drink. This phase of treatment is referred toas rehabilitation . The best programs incorporate the

family into the therapy, because the family has undoubt-edly been severely affected by the patient’s drinking.Some therapists believe that family members, in an effortto deal with their loved one’s drinking problem, some-times develop patterns of behavior that accidentally sup-port or “enable” the patient’s drinking. This situation isreferred to as “co-dependence,” and must be addressed inorder to successfully treat a person’s alcoholism.
Sessions led by peers, where recovering alcoholics

meet regularly and provide support for each other’srecoveries, are considered some of the best methods ofpreventing a return to drinking (relapse). Perhaps themost well-known such group is called AlcoholicsAnonymous, which uses a “12-step” model to help peo-ple avoid drinking. These steps involve recognizing thedestructive power that alcohol has held over the alco-holic’s life, looking to a higher power for help in over-coming the problem, and reflecting on the ways inwhich the use of alcohol

reflecting on the ways inwhich the use of alcohol has hurt others and, if possi-ble, making amends to those people. According to arecent study reported by the American PsychologicalAssociation (APA), anyone, regardless of his or herreligious beliefs or lack of religious beliefs, can benefitfrom participation in 12-step programs such as Alco-holics Anonymous (AA) or Narcotics Anonymous(NA). The number of visits to 12-step self-help groupsexceeds the number of visits to all mental health

the number of visits to all mental health profes-sionals combined.

There are also medications that may help an alco-
holic avoid returning to drinking. These have been usedwith variable success. Disulfiram (Antabuse) is a drug

which, when mixed with alcohol, causes unpleasant reac-tions including nausea, vomiting, diarrhea, and trembling.Naltrexone, along with a similar compound, Nalmefene,can be helpful in limiting the effects of a relapse. Acam-prosate is helpful in preventing relapse. None of thesemedications would be helpful unless the patient was alsowilling to work very hard to change his or her behavior.
Alternative treatments can be a helpful adjunct for the

alcoholic patient, once the medical danger of withdrawalhas passed. Because many alcoholics have very stressfullives (whether because of or leading to the alcoholism issometimes a matter of debate), many of the treatments foralcoholism involve dealing with and relieving stress . These
include massage, meditation , and hypnotherapy . The

malnutrition of long-term alcohol use is addressed by nutri-tion-oriented practitioners with careful attention to ahealthy diet and the use of nutritional supplements such asvitamins A, B complex, and C, as well as certain fatty
acids, amino acids, zinc, magnesium, and selenium. Herbaltreatments include milk thistle( Silybum marianum ), which

is thought to protect the liver against damage. Other herbsare thought to be helpful for the patient suffering throughwithdrawal. Some of these include lavender ( Lavandula
officinalis ), skullcap ( Scutellaria lateriflora ), chamomile
(Matricaria recutita ), peppermint ( Mentha piperita )
yarrow ( Achillea millefolium ), and valerian ( Valeriana
officinalis ). Acupuncture is believed to both decrease

withdrawal symptoms and to help improve a patient’schances for continued recovery from alcoholism.
Prognosis
Recovery from alcoholism is a life-long process. In

fact, people who have suffered from alcoholism are encour-aged to refer to themselves ever after as “a recovering alco-holic,” never a recovered alcoholic. This is because mostresearchers in the field believe that since the potential foralcoholism is still part of the individual’s biological andpsychological makeup, one can never fully recover fromalcoholism. The potential for relapse (returning to illness)is always there, and must be acknowledged and respected.Statistics suggest that, among

and respected.Statistics suggest that, among middle-class alcoholics instable financial and family situations who have undergonetreatment, 60% or more can be successful at an attempt tostop drinking for at least a year, and many for a lifetime.

Prevention must begin at a relatively young age
since the first instance of intoxication (drunkenness) usu-
GALE ENCYCLOPEDIA OF MEDICINE 2 98AlcoholismGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 98

important that teenagers who are at high risk for alco-holism—those with a family history of alcoholism, anearly or frequent use of alcohol, a tendency to drink todrunkenness, alcohol use that interferes with schoolwork, a poor family environment, or a history of domes-tic violence—receive education about alcohol and itslong-term effects. How this is best achieved, without irri-tating the youngsters and thus losing their attention, isthe subject of continuing debate and study.
Resources
BOOKS

Resources
BOOKS
American Psychiatric Association. Diagnostic and Statistical
Manual of Mental Disorders. 4th ed. Washington, D.C.:
American Psychiatric Association, 1994.
National Institute on Alcohol Abuse and Alcoholism. 10th Spe-
cial Report to the U.S. Congress on Alcohol and Health.National Institute of Health, 2000.
Schuckit, Marc A. “Alcohol and Alcoholism.” In Harrison’s
Principles of Internal Medicine. Ed. Anthony S. Fauci, et
al. New York: McGraw-Hill, 1998.

ful regardless of participants’ religious background, studyKEY TERMS
Blood-brain barrier —A network of blood vessels
characterized by closely spaced cells that preventsmany potentially toxic substances from penetrat-ing the blood vessel walls to enter the brain. Alco-hol is able to cross this barrier.
Detoxification —The phase of treatment during

which a patient stops drinking and is monitoredand cared for while he or she experiences with-drawal from alcohol.
Relapse —A return to a disease state, after recovery
appeared to be occurring; in alcoholism, relapserefers to a patient beginning to drink alcohol againafter a period of avoiding alcohol.
Tolerance —A phenomenon during which a drinker

becomes physically accustomed to a particularquantity of alcohol, and requires ever-increasingquantities in order to obtain the same effects.
Withdrawal —Those signs and symptoms experi-
enced by a person who has become physicallydependent on a drug, experienced upon decreas-ing the drug’s dosage or discontinuing its use.suggests.” APA Monitor Online. volume 30, number 11,
December 1999. <http://www.apa.org/monitor/>.

Al-Anon, Alanon Family Group, Inc. P.O. Box 862, Midtown
Station, New York, NY 10018-0862. (800)356-9996.<http://www.recovery.org/aa>.
Alcoholics Anonymous. Grand Central Station, Box 459, New
York, NY 10163. <http://www.alcoholics-anonymous.org/>.

ALD seeAdrenoleukodystrophy
Aldolase test
Aldolase is an enzyme found throughout the body,

particularly in muscles. Like all enzymes, it is needed totrigger specific chemical reactions. Aldolase helps mus-cle turn sugar into energy. Testing for aldolase is done todiagnose and monitor skeletal muscle diseases.
Purpose
Skeletal muscle diseases increase the aldolase level

found in a person’s blood. Skeletal muscles are thosemuscles attached to bones and whose contractions makethose bones move. When the muscles are diseased ordamaged, such as in muscular dystrophy , the cells dete-
riorate and break open. The contents of the cells, includ-ing aldolase, spill into the bloodstream. Measuring theamount of aldolase in the blood indicates the degree ofmuscle damage.
As muscles continue to deteriorate, aldolase levels

decrease and eventually fall below normal. Less musclemeans fewer cells and less aldolase.
Muscle weakness may be caused by neurologic as
well as muscular problems. The measurement of aldolaselevels can help pinpoint the cause. Aldolase levels will benormal where muscle weakness is caused by neurologi-cal disease, such as poliomyelitis or multiple sclerosis ,
but aldolase levels will be elevated in cases of musculardisease, such as muscular dystrophy.

GALE ENCYCLOPEDIA OF MEDICINE 2 99AlcoholismGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 99

KEY TERMS
Aldolase —An enzyme, found primarily in the
muscle, that helps convert sugar into energy.
Neurologic —Having to do with the nervous sys-
tem.
Skeletal muscle —Muscle connected to, and nec-
essary for the movement of, bones.Aldolase is also found in the liver and cardiac mus-
cle of the heart. Damage or disease to these organs, suchas chronic hepatitis or a heart attack , will also increase

aldolase levels in the blood, but to a lesser degree.
Aldolase is measured by mixing a person’s serum
with a substance with which aldolase is known to triggera reaction. The end product of this reaction is measured,and, from that measurement, the amount of aldolase inthe person’s serum is determined.
The test is covered by insurance when medically
necessary. Results are usually available the next day.
To collect the 5-10 ml of blood needed for this test, a

healthcare worker ties a tourniquet on the patient’s upperarm, locates a vein in the inner elbow region, and insertsa needle into that vein. Vacuum action draws the bloodthrough the needle into an attached tube. Collection ofthe sample takes only a few minutes.
The patient should avoid strenuous exercise and
have nothing to eat or drink, except water, for eight to tenhours before this test.
Aftercare

site and the person may feel dizzy or faint. Pressure tothe puncture site until the bleeding stops will reducebruising. Warm packs to the puncture site will relievediscomfort.
Newborns have the highest normal aldolase levels
and adults the lowest. Normal values will vary based onthe laboratory and the method used.
As noted, aldolase is elevated in skeletal muscle dis-

eases, such as muscular dystrophies. Duchenne’s muscu-lar dystrophy, the most common type of muscular dystro-phy, will increase the aldolase level more than any otherdisease.
Nondisease conditions that affect the muscle, such
as injury, gangrene , or an infection, can also increase the
aldolase level. Also, strenuous exercise can temporarilyincrease a person’s aldolase level.Certain medications can increase the aldolase level,

while others can decrease it. To interpret what the resultsof the aldolase test mean, a physician will evaluate theresult, the person’s clinical symptoms, and other teststhat are more specific for muscle damage and disease.
Resources
BOOKS
Garza Diana, and Kathleen Becan-McBride. Phlebotomy

Henry, John B., ed. Clinical Diagnosis and Management by
Laboratory Methods. 19th ed. Philadelphia: W. B. Saun-
Mayo Medical Laboratories. Interpretive Handbook.
Rochester, MN: Mayo Medical Laboratories, 1997.
Aldosterone assay
This test measures the levels of aldosterone, a hor-

mone produced by the outer part (cortex) of the twoadrenal glands, organs which sit one on top of each ofthe kidneys. Aldosterone regulates the amounts of sodi-um and potassium in the blood. This helps maintainwater balance and blood volume, which, in turn, affectsblood pressure.
Purpose
Aldosterone measurement is useful in detecting a
condition called aldosteronism, which is caused byexcess secretion of the hormone from the adrenal glands.

GALE ENCYCLOPEDIA OF MEDICINE 2 100Aldosterone assayGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 100

There are two types of aldosteronism: primary and sec-
ondary. Primary aldosteronism is most commonly causedby an adrenal tumor, as in Conn’s syndrome. Idiopathic(of unknown cause) hyperaldosteronism is another type
of primary aldosteronism. Secondary aldosteronism ismore common and may occur with congestive heart fail-
ure,cirrhosis with fluid in the abdominal cavity
(ascites ), certain kidney diseases, excess potassium,
sodium-depleted diet, and toxemia of pregnancy .

To differentiate primary aldosteronism from sec-
ondary aldosteronism, a plasma renin test should be per-formed at the same time as the aldosterone assay. Renin,an enzyme produced in the kidneys, is high in secondaryaldosteronism and low in primary aldosteronism.
Aldosterone testing can be performed on a blood

sample or on a 24-hour urine specimen. Several factors,including diet, posture (upright or lying down), and timeof day that the sample is obtained can cause aldosteronelevels to fluctuate. Blood samples are affected by short-term fluctuations. A urine specimen collected over anentire 24-hour period lessens the effects of those inter-fering factors and provides a more reliable aldosteronemeasurement.

Fasting is not required for either the blood sample
or urine collection, but the patient should maintain a nor-mal sodium diet (approximately 0.1 oz [3 g] /day) for atleast two weeks before either test. The doctor shoulddecide if drugs that alter sodium, potassium, and fluidbalance (e.g., diuretics , antihypertensives, steroids, oral
contraceptives ) should be withheld. The test will be

more accurate if these are suspended at least two weeksbefore the test. Renin inhibitors (e.g., propranolol)should not be taken one week before the test, unless per-mitted by the physician. The patient should avoid licoricefor at least two weeks before the test, because of itsaldosterone-like effect. Strenuous exercise and stress

can increase aldosterone levels as well. Because the testis usually performed by a method called radioimmunoas-say, recently administered radioactive medications willaffect test results.
Since posture and body position affect aldosterone,

hospitalized patients should remain in an upright position(at least sitting) for two hours before blood is drawn.Occasionally blood will be drawn again before thepatient gets out of bed. Nonhospitalized patients shouldarrive at the laboratory in time to maintain an uprightposition for at least two hours.Risks
Risks for this test are minimal, but may include
slight bleeding from the blood-drawing site, fainting or

feeling lightheaded after venipuncture, or hematoma(blood accumulating under the puncture site).
Normal results are laboratory-specific and also vary
with sodium intake, with time of day, source of specimen(e.g., peripheral vein, adrenal vein, 24-hour urine), age,sex, and posture.
Reference ranges for blood include:
• supine (lying down): 3-10 ng/dL• upright (sitting for at least two hours): Female: 5-
30ng/dL; Male: 6-22 ng/dL
Reference ranges for urine: 2-80 mg/24 hr.

Increased levels of aldosterone are found in Conn’s
disease (aldosterone-producing adrenal tumor), and incases of Bartter’s syndrome (a condition in which thekidneys overexcrete potassium, sodium and chloride,resulting in low blood levels of potassium and high bloodlevels of aldosterone and renin). Among other condi-tions, elevated levels are also seen in secondary aldos-teronism, stress, and malignant hypertension .

Decreased levels of aldosterone are found in aldos-
terone deficiency, steroid therapy, high-sodium diets ,
certain antihypertensive therapies, and Addison’s dis-
ease (an autoimmune disorder).
Resources
BOOKS
GALE ENCYCLOPEDIA OF MEDICINE 2 101Aldosterone assay
KEY TERMS

KEY TERMS
Aldosteronism —A condition in which the adrenal
glands secrete excessive levels of the hormonealdosterone.
Renin —An enzyme produced in the kidneys that
controls the activation of the hormone angiotensin,which stimulates the adrenal glands to producealdosterone.GEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 101

Alemtuzumab
Alemtuzumab is sold as Campath in the United
States. Alemtuzumab is a humanized monoclonal anti-body that selectively binds to CD52, a protein found onthe surface of normal and malignant B and T cells, that isused to reduce the numbers of circulating malignant cellsof patients who have B-cell chronic lymphocyticleukemia (B-CLL).
Purpose
Alemtuzumab is a monoclonal antibody used to treat

B-CLL, one of the most prevalent forms of adult chronicleukemia. It specifically binds CD52, a protein found onthe surface of essentially all B and T cells of the immunesystem. By binding the CD52 protein on the malignant Bcells, the antibody targets it for removal from the circula-tion. Scientists believe that alemtuzumab triggers anti-body-mediated lysis of the B cells, a method that theimmune system uses to eliminate foreign cells.
Alemtuzumab has been approved by the FDA for

treatment of refractory B-CLL. For a patient’s disease tobe classified as refractory, both alkylating agents and flu-darabine treatment must have been tried and failed. Thus,this drug gives patients who have tried all approved treat-ments for B-CLL another option. As most patients withB-CLL are in stage III or IV by the time both alkylatingagents and fludarabine have been tried, the experiencewith alemtuzumab treatment are primarily with thosestages of the disease. In clinical trials, about 30%

of the disease. In clinical trials, about 30% ofpatients had a partial response to the drug, with 2% ofthese being complete responses.

This antibody has been tested with limited success
in the treatment of non-Hodgkin’s lymphoma (NHL) andfor the preparation of patients with various immune cellmalignancies for bone marrow transplantation. There isalso a clinical trial ongoing to test the ability of this anti-body to prevent rejection in kidney transplantation.
Alemtuzumab is produced in the laboratory using

genetically engineered single clones of B-cells. Like allantibodies, it is a Y-shaped molecule can bind one partic-ular substance, the antigen for that monoclonal antibody.For alemtuzumab, the antigen is CD52, a protein foundon the surface of normal and malignant B and T cells aswell as other cells of the immune and male reproductivesystems. Alemtuzumab is a humanized antibody, mean-ing that the regions that bind CD52, located on the tips ofthe Y branches, are derived from rat antibodies, but

Y branches, are derived from rat antibodies, but therest of the antibody is human sequence. The presence ofthe human sequences helps to reduce the immuneresponse by the patient against the antibody itself, aproblem seen when complete mouse antibodies are usedfor cancer therapies. The human sequences also help toensure that the various cell-destroying mechanisms ofthe human immune system are properly triggered withbinding of the antibody.

Alemtuzumab was approved in May of 2001 for the
treatment of refractory B-CLL. It is approved for usealone but clinical trials have tested the ability of the anti-body to be used in combination with the purine analogspentostatin, fludarabine, and cladribine, and rituximab, amonoclonal antibody specific for the CD20 antigen,another protein found on the surface of B cells.
This antibody should be administered in a gradually

escalating pattern at the start of treatment and any timeadministration is interrupted for seven or more days. Therecommended beginning dosage for B-CLL patients is adaily dose of 3 mg of Campath administered as a two-hour IV infusion. Once this amount is tolerated, the doseis increased to 10 mg per day. After tolerating this dose,it can be increased to 30 mg, administered three days aweek. Acetominophen and diphenhydramine hydro-choride are given thirty to sixty minutes before the infu-sion to

thirty to sixty minutes before the infu-sion to help reduce side effects.

Additionally, patients generally receive anti-infec-
tive medication before treatment to help minimize theserious opportunistic infections that can result from thistreatment. Specifically, trimethoprim/sulfamethoxazole(to prevent bacterial infections) and famciclovir (to pre-vent viral infections) were used during the clinical trial todecrease infections, although they were not eliminated.
Blood studies should be done on a weekly basis

while patients are receiving the alemtuzumab treat-ment. Vaccination during the treatment session is notrecommended, given the T cell depletion that occursduring treatment. Furthermore, given that antibodieslike alumtuzumab can pass through the placenta to thedeveloping fetus and in breast milk, use during preg-nancy and breastfeeding is not recommended unlessclearly needed.
A severe side effect of alemtuzumab treatment is the

possible depletion of one or more types of blood cells.
GALE ENCYCLOPEDIA OF MEDICINE 2 102AlemtuzumabGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 102

T cells, as well as on the surface of the abnormal B cells,the treatment eliminates both normal and cancerouscells. The treatment also seems to trigger autoimmunereactions against various other blood cells. This results insevere reduction of the many circulating blood cellsincluding red blood cells (anemia), white blood cells(neutropenia), and clotting cells (thrombopenia). Theseconditions are treated with blood transfusions. The greatmajority of patients treated exhibit some type of bloodcell

A second serious side effect of this drug is the preva-
lence of opportunistic infections that occurs during thetreatment. Serious, and sometimes fatal bacterial, viral,fungal, and protozoan infections have been reported.Treatments to prevent pneumonia and herpes infectionsreduce, but do not eliminate these infections.
The majority of other side effects occur after or dur-

ing the first infusion of the drug. Some common sideeffects of this drug include fever and chills, nausea andvomiting, diarrhea, shortness of breath, skin rash, andunusual fatigue. This drug can also cause low blood pres-sure (hypotension).KEY TERMS
Alkylating agent —A chemical that alters the com-
position of the genetic material of rapidly dividingcells, such as cancer cells, causing selective celldeath; used as a chemotherapeutic agent to treatB-CLL.

Antibody —A protective protein made by the
immune system in response to an antigen, alsocalled an immunoglobulin.
Autoimmune —An immune reaction of a patient
against their own cells.
Humanization —Fusing the constant and variable
framework region of one or more humanimmunoglobulins with the binding region of ananimal immunoglobulin, done to reduce humanreaction against the fusion antibody.
Monoclonal —Genetically engineered antibodies
specific for one antigen.

Tumor lysis syndrome —A side effect of some
immunotherapies, like monoclonal antibodies,that lyse the tumor cells, due to the toxicity offlooding the bloodstream with such a quantity ofcellular contents.In patients with high tumor burden (a large number

of circulating malignant B cells) this drug can cause aside effect called tumor lysis syndrome. Thought to bedue to the release of the lysed cells’ contents into theblood stream, it can cause a misbalance of urea, uricacid, phosphate, potassium, and calcium in the urine andblood. Patients at risk for this side effect must keephydrated and can be given allopurinol before infusion.
There have been no formal drug interaction studies
done for alemtuzumab.
Michelle Johnson, M.S., J.D.

Alendronate seeBone disorder drugs
Alexander technique
The Alexander technique is a somatic method for
improving physical and mental functioning. Excessivetension, which Frederick Alexander, the originator, rec-ognized as both physical and mental, restricts movementand creates pressure in the joints, the spine, the breathingmechanism, and other organs. The goal of the techniqueis to restore freedom and expression to the body andclear thinking to the mind.

improve overall functioning, both mental and physical, itoffers a wide range of benefits. Nikolaas Tinbergen, in his1973 Nobel lecture, hailed the “striking improvements insuch diverse things as high blood pressure, breathing,depth of sleep, overall cheerfulness and mental alertness,resilience against outside pressures, and the refined skillof playing a musical instrument.” He went on to quote alist of other conditions helped by the Alexander tech-nique: “rheumatism, including various forms of

“rheumatism, including various forms of arthritis,then respiratory troubles, and even potentially lethal asth-

ma; following in their wake, circulation defects, which
may lead to high blood pressure and also to some danger-ous heart conditions; gastrointestinal disorders of manytypes, various gynecological conditions, sexual failures,migraines and depressive states.”
Literature in the 1980s and 1990s went on to include
improvements in back pain , chronic pain, postural prob-
GALE ENCYCLOPEDIA OF MEDICINE 2 103Alexander techniqueGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 103

lems, repetitive strain injury, benefits during pregnancy
and childbirth , help in applying physical therapy and
rehabilitative exercises, improvements in strain caused bycomputer use, improvements in the posture and perfor-mance of school children, and improvements in vocal anddramatic performance among the benefits offered by thetechnique.
Origins
Frederick Matthias Alexander was born in 1869 in

Tasmania, Australia. He became an actor and Shake-spearean reciter, and early in his career he began to sufferfrom strain on his vocal chords. He sought medical atten-tion for chronic hoarseness, but after treatment with arecommended prescription and extensive periods of rest,his problem persisted.
Alexander realized that his hoarseness began about

an hour into a dramatic performance and reasoned that itwas something he did in the process of reciting thatcaused him to lose his voice. Returning to his medicaldoctor, Alexander told him of his observation. When thedoctor admitted that he didn’t know what Alexander wasdoing to injure his vocal chords, Alexander decided to tryand find out for himself.
Thus began a decade of self-observation and discov-

ery. Using as many as three mirrors to observe himself inthe act of reciting, normal speaking, and later standing,walking, and sitting, Alexander managed to improve hiscoordination and to overcome his vocal problems. One ofhis most startling discoveries was that in order to changethe way he used his body he had to change the way hewas thinking, redirecting his thoughts in such a way thathe did not produce unnecessary tension when he attempt-ed speech or movement. After making this discovery

speech or movement. After making this discovery atthe end of the nineteenth century, Alexander became apioneer in body-mind medicine.

At first, performers and dancers sought guidance
from Alexander to overcome physical complaints andto improve the expression and spontaneity of theirperformances. Soon a great number of people soughthelp from his teaching for a variety of physical andmental disorders.
The Alexander technique is primarily taught one-

on-one in private lessons. Introductory workshops orworkshops for special applications of the technique(e.g.,workshops for musicians) are also common. Pri-vate lessons range from a half-hour to an hour in length,and are taught in a series. The number of lessons variesaccording to the severity of the student’s difficultieswith coordination or to the extent of the student’s inter-est in pursuing the improvements made possible by con-

tinued study. The cost of lessons ranges from $40-80 perhour. Insurance coverage is not widely available, butdiscounts are available for participants in some comple-mentary care insurance plans. Pre-tax Flexible SpendingAccounts for health care cover Alexander techniquelessons if they are prescribed by a physician.
In lessons teachers guide students through simple

movements (while students are dressed in comfortableclothing) and use their hands to help students identifyand stop destructive patterns of tension. Tensing arisesfrom mental processes as well as physical, so discussionsof personal reactions or behavior are likely to arise in thecourse of a lesson.
The technique helps students move with ease and

improved coordination. At the beginning of a move-ment (the lessons are a series of movements), mostpeople pull back their heads, raise their shoulderstoward their ears, over-arch their lower backs, tightentheir legs, and otherwise produce excessive tension intheir bodies. Alexander referred to this as misuse ofthe body.
At any point in a movement, proper use can be

established. If the neck muscles are not over-tensed, thehead will carry slightly forward of the spine, simplybecause it is heavier in the front. When the head is out ofbalance in the forward direction, it sets off a series ofstretch reflexes in the extensor muscles of the back. It isskillful use of these reflexes, along with reflex activity inthe feet and legs, the arms and hands, the breathingmechanism, and other parts of the body, that lessons inthe technique aim to develop.

body was very hard to maintain, even for the short periodof time it took to complete a single movement. People,especially adults, have very strong tension habits associ-ated with movement. Chronic misuse of the muscles iscommon. It may be caused by slouching in front of tele-visions or video monitors, too much sitting or drivingand too little walking, or by tension associated with pasttraumas and injuries. Stiffening the neck after awhiplash injury or favoring a broken or sprained leg

long after it has healed are examples of habitual tensioncaused by injury.
The first thing a teacher of the Alexander tech-

nique does is to increase a student’s sensory awarenessof this excessive habitual tension, particularly that inthe neck and spine. Next the student is taught to inhibitthe tension. If the student prepares to sit down, forexample, he will tense his muscles in his habitual way.If he is asked to put aside the intention to sit andinstead to free his neck and allow less constriction in

GALE ENCYCLOPEDIA OF MEDICINE 2 104Alexander techniqueGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 104

his muscles, he can begin to change his tense habitual
response to sitting.
By leaving the head resting on the spine in its natur-
al free balance, by keeping eyes open and focused, notheld in a tense stare, by allowing the shoulders to release,the knees to unlock and the back to lengthen and widen,a student greatly reduces strain. In Alexander lessons stu-dents learn to direct themselves this way in activity andbecome skilled in fluid, coordinated movement.

The focus of the Alexander technique is educational.
Teachers use their hands simply to gently guide studentsin movement. Therefore, both contraindications andpotential physiological side effects are kept to a mini-mum. No forceful treatment of soft tissue or bony struc-ture is attempted, so damage to tissues, even in the caseof errors in teaching, is unlikely.
As students’ sensory awareness develops in the

course of Alexander lessons, they become more acutelyaware of chronic tension patterns. As students learn torelease excessive tension in their muscles and to sustainthis release in daily activity, they may experience tight-ness or soreness in the connective tissue. This is causedby the connective tissue adapting to the lengthened andreleased muscles and the expanded range of movementin the joints.
Occasionally students may get light-headed during a

lesson as contracted muscles release and effect the circu-latory or respiratory functioning.
Forceful contraction of muscles and rigid postures
often indicate suppression of emotion. As musclesrelease during or after an Alexander lesson, students mayexperience strong surges of emotion or sudden changesin mood. In some cases, somatic memories surface,bringing to consciousness past injury or trauma. This cancause extreme anxiety , and referrals may be made by the
teacher for counseling.

Alexander became well known among the intellectu-
al, artistic, and medical communities in London, Eng-land, during the first half of the twentieth century.Among Alexander’s supporters were John Dewey,Aldous Huxley, Bernard Shaw, and renowned scientistsRaymond Dart, G.E. Coghill, Charles Sherrington, andNikolaas Tinbergen.
Researchers continue to study the effects and appli-

cations of the technique in the fields of education, pre-KEY TERMS
Direction —Bringing about the free balance of the
head on the spine and the resulting release of theerector muscles of the back and legs which estab-lish improved coordination.
Habit —Referring to the particular set of physical
and mental tensions present in any individual.
Inhibition —Referring to the moment in an Alexan-
der lesson when the student refrains from begin-ning a movement in order to avoid tensing of themuscles.

Sensory awareness —Bringing attention to the sen-
sations of tension and/or release in the muscles.
ventive medicine, and rehabilitation . The Alexander
technique has proven an effective treatment for reducingstress , for improving posture and performance in

schoolchildren, for relieving chronic pain, and forimproving psychological functioning. The technique hasbeen found to be as effective as beta-blocker medica-tions in controlling stress responses in professionalmusicians, to enhance respiratory function in normaladults, and to mediate the effects of scoliosis in adoles-
cents and adults.
Resources
BOOKS
Caplan, Deborah. Back Trouble - A new approach to prevention
and recovery based on the Alexander Technique. Triad
Communications: 1987.

Dimon, Theodore. THE UNDIVIDED SELF: Alexander Tech-
nique and the Control of Stress. North Atlantic Books:
1999.
Jones, Frank Pierce. Freedom To Change - The Development
and Science of the Alexander Technique. Mouritz: 1997,
imported (First published 1976 as Body Awareness in
Action. )
Stern, Judith C. “The Alexander Technique:An Approach to
Pain Control.” Lifeline (Summer 1992).
Tinbergen, Nikolaas. “Ethology and Stress Diseases.” England

Science 185:20-27,(1974).
American Society for the Alexander Technique, 401 East Mar-
ket Street (P.O. Box 835) Charlottesville, V A 22902 USA.(800) 473-0620; or (804) 295-2840. Fax: 804-295-3947.alexandertec@earthlink.net. <http://www.alexandertech.org>.
GALE ENCYCLOPEDIA OF MEDICINE 2 105Alexander techniqueGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 105

Alexander Technique International, 1692 Massachusetts
Ave.,3rd Floor, Cambridge, MA 02138 USA. (888) 321-0856. Fax: 617-497-2615. ati@ati-net.com. <http://www.ati-net.com>.
OTHER
Alexander Technique Resource Guide. (includes list of teach-
ers) AmSAT Books, (800) 473-0620 or (804) 295-2840.
Nielsen, Michael. “A Study of Stress Amongst Professional
Musicians.” STAT Books London, 1994.
Reiser, Samuel. “Stress Reduction and Optimal Psychological

Functioning.” Lecture given at Sixth International Mon-treaus Congress on Stress, 1994.
Alkali-resistant hemoglobin test seeFetal
hemoglobin test
Alkaline phosphatase test
Alkaline phosphatase is an enzyme found through-
out the body. Like all enzymes, it is needed, in smallamounts, to trigger specific chemical reactions. When itis present in large amounts, it may signify bone or liverdisease or a tumor.
Purpose
Medical testing of alkaline phosphatase is concerned

with the enzyme that is found in liver, bone, placenta,and intestine. In a healthy liver, fluid containing alkalinephosphate and other substances is continually drainedaway through the bile duct. In a diseased liver, this bileduct is often blocked, keeping fluid within the liver.Alkaline phosphatase accumulates and eventuallyescapes into the bloodstream.
The alkaline phosphatase of the liver is produced by

the cells lining the small bile ducts (ductoles) in the liver.Its origin differs from that of other enzymes calledaminotransferases. If the liver disease is primarily of anobstructive nature (cholestatic), i.e. involving the biliarydrainage system, the alkaline phosphatase will be thefirst and foremost enzyme elevation. If, on the otherhand, the disease is primarily of the liver cells (hepato-cytes), the aminotransferases will rise prominently.Thus,these enzymes are very useful in

prominently.Thus,these enzymes are very useful in distinguishing the typeof liver disease—cholestatic or hepatocellular.

Growing bones need alkaline phosphatase. Any con-
dition of bone growth will cause alkaline phosphataselevels to rise. The condition may be normal, such as achildhood growth spurt or the healing of a broken bone;or the condition may be a disease, such as bone cancer ,
Paget’s disease, or rickets.
During pregnancy , alkaline phosphatase is made by

the placenta and leaks into the mother’s bloodstream.This is normal. Some tumors, however, start productionof the same kind of alkaline phosphatase produced by theplacenta. These tumors are called germ cell tumors andinclude testicular cancer and certain brain tumors.
Alkaline phosphatase from the intestine is increased
in a person with inflammatory bowel disease, such asulcerative colitis .
Alkaline phosphatase is measured by combining the

person’s serum with specific substances with which alka-line phosphatase is known to react. The end product ofthis reaction is measured; and from that measurement,the amount of alkaline phosphatase in the person’s serumis determined.
Each tissue—liver, bone, placenta, and intestine—

produces a slightly different alkaline phosphatase. Thesevariations are called isoenzymes. In the laboratory, alka-line phosphatase is measured as the total amount or theamount of each of the the four isoenzymes. The isoen-zymes react differently to heat, certain chemicals, andother processes in the laboratory. Methods to measurethem separately are based on these differences.

To collect the 5-10 ml blood needed for this test, a
healthcare worker ties a tourniquet on the person’s upperarm, locates a vein in the inner elbow region, and insertsa needle into that vein. Vacuum action draws the bloodthrough the needle into an attached tube. Collection ofthe sample takes only a few minutes.
A person being tested for alkaline phosphatase

shouldn’t have anything to eat or drink, except water, foreight to ten hours before the test. Some people releasealkaline phosphatase from the intestine into the blood-stream after eating. This will temporarily increase theresult of the test.
Aftercare
Discomfort or bruising may occur at the puncture site
or the person may feel dizzy or faint. Pressure to the

GALE ENCYCLOPEDIA OF MEDICINE 2 106Alkaline phosphatase testGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 106

puncture site until the bleeding stops will reduce bruising.
Warm packs to the puncture site will relieve discomfort.
Normal results vary by age and by sex. They also
vary based on the laboratory and the method used.
Bone and liver disease increase alkaline phosphatase

more than any other disease, up to five times the normallevel. Irritable bowel disease, germ cell tumors, andinfections involving the liver, such as viral hepatitis andinfectious mononucleosis , increase the enzyme also, but
to a lesser degree. Healing bones, pregnancy, and normalgrowth in children also increase levels.
Resources
BOOKS
Garza, Diana, and Kathleen Becan-MacBride. Phlebotomy

Laboratory Methods. 19th ed. Philadephia: W. B. Saun-
Lehmann, Craig A., ed. Saunders Manual of Clinical Labora-
tory Science. Philadelphia: W. B. Saunders Co., 1998.
Sacher, Ronald A., Richard A. McPherson, and J. M. Campos.
“Transfusion Medicine.” In Widmann’s Clinical Interpre-
tation of Laboratory Tests. 10th ed. Philadelphia: F. A.
Davis, 1991.

Alkalosis seeMetabolic alkalosis;
Respiratory alkalosisKEY TERMS
Alkaline phosphatase —An enzyme found
throughout the body, primarily in liver, bone, pla-centa, and intestine.
Cholestatis —Stoppage or suppression of the flow
of bile.
Hepatocellular —Of or pertaining to liver cells.
Hepatocyte —A liver cell.
Isoenzyme —A variation of an enzyme.Allergic alveolitis seeHypersensitivity
pneumonitis

Allergic bronchopulmonary
aspergillosis
Allergic bronchopulmonary aspergillosis , or ABPA,
is one of four major types of infections in humans causedby Aspergillus fungi. ABPA is a hypersensitivity reaction
that occurs in asthma patients who are allergic to this
specific fungus.
ABPA is an allergic reaction to a species of
Aspergillus called Aspergillus fumigatus . It is sometimes

grouped together with other lung disorders characterizedby eosinophilia—an abnormal increase of a certain typeof white blood cell in the blood—under the heading ofeosinophilic pneumonia . These disorders are also called
hypersensitivity lung diseases.
ABPA appears to be increasing in frequency in the
United States, although the reasons for the increase are notclear. The disorder is most likely to occur in adult asthmat-ics aged 20-40. It affects males and females equally.

ABPA develops when the patient breathes air con-
taining Aspergillus spores. These spores are found
worldwide, especially around riverbanks, marshes, bogs,forests, and wherever there is wet or decaying vegetation.They are also found on wet paint, construction materials,and in air conditioning systems. ABPA is a nosocomialinfection, which means that a patient can get it in a hos-pital. When Aspergillus spores reach the bronchi, which

are the branches of the windpipe that lead into the lungs,the bronchi react by contracting spasmodically. So thepatient has difficulty breathing and usually wheezes orcoughs. Many patients with ABPA also run a low-gradefever and lose their appetites.
Complications
Patients with ABPA sometimes cough up large
amounts of blood, a condition that is called hemoptysis .
They may also develop a serious long-term form ofbronchiectasis , the formation of fibrous tissue in the

lungs. Bronchiectasis is a chronic bronchial disorder
GALE ENCYCLOPEDIA OF MEDICINE 2 107Allergic bronchopulmonary aspergillosisGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 107

caused by repeated inflammation of the airway, and
marked by the abnormal enlargement of, or damage to,the bronchial walls. ABPA sometimes occurs as a com-plication of cystic fibrosis .
Diagnosis
The diagnosis of ABPA is based on a combination of

the patient’s history and the results of blood tests, sputumtests, skin tests, and diagnostic imaging. The doctor willbe concerned to distinguish between ABPA and a wors-ening of the patient’s asthma, cystic fibrosis, or otherlung disorders. There are seven major criteria for a diag-nosis of allergic bronchopulmonary aspergillosis:
• a history of asthma.• an accumulation of fluid in the lung that is visible on a
chest x ray .
• bronchiectasis (abnormal stretching, enlarging, or

destruction of the walls of the bronchial tubes).
• skin reaction to Aspergillus antigen.
• eosinophilia in the patient’s blood and sputum.•Aspergillus precipitins in the patient’s blood. Precip-
itins are antibodies that react with the antigen to form asolid that separates from the rest of the solution in thetest tube.
• a high level of IgE in the patient’s blood. IgE refers to a
class of antibodies in blood plasma that activate allergicreactions to foreign particles.

Other criteria that may be used to support the diag-
nosis include the presence of Aspergillus in samples of
the patient’s sputum, the coughing up of plugs of brownmucus, or a late skin reaction to the Aspergillus antigen.
Laboratory tests
The laboratory tests that are done to obtain this
information include a complete blood count (CBC), a
sputum culture , a blood serum test of IgE levels, and
a skin test for the Aspergillus antigen. In the skin test, a

small amount of antigen is injected into the upper layerof skin on the patient’s forearm about four inchesbelow the elbow. If the patient has a high level of IgEantibodies in the tissue, he or she will develop what iscalled a “wheal and flare” reaction in about 15-20 min-utes. A “wheal and flare” reaction is characterized bythe eruption of a reddened, itching spot on the skin.

Some patients with ABPA will develop the so-calledlate reaction to the skin test, in which a red, sore,swollen area develops about six to eight hours after theinitial reaction.
Aspergillus can sometimes be seen under a micro-
scope slide made from the patient’s sputum, but the diag-nosis is considered definite only when the fungus is cul-
tured in the laboratory. Aspergillus is easy to culture, and

can be identified when it is stained with periodic acid-Schiff (PAS), Calcofluor, or potassium hydroxide (KOH)preparations.
Diagnostic imaging
Chest x rays and CT scans are used to check for the
presence of fluid accumulation in the lungs and signs ofbronchiectasis.
Treatment
ABPA is usually treated with prednisone (Meti-
corten) or other corticosteroids taken by mouth, and
with bronchodilators .
Antifungal drugs are notused to treat ABPA because

it is caused by an allergic reaction to Aspergillus rather
than by direct infection of tissue.
Follow-up care
Patients with ABPA should be given periodic
checkups with chest x rays and a spirometer test. Aspirometer is an instrument that evaluates the patient’slung capacity.
Prognosis
Most patients with ABPA respond well to corticos-

teroid treatment. Others have a chronic course with grad-ual improvement over time. The best indicator of a goodprognosis is a long-term fall in the patient’s IgE level.Patients with lung complications from ABPA may devel-op severe airway obstruction.
ABPA is difficult to prevent because Aspergillus is a

common fungus; it can be found in the saliva and sputumof most healthy individuals. Patients with ABPA can pro-tect themselves somewhat by avoiding haystacks, com-post piles, bogs, marshes, and other locations with wet orrotting vegetation; by avoiding construction sites ornewly painted surfaces; and by having their air condi-tioners cleaned regularly. Some patients may be helpedby air filtration systems for their bedrooms or offices.
Resources
BOOKS

Resources
BOOKS
“Aspergillosis.” In Professional Guide to Diseases. 5th ed.
Springhouse, PA: Springhouse Corporation, 1995.
Beavis, Kathleen G. “Systemic Mycoses.” In Current Diagno-
sis.V ol. 9. Ed. Rex B. Conn, et al. Philadelphia: W. B.
Saunders Co., 1997.
GALE ENCYCLOPEDIA OF MEDICINE 2 108Allergic bronchopulmonary aspergillosisGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 108

Hamill, Richard J. “Infectious Diseases: Mycotic.” In Current
Medical Diagnosis and Treatment, 1998. 37th ed. Ed.
Stephen McPhee, et al. Stamford: Appleton & Lange,1997.
Larsen, Gary L., et al. “Respiratory Tract & Mediastinum.” In
Current Pediatric Diagnosis & Treatment , ed. William W.
Hay Jr., et al. Stamford: Appleton & Lange, 1997.

Physicians’ Guide to Rare Diseases. Ed. Jess G. Thoene. Mont-
vale, NJ: Dowden Publishing Co., Inc., 1995.
“Pulmonary Disorders: Hypersensitivity Diseases of the
Lungs.” In The Merck Manual of Diagnosis and Therapy.
17th ed. Ed. Robert Berkow. Rahway, NJ: MerckResearch Laboratories, 1997.
Stauffer, John L. “Lung.” In Current Medical Diagnosis and
Treatment, 1998. 37th ed. Ed. Stephen McPhee, et al.
Stamford: Appleton & Lange, 1997.

Centers for Disease Control and Prevention. 1600 Clifton Rd.,
NE, Atlanta, GA 30333. (800) 311-3435, (404) 639-3311.<http://www.cdc.gov>.
National Organization for Rare Disorders. P.O. Box 8923, New
Fairfield, CT 06812-8923. (800) 999-6673. <http://www.rarediseases.org>.KEY TERMS
Antifungal —A medicine used to treat infections
caused by a fungus.
Antigen —A substance that stimulates the produc-
tion of antibodies.

Bronchiectasis —A disorder of the bronchial tubes
marked by abnormal stretching, enlargement, ordestruction of the walls. Bronchiectasis is usuallycaused by recurrent inflammation of the airway andis a diagnostic criterion of ABPA.
Bronchodilator —A medicine used to open up the
bronchial tubes (air passages) of the lungs.
Eosinophil —A type of white blood cell containing
granules that can be stained by eosin (a chemicalthat produces a red stain).

Eosinophilia —An abnormal increase in the number
of eosinophils in the blood.
Hemoptysis —The coughing up of large amounts of
blood. Hemoptysis can occur as a complication ofABPA.
Hypersensitivity —An excessive response by the
body to a foreign substance.Immunoglobulin E (IgE) —A type of protein in blood
plasma that acts as an antibody to activate allergicreactions. About 50% of patients with allergic disor-ders have increased IgE levels in their blood serum.

Nosocomial infection —An infection that can be
acquired in a hospital. ABPA is a nosocomial infec-tion.
Precipitin —An antibody in blood that combines
with an antigen to form a solid that separates fromthe rest of the blood.
Spirometer —An instrument used to test a patient’s
lung capacity.
“Wheal and flare” reaction —A rapid response to a
skin allergy test characterized by the developmentof a red, itching spot in the area where the allergenwas injected.

Wheezing —A whistling or musical sound caused
by tightening of the air passages inside the patient’schest.
National Institute of Allergy and Infectious Disease. Building
31, Room 7A-50, 31 Center Drive MSC 2520, Bethesda,MD 20892-2520. (301) 496-5717. <http://www.niaid.nih.gov/default.htm>.
Allergic purpura
Allergic purpura (AP) is an allergic reaction of

unknown origin causing red patches on the skin and othersymptoms. AP is also called Henoch-Schonlein purpura,named after the two doctors who first described it.
“Purpura” is a bleeding disorder that occurs when
capillaries rupture, allowing small amounts of blood toaccumulate in the surrounding tissues. In AP, this occursbecause the capillaries are blocked by protein complexes

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KEY TERMS
Glomeruli —Knots of capillaries in the kidneys
responsible for filtering the blood (singular,glomerulus).formed during an abnormal immune reaction. The skin is
the most obvious site of reaction, but the joints, gastroin-testinal tract, and kidneys are also often affected.
AP affects approximately 35,000 people in the Unit-
ed States each year. Most cases are children between theages of two and seven. Boys are affected more often thangirls, and most cases occur from late fall to winter.

Causes
AP is caused by a reaction involving antibodies, spe-
cial proteins of the immune system. Antibodies aredesigned to bind with foreign proteins, called antigens.In some situations, antigen-antibody complexes canbecome too large to remain suspended in the blood-stream. When this occurs, they precipitate out andbecome lodged in the capillaries. This can cause the cap-illary to burst, allowing a local hemorrhage.
The source of the antigen causing AP is unknown.

Antigens may be introduced by bacterial or viral infec-tion. More than 75% of patients report having had aninfection of the throat, upper respiratory tract, or gas-trointestinal system several weeks before the onset of AP.Other complex molecules can act as antigens as well,including drugs such as antibiotics or vaccines. Other-

wise harmless substances that stimulate an immune reac-tion are known as allergens. Drug allergens that maycause AP include penicillin, ampicillin, erythromycin,and quinine. Vaccines possibly linked to AP includethose for typhoid, measles ,cholera , and yellow fever .
Symptoms
The onset of AP may be preceded by a headache ,
fever , and loss of appetite. Most patients first develop an

itchy skin rash. The rash is red, either flat or raised, andmay be small and freckle-like. The rash may also be larg-er, resembling a bruise. Rashes become purple and then
rust colored over the course of a day, and fade after sev-eral weeks. Rashes are most common on the buttocks,abdomen, and lower extremities. Rashes higher on thebody may also occur, especially in younger children.
Joint pain and swelling is common, especially in

the knees and ankles. Abdominal pain occurs in almostall patients, along with blood in the body waste (feces).About half of all patients show blood in the urine, lowurine volume, or other signs of kidney involvement.Kidney failure may occur due to widespread obstructionof the capillaries in the filtering structures calledglomeruli. Kidney failure develops in about 5% of allpatients, and in 15% of those with elevated blood or pro-tein in the urine.Less common symptoms include prolonged head-

ache, fever, and pain and swelling of the scrotum. Involve-ment of other organ systems may lead to heart attack
(myocardial infarction), inflammation of the pancreas(pancreatitis ), intestinal obstruction, or bowel perforation.
Diagnosis
Diagnosis of AP is based on the symptoms and their
development, a careful medical history, and blood andurine tests. X rays or computed tomography scans (CT)
may be performed to assess complications in the bowelor other internal organs.
Treatment

Treatment
Most cases of AP resolve completely without treat-
ment. Nonetheless, a hospital stay is required because ofthe possibility of serious complications. Non-aspirin painrelievers may be given for joint pain. Corticosteroids (like
prednisone) are sometimes used, although not all special-ists agree on their utility. Kidney involvement requiresmonitoring and correction of blood fluids and electrolytes.
Patients with severe kidney complications may

require a kidney biopsy so that tissue can be analyzed.
Even after all other symptoms subside, elevated levels ofblood or protein in the urine may persist for months andrequire regular monitoring. Hypertension or kidney fail-
ure may develop months or even years after the acutephase of the disease. Kidney failure requires dialysis ortransplantation.
Plasmapheresis , which removes antibodies from
the blood, has been tried for AP with mixed results.

Prognosis
Most people who develop AP become better on their
own after several weeks. About half of all patients haveat least one recurrence. Cases that do not have kidneycomplications usually have the best prognosis.
Resources
Andreoli, S. P. “Chronic Glomerulonephritis in Childhood.
Membranoproliferative Glomerulonephritis, Henoch-
GALE ENCYCLOPEDIA OF MEDICINE 2 110Allergic purpuraGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 110

Schonlein PurpuraNnephritis, and IgA Nephropathy.”
Pediatric Clinics of North America 42, no. 6 (Dec. 1995):
1487-1503.
OTHER
“Henoch-Schonlein Purpura.” Vanderbilt University Medical
Center. <http://www.mc.vanderbilt.edu/peds/pidl/nephro/henoch.html>.
Allergic rhinitis
Allergic rhinitis , more commonly referred to as hay
fever , is an inflammation of the nasal passages caused by
allergic reaction to airborne substances.

Allergic rhinitis (AR) is the most common allergic
condition and one of the most common of all minorafflictions. It affects between 10-20% of all people inthe United States, and is responsible for 2.5% of all doc-tor visits. Antihistamines and other drugs used to treat
allergic rhinitis make up a significant fraction of bothprescription and over-the-counter drug sales each year.
There are two types of allergic rhinitis: seasonal and

perennial. Seasonal AR occurs in the spring, summer,and early fall, when airborne plant pollens are at theirhighest levels. In fact, the term hay fever is really a mis-nomer, since allergy to grass pollen is only one cause ofsymptoms for most people. Perennial AR occurs all yearand is usually caused by home or workplace airbornepollutants. A person can be affected by one or both types.Symptoms of seasonal AR are worst after being out-doors, while symptoms of perennial AR are worst afterspending

Both types of allergies can develop at any age,
although onset in childhood through early adulthood ismost common. Although allergy to a particular substanceis not inherited, increased allergic sensitivity may “run inthe family.” While allergies can improve on their ownover time, they can also become worse over time.
Causes
Allergic rhinitis is a type of immune reaction. Nor-

mally, the immune system responds to foreign microor-ganisms, or particles, like pollen or dust, by producingspecific proteins, called antibodies, that are capable ofbinding to identifying molecules, or antigens, on the for-eign particle. This reaction between antibody and antigensets off a series of reactions designed to protect the bodyfrom infection. Sometimes, this same series of reactionsis triggered by harmless, everyday substances. This is thecondition known as allergy, and the offending

thecondition known as allergy, and the offending substanceis called an allergen.

set of cells in the immune system known as mast cells.Mast cells, found in the lining of the nasal passagesand eyelids, display a special type of antibody, calledimmunoglobulin type E (IgE), on their surface. Inside,mast cells store reactive chemicals in small packets,called granules. When the antibodies encounter aller-gens, they trigger release of the granules, which spillout their chemicals onto neighboring cells, includingblood vessels and nerve cells. One of these chemicals,histamine,

nerve cells. One of these chemicals,histamine, binds to the surfaces of these other cells,through special proteins called histamine receptors.Interaction of histamine with receptors on blood ves-sels causes neighboring cells to become leaky, leadingto the fluid collection, swelling, and increased rednesscharacteristic of a runny nose and red, irritated eyes.Histamine also stimulates pain receptors, causing the

itchy, scratchy nose, eyes, and throat common in aller-gic rhinitis.
The number of possible airborne allergens is enor-

mous. Seasonal AR is most commonly caused by grassand tree pollens, since their pollen is produced in largeamounts and is dispersed by the wind. Showy flowers,like roses or lilacs, that attract insects produce a stickypollen which is less likely to become airborne. Differentplants release their pollen at different times of the year,so seasonal AR sufferers may be most affected in spring,summer, or fall, depending on which plants provoke aresponse. The amount of pollen in the air is reflected

The amount of pollen in the air is reflected inthe pollen count, often broadcast on the daily news dur-ing allergy season. Pollen counts tend to be lower after agood rain that washes the pollen out of the air and higheron warm, dry, windy days.

Virtually any type of tree or grass may cause AR. A
few types of weeds that tend to cause the most trouble forpeople include the following:
• ragweed• sagebrush
• lamb’s-quarters
• plantain• pigweed• dock/sorrel
GALE ENCYCLOPEDIA OF MEDICINE 2 111Allergic rhinitisGEM - 0001 to 0432 - A  10/22/03 1:41 PM  Page 111

• tumbleweed
Perennial AR is often triggered by house dust, a
complicated mixture of airborne particles, many ofwhich are potent allergens. House dust contains some orall of the following:
• house mite body parts. All houses contain large num-
bers of microscopic insects called house mites. Theseharmless insects feed on fibers, fur, and skin shed bythe house’s larger occupants. Their tiny body parts easi-ly become airborne.
• animal dander. Animals constantly shed fur, skin flakes,

and dried saliva. Carried in the air, or transferred frompet to owner by direct contact, dander can cause allergyin many sensitive people.
• mold spores. Molds live in damp spots throughout the
house, including basements, bathrooms, air ducts, airconditioners, refrigerator drains, damp windowsills,mattresses, and stuffed furniture. Mildew and othermolds release airborne spores which circulate through-
out the house.
Other potential causes of perennial allergic rhinitis
include the following:

• cigarette smoke
• perfume
• cosmetics• cleansers• copier chemicals• industrial chemicals
• construction material gases
Symptoms
Inflammation of the nose, or rhinitis, is the major
symptom of AR. Inflammation causes itching , sneezing,

runny nose, redness, and tenderness. Sinus swelling canconstrict the eustachian tube that connects the inner earto the throat, causing a congested feeling and “ear pop-ping.” The drip of mucus from the sinuses down the backof the throat, combined with increased sensitivity, canalso lead to throat irritation and redness. AR usually alsocauses redness, itching, and watery eyes. Fatigue and
headache are also common.
Diagnosis
Diagnosing seasonal AR is usually easy and can

often be done without a medical specialist. When symp-toms appear in spring or summer and disappear with theonset of cold weather, seasonal AR is almost certainlythe culprit. Other causes of rhinitis, including infection,can usually be ruled out by a physical examination and
a nasal smear, in which a sample of mucus is taken on aswab for examination.
Allergy tests , including skin testing and provoca-

tion testing, can help identify the precise culprit, butmay not be done unless a single source is suspected andsubsequent avoidance is possible. Skin testing involvesplacing a small amount of liquid containing a specificallergen on the skin and then either poking, scratching,or injecting it into the skin surface to observe whetherredness and swelling occurs. Provocation testinginvolves challenging an individual with either a smallamount of an inhalable or ingestable allergen to see if aresponse

Perennial AR can also usually be diagnosed by care-
ful questioning about the timing of exposure and theonset of symptoms. Specific allergens can be identifiedthrough allergy skin testing.
GALE ENCYCLOPEDIA OF MEDICINE 2 112Allergic rhinitis
This illustration depicts excessive mucus production in the
nose after inhalation of airborne pollen. (Photo Researchers,
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Treatment
Avoidance of the allergens is the best treatment, but
this is often not possible. When it is not possible to avoidone or more allergens, there are two major forms of med-ical treatment, drugs and immunotherapy.
Drugs
ANTIHISTAMINES. Antihistamines block the hista-

mine receptors on nasal tissue, decreasing the effect ofhistamine release by mast cells. They may be used aftersymptoms appear, though they may be even more effec-tive when used preventively, before symptoms appear. Awide variety of antihistamines are available.
Older antihistamines often produce drowsiness as a
major side effect. Such antihistamines include the fol-lowing:

• diphenhydramine (Benadryl and generics)• chlorpheniramine (Chlor-trimeton and generics)
• brompheniramine (Dimetane and generics)
• clemastine (Tavist and generics).
Newer antihistamines that do not cause drowsiness
are available by prescription and include the following:
• astemizole (Hismanal)
• loratidine (Claritin)
• fexofenadine (Allegra)• azelastin HCl (Astelin).
Hismanal has the potential to cause serious heart
arrhythmias when taken with the antibiotic ery-

thromycin, the antifungal drugs ketoconazole and itra-conazole, or the antimalarial drug quinine. Taking morethan the recommended dose of Hismanal can also causearrhythimas. Seldane (terfenadine), the original non-drowsy antihistamine, was voluntarily withdrawn fromthe market by its manufacturers in early 1998 because ofthis potential and because of the availability of an equal-ly effective, safer alternative drug, fexofenadine.

vessels to counteract the effects of histamine. Nasal spraysare available that can be applied directly to the nasal liningand oral systemic preparations are available. Decongestantsare stimulants and may cause increased heart rate and bloodpressure, headaches, and agitation. Use of topical deconges-tants for longer than several days can cause loss of effective-ness and rebound congestion, in which nasal passagesbecome more severely swollen than before treatment.

TOPICAL CORTICOSTEROIDS. Topical corticos-
teroids reduce mucous membrane inflammation and are
available by prescription. Allergies tend to become worseas the season progresses because the immune system

becomes sensitized to particular antigens and can pro-duce a faster, stronger response. Topical corticosteroidsare especially effective at reducing this seasonal sensiti-zation because they work more slowly and last longerthan most other medication types. As a result, they arebest started before allergy season begins. Side effects areusually mild, but may include headaches, nosebleeds,and unpleasant taste sensations.
MAST CELL STABILIZERS. Cromolyn sodium prevents

the release of mast cell granules, thereby preventingrelease of histamine and the other chemicals contained inthem. It acts as a preventive treatment if it is begun sever-al weeks before the onset of the allergy season. It can beused for perennial AR as well.
Immunotherapy
Immunotherapy, also known as desensitization or

allergy shots, alters the balance of antibody types in thebody, thereby reducing the ability of IgE to cause allergicreactions. Immunotherapy is preceded by allergy testingto determine the precise allergens responsible. Injectionsinvolve very small but gradually increasing amounts ofallergen, over several weeks or months, with periodicboosters. Full benefits may take up to several years toachieve and are not seen at all in about one in fivepatients. Individuals receiving all shots will be

Individuals receiving all shots will be monitoredclosely following each shot because of the small risk ofanaphylaxis , a condition that can result in difficulty

breathing and a sharp drop in blood pressure.
Alternative treatments for AR often focus on modu-
lation of the body’s immune response, and frequentlycenter around diet and lifestyle adjustments. Chineseherbal medicine can help rebalance a person’s system, ascan both acute and constitutional homeopathic treatment.Vitamin C in substantial amounts can help stabilize themucous membrane response. For symptom relief, west-ern herbal remedies including eyebright ( Euphrasia

officinalis ) and nettle ( Urtica dioica ) may be helpful.
Bee pollen may also be effective in alleviating or elimi-nating AR symptoms.
Prognosis
Most people with AR can achieve adequate relief
with a combination of preventive strategies and treat-ment. While allergies may improve over time, they mayalso get worse or expand to include new allergens. Earlytreatment can help prevent an increased sensitization toother allergens.

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Reducing exposure to pollen may improve symp-
toms of seasonal AR. Strategies include the following:
• stay indoors with windows closed during the morning
hours, when pollen levels are highest
• keep car windows up while driving• use a surgical face mask when outside
• avoid uncut fields
• learn which trees are producing pollen in which sea-
sons, and avoid forests at the height of pollen season

• wash clothes and hair after being outside• clean air conditioner filters in the home regularly• use electrostatic filters for central air conditioning
Moving to a region with lower pollen levels is rarely
effective, since new allergies often develop
Preventing perennial AR requires identification of
the responsible allergens
Mold spores:KEY TERMS
Allergen —A substance that provokes an allergic
response.
Anaphylaxis —Increased sensitivity caused by pre-

vious exposure to an allergen that can result inblood vessel dilation (swelling) and smooth mus-cle contraction. Anaphylaxis can result in sharpblood pressure drops and difficulty breathing.
Antigen —A foreign protein to which the body
reacts by making antibodies.
Granules —Small packets of reactive chemicals

stored within cells.
Histamine —A chemical released by mast cells
that activates pain receptors and causes cells tobecome leaky.
Mast cells —A type of immune system cell that is

found in the lining of the nasal passages and eye-lids, displays a type of antibody called immuno-globulin type E (IgE) on its cell surface, and partici-pates in the allergic response by releasing hista-mine from intracellular granules.• keep the house dry through ventilation and use of dehu-
midifiers
• use a disinfectant such as dilute bleach to clean surfaces
such as bathroom floors and walls

• have ducts cleaned and disinfected• clean and disinfect air conditioners and coolers• throw out moldy or mildewed books, shoes, pillows, or
furniture
House dust:
• vacuum frequently, and change the bag regularly. Use a
bag with small pores to catch extra-fine particles
• clean floors and walls with a damp mop
• install electrostatic filters in heating and cooling ducts,
and change all filters regularly
Animal dander:

• avoid contact if possible• wash hands after contact• vacuum frequently• keep pets out of the bedroom, and off furniture, rugs,
and other dander-catching surfaces
• have your pets bathed and groomed frequently
Resources
BOOKS
Allergic and Non-Allergic Rhinitis: Clinical Aspects. Ed. N.
Mygund and R. M. Naclerio. Philadelphia: W. B. Saun-ders Co., 1993.
Lawlor, G. J. Jr., T. J. Fischer, and D. C. Adelman. Manual of

Allergy and Immunology. Boston: Little, Brown and Co.,
1995.
Novick, N. L. You Can Do Something About Your Allergies.
New York: Macmillan, 1994.
Weil, A. Natural Health, Natural Medicine: A Comprehensive
Manual for Wellness and Self-Care. New York: Houghton
Mifflin, 1995.
Allergies
Allergies are abnormal reactions of the immune sys-
tem that occur in response to otherwise harmless sub-stances.

GALE ENCYCLOPEDIA OF MEDICINE 2 114AllergiesGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 114

Allergies are among the most common of medical
disorders. It is estimated that 60 million Americans, ormore than one in every five people, suffer from someform of allergy, with similar proportions throughoutmuch of the rest of the world. Allergy is the single largestreason for school absence and is a major source of lostproductivity in the workplace.
An allergy is a type of immune reaction. Normally,

the immune system responds to foreign microorganismsor particles by producing specific proteins called anti-bodies. These antibodies are capable of binding to iden-tifying molecules, or antigens, on the foreign particle.This reaction between antibody and antigen sets off aseries of chemical reactions designed to protect thebody from infection. Sometimes, this same series ofreactions is triggered by harmless, everyday substancessuch as pollen, dust, and animal danders. When thisoccurs, an

dust, and animal danders. When thisoccurs, an allergy develops against the offending sub-stance (an allergen.)

Mast cells, one of the major players in allergic reac-
tions, capture and display a particular type of antibody,called immunoglobulin type E (IgE) that binds to aller-gens. Inside mast cells are small chemical-filled packetscalled granules. Granules contain a variety of potentchemicals, including histamine.
Immunologists separate allergic reactions into two

main types: immediate hypersensitivity reactions, whichare predominantly mast cell-mediated and occur withinminutes of contact with allergen; and delayed hypersen-sitivity reactions, mediated by T cells (a type of whiteblood cells) and occurring hours to days after exposure.
Inhaled or ingested allergens usually cause immedi-

ate hypersensitivity reactions. Allergens bind to IgE anti-bodies on the surface of mast cells, which spill the con-tents of their granules out onto neighboring cells, includ-ing blood vessels and nerve cells. Histamine binds to thesurfaces of these other cells through special proteinscalled histamine receptors. Interaction of histamine withreceptors on blood vessels causes increased leakiness,leading to the fluid collection, swelling and increasedredness. Histamine also stimulates pain

increasedredness. Histamine also stimulates pain receptors, mak-

ing tissue more sensitive and irritable. Symptoms lastfrom one to several hours following contact.
In the upper airways and eyes, immediate hypersen-
sitivity reactions cause the runny nose and itchy, blood-shot eyes typical of allergic rhinitis . In the gastrointesti-
nal tract, these reactions lead to swelling and irritation ofthe intestinal lining, which causes the cramping anddiarrhea typical of food allergy. Allergens that enter thecirculation may cause hives , angioedema, anaphylaxis ,

or atopic dermatitis .
Allergens on the skin usually cause delayed hyper-
sensitivity reaction. Roving T cells contact the allergen,setting in motion a more prolonged immune response.This type of allergic response may develop over severaldays following contact with the allergen, and symptomsmay persist for a week or more.
Allergens enter the body through four main routes:
the airways, the skin, the gastrointestinal tract, and thecirculatory system.

• Airborne allergens cause the sneezing, runny nose,
and itchy, bloodshot eyes of hay fever (allergic rhini-
tis). Airborne allergens can also affect the lining of the
lungs, causing asthma , or the conjunctiva of the eyes,
causing conjunctivitis (pink eye). Exposure to cock-
roach allergans have been associated with the devel-opment of asthma. Airborne allergans from householdpets are another common source of environmentalexposure.
• Allergens in food can cause itching and swelling of the

lips and throat, cramps, and diarrhea. When absorbedinto the bloodstream, they may cause hives (urticaria)or more severe reactions involving recurrent, non-inflammatory swelling of the skin, mucous membranes,organs, and brain (angioedema). Some food allergensmay cause anaphylaxis,a potentially life-threateningcondition marked by tissue swelling, airwayconstric-tion, and drop in blood pressure. Allergies to foods suchcow’s milk, eggs, nuts, fish, and legumes (peanuts andsoybeans) are common.

and legumes (peanuts andsoybeans) are common. Allergies to fruits and vegeta-bles may also occur.

• In contact with the skin, allergens can cause redden-
ing, itching, and blistering, called contact dermatitis .
Skin reactions can also occur from allergens intro-duced through the airways or gastrointestinal tract.This type of reaction is known as atopic dermatitis .
Dermatitis may arise from an allergic response (suchas from poison ivy), or exposure to an irritant causingnonimmune damage to skin cells (such as soap, cold,and chemical agents).

• Injection of allergens, from insect bites and stings or
drug administration, can introduce allergens directlyinto the circulation, where they may cause system-wideresponses (including anaphylaxis), as well as the localones of swelling and irritation at the injection site.
People with allergies are not equally sensitive to
all allergens. Some may have severe allergic rhinitisbut no food allergies, for instance, or be extremely sen-

GALE ENCYCLOPEDIA OF MEDICINE 2 115AllergiesGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 115

sitive to nuts but not to any other food. Allergies may
get worse over time. For example, childhood ragweedallergy may progress to year-round dust and pollenallergy. On the other hand, a person may lose allergicsensitivity. Infant or childhood atopic dermatitis disap-pears in almost all people. More commonly, whatseems to be loss of sensitivity is instead a reducedexposure to allergens or an increased tolerance for thesame level of symptoms.
While allergy to specific allergens is not inherited,

the likelihood of developing some type of allergy seemsto be, at least for many people. If neither parent hasallergies, the chances of a child developing allergy isapproximately 10-20%; if one parent has allergies, it is30-50%; and if both have allergies, it is 40-75%.Onesource of this genetic predisposition is in the ability toproduce higher levels of IgE in response to allergens.Those who produce more IgE will develop a strongerallergic sensitivity.
COMMON ALLERGENS. The most common airborne

allergens are the following:
• plant pollens
• animal fur and dander
• body parts from house mites (microscopic creatures
found in all houses)
• house dust• mold spores• cigarette smoke• solvents• cleaners
Common food allergens include the following:
• nuts, especially peanuts, walnuts, and brazil nuts
• fish, mollusks, and shellfish• eggs• wheat• milk• food additives and preservatives
The following types of drugs commonly cause aller-
gic reactions:

• penicillin or other antibiotics
• flu vaccines
• tetanus toxoid vaccine• gamma globulin
Common causes of contact dermatitis include the
following:• poison ivy, oak, and sumac
• nickel or nickel alloys• latex
Insects and other arthropods whose bites or stings
typically cause allergy include the following:
• bees, wasps, and hornets• mosquitoes• fleas• scabies
Symptoms depend on the specific type of allergic

reaction. Allergic rhinitis is characterized by an itchy,runny nose, often with a scratchy or irritated throat dueto post-nasal drip. Inflammation of the thin membranecovering the eye (allergic conjunctivitis) causes redness,irritation, and increased tearing in the eyes. Asthma caus-es wheezing , coughing, and shortness of breath . Symp-

toms of food allergies depend on the tissues most sensi-tive to the allergen and whether the allergen spread sys-temically by the circulatory system. Gastrointestinalsymptoms may include swelling and tingling in the lips,tongue, palate or throat; nausea; cramping; diarrhea; andgas. Contact dermatitis is marked by reddened, itchy,weepy skin blisters, and an eczema that is slow to heal. Itsometimes has a characteritic man-made pattern, such asa glove allergy with clear demarkation on the

asa glove allergy with clear demarkation on the hands,wrist, and arms where the gloves are worn, or on the ear-lobes by wearing earrings.

any type of allergen, but are more common followingingestion or injection of an allergen. Skin reactionsinclude the raised, reddened, and itchy patches calledhives that characteristically blanch with pressure andresolve within twenty-four hours. A deeper and moreextensive skin reaction, involving more extensive fluidcollection and pain, is called angioedema. This usuallyoccurs on the extremities, fingers, toes, and parts of thehead,neck,and face. Anaphylaxis is marked by airwayconstriction,

Anaphylaxis is marked by airwayconstriction, blood pressure drop, widespread tissueswelling, heart rhythm abnormalities, and in some cases,loss of consciousness. Other syptoms may include, dizzi-

ness, weakness, seizures, coughing,flushing, or cramp-
ing. The symptoms may begin within five minutes afterexposure to the allergan up to one hour or more later.Mast cells in the tissues and basophils in the bloodrelease mediators that give rise to the clinical symptomsof this IgE-mediated hypersensitivity reaction. Common-ly, this is associated with allergies to medications, foods,and insect venoms. In some individuals, anaphylaxis canoccur with exercise , plasma exchange, hemodialysis,

reaction to insulin, radocontrast media used in certain
GALE ENCYCLOPEDIA OF MEDICINE 2 116AllergiesGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 116

types of medical tests. and rarely during the administra-
tion of local anesthetics.
Diagnosis
Allergies can often be diagnosed by a careful med-
ical history, matching the onset of symptoms to theexposure to possible allergens. Allergy is suspected ifthe symptoms presented are characteristic of an allergicreaction and this occurs repeatedly upon exposure tothe suspected allergan. Allergy tests can be used to

identify potential allergens, but these must be supportedby eveidence of allergic responses in the patient’s clini-cal history.
Skin tests
Skin tests are performed by administering a tiny

dose of the suspected allergen by pricking, scratching,puncturing or injecting the skin. The allergen is appliedto the skin as an auqeous extract, usually on the back,forearms, or top of the thighs. Once in the skin, the aller-gen may produce a classic immune wheal and flareresponse (a skin lesion with a raise, white, compressiblearea surrounded by a red flare). The tests usually beginwith prick tests or patch tests that expose the skin to

small amounts of allergen to observe the response. Apositive reaction will occur on the skin even if the aller-gen is at levels normally encountered in food or in theairways. Reactions are usually evaluated approximatelyfifteen minutes after exposure. Intradermal skin testsinvolved injection of the allergan into the dermis of theskin. These tests are more sensitive and are used forallergies associated with risk of death , such as allergies
to antibiotics.
Allergen-Specific IgE Measurement

Tests that measure allergen-specific IgE antibodies

generally follow a basic method. The allergen is boundto a solid support, either in the form of a cellulosesponge, microtiter plate, or paper disk. The patient’sserum is prepared from a blood sample and is incubatedwith the solid phase. If allergen specific IgE antibodiesare present, they will bind to the solid phase and beretained there when the rest of the serum is washedaway. Next, an labeled antibody against the IgE is addedand will bind to any IgE on the solid phase. The excessis washed

any IgE on the solid phase. The excessis washed away and the levels of IgE are determined.The commonly used RAST test (radio allergo sorbent

GALE ENCYCLOPEDIA OF MEDICINE 2 117Allergies
Allergic rhinitis is commonly triggered by
exposure to household dust, animal fur,or pollen. The foreign substance thattriggers an allergic reaction is calledan allergen.
The presence of an allergen causes the
body's lymphocytes to begin producingIgE antibodies. The lymphocytes of an allergy sufferer produce an unusuallylarge amount of IgE.
IgE molecules attach to mast
cells, which contain histamine.HistaminePollen grains
Lymphocyte
FIRST EXPOSURE

IgE
The allergic response. (Illustration by Hans & Cassady.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 117

test) employed radio-labeled Anti-IgE antibodies.
Updated methods now incorporate the use of enyzme-labeled antibodies in ELISA assays (enzyme-linkedimmunosorbent assays).
Total Serum IgE
The total level of IgE in the serum is commonly

measured with a two-site immunometric assay. Someresearch indicates that there is a higher level of totalserum IgE in allergic as compared to non-allergic peo-ple. However, this may not always be the case as there isconsiderable overlap between the two groups.This test isuseful for the diagnosis of allergic fungal sinusitis and
bronchopulmonary aspergillosis . Other conditions that

are not allergic in nature may give rise to higher IgE lev-els such as smoking ,AIDS , infection with parasites,
and IgE myeloma.
Provocation tests
These tests involve the administration of allergen to

ellicit an immune response. Provocation tests, most com-monly done with airborne allergens, present the allergendirectly through the route normally involved. Delayedallergic contact dermatitis diagnosis involves similarmethods by application of a skin patch with allergen toinduce an allergic skin reaction. Food allergen provoca-tion tests require abstinence from the suspect allergen fortwo weeks or more, followed by ingestion of a measuredamount of the test substance administered as an

of the test substance administered as an opaquecapsule along with a placebo control. Provocation testsare not used if anaphylaxis is is a concern due to thepatient’s medical history.

Future diagnostic methods
As of 2000, attempts have been made for direct

measurement of immune mediators such as histamine,eosinophil cationic protein (ECP), and mast celltryptase. Another, somewhat controversial,test is elec-trodermal testing or electro-acupuncture allergy testing.This test has been used in Europe and is under investiga-tion in the United States, though not approved by theFood and Drug Administration. An electric potential isapplied to the skin, the allergen presented, and the elec-trical resistance observed for changes. This method hasnot been

Treatment
Avoiding allergens is the first line of defense to
reduce the possibility of an allergic attack. It is helpful toavoid environmental irritants such as tobacco smoke,perfumes, household cleaning agents, paints, glues, airfresheners, and potpourri. Nitrogen dioxide from poorly

vented gas stoves, woodburing stoves, and artificial fire-places has also been linked to poor asthma control. Dustmite control is particularly important in the bedroomareas by use of allergen-impermeable covers on mattressand pillows, frequent washing of bedding in hotwater,and removal of items that collect dust such asstuffed toys. Mold growth may be reduced by reducingindoor humidity, repair of house foundations to reduceindoor leaks and seepage, and installation of exhaust sys-tems to

seepage, and installation of exhaust sys-tems to ventilate areas where steam is generated such asthe bathroom or kitchen. Allergic individuals shouldavoid pet allergens such as saliva, body excretions, pelts,urine, or feces. For those who insist on keeping a pet,restriction of the animal’s activity to certain areas of thehome may be beneficial.

Complete environmental control is often difficult to
accomplish, hence therapuetic interventions maybecome necessary. A large number of prescription andover-the-counter drugs are available for treatment ofimmediate hypersensitivity reactions. Most of thesework by decreasing the ability of histamine to provokesymptoms. Other drugs counteract the effects of hista-mine by stimulating other systems or reducing immuneresponses in general.
Antihistamines

Antihistamines block the histamine receptors on
nasal tissue, decreasing the effect of histamine releasedby mast cells. They may be used after symptoms appear,though they may be even more effective when used pre-ventively, before symptoms appear. Antihistamines arehelp reduce sneezing, itching, and rhinorrhea. A widevariety of antihistamines are available.
Older, first generation antihistamines often produce
drowsiness as a major side effect, as well as dry mouth ,

tachycardia, blurred vision, constipation , and lower the
threshold for seizures. These medicatios also have simi-lar effects to a alcohol and care should be taken whenoperating motor vehicles, as individuals may not beaware that they are impared. Such antihistamines includethe following:
• diphenhydramine (Benadryl and generics)• chlorpheniramine (Chlor-trimeton and generics)• brompheniramine (Dimetane and generics)• clemastine (Tavist and generics)

or pass the blood-brain barrier are available by prescrip-tion and include the following:
GALE ENCYCLOPEDIA OF MEDICINE 2 118AllergiesGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 118

• fexofenadine (Allegra)

thromycin,the antifungal drugs ketoconazole and itra-conazole, or the antimalarial drug quinine. Taking morethan the recommended dose of Hismanal can also causearrhythimas. Seldane (terfenadine), the original non-drowsy antihistamine, was voluntarily withdrawn fromthe market by its manufacturers in early 1998 because ofthis potential and because of the availability of an equal-ly effective, safer alternative drug, fexofenadine.
Decongestants

mucosa to counteract the effects of histamine. Thisdecreases the amount of blood in the nasopahryngealand sinus mucosa and reduces swelling. Nasal spraysare available that can be applied directly to the nasal lin-ing and oral systemicpreparations are available. Decon-gestants are stimulants and may cause increased heartrate and blood pressure, headaches,insomnia,agitation,and difficulty emptying the bladder. Use of topicaldecongestants for longer than several days can causeloss of effectiveness

than several days can causeloss of effectiveness and rebound congestion, in whichnasal passages become more severely swollen than

before treatment.
Topical corticosteroids
Topical corticosteroids reduce mucous membrane

inflammationas by decreasing the amount of fluidmoved from the vascular spaces into the tissues. Thesemedications reduce the recruitment of inflammatorycells as well as the synthesis of cytokines. They areavailable by prescription. Allergies tend to becomeworse as the season progresses because the immune sys-tem becomes sensitized to particular antigens and canproduce a faster, stronger response. Topical corticos-teroids are especially effective at reducing this seasonalsensitization because

at reducing this seasonalsensitization because they work more slowly and lastlonger than most other medication types. As a result,they are best started before allergy season begins. Sideeffects are usually mild, but may include headaches,nosebleeds, and unpleasant taste sensations.

Bronchodilators or metered-dose inhalers (MDI)
Because allergic reactions involving the lungs cause
the airways or bronchial tubes to narrow, as in asthma,
GALE ENCYCLOPEDIA OF MEDICINE 2 119Allergies
In a future exposure to the same substance,
the antibodies on the mast cells bind to theallergens, and the cells release their histamine.

Histamine travels to receptor sites in the nasalpassages. When histamine molecules enter thesites they trigger dilation of the blood vessels,swelling, irritation, and increased productionof mucus.
Antihistamine drugs block histamine molecules
from entering receptor sites, thus preventing orreducing swelling, congestion and irritation.AntihistaminesSECOND EXPOSURE
Second and subsequent exposure to allergen. (Illustration by Hans & Cassady.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 119

the airways to open or dilate, can be very effective.When inahlers are used, it is important that the patientbe educated in the proper use of these medications.Theinhaler should be shaken, and the patient should breatheout to expel air from the lungs. The inhaler should beplace at least two fingerbreadths in front of the mouth.The medication should be aimed at the back of thethroat, and the inhaler activated while breathing in quiteslowly 3-4 seconds. The breath should be held for atleast ten

The breath should be held for atleast ten seconds, and then expelled. At least thirty tosixty seconds should pass before the inhaler is usedagain. Care should be taken to properly wash out themouth and brush the teeth following use, as residualmedication remains in this area with only a smallamount actually reaching the lungs. Some bronchodila-tors used to treat acute asthma attacks include adrena-line, albuterol, or other “adrenoceptor stimulants,” mostoften administered as aerosols.

stimulants,” mostoften administered as aerosols. Futicasone (Flovent) isanother commonly prescribed inhaler. Some bron-chodilators used to treat acute asthma attacks includeKEY TERMS

response.
Allergic rhinitis —Inflammation of the mucous
membranes of the nose and eyes in response to anallergen.
Anaphylaxis —Increased sensitivity caused by previ-
ous exposure to an allergen that can result in bloodvessel dilation and smooth muscle contraction.Anaphylaxis can result in sharp blood pressuredrops and difficulty breathing.
Angioedema —Severe non-inflammatory swelling of

the skin, organs, and brain that can also be accom-panied by fever and muscle pain.
Asthma —A lung condition in which the airways
become narrow due to smooth muscle contraction,causing wheezing, coughing, and shortness ofbreath.

Atopic dermatitis —Infection of the skin as a result
of exposure to airborne or food allergens.Conjunctivitis —Inflammation of the thin lining of
the eye called the conjunctiva.
Contact dermatitis —Inflammation of the skin as a
result of contact with a substance.
Delayed hypersensitivity reactions —Allergic reac-
tions mediated by T cells that occur hours to daysafter exposure.
Histamine —A chemical released by mast cells that

activates pain receptors and causes cells to becomeleaky.
Immune hypersensitivity reaction —Allergic reac-
tions that are mediated by mast cells and occurwithin minutes of allergen contact.

found in the lining of the nasal passages and eye-lids, displays a type of antibody calledimmunoglobulin type E (IgE) on its cell surface, andparticipates in the allergic response by releasinghistamine from intracellular granules.
T cells —Immune system cells or more specifically,
white blood cells, that stimulate cells to create andrelease antibodies.
adrenaline, albuterol, Maxair, Proventil, or other

“adrenoceptor stimulants,” most often administered asaerosols. Another group of medications, the long-actingbeta agonists, are proving useful to reduce the use ofinhalers.and include salmeterol xinafoate (Serevent).Theophylline,naturally present in coffee and tea, isanother drug that produces brochodilation.It is usuallytaken orally, but in a severe asthma attack is may begiven intravenously. Side effects include gastrointestinaldisturbances, insomnia , headaches, and seizures.
Anticholinergics

Ipratropium bromide (atrovent) and atropine sulfate
are achticholinergic drugs used for the treatment of asth-ma. Ipratropium is used for treating asthmatics in emer-gency situations with a nebulizer.
Nonsteroidal drugs
MAST CELL STABILIZERS. Cromolyn sodium pre-
vents the release of mast cell granules, thereby prevent-
GALE ENCYCLOPEDIA OF MEDICINE 2 120AllergiesGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 120

ing the release of histamine and other chemicals con-
tained in them. It acts as a preventive treatment if it isbegun several weeks before the onset of the allergy sea-son. It can also be used for year round allergy preven-tion. Cromolyn sodium is available as a nasal spray forallergic rhinitis and in aerosol (a suspension of particlesin gas) form for asthma.
LEUKOTRIENE MODIFIERS. These medications are
useful for individuals with aspirin sensitivity,sinusitis,

polposis, urticaria. Examples include zafirlukast (Acco-late),montelukast (Singulair), and zileuton (Zyflo).When zileuton is used, care must be taken to measureliver enzymes.
In this form of therapy, allergen is injected into the
skin in increasing doses over a specific period of time.This may be helpful for patients who do not respond tomedications or avoidance of allergens in the environ-ment. This type of therapy may reduce the need for med-ications.

Treatment of contact dermatitis
An individual suffering from contact dermatitis

should initially take steps to avoid possible wources ofexposure to the offending agent. Calamine lotion appliedto affected skin can reduce irritation somewhat, as cancold water compresses. Side effects of topical agentsmay include over-drying of the skin.In the case of acutecontact dermatitis, short-term oral corticosteroid therapymay be appropriate. Moderately strong coricosteroidscan also be applied as a wrap for twenty-four hours.Health care workers are especially at risk for hand

care workers are especially at risk for hand erup-tions due to glove use.

Treatment of anaphylaxis
The emergency condition of anaphylaxis is treated

with injection of adrenaline, also known as epinephrine.People who are prone to anaphylaxis because of food orinsect allergies often carry an “Epi-pen” containingadrenaline in a hypodermic needle. Other medicationsmay be given to aid the action of the epi-pen. Promptinjection can prevent a more serious reaction fromdeveloping. Paticular care should be taken to assess theaffected individual’s airway status, and he or she shouldbe placed in a recumbent pose and vital signs deter-mined. If a

recumbent pose and vital signs deter-mined. If a reaction resulted from insect sting or aninjection, a tourniquet may need to be placed proximalto the area where the agent penetrated the skin. Thisshould then be released at intervals of ten minutes at atime, for one to two minutes duration. If the individualdoes not respond to such interventions, then emergency

treatment is appropriate.
Any alternative treatment for allergies begins with

finding the cause and then helping the patient to avoidor eliminate the allergen, although this is not alwayspossible. As with any alternative therapy, a physicianshould be consulted before initiating a new form oftreatment. Education on the use of alternative agents iscritical, as they are still “drugs” even though they arederived from natural sources.Various categories ofalternative remedies may be helpful in allergy treat-ment, including:
• antihistamines: vitamin C and the bioflavonoid hes-

peridin act as natural anithistamines.
• decongestants: vitamin C, the homeopathic remedies
Ferrum phosphoricum and Kali muriaticum (used alter-
nately), and the dietary supplement N-acetylcysteineare believed to have decongestant effects.
• mast cell stabilizers: the bioflavonoids quercetin and
hesperidin may help stabilize mast cells.
• immunotherapy: the herbs echinacea (Echinacea spp.)
and astragalus or milk-vetch root ( Astragalus mem-
branaceus ) may possibly help to strengthen the

immune system.
• bronchodilators: the herbal remedies ephedra ( Ephedra
sinica , also known as ma huang in traditional Chinese
medicine ), khellin ( Ammi visnaga ) and cramp bark
(Viburnum opulus ) are believed to help open the airways.
A variety of herbal remedies, either applied topical-

ly or taken internally, may possibly assist in the treat-ment of contact dermatitis. A poultice (crushed herbsapplied directly to the affected area) made of jewelweed(Impatiens spp.) or chickweed ( Stellaria media ) may
soothe the skin. A cream or wash containing calendula(Calendula officinalis ), a natural antiseptic and anti-
inflammatory agent, may help heal the rash whenapplied topically. Homeopathic treatment may includesuch remedies as Rhus toxicodendron ,Apis mellifica ,o r

Anacardium taken internally. A qualified homeopathic
practitioner should be consulted to match the symptomswith the correct remedy. Care should be taken with anyagent taken internally.
Prognosis
Allergies can improve over time, although they often
worsen. While anaphylaxis and severe asthma are life-
GALE ENCYCLOPEDIA OF MEDICINE 2 121AllergiesGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 121

threatening, other allergic reactions are not. Learning to
recognize and avoid allergy-provoking situations allowsmost people with allergies to lead normal lives.
Avoiding allergens is the best means of limiting

allergic reactions. For food allergies, there is no effectivetreatment except avoidance. By determining the allergensthat are causing reactions, most people can learn to avoidallergic reactions from food, drugs, and contact allergenssuch as poison ivy or latex. Airborne allergens are moredifficult to avoid, although keeping dust and animal dan-der from collecting in the house may limit exposure.Cromolyn sodium can prevent mast cell degranulation,thereby limiting the allergic response.

allergy shots, alters the balance of antibody types inthe body, thereby reducing the ability of IgE to causeallergic reactions. Immunotherapy is preceded by aller-gy testing to determine the precise allergens responsi-ble. Injections involve very small but graduallyincreasing amounts of allergen, over several weeks ormonths, with periodic boosters. Full benefits may takeup to several years to achieve and are not seen at all inabout one in five patients. Individuals receiving allshots will be

patients. Individuals receiving allshots will be monitored closely following each shotbecause of the small risk of anaphylaxis, a conditionthat can result in difficulty breathing and a sharp dropin blood pressure.

Other drugs, including steroids, are used to prevent
asthma attacks and in the long-term management of asthma.
Resources
BOOKS
Kemp, Stephen F. and Richard Lockey, editors. Diagnostic
Testing of Allergic Disease. New York: Marcel Dekker,
Inc., 2000.
Lawlor, G. J., T. J. Fischer, and D. C. Adelman. Manual of
1995.
Lieberman, Phil, and Johh Anderson, editors. Allergic Dis-
eases: Diagnosis and Treatment, 2nd edition. Totowa:

Humana Press, Inc., 2000.
Hans-Uwe, Simon, editor. CRC Desk Reference for Allergy and
Asthma. Boca Raton: CRC Press, 2000.
Manual for Wellness and Self-Care. Boston: Houghton
Jill Granger, MSAllergy tests
Allergy tests indicate a person’s allergic sensitivity
to commonly encountered environmental substances.

Purpose
Allergy is a reaction of the immune system. Nor-

mally, the immune system responds to foreign microor-ganisms and particles, like pollen or dust, by producingspecific proteins called antibodies that are capable ofbinding to identifying molecules, or antigens, on theforeign organisms. This reaction between antibody andantigen sets off a series of reactions designed to protectthe body from infection. Sometimes, this same series ofreactions is triggered by harmless, everyday substances.This is the condition known as allergy, and the offend-ing

condition known as allergy, and the offend-ing substance is called an allergen. Common inhaledallergens include pollen, dust, and insect parts from tinyhouse mites. Common food allergens include nuts, fish,and milk.

the immune system known as mast cells. Mast cellsserve as guards in the tissues where the body meets theoutside world: the skin, the mucous membranes of theeyes and other areas, and the linings of the respiratoryand digestive systems. Mast cells display a special typeof antibody, called immunoglobulin type E (IgE), ontheir surface. Inside, mast cells store reactive chemicalsin small packets, called granules. When the antibodiesencounter allergens, they trigger the release of granules,which

they trigger the release of granules,which spill out their chemicals onto neighboring cells,including blood vessels and nerve cells. One of thesechemicals, histamine, binds to the surfaces of theseother cells, through special proteins called histaminereceptors. Interaction of histamine with receptors onblood vessels causes neighboring cells to become leaky,leading to the fluid collection, swelling, and increasedredness characteristic of a runny nose and red, irritatedeyes. Histamine also

runny nose and red, irritatedeyes. Histamine also stimulates pain receptors, causing

the itchy, scratchy nose, eyes, and throat common inallergic rhinitis .
The particular allergens to which a person is sensi-

tive can be determined through allergy testing. Allergytests may be performed on the skin or using blood serumin a test tube. During skin tests, potential allergens areplaced on the skin and the reaction is observed. In radio-allergosorbent allergy testing (RAST), a patient’s bloodserum is combined with allergen in a test tube to deter-mine if serum antibodies react with the allergen. Provo-cation testing involves direct exposure to a likely aller-

GALE ENCYCLOPEDIA OF MEDICINE 2 122Allergy testsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 122

gen, either through inhalation or ingestion. Positive reac-
tions from any of these tests may be used to narrow thecandidates for the actual allergen causing the allergy.
Identification of the allergenic substance may allow
the patient to avoid the substance and reduce allergicreactions. In addition, allergy testing may be done inthose with asthma that is difficult to manage, eczema, or
skin rashes to determine if an allergy is causing the con-

dition or making it worse. Allergy tests may also be donebefore allergen desensitization to ensure the safety ofmore extensive exposure.
Skin testing is the most common type of allergy test.

There are two forms: percutaneous and intradermal. Inpercutaneous or prick testing, allergen solutions areplaced on the skin, and the skin is then pricked with aneedle, allowing the allergen to enter the skin andbecome exposed to mast cells. Scratch testing, in whichthe skin is scratched instead of punctured, is used lessoften. Intradermal testing involves directly injectingallergen solutions into the skin. In both tests, a reddened,swollen spot develops at the injection site for each

spot develops at the injection site for each sub-stance to which the person is sensitive. Skin reactivity isseen for allergens regardless of whether they usuallyaffect the skin. In other words, airborne and food aller-gens cause skin reactions equally well.

The range of allergens used for testing is chosen to
reflect possible sources in the environment and mayinclude the following:
• pollen from a variety of trees, common grasses, and
weeds
• mold and fungus spores• house dust• house mites• animal skin cells (dander) and saliva• food extracts• antibiotics• insect venoms
Radio-allergosorbent testing (RAST) is a laboratory
test performed when a person may be too sensitive to riskskin testing or when medications or skin conditions pre-vent it.

Provocation testing is done to positively identify
suspected allergens after preliminary skin testing. A puri-fied preparation of the allergen is inhaled or ingested inincreasing concentrations to determine if it will provokea response. Food testing is much more tedious thaninhalation testing, since full passage through the diges-tive system may take a day or more.Precautions
While allergy tests are quite safe for most people,
the possibility of a condition known as anaphylaxis does

exist. Anaphylaxis is a potentially dangerous conditionthat can result in difficulty breathing and a sharp drop inblood pressure. People with a known history of anaphy-laxis should inform the testing clinician. Skin testsshould never include a substance known to cause ana-phylaxis in the person being tested.
Provocation tests may cause an allergic reaction.
Therefore, treatment medications should be available fol-lowing the tests, to be administered, if needed.

In prick testing, a drop of each allergen to be tested

is placed on the skin, usually on the forearm or the back.A typical battery of tests may involve two dozen allergendrops, including a drop of saline solution that should notprovoke a reaction (negative control) and a drop of hista-mine that should provoke a reaction (positive control). Asmall needle is inserted through the drop, and used toprick the skin below. A new needle is used for each prick.The sites are examined over the next twenty minutes forevidence of swelling and redness, indicating

forevidence of swelling and redness, indicating a positivereaction. In some instances, a tracing of the set of reac-tions may be made by placing paper over the tested area.Similarly, in intradermal testing, separate injections aremade for each allergen tested. Observations are madeover the next twenty minutes.

In RAST testing, a blood sample is taken for use in
the laboratory, where the antibody- containing serum isseparated from the blood cells. The serum is thenexposed to allergens bound to a solid medium. If a per-son has antibodies to a particular allergen, those antibod-
GALE ENCYCLOPEDIA OF MEDICINE 2 123Allergy tests
This patient is being exposed to certain allergens as part of
an allergy test. (Custom Medical Stock Photo. Reproduced by

KEY TERMS
response.

found in the lining of the nasal passages and eye-lids, displays a type of antibody called immuno-globulin type E (IgE) on its cell surface, and partici-pates in the allergic response by releasing hista-mine from intracellular granules.ies will bind to the solid medium and remain behind after

a rinse. Location of allergen-antibody combinations isdone by adding antibody-reactive antibodies, so calledanti-antibodies, that are chemically linked with aradioactive dye. By locating radioactive spots on thesolid medium, the reactive allergens are discovered.
Provocation testing may be performed to identify air-

borne or food allergens. Inhalation testing is performedonly after a patient’s lung capacity and response to themedium used to dilute the allergen has been determined.Once this has been determined, the patient inhales increas-ingly concentrated samples of a particular allergen, fol-lowed each time by measurement of the exhalation capaci-ty. Only one allergen is tested per day. Testing for foodallergies is usually done by removing the suspect food

from the diet for two weeks, followed by eating a singleportion of the suspect food and follow-up monitoring.
Skin testing is preceded by a brief examination of

the skin. The patient should refrain from using anti-aller-gy drugs for at least 48 hours before testing. Prior toinhalation testing, patients with asthma who can tolerateit may be asked to stop any asthma medications. Testingfor food allergies requires the person to avoid all suspectfood for at least two weeks before testing.
Aftercare
Skin testing does not usually require any aftercare. A

generalized redness and swelling may occur in the testarea, but it will usually resolve within a day or two.
Inhalation tests may cause delayed asthma attacks,
even if the antigen administered in the test initially pro-duced no response. Severe initial reactions may justifyclose professional observation for at least 12 hours aftertesting.Risks
Intradermal testing may inadvertently result in the

injection of the allergen into the circulation, with anincreased risk of adverse reactions. Inhalation tests mayprovoke an asthma attack. Exposure to new or unsuspect-ed allergens in any test carries the risk of anaphylaxis.Because patients are monitored following allergy testing,an anaphylactic reaction is usually recognized and treat-ed promptly. Occasionally, a delayed anaphylacticresponse can occur that will require immediate care.Proper patient education regarding how to recognize

patient education regarding how to recognize ana-phylaxis is vital.

Lack of redness or swelling on a skin test indicates
no allergic response. In an inhalation test, the exhalationcapacity should remain unchanged. In a food challenge,no symptoms should occur.
Presence of redness or swelling, especially over 5
mm (1/4 inch) in diameter, indicates an allergic response.
GALE ENCYCLOPEDIA OF MEDICINE 2 124Allergy tests
A close-up of a patient’s arm after allergy testing. (Custom

Medical Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 124

This does not mean the substance actually causes the
patient’s symptoms, however, since he or she may haveno regular exposure to the allergen. In fact, the actualallergen may not have been included in the test array.
Following allergen inhalation, reduction in exhala-
tion capacity of more than 20%, and for at least 10-20minutes, indicates a positive reaction to the allergen.
Gastrointestinal symptoms within 24 hours follow-

ing the ingestion of a suspected food allergen indicates apositive response.
Resources
BOOKS
Davies, R., and S. Ollier. Allergy: The Facts. Oxford, England:
Oxford University Press, 1989.
Lawlor Jr., G. J., T. J. Fischer, and D. C. Adelman. Manual of
1995.
Allogenic transplant seeBone marrow
transplantation
Allopurino seeGout drugs
Alopecia

Alopecia
Alopecia simply means hair loss (baldness).
Hair loss occurs for a great many reasons—from
pulling it out to having it killed off by cancer chemo-
therapy . Some causes are considered natural, while oth-
ers signal serious health problems. Some conditions areconfined to the scalp. Others reflect disease throughoutthe body. Being plainly visible, the skin and its compo-nents can provide early signs of disease elsewhere in thebody.

Oftentimes, conditions affecting the skin of the scalp
will result in hair loss. The first clue to the specific causeis the pattern of hair loss, whether it be complete bald-ness (alopecia totalis), patchy bald spots, thinning, orhair loss confined to certain areas. Also a factor is thecondition of the hair and the scalp beneath it. Sometimesonly the hair is affected; sometimes the skin is visiblydiseased as well.Causes and symptoms
• Male pattern baldness (androgenic alopecia) is consid-

ered normal in adult males. It is easily recognized bythe distribution of hair loss over the top and front of thehead and by the healthy condition of the scalp.
• Alopecia areata is a hair loss condition of unknown
cause that can be patchy or extend to complete baldness.
• Fungal infections of the scalp usually cause patchy hair
loss. The fungus, similar to the ones that cause athlete’s
footand ringworm , often glows under ultraviolet light.

• Trichotillomania is the name of a mental disorder that
causes a person to pull out his/her own hair.
• Complete hair loss is a common result of cancer
chemotherapy, due to the toxicity of the drugs used.Placing a tourniquet around the skull just above the earsduring the intravenous infusion of the drugs mayreduce or eliminate hair loss by preventing the drugsfrom reaching the scalp.
• Systemic diseases often affect hair growth either selec-

tively or by altering the skin of the scalp. One exampleis thyroid disorders. Hyperthyroidism (too much thy-
roid hormone) causes hair to become thin and fine.
GALE ENCYCLOPEDIA OF MEDICINE 2 125Alopecia
Top of balding male’s head. (Photograph by Kelly A. Quin.
Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 125

Hypothyroidism (too little thyroid hormone) thickens
both hair and skin.
• Several autoimmune diseases (when protective cells
begin to attack self cells within the body) affect theskin, notably lupus erythematosus.
Diagnosis
Dermatologists are skilled in diagnosis by sight
alone. For more obscure diseases, they may have toresort to a skin biopsy , removing a tiny bit of skin using

a local anesthetic so that it can examined under a micro-scope. Systemic diseases will require a complete evalua-tion by a physician, including specific tests to identifyand characterize the problem.
Treatment
Successful treatment of underlying causes is most

likely to restore hair growth, be it the completion ofchemotherapy, effective cure of a scalp fungus, or controlof a systemic disease. Two relatively new drugs—minox-idil (Rogaine) and finasteride (Proscar)—promote hairgrowth in a significant minority of patients, especiallythose with male pattern baldness and alopecia areata.While both drugs have so far proved to be quite safewhen used for this purpose, minoxidil is a liquid that is

applied to the scalp and finasteride is the first and onlyapproved treatment in a pill form.
Minoxidil was approved for over-the-counter sales
in 1996. When used continuously for long periods ofKEY TERMS
Athlete’s foot —A fungal infection between the
toes, officially known as tinea pedis.
Autoimmune disease —Certain diseases caused by
the body’s development of an immune reaction toits own tissues.
Chemotherapy —The treatment of diseases, usual-
ly cancer, with drugs (chemicals).

Hair follicles —Tiny organs in the skin, each one of
which grows a single hair.
Lupus erythematosus —An autoimmune disease
that can damage skin, joints, kidneys, and otherorgans.
Ringworm —A fungal infection of the skin, usually
known as tinea corporis.
Systemic —Affecting all or most parts of the body.time, minoxidil produces satisfactory results in about one

quarter of patients with androgenic alopecia and as manyas half the patients with alopecia areata. There is also anover-the-counter extra-strength version of minoxidil (5%concentration) approved for use by men only. The treat-ment often results in new hair that is thinner and lighterin color. It is important to note that new hair stops grow-ing soon after the use of minoxidil is discontinued.
Over the past few decades there have appeared a

multitude of hair replacement methods performed byboth physicians and non-physicians. They range fromsimply weaving someone else’s hair in with the remainsof your own to surgically transplanting thousands of hairfollicles one at a time.
Hair transplantation is completed by taking tiny

plugs of skin, each containing one to several hairs,from the back side of the scalp. The bald sections arethen implanted with the plugs. Research completed in2000 looked at the new technique of hair grafting, andfound that micrografts (one to two hairs transplantedper follicle) resulted in fewer complications and thebest results
Another surgical procedure used to treat androgenic

alopecia is scalp reduction. By stretching skin the hair-less scalp can be removed and the area of bald skindecreased by closing the space with hair-covered scalp.Hair-bearing skin can also be folded over an area of baldskin with a technique called a flap.
Prognosis
The prognosis varies with the cause. It is generally
much easier to lose hair than to regrow it. Even when itreturns, it is often thin and less attractive than the original.
Resources
BOOKS

Resources
BOOKS
American Society of Health-System Pharmacists Inc. Ameri-
can Hospital Formulary Service Drug Information.Bethesda, MD: American Society of Health-System Phar-macists Inc., 1998.
Bennett, J. Claude, and Fred Plum, ed. Cecil Textbook of Medi-
cine. Philadelphia: W. B. Saunders, 1996.
The Burton Goldberg Group. “Hair loss.” In Alternate Medi-
cine: The Definitive Guide. Puyallup, WA: Future Medi-
cine Publishing, 1993.

Isselbacher, Kurt, et al., ed. Harrison’s Principles of Internal
Medicine. New York: McGraw-Hill, 1994.
Amichai B., M. H. Grunwald, and R. Sobel. “5 Alpha-reduc-
tase Inhibitors—A New Hope in Dermatology?” Interna-
tional Journal of Dermatology , March 1997, 182-4.
GALE ENCYCLOPEDIA OF MEDICINE 2 126AlopeciaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 126

Nielsen, Timothy A., and Martin Reichel. “Alopecia: Diagnosis
and Management.” American Family Physician .
OTHER
Androgenetic Alopecia.com. “How can minoxidil be used to
treat baldness?”. <http://androgenetic-alopecia.com/baldnesstreatments/minoxidil/002minoxidilbaldnessusee.shtml> (1 May 2001).
Hairloss Information Center. “Rogaine: Does It Really Work?”
1997. <http://www.hairloss.com/rogaine.htm> (19 April1998).
Houston Academy of Medicine. “Propecia: Male Baldness

Pill.” December 30, 1997. <http://library.tmc.edu/t-prop.html> (19 April 1998).
Mayo Clinic. “Alopecia” January 26, 2001. <http://www.mayo
health.org> (1 May 2001).
WebMD Medical News. “Hair Today, Gone Tomorrow, Hair
Again” 2000. <http://my.webmd.com/content/article/1728.53923> (1 May 2001).
Beth Kapes
Alpha-fetoprotein test
The alpha-fetoprotein (AFP) test is a blood test that
is performed during pregnancy . This screening test mea-

sures the level of AFP in the mother’s blood and indi-cates the probability that the fetus has one of several seri-ous birth defects . The level of AFP can also be deter-
mined by analyzing a sample of amniotic fluid. Thisscreening test cannot diagnose a specific condition; itonly indicates the increase of risk for several birthdefects. Outside pregnancy, the AFP test is used to detectliver disease, certain cancerous tumors, and to monitorthe progress of cancer treatment.
Purpose

liver of a fetus. The exact function of this protein isunknown. After birth, the infant’s liver stops producingAFP, and an adult liver contains only trace amounts.During pregnancy, the fetus excretes AFP in urine andsome of the protein crosses the fetal membranes to enterthe mother’s blood. The level of AFP can then be deter-mined by analyzing a sample of the mother’s blood. Byanalyzing the amount of AFP found in a blood or amni-otic fluid sample, doctors can determine the probabilitythat the

doctors can determine the probabilitythat the fetus is at risk for certain birth defects. It is veryimportant that the doctor know precisely how old thefetus is when the test is performed since the AFP levelchanges over the length of the pregnancy. Alone, AFPscreening cannot diagnose a birth defect. The test isused as an indicator of risk and then an appropriate lineof testing (like amniocentesis or ultrasound) follows,

based on the results.
Abnormally high AFP may indicate that the fetus
has an increased risk of a neural tube defect, the mostcommon and severe type of disorder associated withincreased AFP. These types of defects include spinalcolumn defects ( spina bifida ) and anencephaly (a

severe and usually fatal brain abnormality). If the tubethat becomes the brain and spinal cord does not closecorrectly during fetal development, AFP may leakthrough this abnormal opening and enter the amnioticfluid. This leakage creates abnormally high levels ofAFP in amniotic fluid and in maternal blood. If thescreening test indicates abnormally high AFP, ultra-sound is used to diagnosis the problem.
Other fetal conditions that can raise AFP levels
above normal include:

• cysts at the end of the spine• blockage in the esophagus or intestines
• liver disease causing liver cells to die
• defects in the abdominal wall• kidney or urinary tract defects or disease
• brittle bone disease
Levels may also be high if there is too little fluid in
the amniotic sac around the fetus, more than one devel-oping fetus, or a pregnancy that is farther along thanestimated.
For unknown reasons, abnormally low AFP may

indicate that the fetus has an increased risk of Down
syndrome . Down syndrome is a condition that
includes mental retardation and a distinctive physical
appearance linked to an abnormality of chromosome21 (called trisomy 21). If the screening test indicatesan abnormally low AFP, amniocentesis is used to diag-nosis the problem. Abnormally low levels of AFP canalso occur when the fetus has died or when the motheris overweight.

AFP is often part of a “triple check” blood test that
analyzes three substances as risk indicators of possiblebirth defects: AFP, estriol, and human chorionicgonadotropin (HCG). When all three substances are mea-sured in the mother’s blood, the accuracy of the testresults increases.
Although AFP in human blood gradually disappears

after birth, it never disappears entirely. It may reappear inliver disease, or tumors of the liver, ovaries, or testicles.The AFP test is used to screen people at high risk forthese conditions. After a cancerous tumor is removed, an
GALE ENCYCLOPEDIA OF MEDICINE 2 127Alpha-fetoprotein testGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 127

AFP test can monitor the progress of treatment. Contin-
ued high AFP levels suggest the cancer is growing.
It is very important that the doctor know precisely

how old the fetus is when the test is performed since theAFP level considered normal changes over the length ofthe pregnancy. Errors in determining the age of the fetuslead to errors when interpreting the test results. Since anAFP test is only a screening tool, more specific testsmust follow to make an accurate diagnosis. An abnormaltest result does not necessarily mean that the fetus has abirth defect. The test has a high rate of abnormal results(either high or low) in order to prevent missing

high or low) in order to prevent missing a fetusthat has a serious condition.

The AFP test is usually performed at week 16 of
pregnancy. Blood is drawn from a vein, usually on theinside of the elbow. AFP can also be measured in the sam-ple of amniotic fluid taken at the time of amniocentesis.Test results are usually available after about one week.
There is no specific physical preparation for the AFP
test.
Aftercare
There is no specific aftercare involved with this
screening test.
Risks
The risks associated with drawing blood are mini-

mal, but may include bleeding from the puncture site,feeling faint or lightheaded after the blood is drawn, orblood accumulating under the puncture site (hematoma).
Alpha-fetoprotein is measured in nanograms per
milliliter (ng/mL) and is expressed as a probability. TheKEY TERMS
Amniotic fluid —Fluid within the uterine sac in
which the fetus lives until born.
Fetus —The stage in human development from the

second month of pregnancy until birth.probability (1:100, for example) translates into the
chance that the fetus has a defect (a one in 100 chance,for example).
When testing for cancer or liver diseases, AFP
results are reported as nanograms per milliliter. An AFPlevel less than or equal to 50 ng/mL is considered nor-mal.
The doctor will inform the woman of her specific

increased risk as compared to the “normal” risk of a stan-dard case. If the risk of Down syndrome is greater thanthe standard risk for women who are 35 years old orolder (one in 270), then amniocentesis is recommended.Again, the test has a high rate of showing an abnormalAFP level in order to prevent missing a fetus that hasDown’s syndrome. This screening test only predicts risk;appropriate diagnostic testing will follow after an abnor-mal screening result.

In tumor or liver disease testing, an AFP level
greater than 50 ng/mL is considered abnormal.
Resources
BOOKS
Cunningham, Gary, et al. Williams Obstetrics. 20th ed. Stam-
ford: Appleton & Lange, 1997.
Eisenberg, Arlene, et al. What To Expect When You’re Expect-
ing.2nd ed. New York: Workman Publishing, 1996.
Johnson, Robert, ed. Mayo Clinic Complete Book of Pregnancy
and Baby’s First Year. New York: William Morrow and
Co., 1997.

Co., 1997.
Haddow, James, et al. “Reducing the Need for Amniocentesis
in Women 35 Years of Age or Older with Serum Markersfor Screening.” The New England Journal Of Medicine
330, no. 16 (21 Apr. 1994): 1114-8.
Kase, Lori. “Do Pregnant Women Need All Those Tests?”
American Baby (Aug. 1994): 42-3.
Lieberman, Adrienne. “AFP Screening: A Test for Birth
Defects.” American Baby (Nov. 1993): 6.
McCabe, Edward, et al. “Maternal Serum Alpha-fetoprotein

Screening.” Pediatrics 88, no. 6 (Dec. 1991): 1282-3.
March of Dimes Birth Defects Foundation. 1275 Mamaroneck
Ave., White Plains, NY 10605. (914) 428-7100. <http://www.modimes.org>.
National Cancer Institute. Building 31, Room 10A31, 31 Cen-
ter Drive, MSC 2580, Bethesda, MD 20892-2580. (800)422-6237. <http://www.nci.nih.gov>.
Adrienne Massel, RN
Alpha-thalassemia seeThalassemia

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Alpha1-adrenergic blockers
Alpha1-adrenergic blockers are drugs that work by
blocking the alpha1-receptors of vascular smooth muscle,
thus preventing the uptake of catecholamines by thesmooth muscle cells. This causes vasodilation and allowsblood to flow more easily.
Purpose
These drugs, called alpha blockers for short, are
used for two main purposes: to treat high blood pressure(hypertension ) and to treat benign prostatic hyperplasia

(BPH), a condition that affects men and is characterizedby an enlarged prostate gland.
High blood pressure
High blood pressure puts a strain on the heart and
the arteries. Over time, hypertension can damage theblood vessels to the point of causing stroke ,heart fail-
ureor kidney failure. People with high blood pressure

may also be at higher risk for heart attacks. Controllinghigh blood pressure makes these problems less likely.Alpha blockers help lower blood pressure by causingvasodilation, meaning an increase in the diameter of theblood vessels, which allows blood to flow more easily.
Benign prostatic hyperplasia (BPH)
This condition particularly affects older men. Over

time, the prostate, a donut-shaped gland below the blad-der, enlarges. When this happens, it may interfere withthe passage of urine from the bladder out of the body.Men who are diagnosed with BPH may have to urinatemore often. Or they may feel that they can not complete-ly empty their bladders. Alpha blockers inhibit the con-traction of prostatic smooth muscle and thus relax mus-cles in the prostate and the bladder, allowing urine toflow more freely.

Commonly prescribed alpha blockers for hyperten-
sion and BPH include doxazosin (Cardura, prazosin(Minipress) and terazosin (Hytrin). Prazosin is also usedin the treatment of heart failure. All are available onlywith a physician’s prescription and are sold in tablet form.
The recommended dose depends on the patient and

the type of alpha blocker and may change over the courseof treatment. The prescribing physician will graduallyincrease the dosage, if necessary. Some patients may needas much as 15-20 mg per day of terazosin, 16 mg per dayof doxazosin, or as much as 40 mg per day of prazosin,but most people benefit from lower doses. As the dosageincreases, so does the possibility of unwanted side effects.
Alpha blockers should be taken exactly as directed,

even if the medication does not seem to be working atfirst. It should not be stopped even if symptoms improvebecause it needs to be taken regularly to be effective.Patients should avoid missing any doses, and should nottake larger or more frequent doses to make up formissed doses.
Alpha blockers may lower blood pressure to a
greater extent than desired. This can cause dizziness ,
lightheadedness, heart palpitations , and fainting . Activ-

ities such as driving, using machines, or doing anythingelse that might be dangerous for 24 hours after taking thefirst dose should be avoided. Patients should be remindedto be especially careful not to fall when getting up in themiddle of the night. The same precautions are recom-mended if the dosage is increased or if the drug has beenstopped and then started again. Anyone whose safety onthe job could be affected by taking alpha blockers shouldinform his or her physician, so that the

shouldinform his or her physician, so that the physician cantake this factor into account when increasing dosage.

Dizziness, lightheadedness, and fainting are more like-
ly to occur when people taking alpha blockers also drinkalcohol, exercise , stand for a long time, or are exposed to
hot weather. Extra care should be used under these condi-tions and alcohol consumption should be limited.
Some people may feel drowsy or less alert when
using these drugs. They should accordingly avoid drivingor performing activities that require full attention.
People diagnosed with kidney disease or liver disease

may also be more sensitive to alpha blockers. They shouldinform their physicians about these conditions if alphablockers are prescribed. Older people may also be moresensitive and may be more likely to have unwanted sideeffects, such as fainting, dizziness, and lightheadedness.
It should be noted that alpha blockers do not cure

high blood pressure. They simply help to keep the condi-tion under control. Similarly, these drugs will not shrinkan enlarged prostate gland. Although they will helprelieve the symptoms of prostate enlargement, theprostate may continue to grow, and it eventually may benecessary to have prostate surgery.
Alpha blockers may lower blood counts. Patients
may need to have their blood checked regularly whiletaking this medicine.

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Anyone who has had unusual reactions to alpha
blockers in the past should let his or her physician knowbefore taking the drugs again. The physician should alsobe told about any allergies to foods, dyes, preservatives,
or other substances.
The effects of taking alpha blockers during preg-
nancy are not fully understood. Women who are preg-

nant or planning to become pregnant should inform theirphysicians. Breastfeeding mothers who need to takealpha blockers should also talk to their physicians. Thesedrugs can pass into breast milk and may affect nursingbabies. It may be necessary to stop breastfeeding whilebeing treated with alpha blockers.
The most common side effects are dizziness, drowsi-
ness, tiredness, headache , nervousness, irritability,
stuffy or runny nose, nausea, pain in the arms and legs,

and weakness. These problems usually go away as theKEY TERMS
Adrenergic —Refers to neurons (nerve cells) that use
catecholamines as neurotransmitters at a synapse.
Adrenergic receptor —There are three families of
adrenergic receptors, alpha1, alpha2and beta, and
each family contains three distinct subtypes. Eachof the nine subtypes are coded by separate genes,and display specific drug specificities and regulato-ry properties.
Alpha blockers —Medications that bind alpha

adrenergic receptors and decrease the workload ofthe heart and lower blood pressure. They are com-monly used to treat hypertension, peripheral vascu-lar disease, and hyperplasia.
Arteries —Blood vessels that carry oxygenated
blood away from the heart to the cells, tissues, andorgans of the body.
Catecholamines —Family of neurotransmitters con-

taining dopamine, norepinephrine and epineph-rine, produced and secreted by cells of the adrenalmedulla in the brain. Catecholamines have excita-tory effects on smooth muscle cells of the vesselsthat supply blood to the skin and mucous mem-branes and have inhibitory effects on smooth mus-cle cells located in the wall of the gut, the bronchialtree of the lungs, and the vessels that supply bloodto skeletal muscle. There are two different maintypes of receptors for these neurotransmitters,

called alpha and beta adrenergic receptors. The cat-echolamines are therefore are also known as adren-ergic neurotransmitters.
Hyperplasia —The abnormal increase in the num-
ber of normal cells in a given tissue.
Hypertension —Persistently high arterial blood pres-
sure.
Neurotransmitter —Substance released from neu-
rons of the peripheral nervous system that travelsacross the synaptic clefts (gaps) of other neurons toexcite or inhibit the target cell.

Palpitation —Rapid, forceful, throbbing, or fluttering
heartbeat.
Receptor —A molecular structure in a cell or on the
surface of a cell that allows binding of a specificsubstance that causes a specific physiologicresponse.
Synapse —A connection between nerve cells, by
which nervous excitation is transferred from onecell to the other.
Vasodilation —The increase in the internal diameter

of a blood vessel that results from relaxation ofsmooth muscle within the wall of the vessel thuscausing an increase in blood flow.
body adjusts to the drug and do not require medical treat-
ment. If they do not subside or if they interfere with nor-mal activities, the physician should be informed.
If any of the following side effects occur, the pre-
scribing physician should be notified as soon as possible:
• fainting
• shortness of breath or difficulty breathing

• fast, pounding, or irregular heartbeat• swollen feet, ankles, wrists
Other side effects may occur. Anyone who has
unusual symptoms after taking alpha blockers shouldcontact his or her physician.
Doxazosin (Cardura) is not known to interact with
any other drugs. Terazosin (Hytrin) may interact withnonsteroidal anti-inflammatory drugs , such as ibupro-

GALE ENCYCLOPEDIA OF MEDICINE 2 130Alpha1-adrenergic blockersGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 130

fen (Motrin), and with other blood pressure drugs, such
as enalapril (Vasotec), and verapamil (Calan,Verelan).Prazosin (Minipress) may interact with beta adrenergicblocking agents such as propranolol (Inderal) and others,and with verapamil (Calan, Isoptin.) When drugs inter-act, the effects of one or both of the drugs may change orthe risk of side effects may be greater.
Alport syndrome
A hereditary disease of the kidneys that primarily

affects men, causing blood in the urine, hearing loss and
eye problems. Eventually, kidney dialysis or transplant
may be necessary.
Alport syndrome affects about one in 5,000 Ameri-

cans, striking men more often and severely than women.There are several varieties of the syndrome, some occur-ring in childhood and others not causing symptoms untilmen reach their 20s or 30s. All varieties of the syndromeare characterized by kidney disease that usually pro-gresses to chronic kidney failure and by uremia (the
presence of excessive amounts of urea and other wasteproducts in the blood).

Alport syndrome in most cases is caused by a defect
in one or more genes located on the X chromosome. It isusually inherited from the mother, who is a normal carri-er. However, in up to 20% of cases there is no family his-tory of the disorder. In these cases, there appears to be aspontaneous genetic mutation causing Alport syndrome.
Blood in the urine (hematuria) is a hallmark of
Alport syndrome. Other symptoms that may appear invarying combinations include:

• protein in the urine (proteinuria)• sensorineural hearing loss• eye problems [involuntary, rhythmic eye movements
(nystagmus ),cataracts , or cornea problems]
• skin problems• platelet disorders• abnormal white blood cells• smooth muscle tumorsKEY TERMS
Albumin —A protein that is important in maintain-
ing blood volume. Low albumin levels is one signof Alport syndrome.
Dialysis —A technique of removing waste material

from the blood. It is used with patients whose kid-neys have stopped functioning and can no longercleanse the blood on their own.
Diuretic —A drug that increases the amount of
urine a person produces.
Hematuria —Blood in the urine, Hematuria is a
hallmark of Alport syndrome.
Pulmonary edema —Excess fluid in the air spaces
of the lungs.
Uremia —The presence of excessive amounts of
urea and other waste products in the blood.

Not all patients with Alport syndrome have hearing
problems. In general, those with normal hearing haveless severe cases of Alport syndrome.
Diagnosis
Alport syndrome is diagnosed with a medical evalu-
ation and family history, together with a kidney biopsy
that can detect changes in the kidney typical of the condi-tion. Urinalysis may reveal blood or protein in the urine.
Blood tests can reveal a low platelet level.

In addition, tests for the Alport gene are now avail-
able. Although testing is fairly expensive, it is covered bymany types of health insurance. DNA tests can diagnoseaffected children even before birth, and genetic linkagetests tracing all family members at risk for Alport syn-drome are also available.
Treatment
There is no specific treatment that can “cure” Alport

syndrome. Instead, care is aimed at easing the problemsrelated to kidney failure, such as the presence of toomany waste products in the blood (uremia).
To control kidney inflammation ( nephritis ), patients
should:
• restrict fluids• control high blood pressure• manage pulmonary edema
GALE ENCYCLOPEDIA OF MEDICINE 2 131Alport syndromeGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 131

• control high blood levels of potassium
Rarely patients with Alport syndrome may develop
nephrotic syndrome , a group of symptoms including
too much protein in the urine, low albumin levels, andswelling. To ease these symptoms, patients should:
• drink less
• eat a salt-free diet• use diuretics
• have albumin transfusions
The treatment for chronic kidney failure is dialysis
or a kidney transplant.
Prognosis
Women with this condition can lead a normal life,

although they may have slight hearing loss. An affectedwoman may notice blood in her urine only when understress or pregnant.
Men generally have a much more serious problem
with the disease. Most will experience kidney disease intheir 20s or 30s, which may eventually require dialysis ortransplantation, and many develop significant hearingloss. Men with Alport syndrome often die of complica-tions by middle age.

Alport syndrome is a genetic disease and prevention
efforts are aimed at providing affected individuals andtheir families with information concerning the geneticmechanisms responsible for the disease. Since it is possi-ble to determine if a woman is a carrier, or if an unbornchild has the condition, genetic counseling can provide
helpful information and support for the decisions thataffected individuals and their families may have to make.
Resources
BOOKS

Resources
BOOKS
Schrier, R. W., and C. W. Gottschalk, eds. Diseases of the Kid-
ney.6th ed. Boston: Little, Brown, 1996.
American Association of Kidney Patients. 100 S. Ashley Dr.,
#280, Tampa, FL 33602. (800) 749-2257. <http://www.aakp.org>.
National Kidney and Urologic Disease Information Clearing-

house. 3 Information Way, Bethesda, MD 20892. (301)654-4415. <http://www.niddk.nih.gov>.
10016. (800) 622-9010.<http://www.kidney.org>.National Organization for Rare Diseases. P.O. Box 8923, Fair-
field, CT 06812. (213) 745-6518. <http://www.w2.com>.
OTHER
“Alport Syndrome.” Pediatric Database Home Page. <http://
www.icondata.com/health/pedbase/files/ALPORTSY .HTM>.
Alport Syndrome Home Page. <http://www.cc.utah.edu/
~cla6202/ASHP.htm>.

The Hereditary Nephritis Foundation (HNF) Home Page.
<http://www.cc.utah.edu/~cla6202/HNF.htm>.
Alprazolam seeBenzodiazepines
ALS seeAmyotrophic lateral sclerosis
Alteplase seeThrombolytic therapy
Altitude sickness
Altitude sickness is a general term encompassing a

spectrum of disorders that occur at higher altitudes.Since the severity of symptoms varies with altitude, it isimportant to understand the range of the different alti-tudes that may be involved. High altitude is defined asheight greater than 8,000 feet (2,438 m); medium altitudeis defined as height between 5,000 and 8,000 feet(1,524–2,438 m); and extreme altitude is defined asheight greater than 19,000 feet (5,791 m). The majorityof healthy individuals suffer from altitude sickness whenthey

suffer from altitude sickness whenthey reach very high altitudes. In addition, about 20% ofpeople ascending above 9,000 (2,743 m) feet in one daywill develop altitude sickness. Children under six yearsand women in the premenstrual part of their cycles maybe more vulnerable. Individuals with preexisting medicalconditions—even a minor respiratory infection—maybecome sick at more moderate altitudes.

There are three major clinical syndromes that fall
under the heading of altitude sickness: acute mountainsickness (AMS), high-altitude pulmonary edema
(HAPE), and high-altitude cerebral edema (HACE).
These syndromes are not separate, individual syndromesas much as they are a continuum of severity, all resultingfrom a decrease in oxygen in the air. AMS is the mildest,and the other two represent severe, life-threatening formsof altitude sickness.

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of oxygen decreases with altitude. (Partial pressure is aterm applied to gases that is similar to the way the termconcentration is applied to liquid solutions.) For instance,at 18,000 feet (5,486 m) the partial pressure of oxygendrops to one-half its value at sea level and, therefore, thereis a substantially lower amount of oxygen available for theindividual to inhale. This is known as hypoxia. Further-more, since there is less oxygen to inhale, less oxygenreaches the blood. This is known as

less oxygenreaches the blood. This is known as hypoxemia. These twoconditions are the major factors that form the basis for allthe medical problems associated with altitude sickness.

response is to breathe more rapidly (hyperventilate). Thisis the body’s attempt to bring in more oxygen at a rapidrate. This attempt at alleviating the effects of the hypoxiaat higher altitudes is known as acclimatization, and itoccurs during the first few days. Acclimatization is aresponse that occurs in individuals who travel from lowerto higher altitudes. There are groups of people who havelived at high altitudes (for example, in the Himalayanand Andes mountains) for generations, and they

Andes mountains) for generations, and they are sim-ply accustomed to living at such altitudes, perhapsthrough a genetic ability.

Acute mountain sickness (AMS) is a mild form of

altitude sickness that results from ascent to altitudes highergreater than 8,000 feet (2,438 m)—even 6,500 feet (1,981m) in some susceptible individuals. Although hypoxia isassociated with the development of AMS, the exact mech-anism by which this condition develops has yet to be con-firmed. It is important to realize that some individualsacclimatize to higher altitudes more efficiently than others.As a result, under similar conditions some will suffer fromAMS while others will not. At present,

suffer fromAMS while others will not. At present, the susceptibilityof otherwise healthy individuals to contracting AMS can-not be accurately predicted. Of those who do suffer fromAMS, the condition tends to be most severe on the secondor third day after reaching the high altitude, and it usuallyabates after three to five days if they remain at the samealtitude. However, it can recur if the individuals travel toan even higher altitude. Symptoms usually appear a fewhours to a few days following

usually appear a fewhours to a few days following ascent, and they includedizziness ,headache ,shortness of breath , nausea, vomit-

ing, loss of appetite, and insomnia .
High-altitude pulmonary edema (HAPE) is a life-
threatening condition that afflicts a small percentage ofthose who suffer from AMS. In this condition, fluid leaksfrom within the pulmonary blood vessels into the lungtissue. As this fluid begins to accumulate within the lungtissue (pulmonary edema), the individual begins toKEY TERMS
Cerebral —Pertaining to the brain.
Edema —Accumulation of excess fluid in the tis-
sues of the body.

Hypoxemia —Insufficient oxygenation of the blood.
Hypoxia —A deficiency in the amount of oxygen
required for effective ventilation.
Pulmonary —Pertaining to the lungs.
become more and more short of breath. HAPE is known
to afflict all types of individuals, regardless of their levelof physical fitness.
Typically, the individual who suffers from HAPE

ascends quickly to a high altitude and almost immediate-ly develops shortness of breath, a rapid heart rate, acough productive of a large amount of sometimes bloody
sputum, and a rapid rate of breathing. If no medical assis-tance is provided by this point, the patient goes into acoma and dies within a few hours.
High-altitude cerebral edema (HACE), the rarest and

most severe form of altitude sickness, involves cerebraledema, and its mechanism of development is also poorlyunderstood. The symptoms often begin with those ofAMS, but neurologic symptoms such as an altered levelof consciousness, speech abnormalities, severe headache,loss of coordination, hallucinations , and even seizures.
If no intervention is implemented, death is the result.
Diagnosis
The diagnosis for altitude sickness may be made

from the observation of the individual’s symptoms dur-ing travel to higher altitudes.
Treatment
Mild AMS requires no treatment other than an
aspirin or ibuprofen for headache, and avoidance of fur-

ther ascent. Narcotics should be avoided because theymay blunt the respiratory response, making it even moredifficult for the person to breathe deeply and rapidlyenough to compensate for the lower levels of oxygen inthe environment. Oxygen may also be used to alleviatesymptoms of mild AMS.
As for HAPE and HACE, the most important course
of action is descent to a lower altitude as soon as possi-ble. Even a 1,000-2,000 -foot (305–610 m) descent can

GALE ENCYCLOPEDIA OF MEDICINE 2 133Altitude sicknessGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 133

dramatically improve one’s symptoms. If descent is not
possible, oxygen therapy should be started. In addition,dexamethasone (a steroid) has been suggested in order toreduce cerebral edema.
Prognosis
The prognosis for mild AMS is good, if appropriate
measures are taken. As for HAPE and HACE, the prog-nosis depends upon the rapidity and distance of descentand the availability of medical intervention. Descentoften leads to improvement of symptoms, however,recovery times vary among individuals.

mended that they spend at least one night at an interme-diate altitude prior to ascending to higher elevations. Ingeneral, climbers should take at least two days to gofrom sea level to 8,000 feet (2,438 m). After reachingthat point, healthy climbers should generally allow oneday for each additional 2,000 feet (610 m), and one dayof rest should be taken every two or three days. Shouldmild symptoms begin to surface, further ascent should beavoided. If the symptoms are severe, the individualshould

If the symptoms are severe, the individualshould return to a lower altitude. Some reports indicatethat acetazolamide (a diuretic) may be taken beforeascent as a preventative measure for AMS.

Paying attention to diet can also help prevent alti-
tude sickness. Water loss is a problem at higher altitudes,so climbers should drink ample water (enough to pro-duce copious amounts of relatively light-colored or clearurine). Alcohol and large amounts of salt should beavoided. Eating frequent small, high-carbohydratesnacks (for example, fruits, jams and starchy foods) canhelp, especially in the first few days of climbing.
Resources
BOOKS

Resources
BOOKS
Crystal, R. G., ed., et al. The Lung: Scientific Foundations. Lip-
pincott-Raven Publishers, 1997.
Kravis, T. C., C. G. Warner, and L. M. Jacobs Jr., eds. Emer-
gency Medicine. Raven Press, 1993.
Rosen, Peter, ed., et al. Emergency Medicine: Concepts and
Clinical Practice. Mosby Year Book, 1992.
Coote, J. H. “Medicine and Mechanisms in Altitude Sickness.”
Sports Medicine 20 (Sept. 1995): 148-159.
Kapil Gupta, MD
Aluminum hydroxide seeAntacidsAlzheimer’s disease

Alzheimer’s disease (AD) is the most common form
of dementia , a neurologic disease characterized by loss
of mental ability severe enough to interfere with normalactivities of daily living, lasting at least six months, andnot present from birth. AD usually occurs in old age, andis marked by a decline in cognitive functions such asremembering, reasoning, and planning.
A person with AD usually has a gradual decline in

mental functions, often beginning with slight memoryloss, followed by losses in the ability to maintainemployment, to plan and execute familiar tasks, and toreason and exercise judgment. Communication ability,
mood, and personality may also be affected. Most peoplewho have AD die within eight years of their diagnosis,although that interval may be as short as one year or aslong as 20 years. AD is the fourth leading cause of death

in adults after heart disease, cancer , and stroke .
Between two and four million Americans have AD;

that number is expected to grow to as many as 14 million bythe middle of the 21st century as the population as a wholeages. While a small number of people in their 40s and 50sdevelop the disease (called early-onset AD), AD predomi-nantly affects the elderly. AD affects about 3% of all peoplebetween ages 65 and 74, about 19% of those between 75and 84, and about 47% of those over 85. Slightly morewomen than men are affected with AD, but this may bebecause women tend to live longer, and so there

bebecause women tend to live longer, and so there is a higherproportion of women in the most affected age groups.

erable. The annual cost of caring for one AD patient in1998 was estimated as about $18,400 for a patient withmild AD, $30,100 for a patient with moderate AD, and$36,100 for a patient with severe AD. The annual directand indirect costs of caring for AD patients in the UnitedStates was estimated to be as much as $100 billion.Slightly more than half of AD patients are cared for athome, while the remainder are cared for in a variety ofhealth care institutions.
Causes

Causes
The cause or causes of Alzheimer’s disease are
unknown. Some strong leads have been found throughrecent research, however, and these have also given sometheoretical support to several new experimental treatments.
GALE ENCYCLOPEDIA OF MEDICINE 2 134Alzheimer’s diseaseGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 134

the brain that control memory, including the hippocam-pus, which is a structure deep in the deep that controlsshort-term memory. As these neurons in the hippocampusstop functioning, the short-term memory of the personfails, and the ability to perform familiar tasks decreases.Later AD affects the cerebral cortex, particularly the areasresponsible for language and reasoning; this languageskills are lost and the ability to make judgments ischanged. Personality changes occur, which may

ischanged. Personality changes occur, which may includeemotional outbursts, wandering, and agitation. The sever-ity of these changes increases with the progression of thedisease. Eventually many other areas of the brain becomeinvolved, the brain regions affected atrophy (shrink andlose function), and the person with AD becomes bedrid-den, incontinent, helpless, and non-responsive.

of the brain affected by the disease become clogged withtwo abnormal structures, called neurofibrillary tanglesand amyloid plaques. Neurofibrillary tangles are twistedmasses of protein fibers inside nerve cells, or neurons. InAD, tau proteins, which normally help bind and stabilizeparts of neurons, is changed chemically, become twistedand tangled, and no longer can stabilize the neurons.Amyloid plaques consist of insoluble deposits of beta-amyloid (a protein fragment from a larger protein

(a protein fragment from a larger protein calledamyloid precursor protein (APP) mixed with parts of neu-rons and non-nerve cells. Plaques are found in the spacesbetween the nerve cells of the brain. While it is not clearexactly how these structures cause problems, manyresearchers believe that their formation is responsible forthe mental changes of AD, presumably by interferingwith the normal communication between neurons in thebrain and later leading to the death of neurons. As of2000, three

leading to the death of neurons. As of2000, three drugs for the treatment of AD symptoms havebeen approved by the United States Food and DrugAdministration (FDA). They act by increasing the level ofchemical signaling molecules in the brain, known as neu-rotransmitters, to make up for this decreased communica-tion ability. All act by inhibiting the activity of acetyl-cholinesterase, which is an enzyme that breaks downacetylcholine, an important neurotransmitter released byneurons that is

neurotransmitter released byneurons that is necessary for cognitive function. Thesedrugs modestly increase cognition and improve one’sability to perform normal activities of daily living.

What triggers the formation of plaques and tangles
and the development of AD are unknown. AD likelyresults from many interrelated factors, including genetic,environmental, and others not yet identified. Two typesof AD exist: familial AD (FAD), which is a rare autoso-mal dominant inherited disease, and sporadic AD, withno obvious inheritance pattern. AD is also described interms of age at onset, with early on-set AD occurring inpeople younger than 65, and late-onset occurring in those

65 and older. Early on-set AD comprises about 5-10 ofAD cases and affects people aged 30 to 60. Some casesof early on-set AD are inherited and are common in somefamilies. Early-onset AD often progresses faster than themore common late-on-set type.
All FAD, which are relatively uncommon, that have

been identified so far are the early on-set type. As manyas 50% of the FAD cases are known to be caused by threegenes located on three different chromosomes. Somefamilies have mutations in the APP gene located on chro-mosome 21, which causes the production of abnormalAPP protein. Others have mutations in a gene called pre-senilin 1 located on chromosome 14, which causes theproduction of abnormal presenilin 1 protein, and othershave mutations in a similar gene called presenilin 2 locat-ed on

in a similar gene called presenilin 2 locat-ed on chromosome 1, which causes production of abnor-mal presenilin 2. Presenilin 1 may be one of the enzymesthat clips APP into beta-amyloid; it may also be importantin the synaptic connections between brain cells.

cause early on-set FAD also cause late on-set AD, butgenetics does appear to play a role in this more commonform of AD. Discovered by researchers at Duke Univer-sity in the early 1990s, potentially the most importantgenetic link to AD was on chromosome 19. A gene onthis chromosome, called APOE (apolipoprotein E), codesfor a protein involved in transporting lipids into neurons.APOE occurs in at least three forms (alleles), calledAPOE e2, APOE e3, and APOE e4. Each person inheritsone APOE from

and APOE e4. Each person inheritsone APOE from each parent, and therefore can eitherhave one copy of two different forms, or two copies ofone. The relatively rare APOE e2 appears to protect somepeople from AD, as it seems to be associated with alower risk of AD and a later age of onset if AD doesdevelop. APOE e3 is the most common version found inthe general population, and only appears to have a neu-tral role in AD. However, APOE e4 appears to increasethe risk of developing late onset AD with

increasethe risk of developing late onset AD with the inheritanceof one or two copies of APOE e4. Compared to thosewithout APOE e4, people with one copy are about threetimes as likely to develop late-onset AD, and those withtwo copies are almost four times as likely to do so. Hav-ing APOE e4 can also lower the age of onset by as muchas 17 years. However, APOE e4 only increases the risk ofdeveloping AD and does not cause it, as not everyonewith APOE e4 develops AD, and people without it canstill

e4 develops AD, and people without it canstill have the disease. Why APOE e4 increases thechances of developing AD is not known with certainty.However, one theory is that APOE e4 facilitates beta-amyloid buildup in plaques, thus contributing to the low-ering of the age of onset of AD; other theories involveinteractions with cholesterol levels and effects on nerve

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cell death independent of its effects on plaque buildup. In
2000, four new AD-related regions in the human genomewere identified, where one out of several hundred genesin each of these regions may be a risk factor gene for AD.These genes, which are not yet identified, appear to makea contribution to the risk of developing late-onset ADthat is at least as important as APOE e4.
Other non-genetic factors have also been studied in

relation to the causes of AD. Inflammation of the brainmay play a role in development of AD, and use of nons-
teroidal anti-inflammatory drugs (NSAIDs) seems to

reduce the risk of developing AD. Restriction of bloodflow may be part of the problem, perhaps accounting forthe beneficial effects of estrogen, which increases bloodflow in the brain, among its other effects. Highly reactivemolecular fragments called free radicals damage cells ofall kinds, especially brain cells, which have smaller sup-plies of protective antioxidants thought to protect againstfree radical damage. Vitamin E is one such antioxidant,and its use in AD may be of possible

antioxidant,and its use in AD may be of possible theoretical benefit.

disease are still unknown, there are several risk factorsthat increase a person’s likelihood of developing the dis-ease. The most significant one is, of course, age; olderpeople develop AD at much higher rates than youngerones. There is some evidence that strokes and AD may belinked, with small strokes that go undetected clinicallycontributing to the injury of neurons. Blood cholesterollevels may also be important. Scientists have shown thathigh blood cholesterol levels in special breeds of

blood cholesterol levels in special breeds of geneti-cally engineered (transgenic) mice may increase the rateof plaque deposition. There are also parallels betweenAD and other progressive neurodegenerative disordersthat cause dementia, including prion diseases, Parkin-son’s disease, and Huntington’s disease.

also being conducted to learn more about whether and towhat extent early life events, socioeconomic factors, andethnicity have an impact on the development of AD. Forexample, results from one study indicated that rural resi-dence in childhood, along with fewer than six years ofschooling, was associated with increased AD risk. How-ever, the low educational attainment that was identified asa risk factor might be a marker or surrogate for other dele-terious socioeconomic or environmental

other dele-terious socioeconomic or environmental influences inchildhood, thus illustrating the difficulties in interpretingepidemiological findings, due to the complexity of theissues and the large number of variables involved.

Many environmental factors have been suspected of
contributing to AD, but epidemiological population stud-ies have not borne out these links. Among these havebeen pollutants in drinking water, aluminum from com-mercial products, and metal dental fillings. To date, none
of these factors has been shown to cause AD or increaseits likelihood. Further research may yet turn up links toother environmental factors.
Symptoms
The symptoms of Alzheimer’s disease begin gradu-

ally, usually with memory lapses. Occasional memorylapses are of course common to everyone, and do not bythemselves signify any change in cognitive function. Theperson with AD may begin with only the routine sort ofmemory lapse—forgetting where the car keys are—butprogress to more profound or disturbing losses, such asforgetting that he or she can even drive a car. Becominglost or disoriented on a walk around the neighborhoodbecomes more likely as the disease progresses. A personwith AD may

as the disease progresses. A personwith AD may forget the names of family members, orforget what was said at the beginning of a sentence bythe time he hears the end.

ing inability to perform routine tasks, loss of judgment,and personality or behavior changes. Some patients havetrouble sleeping and may suffer from confusion or agita-tion in the evening (“sunsetting” or Sundowner’s Syn-drome). In some cases, people with AD repeat the sameideas, movements, words, or thoughts, a behavior knownas perseveration. In the final stages people may havesevere problems with eating, communicating, and con-trolling their bladder and bowel functions.

The Alzheimer’s Association has developed a list of ten
warning signs of AD. A person with several of these symp-toms should see a physician for a thorough evaluation:
• memory loss that affects job skills
• difficulty performing familiar tasks• problems with language
• disorientation of time and place
• poor or decreased judgment• problems with abstract thinking
• misplacing things
• changes in mood or behavior
• changes in personality
• loss of initiative

Other types of dementia, including some that are
reversible, can cause similar symptoms. It is important forthe person with these symptoms to be evaluated by a pro-fessional who can weigh the possibility that his or hersymptoms may have another cause. Approximately 20% ofthose originally suspected of having AD turn out to havesome other disorder; about half of these cases are treatable.

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Diagnosis
Diagnosis of Alzheimer’s disease is complex, and
may require office visits to several different specialistsover several months before a diagnosis can be made.While a confident provisional diagnosis may be made inmost cases after thorough testing, AD cannot be defini-tively diagnosed until autopsy examination of the brainfor plaques and neurofibrillary tangles.
The diagnosis of AD begins with a thorough physi-

cal exam and complete medical history. Except in thedisease’s earliest stages, accurate history from familymembers or caregivers is essential. Since there are bothprescription and over-the-counter drugs that can causethe same mental changes as AD, a careful review of thepatient’s drug, medicine, and alcohol use is important.AD-like symptoms can also be provoked by other med-ical conditions, including tumors, infection, and demen-tia caused by mild strokes (multi-infarct dementia).These

by mild strokes (multi-infarct dementia).These possibilities must be ruled out as well throughappropriate blood and urine tests, brain magnetic reso-

nance imaging (MRI), positron emission tomography
(PET ) or single photon emission computed tomography
(SPECT) scans, tests of the brain’s electrical activity(electroencephalographs or EEGs), or other tests. Severaltypes of oral and written tests are used to aid in the ADdiagnosis and to follow its progression, including tests ofmental status, functional abilities, memory, and concen-tration. Still, the neurologic exam is normal in most
patients in early stages.

One of the most important parts of the diagnostic
process is to evaluate the patient for depression anddelirium , since each of these can be present with AD,

or may be mistaken for it. (Delirium involves adecreased consciousness or awareness of one’s environ-ment.) Depression and memory loss are both commonin the elderly, and the combination of the two can oftenbe mistaken for AD. Depression can be treated withdrugs, although some antidepressants can worsendementia if it is present, further complicating both diag-nosis and treatment.
An early and accurate diagnosis of AD is important

in developing strategies for managing symptoms and forhelping patients and their families planning for the futureand pursuing care options while the patient can still takepart in the decision-making process.
A genetic test for the APOE e4 gene is available, but

is not used for diagnosis, since possessing even twocopies does not ensure that a person will develop AD. Inaddition, access to genetic information could affect theinsurability of a patient if disclosed, and also affectemployment status and legal rights.Treatment
Alzheimer’s disease is presently incurable, so there-

fore the mainstay of treatment for a person with AD isgood nursing care, providing both physical and emotion-al support for a person who is gradually able to do lessand less for himself, and whose behavior is becomingmore and more erratic. Modifications of the home toincrease safety and security are often necessary. Thecaregiver also needs support to prevent anger, despair,and burnout from becoming overwhelming. Becomingfamiliar with the issues likely to lie ahead, and consider-ing the

issues likely to lie ahead, and consider-ing the appropriate financial and legal issues early on,can help both the patient and family cope with the diffi-cult process of the disease. Regular medical care by apractitioner with a non-defeatist attitude toward AD isimportant so that illnesses such as urinary or respiratoryinfections can be diagnosed and treated properly, ratherthan being incorrectly attributed to the inevitable declineseen in AD.

People with AD are also often depressed or anxious,
and may suffer from sleeplessness, poor nutrition , and

general poor health. Each of these conditions is treatableto some degree. It is important for the person with AD toeat well and continue to exercise. Professional advicefrom a nutritionist may be useful to provide healthy,easy-to-prepare meals. Finger foods may be preferable tothose requiring utensils to be eaten. Regular exercise(supervised if necessary for safety) promotes overallhealth. A calm, structured environment with simple ori-entation aids (such as calendars and clocks) may

aids (such as calendars and clocks) may reduceanxiety and increase safety. Other psychiatric symptoms,

such as depression, anxiety, hallucinations (seeing or
hearing things that aren’t there), and delusions (false
beliefs) may be treated with drugs if necessary.
GALE ENCYCLOPEDIA OF MEDICINE 2 137Alzheimer’s disease
Diseased tissue from the brain of an Alzheimer’s patient
showing senile plaques within the brain’s gray matter. (Pho-
tograph by Cecil Fox, Photo Researchers, Inc. Reproduced bypermission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 137

donepezil hydrochloride (Aricept), and rivastigmine(Exelon)—have been approved by the FDA for its treat-ment. Tacrine has been shown to be effective for improv-ing memory skills, but only in patients with mild-to-mod-erate AD, and even then in less than half of those who takeit. Its beneficial effects are usually mild and temporary, butit may delay the need for nursing home admission. Themost significant side effect is an increase in a liver enzymeknown as alanine aminotransferase, or ALT.

enzymeknown as alanine aminotransferase, or ALT. Patients tak-ing tacrine must have a weekly blood test to monitor theirALT levels. Other frequent side effects include nausea,vomiting, diarrhea , abdominal pain ,indigestion , and

skin rash. The cost of tacrine was about $125 per month inearly 1998, with additional costs for the weekly bloodmonitoring. Despite its high cost, tacrine appears to becost-effective for those who respond to it, since it maydecrease the number of months a patient needs nursingcare. Donepezil is the drug most commonly used to treatmild to moderate symptoms of AD, although it only helpssome patients for periods of time ranging from months toabout two years. Donepezil has two advantages

toabout two years. Donepezil has two advantages overtacrine: it has fewer side effects, and it can be given oncedaily rather than three times daily. Donepezil does notappear to affect liver enzymes, and therefore does notrequire weekly blood tests. The frequency of abdominalside effects is also lower. The monthly cost is approxi-mately the same. Rivastigmine, approved for use in Aprilof 2000, has been shown to improve the ability of patientsto carry out daily activities, such as eating and

carry out daily activities, such as eating and dressing,decrease behavioral symptoms such as delusions and agi-tation, and improve cognitive functions such as thinking,memory, and speaking. The cost is similar to those of theother two drugs. However, none of these three drugs stopsor reverses the progression of AD.

Estrogen, the female sex hormone, is widely pre-
scribed for post-menopausal women to prevent osteo-
porosis . Several preliminary studies have shown that
women taking estrogen have lower rates of AD, and thosewho develop AD have a slower progression and lesssevere symptoms.However, estrogen does not appear tohave a beneficial effect on women who already have AD.
Preliminary studies have also suggested a reduced

risk for developing AD in older people who regularly usenonsteroidal anti-inflammatory drugs (NSAIDs), includ-ing aspirin , ibuprofen, and naproxen, although not aceta-
minophen.Inflammation of the brain is a distinctive char-acteristic of AD, but whether it is a cause or an effect ofthe disease is not yet known.
Antioxidants, which act to inhibit and protect

against oxidative damage caused by free radicals, havebeen shown to inhibit toxic effects of beta-amyloid in tis-
sue culture. Therefore, research is being conducted to seewhether antioxidants may delay or prevent AD.
Another antioxidant, vitamin E, is also thought to
delay AD onset. It is not yet clear whether this is due tothe specific action of vitamin E on brain cells, or to anincrease in the overall health of those taking it.

Drugs such as antidepressants, anti-psychotics, and
sedatives are used to treat the behavioral symptoms(agitation, aggression, wandering, and sleep disorders )
of AD. Research is being conducted to search for bettertreatments, including non-drug approaches for ADpatients.
Nursing care and safety
The person with Alzheimer’s disease will gradually

lose the ability to dress, groom, feed, bathe, or use thetoilet by himself; in the later stages of the disease, hemay be unable to move or speak. In addition, the per-son’s behavior becomes increasing erratic. A tendency towander may make it difficult to leave him unattended foreven a few minutes and make even the home a potentiallydangerous place. In addition, some patients may exhibitinappropriate sexual behaviors.
The nursing care required for a person with AD is

well within the abilities of most people to learn. The dif-ficulty for many caregivers comes in the constant butunpredictable nature of the demands put on them. Inaddition, the personality changes undergone by a personwith AD can be heartbreaking for family members, as aloved one deteriorates, seeming to become a differentperson. Not all AD patients develop negative behaviors:some become quite gentle, and spend increasing amountsof time in dreamlike states.

symptoms of AD. Mismatched clothing, unkempt hair,and decreased interest in personal hygiene become morecommon. Caregivers, especially spouses, may find thesechanges socially embarrassing and difficult to cope with.The caregiver will usually need to spend increasingamounts of time for grooming to compensate for the lossof attention from the patient, although some adjustmentof expectations (while maintaining cleanliness) is oftenneeded as the disease progresses.

Proper nutrition is important for a person with AD,
and may require assisted feeding early on, to make sure theperson is taking in enough nutrients. Later on, as move-ment and swallowing become difficult, a feeding tube maybe placed into the stomach through the abdominal wall. Afeeding tube requires more attention, but is generally easyto care for if the patient is not resistant to its use.
GALE ENCYCLOPEDIA OF MEDICINE 2 138Alzheimer’s diseaseGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 138

For many caregivers, incontinence becomes the
most difficult problem to deal with at home, and is aprincipal reason for pursuing nursing home care. In theearly stages, limiting fluid intake and increasing the fre-quency of toileting can help. Careful attention to hygieneis important to prevent skin irritation and infection fromsoiled clothing.
Persons with dementia must deal with six basic safe-

ty concerns: injury from falls, injury from ingesting dan-gerous substances, leaving the home and getting lost,injury to self or others from sharp objects, fire or burns ,

and the inability to respond rapidly to crisis situations. Inall cases, a person diagnosed with AD should no longerbe allowed to drive, because of the increased potentialfor accidents and the increased likelihood of wanderingvery far from home while disoriented. In the home, sim-ple measures such as grab bars in the bathroom, bed railson the bed, and easily negotiable passageways can great-ly increase safety. Electrical appliances should beunplugged and put away when not in use, and

beunplugged and put away when not in use, and matches,lighters, knives, or weapons should be stored safely outof reach. The hot water heater temperature may be setlower to prevent accidental scalding. A list of emergencynumbers, including the poison control center and thehospital emergency room, should be posted by thephone. As the disease progresses, caregivers need to peri-odically reevaluate the physical safety of the home andintroduce new strategies for continued safety.

Care for the caregiver
Family members or others caring for a person with

AD have an extremely difficult and stressful job, whichbecomes harder as the disease progresses. Dementiacaregivers spend significantly more time on caregivingthan do people providing care for those with other typesof illnesses. This type of caregiving also has a greaterimpact in terms of employment complications, caregiverstrain, mental and physical health problems, time forleisure and other family members, and family conflictthan do other types of caregiving. It is common for ADcaregivers to

of caregiving. It is common for ADcaregivers to develop feelings of anger, resentment, guilt,and hopelessness, in addition to the sorrow they feel fortheir loved one and for themselves. Depression is anextremely common consequence of being a full-timecaregiver for a person with AD. Support groups are animportant way to deal with the stress of caregiving.

Becoming a member of an AD caregivers’ support groupcan be one of the most important things a family memberdoes, not only for him or herself, but for the person withAD as well. The location and contact numbers for ADcaregiver support groups are available from theAlzheimer’s Association; they may also be availablethrough a local social service agency, the patient’s physi-cian, or pharmaceutical companies that manufacture the

drugs used to treat AD. Medical treatment for depressionmay be an important adjunct to group support.
Outside help, nursing homes, and governmental
assistance
Most families eventually need outside help to relieve

some of the burden of around-the-clock care for a personwith AD. Personal care assistants, either volunteer orpaid, may be available through local social service agen-cies. Adult daycare facilities are becoming increasinglycommon. Meal delivery, shopping assistance, or respitecare may be available as well.
Providing the total care required by a person with

late-stage AD can become an overwhelming burden for afamily, even with outside help. At this stage, many fami-lies consider nursing home care. This decision is often oneof the most difficult for the family, since it is often seen asan abandonment of the loved one and a failure of the fami-ly. Careful counseling with a sympathetic physician, cler-gy, or other trusted adviser may ease the difficulties of thistransition. Selecting a nursing home may require a difficultbalancing of cost, services,

require a difficultbalancing of cost, services, location, and availability.Keeping the entire family involved in the decision mayhelp prevent further stress from developing later on.

cost of caring for a person with AD, including SocialSecurity Disability, Medicare, and Supplemental Securi-ty Income. Each of these programs may provide someassistance for care, medication, or other costs, but noneof them will pay for nursing home care indefinitely.Medicaid is a state-funded program that may provide forsome or all of the cost of nursing home care, althoughthere are important restrictions. Details of the benefitsand eligibility requirements of these programs are avail-able

requirements of these programs are avail-able through the local Social Security or Medicaid office,or from local social service agencies.

Private long-term care insurance, special “reverse
mortgages,” viatical insurance, and other financial devicesare other ways of paying for care for those with the appro-priate financial situations. Further information on theseoptions may be available through resources listed below.
Several substances are currently being tested for

their ability to slow the progress of Alzheimer’s disease.These include acetylcarnitine, a supplement that acts onthe cellular energy structures known as mitochondria.Ginkgo extract, derived from the leaves of the Ginkgo
biloba tree, appears to have antioxidant as well as anti-
inflammatory and anticoagulant properties. Ginkgo
GALE ENCYCLOPEDIA OF MEDICINE 2 139Alzheimer’s diseaseGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 139

widely prescribed in Europe for treatment of circulatoryproblems. A 1997 study of patients with dementiaseemed to show that ginkgo extract could improve theirsymptoms, though the study was criticized for certainflaws in its method.Large scale follow-up studies arebeing conducted to determine whether Ginkgo extractcan prevent or delay the development of AD. Ginkgoextract is available in many health food or nutritionalsupplement stores. Some alternative practitioners alsoadvise people with AD to

practitioners alsoadvise people with AD to take supplements of phos-phatidylcholine, vitamin B

12, gotu kola, ginseng, St.
John’s Wort, rosemary, saiko-keishi-to-shakuyaku (AJapanese herbal mixture), and folic acid .
Prognosis
While Alzheimer’s disease may not be the direct
cause of death, the generally poorer health of a personwith AD increases the risk of life-threatening infection,including pneumonia . In addition, other diseases com-

mon in old age—cancer, stroke, and heart disease—maylead to more severe consequences in a person with AD.On average, people with AD live eight years past theirdiagnosis, with a range from one to 20 years.
There is currently no sure way to prevent Alzheimer’s
disease, although some of the drug treatments discussedabove may eventually be proven to reduce the risk ofdeveloping the disease. The most likely current candidatesare estrogen, NSAIDs, vitamin E, and ginkgo biloba ,

although this list may grow or shrink with further research.KEY TERMS
Acetylcholine— One of the substances in the body
that helps transmit nerve impulses.
Dementia —Impaired intellectual function that
interferes with normal social and work activities.
Ginkgo —An herb from the Ginkgo biloba tree that
some alternative practitioners recommend for theprevention and treatment of AD.
Neurofibrillary tangle— Twisted masses of protein
inside nerve cells that develop in the brains ofpeople with AD.

Senile plaque— Structures composed of parts of
neurons surrounding brain proteins called beta-amyloid deposits and found in the brains of peo-ple with AD.Research on the prevention of AD is focusing on

blocking the production of amyloid in the brain as wellas breaking down beta-amyloid once it is released fromcells but before it has a chance to aggregate into insolu-ble plaques. There are also promising studies being con-ducted to develop an AD vaccine, where immuneresponses may result in the elimination of the formationof amyloid plaques.
The Alzheimer’s Disease Research Centers (ADCs)

program promotes research, training and education,technology transfer, and multicenter and cooperativestudies in AD, other dementias, and normal brain aging .

Each ADC enrolls and performs studies on AD patientsand healthy older people. Persons can participate inresearch protocols and clinical drug trials at these cen-ters. Data from the ADCs as well as from other sourcesare coordinated and made available for use byresearchers at the National Alzheimer’s CoordinatingCenter, established in 1999.
Resources
BOOKS
Cohen, Donna, and Carl Eisdorfer. The Loss of Self: A Family

Resource for the Care of Alzheimer’s Disease and RelatedDisorders, Revised Edition. New York: W.W. Norton &
Company, 2001.
Cohen, Elwood. Alzheimer’s Disease: Prevention, Interven-
tion, and Treatment. Los Angeles: Keats Publishing, 1999.
Geldmacher, David S. Contemporary Diagnosis and Manage-
ment of Alzheimer’s Disease. Newtown, PA: Associates in
Medical Marketing Co., Inc., 2001.
Gruetzner, Howard. Alzheimer’s: A Caregiver’s Guide and
Sourcebook, 3rd Edition. New York: John Wiley & Sons,

2001.
Mace, Nancy L., and Peter V . Rabins. The 36-Hour Day: A
Family Guide for Caring with Persons with AlzheimerDisease, Related Dementing Illnesses, and Memory Lossin Later Life. New York: Warner Books, 2001.
Teitel, Rosette, and Marc L. Gordon. The Handholder’s Hand-
book: A Guide for Caregivers of Alzheimer’s and otherDementias. New Brunswick, NJ: Rutgers University
Gitlin, L.N., and M. Corcoran. “Making Homes Safer: Envi-

ronmental Adaptations for People with Dementia.”Alzheimer’s Care Quarterly 1 (2000): 50-58.
Helmuth, L. “Alzheimer’s Congress: Further Progress on a B-
Amyloid Vaccine.” Science 289, No. 5476 (2000): 375.
Alzheimer’s Association. 919 North Michigan Ave., Suite 1000
Chicago, IL 60611. (800) 272-3900. <http://www.alz.org>.
Alzheimer’s Disease Education and Referral Center. P.O. Box

8250, Silver Spring, MD. (800) 438-4380.Fax: (301) 495-3334. adear@alzheimers.org. <http://www.alzheimers.org>.
GALE ENCYCLOPEDIA OF MEDICINE 2 140Alzheimer’s diseaseGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 140

Alzheimer’s Research Foundation. <http:// www. alzheimers-
research.org>.
OTHER
National Institute on Aging, National Institutes of Health.
2000: Progress Report on Alzheimer’s Disease - Takingthe Next Steps. NIH Publication No. 4859 (2000). <http://
www.alzheimers.org/pubs/prog00.htm#References>.
Alzheimer’s Disease Books and Videotapes. <http://www.
alzheimersbooks.com>.
Judith Sims
Ambiguous genitals seeIntersex states
Amblyopia
Amblyopia is an uncorrectable decrease in vision in

one or both eyes with no apparent structural abnormalityseen to explain it. It is a diagnosis of exclusion, meaningthat when a decrease in vision is detected, other causesmust be ruled out. Once no other cause is found, ambly-opia is the diagnosis. Generally, a difference of two linesor more (on an eye-chart test of visual acuity) betweenthe two eyes or a best corrected vision of 20/30 or worsewould be defined as amblyopia. For example, if someonehas 20/20 vision with the right eye and only

20/20 vision with the right eye and only 20/40 withthe left, and the left eye cannot achieve better vision withcorrective lenses, the left eye is said to be amblyopic.

describe amblyopia because the eye with poorer visiondoesn’t seem to be doing its job of seeing. Amblyopia isthe most common cause of impaired vision in children,affecting nearly three out of every 100 people or 2-4%of the population. Vision is a combination of the clarityof the images of the eyes (visual acuity) and the process-ing of those images by the brain. If the images producedby the two eyes are substantially different, the brain maynot be able to fuse the images. Instead of seeing two

be able to fuse the images. Instead of seeing two dif-ferent images or double vision (diplopia), the brain sup-presses the blurrier image. This suppression can lead toamblyopia. During the first few years of life, preferringone eye over the other may lead to poor visual develop-ment in the blurrier eye.

Some of the major causes of amblyopia are as follows:•Strabismus . A misalignment of the eyes (strabismus) is
the most common cause of functional amblyopia. Thetwo eyes are looking in two different directions at thesame time. The brain is sent two different images andthis causes confusion. Images from the misaligned or“crossed” eye are turned off to avoid double vision.
• Anisometropia. This is another type of functional

amblyopia. In this case, there is a difference of refrac-tive states between the two eyes (in other words, a dif-ference of prescriptions between the two eyes). Forexample, one eye may be more nearsighted than theother eye, or one eye may be farsighted and the othereye nearsighted. Because the brain cannot fuse the twodissimilar images, the brain will suppress the blurrierimage, causing the eye to become amblyopic.
• Cataract. Clouding of the lens of the eye will cause the

image to be blurrier than the other eye. The brain“prefers” the clearer image. The eye with the cataractmay become amblyopic.
•Ptosis . This is the drooping of the upper eyelid. If light
cannot enter the eye because of the drooping lid, theeye is essentially not being used. This can lead toamblyopia.
•Nutrition . A type of organic amblyopia in which nutri-

tional deficiencies or chemical toxicity may result inamblyopia. Alcohol, tobacco, or a deficiency in the Bvitamins may result in toxic amblyopia.
• Heredity. Amblyopia can run in families.
Barring the presence of strabismus or ptosis, chil-

dren may or may not show signs of amblyopia. Childrenmay hold their heads at an angle while trying to favor theeye with normal vision. They may have trouble seeing orreaching for things when approached from the side of theamblyopic eye. Parents should see if one side of
GALE ENCYCLOPEDIA OF MEDICINE 2 141Amblyopia
Man with a lazy eye. (Custom Medical Stock Photo. Repro-
duced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 141

approach is preferred by the child or infant. If an infant’s
good eye is covered, the child may cry.
Diagnosis
Because children with outwardly normal eyes may
have amblyopia, it is important to have regular visionscreenings performed for all children. While there issome controversy regarding the age children should havetheir first vision examination, their eyes can, in actuality,be examined at any age, even at one day of life.
Some recommend that children have their vision

checked by their pediatrician, family physician, ophthal-mologist, or optometrist at or before six months of age.Others recommend testing by at least the child’s fourthbirthday. There may be a “critical period” in the develop-ment of vision, and amblyopia may not be treatable afterage eight or nine. The earlier amblyopia is found, the betterthe possible outcome. Most physicians test vision as part ofa child’s medical examination. If there is any sign of an eyeproblem, they may refer a child to

sign of an eyeproblem, they may refer a child to an eye specialist.

measure the refractive status of the eyes. This can helpdetermine anisometropia. In retinoscopy, a hand-heldinstrument is used to shine a light in the child’s (orinfant’s) eyes. Using hand-held lenses, a rough prescrip-tion can be obtained. Visual acuity can be determinedusing a variety of methods. Many different eye charts areavailable (e.g., tumbling E, pictures, or letters). In ambly-opia, single letters are easier to recognize than when aKEY TERMS

Anisometropia —An eye condition in which there
is an inequality of vision between the two eyes.There may be unequal amounts of nearsighted-ness, farsightedness, or astigmatism, so that oneeye will be in focus while the other will not.
Cataract —Cloudiness of the eye’s natural lens.
Occulsion therapy —A type of treatment for ambly-
opia in which the good eye is patched for a periodof time. This forces the weaker eye to be used.
Strabismus —A condition in which the eyes are

misaligned and point in different directions. Oneeye may look straight ahead, while the other turnsinward, outward, upward, or downward. This isalso called crossed-eyes.
Visual acuity —Acuity is the acuteness or sharp-
ness of vision.whole line is shown. This is called the “crowding effect”

and helps in diagnosing amblyopia. Neutral density filtersmay also be held over the eye to aid in the diagnosis.Sometimes visual fields to determine defects in the areaof vision will be performed. Color vision testing may alsobe performed. Again, it must be emphasized that ambly-opia is a diagnosis of exclusion. Visual or life-threateningproblems can also cause a decrease in vision. An exami-nation of the eyes and visual system is very importantwhen there is an unexplained decrease in vision.

The primary treatment for amblyopia is occlusion
therapy. It is important to alternate patching the good eye(forcing the amblyopic eye to work) and the amblyopiceye. If the good eye is constantly patched, it too maybecome amblyopic because of disuse. The treatment planshould be discussed with the doctor to fully understandhow long the patch will be on. When patched, eye exercis-es may be prescribed to force the amblyopic eye to focusand work. This is called vision therapy or vision training

(eye exercises). Even after vision has been restored in theweak eye, part-time patching may be required over a peri-od of years to maintain the improvement.
While patching is necessary to get the amblyopic

eye to work, it is just as important to correct the reasonfor the amblyopia. Glasses may also be worn if there areerrors in refraction. Surgery or vision training may benecessary in the case of strabismus. Better nutrition isindicated in some toxic amblyopias. Occasionally,amblyopia is treated by blurring the vision in the goodeye with eye drops or lenses to force the child to use theamblyopic eye.
Prognosis

Prognosis
The younger the person, the better the chance for
improvement with occlusion and vision therapy. Howev-er, treatment may be successful in older children—evenadults. Success in the treatment of amblyopia alsodepends upon how severe the amblyopia is, the specifictype of amblyopia, and patient compliance. It is impor-tant to diagnose and treat amblyopia early because sig-nificant vision loss can occur if left untreated. The bestoutcomes result from early diagnosis and treatment.

To protect their child’s vision, parents must be aware
of amblyopia as a potential problem. This awareness mayencourage parents to take young children for vision examsearly on in life—certainly before school age. Proper nutri-tion is important in the avoidance of toxic amblyopia.
GALE ENCYCLOPEDIA OF MEDICINE 2 142AmblyopiaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 142

Resources
BOOKS
D’Alonzo, T. L., O.D. Your Eyes! A Comprehensive Look at the
Understanding and Treatment of Vision Problems. Clifton
Heights, PA: Avanti, 1992.
Newell, Frank W. Ophthalmology: Principles and Concepts.
8th ed. St. Louis: Mosby, 1996.
American Academy of Ophthalmology. 655 Beach Street, P.O.
Box 7424, San Francisco, CA 94120-7424. <http://www.eyenet.org>.
American Optometric Association. 243 North Lindbergh Blvd.,

St. Louis, MO 63141. (314) 991-4100. <http://www.aoanet.org>.
Lorraine Steefel, RN
Amebiasis
Amebiasis is an infectious disease caused by a para-
sitic one-celled microorganism (protozoan) called Enta-
moeba histolytica . Persons with amebiasis may experi-
ence a wide range of symptoms, including diarrhea ,
fever , and cramps. The disease may also affect the
intestines, liver, or other parts of the body.
Amebiasis, also known as amebic dysentery, is one

of the most common parasitic diseases occurring inhumans, with an estimated 500 million new cases eachyear. It occurs most frequently in tropical and subtropicalareas where living conditions are crowded, with inade-quate sanitation. Although most cases of amebiasis occurin persons who carry the disease but do not exhibit anysymptoms (asymptomatic), as many as 100,000 peopledie of amebiasis each year. In the United States, between1 and 5% of the general population will develop amebia-sis in any

general population will develop amebia-sis in any given year, while male homosexuals, migrantworkers, institutionalized people, and recent immigrantsdevelop amebiasis at a higher rate.

Human beings are the only known host of the amebi-
asis organism, and all groups of people, regardless of ageor sex, can become affected. Amebiasis is primarilyspread in food and water that has been contaminated byhuman feces but is also spread by person-to-person con-tact. The number of cases is typically limited, but region-al outbreaks can occur in areas where human feces areused as fertilizer for crops, or in cities with water sup-plies contaminated with human feces.Causes and symptoms

Recently, it has been discovered that persons with
symptom-causing amebiasis are infected with Entamoe-
ba histolytica , and those individuals who exhibit no
symptoms are actually infected with an almost identical-looking ameba called Entamoeba dispar . During their

life cycles, the amebas exist in two very different forms:the infective cyst or capsuled form, which cannot movebut can survive outside the human body because of itsprotective covering, and the disease-producing form, thetrophozoite, which although capable of moving, cannotsurvive once excreted in the feces and, therefore, cannotinfect others. The disease is most commonly transmittedwhen a person eats food or drinks water containing E.
histolytica cysts from human feces. In the digestive tract

the cysts are transported to the intestine where the wallsof the cysts are broken open by digestive secretions,releasing the mobile trophozoites. Once released withinthe intestine, the trophozoites multiply by feeding onintestinal bacteria or by invading the lining of the largeintestine. Within the lining of the large intestine, thetrophozoites secrete a substance that destroys intestinaltissue and creates a distinctive bottle-shaped sore (ulcer).The trophozoites may remain inside the

(ulcer).The trophozoites may remain inside the intestine, in theintestinal wall, or may break through the intestinal walland be carried by the blood to the liver, lungs, brain, orother organs. Trophozoites that remain in the intestineseventually form new cysts that are carried through thedigestive tract and excreted in the feces. Under favorabletemperature and humidity conditions, the cysts can sur-vive in soil or water for weeks to months, ready to beginthe cycle again.

Although 90% of cases of amebiasis in the United
States are mild, pregnant women, children under twoyears of age, the elderly, malnourished individuals, and
GALE ENCYCLOPEDIA OF MEDICINE 2 143Amebiasis
A micrograph of Entameoba histolytica, a parasitic amoeba
which invades and destroys the tissues of the intestines,causing amebiasis and ulceration to the intestinal wall.(Photo Researchers, Inc. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 143

people whose immune systems may be compressed, such
as cancer or AIDS patients and those individuals taking
prescription medications that suppress the immune sys-tem, are at a greater risk for developing a severe infection.
The signs and symptoms of amebiasis vary accord-
ing to the location and severity of the infection and areclassified as follows:
Intestinal amebiasis
Intestinal amebiasis can be subdivided into several
categories:
ASYMPTOMATIC INFECTION. Most persons with

amebiasis have no noticeable symptoms. Even thoughthese individuals may not feel ill, they are still capable ofinfecting others by person-to-person contact or by conta-minating food or water with cysts that others may ingest,for example, by preparing food with unwashed hands.
CHRONIC NON-DYSENTERIC INFECTION. Individu-

als may experience symptoms over a long period of timeduring a chronic amebiasis infection and experiencerecurrent episodes of diarrhea that last from one to fourweeks and recur over a period of years. These patientsmay also suffer from abdominal cramps, fatigue , and
weight loss.
AMEBIC DYSENTERY. In severe cases of intestinal

amebiasis, the organism invades the lining of the intes-tine, producing sores (ulcers), bloody diarrhea, severeabdominal cramps, vomiting, chills, and fevers as high as104-105°F (40-40.6°C). In addition, a case of acute ame-bic dysentery may cause complications, includinginflammation of the appendix ( appendicitis ), a tear in
the intestinal wall (perforation), or a sudden, severeinflammation of the colon (fulminating colitis).

AMEBOMA. An ameboma is a mass of tissue in the
bowel that is formed by the amebiasis organism. It canresult from either chronic intestinal infection or acuteamebic dysentery. Amebomas may produce symptomsthat mimic cancer or other intestinal diseases.
PERIANAL ULCERS. Intestinal amebiasis may pro-
duce skin infections in the area around the patient’s anus(perianal). These ulcerated areas have a “punched-out”appearance and are painful to the touch.
Extraintestinal amebiasis

Extraintestinal amebiasis accounts for approximate-
ly 10% of all reported amebiasis cases and includes allforms of the disease that affect other organs.
The most common form of extraintestinal amebiasis
is amebic abscess of the liver. In the United States, ame-bic liver abscesses occur most frequently in young His-
panic adults. An amebic liver abscess can result fromdirect infection of the liver by E. histolytica or as a com-

plication of intestinal amebiasis. Patients with an amebicabscess of the liver complain of pain in the chest or
abdomen, fever, nausea, and tenderness on the right sidedirectly above the liver.
Other forms of extraintestinal amebiasis, though
rare, include infections of the lungs, chest cavity, brain,or genitals. These are extremely serious and have a rela-tively high mortality rate.
Diagnosis
Diagnosis of amebiasis is complicated, partly

because the disease can affect several areas of the bodyand can range from exhibiting few, if any, symptoms tobeing severe, or even life-threatening. In most cases, aphysician will consider a diagnosis of amebiasis when apatient has a combination of symptoms, in particular,diarrhea and a possible history of recent exposure toamebiasis through travel, contact with infected persons,or anal intercourse.
It is vital to distinguish between amebiasis and

another disease, inflammatory bowel disease (IBD) thatproduces similar symptoms because, if diagnosed incor-rectly, drugs that are given to treat IBD can encourage thegrowth and spread of the amebiasis organism. Because ofthe serious consequences of misdiagnosis, potential casesof IBD must be confirmed with multiple stool samplesand blood tests, and a procedure involving a visualinspection of the intestinal wall using a thin lighted, tubu-lar instrument ( sigmoidoscopy ) to rule out amebiasis.

A diagnosis of amebiasis may be confirmed by one
or more tests, depending on the location of the disease.
Stool examination
This test involves microscopically examining a stool
sample for the presence of cysts and/or trophozoites of E.
histolytica and not one of the many other intestinal ame-

bas that are often found but that do not cause disease. Aseries of three stool tests is approximately 90% accuratein confirming a diagnosis of amebic dysentery. Unfortu-nately, however, the stool test is not useful in diagnosingamebomas or extraintestinal infections.
Sigmoidoscopy
Sigmoidoscopy is a useful diagnostic procedure in

which a thin, flexible, lighted instrument, called a sig-moidoscope, is used to visually examine the lower part ofthe large intestine for amebic ulcers and take tissue orfluid samples from the intestinal lining.
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Blood tests
Although tests designed to detect a specific protein

produced in response to amebiasis infection (antibody) arecapable of detecting only about 10% of cases of mild ame-biasis, these tests are extremely useful in confirming 95%of dysentery diagnoses and 98% of liver abscess diag-noses. Blood serum will usually test positive for antibodywithin a week of symptom onset. Blood testing, however,cannot always distinguish between a current or past infec-tion since the antibodies may be detectable in the blood foras long as 10 years following initial

Imaging studies
A number of sophisticated imaging techniques, such
as computed tomography scans (CT), magnetic reso-
nance imaging (MRI), and ultrasound, can be used to
determine whether a liver abscess is present. Once locat-ed, a physician may then use a fine needle to withdraw asample of tissue to determine whether the abscess isindeed caused by an amebic infection.
Treatment
Asymptomatic or mild cases of amebiasis may

require no treatment. However, because of the potentialfor disease spread, amebiasis is generally treated with amedication to kill the disease-causing amebas. Moresevere cases of amebic dysentery are additionally treatedby replacing lost fluid and blood. Patients with an ame-bic liver abscess will also require hospitalization and bedrest. For those cases of extraintestinal amebiasis, treat-ment can be complicated because different drugs may berequired to eliminate the parasite, based on the

to eliminate the parasite, based on the locationof the infection within the body. Drugs used to treat ame-biasis, called amebicides, are divided into two categories:

Luminal amebicides
These drugs get their name because they act on
organisms within the inner cavity (lumen) of the bowel.They include diloxanide furoate, iodoquinol, metronida-zole, and paromomycin.
Tissue amebicides
Tissue amebicides are used to treat infections in the

liver and other body tissues and include emetine, dehy-droemetine, metronidazole, and chloroquine. Becausethese drugs have potentially serious side effects, patientsgiven emetine or dehydroemetine require bed rest andheart monitoring. Chloroquine has been found to be themost useful drug for treating amebic liver abscess.Patients taking metronidazole must avoid alcoholbecause the drug-alcohol combination causes nausea,vomiting, and headache .KEY TERMS

Ameboma —A mass of tissue that can develop on
the wall of the colon in response to amebic infec-tion.
Appendicitis —Condition characterized by the
rapid inflammation of the appendix, a part of theintestine.
Asymptomatic —Persons who carry a disease and

are usually capable of transmitting the disease butwho do not exhibit symptoms of the disease aresaid to be asymptomatic.
Dysentery —Intestinal infection marked by diar-
rhea containing blood and mucus.
Fulminating colitis —A potentially fatal complica-
tion of amebic dysentery marked by sudden andsevere inflammation of the intestinal lining, severebleeding or hemorrhaging, and massive sheddingof dead tissue.

Inflammatory bowel disease (IBD) —Disease in
which the lining of the intestine becomes inflamed.
Lumen —The inner cavity or canal of a tube-
shaped organ, such as the bowel.
organism that is eukaryotic and, therefore, differ-ent from bacteria (prokaryotic).
Most patients are given a combination of luminal and

tissue amebicides over a treatment period of seven to tendays. Follow-up care includes periodic stool examinationsbeginning two to four weeks after the end of medicationtreatment to check the effectiveness of drug therapy.
Prognosis
The prognosis depends on the location of the infection

and the patient’s general health prior to infection. The prog-nosis is generally good, although the mortality rate is high-er for patients with ameboma, perforation of the bowel, andliver infection. Patients who develop fulminant colitis havethe most serious prognosis, with over 50% mortality.
There are no immunization procedures or medica-
tions that can be taken prior to potential exposure to pre-

GALE ENCYCLOPEDIA OF MEDICINE 2 145AmebiasisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 145

vent amebiasis. Moreover, people who have had the dis-
ease can become reinfected. Prevention requires effectivepersonal and community hygiene.
Specific safeguards include the following:
• Purification of drinking water. Water can be purified by
filtering, boiling, or treatment with iodine.
• Proper food handling. Measures include protecting

food from contamination by flies, cooking food proper-ly, washing one’s hands after using the bathroom andbefore cooking or eating, and avoiding foods that can-not be cooked or peeled when traveling in countrieswith high rates of amebiasis.
• Careful disposal of human feces.
• Monitoring the contacts of amebiasis patients. The
stools of family members and sexual partners of infect-ed persons should be tested for the presence of cysts ortrophozoites.
Resources
BOOKS

Resources
BOOKS
Ackers, John P. “Amebiasis.” In Encyclopedia of Immunology.
V ol. 3. Ed. Ivan M. Roitt and Peter J. Delves. London:Academic Press, 1992.
Friedman, Lawrence S. “Liver, Biliary Tract, & Pancreas.” In
Current Medical Diagnosis and Treatment, 1998. 37th ed.
Ed. Stephen McPhee, et al. Stamford: Appleton & Lange,1997.
Goldsmith, Robert S. “Infectious Diseases: Protozoal &
Helminthic.” In Current Medical Diagnosis and Treat-
ment, 1998. 37th ed. Ed. Stephen McPhee, et al. Stam-

Hasbun, Rodrigo, and Frank J. Bia. “Amebiasis.” In Conn’s
Current Therapy, 1996 , ed. Robert E. Rakel. Philadelphia:
W. B. Saunders Co., 1996.
“Infectious Disease: Parasitic Infections.” In The Merck Manu-
al of Diagnosis and Therapy. 16th ed. Ed. Robert Berkow.
Rahway, NJ: Merck Research Laboratories, 1992.
Weinberg, Adriana, and Myron J. Levin. “Infections: Parasitic
& Mycotic.” In Current Pediatric Diagnosis & Treatment ,

ed. William W. Hay Jr., et al. Stamford: Appleton &Lange, 1997.
Amebic dysentery seeAmebiasis
Amenorrhea
The absence of menstrual periods is called amenor-

rhea. Primary amenorrhea is the failure to start having aperiod by the age of 16. Secondary amenorrhea is morecommon and refers to either the temporary or permanentending of periods in a woman who has menstruated nor-mally in the past. Many women miss a period occasional-ly. Amenorrhea occurs if a woman misses three or moreperiods in a row.
The absence of menstrual periods is a symptom, not

a disease. While the average age that menstruation beginsis 12, the range varies. The incidence of primary amenor-rhea in the United States is just 2.5%.
Some female athletes who participate in rowing,
long distance running, and cycling, may notice a fewmissed periods. Women athletes at a particular risk fordeveloping amenorrhea include ballerinas and gymnasts,who typically exercise strenuously and eat poorly.
Amenorrhea can have many causes. Primary amenor-

rhea can be the result of hormonal imbalances, psychi-atric disorders, eating disorders, malnutrition , excessive
thinness or fatness, rapid weight loss, body fat content toolow, and excessive physical conditioning. Intense physicaltraining prior to puberty can delay menarche (the onset

of menstruation). Every year of training can delay menar-che for up to five months. Some medications such as anti-depressants, tranquilizers, steroids, and heroin can induceamenorrhea.
Primary amenorrhea
However, the main cause is a delay in the beginning
of puberty either from natural reasons (such as heredity orpoor nutrition ) or because of a problem in the endocrine
system, such as a pituitary tumor or hypothyroidism . An

obstructed flow tract or inflammation in the uterus maybe the presenting indications of an underlying metabolic,endocrine, congenital or gynecological disorder.
Typical causes of primary amenorrhea include:
• excessive physical activity• drastic weight loss (such as occurs in anorexia or
bulimia)
• extreme obesity
• drugs (antidepressants or tranquilizers)
• chronic illness
• turner’s syndrome. (A chromosomal problem in place
at birth, relevant only in cases of primary amenorrhea)

• the absence of a vagina or a uterus
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• imperforate hymen (lack of an opening to allow the
menstrual blood through)
Secondary amenorrhea
Some of the causes of primary amenorrhea can also
cause secondary amenorrhea—strenuous physical activi-ty, excessive weight loss, use of antidepressants or tran-quilizers, in particular. In adolescents, pregnancy and
stress are two major causes. Missed periods are usually

caused in adolescents by stress and changes in environ-ment. Adolescents are especially prone to irregular peri-ods with fevers, weight loss, changes in environment, orincreased physical or athletic activity. However, any ces-sation of periods for four months should be evaluated.
The most common cause of seconardy amenorrhea is

pregnancy. Also, a woman’s periods may halt temporarilyafter she stops taking birth control pills. This temporaryhalt usually lasts only for a month or two, though in somecases it can last for a year or more. Secondary amenor-rhea may also be related to hormonal problems related tostress, depression, anorexia nervosa or drugs, or it may

be caused by any condition affecting the ovaries, such as atumor. The cessation of menstruation also occurs perma-nently after menopause or a hysterectomy .
Polycystic ovary syndrome is another common cause

of secondary amenorrhea. It is caused by ovaries contain-ing many fluid filled sacs (cysts) with abnormal levels ofmale hormones (androgens). This condition is related toimproper functioning of the pituitary gland, as it releaseshormones necessary for pregnancy (leuteinizing hor-mones), and can cause women to develop male characteris-tics, such as acne and coarse body hair. If the condition is

not treated, some of the androgens may convert to estrogen,and chronically high levels of estrogen may increase thechance of developing cancer of the uterine lining.
Diagnosis
It may be difficult to find the cause of amenorrhea,

but the exam should start with a pregnancy test; pregnan-cy needs to be ruled out whenever a woman’s period istwo to three weeks overdue. Androgen excess, estrogendeficiency, or other problems with the endocrine systemneed to be checked. Prolactin in the blood and the thy-roid stimulating hormone (TSH) should also be checked.
The diagnosis usually includes a patient history and
a physical exam (including a pelvic exam ). If a woman

has missed three or more periods in a row, a physicianmay recommend blood tests to measure hormone levels,a scan of the skull to rule out the possibility of a pituitarytumor, and ultrasound scans of the abdomen and pelvis torule out a tumor of the adrenal gland or ovary.Treatment
Treatment of amenorrhea depends on the cause. Pri-

mary amenorrhea often requires no treatment, but it’salways important to discover the cause of the problem inany case. Not all conditions can be treated, but anyunderlying condition that is treatable should be treated.
If a hormonal imbalance is the problem, proges-

terone for one to two weeks every month or two may cor-rect the problem. With polycystic ovary syndrome, birthcontrol pills are often prescribed. A pituitary tumor istreated with bromocriptine, a drug that reduces certainhormone (prolactin) secretions. Weight loss may bringon a period in an obese woman. Easing up on excessiveexercise and eating a proper diet may bring on periods inteen athletes. In very rare cases, surgery may be neededfor women with ovarian or uterine cysts.
Prognosis

Prognosis
Prolonged amenorrhea can lead to infertility and other
medical problems such as osteoporosis (thinning of the
bones). If the halt in the normal period is caused by stressor illness, periods should begin again when the stress pass-es or the illness is treated. Amenorrhea that occurs with dis-continuing birth control pills usually go away within six toeight weeks, although it may take up to a year.
The prognosis for polycystic ovary disease depends

on the severity of the symptoms and the treatment plan.Spironolactone, a drug that blocks the production ofmale hormones, can help in reducing body hair. If awoman wishes to become pregnant, treatment withclomiphene may be required or, on rare occasions,surgery on the ovaries.
Primary amenorrhea caused by a congenital condi-

tion cannot be prevented. In general, however, womenshould maintain a healthy diet, with plenty of exercise,rest, and not too much stress, avoiding smoking and sub-
stance abuse. Female athletes should be sure to eat a bal-anced diet and rest and exercise normally. However,many cases of amenorrhea cannot be prevented.
Resources
BOOKS
Carlson, Karen J., Stephanie Eisenstat, and Ziporyn Eisenstat.
The Harvard Guide to Women’s Health. Cambridge, MA:

Harvard University Press, 1996.
Hogg, Anne Cahill. “Breaking the Cycle: Often Confused and
Frustrated, Sufferers of Amenorrhea Now have Better
GALE ENCYCLOPEDIA OF MEDICINE 2 147AmenorrheaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 147

Treatment Options.” American Fitness 15, no. 4 (July-
Aug. 1997): 30-4.
Kiningham, Robert B., Barbara Apgar, and Thomas Schwenk.
“Evaluation of Amenorrhea.” American Family Physician
53, no. 3 (Mar. 1996): 1185-95.
Mayo editors. “Amenorrhea: Can Athletics Disrupt a Girl’s
Menstrual Cycle During the Growing Years?” Mayo Clin-
ic Nutrition Letter 2, no. 9 (Sept. 1989): 4-5.
American College of Obstetricians and Gynecologists. 409
12th Street, S.W., P.O. Box 96920

Federation of Feminist Women’s Health Centers.1469 Hum-
boldt Rd, Suite 200, Chico, CA 96928. (530) 891-1911.
National Women’s Health Network. 514 10th St. NW, Suite
400, Washington, DC 20004. (202) 628-7814. <http://www.womenshealthnetwork.org>.
Amikiacin seeAminoglycosides
Amiloride seeDiuretics
Amino acid disorders
screening
Amino acid disorder screening checks for inherited

disorders in amino acid metabolism. Tests are most com-monly done on newborns. Two tests are available, oneusing a blood sample and the other a urine sample.
Purpose
Amino acid disorder screening is done in newborns,
and sometimes children and adults, to detect inbornerrors in metabolism of amino acids. Twenty of the 100known amino acids are the main building blocks forhuman proteins. Proteins regulate every aspect of cellularKEY TERMS
Hymen —Membrane that stretches across the

opening of the vagina.
Hypothyroidism —Underactive thyroid gland.
Hysterectomy —Surgical removal of the uterus.
Turner’s syndrome —A condition in which one
female sex chromosome is missing.function. Of these 20 amino acids, ten are not made by

the body and must be acquired through diet. Congenital(present at birth) enzyme deficiencies that affect aminoacid metabolism or congenital abnormalities in theamino acid transport system of the kidneys creates a con-dition called aminoaciduria.
Screening is especially important in newborns.
Some congenital amino acid metabolic defects causemental retardation that can prevented with prompt

treatment of the newborn. One of the best known exam-ples of this is phenylketonuria (PKU). This is an genetic
error in metabolism of phenylalanine, an amino acidfound in milk. Individuals with PKU do not produce theenzyme necessary to break down phenylalanine.
PKU occurs in about one out of 16,000 live births in

the United States, but is more prevalent in caucasians andless prevalent in Ashkenazi Jews and African Americans.Newborns in the United States are routinely screened forPKU by a blood test.
There are two types of aminoacidurias. Primary or
overflow aminoaciduria results from deficiencies in theenzymes necessary to metabolize amino acids. Overflowaminoaciduria is best detected by a blood plasma test.
Secondary or renal aminoaciduria occurs because of

a congenital defect in the amino acid transport system inthe tubules of the kidneys. This produces increasedamino acids in the urine. Blood and urine test in combi-nation are used to determine if the aminoaciduria is ofthe overflow or renal type. Urine tests are also used tomonitor specific amino acid disorders.
Newborns are screened for amino acid disorders.
Young children with acidosis (accumulation of acid inthe body), severe vomiting and diarrhea , or urine with

an abnormal color or odor, are also screened with a urinetest for specific amino acid levels.
Both blood and urine tests are simple tests that can
be done in a doctor’s office or clinic. These tests can bedone on even the youngest patients.
Two types of amino acid screening tests are used
together to diagnose amino acid disorders.
Blood plasma screening
In the blood test, a medical technician draws a small

amount of blood from a baby’s heel. The procedure israpid and relatively painless. Total time for the test is lessthan ten minutes. The blood is sent to a laboratory whereresults will be available in about two days.
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Urine test
In the urine test, the patient is asked to urinate into a
collecting cup. For an infant, the urine is collected in a pedi-atric urine collector. The process is painless. The length oftime the test takes is determined by how long it takes thepatient to urinate. Results also take about two days.
Both these tests use thin layer chromatography to

separate the amino acids present. Using this technique,the amino acids form a characteristic patterns on a glassplate coated with a thin layer of silica gel. This pattern isthen compared to the normal pattern to determine if thereare abnormalities.
Before the blood test, the patient must not eat or
drink for four hours. Failure to fast will alter the resultsof the test.
The patient should eat and drink normally before the

urine test. Some drugs may affect the results of the urinetest. The technician handling the urine sample should beinformed of any medications the patient is taking. Moth-ers of breastfeeding infants should report any medica-tions they are taking, since these can pass from mother tochild in breast milk.
Aftercare
The blood screening is normally done first. Depend-

ing on the results, it is followed by the urine test. It takesboth tests to distinguish between overflow and renalaminoaciduria. Also, if the results are abnormal, a 24-hour urine test is performed along with other tests todetermine the levels of specific amino acids. In the eventof abnormal results, there are many other tests that willbe performed to determine the specific amino acidinvolved in the abnormality.
Risks
There are no particular risks associated with either

of these tests. Occasionally minor bruising may occur atthe site where the blood was taken.
The pattern of amino acid banding on the thin layer
chromatography plates will be normal.
The blood plasma amino acid pattern is abnormal in
overflow aminoaciduria and is normal in renalaminoaciduria. The pattern is abnormal in the urine test,suggesting additional tests need to be done to determineKEY TERMS
Amino acid —An organic compound composed of

both an amino group and an acidic carboxylgroup; amino acids are the basic building blocksof proteins.
Aminoaciduria —The abnormal presence of amino
acids in the urine.
Chromatography —A family of laboratory tech-
niques that separate mixtures of chemicals intotheir individual components.
Enzyme —A biological catalyst that increases the
rate of a chemical reaction without being used upin the reaction.
Metabolism —The sum of all the chemical and

energy reactions that take place in the human body.
which amino acids are involved. In addition to PKU, a
variety of other amino acid metabolism disorders can bedetected by these tests, including tyrosinosis, histidine-mia, maple syrup urine disease, hypervalinemia, hyper-prolinemia, and homocystinuria.
Resources
BOOKS
Everything You Need to Know About Medical Tests. Ed.
Michael Shaw, et al. Springhouse, PA: Springhouse Cor-poration, 1996.

Association for Neuro-Metabolic Disorders. 5223 Brookfield
Lane, Sylvania, OH 43560-1809. (419) 885-1497.
Children’s PKU Network (CPN). 3790 Via De La Valle, Ste
120, Del Mar, CA 92014. (800) 377-6677. <http://www.pkunetwork.org/>.
National Phenylketonuria Foundation. 6301 Tejas Drive,
Pasadena, TX 77503. (713) 487-4802.
Aminoglycosides

Aminoglycosides are a group of antibiotics that are
used to treat certain bacterial infections. This group of
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antibiotics includes at least eight drugs: amikacin, gen-
tamicin, kanamycin, neomycin, netilmicin, paro-momycin, streptomycin, and tobramycin. All of thesedrugs have the same basic chemical structure.
Purpose
Aminoglycosides are primarily used to combat infec-

tions due to aerobic, Gram-negative bacteria. These bacte-ria can be identified by their reaction to Gram’s stain. InGram’s staining, a film of material containing the possiblebacteria is placed on a glass slide and dried. The slide isstained with crystal violet for one minute, cleaned off withwater and then placed into a solution of Gram’s iodinesolution for one minute. The iodine solution is rinsed offand the slide is immersed in 95% ethyl alcohol. The slide isthen stained again with reddish

The slide isthen stained again with reddish carbolfuchsin or safraninefor 30 seconds, rinsed in water, dried and examined. Gram-positive bacteria retain the violet purple stain. Gram-nega-tive bacteria accept the red stain. Bacteria that can success-fully be combated with aminoglycosides includePseudomonas ,Acinetobacter , and Enterobacter species,

among others. Aminoglycosides are also effective againstmycobacteria, the bacteria responsible for tuberculosis .
The aminoglycosides can be used against certain
Gram-positive bacteria, but are not typically employedbecause other antibiotics are more effective and havefewer side effects. Aminoglycosides are ineffectiveagainst anaerobic bacteria (bacteria that cannot grow inthe presence of oxygen), viruses, and fungi. And onlyone aminoglycoside, paromomycin, is used against para-sitic infection.

Like all other antibiotics, aminoglycosides are not
effective against influenza , the common cold , or other
viral infections.
Pre-existing medical conditions—such as kidney dis-
ease, eighth cranial nerve disease, myasthenia gravis , and

Parkinson’s disease—should be discussed prior to takingany aminoglycosides. Pregnant women are usually advisedagainst taking aminoglycosides, because their infants maysuffer damage to their hearing, kidneys, or sense of bal-ance. However, those factors need to be considered along-side the threat to the mother’s health and life in cases ofserious infection. Aminoglycosides do not pass into breastmilk to any great extent, so nursing mothers may be pre-scribed aminoglycosides without injuring

Streptomycin, the first aminoglycoside, was isolated
from Streptomyces griseus in the mid-1940s. This antibiot-ic was very effective against tuberculosis. One of the main

drawbacks to streptomycin is its toxicity, especially to cellsin the inner and middle ear and the kidney. Furthermore,some strains of tuberculosis are resistant to treatment withstreptomycin. Therefore, medical researchers have put con-siderable effort into identifying other antibiotics with strep-tomycin’s efficacy, but without its toxicity.
Aminoglycosides are absorbed very poorly from the

gastrointestinal tract; in fact, aminoglycosides taken oral-ly are excreted virtually unchanged and undiminished inquantity. The route of drug administration depends on thetype and location of the infection being treated. The typi-cal routes of administration are by intramuscular (injec-tion into a muscle) or intravenous injection (injection intoa vein), irrigation, topical skin application, or inhalation.If the infection being treated involves the central nervoussystem, the drug can be

the central nervoussystem, the drug can be injected into the spinal canal.

been fully explained. It is known that the drug attaches toa bacterial cell wall and is drawn into the cell via chan-nels made up of the protein, porin. Once inside the cell,the aminoglycoside attaches to the cell’s ribosomes.Ribosomes are the intracellular structures responsible formanufacturing proteins. This attachment either shutsdown protein production or causes the cell to produceabnormal, ineffective proteins. The bacterial cell cannotsurvive with this impediment.

Antibiotic treatment using aminoglycosides may
pair the drug with a second type of antibiotic, usually abeta-lactam or vancomycin, administered separately.Beta-lactams disrupt the integrity of the bacteria cellwall, making it more porous. The increased porosityallows more of the aminoglycoside into the bacteria cell.
Traditionally, aminoglycosides were administered at

even doses given throughout the day. It was thought thata steady plasma concentration was necessary to combatinfection. However, this administration schedule is timeand labor intensive. Furthermore, administering a singledaily dose can be as effective, or more effective, thanseveral doses throughout the day.
Dosage depends on the patient’s age, weight, gender,

and general health. Since the drug is cleared by the kid-neys, it is important to assess any underlying problemswith kidney function. Kidney function is assessed bymeasuring the blood levels of creatinine, a protein nor-mally found in the body. If these levels are high, it is anindication that the kidneys may not be functioning at anoptimal rate and dosage will be lowered accordingly.
Risks
Aminoglycosides have been shown to be toxic to cer-

tain cells in the ears and in the kidneys. Approximately 5-
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10% of the people who are treated with aminoglycosides
experience some side effect, affecting their hearing, senseof balance, or kidneys. However, in most cases the dam-age is minor and reversible once medication is stopped.
If cells in the inner ear are damaged or destroyed, an
individual may experience a loss of balance and feelingsof dizziness . Damage to the middle ear may result in
hearing loss or tinnitus . Neomycin, kanamycin, and

amikacin are the most likely to cause problems withhearing, and streptomycin and gentamicin carry thegreatest risk of causing vertigo and loss of balance. Kid-ney damage, apparent with changes in urination frequen-cy or urine production, is most likely precipitated byneomycin, tobramycin, and gentamicin.
Young children and the elderly are at the greatest
risk of suffering side effects. Excessive dosage or poorclearance of the drug from the body can be injurious atany age.

Less common side effects include skin rashes and
itching . Very rarely, certain aminoglycosides may cause
difficulty in breathing, weakness, or drowsiness. Gen-tamicin, when injected, may cause leg cramps, skin rash,fever , or seizures.
If side effects linger or become worse after medica-

tion is stopped, it is advisable to seek medical advice.Side effects that may be of concern include tinnitus orloss of hearing, dizziness or loss of balance, changes inurination frequency or urine production, increased thirst,appetite loss, and nausea or vomiting.
At the proper dosage and in the presence of gram-
negative enteric (intestinal) bacteria, aminoglycosidesare very effective in treating an infection.
In some cases, bacteria are resistant to antibiotics

that would normally kill them. This resistance becomesapparent after repeated exposure to the antibiotic andarises from a mutation that alters the bacteria’s suscepti-bility to the drug. Various degrees of resistance have beenobserved in bacteria that normally would be destroyed byaminoglycosides. In general, though, aminoglycosideeffectiveness has held up well over time.
Resources
BOOKS
Chambers, Henry F., W. Keith Hadley, and Ernest Jawetz.

“Aminoglycosides & Spectinomycin.” In Basic and Clini-
cal Pharmacology. 7th ed. Ed. Bertram G. Katzung. Stam-
ford: Appleton & Lange, 1998.KEY TERMS
Aerobic bacteria —Bacteria which require oxygen
in order to grow and survive.
Anaerobic bacteria —Bacteria which cannot grow
or reproduce in the presence of oxygen.
Eighth cranial nerve disease —A disorder affecting
the eighth cranial nerve, characterized by a loss ofhearing and/or balance.
Gram-negative —Referring to a bacteria that take

on a pink color when exposed to Gram’s stain.
Gram-positive —Referring to a bacteria that takes
on a purplish- black color when exposed toGram’s stain.
Gram’s stain —A stain used in microbiology to
classify bacteria and help identify the species towhich they belong. This identification aids indetermining treatment.
Kidney disease —Any disorder which impairs the
kidney’s ability to remove waste and toxins fromthe body.

Myasthenis gravis —A neuromuscular disease
characterized by muscle weakness in the limbsand face.
Parkinson’s disease —A neurological disorder
caused by deficiency of dopamine, a neurotrans-mitter, that is a chemical that assists in transmittingmessages between the nerves within the brain. It ischaracterized by muscle tremor or palsy and rigidmovements.
Lerner, Stephen A., Robert P. Gaynes, and Lisbeth Nördstrom-
Lerner. “Aminoglycosides.” In Infectious Diseases. 2nd

ed. Ed. Sherwood L. Gorbach, John G. Bartlett, and NeilR. Blacklow. Philadelphia: W. B. Saunders Co., 1998.
Julia Barrett
Amitriptyline seeAntidepressants, tricyclic
Amlodipine seeCalcium channel blockers
Amnesia
Amnesia refers to the loss of memory. Memory loss
may result from two-sided (bilateral) damage to parts of
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the brain vital for memory storage, processing, or recall
(the limbic system, including the hippocampus in themedial temporal lobe).
Amnesia can be a symptom of several neurodegen-
erative diseases; however, people whose primary symp-tom is memory loss (amnesiacs), typically remain lucidand retain their sense of self. They may even be awarethat they suffer from a memory disorder.
People who experience amnesia have been instrumen-

tal in helping brain researchers determine how the brainprocesses memory. Until the early 1970s, researchersviewed memory as a single entity. Memory of new experi-ences, motor skills, past events, and previous conditioningwere grouped together in one system that relied on a spe-cific area of the brain.
If all memory were stored in the same way, it would

be reasonable to deduce that damage to the specific brainarea would cause complete memory loss. However, stud-ies of amnesiacs counter that theory. Such researchdemonstrates that the brain has multiple systems for pro-cessing, storing, and drawing on memory.
Amnesia has several root causes. Most are traceable
to brain injury related to physical trauma, disease, infec-tion, drug and alcohol abuse, or reduced blood flow to

the brain (vascular insufficiency). In Wernicke-Korsakoffsyndrome, for example, damage to the memory centersof the brain results from the use of alcohol or malnutri-
tion. Infections that damage brain tissue, including
encephalitis and herpes, can also cause amnesia. If the
amnesia is thought to be of psychological origin, it istermed psychogenic.
There are at least three general types of amnesia:
• Anterograde. This form of amnesia follows brain trau-

ma and is characterized by the inability to remembernew information. Recent experiences and short-termmemory disappear, but victims can recall events priorto the trauma with clarity.
• Retrograde. In some ways, this form of amnesia is the
opposite of anterograde amnesia: the victim can recallevents that occurred after a trauma, but cannot remem-ber previously familiar information or the events pre-ceding the trauma.
• Transient global amnesia. This type of amnesia has no

consistently identifiable cause, but researchers havesuggested that migraines or transient ischemic attacksmay be the trigger. (A transient ischemic attack ,

sometimes called “a small stroke,” occurs when ablockage in an artery temporarily blocks off blood sup-ply to part of the brain.) A victim experiences suddenconfusion and forgetfulness. Attacks can be as brief as30-60 minutes or can last up to 24 hours. In severeattacks, a person is completely disoriented and mayexperience retrograde amnesia that extends back sever-al years. While very frightening for the patient, tran-sient global amnesia generally has an excellent progno-sis for recovery.

Diagnosis
In diagnosing amnesia and its cause, doctors look at
several factors. During a physical examination , the doc-
tor inquires about recent traumas or illnesses, drug andmedication history, and checks the patient’s generalhealth. Psychological exams may be ordered to deter-mine the extent of amnesia and the memory systemaffected. The doctor may also order imaging tests such asmagnetic resonance imaging (MRI) to reveal whether

the brain has been damaged, and blood work to excludetreatable metabolic causes or chemical imbalances.
Treatment
Treatment depends on the root cause of amnesia and
is handled on an individual basis. Regardless of cause,cognitive rehabilitation may be helpful in learning
strategies to cope with memory impairment.
GALE ENCYCLOPEDIA OF MEDICINE 2 152Amnesia
AmygdalaHippocampus
Memory loss may result from bilateral damage to the limbic

system of the brain responsible for memory storage, pro-cessing, and recall. (Illustration by Electronic Illustrators Group).GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 152

Prognosis
Some types of amnesia, such as transient global
amnesia, are completely resolved and there is no perma-nent loss of memory. Others, such as Korsakoff syn-drome, associated with prolonged alcohol abuse oramnesias caused by severe brain injury, may be perma-nent. Depending on the degree of amnesia and its cause,victims may be able to lead relatively normal lives.Amnesiacs can learn through therapy to rely on othermemory systems to compensate for what is lost.

Amnesia is only preventable in so far as brain injury
can be prevented or minimized. Common sense approach-es include wearing a helmet when bicycling or participat-ing in potentially dangerous sports, using automobile seatbelts, and avoiding excessive alcohol or drug use. Braininfections should be treated swiftly and aggressively tominimize the damage due to swelling. Victims of strokes,brain aneurysms, and transient ischemic attacks shouldseek immediate medical treatment.
Resources

Resources
BOOKS
Cohen, Neal J., and Howard Eichenbaum. Memory, Amnesia,
and the Hippocampal System. Cambridge, MA: MIT
Press, 1993.KEY TERMS
Classical conditioning —The memory system that
links perceptual information to the proper motorresponse. For example, Ivan Pavlov conditioned adog to salivate when a bell was rung.
Emotional conditioning —The memory system that
links perceptual information to an emotionalresponse. For example, spotting a friend in a crowdcauses a person to feel happy.

Explicit memory —Conscious recall of facts and
events that is classified into episodic memory(involves time and place) and semantic memory(does not involve time and place). For example, anamnesiac may remember he has a wife (semanticmemory), but cannot recall his last conversationwith her (episodic memory).
Limbic system —The brain structures involved in
memory.
Magnetic resonance imaging (MRI) —MRI uses a

large circular magnet and radio waves to generatesignals from atoms in the body. These signals are
used to construct images of internal structures.
Motor skill learning —This memory system is asso-
ciated with physical movement and activity. Forexample, learning to swim is initially difficult, butonce an efficient stroke is learned, it requires littleconscious effort.
Neurodegenerative disease —A disease in which

the nervous system progressively and irreversiblydeteriorates.
Priming memory —The memory system that joins
perceptual and conceptual representations.
Transient ischemic attack —A sudden and brief
blockage of blood flow in the brain.
Working memory —The memory system that relates
to the task at hand and coordinates recall of memo-ries necessary to complete it.
Kaufman, Leslie. “The Forgetting People: Amnesiacs.” Health

9, no. 6 (Oct. 1995): 86.
Squire, Larry R., and Stuart M. Zola. “Amnesia, Memory and
Brain Systems.” Philosophical Transactions of the Royal
Society of London, Series B 352 (1997): 1663.
“The Man Who Lost Himself.” World Press Review 44, no. 6
(June 1997): 36. (Reprinted from Der Spiegel 17 Mar.
1997.)
Amniocentesis
Amniocentesis is a procedure used to diagnose fetal
defects in the early second trimester of pregnancy . A

sample of the amniotic fluid, which surrounds a fetus inthe womb, is collected through a pregnant woman’sabdomen using a needle and syringe. Tests performed onfetal cells found in the sample can reveal the presence ofmany types of genetic disorders, thus allowing doctorsand prospective parents to make important decisionsabout early treatment and intervention.
GALE ENCYCLOPEDIA OF MEDICINE 2 153AmniocentesisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 153

Purpose
Since the mid-1970s, amniocentesis has been used
routinely to test for Down syndrome , by far the most
common, nonhereditary, genetic birth defect, afflictingabout one in every 1,000 babies. By 1997, approximately800 different diagnostic tests were available, most ofthem for hereditary genetic disorders such as Tay-Sachs
disease , sickle cell anemia, hemophilia ,muscular dys-
trophy and cystic fibrosis .
Amniocentesis, often called amnio, is recommended

for women who will be older than 35 on their due-date. Itis also recommended for women who have already bornechildren with birth defects , or when either of the parents
has a family history of a birth defect for which a diagnos-tic test is available. Another reason for the procedure is toconfirm indications of Down syndrome and certain otherdefects which may have shown up previously during rou-tine maternal blood screening.

The risk of bearing a child with a nonhereditary
genetic defect such as Down syndrome is directly relat-ed to a woman’s age—the older the woman, the greaterthe risk. Thirty-five is the recommended age to beginamnio testing because that is the age at which the risk ofcarrying a fetus with such a defect roughly equals therisk of miscarriage caused by the procedure—about

one in 200. At age 25, the risk of giving birth to a childwith this type of defect is about one in 1,400; by age 45it increases to about one in 20. Nearly half of all preg-nant women over 35 in the United States undergoamniocentesis and many younger women also decide tohave the procedure. Notably, some 75% of all Downsyndrome infants born in the United States each year areto women younger than 35.
One of the most common reasons for performing

amniocentesis is an abnormal alpha-fetoprotein (AFP)test. Alpha-fetoprotein is a protein produced by the fetusand present in the mother’s blood. A simple bloodscreening, usually conducted around the 15th week ofpregnancy, can determine the AFP levels in the mother’sblood. Levels that are too high or too low may signalpossible fetal defects. Because this test has a high false-positive rate, another test such as amnio is recommendedwhenever the AFP levels fall outside the normal range.

16th week of pregnancy, with results usually availablewithin three weeks. It is possible to perform an amnio asearly as the 11th week but this is not usually recommend-ed because there appears to be an increased risk of mis-carriage when done at this time. The advantage of earlyamnio and speedy results lies in the extra time for deci-sion making if a problem is detected. Potential treatmentof the fetus can begin earlier. Important, also, is the factthat elective abortions are safer and less

factthat elective abortions are safer and less controversial the

earlier they are performed.
As an invasive surgical procedure, amnio poses a real,
although small, risk to the health of a fetus. Parents mustweigh the potential value of the knowledge gained, orindeed the reassurance that all is well, against the small riskof damaging what is in all probability a normal fetus. Theserious emotional and ethical dilemmas that adverse testresults can bring must also be considered. The decision toundergo amnio is always a matter of personal choice.

The word amniocentesis literally means “puncture
of the amnion,” the thin-walled sac of fluid in which adeveloping fetus is suspended during pregnancy. Duringthe sampling procedure, the obstetrician inserts a veryfine needle through the woman’s abdomen into the uterusand amniotic sac and withdraws approximately oneounce of amniotic fluid for testing. The relatively pain-less procedure is performed on an outpatient basis, some-times using local anesthesia.

The physician uses ultrasound images to guide nee-
dle placement and collect the sample, thereby minimiz-ing the risk of fetal injury and the need for repeated nee-dle insertions. Once the sample is collected, the womancan return home after a brief observation period. Shemay be instructed to rest for the first 24 hours and toavoid heavy lifting for two days.
The sample of amniotic fluid is sent to a laboratory

where fetal cells contained in the fluid are isolated andgrown in order to provide enough genetic material fortesting. This takes about seven to 14 days. The material isthen extracted and treated so that visual examination fordefects can be made. For some disorders, like Tay-Sachs,the simple presence of a telltale chemical compound inthe amniotic fluid is enough to confirm a diagnosis.Depending on the specific tests ordered, and the skill ofthe lab conducting them, all the results are

ofthe lab conducting them, all the results are availablebetween one and four weeks after the sample is taken.

Cost of the procedure depends on the doctor, the lab,
and the tests ordered. Most insurers provide coverage forwomen over 35, as a follow-up to positive maternalblood screening results, and when genetic disorders runin the family.
An alternative to amnio, now in general use, is chori-
onic villus sampling , or CVS, which can be performed as

early as the eighth week of pregnancy. While this allowsfor the possibility of a first trimester abortion, if warrant-ed, CVS is apparently also riskier and is more expensive.
GALE ENCYCLOPEDIA OF MEDICINE 2 154AmniocentesisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 154

The most promising area of new research in prenatal test-
ing involves expanding the scope and accuracy of mater-nal blood screening as this poses no risk to the fetus.
It is important for a woman to fully understand the

procedure and to feel confident in the obstetrician per-forming it. Evidence suggests that a physician’s experi-ence with the procedure reduces the chance of mishap.Almost all obstetricians are experienced in performingamniocentesis. The patient should feel free to ask ques-tions and seek emotional support before, during and afterthe amnio is performed.
Aftercare
Necessary aftercare falls into two categories, physi-
cal and emotional.
Physical aftercare

During and immediately following the sampling
procedure, a woman may experience dizziness , nausea, arapid heartbeat, and cramping. Once past these immedi-
ate hurdles, the physician will send the woman homewith instructions to rest and to report any complicationsrequiring immediate treatment, including:
• vaginal bleeding. The appearance of blood could signal
a problem.
•premature labor . Unusual abdominal pain and/or

cramping may indicate the onset of premature labor.Mild cramping for the first day or two following theprocedure is normal.
• signs of infection. Leaking of amniotic fluid or unusual
vaginal discharge, and fever could signal the onset of
infection.
Emotional aftercare
Once the procedure has been safely completed, the
anxiety of waiting for the test results can prove to be the

worst part of the process. A woman should seek andreceive emotional support from family and friends, aswell as from her obstetrician and family doctor. Profes-sional counseling may also prove necessary, particularlyif a fetal defect is discovered.
GALE ENCYCLOPEDIA OF MEDICINE 2 155Amniocentesis
A physician uses an ultrasound monitor (left) to position the needle for insertion into the amnion when performing amnio-

centesis. (Photograph by Will and Deni McIntyre, Photo Researchers, Inc. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 155

Risks
Most of the risks and short-term side effects associ-
ated with amniocentesis relate to the sampling procedureand have been discussed above. A successful amnio sam-pling results in no long-term side effects. Risks include:
• maternal/fetal hemorrhaging. While spotting in preg-
nancy is fairly common, bleeding following amnioshould always be investigated.
• infection. Infection, although rare, can occur after
amniocentesis. An unchecked infection can lead tosevere complications.

• fetal injury. A very slight risk of injury to the fetus
resulting from contact with the amnio needle does exist.
• miscarriage. The rate of miscarriage occurring during
standard, second trimester amnio appears to be approx-imately 0.5%. This compares to a miscarriage rate ofKEY TERMS
Alpha-fetoprotein (AFP) —A protein normally pro-

duced by the liver of a fetus and detectable inmaternal blood samples. AFP screening measuresthe amount of alpha-fetoprotein in the blood. Levelsoutside the norm may indicate fetal defects.
Anencephaly —A hereditary defect resulting in the
partial to complete absence of a brain and spinalcord. It is fatal.
Chorionic villus sampling (CVS) —A procedure simi-

lar to amniocentesis, except that cells are taken fromthe chorionic membrane for testing. These cells,called chorionic villus cells, eventually become theplacenta. The samples are collected either throughthe abdomen, as in amnio, or through the vagina.CVS can be done earlier in the pregnancy thanamnio, but carries a somewhat higher risk.
Chromosome —Chromosomes are the strands of

genetic material in a cell that occur in nearly identi-cal pairs. Normal human cells contain 23 chromo-some pairs—one in each pair inherited from themother, and one from the father. Every human cellcontains the exact same set of chromosomes.
Down syndrome —The most prevalent of a class of

genetic defects known as trisomies, in which cellscontain three copies of certain chromosomes ratherthan the usual two. Down syndrome, or trisomy 21,usually results from three copies of chromosome 21.Genetic —The term refers to genes, the basic units
of biological heredity, which are contained on thechromosomes, and contain chemical instructionswhich direct the development and functioning of anindividual.

Hereditary —Something which is inherited—passed
down from parents to offspring. In biology andmedicine, the word pertains to inherited geneticcharacteristics.
Maternal blood screening —Maternal blood screen-
ing is normally done early in pregnancy to test for avariety of conditions. Abnormal amounts of certainproteins in a pregnant woman’s blood raise theprobability of fetal defects. Amniocentesis is recom-mended if such a probability occurs.
Tay-Sachs disease —An inherited disease prevalent

among the Ashkenazi Jewish population of theUnited States. Infants with the disease are unable toprocess a certain type of fat which accumulates innerve and brain cells, causing mental and physicalretardation, and death by age four.
Ultrasound —A technique which uses high-frequen-
cy sound waves to create a visual image (a sono-gram) of soft tissues. The technique is routinely usedin prenatal care and diagnosis.

1% for CVS. Many fetuses with severe genetic defects
miscarry naturally during the first trimester.
• the trauma of difficult family-planning decisions. The
threat posed to parental and family mental health fromthe trauma accompanying an abnormal test result cannot be underestimated.
Negative results from an amnio analysis indicate

that everything about the fetus appears normal and thepregnancy can continue without undue concern. A nega-tive result for Down syndrome means that it is 99% cer-tain that the disease does not exist.
An overall “normal” result does not, however, guar-

antee that the pregnancy will come to term, or that thefetus does not suffer from some other defect. Laboratorytests are not 100% accurate at detecting targeted condi-tions, nor can every possible fetal condition be tested for.
GALE ENCYCLOPEDIA OF MEDICINE 2 156AmniocentesisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 156

Positive results on an amnio analysis indicate the
presence of the fetal defect being tested for, with anaccuracy approaching 100%. Prospective parents arethen faced with emotionally and ethically difficult choic-es regarding treatment options, the prospect of dealingwith a severely affected newborn, and the option of elec-tive abortion. At this point, the parents need expert med-ical advice and counseling.
Resources
BOOKS

Resources
BOOKS
Elias, Sherman, and Joe Leigh Simpson. “Techniques for Pre-
natal Diagnosis—Amniocentesis.” In Essentials of Prena-
tal Diagnosis. Ed. Joe Leigh Simpson and Sherman Elias.
New York: Churchill Livingstone, 1993.
Genetic Disorders and the Fetus: Diagnosis, Prevention and
Treatment. Ed. Aubrey Milunsky. Baltimore: Johns Hop-
kins University Press, 1992.
Kolker, Aliza. Prenatal Testing: A Sociological Perspective.
Westport, CT: Bergin & Garvey, 1994.

Rapp, Rayna. “The Power of Positive Diagnosis: Medical and
Maternal Discourses on Amniocentesis.” In Repre-senta-
tions of Motherhood , ed. Donna Bassin, et al. New Haven,
CT: Yale University Press, 1994.
Women and Prenatal Testing: Facing the Challenges of Genetic
Technology. Ed. Karen H. Rothenberg and Elizabeth J.
Thomson. Columbus, OH: Ohio State University Press,1994.
Bonner, John. “Simple Blood Test May Replace Amniocente-

sis.” New Scientist (5 Oct. 1996): 26.
Boss, Judith A. “First Trimester Prenatal Diagnosis: Earlier is
Not Necessarily Better.” Journal of Medical Ethics 20
(Sept. 1994): 146-151.
“Complications Associated with Early Amniocentesis.” Ameri-
can Family Physician 54 (1 Oct. 1996): 1716.
Dreisbach, Shaun. “Amnio Alternative.” Working Mother , Mar.
1997, 11.
Josephson, N. F. “What You May Not Know About Pregnancy

Tests and What They Tell Your Doctor About Your Baby’sHealth.” Parents , Apr. 1996, 77-8.
Marble, Michelle. “Testing During First Trimester Proves
Risky.” Women’s Health Weekly , 8 July 1996, 12.
Sher, Emil. “Everything is Perfectly Normal.” Chatelaine , June
1996, 22.
Stranc, Leonie C., et al. “Chorionic Villus Sampling and
Amniocentesis for Prenatal Diagnosis.” The Lancet (8
Mar. 1997): 711-4.
Sundberg, K., et al. “Randomized Study of Risk of Fetal Loss

Related to Early Amniocentesis versus Chorionic VillusSampling.” The Lancet (6 Sept. 1997): 697-703.
12th Street, S.W., P.O. Box 96920OTHER
Holbrook Jr., Harold R. Stanford University School of Medi-
cine Web Home Page. Feb. 2001 <http://www.stanford.edu/~holbrook>.
Amniotic fluid analysis seeAmniocentesis
Amoxicillin seePenicillins
Amphetamines seeCentral nervous system
stimulants

Amphotericin B seeAntifungal drugs,
systemic
Amputation
Amputation is the intentional surgical removal of a
limb or body part. It is performed to remove diseased tis-sue or relieve pain .
Purpose
Arms, legs, hands, feet, fingers, and toes can all be
amputated. Most amputations involve small body partssuch as a finger, rather than an entire limb. About 65,000amputations are performed in the United States each year.

Amputation is performed for the following reasons:
• to remove tissue that no longer has an adequate blood
supply
• to remove malignant tumors• because of severe trauma to the body part
The blood supply to an extremity can be cut off
because of injury to the blood vessel, hardening of thearteries, arterial embolism , impaired circulation as a
complication of diabetes mellitus , repeated severe infec-
tion that leads to gangrene , severe frostbite, Raynaud’s
disease , or Buerger’s disease .

More than 90% of amputations performed in the
United States are due to circulatory complications of dia-betes. Sixty to eighty percent of these operations involvethe legs.
Amputations cannot be performed on patients with
uncontrolled diabetes mellitus, heart failure , or infec-
GALE ENCYCLOPEDIA OF MEDICINE 2 157AmputationGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 157

tion. Patients with blood clotting disorders are also not
good candidates for amputation.
Amputations can be either planned or emergency
procedures. Injury and arterial embolisms are the mainreasons for emergency amputations. The operation isperformed under regional or general anesthesia by a gen-eral or orthopedic surgeon in a hospital operating room.
Details of the operation vary slightly depending on

what part is to be removed. The goal of all amputations istwofold: to remove diseased tissue so that the wound willheal cleanly, and to construct a stump that will allow theattachment of a prosthesis or artificial replacement part.
The surgeon makes an incision around the part to be

amputated. The part is removed, and the bone is smoothed.A flap is constructed of muscle, connective tissue, andskin to cover the raw end of the bone. The flap is closedover the bone with sutures (surgical stitches) that remainin place for about one month. Often, a rigid dressing or
cast is applied that stays in place for about two weeks.
Before an amputation is performed, extensive testing

is done to determine the proper level of amputation. Thegoal of the surgeon is to find the place where healing ismost likely to be complete, while allowing the maximumamount of limb to remain for effective rehabilitation .
The greater the blood flow through an area, the more
likely healing is to occur. These tests are designed to mea-sure blood flow through the limb. Several or all of themcan be done to help choose the proper level of amputation.

• measurement of blood pressure in different parts of the
limb
• xenon 133 studies, which use a radiopharmaceutical to
measure blood flow
• oxygen tension measurements in which an oxygen elec-
trode is used to measure oxygen pressure under the skin
GALE ENCYCLOPEDIA OF MEDICINE 2 158Amputation
Figure D Figure BFigure AFemurSkin flap Exposed
muscle
Figure CSciatic
nerve
Amputation of leg. Figure A: After the surgeon creates two flaps of skin and tissue, the muscle is cut and the main artery and

veins of the femur bone are exposed. Figure B:The surgeon severs the main artery and veins. New connections are formedbetween them, restoring blood circulation.The sciatic nerve is then pulled down, clamped and tied, and severed. Figure C:The surgeon saws through the exposed femur bone. Figure D:The muscles are closed and sutured over the bone.Theremaining skin flaps are then sutured together, creating a stump. (Illustration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03

If the pressure is 0, the healing will not occur. If the
pressure reads higher than 40mm Hg (40 milliliters ofmercury), healing of the area is likely to be satisfactory.
• laser Doppler measurements of the microcirculation of
the skin
• skin fluorescent studies that also measure skin micro-
circulation
• skin perfusion measurements using a blood pressure
cuff and photoelectric detector
• infrared measurements of skin temperature
No one test is highly predictive of healing, but taken

together, the results give the surgeon an excellent idea ofthe best place to amputate.
Aftercare
After amputation, medication is prescribed for pain,
and patients are treated with antibiotics to discourage

infection. The stump is moved often to encourage goodcirculation. Physical therapy and rehabilitation are startedas soon as possible, usually within 48 hours. Studies haveshown that there is a positive relationship between earlyrehabilitation and effective functioning of the stump andprosthesis. Length of stay in the hospital depends on theseverity of the amputation and the general health of theamputee, but ranges from several days to two weeks.

for above the knee amputees. Twice daily physical thera-py is not uncommon. In addition, psychological counsel-ing is an important part of rehabilitation. Many peoplefeel a sense of loss and grief when they lose a body part.Others are bothered by phantom limb syndrome, wherethey feel as if the amputated part is still in place. Theymay even feel pain in this limb that does not exist. Manyamputees benefit from joining self-help groups andmeeting others who are also living with

groups andmeeting others who are also living with amputation.Addressing the emotional aspects of amputation oftenspeeds the physical rehabilitation process.

Risks
Amputation is major surgery. All the risks associated
with the administration of anesthesia exist, along withthe possibility of heavy blood loss and the developmentof blood clots. Infection is of special concern toamputees. Infection rates in amputations average 15%. Ifthe stump becomes infected, it is necessary to remove theprosthesis and sometimes to amputate a second time at ahigher level.
Failure of the stump to heal is another major compli-

cation. Nonhealing is usually due to an inadequate bloodsupply. The rate of nonhealing varies from 5-30%KEY TERMS
Arterial embolism —A blood clot arising from
another location that blocks an artery.
Buerger’s disease —An episodic disease that caus-
es inflammation and blockage of the veins andarteries of the limbs. It tends to be present almostexclusively on men under age 40 who smoke, andmay require amputation of the hand or foot.
Diabetes mellitus —A disease in which insufficient

insulin is made by the body to metabolize sugars.
Raynaud’s disease —A disease found mainly in
young women that causes decreased circulation tothe hands and feet. Its cause is unknown.
depending on the facility. Centers that specialize in ampu-
tation usually have the lowest rates of complication.
Persistent pain in the stump or pain in the phantom

limb is experienced by most amputees to some degree.Treatment of phantom limb pain is difficult. One finalcomplication is that many amputees give up on the reha-bilitation process and discard their prosthesis. Better fit-ting prosthetics and earlier rehabilitation have decreasedthe incidence of this problem.
The five year survival rate for all lower extremity

amputees is less than 50%. For diabetic amputees, therate is less than 40%. Up to 50% of people who haveone leg amputated because of diabetes will lose theother within five years. Amputees who walk using aprosthesis have a less stable gait. Three to five percentof these people fall and break bones because of thisinstability. Although the fractures can be treated, about
half the amputees who suffer them then remain wheel-chair bound.
Resources

Resources
American Diabetes Association. 1701 North Beauregard Street,
Alexandria, V A 22311. (800) 342-2383. <http://www.diabetes.org>.
OTHER
Amputation Prevention Global Resource Center Page. Feb.
2001. <http://www.diabetesresource.com>.
GALE ENCYCLOPEDIA OF MEDICINE 2 159AmputationGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 159

Amylase tests
Amylase is a digestive enzyme made primarily by
the pancreas and salivary glands. Enzymes are sub-stances made and used by the body to trigger specificchemical reactions. The primary function of the enzymeamylase is to break down starches in food so that theycan be used by the body. Amylase testing is usually doneto determine the cause of sudden abdominal pain .
Purpose
Amylase testing is performed to diagnose a number

of diseases that elevate amylase levels. Pancreatitis , for
example, is the most common reason for a high amylaselevel. When the pancreas is inflamed, amylase escapesfrom the pancreas into the blood. Within six to 48 hoursafter the pain begins, amylase levels in the blood start torise. Levels will stay high for several days before gradu-ally returning to normal.
There are other causes of increased amylase. An

ulcer that erodes tissue from the stomach and goes intothe pancreas will cause amylase to spill into the blood.During a mumps infection, amylase from the inflamed
salivary glands increases. Amylase is also found in theliver, fallopian tubes, and small intestine; inflammation ofthese tissues also increases levels. Gall bladder disease,tumors of the lung or ovaries, alcohol poisoning , ruptured

aortic aneurysm , and intestinal strangulation or perfora-
tion can also cause unusually high amylase levels.
This is not a screening test for future pancreatic dis-
ease.
Amylase testing is done on both blood and urine.

The laboratory may use any of several testing methodsthat involve mixing the blood or urine sample with a sub-stance with which amylase is known to react. By measur-ing the end-product or the reaction time, technicians cancalculate the amount of amylase present in the sample.More sophisticated methods separately measure the amy-lase made by the pancreas and the amylase made by thesalivary glands.

Urine testing is a better long-term monitor of amy-
lase levels. The kidneys quickly move extra amylasefrom the blood into the urine. Urine levels rise six to 10hours after blood levels and stay high longer. Urine isusually collected throughout a 2- or 24-hour time period.Results are usually available the same day.
In most cases, no special preparation is necessary for

a person undergoing an amylase blood test. Patients takinglonger term urine amylase tests will be given a containerand instructions for collecting the urine at home. The urineshould be refrigerated until it is brought to the laboratory.
Aftercare
or the person may feel dizzy or faint. Pressure to the punc-ture site until the bleeding stops reduces bruising. Apply-ing warm packs to the puncture site relieves discomfort.

Eight out of ten persons with acute pancreatitis will
have high amylase levels, up to four times the normallevel. Other causes of increased amylase, such asmumps, kidney failure, pregnancy occurring in the
abdomen but outside the uterus ( ectopic pregnancy ),
certain tumors, a penetrating ulcer, certain complicationsof diabetes, and advanced pancreatic cancer , are further

investigated based on the person’s symptoms, medicalhistory, and the results of other tests.
In kidney disease, the kidneys are not as efficient at
removing amylase from the blood. Amylase rises in theblood, but stays at normal levels in the urine.
People with macroamylasia have large clumps of
amylase in their blood. These clumps are too large tomove through the kidney, so they stay in the blood. Amy-lase levels in the blood will be high; levels in the urinewill be low.

Amylase levels may be low in severe liver disease
(including hepatitis), conditions in which the pancreasfails to secrete enough enzyme for proper digestions(pancreatic insufficiency), when toxic materials build upin the blood during pregnancy (pre-eclampsia), followingburns , in thyroid disorders, and in advanced cystic
fibrosis . Some medications can raise or lower levels.
Resources
BOOKS

GALE ENCYCLOPEDIA OF MEDICINE 2 160Amylase testsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 160

Lehman, Craig A. Saunders Manual of Clinical Laboratory
Science. Philadelphia: W. B. Saunders Co., 1998.
Amyloidosis

Amyloidosis is a progressive, incurable, metabolic
disease characterized by abnormal deposits of protein inone or more organs or body systems.
Amyloid proteins are manufactured by malfunction-
ing bone marrow. Amyloidosis, which occurs when accu-mulated amyloid deposits impair normal body function,can cause organ failure or death . It is a rare disease,

occurring in about eight of every 1,000,000 people. Itaffects males and females equally and usually developsafter the age of 40. At least 15 types of amyloidosis havebeen identified. Each one is associated with deposits of adifferent kind of protein.
Types of amyloidosis
The major forms of this disease are primary sys-
temic, secondary, and familial or hereditary amyloidosis.There is also another form of amyloidosis associatedwith Alzheimer’s disease .

Primary systemic amyloidosis usually develops
between the ages of 50 and 60. With about 2,000 newcases diagnosed annually, primary systemic amyloidosisKEY TERMS
Amylase —A digestive enzyme made primarily by
the pancreas and salivary glands.
Enzyme —A substance made and used by the body
to trigger specific chemical reactions.
Pancreatitis —Inflammation of the pancreas.is the most common form of this disease in the United

States. Also known as light-chain-related amyloidosis, itmay also occur in association with multiple myeloma
(bone marrow cancer ).
Secondary amyloidosis is a result of chronic infec-
tion or inflammatory disease. It is often associated with:
•familial Mediterranean fever (a bacterial infection
characterized by chills, weakness, headache , and
recurring fever )
• granulomatous ileitis (inflammation of the small intes-
tine)

tine)
• Hodgkin’s disease (cancer of the lymphatic system)• leprosy• osteomyelitits (bacterial infection of bone and bone
marrow)
• rheumatoid arthritis
Familial or hereditary amyloidosis is the only inher-

ited form of the disease. It occurs in members of mostethnic groups, and each family has a distinctive patternof symptoms and organ involvement. Hereditary amyloi-dosis is though to be autosomal dominant, which meansthat only one copy of the defective gene is necessary tocause the disease. A child of a parent with familial amy-loidosis has a 50-50 chance of developing the disease.
Amyloidosis can involve any organ or system in the

body. The heart, kidneys, gastrointestinal system, andnervous system are affected most often. Other commonsites of amyloid accumulation include the brain, joints,liver, spleen, pancreas, respiratory system, and skin.
The cause of amyloidosis is unknown. Most patients
have gastrointestinal abnormalities, but other symptomsvary according to the organ(s) or system(s) affected bythe disease. Usually the affected organs are rubbery, firm,and enlarged.
Heart

Heart
Because amyloid protein deposits can limit the
heart’s ability to fill with blood between beats, even theslightest exertion can cause shortness of breath . If the
heart’s electrical system is affected, the heart’s rhythmmay become erratic. The heart may also be enlarged andheart murmurs may be present. Congestive heart fail-
uremay result.
Kidneys
The feet, ankles, and calves swell when amyloidosis
damages the kidneys. The kidneys become small and

GALE ENCYCLOPEDIA OF MEDICINE 2 161AmyloidosisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 161

hard, and kidney failure may result. It is not unusual for a
patient to lose 20-25 pounds and develop a distaste formeat, eggs, and other protein-rich foods. Cholesterol ele-vations that don’t respond to medication and protein inthe urine (proteinuria) are common.
Nervous system
Nervous system symptoms often appear in patients
with familial amyloidosis. Inflammation and degenera-tion of the peripheral nerves ( peripheral neuropathy )

may be present. One of four patients with amyloidosishas carpal tunnel syndrome , a painful disorder that
causes numbness or tingling in response to pressure onnerves around the wrist. Amyloidosis that affects nervesto the feet can cause burning or numbness in the toes andsoles and eventually weaken the legs. If nerves control-ling bowel function are involved, bouts of diarrhea
alternate with periods of constipation . If the disease

affects nerves that regulate blood pressure, patients mayfeel dizzy or faint when they stand up suddenly.
Liver and spleen
The most common symptoms are enlargement of
these organs. Liver function is not usually affected untilquite late in the course of the disease. Protein accumula-tion in the spleen can increase the risk of rupture of thisorgan due to trauma.
Gastrointestinal system
The tongue may be inflammed, enlarged, and stiff.

Intestinal movement (motility) may be reduced. Absorp-tion of food and other nutrients may be impaired (andmay lead to malnutrition ), and there may also be bleed-
ing, abdominal pain , constipation, and diarrhea.
Skin
Skin symptoms occur in about half of all cases of
primary and secondary amyloidosis and in all caseswhere there is inflammation or degeneration of theperipheral nerves. Waxy-looking raised bumps (papules)KEY TERMS

Amyloid —A waxy, starch-like protein.
Peripheral nerves —Nerves that carry information
to and from the spinal cord.
Stem cells —Parent cells from which other cells are
made.may appear on the face and neck, in the groin, armpits, or
anal area, and on the tongue or in the ear canals.Swelling, hemorrhage beneath the skin (purpura), hairloss, and dry mouth may also occur.
Respiratory system
Airways may be obstructed by amyloid deposits in
the nasal sinus, larynx and traches (windpipe).
Diagnosis

Diagnosis
Blood and urine tests can reveal the presence of
amyloid protein, but tissue or bone-marrow biopsy isnecessary to positively diagnose amyloidosis. Once thediagnosis has been confirmed, additional laboratory testsand imaging procedures are performed to determine:
• which type of amyloid protein is involved
• which organ(s) or system(s) have been affected• how far the disease has progressed
Treatment
The goal of treatment is to slow down or stop pro-

duction of amyloid protein, eliminate existing amyloiddeposits, alleviate underlying disorders (that give rise tosecondary amyloidosis), and relieve symptoms caused byheart or kidney damage. Specialists in cardiology, hema-tology (the study of blood and the tissues that form it),nephrology (the study of kidney function and abnormali-ties), neurology (the study of the nervous system), andrheumatology (the study of disorders characterized byinflammation or degeneration of connective tissue)

or degeneration of connective tissue) worktogether to assess a patient’s medical status and evaluatethe effects of amyloidosis on every part of the body.

Colchicine (Colebenemid, Probeneaid), prednisone,
(Prodium), and other anti-inflammatory drugs can slowor stop disease progression. Bone-marrow and stem-celltransplants can enable patients to tolerate higher andmore effective doses of melphalan (Alkeran) and otherchemotherapy drugs prescribed to combat this non-

malignant disease. Surgery can relieve nerve pressureand may be performed to correct other symptom-produc-ing conditions. Localized amyloid deposits can also beremoved surgically. Dialysis or kidney transplantation
can lengthen and improve the quality of life for patientswhose amyloidosis results in kidney failure. Heart trans-plants are rarely performed.
Supportive measures
Although no link has been established between diet

and development of amyloid proteins, a patient whoseheart or kidneys have been affected by the disease maybe advised to use a diuretic or follow a low-salt diet.
GALE ENCYCLOPEDIA OF MEDICINE 2 162AmyloidosisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 162

Prognosis
Most cases of amyloidosis are diagnosed after the
disease has reached an advanced stage. The course ofeach patient’s illness is unique but death, usually a resultof heart disease or kidney failure, generally occurs withina few years. Amyloidosis associated by multiple myelo-ma usually has a poor prognosis. Most patients with bothdiseases die within one to two years.
Genetic counseling may be helpful for patients with

hereditary amyloidosis and their families. Use ofcholchicine in patients with familial Mediterranean feverhas successfully prevented amyloidosis.
Resources
BOOKS
Amyloidosis Network International. 7118 Cole Creek Drive,
Houston, TX 77092-1421. (888) 1AMYLOID. <http://www.health.gov/nhic/Scripts/Entry.cfm?HRCode=HR2397>.

Fairfield, CT 06812-8923. (800) 999-6673. <http://www.rarediseases.org>.
OTHER
Mayo Clinic Online. 5 March 1998. <http://www.mayohealth.org>.
Amyotrophic lateral sclerosis
Amyotrophic lateral sclerosis (ALS) is a disease that

breaks down tissues in the nervous system (a neurode-generative disease) of unknown cause that affects thenerves responsible for movement. It is also known asmotor neuron disease and Lou Gehrig’s disease, after thebaseball player whose career it ended.
ALS is a disease of the motor neurons, those nerve

cells reaching from the brain to the spinal cord (uppermotor neurons) and the spinal cord to the peripheralnerves (lower motor neurons) that control muscle move-ment. In ALS, for unknown reasons, these neurons die,leading to a progressive loss of the ability to move virtual-ly any of the muscles in the body. ALS affects “volun-tary” muscles, those controlled by conscious thought,such as the arm, leg, and trunk muscles. ALS, in and ofitself, does not affect sensation, thought processes, theheart

not affect sensation, thought processes, theheart muscle, or the “smooth” muscle of the digestive sys-tem, bladder, and other internal organs. Most people withALS retain function of their eye muscles as well. Howev-er, various forms of ALS may be associated with a loss ofintellectual function ( dementia ) or sensory symptoms.

“Amyotrophic” refers to the loss of muscle bulk, a
cardinal sign of ALS. “Lateral” indicates one of theregions of the spinal cord affected, and “sclerosis”describes the hardened tissue that develops in place ofhealthy nerves. ALS affects approximately 30,000 peoplein the United States, with about 5,000 new cases eachyear. It usually begins between the ages of 40 and 70,although younger onset is possible. Men are slightlymore likely to develop ALS than women.

ALS progresses rapidly in most cases. It is fatal
within three years for 50% of all people affected, andwithin five years for 80%. Ten percent of people withALS live beyond eight years.
Causes
The symptoms of ALS are caused by the death of

motor neurons in the spinal cord and brain. Normally, theseneurons convey electrical messages from the brain to themuscles to stimulate movement in the arms, legs, trunk,neck, and head. As motor neurons die, the muscles theyenervate cannot be moved as effectively, and weaknessresults. In addition, lack of stimulation leads to musclewasting, or loss of bulk. Involvement of the upper motorneurons causes spasms and increased tone in the limbs, andabnormal reflexes. Involvement of the lower motor

reflexes. Involvement of the lower motor neuronscauses muscle wasting and twitching (fasciculations).

tion have been suggested for ALS, none has yet beenproven responsible. Results of recent research haveimplicated toxic molecular fragments known as free radi-cals. Some evidence suggests that a cascade of eventsleads to excess free radical production inside motor neu-rons, leading to their death. Why free radicals should beproduced in excess amounts is unclear, as is whether thisexcess is the cause or the effect of other degenerativeprocesses. Additional agents within this toxic cascademay

Additional agents within this toxic cascademay include excessive levels of a neurotransmitterknown as glutamate, which may over-stimulate motorneurons, thereby increasing free-radical production, anda faulty detoxification enzyme known as SOD-1, for

GALE ENCYCLOPEDIA OF MEDICINE 2 163Amyotrophic lateral sclerosisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 163

superoxide dismutase type 1. The actual pathway of
destruction is not known, however, nor is the trigger forthe rapid degeneration that marks ALS. Further researchmay show that other pathways are involved, perhaps oneseven more important than this one. Autoimmune factorsor premature aging may play some role, as could viral
agents or environmental toxins.
Two major forms of ALS are known: familial and

sporadic. Familial ALS accounts for about 10% of all ALScases. As the name suggests, familial ALS is believed to becaused by the inheritance of one or more faulty genes.About 15% of families with this type of ALS have muta-tions in the gene for SOD-1. SOD-1 gene defects are dom-inant, meaning only one gene copy is needed to developthe disease. Therefore, a parent with the faulty gene has a50% chance of passing the gene along to a child.Sporadic ALS has no known cause. While many

environmental toxins have been suggested as causes, todate no research has confirmed any of the candidatesinvestigated, including aluminum and mercury and leadfrom dental fillings. As research progresses, it is likelythat many cases of sporadic ALS will be shown to have agenetic basis as well.
A third type, called Western Pacific ALS, occurs in
Guam and other Pacific islands. This form combinessymptoms of both ALS and Parkinson’s disease .
Symptoms

Symptoms
The earliest sign of ALS is most often weakness in
the arms or legs, usually more pronounced on one sidethan the other at first. Loss of function is usually more
GALE ENCYCLOPEDIA OF MEDICINE 2 164Amyotrophic lateral sclerosis
Normal nerve fiberNORMAL SPINAL NEURON DISEASED SPINAL NEURON
Normal skeletal muscle Wasted skeletal muscleAffected nerve fiber
Amyotrophic lateral sclerosis (ALS) is caused by the degeneration and death of motor neurons in the spinal cord and brain.

These neurons convey electrical messages from the brain to the muscles to stimulate movement in the arms, legs, trunk,neck, and head. As motor neurons degenerate, the muscles are weakened and cannot move as effectively, leading to musclewasting. (Illustration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 164

rapid in the legs among people with familial ALS and in
the arms among those with sporadic ALS. Leg weaknessmay first become apparent by an increased frequency ofstumbling on uneven pavement, or an unexplained diffi-culty climbing stairs. Arm weakness may lead to difficul-ty grasping and holding a cup, for instance, or loss ofdexterity in the fingers.
Less often, the earliest sign of ALS is weakness in
the bulbar muscles, those muscles in the mouth and

throat that control chewing, swallowing, and speaking. Aperson with bulbar weakness may become hoarse or tiredafter speaking at length, or speech may become slurred.
In addition to weakness, the other cardinal signs of
ALS are muscle wasting and persistent twitching (fascic-ulation). These are usually seen after weakness becomesobvious. Fasciculation is quite common in people withoutthe disease, and is virtually never the first sign of ALS.
While initial weakness may be limited to one region,

ALS almost always progresses rapidly to involve virtuallyall the voluntary muscle groups in the body. Later symp-toms include loss of the ability to walk, to use the arms andhands, to speak clearly or at all, to swallow, and to hold thehead up. Weakness of the respiratory muscles makesbreathing and coughing difficult, and poor swallowing con-trol increases the likelihood of inhaling food or saliva (aspi-ration). Aspiration increases the likelihood of lung infec-tion, which is often the cause of

of lung infec-tion, which is often the cause of death. With a ventilatorand scrupulous bronchial hygiene, a person with ALS maylive much longer than the average, although weakness andwasting will continue to erode any remaining functionalabilities. Most people with ALS continue to retain functionof the extraocular muscles that move their eyes, allowingsome communication to take place with simple blinks orthrough use of a computer-assisted device.

ical history and physical exam, plus a neurological exam-ination to determine the distribution and extent of weak-ness. An electrical test of muscle function, called an elec-tromyogram, or EMG, is an important part of the diag-nostic process. Various other tests, including blood andurine tests, x rays, and CT scans, may be done to rule outother possible causes of the symptoms, such as tumors ofthe skull base or high cervical spinal cord, thyroid dis-ease, spinal arthritis, lead poisoning , or

deficiency. ALS is rarely misdiagnosed following a care-ful review of all these factors.
Treatment
There is no cure for ALS, and no treatment that can
significantly alter its course. There are many thingsKEY TERMS
Aspiration —Inhalation of food or liquids into the
lungs.
Bulbar muscles —Muscles of the mouth and throat
responsible for speech and swallowing.
Fasciculations —Involuntary twitching of muscles.
Motor neuron —A nerve cell that controls a mus-
cle.

cle.
Riluzole (Rilutek) —The first drug approved in the
United States for the treatment of ALS.
Voluntary muscle —A muscle under conscious
control; contrasted with smooth muscle and heartmuscle which are not under voluntary control.
which can be done, however, to help maintain quality of
life and to retain functional ability even in the face ofprogressive weakness.
As of early 1998, only one drug had been approved

for treatment of ALS. Riluzole (Rilutek) appears to pro-vide on average a three-month increase in life expectancywhen taken regularly early in the disease, and shows asignificant slowing of the loss of muscle strength. Rilu-zole acts by decreasing glutamate release from nerve ter-minals. Experimental trials of nerve growth factor havenot demonstrated any benefit. No other drug or vitamincurrently available has been shown to have any effect onthe course of ALS.

A physical therapist works with an affected person
and family to implement exercise and stretching pro-
grams to maintain strength and range of motion, and topromote general health. Swimming may be a goodchoice for people with ALS, as it provides a low-impactworkout to most muscle groups. One result of chronicinactivity is contracture, or muscle shortening. Contrac-
tures limit a person’s range of motion, and are often

painful. Regular stretching can prevent contracture. Sev-eral drugs are available to reduce cramping, a commoncomplaint in ALS.
An occupational therapist can help design solutions
to movement and coordination problems, and provideadvice on adaptive devices and home modifications.
Speech and swallowing difficulties can be mini-

mized or delayed through training provided by a speech-language pathologist. This specialist can also provideadvice on communication aids, including computer-assisted devices and simpler word boards.
GALE ENCYCLOPEDIA OF MEDICINE 2 165Amyotrophic lateral sclerosisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 165

Nutritional advice can be provided by a nutritionist.
A person with ALS often needs softer foods to preventjaw exhaustion or choking . Later in the disease, nutri-
tion may be provided by a gastrostomy tube inserted
into the stomach.
Mechanical ventilation may be used when breathing

becomes too difficult. Modern mechanical ventilators aresmall and portable, allowing a person with ALS to main-tain the maximum level of function and mobility. Ventila-tion may be administered through a mouth or nose piece,or through a tracheostomy tube. This tube is insertedthrough a small hole made in the windpipe. In addition toproviding direct access to the airway, the tube alsodecreases the risk aspiration. While many people withrapidly progressing ALS choose not to use ventilators

progressing ALS choose not to use ventilators forlengthy periods, they are increasingly being used to pro-long life for a short time.

The progressive nature of ALS means that most per-
sons will eventually require full-time nursing care. Thiscare is often provided by a spouse or other family mem-ber. While the skills involved are not difficult to learn,the physical and emotional burden of care can be over-whelming. Caregivers need to recognize and provide fortheir own needs as well as those of people with ALS, toprevent depression, burnout, and bitterness.
Throughout the disease, a support group can provide

important psychological aid to affected persons and theircaregivers as they come to terms with the losses ALSinflicts. Support groups are sponsored by both the ALSSociety and the Muscular Dystrophy Association.
Given the grave prognosis and absence of tradition-

al medical treatments, it is not surprising that a largenumber of alternative treatments have been tried forALS. Two studies published in 1988 suggested thatamino-acid therapies may provide some improvementfor some people with ALS. While individual reportsclaim benefits for megavitamin therapy, herbal medi-cine, and removal of dental fillings, for instance, no evi-dence suggests that these offer any more than a briefpsychological boost, often followed by a more severeletdown when it becomes

followed by a more severeletdown when it becomes apparent the disease has con-tinued unabated. However, once the causes of ALS arebetter understood, alternative therapies may be moreintensively studied. For example, if damage by free radi-cals turns out to be the root of most of the symptoms,antioxidant vitamins and supplements may be used

more routinely to slow the progression of ALS. Or, ifenvironmental toxins are implicated, alternative thera-pies with the goal of detoxifying the body may be ofsome use.Prognosis
ALS usually progresses rapidly, and leads to death
from respiratory infection within three to five years inmost cases. The slowest disease progression is seen inthose who are young and have their first symptoms in thelimbs. About 10% of people with ALS live longer thaneight years.

There is no known way to prevent ALS or to alter its
course.
Resources
BOOKS
Adams, Raymond D, Victor, Maurice and Ropper, Allan H.
Adam’s & Victor’s Principles of Neurology, 6th ed. New
York, McGraw Hill, 1997.
Brown, Robert H. “The motor neuron diseases.” In Harrison’s
Principles of Internal Medicine, 14th ed., edited by
Anthony S. Fauci, et al. New York: McGraw-Hill, 1998,2368-2372.
Feldman, Eva L. “Motor neuron diseases.” In Cecil Textbook of

Medicine, 21st ed., edited by Goldman, Lee and Bennett,
J. Claude. Philadelphia: W.B. Saunders, 2000, 2089-2092.
Kimura, Jun and Kaji, Ryuji. Physiology of ALS and Related
Diseases. Amsterdam, Elsevier Science, 1997.
Mitsumoto, Hiroshi, Chad, David A, Pioro, Erik and Gilman,
Sid. Amyotrophic Lateral Sclerosis. New York, Oxford
University Press, 1997.
Ansevin CF. Treatment of ALS with pleconaril. Neurology,
56(5): 691-692, 2001.

Eisen A, Weber M. The motor cortex and amyotrophic lateral
sclerosis. Muscle and Nerve, 24(4): 564-573, 2001.
Gelanis DF. Respiratory Failure or Impairment in Amyotrophic
Lateral Sclerosis. Current treatment options in neurology,
3(2): 133-138, 2001.
Ludolph AC. Treatment of amyotrophic lateral sclerosis—what
is the next step? Journal of Neurology, 246 Suppl 6:13-18,
2000.
Pasetti C, Zanini G. The physician-patient relationship in amy-

otrophic lateral sclerosis. Neurological Science, 21(5):
318-323, 2000.
Robberecht W. Genetics of amyotrophic lateral sclerosis. Jour-
nal of Neurology, 246 Suppl 6: 2-6, 2000.
Robbins RA, Simmons Z, Bremer BA, Walsh SM, Fischer S.
Quality of life in ALS is maintained as physical functiondeclines. Neurology, 56(4): 442-444, 2001.
ALS Association of America. 27001 Agoura Road, Suite 150,

Calabasas Hills, CA 91301-5104. (800) 782-4747 (Infor-mation and Referral Service) or (818) 880-9007. Fax:(818) 880-9006. <http://www.alsa.org/als/>.
GALE ENCYCLOPEDIA OF MEDICINE 2 166Amyotrophic lateral sclerosisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 166

American Academy of Family Physicians. 11400 Tomahawk
Creek Parkway, Leawood, KS 66211-2672. (913) 906-6000, <http://www.aafp.org/>. fp@aafp.org.
American Academy of Neurology. 1080 Montreal Avenue, St.
Paul, Minnesota 55116. (651) 695-1940. Fax: (651) 695-2791. <http://www.aan.com/>. info@aan.org.
American Medical Association. 515 N. State Street, Chicago,
IL 60610. (312) 464-5000. <http:// www.ama-assn.org/>.
Centers for Disease Control and Prevention. 1600 Clifton

Road, Atlanta, GA 30333. (404) 639-3534 or (800) 311-3435. <http://www.cdc.gov/ncidod/ eid/vol7no1/brown.htm>. http://www.cdc.gov/ netinfo.htm.
Muscular Dystrophy Association. 3300 East Sunrise Drive, Tuc-
son AZ 85718-3208. (520) 529-2000 or (800) 572-1717.Fax: (520) 529-5300. <http://www.mdausa.org>.
OTHER
ALS Society of Canada: <http://www.als.ca/>.
ALS Survival Guide: <http://www.lougehrigsdisease.net/>.American Academy of Family Physicians: <http://www.aafp.
org/afp/990315ap/1489.html>.

National Institute of Neurological Disorders and Stroke:
<http://www.ninds.nih.gov/health_and_medical/disor-ders/amyotrophiclateralsclerosis_doc.htm>.
National Library of Medicine: <http://www.nlm.nih.gov/med-
lineplus/amyotrophiclateralsclerosis.html>.
National Organization for Rare Diseases: <http://www.stepstn.
com/cgi-win/nord.exe?proc=Redirect&type=rdb_sum&id=57.htm>.
World Federation of Neurology: <http://www.wfnals.org/>.
L. Fleming Fallon, Jr., MD, DrPH

Anaerobic infections
An anaerobic infection is an infection caused by
bacteria (called anaerobes) which cannot grow in thepresence of oxygen. Anaerobic bacteria can infect deepwounds , deep tissues, and internal organs where there is
little oxygen. These infections are characterized byabscess formation, foul-smelling pus, and tissue
destruction.
Anaerobic means “life without air.” Anaerobic bac-

teria grow in places which completely, or almost com-pletely, lack oxygen. They are normally found in themouth, gastrointestinal tract, and vagina, and on the skin.Commonly known diseases caused by anaerobic bacteriainclude gas gangrene ,tetanus , and botulism . Nearly all
dental infections are caused by anaerobic bacteria.Anaerobic bacteria can cause an infection when a

normal barrier (such as skin, gums, or intestinal wall)is damaged due to surgery, injury, or disease. Usually,the immune system kills any invading bacteria, butsometimes the bacteria are able to grow and cause aninfection. Body sites that have tissue destruction(necrosis) or a poor blood supply are low in oxygenand favor the growth of anaerobic bacteria. The lowoxygen condition can result from blood vessel disease,shock , injury, and surgery.
Anaerobic bacteria can cause infection practically

anywhere in the body. For example:
• Mouth, head, and neck. Infections can occur in the root
canals, gums (gingivitis), jaw, tonsils, throat, sinuses,and ears.
• Lung. Anaerobic bacteria can cause pneumonia , lung
abscesses, infecton of the lining of the lung ( empye-
ma), and dilated lung bronchi ( bronchiectasis ).
• Intraabdominal. Anaerobic infections within the
abdomen include abscess formation, peritonitis , and
appendicitis .
• Female genital tract. Anaerobic bacteria can cause

pelvic abscesses, pelvic inflammatory disease ,
inflammation of the uterine lining (endometritis), andpelvic infections following abortion, childbirth , and
surgery.
• Skin and soft tissue. Anaerobic bacteria are common
causes of diabetic skin ulcers, gangrene, destructiveinfection of the deep skin and tissues (necrotizing fasci-tis), and bite wound infections.
• Central nervous system. Anaerobic bacteria can cause
brain and spinal cord abscesses.

• Bloodstream. Anaerobic bacteria can be found in the
bloodstream of ill patients (a condition called bac-teremia).
People who have experienced shock, injury, or

surgery, and those with blood vessel disease or tumorsare at an increased risk for infection by anaerobic bacte-ria. There are many different kinds of anaerobic bacteriawhich can cause an infection. Indeed, most anaerobicinfections are “mixed infections” which means thatthere is a mixture of different bacteria growing. Theanaerobic bacteria that most frequently cause infectionsare Bacteroides fragilis ,Peptostreptococcus , and
Clostridium species.

The signs and symptoms of anaerobic infection
can vary depending on the location of the infection. Ingeneral, anaerobic infections result in tissue destruc-
GALE ENCYCLOPEDIA OF MEDICINE 2 167Anaerobic infectionsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 167

tion, an abscess which drains foul-smelling pus, and
possibly fever . Symptoms for specific infections are
as follows:
• Tooth and gum infections. Swollen, tender bleeding
gums, bad breath , and pain . Severe infections may
produce oozing sores.
• Throat infection. An extremely sore throat , bad breath,
a bad taste in the mouth, fever, and a sense of choking .
• Lung infection. Chest pain, coughing, difficulty breath-
ing, fever, foul-smelling sputum, and weight loss.

• Intraabdominal infection. Pain, fever, and possibly, if fol-
lowing surgery, foul- smelling drainage from the wound.
• Pelvic infection. Foul-smelling pus or blood draining
from the uterus, general or localized pelvic pain, fever,and chills.
• Skin and soft tissue infection. Infected wounds are red,

painful, swollen, and may drain a foul-smelling pus.Skin infection causes localized swelling, pain, redness,and possibly a painful, open sore (ulcer) which drainsfoul-smelling pus. Severe skin infections may causeextensive tissue destruction (necrosis).
• Bloodstream. Bloodstream invasion causes high fever
(up to 105°F [40.6°C]), chills, a general ill feeling, andis potentially fatal.
Diagnosis
The diagnosis of anaerobic infection is based pri-

marily on symptoms, the patient’s medical history, andlocation of the infection. A foul-smelling infection ordrainage from an abscess is diagnostic of anaerobicinfection. This foul smell is produced by anaerobic bac-teria and occurs in one third to one half of patients late inthe infection. Other clues to anaerobic infection includetissue necrosis and gas production at the infection site. Asample from the infected site may be obtained, using aswab or a needle and syringe, to determine which

aswab or a needle and syringe, to determine which bacte-ria is (are) causing the infection. Because these bacteriacan be easily killed by oxygen, they rarely grow in thelaboratory cultures of tissue or pus samples.KEY TERMS

Abscess —A lump filled with pus resulting from an
Anaerobic —Living and growing in the absence of
oxygen.
Necrosis —Tissue death and destruction resulting
from infection or disease.The recent medical history of the patient is helpful
in diagnosing anaerobic infection. A patient who has orrecently had surgery, dental work, tumors, blood vesseldisease, or injury are susceptible to this infection. Thefailure to improve following treatment with antibiotics

that aren’t able to kill anaerobes is another clue that theinfection is caused by anaerobes. The location and typeof infection also help in the diagnosis.
Diagnostic tests may include blood tests to see if
bacteria are in the bloodstream and x rays to look atinternal infections.
Treatment
Serious infections may require hospitalization for

treatment. Immediate antibiotic treatment of anaerobicinfections is necessary. Laboratory testing may identifythe bacteria causing the infection and also which antibi-otic will work best. Every antibiotic does not workagainst all anaerobic bacteria but nearly all anaerobes arekilled by chloramphenicol (Chloromycetin), metronida-zole (Flagyl or Protostat), and imipenem (Primaxin).Other antibiotics which may be used are clindamycin(Cleocin) or cefoxitin (Mefoxin).

Surgical removal or drainage of the abscess is
almost always required. This may involve drainage byneedle and syringe to remove the pus from a skin abscess(called “aspiration”). The area would be numbed prior tothe aspiration procedure. Also, some internal abscessescan be drained using this procedure with the help ofultrasound (a device which uses sound waves to visualizeinternal organs). This type of abscess drainage may beperformed in the doctor’s office.
Prognosis

Prognosis
Complete recovery should be achieved with the
appropriate surgery and antibiotic treatment. Untreatedor uncontrolled infections can cause severe tissue andbone destruction, which would require plastic surgery torepair. Serious infections can be life threatening.
Although anaerobic infections can occur in anyone,
good hygiene and general health may help to preventinfections.
Resources
BOOKS

GALE ENCYCLOPEDIA OF MEDICINE 2 168Anaerobic infectionsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 168

Anaerobic myositis seeGangrene
Anal atresia
The anus is either not present or it is in the wrong
place.
There are basically two kinds of anal atresia. In boys

with high anal atresia, there may be a channel (fistula)connecting the large intestine to either the urethra (whichdelivers urine from the bladder) or the bladder itself. Ingirls, the channel may connect with the vagina. Sixtypercent of children with high anal atresia have otherdefects, including problems with the esophagus, urinarytract, and bones. In low anal atresia, the channel mayopen in front of the circular mass of muscles that con-strict to close the anal opening (anal sphincter) or,

to close the anal opening (anal sphincter) or, inboys, below the scrotum. Occasionally, the intestine endsjust under the skin. It is estimated that overall abnormali-ties of the anus and rectum occur in about one in every5,000 births and are slightly more common among boys.A mother who has one child with these kind of condi-tions has a 1% chance of having another child who suf-fers from this ailment.

Cause and symptoms
Anal atresia is a defect in the development of the
fetus. The cause is unknown, but genetics seem to play aminor role.
Diagnosis
Usually a physician can make an obvious visual

diagnosis of anal atesia right after birth. Occasionally,however, anal atresia is missed until the baby is fed andsigns of intestinal obstruction appear. At the end of thefirst or second day, the abdomen swells and there is vom-iting of fecal material. To determine the type of anal atre-sia and the exact position, x rays will be taken whichinclude injecting opaque dye into the opening. Magnetic
resonance imaging (MRI) or computed tomography

scans (CT), as well as ultrasound, are the imaging tech-
niques used to determine the type and size of the analatresia. Ultrasound uses sound waves, CT scans pass xrays through the body at different angles, and an MRIuses a magnetic field and radio waves.KEY TERMS
Anus —The canal at the end of the large intestine
through which waste is excreted to the outside ofthe body.
Bowel obstruction —Anything that prevents waste

from moving normally to the anal opening.
Colostomy —An operation where the large intes-
tine is diverted through an opening in theabdomen and waste is excreted.
Feces —Bodily waste material that normally passes
through the anus.
Fistula —An abnormal channel that connects two
organs or connects an organ to the skin.
Treatment
Surgery is the only treatment for anal atresia. For

high anal atresia, immediately after the diagnosis is made,a surgical incision is made in the large intestine to make atemporary opening ( colostomy ) in the abdomen where

waste is excreted. Several months later, the intestine ismoved into the ring of muscle (sphincter) that is part ofthe anus and a hole is made in the skin. The colostomy isclosed several weeks later. In low anal atresia, immediate-ly after diagnosis, a hole is made in the skin to open thearea where the anus should be. If the channel is in thewrong place, the intestine is moved into the correct posi-tion sometime during the child’s first year. After surgery,the pediatric surgeon uses an

year. After surgery,the pediatric surgeon uses an instrument to dilate orwiden the rectum and teaches the parents how to do thisdaily at home to prevent scar tissue from contracting.

Prognosis
With high anal atresia, many children have problems
controlling bowel function. Most also become constipat-ed. With low anal atresia, children generally have goodbowel control, but they may still become constipated.
There is no known way to prevent anal atresia.
Resources
BOOKS
Freeman, Neill V . “Anorectal Malformations.” In Surgery of the
Newborn. Edinburgh: Churchill Livingstone, 1994.
Paidas, Charles N., and Alberto Pena. “Rectum and Anus.” In

Surgery of Infants and Children. Philadelphia: Lippincott-
Raven, 1997.
Jeanine Barone, Physiologist
GALE ENCYCLOPEDIA OF MEDICINE 2 169Anal atresiaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 169

Anal cancer
Anal cancer is an uncommon form of cancer affect-
ing the anus. The anus is the inch-and-a-half-long endportion of the large intestine, which opens to allow solidwastes to exit the body. Other parts of the large intestineinclude the colon and the rectum.
Different cancers can develop in different parts of

the anus, part of which is inside the body and part ofwhich is outside. Sometimes abnormal changes of theanus are harmless in their early stages but may laterdevelop into cancer. Some anal warts , for example, con-
tain precancerous areas and can develop into cancer.Types of anal cancer include:
• Squamous Cell Carcinomas. Approximately half of

anal cancers are squamous cell carcinomas, which arisefrom the cells lining the anal margin and the anal canal.The anal margin is the part of the anus that is half insideand half outside the body, and the anal canal is the partof the anus that is inside the body. The earliest form ofsquamous cell carcinoma is known as carcinoma insitu, or Bowen’s disease.
• Cloacogenic Carcinomas. Approximately one-fourth to

one-third of anal tumors are cloacogenic carcinomas.These tumors develop in the transitional zone, or cloa-ca, which is a ring of tissue between the anal canal andthe rectum.
• Adenocarcinomas. About 15% of anal cancers are ade-
nocarcinomas, which affect glands in the anal area. Onetype of adenocarcinoma that can occur in the anal areais called Paget’s disease, which can also affect thevulva, breasts, and other areas of the body.
• Skin cancers. A small percentage of anal cancers are

either basal cell carcinomas, or malignant melanomas,two types of skin cancer. Malignant melanomas, whichdevelop from skin cells that produce the brown pigmentcalled melanin, are far more common on areas of thebody exposed to the sun.
Approximately 3,500 Americans will be diagnosed

with anal cancer in 2001, and an estimated 500 individu-als will die of the disease during this same interval,according to the American Cancer Society. Anal cancersare fairly rare: they make up only 1% to 2% of cancersaffecting the digestive system. The disease affectswomen somewhat more often than men, although thenumber of cases among men, particularly homosexualmen, seems to be increasing.Causes and symptoms

although certain individuals appear to have a higher riskof developing the disease. Smokers are at higher risk, asare individuals with certain types of the human papillo-mavirus (HPV), and those with long-term problems inthe anal area, such as abnormal openings known as fistu-las. Since it increases the risk of HPV infection, the prac-tice of anal sex appears to increase the risk of analcancer—male homosexuals who practice anal sex areabout 33 times more likely to have anal cancers than

33 times more likely to have anal cancers than het-erosexual men. Those with weakened immune systems,such individuals with HIV, or transplant patients takingimmunosuppressant drugs , are also at higher risk.

Most individuals with anal cancer are over the age of 50.
Symptoms of anal cancer resemble those found in
other harmless conditions. They include pain ,itching
and bleeding, straining during a bowel movement,change in bowel habits, change in the diameter of thestool, discharge from the anus, and swollen lymph nodesin the anal or groin area.
Diagnosis
Anal cancer is sometimes diagnosed during routine

physicals, or during minor procedures such as hemorrhoidremoval. It may also be diagnosed during a digital rectal
examination (DRE), when a physician inserts a gloved,
lubricated finger into the anus to feel for unusual growths.Individuals over the age of 50 who have no symptomsshould have a digital rectal examination (DRE) every  fiveto 10 years, according to American Cancer Society (ACS)guidelines for early detection of colorectal cancer.

Other diagnostic procedures for anal cancer include:
Anoscopy . A procedure that involves use of a special
device to examine the anus. Proctoscopy. A procedure thatinvolves use of a lighted scope to see the anal canal. Tran-srectal ultrasound. A procedure in which sound waves areused to create an image of the anus and nearby tissues.
A biopsy is performed on any suspicious growths;

that is, a tiny piece of the growth is examined under amicroscope for cancer cells. The physician may also per-form a procedure called a fine needle aspiration biopsy,in which a needle is used to withdraw fluid from lymphnodes located near the growth, to make sure the cancerhasn’t spread to these nodes.
Anal cancer severity is categorized by the following
stages:
• Stage 0 anal cancer is found only in the top layer of
anal tissue.

• Stage I anal cancer has spread beyond the top layer of
anal tissue, but is less than 1 inch in diameter.
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• Stage II anal cancer has spread beyond the top layer of
anal tissue and is larger than 1 inch in diameter, but hasnot spread to nearby organs or lymph nodes.
• Stage IIIA anal cancer has spread to the lymph nodes
around the rectum or to nearby organs such as the vagi-na or bladder.
• Stage IIIB anal cancer has spread to lymph nodes in the
mid-abdomen or groin, or to nearby organs and thelymph nodes around the rectum.
• Stage IV anal cancer has spread to distant lymph nodes

within the abdomen or to distant organs.
Treatment
Anal cancer is treated using three methods, used
either in concert or individually: surgery, radiation ther-
apy, and chemotherapy .
Two types of surgery may be performed. A local

resection, performed if the cancer has not spread,removes the tumor and an area of tissue around the tumor.An abdominoperineal resection is a more complex proce-dure in which the anus and the lower rectum are removed,and an opening called a colostomy is created for body
wastes to exit. This procedure is fairly uncommon todaybecause radiation and chemotherapy are just as effective.
Radiation therapy uses high-energy rays to fight

cancer cells. It is usually delivered via a machine outsidethe body, but may also be delivered via surgicallyimplanted radioactive pellets. This latter method is calledinternal radiation, brachytherapy, or interstitial radiation.Side effects of radiation may include tiredness, skin dam-age resembling sunburn , and damage to anal tissues.
Chemotherapy fights cancer using drugs, which may

be delivered via pill or needle. Some chemotherapy typeskill cancer cells directly, while others act indirectly bymaking cancer cells more vulnerable to radiation. Themain drugs used to treat anal cancer are 5-fluorouracil (5-FU) and mitomycin or 5-FU and cisplatin. Side effects ofchemotherapy, which damages normal cells in addition tocancer cells, may include nausea and vomiting , hair
loss, loss of appetite, diarrhea , mouth sores, fatigue ,

shortness of breath , and a weakened immune system.
Research suggests acupuncture can help manage
chemotherapy-related nausea and vomiting and controlpain associated with surgery.
Prognosis
Anal cancer is often curable. The chance of recovery
depends on the cancer stage and the patient’s general health.KEY TERMS
Biopsy —A procedure in which a small piece of
body tissue is removed and examined under amicroscope for cancer.
Chemotherapy —A cancer treatment in which

drugs delivered into the blood stream kill cancercells or make them more vulnerable to radiationtherapy.
Human papillomavirus (HPV) —A virus with many
subtypes, some of which cause cell changes thatincrease the risk of certain cancers.
Human immunodeficiency virus (HIV) —The virus
that causes acquired immune deficiency syn-drome (AIDS).
Lymph nodes —Bean-shaped structures found
throughout the body that produce and store infec-tion-fighting cells.

Radiation therapy —A cancer treatment that uses
high-energy rays to kill or weaken cancer cells.Radiation may be delivered externally or internal-ly via surgically implanted pellets.
Reducing the risks of the sexually transmitted dis-
eases HPV and HIV also reduces the risk of anal cancer. In
addition, quitting smoking lowers the risk of anal cancer.
Resources
BOOKS
American Joint Committee on Cancer: AJCC Cancer Staging
Manual. Philadelphia, Pa: Lippincott-Raven Publishers,
1997.

1997.
Murakami, M, KJ Gurski and MA Steller. “Human Papillo-
mavirus Vaccines For Cervical Cancer.” Journal of
Immunotherapy 1999, 22(3):212-8.
American Cancer Society. (800) ACS-2345. <http://www.
cancer.org>.
American College of Gastroenterology. <http://www.acg.gi.org/>.American Gastroenterological Association. 7910 Woodmont
Ave., Seventh Floor, Bethesda, MD 20814. (301) 654-2055. <http://www.gastro.org>.
American Society of Colon and Rectal Surgeons. 85 W. Algo-

nquin Road, Suite 550, Arlington Heights, IL 60005.(847)290-9184.
The NCI Office of Cancer Complementary and Alternative
Medicine. <http://occam.nci.nih.gov>.
GALE ENCYCLOPEDIA OF MEDICINE 2 171Anal cancerGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 171

National Cancer Institute. 31 Center Drive, MSC 2580, Bethes-
da, MD 20892-2580. (800) 4-CANCER. <http://www.nci.nih.gov>.
National Coalition for Cancer Survivorship. 1010 Wayne
Avenue, 5th Floor, Suite 300, Silver Spring, MD 20910.(888) 650-9127.
The NIH National Center for Complementary and Alternative
Medicine. Post Office Box 8218, Silver Spring, MD20907-8218. (888) 644-6226. <http://nccam.nih.gov>.
United Ostomy Association. (800) 826-0826. <http://www.uoa.
org>.

org>.
Anal fissure seeAnorectal disorders
Anal warts
Anal warts , also known as condyloma acuminata,
are small warts that can occur in the rectum.
Initially appear as tiny blemishes that can be as

small as the head of a pin or grow into larger cauliflower-like protuberances. They can be yellow, pink, or lightbrown in color, and only rarely are painful or uncomfort-able. In fact, infected individuals often are unaware thatthey exist. Most cases are caused by sexual transmission.
Most individuals have between one to 10 genital
warts thtat range in size from roughly 0.5–1.9 cm
2. Some
will complain of painless bumps or itching , but often,

these warts can remain completely unnoticed.
Condyloma acuminatum is one of the most common
sexually transmitted disease (STD) in the United States.Young adults aged 17 to 33 years are at greatest risk.Risk factors include smoking , using oral contracep-
tives , having multiple sexual partners, and an early coital
age. In addition, individuals who have a history ofimmunosuppression or anal intercourse are also at risk.
Roughly 90% of all anal warts are caused by the

human papilloma virus (HPV) types 6 and 11, which arethe least likely of over 60 types of HPV to become can-cerous. Anal warts are usually transmitted through directsexual contact with someone who is infected with condy-loma acuminata anywhere in the genital area, includingthe penis and vagina. Studies have shown that roughly75% of those who engage in sexual contact with some-one infected with condyloma acuminata will developthese warts within three months.
Treatment

Treatment
According to guidelines from the Centers for Dis-
ease Control (CDC), the treatment of all genital warts,including anal warts, should be conducted according tothe methods preferred by the patient, the medications orprocedures most readily available, and the experience ofthe patient’s physician in removing anal warts.
Treatment options include electrical cautery, surgi-

cal removal, or both. Warts that appear inside the analcanal will almost always be treated with cauterization orsurgical removal. Surgical removal, also known as exci-sion, has the highest success rates and lowest recurrencerates. Indeed, studies have shown that initial cure ratesrange from 63–91%.
Unfortunately, most cases require numerous treat-

ments because the virus that causes the warts can live inthe surrounding tissue. The area may seem normal andwart-free for six months or longer before another wartdevelops.
Laser surgery is another possibility, but requires
local, general, or spinal anesthesia, depending on thenumber warts and where they are.
Electrocoagulation, a technique that uses electrical

energy to destroy the warts, is usually the most painful ofthe procedures done to eliminate condyloma acuminataof the anus, and is usually reserved for larger warts. It isdone with local anesthesia, and may cause discharge orbleeding from the anus.
Follow-up visits to the physician are necessary to

make sure that the warts have not recurred. It is recom-mended that these patients see their physicians everythree to six months for up to 1.5 years, which is how longthe incubation period is for the HPV virus.
Carbon dioxide laser treatment and electrodesicca-

tion are other options, but these are usually reserved forextensive warts or those that continue to recur despitenumerous treatments. However, because HPV virus canbe transmitted via the smoke caused by these procedures,they are usually reserved for the worst infections.
For small warts that affect only the skin around the
anus, several medications are available, which can beapplied directly to the surface of the warts by a physicianor by the patients themselves.

Such medications include podophyllum resin
(Podocon-25, Pod-Ben-25), a substance made from thecytotoxic extracts of several plants. This agent offers a
GALE ENCYCLOPEDIA OF MEDICINE 2 172Anal wartsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 172

cure rate of 20–50% when used alone, and is applied by
the physician weekly and then washed off 6 hours laterby the patient.
Podofilox (Condylox) is another agent, and is avail-
able for patients to use at home. It can be applied twicedaily for up to 4 weeks. Podofilox offers a slightly highercure rate than podophyllin, and can also be used to pre-vent warts.
Trichloroacetic and bichloroacetic acids are avail-

able in several concentrations up to 80% for the treat-ment of condyloma acuminata. These acids work to cau-terize the skin, and are quite caustic. Nevertheless, theycause less irritation and overall body effects than theother agents mentioned above. Recurrence, however, ishigher with these acids.
Bleomycin (Blenoxane) is another treatment option,

but it has several drawbacks. First, it must be adminis-tered by a physician into each lesion via injection, but iscan have a host of side effects, and patients must be fol-lowed carefully by their physician.
Imiquimod 5% cream is also available for patients to
apply themselves. It is to be applied three times weekly,for up to 16 weeks, and has been shown to clear wartswithin eight to 10 weeks.
Finally, the interferon drugs, which are naturally

occurring proteins that have antiviral and antitumoreffects, are available. These include interferon alfa 2aand 2b (Roferon, Intron A), which are to be injected intoeach lesion twice a week for up to eight weeks.
Prognosis
Once a diagnosis of anal warts has been made, fur-

ther outbreaks can be controlled or sometimes preventedwith proper care. Unfortunately, many cases of anal wartseither fail to respond to treatment or recur. Patients haveto undergo roughly six to nine treatments over severalmonths to assure that the warts are completely eradicated.
Recurrence rates have been estimated to be over 50%

after one year and may be due to the long incubation ofHPV (up to 1.5 years), deep lesions, undetected lesions,virus present in surrounding skin that is not treated.
Sexual abstinence and monogamous relationships can

be the most effective form of prevention, and condomsmay also decrease the chances of transmission of condylo-ma acuminata. Abstinence from sexual relations with peo-ple who have anal or genital warts can prevent infection.Unfortunately, since many people may not be aware thatthey have this condition, this is not always possible.KEY TERMS
Electrocoagulation —a technique using electrical

energy to destroy the warts. Usually done for wartswithin the anus with a local anesthesia, electroco-agulation is most painful form of therapy, and cancause both bleeding and discharge from the anus.
Individuals infected with anal warts should have fol-
low-up checkups every few weeks after their initial treat-ment, after which self-exams can be done.
Sexual partners of people who have anal warts

should also be examined, as a precautionary preventivemeasure.
Finally, 5-flourouracil (Adrucil, Efudex, Fluoroplex)
may be useful to prevent recurrence once the warts havebeen removed. Treatment must, however, be initiatedwithin 1 month of wart removal.
Resources
Maw, Raymond, and Geo von Krogh. “The Management of
Anal Warts.” British Medical Journal , no. 321 (October
14, 2000):910-11.

Centers for Disease Control and Prevention, Sexually Trans-
mitted Diseases Hotline: (800) 227-8922.
OTHER
<http://www.arthritis-baldness-impotency- obesity.com/
medcenter/NF009.html>.
<http://www.emedicine.com>.<http://wwwmedlineplus.adam.com>.<http://www.mayohealth.org>.
Analgesics
Analgesics are medicines that relieve pain .
Purpose
Analgesics are those drugs whose primary purpose

is pain relief. The primary classes of analgesics are thenarcotics, including additional agents that are chemically
GALE ENCYCLOPEDIA OF MEDICINE 2 173AnalgesicsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 173

based on the morphine molecule but have minimal abuse
potential; nonsteroidal anti-inflammatory drugs
(NSAIDs) including the salicylates; andacetaminophen . Other drugs, notably the tricyclic anti-

depressants and anti-epileptic agents such as gabapentin,have been used to relieve pain, particularly neurologicpain, but are not routinely classified as analgesics. Anal-gesics provide symptomatic relief, but have no effect oncausation, although clearly the NSAIDs, by virtue oftheir dual activity, may be beneficial in both regards.
Pain has been classified as “productive” pain and

“non-productive” pain. While this distinction has nophysiologic meaning, it may serve as a guide to treat-ment. “Productive” pain has been described as a warningof injury, and so may be both an indication of need fortreatment and a guide to diagnosis. “Non-productive”pain by definition serves no purpose either as a warningor diagnostic tool.
Although pain syndromes may be dissimilar, the

common factor is a sensory pathway from the affectedorgan to the brain. Analgesics work at the level of thenerves, either by blocking the signal from the peripheralnervous system, or by distorting the interpretation by thecentral nervous system. Selection of an appropriate anal-gesic is based on consideration of the risk-benefit factorsof each class of drugs, based on type of pain, severity ofpain, and risk of adverse effects. Traditionally, pain hasbeen divided into two classes, acute and

pain hasbeen divided into two classes, acute and chronic,although severity and projected patient survival are otherfactors that must be considered in drug selection.

Acute pain
Acute pain is self limiting in duration, and includes
post-operative pain, pain of injury, and childbirth .

Because pain of these types is expected to be short term,the long-term side effects of analgesic therapy may rou-tinely be ignored. Thus, these patients may safely betreated with narcotic analgesics without concern for theiraddictive potential, or NSAIDs with only limited concernfor their ulcerogenic risks. Drugs and doses should beadjusted based on observation of healing rate, switchingpatients from high to low doses, and from narcotic anal-gesics to non-narcotics when circumstances permit.

An important consideration of pain management in
severe pain is that patients should not be subject to thereturn of pain. Analgesics should be dosed adequately toassure that the pain is at least tolerable, and frequentlyenough to avoid the anxiety that accompanies the antici-
pated return of pain. Analgesics should never be dosed ona “prn” (as needed) basis, but should be administered oftenenough to assure constant blood levels of analgesic. This

applies to both the narcotic and non-narcotic analgesics.
Chronic pain
Chronic pain, pain lasting over three months and
severe enough to impair function, is more difficult totreat, since the anticipated side effects of the analgesicsare more difficult to manage. In the case of narcotic anal-gesics this means the addiction potential, as well as res-
piratory depression and constipation . For the NSAIDs,

the risk of gastric ulcers may be dose limiting. Whilesome classes of drugs, such as the narcotic agonist/antag-onist drugs bupronophine, nalbuphine and pentazocine,and the selective COX-2 inhibitors celecoxib and rofe-coxib represent advances in reduction of adverse effects,they are still not fully suitable for long-term managementof severe pain. Generally, chronic pain managementrequires a combination of drug therapy, life-style modifi-cation, and other treatment modalities.

Narcotic analgesics
The narcotic analgesics, also termed opioids, are all

derived from opium. The class includes morphine,codeine, and a number of semi-synthetics includingmeperidine (Demerol), propoxyphen (Darvon) and oth-ers. The narcotic analgesics vary in potency, but all areeffective in treatment of visceral pain when used in ade-quate doses. Adverse effects are dose related. Becausethese drugs are all addictive, they are controlled underfederal and state laws. A variety of dosage forms areavailable, including oral solids, liquids, intravenous andintrathecal

oral solids, liquids, intravenous andintrathecal injections, and transcutaneous patches.

NSAIDs, non-steroidal anti-inflammatory drugs, are
effective analgesics even at doses too low to have anyanti-inflammatory effects. There are a number of chemi-cal classes, but all have similar therapeutic effects andside effects. Most are appropriate only for oral adminis-tration; however ketorolac (Toradol) is appropriate forinjection and may be used in moderate to severe pain forshort periods.
Acetaminophen is a non-narcotic analgesic with no

anti-inflammatory properties. It is appropriate for mild tomoderate pain. Although the drug is well tolerated in nor-mal doses, it may have significant toxicity at high doses.Because acetaminophen is largely free of side effects attherapeutic doses, it has been considered the first choicefor mild pain, including that of osteoarthritis .
Appropriate dosage varies by drug, and should con-

sider the type of pain, as well as other risks associated
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with patient age and condition. For example, narcotic
analgesics should usually be avoided in patients with ahistory of substance abuse, but may be fully appropriatein patients with cancer pain. Similarly, because narcotics

are more rapidly metabolized in patients who have usedthese drugs for a long period, higher than normal dosesmay be needed to provide adequate pain management.NSAIDs, although comparatively safe in adults, repre-sent an increased risk of gastrointestinal bleeding inpatients over the age of 60.
Narcotic analgesics may be contraindicated in

patients with respiratory depression. NSAIDS may behazardous to patients with ulcers or an ulcer history.They should be used with care in patients with renalinsufficiency or coagulation disorders . NSAIDs are
contraindicated in patients allergic to aspirin .
Review adverse effects of each drug individually.
Drugs within a class may vary in their frequency andseverity of adverse effects.
The primary adverse effects of the narcotic anal-

gesics are addiction, constipation, and respiratorydepression. Because narcotic analgesics stimulate theproduction of enzymes that cause the metabolism ofthese drugs, patients on narcotics for a prolonged periodmay require increasing doses. This is not the same thingas addiction, and is not a reason for withholding medica-tion from patients in severe pain.
NSAIDs are ulcerogenic and may cause kidney

problems. Gastrointestinal discomfort is common,although in some cases, these drugs may cause ulcersKEY TERMS
Acute pain —Pain that is usually temporary and
results from something specific, such as a surgery,an injury, or an infection.
Analgesic —Medicine used to relieve pain.
Chronic pain —Pain that lasts more than three
months and threatens to disrupt daily life.
Inflammation —Pain, redness, swelling, and heat

that usually develop in response to injury or illness.
Osteoarthritis —Joint pain resulting from damage
to the cartilage.without the prior warning of gastrointestinal distress.
Platelet aggregation problems may occur, although not tothe same extent as if seen with aspirin.
Interactions depend on the specific type of anal-
gesic. See specific references.
Samuel Uretsky, PharmD
Analgesics, opioid

Opioid analgesics , also known as narcotic anal-
gesics, are pain relievers that act on the central nervous
system. Like all narcotics, they may become habit-form-ing if used over long periods.
Purpose
Opioid analgesics are used to relieve pain from a

variety of conditions. Some are used before or duringsurgery (including dental surgery) both to relieve pain andto make anesthetics work more effectively. They may alsobe used for the same purposes during labor and delivery.
Opioid analgesics relieve pain by acting directly on
the central nervous system. However, this can also leadto unwanted side effects, such as drowsiness, dizziness ,

breathing problems, and physical or mental dependence.
Among the drugs in this category are codeine, pro-
poxyphene (Darvon), propoxyphene and acetaminophen

(Darvocet N), meperidine (Demerol), hydromorphone(Dilaudid), morphine, oxycodone, oxycodone and aceta-minophen (Percocet, Roxicet), and hydrocodone andacetaminophen (Lortab, Anexsia). These drugs come inmany forms—tablets, syrups, suppositories, and injec-tions, and are sold only by prescription. For some, a newprescription is required for each new supply—refills areprohibited according to federal regulations.
Recommended doses vary, depending on the type of

opioid analgesic and the form in which it is being used.Doses may be different for different patients. Check withthe physician who prescribed the drug or the pharmacist
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who filled the prescription for correct dosages, and make
sure to understand how to take the drug.
Always take opioid analgesics exactly as directed.
Never take larger or more frequent doses, and do not takethe drug for longer than directed. Do not stop taking thedrug suddenly without checking with the physician ordentist who prescribed it. Gradually tapering the dosemay the chance of withdrawal symptoms.
Anyone who uses opioid analgesics—or any narcot-

ic—over a long time may become physically or mentallydependent on the drug. Physical dependence may lead towithdrawal symptoms when the person stops taking the
medicine. Building tolerance to these drugs is also possi-ble when they are used for a long period. Over time, thebody needs larger and larger doses to relieve pain.
Take these drugs exactly as directed. Never take

more than the recommended dose, and do not take thedrugs more often than directed. If the drugs do not seemto be working, consult your physician. Do not share theseor any other prescription drugs with others because thedrug may have a completely different effect on the per-son for whom it was not prescribed.
Children and older people are especially sensitive to
opioid analgesics and may have serious breathing prob-

GALE ENCYCLOPEDIA OF MEDICINE 2 176Analgesics, opioidOpioid analgesics
Route of Onset of Time to Duration of
Drug administration action (min) peak effect (min) action (h)
Strong agonists
Fentanyl (Sublimaze) IM 7–15 20–30 1–2
IV 1–2 3–5 0.5–1
Hydromorphone (Dilaudid) Oral 30 90–120 4
IM 15IV 10–15 30–60 2–3Sub-Q 30 15–30
Levorphanol (Levo-Dromoran) Oral 10–60 90–120 4–5
IMIV — 60 4–5Sub-Q 10–60 within 20
Meperidine (Demerol) Oral 15 60–90 2–4
IM 10–15IV 30–50 2–4Sub-Q 1

Methadone (Dolophine) Oral 30–60 90–120 4–6
IMIV 10–20 60–120 4–5
Morphine (many trade names) Oral — 60–120 4–5
IM 10–30IV 30–60 4–5Sub-Q —Epidural 10–30 20 4–5
Oxymorphone (Numorphan) IM 10–15 30–90 3–6
IVSub-Q 5–10 15–30 3–4Rectal
Mild-to-moderate agonists
Codiene (many trade names) Oral 30–40 60–120 4
Im 10–30 30–60 4Sub-Q 10–30 4

Hydrocodone (Hycodan) Oral 10–30 30–60 4–6Oxycodone (Percodan) Oral — 60 3–4Propoxyphene (Darvon, Dolene) Oral 15–60 120 4–6Butophanol (Stadol) IM 10–30 30–60 3–4
IV 2–3 30 2–4
Nalbuphine (Nubian) IM within 15 60 3–6
IV 2–3 30 3–4Sub-Q within 15 — 3–6
Pentazocine (Talwin) Oral 15–30 60–90 3
IM 15–20 30–60 2–3IV 2–3 15–30 2–3Sub-Q 15–20 30–60 2–3GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 176

lems after taking them. Children may also become
unusually restless or agitated when given these drugs.
Opioid analgesics increase the effects of alcohol.
Anyone taking these drugs should not drink alcoholicbeverages.
Some of these drugs may also contain aspirin ,caf-
feine , or acetaminophen. Refer to the entries on each of
these drugs for additional precautions.
Special conditions
People with certain medical conditions or who are

taking certain other medicines can have problems if theytake opioid analgesics. Before taking these drugs, be sureto let the physician know about any of these conditions.
ALLERGIES. Let the physician know about any aller-
gies to foods, dyes, preservatives, or other substances
and about any previous reactions to opioid analgesics.
PREGNANCY. Women who are pregnant or plan to

become pregnant while taking opioid analgesics shouldlet their physicians know. No evidence exists that thesedrugs cause birth defects in people, but some do cause
birth defects and other problems when given to pregnantanimals in experiments. Babies can become dependenton opioid analgesics if their mothers use too much duringpregnancy . This can cause the baby to go through with-

drawal symptoms after birth. If taken just before deliv-ery, some opioid analgesics may cause serious breathingproblems in the newborn.
BREAST FEEDING. Some opioid analgesics can pass
into breast milk. Women who are breast feeding shouldcheck with their physicians about the safety of takingthese drugs.
OTHER MEDICAL CONDITIONS. These conditions
may influence the effects of opioid analgesics:
• head injury. The effects of some opioid analgesics may

be stronger and may interfere with recovery in peoplewith head injuries.
• history of convulsions. Some of these drugs may trigger
convulsions.
• asthma, emphysema , or any chronic lung disease
• heart disease• kidney disease
• liver disease
• underactive thyroid. The chance of side effects may be
greater.
• addison’s disease (a disease of the adrenal glands)• colitis• gallbladder disease or gallstones . Side effects can be
dangerous in people with these conditions.

• enlarged prostate or other urinary problems• current or past alcohol abuse• current or past drug abuse, especially narcotic abuse• current or past emotional problems. The chance of side
effects may be greater.
USE OF CERTAIN MEDICINES. Taking opioid nar-
cotics with certain other drugs may increase the chancesof serious side effects.
Some people experience drowsiness, dizziness, light-

headedness, or a false sense of well-being after taking opi-oid analgesics. Anyone who takes these drugs should notdrive, use machines, or do anything else that might be dan-gerous until they know how the drug affects them. Nausea
and vomiting are common side effects, especially when
first beginning to take the medicine. If these symptoms donot go away after the first few doses, check with the physi-cian or dentist who prescribed the medicine.
Dry mouth is another common side effect. Dry

mouth can be relieved by sucking on sugarless hardcandy or ice chips or by chewing sugarless gum. Salivasubstitutes, which come in liquid or tablet forms, alsomay help. Patients who must use opioid analgesics overlong periods and who have dry mouth should see theirdentists, as the problem can lead to tooth decay and
other dental problems.
The following side effects are less common. They

usually do not need medical attention and will go awayafter the first few doses. If they continue or interfere withnormal activity, check with the physician who prescribedthe medicine.

• headache• loss of appetite• restlessness or nervousness• nightmares, unusual dreams, or problems sleeping• weakness or tiredness• mental sluggishness• stomach pain or cramps• blurred or double vision or other vision problems• problems urinating, such as pain, difficulty urinating,
frequent urge to urinate, or decreased amount of urine
• constipation.
Other side effects may be more serious and may
require quick medical attention. These symptoms could

GALE ENCYCLOPEDIA OF MEDICINE 2 177Analgesics, opioidGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 177

be signs of an overdose. Get emergency medical care
immediately.
• cold, clammy skin
• bluish discoloration of the skin
• extremely small pupils
• serious difficulty breathing or extremely slow breathing
• extreme sleepiness or unresponsiveness• severe weakness
• confusion
• severe dizziness
• severe drowsiness
• slow heartbeat• low blood pressure
• severe nervousness or restlessness
In addition, these less common side effects do not

require emergency medical care, but should have medicalattention as soon as possible:
•hallucinations or a sense of unreality
• depression or other mood changes
• ringing or buzzing in the ears
• pounding or unusually fast heartbeat
• itching, hives , or rash
• facial swelling
• trembling or twitching
• dark urine, pale stools, or yellow eyes or skin (after tak-
ing propoxyphene)
• increased sweating, red or flushed face (more common
after taking hydrocodone and meperidine)

Anyone taking these drugs should notify his or her
physician before taking opioid analgesics:
• Central nervous system (CNS) depressants, such as anti-
histamines and other medicines for allergies, hay fever ,
or colds; tranquilizers; some other prescription painrelievers; seizure medicines; muscle relaxants ; sleeping
pills; some anesthetics (including dental anesthetics).
• Monoamine oxidase (MAO) inhibitors, such as phenel-

zine (Nardil) and tranylcypromine (Parnate). The com-bination of the opioid analgesic meperidine (Demerol)and MAO inhibitors is especially dangerous.
• Tricyclic antidepressants, such as amitriptyline (Elavil).
• Anti-seizure medicines, such as carbamazepine (Tegre-
tol). May lead to serious side effects, including coma ,
when combined with propoxyphene and acetaminophen(Darvocet-N) or propoxyphene (Darvon).KEY TERMS

Central nervous system —The brain, spinal cord
and nerves throughout the body.
Colitis —Inflammation of the colon (large bowel)
Hallucination —A false or distorted perception of
objects, sounds, or events that seems real. Halluci-nations usually result from drugs or mental disor-ders.
Narcotic —A drug derived from opium or com-

pounds similar to opium. Such drugs are potentpain relievers and can affect mood and behavior.Long-term use of narcotics can lead to depen-dence and tolerance.
Tolerance —A decrease in sensitivity to a drug.
When tolerance occurs, a person must take moreand more of the drug to get the same effect.
Withdrawal symptoms —A group of physical or
mental symptoms that may occur when a personsuddenly stops using a drug to which he or she hasbecome dependent.

• Muscle relaxants, such as cyclobenzaprine (Flexeril).
• Sleeping pills, such as triazolam (Halcion).• Blood-thinning drugs, such as warfarin (Coumadin).• Naltrexone (Trexan, Revia). Cancels the effects of opi-
oid analgesics.
• Rifampin (Rifadin).
• Zidovudine (AZT, Retrovir). Serious side effects when
combined with morphine.
Anaphylactic shock seeAnaphylaxis
Anaphylactoid purpura seeAllergic purpura
Anaphylaxis

Anaphylaxis is a rapidly progressing, life-threaten-
ing allergic reaction.
GALE ENCYCLOPEDIA OF MEDICINE 2 178AnaphylaxisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 178

Anaphylaxis is a type of allergic reaction, in which
the immune system responds to otherwise harmless sub-stances from the environment. Unlike other allergicreactions, however, anaphylaxis can kill. Reaction maybegin within minutes or even seconds of exposure, andrapidly progress to cause airway constriction, skin andintestinal irritation, and altered heart rhythms. In severecases, it can result in complete airway obstruction,shock , and death .
Causes

Causes
Like the majority of other allergic reactions, anaphy-
laxis is caused by the release of histamine and otherchemicals from mast cells. Mast cells are a type of whiteblood cell and they are found in large numbers in the tis-sues that regulate exchange with the environment: theairways, digestive system, and skin.
On their surfaces, mast cells display antibodies

called IgE (immunoglobulin type E). These antibodiesare designed to detect environmental substances towhich the immune system is sensitive. Substances froma genuinely threatening source, such as bacteria orviruses, are called antigens. A substance that most peo-ple tolerate well, but to which others have an allergicresponse, is called an allergen. When IgE antibodiesbind with allergens, they cause the mast cell to releasehistamine and other chemicals, which spill out ontoneighboring cells.

The interaction of these chemicals with receptors on
the surface of blood vessels causes the vessels to leakfluid into surrounding tissues, causing fluid accumula-tion, redness, and swelling. On the smooth muscle cellsof the airways and digestive system, they cause constric-tion. On nerve endings, they increase sensitivity andcause itching .
In anaphylaxis, the dramatic response is due both to

extreme hypersensivity to the allergen and its usuallysystemic distribution. Allergens are more likely to causeanaphylaxis if they are introduced directly into the circu-latory system by injection. However, exposure by inges-tion, inhalation, or skin contact can also cause anaphy-laxis. In some cases, anaphylaxis may develop over timefrom less severe allergies .
Anaphylaxis is most often due to allergens in foods,
drugs, and insect venom. Specific causes include:

• fish, shellfish, and mollusks• nuts and seeds• stings of bees, wasps, or hornets
• papain from meat tenderizers• vaccines, including flu and measles vaccines
• penicillin• cephalosporins
• streptomycin
• gamma globulin• insulin• hormones (ACTH, thyroid-stimulating hormone)•aspirin and other NSAIDs
• latex, from exam gloves or condoms, for example
Exposure to cold or exercise can trigger anaphylaxis
in some individuals.
Symptoms

Symptoms
Symptoms may include:
• urticaria ( hives )
• swelling and irritation of the tongue or mouth• swelling of the sinuses• difficulty breathing• wheezing• cramping, vomiting, or diarrhea
• anxiety or confusion
• strong, very rapid heartbeat ( palpitations )
• loss of consciousness
Not all symptoms may be present.
Diagnosis
Anaphylaxis is diagnosed based on the rapid devel-

opment of symptoms in response to a suspect allergen.Identification of the culprit may be done with RAST test-ing, a blood test that identifies IgE reactions to specificallergens. Skin testing may be done for less severe ana-phylactic reactions.
Treatment
Emergency treatment of anaphylaxis involves injec-

tion of adrenaline (epinephrine) which constricts bloodvessels and counteracts the effects of histamine. Oxygenmay be given, as well as intravenous replacement fluids.Antihistamines may be used for skin rash, and amino-
phylline for bronchial constriction. If the upper airway isobstructed, placement of a breathing tube or tracheosto-my tube may be needed.
GALE ENCYCLOPEDIA OF MEDICINE 2 179AnaphylaxisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 179

Prognosis
The rapidity of symptom development is an indica-
tion of the likely severity of reaction: the faster symp-toms develop, the more severe the ultimate reaction.Prompt emergency medical attention and close monitor-ing reduces the likelihood of death. Nonetheless, death ispossible from severe anaphylaxis. For most people whoreceive rapid treatment, recovery is complete.
Avoidance of the allergic trigger is the only reliable

method of preventing anaphylaxis. For insect allergies,this requires recognizing likely nest sites. Preventing foodallergies requires knowledge of the prepared foods ordishes in which the allergen is likely to occur, and carefulquestioning about ingredients when dining out. Use of aMedic-Alert tag detailing drug allergies is vital to preventinadvertent administration during a medical emergency.
People prone to anaphylaxis should carry an “Epi-

pen” or “Ana-kit,” which contain an adrenaline doseready for injection.
Resources
BOOKS
Holgate, Stephen T., and Martin K. Church. Allergy. New York:
Gower Medical Publishing, 1993.
Lawlor Jr., G. J., T. J. Fischer, and D. C. Adelman. Manual of Aller-
gy and Immunology. Boston: Little, Brown and Co., 1995.
OTHER

OTHER
The Merck Page. 20 Feb. 1998. <http://www.merck.com>.
Richard RobinsonKEY TERMS
ACTH —Adrenocorticotropic hormone, a hor-
mone normally produced by the pituitary gland,sometimes taken as a treatment for arthritis andother disorders.
Antibody —An immune system protein which
binds to a substance from the environment.
NSAIDs —Non-steroidal antiinflammatory drugs,
including aspirin and ibuprofen.
Tracheostomy tube —A tube which is inserted into

an incision in the trachea (tracheostomy) to relieveupper airway obstruction.Anemias
Anemia is a condition characterized by abnormally
low levels of healthy red blood cells or hemoglobin (thecomponent of red blood cells that delivers oxygen to tis-sues throughout the body).
The tissues of the human body need a regular supply

of oxygen to stay healthy. Red blood cells, which containhemoglobin that allows them to deliver oxygen throughoutthe body, live for only about 120 days. When they die, theiron they contain is returned to the bone marrow and usedto create new red blood cells. Anemia develops whenheavy bleeding causes significant iron loss or when some-thing happens to slow down the production of red bloodcells or to increase the rate at which they are destroyed.
Types of anemia

Anemia can be mild, moderate, or severe enough to
lead to life-threatening complications. More than 400different types of anemia have been identified. Many ofthem are rare.
IRON DEFICIENCY ANEMIA. Iron deficiency ane-
miais the most common form of anemia in the world. In

the United States, iron deficiency anemia affects about240,000 toddlers between one and two years of age and3.3 million women of childbearing age. This condition isless common in older children and in adults over 50 andrarely occurs in teenage boys and young men.
The onset of iron deficiency anemia is gradual and,

at first, there may not be any symptoms. The deficiencybegins when the body loses more iron than it derivesfrom food and other sources. Because depleted ironstores cannot meet the red blood cell’s needs, fewer redblood cells develop. In this early stage of anemia, the redblood cells look normal, but they are reduced in number.Then the body tries to compensate for the iron deficiencyby producing more red blood cells, which are character-istically small in size. Symptoms develop at this stage.

FOLIC ACID DEFICIENCY ANEMIA. Folic acid defi-
ciency anemia is the most common type of megaloblas-
tic anemia (in which red blood cells are bigger than nor-mal). It is caused by a deficiency of folic acid , a vitamin
that the body needs to produce normal cells.
Folic acid anemia is especially common in infants
and teenagers. Although this condition usually resultsfrom a dietary deficiency, it is sometimes due to inabilityto absorb enough folic acid from such foods as:

GALE ENCYCLOPEDIA OF MEDICINE 2 180AnemiasGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 180

• cheese
• eggs
• fish
• green vegetables
• meat
• milk
• mushrooms
• yeast
Smoking raises the risk of developing this condition
by interfering with the absorption of Vitamin C, which thebody needs to absorb folic acid. Folic acid anemia can bea complication of pregnancy , when a woman’s body
needs eight times more folic acid than it does otherwise.
VITAMIN B 12DEFICIENCY ANEMIA. Less common in
this country than folic acid anemia, vitamin B12deficien-

cy anemia is another type of megaloblastic anemia thatdevelops when the body doesn’t absorb enough of thisnutrient. Necessary for the creation of red blood cells, B
12
is found in meat and vegetables.
Large amounts of B12are stored in the body, so this
condition may not become apparent until as much as fouryears after B
12absorption stops or slows down. The
resulting drop in red blood cell production can cause:
• loss of muscle control
• loss of sensation in the legs, hands, and feet

• soreness or burning of the tongue
• weight loss
• yellow-blue color blindness
The most common form of B12deficiency is perni-
cious anemia . Since most people who eat meat or eggs
get enough B12in their diets , a deficiency of this vitamin

usually means that the body is not absorbing it properly.This can occur among people who have had intestinalsurgery or among those who do not produce adequateamounts of intrinsic factor, a chemical secreted by thestomach lining that combines with B
12to help its absorp-
tion in the small intestine.
Pernicious anemia usually strikes between the ages
of 50–60. Eating disorders or an unbalanced diet increas-es the risk of developing pernicious anemia. So do:

• diabetes mellitus•gastritis ,stomach cancer , or stomach surgery
• thyroid disease
• family history of pernicious anemia
VITAMIN C DEFICIENCY ANEMIA. A rare disorder
that causes the bone marrow to manufacture abnormallysmall red blood cells, Vitamin C deficiency anemia
results from a severe, long-standing dietary deficiency.
HEMOLYTIC ANEMIA. Some people are born with
hemolytic anemia . Some acquire this condition, in

which infection or antibodies destroy red blood cellsmore rapidly than bone marrow can replace them.
Hemolytic anemia can enlarge the spleen, accelerat-
ing the destruction of red blood cells (hemolysis). Othercomplications of hemolytic anemia include:
•pain
• shock• gallstones and other serious health problems
THALASSEMIAS. An inherited form of hemolytic
anemia, thalassemia stems from the body’s inability to

manufacture as much normal hemoglobin as it needs.There are two categories of thalassemia, depending onwhich of the amino acid chains is affected. (Hemoglobinis composed of four chains of amino acids.) In alpha-tha-lassemia, there is an imbalance in the production of thealpha chain of amino acids; in beta-thalassemia, there isan imbalance in the beta chain. Alpha-thalassemias mostcommonly affect blacks (25% have at least one gene);beta-thalassemias most commonly affect people ofMediterranean

most commonly affect people ofMediterranean ancestry and Southeast Asians.

Characterized by production of red blood cells that
are unusually small and fragile, thalassemia only affectspeople who inherit the gene for it from each parent (auto-somal recessive inheritance).
AUTOIMMUNE HEMOLYTIC ANEMIAS. Warm anti-
body hemolytic anemia is the most common type of thisdisorder. This condition occurs when the body producesautoantibodies that coat red blood cells. The coated cellsare destroyed by the spleen, liver, or bone marrow.

Warm antibody hemolytic anemia is more common
in women than in men. About one-third of patients whohave warm antibody hemolytic anemia also have lym-phoma, leukemia, lupus, or connective tissue disease.
In cold antibody hemolytic anemia, the body attacks
red blood cells at or below normal body temperature. Theacute form of this condition frequently develops in peo-ple who have had pneumonia , mononeucleosis, or other

acute infections. It tends to be mild and short-lived, anddisappears without treatment.
Chronic cold antibody hemolytic anemia is most
common in women and most often affects those who areover 40 and who have arthritis. This condition usuallylasts for a lifetime, generally causing few symptoms.However, exposure to cold temperatures can accelerate
GALE ENCYCLOPEDIA OF MEDICINE 2 181AnemiasGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 181

red blood cell destruction, causing fatigue , joint aches,
and discoloration of the arms and hands.
SICKLE CELL ANEMIA. Sickle cell anemia is a chron-

ic, incurable condition that causes the body to producedefective hemoglobin, which forces red blood cells toassume an abnormal crescent shape. Unlike normal ovalcells, fragile sickle cells can’t hold enough hemoglobinto nourish body tissues. The deformed shape makes ithard for sickle cells to pass through narrow blood ves-sels. When capillaries become obstructed, a life-threaten-ing condition called sickle cell crisis is likely to occur.
Sickle cell anemia is hereditary. It almost always

affects blacks and people of Mediterranean descent. Achild who inherits the sickle cell gene from each parentwill have the disease. A child who inherits the sickle cellgene from only one parent carries the sickle cell trait, butdoes not have the disease.
APLASTIC ANEMIA. Sometimes curable by bone
marrow transplant, but potentially fatal, aplastic anemia

is characterized by decreased production of red andwhite blood cells and platelets (disc-shaped cells thatallow the blood to clot). This disorder may be inheritedor acquired as a result of:
• recent severe illness
• long-term exposure to industrial chemicals
• use of anticancer drugs and certain other medications
ANEMIA OF CHRONIC DISEASE. Cancer , chronic

infection or inflammation, and kidney and liver diseaseoften cause mild or moderate anemia. Chronic liver fail-ure generally produces the most severe symptoms.
Anemia is caused by bleeding, decreased red blood

cell production, or increased red blood cell destruction.Poor diet can contribute to vitamin deficiency and irondeficiency anemias in which fewer red blood cells areproduced. Hereditary disorders and certain diseases cancause increased blood cell destruction. However, exces-sive bleeding is the most common cause of anemia, andthe speed with which blood loss occurs has a significanteffect on the severity of symptoms. Chronic blood loss isusually a consequence of:
• cancer

• cancer
• gastrointestinal tumors
• diverticulosis
• polyposis
• heavy menstrual flow
• hemorrhoids• nosebleeds
• stomach ulcers
• long-standing alcohol abuse
Acute blood loss is usually the result of:
• childbirth• injury
• a ruptured blood vessel
• surgery
When a lot of blood is lost within a short time, blood
pressure and the amount of oxygen in the body drop sud-denly. Heart failure and death can follow.
Loss of even one-third of the body’s blood volume in

the space of several hours can be fatal. More gradual bloodloss is less serious, because the body has time to createnew red blood cells to replace those that have been lost.
Symptoms
Weakness, fatigue, and a run-down feeling may be

signs of mild anemia. Skin that is pasty or sallow, or lackof color in the creases of the palm, gums, nail beds, orlining of the eyelids are other signs of anemia. Someonewho is weak, tires easily, is often out of breath, and feelsfaint or dizzy may be severely anemic.
Other symptoms of anemia are:
• angina pectoris (chest pain, often accompanied by a
choking sensation that provokes severe anxiety )
• cravings for ice, paint, or dirt
• headache

• headache
• inability to concentrate, memory loss
• inflammation of the mouth ( stomatitis ) or tongue
(glossitis)
• insomnia
• irregular heartbeat
• loss of appetite
• nails that are dry, brittle, or ridged
• rapid breathing
• sores in the mouth, throat, or rectum
• sweating
• swelling of the hands and feet
• thirst
• tinnitus (ringing in the ears)
• unexplained bleeding or bruising
In pernicious anemia, the tongue feels unusually

slick. A patient with pernicious anemia may have:
GALE ENCYCLOPEDIA OF MEDICINE 2 182AnemiasGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 182

• problems with movement or balance
• tingling in the hands and feet
• confusion, depression, and memory loss
Pernicious anemia can damage the spinal cord. A
doctor should be notified whenever symptoms of thiscondition occur.
A doctor should also be notified if a patient who has
been taking iron supplements develops:
• diarrhea
• cramps
• vomiting
Diagnosis
Personal and family health history may suggest the

presence of certain types of anemia. Laboratory tests thatmeasure the percentage of red blood cells or the amountof hemoglobin in the blood are used to confirm diagnosisand determine which type of anemia is responsible for apatient’s symptoms. X rays and examinations of bonemarrow may be used to identify the source of bleeding.
Treatment
Anemia due to nutritional deficiencies can usually
be treated at home with iron supplements or self adminis-tered injections of vitamin B

12. People with folic acid
anemia should take oral folic acid replacements. VitaminC deficiency anemia can be cured by taking one vitaminC tablet a day.
Surgery may be necessary to treat anemia caused by
excessive loss of blood. Transfusions of red blood cellsmay be used to accelerate production of red blood cells.
Medication or surgery may also be necessary to con-
trol heavy menstrual flow, repair a bleeding ulcer, orremove polyps (growths or nodules) from the bowels.

Patients with thalassemia usually do not require
treatment. However people with a severe form mayrequire periodic hospitalization for blood transfusionsand/or bone marrow transplantation .
SICKLE CELL ANEMIA. Treatment for sickle cell ane-
mia involves regular eye examinations, immunizationsfor pneumonia and infectious diseases, and prompt treat-ment for sickle cell crises and infections of any kind.Psychotherapy or counseling may help patients deal withthe emotional impact of this condition.

VITAMIN B12DEFICIENCY ANEMIA. A life-long regi-
men of B12shots is necessary to control symptoms of per-
nicious anemia. The patient may be advised to limit phys-ical activity until treatment restores strength and balance.APLASTIC ANEMIA. People who have aplastic ane-
mia are especially susceptible to infection. Treatment foraplastic anemia may involve blood transfusions and bonemarrow transplant to replace malfunctioning cells withhealthy ones.
ANEMIA OF CHRONIC DISEASE. There is no specific

treatment for anemia associated with chronic disease, buttreating the underlying illness may alleviate this condi-tion. This type of anemia rarely becomes severe. If itdoes, transfusions or hormone treatments to stimulate redblood cell production may be prescribed.
HEMOLYTIC ANEMIA. There is no specific treatment

for cold-antibody hemolytic anemia. About one-third ofpatients with warm-antibody hemolytic anemia respondwell to large doses of intravenous and oral corticos-
teroids , which are gradually discontinued as the patient’s

condition improves. Patients with this condition whodon’t respond to medical therapy must have the spleensurgically removed. This operation controls anemia inabout half of the patients on whom it’s performed.Immune-system suppressants are prescribed for patientswhose surgery is not successful.
Self-care
Anyone who has anemia caused by poor nutrition
should modify his or her diet to include more vitamins ,
minerals , and iron. Vitamin C can stimulate iron absorp-

tion. The following foods are also good sources of iron:
• almonds
• broccoli
GALE ENCYCLOPEDIA OF MEDICINE 2 183Anemias
An illustration of normal red blood cells (left) and those in
three different types of anemia (from left), iron-deficiencyanemia, megaloblastic anemia, and sickle cell anemia. (Illus-
tration by John Bavosi, Custom Medical Stock Photo. Repro-duced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 183

• dried beans
• dried fruits
• enriched breads and cereals
• lean red meat•l i v e r
• potatoes
• poultry• rice
• shellfish
• tomatoes
Because light and heat destroy folic acid, fruits and
vegetables should be eaten raw or cooked as little as pos-sible.
As is the case in standard medical treatment, the
cause of the specific anemia will determine the alterna-tive treatment recommended. If the cause is a deficiency,for example iron deficiency, folic acid deficiency, B
12

12
deficiency, or vitamin C deficiency, supplementation isthe treatment. For extensive blood loss, the cause shouldbe identified and corrected. Other types of anemiasshould be addressed on a deep healing level with crisisintervention when necessary.
Many alternative therapies for iron-deficiency ane-

mia focus on adding iron-rich foods to the diet or ontechniques to improve circulation and digestion. Ironsupplementation, especially with iron citrate (less likelyto cause constipation ), is used by alternative practition-
ers. This can be given in combination with herbs that arerich in iron. Some examples of iron-rich herbs are dande-lion ( Taraxacum officinale ), parsley ( Petroselinum
crispum ), and nettle ( Urtica dioica ). The homeopathic
remedy ferrum phosphoricum can also be helpful.

An iron-rich herbal tonic can also me made using
the following recipe:
• soak 1/2 oz of yellow dock root and 1/2 oz dandelion
root in 1 qt of boiled water for  four to 8 hours
• strain and simmer until the amount of liquid is reduced
to 1 cup
• remove from heat and add 1/2 cup black strap molasses,
mixing well
• store in refrigerator; take 1 tsp-2 Tbsp daily
Other herbal remedies used to treat iron-deficiency

anemia aim to improve the digestion. Gentian ( Gentiana
lutea ) is widely used in Europe to treat anemia and other
nutritionally based disorders. The bitter qualities of gen-tian help stimulate the digestive system, making iron and
other nutrients more available for absorption. This bitterherb can be brewed into tea or purchased as an alcoholicextract (tincture).
Other herbs recommended to promote digestion
include:
• anise ( Pimpinella anisum )
• caraway ( Carum carvi )

• cumin ( Cuminum cyminum )
• linden ( Tilia spp.)
• licorice ( Glycyrrhiza glabra )
Traditional Chinese treatments for anemia include:
• acupuncture to stimulate a weakened spleen• asian ginseng ( Panax ginseng ) to restore energy
• dong quai ( Angelica sinensis ) to control heavy men-
strual bleeding
• a mixture of dong quai and Chinese foxglove( Rehman-
nia glutinosa ) to clear a sallow complexion
Prognosis
Folic-acid and iron-deficiency anemias

Prognosis
It usually takes three to six weeks to correct folic
acid or iron deficiency anemia. Patients should continuetaking supplements for another six months to replenishiron reserves and should have periodic blood tests tomake sure the bleeding has stopped and the anemia hasnot recurred.
Pernicious anemia
Although pernicious anemia is considered incurable,
regular B
12shots will alleviate symptoms and reverse

complications. Some symptoms will disappear almost assoon as treatment begins.
Aplastic anemia
Aplastic anemia can sometimes be cured by bone
marrow transplantation. If the condition is due toimmunosuppressive drugs, symptoms may disappearafter the drugs are discontinued.
Sickle cell anemia
Although sickle cell anemia cannot be cured, effec-
tive treatments enable patients with this disease to enjoylonger, more productive lives.
Thalassemia

People with mild thalassemia (alpha thalassemia
trait or beta thalassemia minor) lead normal lives and do
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not require treatment. Those with severe thalassemia
may require bone marrow transplantation. Genetic thera-py is is being investigated and may soon be available.
Hemolytic anemia
Acquired hemolytic anemia can generally be cured
when the cause is removed.
Inherited anemias cannot be prevented. Genetic
counseling can help parents cope with questions and
concerns about transmitting disease-causing genes totheir children.
Avoiding excessive use of alcohol, eating a balanced

diet that contains plenty of iron-rich foods, and taking adaily multivitamin can help prevent anemia.
Methods of preventing specific types of anemia
include:
• avoiding lengthy exposure to industrial chemicals and
drugs known to cause aplastic anemia
• not taking medication that has triggered hemolytic ane-
mia and not eating foods that have caused hemolysis(breakdown of red blood cells)
• receiving regular B
12shots to prevent pernicious anemia
resulting from gastritis or stomach surgery

Resources
BOOKS
Berkow, Robert, ed. The Merck Manual of Medical Informa-
tion: Home Edition. Whitehouse Station, NJ: Merck &
Co., Inc., 1997.KEY TERMS
Aplastic —Exhibiting incomplete or faulty devel-
opment.
Diabetes mellitus —A disorder of carbohydrate
metabolism brought on by a combination ofhereditary and enviornmental factors.
Hemoglobin —An iron-containing pigment of red

blood cells composed of four amino acid chains(alpha, beta, gamma, delta) that delivers oxygenfrom the lungs to the tissues of the body.
Megaloblast —A large erythroblast (a red marrow
cell that synthesizes hemoglobin).Current Medical Diagnosis and Treatment, 1998. 37th ed. Ed.
Stephen McPhee, et al. Stamford: Appleton & Lange, 1997.
The Editors of Time-Life Books. The Medical Advisor: The

Complete Guide to Alternative and Conventional Treat-ments. Alexandria, V A: Time Life, Inc., 1996.
OTHER
“Aplastic Anemia.” ThriveOnline. 2 June 1998 <http://thrive
online.oxygen.com>.
“Folic Acid Deficiency Anemia.” ThriveOnline. 2 June 1998
<http://thriveonline.oxygen.com>.
“Hemolytic Anemia.” ThriveOnline. 2 June 1998 <http://thrive
“Iron Deficiency Anemia.” ThriveOnline. 2 June 1998 <http://
thriveonline.oxygen.com>.

“Pernicious Anemia.” ThriveOnline. 3 June 1998 <http://thrive
“Prevalence of Iron Deficiency in the United States.” ThriveOn-
line. 2 June 1998 <http://thriveonline.oxygen.com>.
“Sickle Cell Anemia & Sickle Cell Trait.” ThriveOnline. 2 June
1995 <http://thriveonline.oxygen.com>.
“Thalassemia.” ThriveOnline. 2 June 1998 <http://thriveonline.
oxygen.com>.
Anencephaly seeCongenital brain defects
Anesthesia, general

General anesthesia is the induction of a state of uncon-
sciousness with the absence of pain sensation over the
entire body, through the administration of anesthetic drugs.It is used during certain medical and surgical procedures.
Purpose
General anesthesia has many purposes including:
• pain relief (analgesia)
• blocking memory of the procedure ( amnesia )
• producing unconsciousness• inhibiting normal body reflexes to make surgery safe
and easier to perform

• relaxing the muscles of the body
Anesthesia performed with general anesthetics
occurs in four stages which may or may not be observ-able because they can occur very rapidly:
GALE ENCYCLOPEDIA OF MEDICINE 2 185Anesthesia, generalGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 185

• Stage One: Analgesia. The patient experiences analge-
sia or a loss of pain sensation but remains consciousand can carry on a conversation.
• Stage Two: Excitement. The patient may experience
delirium or become violent. Blood pressure rises and
becomes irregular, and breathing rate increases. Thisstage is typically bypassed by administering a barbitu-rate, such as sodium pentothal, before the anesthesia.
• Stage Three: Surgical Anesthesia. During this stage, the

skeletal muscles relax, and the patient’s breathingbecomes regular. Eye movements slow, then stop, andsurgery can begin.
• Stage Four: Medullary Paralysis . This stage occurs if
the respiratory centers in the medulla oblongata of thebrain that control breathing and other vital functionscease to function. Death can result if the patient cannot
be revived quickly. This stage should never be reached.Careful control of the amounts of anesthetics adminis-tered prevent this occurrence.

gases or volatile liquids that are vaporized and inhaledwith oxygen, or drugs delivered intravenously. A combi-nation of inhaled anesthetic gases and intravenous drugsare usually delivered during general anesthesia; thispractice is called balanced anesthesia and is used becauseit takes advantage of the beneficial effects of each anes-thetic agent to reach surgical anesthesia. If necessary, theextent of the anesthesia produced by inhaling a generalanesthetic can be rapidly modified by adjusting

can be rapidly modified by adjusting the con-centration of the anesthetic in the oxygen that is breathedby the patient. The degree of anesthesia produced by anintravenously injected anesthesic is fixed and cannot bechanged as rapidly. Most commonly, intravenous anes-thetic agents are used for induction of anesthesia andthen followed by inhaled anesthetic agents.

sodium molecules into nerve cells (neurons) through thecell membrane. Exactly how the anesthetic does this isnot understood since the drug apparently does not bind toany receptor on the cell surface and does not seem toaffect the release of chemicals that transmit nerveimpulses (neurotransmitters) from the nerve cells. It isknown, however, that when the sodium molecules do notget into the neurons, nerve impulses are not generatedand the brain becomes unconscious, does not store mem-ories, does

unconscious, does not store mem-ories, does not register pain impulses from other areas ofthe body, and does not control involuntary reflexes.Although anesthesia may feel like deep sleep, it is not thesame. In sleep, some parts of the brain speed up whileothers slow down. Under anesthesia, the loss of con-sciousness is more widespread.When general anesthesia was first introduced in

medical practice, ether and chloroform were inhaled withthe physician manually covering the patient’s mouth.Since then, general anesthesia has become much moresophisticated. During most surgical procedures, anesthet-ic agents are now delivered and controlled by computer-ized equipment that includes anesthetic gas monitoringas well as patient monitoring equipment. Anesthesiolo-gists are the physicians that specialize in the delivery ofanesthetic agents. Currently used inhaled general

agents. Currently used inhaled general anes-thetics include halothane, enflurane, isoflurane, desfluo-rane, sevofluorane, and nitrous oxide.

easily be overadministered. This drug causes uncon-sciousness but little pain relief so it is often used withother agents to control pain. Very rarely, it can be toxicto the liver in adults, causing death. It also has thepotential for causing serious cardiac dysrhythmias.Halothane has a pleasant odor, and was frequently theanesthetic of choice for use with children, but since theintroduction of sevofluorane in the 1990s, halothaneuse has declined.

• Enflurane (Ethrane) is less potent and results in a
more rapid onset of anesthesia and faster awakeningthan halothane. In addition, it acts as an enhancer ofparalyzing agents. Enflurane has been found toincrease intracranial pressure and the risk of seizures;therefore, its use is contraindicated in patients withseizure disorders.
• Isoflurane (Forane) is not toxic to the liver but can

cause some cardiac irregularities. Isofluorane is oftenused in combination with intravenous anesthetics foranesthesia induction. Awakening from anesthesia isfaster than it is with halothane and enfluorane.
• Desfluorane (Suprane) may increase the heart rate and
should not be used in patients with aortic valve steno-
sis; however, it does not usually cause heart arrhyth-
mias . Desflurane may cause coughing and excitation

during induction and is therefore used with intravenousanesthetics for induction. Desflurane is rapidly elimi-nated and awakening is therefore faster than with otherinhaled agents.
• Sevofluorane (Ultane) may also cause increased heart

rate and should not be used in patients with narrowedaortic valve (stenosis); however, it does not usuallycause heart arrhythmias. Unlike desfluorane, sevofluo-rane does not cause any coughing or other related sideeffects, and can therefore be used without intravenousagents for rapid induction. For this reason, sevofluoraneis replacing halothane for induction in pediatricpatients. Like desfluorane, this agent is rapidly elimi-nated and allows rapid awakening.

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• Nitrous oxide (laughing gas) is a weak anesthetic and is
used with other agents, such as thiopental, to producesurgical anesthesia. It has the fastest induction andrecovery and is the safest because it does not slowbreathing or blood flow to the brain. However, it diffus-es rapidly into air-containing cavities and can result in acollapsed lung ( pneumothorax ) or lower the oxygen
contents of tissues (hypoxia).
Commonly administered intravenous anesthetic

agents include ketamine, thiopental, opioids, and propofol.
• Ketamine (Ketalar) affects the senses, and produces a
dissociative anesthesia ( catatonia , amnesia, analgesia)

in which the patient may appear awake and reactive, butcannot respond to sensory stimuli. These propertiesmake it especially useful for use in developing coun-tries and during warfare medical treatment. Ketamine isfrequently used in pediatric patients because anesthesiaand analgesia can be achieved with an intramuscularinjection. It is also used in high-risk geriatric patientsand in shock cases, because it also provides cardiac
stimulation.

• Thiopental (Pentothal) is a barbiturate that induces a
rapid hypnotic state of short duration. Because thiopen-tal is slowly metabolized by the liver, toxic accumula-tion can occur; therefore, it should not be continuouslyinfused. Side effects include nausea and vomiting
upon awakening.
• Opioids include fentanyl, sufentanil, and alfentanil, and

are frequently used prior to anesthesia and surgery as asedative and analgesic, as well as a continuous infusionfor primary anesthesia. Because opioids rarely affectthe cardiovascular system, they are particularly usefulfor cardiac surgery and other high-risk cases. Opioidsact directly on spinal cord receptors, and are freqentlyused in epidurals for spinal anesthesia. Side effects mayinclude nausea and vomiting, itching , and respiratory
depression.

• Propofol (Diprivan) is a nonbarbiturate hypnotic agent

and the most recently developed intravenous anesthetic.Its rapid induction and short duration of action are iden-tical to thiopental, but recovery occurs more quicklyand with much less nausea and vomiting. Also, propo-fol is rapidly metabolized in the liver and excreted inthe urine, so it can be used for long durations of anes-thesia, unlike thiopental. Hence, propofol is rapidlyreplacing thiopental as an intravenous induction agent.It is used for general surgery , cardiac surgery, neuro-

surgery, and pediatric surgery.
General anesthetics are given only by anesthesiolo-
gists, the medical professionals trained to use them. Thesespecialists consider many factors, including a patient’sage, weight, medication allergies , medical history, andgeneral health, when deciding which anesthetic or combi-
nation of anesthetics to use. General anesthetics are usual-ly inhaled through a mask or a breathing tube or injectedinto a vein, but are also sometimes given rectally.

General anesthesia is much safer today than it was in
the past. This progress is due to faster-acting anesthetics,improved safety standards in the equipment used todeliver the drugs, and better devices to monitor breath-ing, heart rate, blood pressure, and brain activity duringsurgery. Unpleasant side effects are also less common.
The dosage depends on the type of anesthetic, the

patient’s age and physical condition, the type of surgeryor medical procedure being done, and other medicationthe patient takes before, during, or after surgery.
Although the risks of serious complications from
general anesthesia are very low, they can include heart
attack ,stroke , brain damage, and death. Anyone sched-

uled to undergo general anesthesia should thoroughlydiscuss the benefits and risks with a physician. The risksof complications depend, in part, on a patient’s age, sex,weight, allergies, general health, and history of smoking ,

drinking alcohol, or drug use. Some of these risks can beminimized by ensuring that the physician and anesthesi-ologist are fully informed of the detailed health conditionof the patient, including any drugs that he or she may beusing. Older people are especially sensitive to the effectsof certain anesthetics and may be more likely to experi-ence side effects from these drugs.
Patients who have had general anesthesia should not

drink alcoholic beverages or take medication that slowdown the central nervous system (such as antihista-
mines , sedatives, tranquilizers, sleep aids, certain pain
relievers, muscle relaxants , and anti-seizure medication)
for at least 24 hours, except under a doctor’s care.
People with certain medical conditions are at greater

risk of developing problems with anesthetics. Beforeundergoing general anesthesia, anyone with the follow-ing conditions should absolutely inform their doctor.
ALLERGIES. Anyone who has had allergic or other
unusual reactions to barbiturates or general anesthetics
in the past should notify the doctor before having generalanesthesia. In particular, people who have had malignanthyperthermia or whose family members have had malig-nant hyperthermia during or after being given an anes-

GALE ENCYCLOPEDIA OF MEDICINE 2 187Anesthesia, generalGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 187

thetic should inform the physician. Signs of malignant
hyperthermia include rapid, irregular heartbeat, breath-ing problems, very high fever , and muscle tightness or
spasms. These symptoms can occur following the admin-istration of general anesthesia using inhaled agents, espe-cially halothane. In addition, the doctor should also betold about any allergies to foods, dyes, preservatives, orother substances.
PREGNANCY. The effects of anesthetics on pregnant

women and fetuses vary, depending on the type of drug. Ingeneral, giving large amounts of general anesthetics to themother during labor and delivery may make the baby slug-gish after delivery. Pregnant women should discuss the useof anesthetics during labor and delivery with their doctors.Pregnant women who may be given general anesthesia forother medical procedures should ensure that the treatingphysician is informed about the pregnancy .

BREASTFEEDING. Some general anesthetics pass into
breast milk, but they have not been reported to cause prob-lems in nursing babies whose mothers were given the drugs.
OTHER MEDICAL CONDITIONS. Before being given
a general anesthetic, a patient who has any of the follow-ing conditions should inform his or her doctor:
• neurological conditions, such as epilepsy or stroke
• problems with the stomach or esophagus, such as ulcers
or heartburn
• eating disorders• loose teeth, dentures, bridgework

• heart disease or family history of heart problems
• lung diseases, such as emphysema or asthma
• history of smoking• immune system diseases• arthritis or any other conditions that affect movement• diseases of the endocrine system, such as diabetes or
thyroid problemsSide effects
Because general anesthetics affect the central ner-

vous system, patients may feel drowsy, weak, or tiredfor as long as a few days after having general anesthesia.Fuzzy thinking, blurred vision, and coordination prob-lems are also possible. For these reasons, anyone whohas had general anesthesia should not drive, operatemachinery, or perform other activities that could endan-ger themselves or others for at least 24 hours, or longerif necessary.
Most side effects usually disappear as the anesthetic

wears off. A nurse or doctor should be notified if these orother side effects persist or cause problems, such as:
•Headache
• vision problems, including blurred or double vision
• shivering or trembling• muscle pain• dizziness, lightheadedness, or faintness• drowsiness
• mood or mental changes
• nausea or vomiting• sore throat• nightmares or unusual dreams
A doctor should be notified as soon as possible if
any of the following side effects occur within two weeksof having general anesthesia:

• severe headache
• pain in the stomach or abdomen• back or leg pain• severe nausea
• black or bloody vomit
• unusual tiredness or weakness• weakness in the wrist and fingers• weight loss or loss of appetite
GALE ENCYCLOPEDIA OF MEDICINE 2 188Anesthesia, generalAnesthetics: How They Work
Type Name(s) Administered Affect
General Halothane, Enflurane Isoflurane, Intravenously, Inhalation Produces total unconsciousness affecting the
Ketamine, Nitrous Oxide, Thiopental entire body

Regional Mepivacaine, Chloroprocaine, Lidocaine Intravenously Temporarily interrupts transmission of nerve impuls-
es (temperature, touch, pain) and motor functions ina large area to be treated; does not produce uncon-sciousness
Local Procaine, Lidocaine, Tetracaine, Bupivacaine Intravenously Temporarily blocks transmission of nerve impulses
and motor functions in a specific area; does not pro-duce unconsciousness

Topical Benzocaine, Lidocaine Dibucaine, Demal (Sprays, Drope, Ointments, Temporarily blocks nerve endings in skin and
Pramoxine, Butamben, Tetracaine Creams, Gels) mucous membranes; does not produce uncon-
sciousnessGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 188

• increase or decrease in amount of urine
• pale skin
• yellow eyes or skin
General anesthetics may interact with other medi-

cines. When this happens, the effects of one or both ofthe drugs may be altered or the risk of side effects maybe greater. Anyone scheduled to undergo general anes-thesia should inform the doctor about all other medica-tion that he or she is taking. This includes prescriptiondrugs, nonprescription medicines, and street drugs. Seri-ous and possibly life-threatening reactions may occurwhen general anesthetics are given to people who usestreet drugs, such as cocaine , marijuana, phencyclidine

(PCP or angel dust), amphetamines (uppers), barbiturates(downers), heroin, or other narcotics. Anyone who usesthese drugs should make sure their doctor or dentistknows what they have taken.
Resources
BOOKS
Dobson, Michael B. Anaesthesia at the District Hospital. 2nd
ed. World Health Organization, 2000.
U.S. Pharmacopeia Staff. Complete Drug Reference. 1997 ed.
Yonkers, NY: Consumer Reports Books, 1997.KEY TERMS
Amnesia —The loss of memory.
Analgesia —A state of insensitivity to pain even

though the person remains fully conscious.
Anesthesiologist —A medical specialist who admin-
isters an anesthetic to a patient before he is treated.
Anesthetic —A drug that causes unconsciousness or
a loss of general sensation.
Arrhythmia— Abnormal heart beat.
Barbiturate —A drug with hypnotic and sedative
effects.
Catatonia —Psychomotor disturbance characterized
by muscular rigidity, excitement or stupor.

Hypnotic agent —A drug capable of inducing a
hypnotic state.
Hypnotic state —A state of heightened awareness
that can be used to modulate the perception ofpain.Hypoxia —Reduction of oxygen supply to the tis-
sues.
Malignant hyperthermia —A type of reaction (prob-
ably with a genetic origin) that can occur duringgeneral anesthesia and in which the patient experi-ences a high fever, muscle rigidity, and irregularheart rate and blood pressure.

Medulla oblongata —The lowest section of the
brainstem, located next to the spinal cord. Themedulla is the site of important cardiac and respira-tory regulatory centers.
Opioid —Any morphine-like synthetic narcotic that
produces the same effects as drugs derived from theopium poppy (opiates), such as pain relief, seda-tion, constipation and respiratory depression.
Pneumothorax —A collapse of the lung.
Stenosis —A narrowing or constriction of the diame-

ter of a passage or orifice, such as a blood vessel.
Adachi, Y .U. K. Watanabe, H. Higuchi, and T. Satoh. “The
Determinants of Propofol Induction of Anesthesia Dose.Anesthesia and Analgesia , 92 (2001): 656-661.
Marcus, Mary Brophy. “How Does Anesthesia Work? A State
That Is Nothing Like Sleep: No Memory, No Fight-or-Flight Response, No Pain.” U.S. News & World Report
123 (August 18, 1997): 66.
American Society of Anesthesiologists. “Anesthesia and You.”

1999. <http://www.asahq.org/PublicEducation/anesth.and_you.html>.
OTHER
Wenker, O. “Review of Currently Used Inhalation Anesthetics
Part I.”(1999) The Internet Journal of Anesthesiology<http://www.ispub.com/journals/IJA/V ol3N2/ inhal1.htm.April 1, 1999.
Anesthesia, local
Local or regional anesthesia involves the injection or
application of an anesthetic drug to a specific area of thebody, as opposed to the entire body and brain as occursduring general anesthesia.

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Purpose
Local anesthetics are used to prevent patients from
feeling pain during medical, surgical, or dental proce-
dures. Over-the-counter local anesthetics are also avail-able to provide temporary relief from pain, irritation, anditching caused by various conditions, such as cold sores,
canker sores , sore throats, sunburn , insect bites, poison
ivy, and minor cuts and scratches.
Types of surgery or medical procedures that regular-

ly make use of local or regional anesthesia include thefollowing:
• biopsies in which skin or tissue samples are taken for
diagnostic procedures
• childbirth
• surgeries on the arms, hands, legs, or feet
• eye surgery
• surgeries involving the urinary tract or sexual organs
Surgeries involving the chest and abdomen are usu-
ally performed under general anesthesia.
Local and regional anesthesia have advantages over

general anesthesia in that patients can avoid someunpleasant side effects, can receive longer lasting painrelief, have reduced blood loss, and maintain a sense ofpsychological comfort by not losing consciousness.
Regional anesthesia typically affects a larger area than

local anesthesia, for example, everything below the waist.As a result, regional anesthesia may be used for moreinvolved or complicated surgical or medical procedures.Regional anesthetics are injected. Local anesthesia involvesthe injection into the skin or muscle or application to theskin of an anesthetic directly where pain will occur. Localanesthesia can be divided into four groups: injectable, topi-cal, dental (non-injectable), and ophthalmic.

flow of sodium molecules into nerve cells or neuronsthrough the cell membrane. Exactly how the anestheticdoes this is not understood, since the drug apparentlydoes not bind to any receptor on the cell surface and doesnot seem to affect the release of chemicals that transmitnerve impulses (neurotransmitters) from the nerve cells.It is known, however, that when the sodium molecules donot get into the neurons, nerve impulses are not generat-ed and pain impulses are not transmitted to the brain.

pain impulses are not transmitted to the brain. Theduration of action of an anesthetic depends on the typeand amount of anesthetic administered.

Regional anesthesia
Types of regional anesthesia include:• Spinal anesthesia. Spinal anesthesia involves the injec-
tion of a small amount of local anesthetic directly intothe cerebrospinal fluid surrounding the spinal cord (thesubarachnoid space). Blood pressure drops are com-mon but are easily treated.
• Epidural anesthesia. Epidural anesthesia involves the

injection of a large volume of local anesthetic directlyinto the space surrounding the spinal fluid sac (theepidural space), not into the spinal fluid. Pain reliefoccurs more slowly but is less likely to produce bloodpressure drops. Also, the block can be maintained forlong periods, even days.
• Nerve blocks. Nerve blocks involve the injection of an

anesthetic into the area around a nerve that supplies aparticular region of the body, preventing the nerve fromcarrying nerve impulses to the brain.
Anesthetics may be administered with another drug,
such as epinephrine (adrenaline), which decreases bleed-ing, and sodium bicarbonate to decrease the acidity of adrug so that it will work faster. In addition, drugs may beadministered to help a patient remain calm and morecomfortable or to make them sleepy.
Local anesthesia

INJECTABLE LOCAL ANESTHETICS. These medicines
are given by injection to numb and provide pain relief tosome part of the body during surgery, dental procedures,or other medical procedures. They are given only by atrained health care professional and only in a doctor’soffice or a hospital. Some commonly used injectablelocal anesthetics are procaine (Novocain), lidocaine(Dalcaine, Dilocaine, L-Caine, Nervocaine, Xylocaine,and other brands), and tetracaine (Pontocaine).

TOPICAL ANESTHETICS. Topical anesthetics, such as
benzocaine, lidocaine, dibucaine, pramoxine, butamben,and tetracaine, relieve pain and itching by deadening thenerve endings in the skin. They are ingredients in a vari-ety of nonprescription products that are applied to theskin to relieve the discomfort of sunburn, insect bites orstings, poison ivy, and minor cuts, scratches, and burns .
These products are sold as creams, ointments, sprays,lotions, and gels.

DENTAL ANESTHETICS (NON-INJECTABLE). Some
local anesthetics are intended for pain relief in the mouthor throat. They may be used to relieve throat pain,teething pain, painful canker sores, toothaches, or dis-comfort from dentures, braces, or bridgework. Somedental anesthetics are available only with a doctor’s pre-scription. Others may be purchased without a prescrip-tion, including products such as Num-Zit, Orajel, Chlo-raseptic lozenges, and Xylocaine.

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OPHTHALMIC ANESTHETICS. Other local anesthetics
are designed for use in the eye. The ophthalmic anestheticsproparacaine and tetracaine are used to numb the eyebefore certain eye examinations. Eye doctors may also usethese medicines before measuring eye pressure or remov-ing stitches or foreign objects from the eye. These drugs
are to be given only by a trained health care professional.
The recommended dosage depends on the type of

local anesthetic and the purpose for which it is beingused. When using a nonprescription local anesthetic, fol-low the directions on the package. Questions concerninghow to use a product should be referred to a medical doc-tor, dentist, or pharmacist.
People who strongly feel that they cannot psycho-

logically cope with being awake and alert during certainprocedures may not be good candidates for local orregional anesthesia. Other medications may be given inconjunction with the anesthetic, however, to relieve anxi-
etyand help the patient relax.
Local anesthetics should be used only for the condi-

tions for which they are intended. For example, a topicalanesthetic meant to relieve sunburn pain should not beused on cold sores. Anyone who has had an unusual reac-tion to any local anesthetic in the past should check witha doctor before using any type of local anesthetic again.The doctor should also be told about any allergies to
foods, dyes, preservatives, or other substances.
Older people may be more sensitive to the effects of

local anesthetics, especially lidocaine. This increased sen-sitivity may increase the risk of side effects. Older peoplewho use nonprescription local anesthetics should be espe-cially careful not to use more than the recommendedamount. Children also may be especially sensitive to theeffects of some local anesthetics, which may increase thechance of side effects. Anyone using these medicines on achild should be careful not to use more than the amountthat is recommended for children. Certain

amountthat is recommended for children. Certain types of localanesthetics should not be used at all young children. Fol-low package directions carefully and check with a doctorof pharmacist if there are any questions.

Regional anesthetics
Serious, possibly life-threatening, side effects may
occur when anesthetics are given to people who usestreet drugs. Anyone who uses cocaine ,marijuana ,
amphetamines, barbiturates , phencyclidine (PCP, or
angel dust), heroin, or other street drugs should makesure their doctor or dentist knows what they have used.Patients who have had a particular kind of reaction

called malignant hyperthermia (or who have one or morefamily members who have had this problem) during orjust after receiving a general anesthetic should informtheir doctors before receiving any kind of anesthetic.Signs of malignant hyperthermia include fast and irregu-lar heartbeat, very high fever , breathing problems, and
muscle spasms or tightness.
Although problems are rare, some unwanted side

effects may occur when regional anesthetics are usedduring labor and delivery. These anesthetics can prolonglabor and increase the risk of Cesarean section . Preg-
nant women should discuss with their doctors the risksand benefits of being given these drugs.
Patients should not drive or operate other machinery

immediately following a procedure involving regionalanesthesia, due to numbness and weakness, or if localanesthesia also included drugs to make the patient sleepor strong pain medications. Injection sites should be keptclean, dry, and uncovered to prevent infection.
Injectable local anesthetics
Until the anesthetic wears off, patients should be
careful not to injure the numbed area. If the anestheticwas used in the mouth, do not eat or chew gum until feel-ing returns.
Topical anesthetics

Unless advised by a doctor, topical anesthetics
should not be used on or near any part of the bodywith large sores, broken or scraped skin, severe injury,or infection. They should also not be used on largeareas of skin. Some topical anesthetics contain alcoholand should not be used near an open flame, or whilesmoking .
Anyone using a topical anesthetic should be careful

not to get this medication in the eyes, nose, or mouth.When using a spray form of this medication, do not sprayit directly on the face, but apply it to the face with a cot-ton swab or sterile gauze pad. After using a topical anes-thetic on a child, make sure the child does not get themedicine in his or her mouth.
Topical anesthetics are intended for the temporary
relief of pain and itching. They should not be used formore than a few days at a time. Check with a doctor if:

• the discomfort continues for more than seven days
• the problem gets worse
• the treated area becomes infected
• new signs of irritation, such as skin rash, burning, sting-
ing, or swelling appear
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Dental anesthetics (non-injectable)
Dental anesthetics should not be used if certain
kinds of infections are present. Check package directionsor check with a dentist or medical doctor if uncertain.Dental anesthetics should be used only for temporarypain relief. If problems such as toothache , mouth sores,
or pain from dentures or braces continue, check with adentist. Check with a doctor if sore throat pain is severe,

lasts more than two days, or is accompanied by othersymptoms such as fever, headache , skin rash, swelling,
nausea, or vomiting.
Patients should not eat or chew gum while the mouth

is numb from a dental anesthetic. There is a risk of acci-dently biting the tongue or the inside of the mouth. Alsonothing should be eaten or drunk for one hour afterapplying a dental anesthetic to the back of the mouth orthroat, since the medicine may interfere with swallowingand may cause choking . If normal feeling does not
return to the mouth within a few hours after receiving adental anesthetic or if it is difficult to open the mouth,check with a dentist.
Ophthalmic anesthetics

When anesthetics are used in the eye, it is important
not to rub or wipe the eye until the effect of the anesthet-ic has worn off and feeling has returned. Rubbing the eyewhile it is numb could cause injury.
Side effects of regional or local anesthetics vary
depending on the type of anesthetic used and the way it isadministered. Anyone who has unusual symptoms fol-lowing the use of an anesthetic should get in touch withhis or her doctor immediately.

Paralysis after regional anesthesia, for example an
epidural or spinal block, is extremely rare, but can occur.Paralysis reportedly occurs even less frequently thandeaths due to general anesthesia.
There is a small risk of developing a severe

headache called a spinal headache following a spinal orepidural block. This headache is severe when the patientis upright and hardly felt when the patient lies down.Though rare, it can occur and can be treated by perform-ing a blood patch, in which a small amount of thepatient’s own blood is injected into the area in the backwhere the anesthetic was injected. The blood clots andcloses up any area that may have been leaking spinalfluid. Relief is almost immediate. Finally, blood clots orabscess

almost immediate. Finally, blood clots orabscess can form in the back, but these are also readily

treatable and so pose little risk.KEY TERMS
Canker sore —A painful sore inside the mouth.
Cold sore —A small blister on the lips or face,
caused by a virus. Also called a fever blister.
Epidural space —The space surrounding the spinal
fluid sac.
Malignant hyperthermia —A type of reaction
(probably with a genetic basis) that can occur dur-ing general anesthesia in which the patient experi-ences a high fever, the muscles become rigid, andthe heart rate and blood pressure fluctuate.

Subarachnoid space —The space surrounding the
spinal cord that is filled with cerebrospinal fluid.
Topical —Not ingested; applied to the outside of
the body, for example to the skin, eye, or mouth.
A physician should be notified immediately if any of
these symptoms occur:
• large swellings that look like hives on the skin, in the
mouth, or in the throat
• severe headache• blurred or double vision
• dizziness or lightheadedness

• drowsiness• confusion• anxiety, excitement, nervousness, or restlessness• convulsions (seizures)
• feeling hot, cold, or numb
• ringing or buzzing in the ears• shivering or trembling• sweating• pale skin• slow or irregular heartbeat
• breathing problems
• unusual weakness or tiredness
Some anesthetic drugs may interact with other medi-

cines. When this happens, the effects of one or both of thedrugs may change or the risk of side effects may begreater. Anyone who receives a regional or local anestheticshould let the doctor know all other drugs he or she is tak-
GALE ENCYCLOPEDIA OF MEDICINE 2 192Anesthesia, localGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 192

ing including prescription drugs, nonprescription drugs,
and street drugs (such as cocaine, marijuana, and heroin).
Resources
BOOKS
“Anesthetics.” In Lippincott’s Illustrated Reviews: Pharmacol-
ogy, ed. Richard A. Harvey, et al. Philadelphia: J.B. Lip-
pincott & Co., 1992.
Aneurysmectomy
Aneurysmectomy is a surgical procedure performed

to repair a weak area in the aorta. The aorta is the largestartery in the body and the main blood vessel leadingaway from the heart.
Purpose
The purpose of aneurysmectomy is to repair an aor-
tic aneurysm that is likely to rupture if left in place.
Aneurysmectomy is indicated for an aortic aneurysm thatgrows to at least 2 in (5 cm) or for an aortic aneurysm ofany size that is symptomatic, tender, or enlarging rapidly.

Aneurysmectomy may not be appropriate for
patients with severely debilitating diseases such as can-
cer,emphysema , and heart failure .
An aortic aneurysm is a bulge in the wall of the aorta
that is usually due to arteriosclerosis or atherosclerosis .
People who are 50-80 years old are most likely to devel-op an aortic aneurysm, with men four times more likelyto develop one than women.
An aortic aneurysm develops and grows slowly. It

rarely produces symptoms and is usually only diagnosedby accident during a routine physical exam or on an x rayor ultrasound done for another reason. As the aneurysmgrows larger, the risk of bursting with no warning, whichcauses catastrophic bleeding, rises. A ruptured aorticaneurysm can cause sudden loss of a fatal amount of bloodwithin minutes or it can leak in a series of small bleedsthat lead within hours or days to massive bleeding. A leak-ing aortic aneurysm that is not treated is always

aortic aneurysm that is not treated is always fatal.Aneurysmectomy is performed to repair the two

most common types of aortic aneurysms: abdominal aor-tic aneurysms that occur in the abdomen below the kid-neys, and thoracic aortic aneurysms that occur in thechest. It is major surgery performed in a hospital undergeneral anesthesia and involves removing debris andthen implanting a flexible tube (graft) to replace theenlarged artery. Aneurysmectomy for an aneurysm of theascending aorta (the first part of the aorta that travelsupward from the heart) requires the use of a heart-lungmachine that

requires the use of a heart-lungmachine that temporarily stops the heart while theaneurysm is repaired. Aneurysmectomy requires a one-week hospital stay; the recovery period is five weeks.

abdomen or the chest) is opened with an incision to exposethe aneurysm. The aorta is clamped above and below theaneurysm to stop the flow of blood. Then, an incision ismade in the aneurysm. An artificial Dacron tube is sewn inplace above and below the opened aneurysm, but theaneurysm is not removed. Plaque or clotted blood arecleaned from the diseased tissue. The clamps are removedand blood flow is re-established through the graft. Thewall of the aneurysm is wrapped around the graft to pro-tect

aneurysm is wrapped around the graft to pro-tect it and the skin of the abdomen or chest is sewn up.

emergency surgery. Elective aneurysmectomy takes aboutan hour and is far safer than emergency aneurysmectomy,with a mortality rate of 3-5% for elective abdominalaneurysmectomy and 5-10% for elective thoracicaneurysmectomy. When an aneurysm ruptures, 62% ofpatients die before they reach the hospital. Of those whomake it into emergency aneurysmectromy, 50% die. Aftera successful aneurysmectomy, the patient has nearly thesame life expectancy as other people of the same age.

Before elective aneurysmectomy, blood studies, a
chest x ray , cardiac catherization, electrocardiogram
(ECG), and ultrasound are performed.
Aftercare
After aneurysmectomy, the patient is monitored in
an Intensive Care Unit for the first 24–48 hours. Follow-up tests include ECG, chest x ray, and ultrasound.
Risks
Elective aneurysmectomy has a 5-10% rate of compli-

cations, such as bleeding, kidney failure, respiratory com-plications, heart attack ,stroke , infection, limb loss, bowel
ischemia , and impotence . These complications are many
times more common in emergency aneurysmectomy.
GALE ENCYCLOPEDIA OF MEDICINE 2 193AneurysmectomyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 193

Resources
BOOKS
“Aneurysmectomy.” In Current Surgical Diagnosis and Treat-
ment. 10th ed. Ed. Lawrence W. Way. Stamford: Appleton
& Lange, 1994.
DeBakey, Michael E., and Antonio M. Gotto Jr. “Aneurysms.”
In The New Living Heart. Holbrook, MA: Adams Media
Corporation, 1997.
“Diseases of the Aorta.” In Current Medical Diagnosis and
“Aortic Aneurysm: Stopping a Silent Killer.” Johns Hopkins

Medical Letter 7 (Aug. 1995): 4-5.
Donaldson, M. C., M. Belkin, and A. D. Whittemore. “Mesen-
teric Revascularization During Aneurysmectomy.”Surgery Clinic of North America 77 (Apr. 1997): 443-459.
OTHER
“Aortic Aneurysm.” American Heart Association. 28 May 1998
<http://www.americanheart.org>.
“Aneurysm” and “Aneurysm Removal.” ThriveOnline. 28 May
1998. <http://thriveonline.oxygen.com>.
“Aortic Aneurysm: Surgery Can Stop This Silent Danger.”
Mayo Clinic Online. 28 May 1998. <http://www.mayo

health.org/mayo/9403/htm/aneurysm.htm>.
“Aneurysm, Diagnosis & Treatment.” Mid Atlantic Surgical
Associates Page. 28 May 1998. <http://www.heartsurgeons.
com>.
Lori De MiltoKEY TERMS
Aneurysm —A weakening in the muscular walls of
a part of the artery which causes the damaged sec-tion to enlarge or sag, giving it a balloon-likeappearance.
Aorta —The main blood vessel that leads away

from the heart and the body’s largest artery. Theaorta carries blood from the heart through thechest and abdomen, providing major branches toall of the organs in the body.
Arteriosclerosis —Hardening of the arteries that
occurs as part of the aging process.
Artery —A blood vessel that carries blood from the
heart to the body’s tissues.
Atherosclerosis —A form of arteriosclerosis in

which cholesterol-containing fatty deposits accu-mulate in the inner most walls of the heart’s arteries.
Thoracic —Relating to the chest.Aneurysms seeAneurysmectomy; Cerebral
aneurysm; Ventricular aneurysm
Angina
Angina is pain , “discomfort,” or pressure localized
in the chest that is caused by an insufficient supply ofblood ( ischemia ) to the heart muscle. It is also some-
times characterized by a feeling of choking , suffocation,

or crushing heaviness. This condition is also called angi-na pectoris.
Often described as a muscle spasm and choking sen-
sation, the term “angina” is used primarily to describechest (thoracic) pain originating from insufficient oxygento the heart muscle. An episode of angina is not an actualheart attack , but rather pain that results from the heart

muscle temporarily receiving too little blood. This tem-porary condition may be the result of demanding activi-ties such as exercise and does not necessarily indicate
that the heart muscle is experiencing permanent damage.In fact, episodes of angina seldom cause permanent dam-age to heart muscle.
Angina can be subdivided further into two cate-
gories: angina of effort and variant angina.
Angina of effort
Angina of effort is a common disorder caused by the

narrowing of the arteries ( atherosclerosis ) that supply
oxygen-rich blood to the heart muscle. In the case ofangina of effort, the heart (coronary) arteries can providethe heart muscle (myocardium) adequate blood duringrest but not during periods of exercise, stress , or excite-

ment—any of which may precipitate pain. The pain isrelieved by resting or by administering nitroglycerin, amedication that reduces ischemia of the heart. Patientswith angina of effort have an increased risk of heartattack (myocardial infarction).
V ariant angina
Variant angina is uncommon and occurs indepen-

dently of atherosclerosis which may, however, be presentas an incidental finding. Variant angina occurs at rest andis not related to excessive work by the heart muscle.Research indicates that variant angina is caused by coro-
GALE ENCYCLOPEDIA OF MEDICINE 2 194AnginaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 194

nary artery muscle spasm of insufficient duration or
intensity to cause an actual heart attack.
Angina causes a pressing pain or sensation of heavi-

ness, usually in the chest area under the breast bone (ster-num). It occasionally is experienced in the shoulder, arm,neck, or jaw regions. Because episodes of angina occurwhen the heart’s need for oxygen increases beyond theoxygen available from the blood nourishing the heart, thecondition is often precipitated by physical exertion. Inmost cases, the symptoms are relieved within a few min-utes by resting or by taking prescribed angina medica-tions. Emotional stress, extreme temperatures,

Emotional stress, extreme temperatures, heavymeals, cigarette smoking , and alcohol can also cause or

contribute to an episode of angina.
Diagnosis
Physicians can usually diagnose angina based on the
patient’s symptoms and the precipitating factors. Howev-er, other diagnostic testing is often required to confirm orrule out angina, or to determine the severity of the under-lying heart disease.
Electrocardiogram (ECG)
An electrocardiogram is a test that records electrical

impulses from the heart. The resulting graph of electricalactivity can show if the heart muscle isn’t functioningproperly as a result of a lack of oxygen. Electrocardio-grams are also useful in investigating other possibleabnormal features of the heart.
Stress test
For many individuals with angina, the results of an

electrocardiogram while at rest will not show any abnor-malities. Because the symptoms of angina occur duringstress, the functioning of the heart may need to be evalu-ated under the physical stress of exercise. The stress test

records information from the electrocardiogram before,during, and after exercise in search of stress-relatedabnormalities. Blood pressure is also measured duringthe stress test and symptoms are noted. A more involvedand complex stress test (for example, thallium scanning)may be used in some cases to picture the blood flow inthe heart muscle during the most intense time of exerciseand after rest.
Angiogram
The angiogram, which is basically an x ray of the

coronary artery, has been noted to be the most accuratediagnostic test to indicate the presence and extent of

coronary disease. In this procedure, a long, thin, flexibletube (catheter) is maneuvered into an artery located inthe forearm or groin. This catheter is passed furtherthrough the artery into one of the two major coronaryarteries. A dye is injected at that time to help the x rays“see” the heart and arteries more clearly. Many brief xrays are made to create a “movie” of blood flowingthrough the coronary arteries, which will reveal any pos-sible narrowing that causes a decrease in blood flow tothe

that causes a decrease in blood flow tothe heart muscle and associated symptoms of angina.

Treatment
Conservative treatment
Artery disease causing angina is addressed initially by
controlling existing factors placing the individual at risk.These risk factors include cigarette smoking, high bloodpressure, high cholesterol levels, and obesity . Angina is

often controlled by medication, most commonly withnitroglycerin. This drug relieves symptoms of angina byincreasing the diameter of the blood vessels carryingblood to the heart muscle. Nitroglycerin is taken wheneverdiscomfort occurs or is expected. It may be taken bymouth by placing the tablet under the tongue or transder-mally by placing a medicated patch directly on the skin. Inaddition, beta blockers or calcium channel blockers

may be prescribed to also decrease the demand on theheart by decreasing the rate and workload of the heart.
Surgical treatment
When conservative treatments are not effective in
the reduction of angina pain and the risk of heart attackremains high, physicians may recommend angioplasty

or surgery. Coronary artery bypass surgery is an opera-tion in which a blood vessel (often a long vein surgicallyremoved from the leg) is grafted onto the blocked arteryto bypass the blocked portion. This newly formed path-way allows blood to flow adequately to the heart muscle.
Another procedure used to improve blood flow to

the heart is balloon angioplasty. In this procedure, thephysician inserts a catheter with a tiny balloon at the endinto a forearm or groin artery. The catheter is then thread-ed up into the coronary arteries and the balloon is inflat-ed to open the vessel in narrowed sections. Other tech-niques using laser and mechanical devices are beingdeveloped and applied, also by means of catheters.

During an angina episode, relief has been noted by
applying massage or kinesiological methods, but thesetechniques are not standard recommendations by physi-
GALE ENCYCLOPEDIA OF MEDICINE 2 195AnginaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 195

cians. For example, one technique places the palm and
fingers of either hand on the forehead while simultane-ously firmly massaging the sternum (breast bone) up anddown its entire length using the other hand. This is fol-lowed by additional massaging by the fingertip andthumb next to the sternum, on each side.
Once the angina has subsided, the cause should be

determined and treated. Atherosclerosis, a major associat-ed cause, requires diet and lifestyle adjustments, primari-ly including regular exercise, reduction of dietary sugarand saturated fats, and increase of dietary fiber. Both con-ventional and alternative medicine agree that increasingexercise and improving diet are important steps to reducehigh cholesterol levels. Alternative medicine has pro-posed specific cholesterol-lowering treatments, with sev-eral gaining the attention and interest

with sev-eral gaining the attention and interest of the public. Oneof the most recent popular treatments is garlic ( Allium

sativum ). Some studies have shown that adequate dosages
of garlic can reduce total cholesterol by about 10%, LDL(bad) cholesterol by 15%, and raise HDL (good) choles-terol by 10%. Other studies have not shown significantbenefit. Although its effect on cholesterol is not as greatas that achieved by medications, garlic may possibly be ofbenefit in relatively mild cases of high cholesterol, with-out causing the side effects associated with cholesterol-

reducing drugs . Other herbal remedies that may help
lower cholesterol include alfalfa ( Medicago sativa ), fenu-
greek ( Trigonella foenum-graecum ), Asian ginseng
(Panax ginseng ), and tumeric ( Curcuma longa ).
Antioxidants, including vitamin A (beta carotene),
vitamin C, vitamin E, and selenium, can limit the oxida-tive damage to the walls of blood vessels that may be aprecursor of atherosclerotic plaque formation.
Prognosis
The prognosis for a patient with angina depends on

its origin, type, severity, and the general health of theindividual. A person who has angina has the best progno-sis if he or she seeks prompt medical attention and learnsthe pattern of his or her angina, such as what causes theattacks, what they feel like, how long episodes usuallylast, and whether medication relieves the attacks. If pat-terns of the symptoms change significantly, or if symp-toms resemble those of a heart attack, medical helpshould be sought immediately.

In most cases, the best prevention involves changing
one’s habits to avoid bringing on attacks of angina. Ifblood pressure medication has been prescribed, compli-ance is a necessity and should be a priority as well. Manyhealthcare professionals—including physicians, dieti-KEY TERMS
Ischemia— Decreased blood supply to an organ or
body part, often resulting in pain.
Myocardial infarction— A blockage of a coronary

artery that cuts off the blood supply to part of theheart. In most cases, the blockage is caused byfatty deposits.
Myocardium— The thick middle layer of the heart
that forms the bulk of the heart wall and contractsas the organ beats.
tians, and nurses—can provide valuable advice on proper

diet, weight control, blood cholesterol levels, and bloodpressure. These professionals also offer suggestionsabout current treatments and information to help stopsmoking. In general, the majority of those with anginaadjust their lives to minimize episodes of angina, by tak-ing necessary precautions and using medications if rec-ommended and necessary. Coronary artery disease is
the underlying problem that should be addressed.
Resources
BOOKS

Resources
BOOKS
Banasik, Jacquelyn L. “Alterations in Cardiac Function.” In
Perspectives on Pathophysiology , ed. Lee-Ellen C. Cop-
stead. Philadelphia: W. B. Saunders Co., 1994.
Chandrasoma, Parakrama, and Clive R. Taylor. Concise Pathol-
ogy.East Norwalk, CT: Appleton & Lange, 1991.
OTHER
“Angina.” Healthtouch Online Page. Sept. 1997. 21 May 1998.

<http://www.healthtouch.com>.
Jeffrey P. Larson, RPT
Angioedema seeHives
Angiogram seeAngiography
Angiography
Angiography is the x-ray study of the blood vessels.
An angiogram uses a radiopaque substance, or dye, to
GALE ENCYCLOPEDIA OF MEDICINE 2 196AngiographyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 196

make the blood vessels visible under x ray. Arteriography is
a type of angiography that involves the study of the arteries.
Purpose
Angiography is used to detect abnormalities or
blockages in the blood vessels (called occlusions)throughout the circulatory system and in some organs.The procedure is commonly used to identify atheroscle-
rosis ; to diagnose heart disease; to evaluate kidney func-

tion and detect kidney cysts or tumors; to detect ananeurysm (an abnormal bulge of an artery that can rup-ture leading to hemorrhage), tumor, blood clot, or arteri-
ovenous malformations (abnormals tangles of arteries
and veins) in the brain; and to diagnose problems withthe retina of the eye. It is also used to give surgeons anaccurate “map” of the heart prior to open-heart surgery,or of the brain prior to neurosurgery.
Patients with kidney disease or injury may suffer

further kidney damage from the contrast mediums usedfor angiography. Patients who have blood clotting prob-lems, have a known allergy to contrast mediums, or areallergic to iodine, a component of some contrast medi-ums, may also not be suitable candidates for an angiogra-phy procedure. Because x rays carry risks of ionizingradiation exposure to the fetus, pregnant women are alsoadvised to avoid this procedure.

Angiography is usually performed at a hospital by a
trained radiologist and assisting technician or nurse. Ittakes place in an x-ray or fluoroscopy suite, and for mosttypes of angiograms, the patient’s vital signs will bemonitored throughout the procedure.
Angiography requires the injection of a contrast dye
that makes the blood vessels visible to x ray. The dye isinjected through a procedure known as arterial puncture .

The puncture is usually made in the groin area, armpit,inside elbow, or neck. The site is cleaned with an antisep-tic agent and injected with a local anesthetic. First, asmall incision is made in the skin to help the needle pass.A needle containing an inner wire called a stylet is insert-ed through the skin into the artery. When the radiologisthas punctured the artery with the needle, the stylet isremoved and replaced with another long wire called aguide wire. It is normal for blood to spout

aguide wire. It is normal for blood to spout out of the nee-dle before the guide wire is inserted.

The guide wire is fed through the outer needle into
the artery and to the area that requires angiographicstudy. A fluoroscopic screen that displays a view of the

patient’s vascular system is used to pilot the wire to thecorrect location. Once it is in position, the needle isremoved and a catheter is slid over the length of theguide wire until it to reaches the area of study. The guidewire is removed and the catheter is left in place in prepa-ration for the injection of the contrast medium, or dye.
Depending on the type of angiography procedure

being performed, the contrast medium is either injectedby hand with a syringe or is mechanically injected withan automatic injector connected to the catheter. Anautomatic injector is used frequently because it is ableto propel a large volume of dye very quickly to theangiogram site. The patient is warned that the injectionwill start, and instructed to remain very still. The injec-tion causes some mild to moderate discomfort. Possibleside effects or reactions include headache ,dizziness ,

irregular heartbeat, nausea, warmth, burning sensation,and chest pain , but they usually last only momentarily.
To view the area of study from different angles or per-spectives, the patient may be asked to change positionsseveral times, and subsequent dye injections may beadministered. During any injection, the patient or thecamera may move.
Throughout the dye injection procedure, x-ray pic-

tures and/or fluoroscopic pictures (or moving x rays) willbe taken. Because of the high pressure of arterial bloodflow, the dye will dissipate through the patient’s systemquickly, so pictures must be taken in rapid succession.
GALE ENCYCLOPEDIA OF MEDICINE 2 197Angiography
An angiogram of a coronary artery. (Phototake NYC. Repro-
duced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 197

An automatic film changer is used because the manual
changing of x-ray plates can eat up valuable time.
Once the x rays are complete, the catheter is slowly
and carefully removed from the patient. Pressure isapplied to the site with a sandbag or other weight for 10-20 minutes in order for clotting to take place and thearterial puncture to reseal itself. A pressure bandage isthen applied.
Most angiograms follow the general procedures out-

lined above, but vary slightly depending on the area ofthe vascular system being studied. A variety of commonangiography procedures are outlined below:
Cerebral angiography
Cerebral angiography is used to detect aneurysms,

blood clots, and other vascular irregularities in the brain.The catheter is inserted into the femoral or carotid arteryand the injected contrast medium travels through theblood vessels on the brain. Patients frequently experienceheadache, warmth, or a burning sensation in the head orneck during the injection portion of the procedure. Acerebral angiogram takes two to four hours to complete.
Coronary angiography

Coronary angiography is administered by a cardiol-

ogist with training in radiology or, occasionally, by aradiologist. The arterial puncture is typically given in thefemoral artery, and the cardiologist uses a guide wire andcatheter to perform a contrast injection and x-ray serieson the coronary arteries. The catheter may also be placedin the left ventricle to examine the mitral and aorticvalves of the heart. If the cardiologist requires a view ofthe right ventricle of the heart or of the tricuspid or pul-monic valves, the catheter will be

or pul-monic valves, the catheter will be inserted through alarge vein and guided into the right ventricle. Thecatheter also serves the purpose of monitoring bloodpressures in these different locations inside the heart. Theangiogram procedure takes several hours, depending onthe complexity of the procedure.

Pulmonary angiography
Pulmonary, or lung, angiography is performed to
evaluate blood circulation to the lungs. It is also consid-ered the most accurate diagnostic test for detecting a pul-
monary embolism . The procedure differs from cerebral

and coronary angiograms in that the guide wire andcatheter are inserted into a vein instead of an artery, andare guided up through the chambers of the heart and intothe pulmonary artery. Throughout the procedure, thepatient’s vital signs are monitored to ensure that thecatheter doesn’t cause arrhythmias , or irregular heart-beats. The contrast medium is then injected into the pul-
monary artery where it circulates through the lung capil-laries. The test typically takes up to 90 minutes.

Kidney angiography
Patients with chronic renal disease or injury can suf-

fer further damage to their kidneys from the contrastmedium used in a kidney angiogram, yet they oftenrequire the test to evaluate kidney function. Thesepatients should be well-hydrated with a intravenoussaline drip before the procedure, and may benefit fromavailable medications (e.g., dopamine) that help to pro-tect the kidney from further injury due to contrast agents.During a kidney angiogram, the guide wire and catheterare inserted into the femoral artery in the groin area andadvanced

the femoral artery in the groin area andadvanced through the abdominal aorta, the main artery inthe abdomen, and into the renal arteries. The procedurewill take approximately one hour.

Fluorescein angiography
Fluorescein angiography is used to diagnose retinal

problems and circulatory disorders. It is typically con-ducted as an outpatient procedure. The patient’s pupilsare dilated with eye drops and he rests his chin and fore-head against a bracing apparatus to keep it still. Sodiumfluorescein dye is then injected with a syringe into a veinin the patient’s arm. The dye will travel through thepatient’s body and into the blood vessels of the eye. Theprocedure does not require x rays. Instead, a rapid seriesof close-up photographs of the patient’s eyes

close-up photographs of the patient’s eyes are taken,one set immediately after the dye is injected, and a sec-ond set approximately 20 minutes later once the dye hasmoved through the patient’s vascular system. The entireprocedure takes up to one hour.

Celiac and mesenteric angiography
Celiac and mesenteric angiography involves x-ray
exploration of the celiac and mesenteric arteries, arterialbranches of the abdominal aorta that supply blood to theabdomen and digestive system. The test is commonlyused to detect aneurysm, thrombosis, and signs ofischemia in the celiac and mesenteric arteries, and to

locate the source of gastrointestinal bleeding. It is alsoused in the diagnosis of a number of conditions, includ-ing portal hypertension , and cirrhosis . The procedure
can take up to three hours, depending on the number ofblood vessels studied.
Splenoportography
A splenoportograph is a variation of an angiogram
that involves the injection of contrast medium directlyinto the spleen to view the splenic and portal veins. It isused to diagnose blockages in the splenic vein and portal

GALE ENCYCLOPEDIA OF MEDICINE 2 198AngiographyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 198

vein thrombosis and to assess the strength and location of
the vascular system prior to liver transplantation .
Most angiography procedures are typically paid for by
major medical insurance. Patients should check with theirindividual insurance plans to determine their coverage.
Patients undergoing an angiogram are advised to

stop eating and drinking eight hours prior to the proce-dure. They must remove all jewelry before the procedureand change into a hospital gown. If the arterial punctureis to be made in the armpit or groin area, shaving may berequired. A sedative may be administered to relax thepatient for the procedure. An IV line will also be insertedinto a vein in the patient’s arm before the procedurebegins in case medication or blood products are requiredduring the angiogram.

Prior to the angiography procedure, patients will be
briefed on the details of the test, the benefits and risks,KEY TERMS
Arteriosclerosis —A chronic condition character-
ized by thickening and hardening of the arteries andthe build-up of plaque on the arterial walls. Arte-riosclerosis can slow or impair blood circulation.
Carotid artery —An artery located in the neck.
Catheter —A long, thin, flexible tube used in angiog-
raphy to inject contrast material into the arteries.

Cirrhosis —A condition characterized by the
destruction of healthy liver tissue. A cirrhotic liver isscarred and cannot break down the proteins in thebloodstream. Cirrhosis is associated with portalhypertension.
Embolism —A blood clot, air bubble, or clot of for-

eign material that travels and blocks the flow ofblood in an artery. When blood supply to a tissue ororgan is blocked by an embolism, infarction, ordeath of the tissue the artery feeds, occurs. Withoutimmediate and appropriate treatment, an embolismcan be fatal.
Femoral artery —An artery located in the groin area
that is the most frequently accessed site for arterialpuncture in angiography.
Fluorescein dye —An orange dye used to illuminate

the blood vessels of the retina in fluorescein angiog-raphy.Fluoroscopic screen —A fluorescent screen which
displays “moving x-rays” of the body. Fluoroscopyallows the radiologist to visualize the guide wireand catheter he is moving through the patient’sartery.
Guide wire —A wire that is inserted into an artery to
guides a catheter to a certain location in the body.
Iscehmia —A lack of normal blood supply to a

organ or body part because of blockages or con-striction of the blood vessels.
Necrosis —Cellular or tissue death; skin necrosis
may be caused by multiple, consecutive doses ofradiation from fluoroscopic or x-ray procedures.
Plaque —Fatty material that is deposited on the
inside of the arterial wall.
Portal hypertension —A condition caused by cirrho-

sis of the liver. It is characterized by impaired orreversed blood flow from the portal vein to the liver,an enlarged spleen, and dilated veins in the esopha-gus and stomach.
Portal vein thrombosis —The development of a
blood clot in the vein that brings blood into theliver. Untreated portal vein thrombosis causes por-tal hypertension.
and the possible complications involved, and asked to
sign an informed consent form.
Aftercare
Because life-threatening internal bleeding is a possi-

ble complication of an arterial puncture, an overnight stayin the hospital is sometimes recommended following anangiography procedure, particularly with cerebral andcoronary angiograms. If the procedure is performed on anoutpatient basis, the patient is typically kept under closeobservation for a period of at six to 12 hours before beingreleased. If the arterial puncture was performed in thefemoral artery, the patient will be instructed to keep hisleg straight and relatively immobile during the

straight and relatively immobile during the observa-tion period. The patient’s blood pressure and vital signswill be monitored and the puncture site observed closely.Pain medication may be prescribed if the patient is expe-riencing discomfort from the puncture, and a cold pack isapplied to the site to reduce swelling. It is normal for thepuncture site to be sore and bruised for several weeks.

GALE ENCYCLOPEDIA OF MEDICINE 2 199AngiographyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 199

The patient may also develop a hematoma, a hard mass
created by the blood vessels broken during the procedure.Hematomas should be watched carefully, as they mayindicate continued bleeding of the arterial puncture site.
Angiography patients are also advised to enjoy two
to three days of rest and relaxation after the procedure inorder to avoid placing any undue stress on the arterial

puncture. Patients who experience continued bleeding orabnormal swelling of the puncture site, sudden dizziness,or chest pains in the days following an angiography pro-cedure should seek medical attention immediately.
Patients undergoing a fluorescein angiography
should not drive or expose their eyes to direct sunlightfor 12 hours following the procedure.
Risks
Because angiography involves puncturing an artery,

internal bleeding or hemorrhage are possible complica-tions of the test. As with any invasive procedure, infec-tion of the puncture site or bloodstream is also a risk, butthis is rare.
A stroke or heart attack may be triggered by an

angiogram if blood clots or plaque on the inside of thearterial wall are dislodged by the catheter and form ablockage in the blood vessels or artery. The heart mayalso become irritated by the movement of the catheterthrough its chambers during pulmonary and coronaryangiography procedures, and arrhythmias may develop.
Patients who develop an allergic reaction to the con-

trast medium used in angiography may experience a vari-ety of symptoms, including swelling, difficulty breath-ing,heart failure , or a sudden drop in blood pressure. If
the patient is aware of the allergy before the test isadministered, certain medications can be administered atthat time to counteract the reaction.
Angiography involves minor exposure to radiation

through the x rays and fluoroscopic guidance used in theprocedure. Unless the patient is pregnant, or multipleradiological or fluoroscopic studies are required, thesmall dose of radiation incurred during a single proce-dure poses little risk. However, multiple studies requiringfluoroscopic exposure that are conducted in a short timeperiod have been known to cause skin necrosis in someindividuals. This risk can be minimized by careful moni-toring and documentation of cumulative radiation

and documentation of cumulative radiation dosesadministered to these patients.

The results of an angiogram or arteriogram depend
on the artery or organ system being examined. Generally,test results should display a normal and unimpeded flow
of blood through the vascular system. Fluoresceinangiography should result in no leakage of fluoresceindye through the retinal blood vessels.
Abnormal results of an angiography may display a

restricted blood vessel or arterial blood flow (ischemia)or an irregular placement or location of blood vessels.The results of an angiography vary widely by the type ofprocedure performed, and should be interpreted andexplained to the patient by a trained radiologist.
Resources
BOOKS
Baum, Stanley, and Michael J. Pentecost, eds. Abrams’Angiog-
raphy. 4th ed. Philadelphia: Lippincott-Raven, 1996.
Angiomas seeBirthmarks

Angioplasty
Angioplasty is a term describing a procedure used to

widen vessels narrowed by stenoses or occlusions. Thereare various types of these procedures and their names areassociated with the type of vessel entry and equipmentused. For example, percutaneous transluminal angioplasty(PTA) describes entry through the skin (percutaneous) andnavigates to the area of the vessel of interest through thesame vessel or one that communicates with it (translumi-nal). In the case of a procedure involving the coronaryarteries, the point of entry could be the femoral

the point of entry could be the femoral artery in thegroin and the catheter/guidewire system is passed throughthe aorta to the heart and the origin of the coronary arteriesat the base of the aorta just outside the aortic valve.

Purpose
In individuals with an occulsive vascular disease
such as atherosclerosis , blood flow is impaired to an
organ (such as the heart) or to a distal body part ( such asthe lower leg) by the narrowing of the vessel’s lumen dueto fatty deposits or calcium accumulation. This narrow-ing may occur in any vessel but may occur anywhere.Once the vessel has been widened, adequate blood flowis returned. The vessel may narrow again over time at thesame location and the procedure could be repeated.

GALE ENCYCLOPEDIA OF MEDICINE 2 200AngioplastyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 200

inpatients in facilities for proper monitoring and recov-ery. If the procedure is to be performed in a coronaryartery, the patient’s care is likely to be provided by spe-cially trained physicians, nurses, and vascular specialists.Typically, patients are given anticoagulants prior to theprocedure to assist in the prevention of thromboses(blood clots). Administration of anticoagulants, however,may impede the sealing of the vascular entry point. Theprocedure will be performed using fluoroscopic

Theprocedure will be performed using fluoroscopic guidanceand contrast media. Since the decision to perform angio-plasty may have been made following a diagnosticangiogram, the patient’s sensitivity to iodinated contrastmedia is likely to known. The procedure may thenrequire the use of non-ionic contrast agents.

Angioplasty was originally performed by dilating the

vessel with the introduction of larger and larger stiffcatheters through the narrowed space. Complications ofthis procedure caused researchers to develop means ofwidening the vessel using a minimally sized device.Today, catheters contain balloons that are inflated to widenthe vessel and stents to provide structural support for thevessel. Lasers may be used to assist in the break up of thefat or calcium plaque. Catheters may also be equippedwith spinning wires or drill tips to clean out the

Angioplasty may be performed while the patient is
sedated or anesthetized, depending on the vesselsinvolved. If a percutaneous transluminal coronary angio-
plasty (PTCA) is to be performed, the patient will bekept awake to report on discomfort and cough if
required. PTCA procedures are performed in cardiac
catheterization labs with sophisticated monitoring

devices. If angioplasty is performed in the radiologydepartment’s angiographic suite, the patient may besedated for the procedure and a nurse will monitor thepatient’s vital signs during the procedure. If performedby a vascular surgeon, the angioplasty procedure will beperformed in an operating room or specially designedvascular procedure suite.
The site of the introduction of the angioplasty equip-

ment is prepared as a sterile surgical site. Although manyprocedures are performed by puncturing the vesselthrough skin, many procedures are also performed bysurgically exposing the site of entry. Direct view of thevessel’s puncture site aids in monitoring damage to thevessel or excessive bleeding at the site. Once the vessel ispunctured and the guidewire is introduced, fluoroscopyis used to monitor small injections of contrast media usedto visualize the path through the vessel. If the

visualize the path through the vessel. If the fluo-roscopy system has a feature called ‘roadmap’, theamount of contrast media injected will be greater in orderto define the full route the guidewire will take. The fluo-roscopy system will then superimpose subsequentimages over the roadmap while the vessel is traversed,that is, the physician moves the guidewire along the mapto the destination.

Having reached the area of stenosis, the physician
will inflate the balloon on the catheter that has been
GALE ENCYCLOPEDIA OF MEDICINE 2 201Angioplasty
Before AfterAngioplasty
Guidewire
Inadequate
flow
PlaqueLumenImproved
flowInflated
balloon
In balloon angioplasty, plaque is pushed out of the clogged artery by the inflation of the balloon device. (Illustration by Argosy Inc.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 201

and duration depending on the size and location of thevessel. In some cases, the use of a stent (a mesh of wirethat resembles a Chinese finger puzzle) may also beused. The vessel may be widened before, during, or afterthe deployment of the stent. Procedures for deployingstents are dependent on the type of stent used. In caseswhere the vessel is tortuous or at intersections of vessels,the use of a graph may be necessary to provide structuralstrength to the vessel. Stents, graphs, and balloon

to the vessel. Stents, graphs, and balloon dila-tion may all be used together or separately.

The procedure is verified using fluoroscopy and
contrast media to produce an angiogram or by usingintravascular ultrasound or both. All equipment is with-drawn from the vessel and the puncture site repaired.
Risks
During the procedure there is a danger of puncturing
the vessel with the guidewire. This is a very small risk.Patients must be monitored for hematoma or hemorrhageat the puncture site. There is also a small risk of heart
attack , emboli, and although unlikely death . Hospital-

ization will vary in length by the patient’s overall condi-tion, any complications, and availability of home care.
Resources
BOOKS
Thomas MD MPH, Clayton L. editor. Taber’s Cyclopedic Med-
ical Dictionary. Philadelphia, PA: F.A. Davis Company,
1985.
Schneider MD, Peter A. Endovascular Skills: Guidewires,
Catheters, Arteriography, Balloon Angioplasty, Stents. St.
Louis, MO: Quality Medical Publishing, Inc., 1998.
Wojtowycz MD, Mryon. Handbooks in Radiology-Interven-

tional Radiology and Agiography. Chicago, IL: Year Book
Medical Publishers, Inc., 1990.
Carnall, Douglas. “Angioplasty.” The Western Journal of Medi-
cine (September 2000):v173 i3 p201
“New Imaging Technique Could Improve Outcome of Popular
Heart Procedure.” Heart Disease Weekly (May 13, 2001):3
“Success clearing clogged arteries.” Science News (February 3,
2001):v159 i5 p72
“The angioplasty correct follow up strategy after stent implan-
tation.” Heart (April, 2001):v85 i4 p363.

OTHER
“Cardiovascular System” Miami Heart Research Institute.
2001. <http://www.miamiheartresearch.org/LearningCenter/YourCardiovascular/Cardiovascular.htm (July 5,2001).
“Coronary angioplasty: Opening clogged arteries” MayoClin-
ic.com, Condition Centers, Treatments and tests. 2000.<http://www.mayoclinic.com> (July 5, 2001).KEY TERMS
Plaque —In atherosclerosis, a swollen area in the
lining of an artery formed by fatty deposits.

Cardiac catheterization —A procedure to pass a
catheter to the heart and its vessels for the purposeof diagnosing coronary artery disease, assessinginjury or disease of the aorta, or evaluating cardiacfunction.
EKG—Electrocardiogram, used to study and record
the electrical activity of the heart.
“Heart & Stroke Guide: Laser Angioplasty.” American Heart
Association online. 2000. <http://www.americanheart.org/

Heart_and_Stroke_A_Z_Guide/angiol.html> (July 5,2001).
“STS Patient Information: What to Expect after your Heart
Surgery.” Society of Thoracic Surgeons online. 2000.<http://www.sts.org/doc/3563> (July 5, 2001).
“When you need to have Angioplast: A patient guide” Heart
Information Network. 2000. <http://www.heartinfo.org/news97/gdangio111897.htm> (July 5, 2001).
Elaine R. Proseus, MBA/TM, BSRT, RT(R)
Angiotensin-converting

Angiotensin-converting enzyme inhibitors (also
called ACE inhibitors) are medicines that block the con-version of the chemical angiotensin I to a substance thatincreases salt and water retention in the body.
Purpose
ACE inhibitors are used in the treatment of high

blood pressure. They may be used alone or in combina-tion with other medicines for high blood pressure. Theywork by preventing a chemical in the blood, angiotensinI, from being converted into a substance that increasessalt and water retention in the body. Increased salt andwater retention lead to high blood pressure. ACEinhibitors also make blood vessels relax, which helpslower blood pressure and allows more oxygen-rich bloodto reach the heart.

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Treating high blood pressure is important because
the condition puts a burden on the heart and the arteries,which can lead to permanent damage over time. Ifuntreated, high blood pressure increases the risk of heartattacks, heart failure ,stroke , or kidney failure.
ACE inhibitors may also be prescribed for other

conditions. For example, captopril (Capoten) is used totreat kidney problems in people who take insulin to con-trol diabetes. Captopril and lisinopril are also given tosome patients after a heart attack . Heart attacks dam-
age and weaken the heart muscle, and the damage con-tinues even after a person recovers from the attack. Thismedicine helps slow down further damage to the heart.ACE inhibitors also may be used to treat congestiveheart failure.

ACE inhibitors are available only with a physician’s
prescription and come in tablet, capsule, and injectableforms. Some commonly used ACE inhibitors arebenazepril (Lotensin), captopril (Capoten), enalapril(Vasotec), fosinopril (Monopril), lisinopril (Prinivil,Zestril), moexipril (Univasc), perindopril (Aceon),quinapril (Accupril), ramipril (Altace) and trandolapril(Mavik).

ACE inhibitor and the medical condition for which it isbeing taken. Check with the physician who prescribedthe drug or the pharmacist who filled the prescription forthe correct dosage.
This medicine may take weeks to noticeably lower
blood pressure. Take it exactly as directed.
Do not stop taking this medicine without checking
with the physician who prescribed it.
A person taking an ACE inhibitor should see a

physician regularly. The physician will check the bloodpressure to make sure the medicine is working as itshould and will note any unwanted side effects. Peoplewho have high blood pressure often feel perfectly fine.However, they should continue to see their physicianseven when they feel well so that the physician can keepa close watch on their condition. It is also important forpatients to keep taking their medicine even when theyfeel fine.

ACE inhibitors will not cure high blood pressure,
but will help control the condition. To avoid the serioushealth problems that high blood pressure can cause,

patients may have to take medicine for the rest of theirlives. Furthermore, medicine alone may not be enough.Patients with high blood pressure may also need to avoidcertain foods, such as salty snacks, and keep their weightunder control. The health care professional who is treat-ing the condition can offer advice on what measures maybe necessary. Patients being treated for high blood pres-sure should not change their diets without consulting
their physicians.

Anyone taking this medicine for high blood pressure
should not take any other prescription or over-the-counter (OTC) medicine without first checking with hisor her physician. Some medicines, such as certain coldremedies, may increase blood pressure.
Some people feel dizzy or lightheaded after taking

the first dose of an ACE inhibitor, especially if theyhave been taking a water pill (diuretic). Anyone whotakes these drugs should not drive, use machines or doanything else that might be dangerous until they havefound out how the drugs affect them. Such symptomsshould be reported to the physician or pharmacist ifthey do not subside within a day or so. For the first oneor two days of taking an ACE inhibitor, patients maybecome lightheaded when arising from bed in themorning. Patienst should

arising from bed in themorning. Patienst should rise slowly to a sitting posi-tion before standing up.

While a goal of treatment with an ACE inhibitor is to
lower the blood pressure, patients must be careful not tolet their blood pressure get too low. Low blood pressurecan lead to dizziness , lightheadedness and fainting . To
prevent the blood pressure from getting too low, observethese precautions:
• Do not drink alcohol without checking with the physi-
cian who prescribed this medicine.
• Captopril and moexipril should be taken one hour

before meals. Other ACE inhinbitors may be taken withor without meals.
• Avoid overheating when exercising or in hot weather.
The loss of water from the body through heavy sweat-ing can cause low blood pressure.
• Check with a physician right away if illness occurs
while taking an ACE inhibitor. This is especially true ifthe illness involves severe nausea, vomiting, or diar-
rhea . V omiting and diarrhea can cause the loss of too
much water from the body, which can lead to low bloodpressure.

Anyone who is taking ACE inhibitors should be sure
to tell the health care professional in charge before hav-ing any surgical or dental procedures or receiving emer-gency treatment.
GALE ENCYCLOPEDIA OF MEDICINE 2 203Angiotensin-converting enzyme inhibitorsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 203

Some ACE inhibitors may change the results of cer-
tain medical tests, such as blood or urine tests. Beforehaving medical tests, anyone taking this medicine shouldalert the health care professional in charge.
Do not use a potassium supplement or a salt substi-
tute that contains potassium without first checking withthe physician who prescribed the ACE inhibitor.
Patients who are being treated with bee or wasp

venom to prevent allergic reactions to stings may have asevere allergic reaction to certain ACE inhibitors.
taking certain other medicines can have problems if theytake ACE inhibitors. Before taking these drugs, be sureto let the physician know about any of these conditions.
ALLERGIES. Anyone who has had unusual reactions

to an ACE inhibitor in the past should let his or herphysician know before taking this type of medicineagain. The physician should also be told about any aller-
giesto foods, dyes, preservatives, or other substances.
PREGNANCY. The use of ACE inhibitors in preg-
nancy can cause serious problems and even death in the

fetus or newborn. Women who are pregnant or who maybecome pregnant should check with their physiciansbefore using this medicine. Women who become preg-nant while taking this medicine should check with theirphysicians immediately.
BREASTFEEDING. Some ACE inhibitors pass into
breast milk. Women who are breastfeeding should checkwith their physicians before using ACE inhibitors.
OTHER MEDICAL CONDITIONS. Before using ACE

inhibitors, people with any of these medical problemsshould make sure their physicians are aware of their con-ditions:
• diabetes
• heart or blood vessel disease• recent heart attack or stroke• liver disease• kidney disease
• kidney transplant
• scleroderma• systemic lupus erythematosus (SLE)
USE OF CERTAIN MEDICINES. Taking ACE inhibitors
with certain other drugs may affect the way the drugswork or may increase the chance of side effects.Side effects

The most common side effect is a dry, continuing
cough . This usually does not subside unless the medica-
tion is stopped. Ask the physician if the cough can betreated. Less common side effects, such as headache ,
loss of taste, unusual tiredness, and nausea or diarrheaalso may occur and do not need medical attention unlessthey are severe or they interfere with normal activities.
More serious side effects are rare, but may occur. If

any of the following side effects occur, check with aphysician immediately:
• swelling of the face, lips, tongue, throat, arms, legs,
hands, or feet
• itchy skin• sudden breathing or swallowing problems
• chest pain
• hoarseness• sore throat• fever and chills• stomach pain• yellow eyes or skin
In addition, anyone who has any of the following
symptoms while taking an ACE inhibitor should checkwith his or her physician as soon as possible:
• dizziness, lightheadedness, fainting

• confusion• nervousness•f e v e r• joint pain• numbness or tingling in hands, feet, or lips
• weak or heavy feeling in the legs
• skin rash• irregular heartbeat• shortness of breath or other breathing problems
unusual symptoms after taking an ACE inhibitor shouldget in touch with his or her physician.
ACE inhibitors may interact with certain foods and

other medicines. For example, captopril (Capoten) inter-acts with food and should be taken one hour beforemeals. Anyone who takes ACE inhibitors should let thephysician know all other medicines he or she is takingand should ask about foods that should be avoided.
GALE ENCYCLOPEDIA OF MEDICINE 2 204Angiotensin-converting enzyme inhibitorsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 204

Among the foods and drugs that may interact with ACE
inhibitors are:
• water pills (diuretics)
• lithium, used to treat bipolar disorder• tetracycline, an antibiotic• medicines or supplements that contain potassium• salt substitutes that contain potassium
The list above may not include everything that inter-
acts with ACE inhibitors. Be sure to check with a physi-cian or pharmacist before combining ACE inhibitorswith any other prescription or nonprescription (over-the-counter) medicine.

enzyme test
This test measures blood levels of angiotensin-con-
verting enzyme (ACE), also known as Serum Angiotensin-Converting Enzyme (SASE). The primary function ofKEY TERMS
Arteries —Blood vessels that carry blood away
from the heart to the cells, tissues, and organs ofthe body.
Chronic —A word used to describe a long-lasting
condition. Chronic conditions often develop grad-ually and involve slow changes.

Enzyme —A type of protein, produced in the body,
that brings about or speeds up chemical reactions.
Fetus —A developing baby inside the womb.
Scleroderma —A disease that first affects the skin
and later affects certain internal organs. The firstsymptoms are the hardening, thickening, andshrinking of the skin.
Systemic lupus erythematosus (SLE) —A chronic
disease that affects the skin, joints, and certaininternal organs.
Venom —A poisonous substance secreted by an

animal, usually delivered through a bite or a sting.ACE is to help regulate arterial pressure by converting
angiotensin I to angiotensin II.
Purpose
The ACE test is used primarily to detect and monitor
the clinical course of sarcoidosis (a disease that affects

many organs, especially the lungs), to differentiatebetween sarcoidosis and similar diseases, and to delin-eate between active and inactive sarcoid disease. Elevat-ed ACE levels are also found in a number of other condi-tions, including Gaucher’s disease (a rare familial disor-der of fat metabolism) and leprosy .
It should be noted that people under 20 years of age

normally have very high ACE levels. Decreased levels maybe seen in the condition of excess fat in the blood (hyper-lipidemia). Drugs that may cause decreased ACE levelsinclude ACE inhibitor antihypertensives and steroids.
ACE plays an important role in the renin/aldosterone

mechanism which controls blood pressure by convertingangiotensin I to angiotensin II, two proteins involved inregulating blood pressure. Angiotensin I by itself is inac-tive, but when converted by ACE to the active form,angiotensin II, it causes narrowing of the small bloodvessels in tissues, resulting in an increase in blood pres-sure. Angiotensin II also stimulates the hormone aldos-terone, which causes an increase in blood pressure. Cer-tain kidney disorders increase the production

Cer-tain kidney disorders increase the production ofangiotensin II, another cause of hypertension . Despite

the action of ACE on blood pressure regulation, determi-nation of this enzyme is not very helpful in the evaluationof hypertension (high blood pressure).
Determination of ACE levels requires a blood sam-
ple. The patient need not be fasting .
Risks
slight bleeding from the puncture site, fainting or feeling
lightheaded after venipuncture, or hematoma (bloodaccumulating under the puncture site).

Normal ranges for this test are laboratory-specific
but can range from 8-57 U/ml for patients over 20 yearsof age.
GALE ENCYCLOPEDIA OF MEDICINE 2 205Angiotensin-converting enzyme testGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 205

Serum ACE levels are elevated in approximately 80-
90% of patients with active sarcoidosis. Thyroid hor-mone may have an effect on ACE activity, as hypothyroid(low thyroid) patients, as well as patients with anorexia
nervosa with associated findings of hypothyroidism ,
may have low serum ACE activity. ACE can also bedecreased in lung cancer (bronchogenic carcinoma).
Resources
BOOKS
Cahill, Mathew. Handbook of Diagnostic Tests. Springhouse,
PA: Springhouse Corporation, 1995.

Animal bite infections
The most common problem following an animal bite

is simple infection. The saliva of dogs and cats is knownto contain a wide variety of bacteria. According to onerecent study, bacteria or other pathogens show up inabout 85 percent of bites. When an animal bites, it canthen transmit pathogens into the wound. These microor-ganisms may grow within the wound and cause an infec-tion. The consequences of infection range from mild dis-comfort to life-threatening complications.

Two to 4.5 million animal bites occur each year in
the United States and about 1% of bites require hospital-ization. Animal bites result in 334,000 emergency roomvisits per year, which represents approximately 1% of allemergency hospital visits, at an annual cost of $100 mil-lion dollars in health care expenses and lost income.KEY TERMS
Sarcoidosis —Sarcoidosis is a rare disease of

unknown cause in which inflammation occurs inlymph nodes and other tissues throughout thebody, usually the lungs, skin, liver, and eyes.Children are the most frequent victims of dog bites, with
5-9 year-old boys having the highest incidence. Men aremore often bitten by dogs than are women (3:1), whereaswomen are more often bitten by cats (3:1).
Dog bites make up 80-85% of all reported incidents.

Cats account for about 10% of reported bites, and otheranimals (including rodents, rabbits, horses, raccoons,bats, skunks, and monkeys) make up the remaining 5-10%. Cat bites become infected more frequently thandog bites. A dog’s mouth is rich in bacteria, but only 15-20% of dog bites become infected. In contrast, approxi-mately 30-50% of cat bites become infected.
Many factors contribute to the infection rates, such

as, for example, the type of wound inflicted, the locationof the wound, pre-existing health conditions in the bittenperson, the extent of delay before treatment, patient com-pliance and the presence of a foreign body in the wound.Dogs usually inflict crush injuries because they haverounded teeth and strong jaws; thus, the bite of an adultdog can exert up to 200 pounds per square inch of pres-sure. This pressure usually results in a crushing injury,causing damage to deep structures such as

injury,causing damage to deep structures such as bones, bloodvessels, tendons, muscles, and nerves. Dog canine teethare also sharp and strong and also inflict lacerations.Cats, with their needle-like fangs, typically cause punc-ture wounds . Puncture wounds appear innocuous on the

surface, but the underlying injury goes deep. Cat teethessentially inject bacteria into the bite, and the deep, nar-row wound is difficult to clean. Persons with impairedimmunocompetence—for example, individuals with HIVinfection—are especially vulnerable to infection.
The bacterial species most commonly found in bite
wounds include Pasteurella multocida ,Staphylococcus
aureus ,Pseudomonas sp , and Streptococcus sp . P . multoci-
da, the root cause of pasteurellosis, is especially prominent

in cat bite infections. Other infectious diseases from animalbites include cat-scratch disease ,tetanus and rabies .
The most common sign of infection from an animal

bite is inflammation. The skin around the wound is redand feels warm, and the wound may exude pus. Nearbylymph glands may be swollen. Complications can arise ifthe infection is not treated and spreads into deeper struc-tures or into the bloodstream. If the bite is deep or occurson the hand or at a joint, complications are more likely.
Live, disease-causing bacteria within the blood-

stream and tissues cause complications far from thewound site. Such complications include meningitis ,
brain abscesses, pneumonia and lung abscesses, and
heart infections, among others. These complications canbe fatal. Deep bites or bites near joints can damage joints
GALE ENCYCLOPEDIA OF MEDICINE 2 206Animal bite infectionsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 206

and bones, causing inflammation of the bone and bone
marrow or septic arthritis.
Cat-scratch disease is caused by Bartonella hense-
lae, a bacterium that is carried in cat saliva; infection

may be transmitted by a bite or scratch. Approximately22,000 cases are reported each year in the United States;worldwide, nine out of every 100,000 individualsbecome infected. More than 80% of reported cases occurin persons under the age of 21. The disease is not nor-mally severe in individuals with healthy immune sys-tems. Symptoms may become serious, however, inimmunocompromised individuals, such as those withacquired immune deficiency syndrome ( AIDS ) or those

undergoing chemotherapy . Common symptoms include
an inflamed sore in the area of the bite or scratch,swollen lymph nodes, fever ,fatigue , and rash.
Rabies is caused by a virus that is transmitted through

the bite of an animal that is already infected. More than90% of animal rabies cases occur in wild animals such asskunks, bats, and raccoons, with domestic animals such asdogs and cats accounting for less than 10%. The WorldHealth Organization (WHO) estimates that between35,000 and 50,000 individuals worldwide die each year asa result of rabies. The highest incidence of rabies occurs inAsia where, in 1997, over 33,000 deaths were noted, mostoccurring in India. Rabies is nowadays rare in the U.S.

in India. Rabies is nowadays rare in the U.S. dueto good animal control practice. The delay of onset is usu-ally weeks to months after being bitten. Early symptomsof rabies include fever, headache , and flu-like symptoms.

These progress to anxiety ,hallucinations , muscle
spasms, partial paralysis , fear of water (hydrophobia), and
other neurological symptoms as the virus spreads to thecentral nervous system. Medical treatment must be soughtsoon after exposure because death invariably follows once
the infection becomes established.
Diagnosis
A medical examination involves taking the history of

the injury and assessing the wound type and damage.Tetanus immunization and general health status arechecked. An x ray may be ordered to assess bone damageand to check for foreign objects in the wound. Wound

cultures are done for infected bites if the victim is at highrisk for complications or if the infection does not respondto treatment. Evaluation of possible exposure to rabies isalso important. A biting animal suspected of having rabiesis usually apprehended, tested, and observed for a periodof time for evidence of pre-existing infection.
Treatment
Treatment depends on the wound type, its site, and

risk factors for infection. All wounds are cleaned and dis-infected as thoroughly as possible. Bites to the head and
face usually receive sutures, as do severe lacerationselsewhere. Puncture wounds are left open. If abscess for-
mation occurs, the physician may perform an incision soas to drain the abscess.
If infection occurs, antibiotics are prescribed.

Antibiotics may also be used for infection prevention.Since a single bite wound may contain many differenttypes of bacteria, no single antibiotic is always effective.Commonly prescribed antibiotics are penicillin or a com-bination of amoxicillin and clavulanate potassium.
Because rabies is caused by a virus, antibiotics are

not effective. In addition, as of 2001, there is no knowncure for the disease once symptoms become apparent. Itis therefore recommended that individuals with a highrisk of contracting the disease (veterinarians, animal han-dlers, some laboratory workers) receive preexposure vac-
GALE ENCYCLOPEDIA OF MEDICINE 2 207Animal bite infections
This snake breeder shows the scar from his surgery after

he was bitten by a venomous West African Gabon viper. Hisarm was cut open in order to relieve swelling from thesnake bite in his middle finger. (Photograph by Joe Crocetta,
AP/Wide World Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 207

cination . Individuals bitten by an unknown or potentially
rapid animal should receive postexposure vaccination,also called postexposure prophylaxis (PEP). The PEP
regimen consists of one vaccine given at the initial visitas well as one dose of human immune globulin. Addi-tional vaccines given on days 3, 7, 14, and 28.
Prognosis
Once a bacterial infection is halted, the bite victim usu-

ally recovers fully. There is no known cure for rabies oncesymptoms become evident and death is almost certain.WHO reports that 114 rabies deaths occurred in the Americ-as in 1997, with only four deaths occurring that year in theUnited States, thus emphasizing the importance of goodanimal control practice and postexposure prophylaxis.
Preventing bites obviously prevents subsequent
infections. Children under 12 years of age are at a higherKEY TERMS

Canines —The two sharp teeth located next to the
front incisor teeth in mammals that are used togrip and tear.
Culture —A laboratory procedure in which a sam-
ple from a wound, the blood or other body fluid istaken from an infected person. The sample is placedin conditions under which bacteria can grow. Ifbacteria grow, identification tests are done to deter-mine the bacteria species causing the infection.
Immunocompetence —An individual’s ability to
fight off infection.

Microorganisms —Microscopic organisms, such as
bacteria, viruses, algae and fungi.
Pasteurellosis —A bacterial infection caused by
Pasteurella multocida . Pasteurellosis is character-
ized by inflammation around the wound site andmay be accompanied by bacteria in the blood-stream and infection in tissues and organs.
Pathogen —Any disease producing microorgan-
ism.
Postexposure prophylaxis (PEP) —Any treatment

given after exposure to a disease to try to prevent thedisease from occurring. In the case of rabies, PEPinvolves a series of vaccines given to an individualwho has been bitten by an unknown animal or onethat is potentially infected with the rabies virus.risk for bites due to their small size and their inexperi-

ence with animals; therefore, they should be supervisedwith animals and taught to act appropriately aroundthem. An animal that is unusually aggressive or behavingstrangely (e.g. a raccoon that is active during the day-time) should be avoided and reported to the local animalcontrol authorities; it may be infected with the rabiesvirus. All pets should be vaccinated against rabies andwild animals should not be taken in as pets. Peopleshould also avoid trying to break up fights between ani-mals and

trying to break up fights between ani-mals and should as a rule approach unknown cats anddogs very cautiously, especially on their territory. Final-ly, animals should not be trained to fight.

Resources
BOOKS
Kizer, Kenneth W. “Animal Bites.” In Infectious Diseases. 2nd
ed. Ed. Sherwood L. Gorbach, John G. Bartlett, and NeilR. Blacklow. Philadelphia: W. B. Saunders, 1998.
Dumyati, Ghinwa K., Nayef El-Daher, and C. Richard Magnussen.
“Animal and Human Bite Wounds: Immunization, Prophylax-is, and Treatment.” Consultant 37 (June 1997): 1501.
Lewis, Katherine T., and Melissa Stiles. “Management of Cat
and Dog Bites.” American Family Physician 52 (August
1995): 479.

Presutti, R. John. “Bite Wounds: Early Treatment and Prophy-
laxis Against Infectious Complications.” Postgraduate
Medicine 101 (April 1997): 243-54.
OTHER
“Farm Animal Zoonotic and Reportable Diseases.” University
of Arizona, University Animal Care. 2000. <http://www.ahsc.arizona.edu/uac/notes/classes/farmzoodisease 00/farmzoo2000.html>.
“Rabies Situation and Trends.” World Health Organization.
2001. <http://www.who.int/emc/diseases/zoo/ rabies.html>.

Ankylosing spondylitis
Ankylosing spondylitis (AS) refers to inflammation
of the joints in the spine. AS is also known as rheumatoidspondylitis or Marie-Strümpell disease (among othernames).
A form of arthritis, AS is characterized by chronic
inflammation, causing pain and stiffness of the back,
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progressing to the chest and neck. Eventually, the whole
back may become curved and inflexible if the bones fuse(this is known as “bamboo spine”). AS is a systemic dis-order that may involve multiple organs, such as the:
• eye (causing an inflammation of the iris, or iritis)
• heart (causing aortic valve disease)
• lungs• skin (causing a scaly skin condition, or psoriasis)• gastrointestinal tract (causing inflammation within the

small intestine, called ileitis, or inflammation of thelarge intestine, called colitis)
Less than 1% of the population has AS; however,
20% of AS sufferers have a relative with the disorder.
Genetics play an important role in the disease, but
the cause of AS is still unknown. More than 90% ofpatients have a gene called HLA-B27, but only 10-15%of those who inherit the gene develop the disease. Symp-toms of AS include:
• low back and hip pain and stiffness

• difficulty expanding the chest
• pain in the neck, shoulders, knees, and ankles• low-grade fever• fatigue
AS is seen most commonly in males 30 years old
and older. Initial symptoms are uncommon after the ageof 30, although the diagnosis may not be establisheduntil after that age. The incidence of AS in Afro-Ameri-cans is about 25% of the incidence in Caucasians.
Diagnosis
Doctors usually diagnose the disease simply by the

patient’s report of pain and stiffness. Doctors also reviewspinal and pelvic x rays since involvement of the hip andpelvic joints is common and may be the first abnormalityseen on the x ray. The doctor may also order a blood testto determine the presence of HLA-B27 antigen. When adiagnosis is made, patients may be referred to a rheuma-tologist, a doctor who specializes in treating arthritis.Patients may also be referred to an orthopedic surgeon, adoctor who can surgically correct joint or bone

Treatment
Nonsteroidal anti-inflammatory drugs (NSAIDs),
like naproxen (Naprosyn) or indomethacin (Indocin) areused to relieve pain and stiffness. In severe cases, sul-

fasalazine (Azulfidine), another drug to reduce inflam-mation, or methotrexate (Rheumatrex), an immune-sup-pressing drug, is recommended. In cases where chronictherapy is needed, potential drug side effects must betaken into consideration. Corticosteroid drugs are effec-tive in relieving symptoms, but are usually reserved forsevere cases that do not improve when NSAIDs are used.To avoid potential side effects, treatment with corticos-
teroids is usually limited to a short amount of time with

a gradual weaning from the drug.
Physical therapists prescribe exercises to prevent a
stooped posture and breathing problems when the spinestarts to fuse and ribs are affected. Back braces may beused to prevent continued deformity of the spine andribs. Only in severe cases of deformity is surgery per-formed to straighten and realign the spine, or to replaceknee, shoulder, or hip joints.
To reduce inflammation various herbal remedies,

including white willow ( Salix alba ), yarrow ( Achillea
millefolium ), and lobelia ( Lobelia inflata ), may be help-
ful. Acupuncture , performed by a trained professional,
has helped some patients manage their pain. Homeopath-ic practitioners may prescribe such remedies as Bryonia
and Rhus toxicodendron for pain relief.
Prognosis
There is no cure for AS, and the course of the disease

is unpredictable. Generally, AS progresses for about 10years and then its progression levels off. Most patientscan lead normal lives with treatment to control symptoms.
There is no known way to prevent AS.
Resources
BOOKS
Brewer Jr., Earl J., and Kathy Cochran Angel. The Arthritis
Sourcebook. Los Angeles: Lowell House, 1993.
Swezey, Robert L. Straight Talk on Spondylitis. Spondylitis
Association of America, 1994.
Taurog, Joel D., and Peter E. Lipsky. “Ankylosing Spondylitis,

Reactive Arthritis, and Undifferentiated Spondy-loarthropathy.” In Harrison’s Principles of Internal Medi-
cine, ed. Anthony S. Fauci, et al. New York: McGraw-Hill,
1997.
Arthritis Foundation.1300 W. Peachtree St., Atlanta, GA
30309. (800) 283-7800. <http://www.arthritis.org>.
GALE ENCYCLOPEDIA OF MEDICINE 2 209Ankylosing spondylitisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 209

Diseases Information Clearinghouse. 1 AMS Circle,Bethesda, MD 29892-3675. (301) 495-4484.
Spondylitis Association of America. P.O. Box 5872, Sherman
Oaks, CA 91413. (800) 777-8189.
OTHER
Matsen III, Frederick, ed. “Ankylosing Spondylitis.” University
of Washington Orthopaedics and Sports Medicine. <http://www.orthop.washington.edu/arthritis/types/ankylosingspondylitis>.

Anorectal abscess seeAnorectal disorders
Anorectal disorders
Anorectal disorders are a group of medical disorders
that occur at the junction of the anal canal and the rec-tum.
The anal canal, also called the anus, is the opening at
the bottom end of the digestive tract and is a combinationof external skin and tissue from the digestive tract. It hasmany sensory nerves and is sensitive to pain . The rectum

is the last section of the digestive tract and has a mucuslayer as its inside surface. It has very few sensory nervesand is, therefore, relatively insensitive to pain. The analcanal has a ring of muscle, called the anal sphincter,which keeps the anus closed. There are a number of dif-ferent anorectal disorders.KEY TERMS
Ankylosing —When bones of a joint are fused,
stiff, or rigid.
HLA-B27 —An antigen or protein marker on cells
that may indicate ankylosing spondylitis.

Immune suppressing —Anything that reduces the
activity of the immune system.
Inflammation —A reaction of tissues to disease or
injury, often associated with pain and swelling.
Spondylitis —An inflammation of the spine.Causes and symptoms
Hemorrhoids are swollen or varicose veins in the

anal canal and rectum. They may become inflamed,enlarged, or protrude from the anorectal area. Hemor-rhoids may bleed when passing a bowel movement. Theamount of bleeding is typically small. Frequently, hem-orrhoids develop because of straining during bowelmovements, especially if the person has constipation .
An anal fissure is a tear in the lining of the anus that

is usually caused by a hard bowel movement. Fissuresare painful and bleed when the tissue is stressed duringbowel movements.
Anorectal abscesses are characterized by pus-form-
ing infections in the anorectal region. Painful abscessesform under the skin.
An anorectal fistula is an abnormal opening or chan-

nel from the anorectal area to another part of the body.Typically, the channel leads to pockets of skin near theanus. When seen in infants, anorectal fistulas are consid-ered birth defects . These are seen more frequently in
boys than in girls. Fistulas are also seen more frequentlyin people who have other diseases, including Crohn’s
disease ,tuberculosis ,cancer , and diverticulitis. Anorec-

tal fistulas also occur following anorectal abscesses orother injury to the anal area. Fistulas are usually painfuland discharge pus.
Proctitis is an inflammation of the internal mucosal
lining of the rectum. Ulcers of the lining may form anddevelop into ulcerative colitis . There are many causes of
proctitis, including the sexually transmitted diseases

chlamydia and herpes simplex infections. Proctitis is fre-quently seen in homosexual males as a consequence ofanorectal infection. Proctitis itself is not painful, but painmay be caused by the infectious agent.
Diagnosis
Diagnosis is made by visual inspection of the skin

around the anus. Also, the doctor may probe the rectumwith a gloved finger. An anoscope is a short instrumentthat allows the physician to view the inside of the anus. Aproctoscope is a longer, rigid viewing tube of approxi-mately six to ten inches in length, which may be used tolook for anorectal disorders. A sigmoidoscope is alonger, flexible tube, that allows the physician to view upto about two feet of the inside of the large intestine. Tis-sue samples and material for microbial culture may

samples and material for microbial culture may beobtained during the examination.

Treatment
Treatment usually isn’t required for hemorrhoids.
Most hemorrhoids will heal if the patient takes stool soft-
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eners to relieve the constipation. Enlarged blood vessels
can be eliminated by surgery if they are considered asevere problem. In the case of fissures, treatmentinvolves stool softeners that eliminate stress on the fis-
sure during bowel movements, which allows the fissureto heal. If the fissure doesn’t heal, surgery is required.Treatment for anorectal abscesses consists of cutting theabscess and draining the pus. Fistulas are treated by
surgery.The usual treatment for proctitis is antibiotics .

Resources
BOOKS
Edwards, C. R. W., I. A. D. Bouchier, and C. Haslett. David-
son’s Principles and Practices of Medicine. Edinburgh:
Churchill Livingstone, 1995.
Anorectal fistula seeAnorectal disorders
Anorexia nervosa

Anorexia nervosa is an eating disorder characterized
by unrealistic fear of weight gain, self-starvation, andconspicuous distortion of body image. The name comesfrom two Latin words that mean nervous inability to eat.In females who have begun to menstruate, anorexia ner-vosa is usually marked by amenorrhea , or skipping at
least three menstrual periods in a row. The fourth editionof the Diagnostic and Statistical Manual of Mental Dis-

orders , or DSM-IV (1994), defines two subtypes of
anorexia nervosa—a restricting type, characterized bystrict dieting and exercise without binge eating; and a
binge-eating/purging type, marked by episodes of com-pulsive eating with or without self-induced vomiting andthe use of laxatives or enemas . DSM-IV defines a binge

as a time-limited (usually under two hours) episode ofcompulsive eating in which the individual consumes asignificantly larger amount of food than most peoplewould eat in similar circumstances.
Anorexia nervosa was not officially classified as a
psychiatric disorder until the third edition of DSM in1980. It is, however, a growing problem among adoles-

cent females. Its incidence in the United States has dou-bled since 1970. The rise in the number of reported casesreflects a genuine increase in the number of personsaffected by the disorder, and not simply earlier or moreaccurate diagnosis. Estimates of the incidence of anorex-ia range between 0.5–1% of caucasian female adoles-cents. Over 90% of patients diagnosed with the disorderas of 1998 are female. It was originally thought that only5% of anorexics are male, but that estimate is

of anorexics are male, but that estimate is beingrevised upward. The peak age range for onset of the dis-order is 14-18 years, although there are patients whodevelop anorexia as late as their 40s. In the 1970s and1980s, anorexia was regarded as a disorder of upper- andmiddle-class women, but that generalization is alsochanging. More recent studies indicate that anorexia isincreasingly common among women of all races andsocial classes in the United States.

Anorexia nervosa is a serious public health problem
not only because of its rising incidence, but also becauseit has one of the highest mortality rates of any psychiatricdisorder. Moreover, the disorder may cause serious long-term health complications, including congestive heart
failure , sudden death , growth retardation, dental prob-
lems, constipation , stomach rupture, swelling of the
salivary glands, anemia and other abnormalities of theblood, loss of kidney function, and osteoporosis .

Anorexia is a disorder that results from the interac-
tion of cultural and interpersonal as well as biologicalfactors. While the precise cause of the disease is notknown, it has been linked to the following:
Social influences
The rising incidence of anorexia is thought to reflect

the present idealization of thinness as a badge of upper-class status as well as of female beauty. In addition, theincrease in cases of anorexia includes “copycat” behav-ior, with some patients developing the disorder from imi-tating other girls.
The onset of anorexia in adolescence is attributed to

a developmental crisis caused by girls’ changing bodiescoupled with society’s overemphasis on women’s looks.The increasing influence of the mass media in spreadingand reinforcing gender stereotypes has also been noted.
Occupational goals
The risk of developing anorexia is higher among
adolescents preparing for careers that require attention toweight and/or appearance. These high-risk groups
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include dancers, fashion models, professional athletes
(including gymnasts, skaters, long-distance runners, andjockeys), and actresses.
Genetic and biological influences
Women whose biological mothers or sisters have the
disorder appear to be at increased risk.
Psychological factors
A number of theories have been advanced to explain
the psychological aspects of the disorder. No singleexplanation covers all cases. Anorexia nervosa has beeninterpreted as:

• A rejection of female sexual maturity. This rejection is
variously interpreted as a desire to remain a child, or asa desire to resemble men as closely as possible.
• A reaction to sexual abuse or assault.
• A desire to appear as fragile and nonthreatening as pos-
sible. This hypothesis reflects the idea that female pas-sivity and weakness are attractive to men.
• Overemphasis on control, autonomy, and indepen-

dence. Some anorexics come from achievement-orient-ed families that stress physical fitness and dieting.
Many anorexics are perfectionistic and “driven” aboutschoolwork and other matters in addition to weightcontrol.
• Evidence of family dysfunction. In some families, a
daughter’s eating disorder serves as a distraction frommarital discord or other family tensions.
• Inability to interpret the body’s hunger signals accu-

rately due to early experiences of inappropriate feeding.
Male anorexics
Although anorexia nervosa is still considered a dis-

order that largely affects women, its incidence in themale population is rising. Less is known about the causesof anorexia in males, but some risk factors are the sameas for females. These include certain occupational goalsand increasing media emphasis on external appearance inmen. Moreover, homosexual males are under pressure toconform to an ideal body weight that is about 20 poundslighter than the standard “attractive” weight for hetero-sexual males.
Diagnosis

Diagnosis
Diagnosis of anorexia nervosa is complicated by a
number of factors. One is that the disorder varies some-what in severity from patient to patient. A second factoris denial, which is regarded as an early sign of the disor-der. Most anorexics deny that they are ill and are usually
brought to treatment by a family member.
Most anorexics are diagnosed by pediatricians or

family practitioners. Anorexics develop emaciated bod-ies, dry or yellowish skin, and abnormally low bloodpressure. There is usually a history of amenorrhea (fail-ure to menstruate) in females, and sometimes of abdomi-nal pain , constipation, or lack of energy. The patient may

feel chilly or have developed lanugo, a growth of downybody hair. If the patient has been vomiting, she may haveeroded tooth enamel or Russell’s sign (scars on the backof the hand). The second step in diagnosis is measure-ment of the patient’s weight loss. DSM-IV specifies a
weight loss leading to a body weight 15% below normal,with some allowance for body build and weight history.
The doctor will need to rule out other physical condi-

tions that can cause weight loss or vomiting after eating,including metabolic disorders, brain tumors (especiallyhypothalamus and pituitary gland lesions), diseases of thedigestive tract, and a condition called superior mesentericartery syndrome. Persons with this condition sometimesvomit after meals because the blood supply to the intes-tine is blocked. The doctor will usually order blood tests,an electrocardiogram, urinalysis , and bone densitometry

(bone density test ) in order to exclude other diseases and
to assess the patient’s nutritional status.
The doctor will also need to distinguish between
anorexia and other psychiatric disorders, including depres-sion, schizophrenia , social phobia, obsessive-compulsive
disorder , and body dysmorphic disorder. Two diagnostic
tests that are often used are the Eating Attitudes Test(EAT) and the Eating Disorder Inventory (EDI).
Treatment
Treatment of anorexia nervosa includes both short-

and long-term measures, and requires assessment bydietitians and psychiatrists as well as medical specialists.Therapy is often complicated by the patient’s resistanceor failure to carry out treatment plan.
Hospital treatment
Hospitalization is recommended for anorexics with
any of the following characteristics:
• weight of 40% or more below normal; or weight loss
over a three-month period of more than 30 pounds
• severely disturbed metabolism
• severe binging and purging• signs of psychosis

• severe depression or risk of suicide
• family in crisis
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Hospital treatment includes individual and group
therapy as well as refeeding and monitoring of the
patient’s physical condition. Treatment usually requirestwo to four months in the hospital. In extreme cases, hos-pitalized patients may be force-fed through a tube insert-ed in the nose (nasogastric tube) or by over-feeding(hyperalimentation techniques).
Outpatient treatment
Anorexics who are not severely malnourished can be

treated by outpatient psychotherapy. The types of treat-ment recommended are supportive rather than insight-ori-ented, and include behavioral approaches as well as indi-vidual or group therapy. Family therapy is often recom-

mended when the patient’s eating disorder is closely tiedto family dysfunction. Self-help groups are often useful inhelping anorexics find social support and encouragement.Psychotherapy with anorexics is a slow and difficultprocess; about 50% of patients continue to have seriouspsychiatric problems after their weight has stabilized.
Medications
Anorexics have been treated with a variety of med-
ications, including antidepressants, antianxiety drugs ,

selective serotonin reuptake inhibitors , and lithium
carbonate. The effectiveness of medications in treatmentregimens is still debated. However, at least one study ofProzac showed it helped the patient maintain weightgained while in the hospital.
Prognosis
Figures for long-term recovery vary from study to

study, but the most reliable estimates are that 40-60% ofanorexics will make a good physical and social recovery,and 75% will gain weight. The long-term mortality ratefor anorexia is estimated at around 10%, although somestudies give a lower figure of 3-4%. The most frequentcauses of death associated with anorexia are starvation ,
electrolyte imbalance, heart failure, and suicide.
Short of major long-term changes in the larger soci-

ety, the best strategy for prevention of anorexia is the cul-tivation of healthy attitudes toward food, weight control,and beauty (or body image) within families.
Resources
BOOKS
“Anorexia Nervosa.” In Diagnostic and Statistical Manual of
Mental Disorders. 4th ed. Washington, DC: The American
Psychiatric Association, 1994.KEY TERMS
Amenorrhea —Absence of the menses in a female
who has begun to have menstrual periods.
Binge eating —A pattern of eating marked by

episodes of rapid consumption of large amounts offood; usually food that is high in calories.
Body dysmorphic disorder —A psychiatric disor-
der marked by preoccupation with an imaginedphysical defect.
Hyperalimentation —A method of refeeding anorex-
ics by infusing liquid nutrients and electrolytesdirectly into central veins through a catheter.
Lanugo —A soft, downy body hair that develops
on the chest and arms of anorexic women.

Purging —The use of vomiting, diuretics, or laxa-
tives to clear the stomach and intestines after abinge.
Russell’s sign —Scraped or raw areas on the patient’s
knuckles, caused by self-induced vomiting.
Superior mesenteric artery syndrome —A condi-
tion in which a person vomits after meals due toblockage of the blood supply to the intestine.
Baron, Robert B. “Nutrition.” In Current Medical Diagnosis

and Treatment, 1998. 37th ed. Ed. Stephen McPhee, et al.
Cassell, Dana K., with Felix E. F. Larocca. The Encyclopedia
of Obesity and Eating Disorders. New York: Facts on File,
Inc., 1994.
Herzog, David B. “Eating Disorders.” In The New Harvard
Guide to Psychiatry , ed. Armand M. Nicholi Jr. Cam-
bridge, MA: The Belknap Press of Harvard UniversityPress, 1988.
Kaplan, David W., and Kathleen A. Mammel. “Adolescence.”

In Current Pediatric Diagnosis & Treatment , ed. William
W. Hay Jr., et al. Stamford: Appleton & Lange, 1997.
Mitchell, James E. “Anorexia Nervosa: Medical and Physiolog-
ical Aspects.” In Handbook of Eating Disorders , ed. Kelly
D. Brownell and John P. Foreyt. New York: Basic Books,Inc., 1986.
“Physical Conditions in Adolescence: Anorexia Nervosa.” In
The Merck Manual of Diagnosis and Therapy. 16th ed.
Ed. Robert Berkow. Rahway, NJ: Merck Research Labo-ratories, 1992.

Pipher, Mary. Reviving Ophelia: Saving the Selves of Adoles-
cent Girls. New York: Ballantine Books, 1994.
American Anorexia/Bulimia Association. 418 East 76th St.,
New York, NY 10021. (212) 734-1114.
GALE ENCYCLOPEDIA OF MEDICINE 2 213Anorectal disordersGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 213

National Institute of Mental Health Eating Disorders Program,
Building 10, Room 3S231. 9000 Rockville Pike, Bethes-da, MD 20892. (301) 496-1891.
Anoscopy
An anoscopy is an examination of the rectum in
which a small tube is inserted into the anus to screen, diag-nose, and evaluate problems of the anus and anal canal.
Purpose
This test may be ordered for the evaluation of peri-
anal or anal pain ,hemorrhoids ,rectal prolapse , digital

rectal examination that shows a mass, perianal abscess
and condyloma (a wart-like growth). An anascopy maybe performed to check for abnormal openings betweenthe anus and the skin, or anal fissures. The test is alsoused to diagnose rectal cancer .
Anoscopy should not be performed on patients with

acute cardiovascular problems due to the vasovagal reac-tion it may cause. This test is also not recommended forpatients with acute abdominal problems and those with aconstricted or narrowed anal canal.
Anoscopy views the anus and anal canal by using an

anoscope. An anoscope is a plastic, tube-shaped specu-lum that is a smaller version of a sigmoidscope. Beforethe anoscope is used, the doctor completes a digital rectalexamination with a lubricated, gloved index finger. Theanoscope is then lubricated and gently inserted a fewinches into the rectum. This procedure enlarges the rec-tum to allow the doctor to view the entire anal canal witha light. If any suspicious areas are noticed, a piece of tis-sue can be biopsied.

During the anoscopy procedure there may be a feel-
ing of pressure or the need to go to the bathroom. If abiopsy is taken, the patient may feel a slight pinch. Theprocedure is performed on an out-patient basis, and takesapproximately an hour to complete.
The patient will be instructed to clear their rectum of
stool before the procedure. This may be done by taking aKEY TERMS
Anal fissure —An ulcer on the margin of the anus.
Digital rectal examination —An examination

where a gloved, lubricated index finger is insertedinto the rectum to check for any abnormalities.
Polyps —A tumor with a small flap that attaches
itself to the wall of various vascular organs such asthe nose, uterus and rectum. Polyps bleed easily,and if they are suspected to be cancerous theyshould be surgically removed.
Vasovagal reaction —Regarding the action of stim-
uli from the vagus nerve on blood vessels.

laxative, enema, or other preparation that may help with
the evacuation.
Aftercare
If a biopsy is needed during an anoscopy, there may
be slight anal bleeding for less than two days followingthe procedure. The patient may be instructed to sit in abathtub of warm water for 10 to 15 minutes, three times aday, to help decrease the pain and swelling.
Risks
A simple anoscopy procedure offers minimal risks.

There is a limited risk of bleeding and mild pain is abiopsy is performed.
Normal values to look for during an anoscopy
include an anal canal that appears healthy in size, color,and shape. The test also looks for no evidence of bleed-ing, polyps, hemorrhoids or other abnormalities.
While an anoscopy is typically performed to deter-

mine is hemorrhoids are present, other abnormal findingcould include polyps, abscesses, inflammation, fissures,colorectal polyps, or cancer .
Resources
BOOKS
Altman, Roberta; Sarg, Michael J. “Anoscopy.” The Cancer
Dictionary. Checkmark Books, 2000. 18
GALE ENCYCLOPEDIA OF MEDICINE 2 214AnoscopyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 214

Colyar, Margaret. “Anascopy Basics.” The Nurse Practitioner
(October 2000): 91.
OTHER
Discovery Health. “Medical Tests: Anoscopy.” <http://health.
discover.com/diseasesandcond/encyclopedia/1038.html>(5 May 2001)
Lycos Health with WebMD. “Anoscopy.” <http://webmd.lycos.
com/content/asset/adam_test_anoscopy> (5 May 2001).
Anosmia
The term anosmia means lack of the sense of smell.

It may also refer to a decreased sense of smell. Ageusia, acompanion word, refers to a lack of taste sensation.Patients who actually have anosmia may complainwrongly of ageusia, although they retain the ability todistinguish salt, sweet, sour, and bitter—humans’ onlytaste sensations.
Of the five senses, smell ranks fourth in importance

for humans, although it is much more pronounced inother animals. Bloodhounds, for example, can smell anodor a thousand times weaker than humans. Taste, consid-ered the fifth sense, is mostly the smell of food in themouth. The sense of smell originates from the first cranialnerves (the olfactory nerves), which sit at the base of thebrain’s frontal lobes, right behind the eyes and above thenose. Inhaled airborne chemicals stimulate these nerves.
There are other aberrations of smell beside a

decrease. Smells can be distorted, intensified, or halluci-nated. These changes usually indicate a malfunction ofthe brain.
The most common cause of anosmia is nasal occlu-
sion caused by rhinitis (inflammation of the nasal mem-
branes). If no air gets to the olfactory nerves, smell willnot happen. In turn, rhinitis and nasal polyps (growths

on nasal membranes) are caused by irritants such asallergens, infections, cigarette smoke, and other air pol-lutants. Tumors such as nasal polyps can also block thenasal passages and the olfactory nerves and cause anos-mia. Head injury or, rarely, certain viral infections can
damage or destroy the olfactory nerves.Diagnosis
It is difficult to measure a loss of smell, and no one

complains of loss of smell in just one nostril. So a physi-cian usually begins by testing each nostril separatelywith a common, non-irritating odor such as perfume,lemon, vanilla, or coffee. Polyps and rhinitis are obviouscausal agents a physician looks for. Imaging studies ofthe head may be necessary in order to detect brain injury,sinus infection, or tumor.
Treatment
Cessation of smoking is the first step. Many smok-

ers who quit discover new tastes so enthusiastically thatthey immediately gain weight. Attention to reducingexposure to other nasal irritants and treatment of respira-tory allergies or chronic upper respiratory infections will
be beneficial. Corticosteroids are particularly helpful.
Finding and treating the cause of the loss of smell is
the first approach in naturopathic medicine . If rhinitis

is the cause, treating acute rhinitis with herbal mast cellstabilizers and herbal decongestants can offer some

relief as the body heals. If chronic rhinitis is present, thisis often related to an environmental irritant or to foodallergies. Removal of the causative factors is the first stepto healing. Nasal steams with essential oils offer relief ofthe blockage and tonification of the membranes. Block-ages can sometimes be resolved through naso-specifictherapy—a way of realigning the nasal cavities. Polypblockage can be addressed through botanical medicinetreatment as well as hydrotherapy . Olfactory

damage may not be regenerable. Some olfactory aberra-tions, like intensified sense of smell, can be resolvedusing homeopathic medicine.
Prognosis
If nasal inflammation is the cause of anosmia, the
chances of recovery are excellent. However, if nervedamage is the cause of the problem, the recovery of smellis much more difficult.
Resources
BOOKS

“Olfactory Dysfunction.” In Current Medical Diagnosis and
Treatment, 1996. 35th ed. Ed. Stephen McPhee, et al.
Stamford: Appleton & Lange, 1995.
GALE ENCYCLOPEDIA OF MEDICINE 2 215AnosmiaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 215

Davidson, T. M., C. Murphy, and A. A. Jalowayski. “Smell
Impairment. Can It Be Reversed?” Postgraduate Medicine
98 (July 1995): 107-109, 112.
Anoxemia seeAnoxia
Anoxia
Anoxia is a condition characterized by an absence of
oxygen supply to an organ or a tissue.
Anoxia results when oxygen is not being delivered to

a part of the body. If the condition does not involve totaloxygen deprivation, it is often called hypoxia, althoughthe two terms have been used interchangeably. A relatedcondition, anoxemia, occurs when the blood circulatesbut contains a below normal amount of oxygen.
The five types of anoxia or hypoxia include hypox-

emic, anemic, affinity, stagnant, and histotoxic. Hypox-emic anoxia happens when the oxygen pressure outsidethe body is so low that the hemoglobin, the chemicalwhich carries oxygen in the red blood cells (RBCs), isunable to become fully loaded with the gas. This results intoo little oxygen reaching the tissues and can occur in suf-focation when a person is at high altitude, where the pres-sure of oxygen in the air is much less than at sea level.
Anemic anoxia results from a decrease in the

amount of hemoglobin or RBCs in the blood, whichreduces the ability to get oxygen to the tissues. Anemiamay result from lack of production of red blood cellsKEY TERMS
Allergen —Any substance that irritates only those
who are sensitive (allergic) to it.
Corticosteroids —Cortisone, prednisone, and
related drugs that reduce inflammation.
Rhinitis —Inflammation and swelling of the nasal
membranes.
Nasal polyps —Drop-shaped overgrowths of the

nasal membranes.(iron deficiency), blood loss (hemorrhage), or shortened
lifespan of red blood cells (autoimmune disease).
Affinity anoxia involves a defect in the chemistry of
the blood such that the hemoglobin can no longer pick upas much oxygen from the air, even though the quantitiesare normal, reducing how much is delivered to the tissues.
Stagnant anoxia occurs when there is interference

with the blood flow, although the blood and its oxygen-carrying abilities are normal. A common cause of generalstagnant anoxia is heart disease or interference with thereturn of blood flow through the veins. Examples of localstagnant anoxia include exposure to cold, diseases thatrestrict circulation to the extremities, and ergot poison-
ing. When the tissue or organ itself has a reduced ability

to accept and use the oxygen, it is called histotoxic anox-ia. The classic example is cyanide poisoning, where thechemical inactivates a cellular enzyme necessary for thecell to use oxygen. Thus, tissue exposed to cyanide can-not use the oxygen even though it is in normal amountsin the bloodstream. Histotoxic anoxia can also be causedby exposure to narcotics, alcohol, formaldehyde, ace-tone, toluene, and certain anesthetic agents.

Anoxia and hypoxia can be caused by any number of
disease states of the blood, lungs, heart and circulationincluding heart attack , severe asthma , or emphysema .
It can also result from smoke or carbon monoxide inhala-tion, improper exposure to anesthesia, poisoning, strangu-lation, near-drowning , or high altitude exposure through

mountain climbing or travel in an insufficiently pressur-ized airplane. Anoxia, and the resultant brain damage, is aparticular problem with newborns during difficult births.
No matter what the cause of anoxia, the symptoms

are similar. In severe cases, the patient is often confusedand commonly stuperous or comatose (in a state ofunconsciousness). Depending on the severity of the injuryto the brain, the organ most sensitive to reduced oxygenintake, this condition can persist for hours, days, weeks,or even months or years. Seizures, myoclonic jerks (invol-untary muscle spasms or twitches), and neck stiffness aresome other symptoms of the anoxic condition.

Symptoms of more localized or less complete oxygen
deprivation (hypoxia) include increased breathing rate,lightheadedness, dizziness , tingling or warm sensation,
sweating, reduced field of vision, sleepiness, a bluish tintto skin, particularly the fingertips and lips, and behaviorchanges, often an inappropriate sense of euphoria.
Diagnosis
Diagnosis of anoxia and hypoxia is commonly made
through the appearance of clinical symptoms. However,

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confirmed using laboratory tests. The exact test that isperformed is dependent on the suspected cause of theanoxia. One systemic measure of tissue anoxia is theserum lactate (lactic acid) test. When cells are forced toproduce energy without oxygen, as would happen duringanoxia, lactic acid is one of the byproducts. Thus, anincrease in lactic acid in the blood would indicate that tis-sues were starved for oxygen and are using non-oxygenpathways to produce energy. Normally, the blood con-tains

to produce energy. Normally, the blood con-tains less than 2mmol/L of lactic acid. However, someforms of anoxia do not increase lactic acid concentrationsin the blood and some increases in lactic acid levels arenot associated with anoxia, so an elevated value for thistest is only suggestive of an anoxic or hypoxic condition.

Treatment
The exact treatment for anoxia is dependent on the
cause of the reduced oxygen reaching the tissues. How-ever, immediate restoration of tissue oxygen levelsthrough supplementing the patient’s air supply with100% oxygen is a common first step. Secondary stepsoften include support of the cardiovascular systemthrough drugs or other treatment, treatment of lung dis-ease, transfusions, or administration of anecdotes for poi-soning, as appropriate.
Prognosis

the underlying cause of the low oxygen levels. If cardio-vascular and respiratory systems can be supported ade-quately, recovery from the injury to the tissue is possible,although extent of injury to the brain can be difficult toassess. The exact amount of recovery varies with theamount of injury sustained, where significant injury bringsa poorer prognosis. As recovery occurs, both psychologi-cal and neurological abnormalities may appear, persist,and can improve. Some problems seen after

persist,and can improve. Some problems seen after anoxiainclude mental confusion, personality changes, amnesia

or other types of memory loss, hallucinations , and persis-
tent myoclonus (involuntary contractions of the muscles).
Hypoxemic anoxia can be avoided by utilizing sup-
plemental oxygen when in high altitudes and beingaware of the early symptoms of altitude sickness and

reducing altitude once recognized. Iron supplements canavoid anemic hypoxia, although more severe anemicstates are usually caused by disease or bleeding. Main-taining good cardiovascular health through proper dietand exercise is a good first step to avoiding the mostKEY TERMS
Amnesia —Loss of memory often traceable to brain
tissue damage.
Anoxemia —An extreme lack of oxygen in the
blood.
Hemoglobin —A chemical found in red blood
cells that transports oxygen.

Myoclonus —Involuntary contractions of a muscle
or group of muscles.
common cause of stagnant anoxia. Avoiding exposure to
the toxic chemicals that cause the condition can preventhistotoxic anoxia.
Resources
BOOKS
Gutierrez, Guillermo. “Metabolic Assessement of Tissue Oxy-
genation” Seminars in Respiratory and Critical Care
Medicine 20 (January 1999):11–15.
Brain Injury Association. 105 N. Alfred St. Alexandria, V A

22314. (800)444-6443. <http://www.biausa.org>.
Phoenix Project/Head Injury Hotline. Box 84151, Seattle, WA
98124. (206)621-8558. <http://www.headinjury.com>.
OTHER
Borron, Stephen W. “Lactic Acidosis.” eMedicine (February 7,
2001). <http://www.emedicine.com/emerg/topic291.htm>. (May 13, 2001).
NINDS Anoxia/Hypoxia Information Page.The National Insti-

tute of Neurological Disorders and Stroke (NINDS). Janu-ary 22, 2001. <http://www.ninds.nih.gov/health_and_medical/disorders/anoxia_doc.htm>. (May 13, 2001).
Michelle Johnson, MS, JD
Antacids
Antacids are medicines that neutralize stomach acid.
Purpose
Antacids are used to relieve acid indigestion , upset
stomach, sour stomach, and heartburn . Additional com-
ponents of some formulations include dimethicone, to

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combination with antacids, may help manage GERD(gastro-esophageal reflux disease). Antacids should notbe confused with gastric acid inhibitors, such as the H-2receptor blockers (cimetidine, ranitide and others) or theproton pump inhibitors (lansoprazole, omeprazole andothers). Although all three classes of drugs act to reducethe levels of gastric acid, their mechanisms are different,and this affects the appropriate use of the drug. Antacidshave a rapid onset and short duration of action, and

a rapid onset and short duration of action, and aremost appropriate for rapid relief of gastric discomfort fora short period of time.

Antacids may be divided into two classes, those that
work by chemical neutralization of gastric acid, mostnotably sodium bicarbonate; and those that act byadsorption of the acid (non-absorbable antacids), such ascalcium and magnesium salts.
The chemical antacids show the most rapid onset of

action, but may cause “acid rebound,” a condition inwhich the gastric acid returns in greater concentrationafter the drug effect has stopped. Also, since theseantacids may contain high concentrations of sodium,they may be inappropriate in patients with hypertension .
Calcium and magnesium salts act by adsorption of

the acid, and are less prone to the rebound effect, butmay have other significant disadvantages. Theseantacids are particularly prone to drug interactions, andpatients taking other medications must often avoidsimultaneous administration of the medications. Theseantacids are more effective in liquid formulations thanin tablet or capsule form, and so may be inconvenientfor routine dosing.
The non-absorbable antacids may have additional

uses beyond control of hyperacidity. Calcium salts maybe used as diet supplements in prevention of osteoporo-
sis. Aluminum carbonate is useful for binding phosphate,

and has been effective in treatment and control of hyper-phosphatemia or for use with a low phosphate diet to pre-vent formation of phosphate urinary stones. This applica-tion is particularly valuable in patients with chronic renalfailure. Antacids with aluminum and magnesium hydrox-ides or aluminum hydroxide alone effectively preventsignificant stress ulcer bleeding in post-operative
patients or those with severe burns .
The dose depends on the type of antacid. Consult

specific references.
When using antacids in chewable tablet form, chew
the tablet well before swallowing. Drink a glass of waterafter taking chewable aluminum hydroxide. Lozengesshould be allowed to dissolve completely in the mouth.
Liquid antacids should be shaken well before using.
Antacids should be avoided if any signs of appen-
dicitis or inflamed bowel are present. These include

cramping, pain , and soreness in the lower abdomen,
bloating, and nausea and vomiting .
Antacids may affect the results of some medical
tests, such as those that measure how much acid thestomach produces. Health care providers and patientsshould keep this in mind when scheduling a medical test.
Antacids that contain magnesium may cause diar-
rhea . Other types of antacids may cause constipation .
Avoid taking antacids containing sodium bicarbon-

ate when the stomach is uncomfortably full from eatingor drinking.
Antacids should not be given to children under six
years of age.
Antacids that contain calcium or sodium bicarbonate
may cause side effects, such as dizziness , nausea, and

vomiting, in people who consume large amounts of calci-um (from dairy products or calcium supplements). Insome cases, this can lead to permanent kidney damage.Before combining antacids with extra calcium, checkwith a physician.
Some antacids contain large amounts of sodium,
particularly sodium bicarbonate (baking soda). Anyonewho is on a low-sodium diet should check the list ofingredients or check with a physician or pharmacistbefore taking an antacid product.

Excessive use of antacids may cause or increase the
severity or kidney problems. Calcium based antacidsmay lead to renal stone formation.
ALLERGIES. Allergies to antacids are extremely rare,
however the inactive ingredients in some formulationsmay include dyes or other products with allergic poten-tial.
PREGNANCY. Antacids are not classified under the
pregnancy safety categories A, B, C, D and X. Occa-

sional use of antacids in small amounts during pregnancyis considered safe. However, pregnant women shouldcheck with their physicians before using antacids or anyother medicines. Pregnant women who are consumingextra calcium should be aware that using antacids thatcontain sodium bicarbonate or calcium can lead to seri-ous side effects.
BREASTFEEDING. Some antacids may pass into
breast milk. However, no evidence exists that the inges-

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tion of antacids through breast milk causes problems for
nursing babies whose mothers use antacids occasionally.
Side effects are very rare when antacids are taken as

directed. They are more likely when the medicine istaken in large doses or over a long time. Minor sideeffects include a chalky taste, mild constipation or diar-rhea, thirst, stomach cramps, and whitish or speckledstools. These symptoms do not need medical attentionunless they do not go away or they interfere with normalactivities.
Other uncommon side effects may occur. Anyone
who has unusual symptoms after taking antacids shouldget in touch with his or her health care provider.

Antacids have multiple drug interactions, usually
due to inhibition of absorption of other medications. Inrare cases, the absorbable antacids may alter the pH ofthe stomach contents or urine sufficiently to alter drugabsoprtion or excretion. Consult specific references.
Antegrade pyelography seeIntravenous
urographyKEY TERMS
Acid indigestion —Indigestion that results from too
much acid in the stomach.

Heartburn —A burning sensation, usually in the
center of the chest, near the breastbone.
Indigestion —A feeling of discomfort or illness that
results from the inability to properly digest food.
Inflamed bowel —Irritation of the intestinal tract.

Pregnancy safety categories —A system for report-
ing the known safety issues of drugs for use duringpregnancy, The ratings range from A, proven safeby well controlled studies, to X, proven harmful.Antenatal testing
Antenatal testing includes any diagnostic procedures
performed before the birth of a baby.
Purpose
These tests and exams are essential for protecting
the health of a pregnant woman and her developing child.
Some tests, such as amniocentisis, carry a small risk

of a miscarriage or other complications that could harm
the mother or baby.
Women who become pregnant undergo a wide vari-
ety of tests throughout the nine months before delivery.In the early stages, physicians order blood tests to screenfor possible disorders or infections, such as humanimmunodeficiency virus (HIV), which can pass from the

mother to the fetus. Later, the focus shifts to checking onfetal well-being with a variety of technological toolssuch as ultrasound scans. Descriptions of the most com-mon tests and procedures used during pregnancy are
listed below.
When a woman first learns she is pregnant, her
physician will run a series of routine urine and bloodtests to determine her blood type, check for anemia andgestational diabetes , make sure she is immune to rubel-
la(German measles ) and check for infectious diseases

like HIV , hepatitis, chlamydia or syphilis . Physicians
also usually do pelvic exam to screen for cervical can-
cerand check the patient’s blood pressure. As the preg-
nancy progresses, more tests will follow.
Ultrasound
Ultrasound is a device that records sound waves as

they bounce off the developing fetus to create an image,which is projected onto a large computer screen. Physi-cians order an ultrasound scan to listen for a fetal heart-beat, determine a woman’s precise due date and check fortwins, among other uses. An ultrasound scan also is knownas a sonogram. The procedure takes a few minutes, is pain-less and usually is covered by health insurance.
The ultrasound technician will ask the pregnant

woman to remove her clothes and change into a gown.The technician may rub some gel on the woman’s stom-ach, which helps the hand-held device pick up sound
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waves better. In certain cases, the technician may insert a
plastic probe into the woman’s vaginal canal to get aclearer picture of the fetus. Early in pregnancy, the testmay need to be done with a full bladder.
Unlike x rays, ultrasound is safe to use during preg-
nancy. It does not cause any known side-effects thatwould harm the mother or baby.
Pregnant women usually will have their first ultra-

sound anytime between 8 and 12 weeks of gestation. Innormal cases, the technician is able to identify a fetalheartbeat, which appears as a flashing light on the screen.Closer to the due date, physicians use ultrasound to makesure the fetus is in the correct position to exit the birthcanal head first.
Sometimes an ultrasound will show that a fetus has

stopped growing, or a gestational sac has formed withouta fetus, and a miscarriage has occurred. Later in pregnan-cy, it also may show that the child is in a breech position,oriented feet first, which can cause a difficult labor.
Tests for birth defects
Most obstetricians offer parents a variety of ways to
find out if their developing child might have birth
defects such as spina bifida and Down Syndrome . An

alpha fetoprotein screen can be done through a simpleblood test in the doctor’s office between the 16th and18th week of gestation. It tells the odds that their childwill have a severe congenital anomaly. The test works bymeasuring the level of alpha fetoprotein, a substance pro-duced by a fetus with birth defects. Low levels of alphafetoprotein in the mother’s blood may indicate Down’sSyndrome. In that case, the next step for most couples isamniocentesis because the alpha fetoprotein test can

give false-positive results. Amniocentesis is a more accu-rate test, but it also has higher risks of complications.
This procedure typically is used to diagnose Down
syndrome while a developing child is still in the womb,at 15-28 weeks.
During amniocentesis, a doctor inserts a needle

through a woman’s vaginal canal and inside her cervix.Using ultrasound as a guide, the doctor pierces the uterusto withdraw a sample of fluid from the amniotic sac.Afterwards, tiny cells shed by the fetus can be studied inthe laboratory. Scientists can analyze DNA samples todetermine if the fetus has Down syndrome or othergenetic conditions. Amniocentesis also can determine thesex of the fetus.
Women who have a history of recurring miscar-

riages may not want to have this procedure.
Amniocentesis is usually performed in a doctor’s
office on an outpatient basis.Common side effects include cramping and bleeding.
In about one out of every 1,000 cases, amniocentesis
causes a needle to puncture the uterine wall, which couldresult in miscarriage.
In most cases, couples find out their baby does not
have a birth defect.
If the results come back positive for Down’s Syn-

drome or other serious conditions, the couple mustdecide if they want to end the pregnancy. Others use theknowledge to plan and prepare any special care neededfor their future child.
Group B Strep
This test is for Group B streptococci (GBS) infection.
By testing for GBS, physicians can determine if a
woman is at risk of passing this infection along to her child.
Women who have had a prior child with GBS, or

who have a fever or prolonged or premature rupture of
the amniotic sac may be at higher risk for this type ofinfection.
GBS is a type of bacteria commonly found in the
vagina and rectum. Unlike regular strep throat , GBS
can be present in a person’s body without causing anysymptoms, so many women do not realize they areinfected with it.
To test for the presence of GBS, doctors may take a

urine sample. They also may collect samples from thevagina or rectum, which are then analyzed in a lab. Thistest is usually performed late in pregnancy, at 35-37weeks of gestation.
This is a routine urine test or pelvic exam with no
side effects.
In many cases, doctors do not find any evidence of
this type of infection.
If a woman is found to be infected with Group B

strep, physicians usually wait to treat it until just beforelabor begins. At that time, they may give the motherantibiotics so the baby is not born with the infection.
Newborns who are exposed to Group B strep can haveinflammation of the brain, spinal cord, blood or lungs.In some cases, this serious complication can result ininfant death .
Resources
BOOKS
Eisenberg, Arlene, et al. What to Expect When You’re Expecting

New York: Workman Publishing Company Inc, 1996.
Planning your Pregnancy and Birth Washington, DC: The
American College of Obstetricians and Gynecologists,2000.
GALE ENCYCLOPEDIA OF MEDICINE 2 220Antenatal testingGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 220

Parkey, Paula. “Birth Defects: Is Prenatal Screening Advis-
able?” CBS HealthWatch (April, 2000). <http://www.
cbshealthwatch.com/cx/viewarticle/214798>.
American College of Obstetricians and Gynecologists.409 12th
Street SW, Washington, DC 20024-2188. (202) 638-5577.<http://www.acog.org>.
March of Dimes Birth Defects Foundation. P.O. Box 1657,
Wilkes-Barre, PA 18703. 1-800-367-6630. <http://www.modimes.org>.
Antepartum testing

Antepartum testing consists of a variety of tests per-
formed late in pregnancy to verify fetal well-being, as
judged by the baby’s heart rate and other characteristics.Antepartum tests include the nonstress test (NST), bio-physical profile, and contraction stress test (CST).
Purpose
Antepartum testing is performed after 32 weeks of
pregnancy so that the couple and the doctor can beKEY TERMS
Ultrasound— A device that records sound waves

as they bounce off a developing fetus to create animage, which is projected onto a large computerscreen
Breech position —When a child is oriented feet
first in the mother’s uterus just before delivery.
Alpha fetoprotein screen— A test that measures the
level of alpha fetoprotein, a substance produced bya fetus with birth defects, in the mother’s blood.
Amniocentesis —An invasive procedure that

allows physicians to check for birth defects by col-lecting a sample of fetal cells from inside theamniotic sac.
GBS—Group B streptococci are a type of bacteria
that, if passed to a can cause inflammation of thebrain, spinal cord, blood or lungs. In some cases,it can result in infant deathwarned of any problems that may necessitate further test-

ing or immediate delivery. The results reflect the adequa-cy of blood flow (and oxygen delivery) to the fetus fromthe placenta.
Antepartum tests are usually done in pregnancies at
high risk for fetal complications. Various reasonsinclude:
• any chronic illness in the mother, such as high blood
pressure or diabetes
• problems with previous pregnancies, such as stillbirth
• fetal complications, such as intrauterine growth retar-
dation (a slowing of growth of the fetus) or birth defects

• problems in the current pregnancy, including pre-
eclampsia (serious pregnancy-induced high blood pres-sure), gestational (pregnancy-related) diabetes, prema-ture rupture of the membranes, excessive amniotic fluid(the liquid that surrounds the fetus), vaginal bleeding,or placenta previa (a condition in which the placenta is
positioned over the cervix instead of near the top of theuterus)
• twins or other multiple fetuses
One of the most common indications for antepartum

testing is post-term pregnancy. A pregnancy should notbe allowed to continue past 42 weeks. (The usual preg-nancy is 40 weeks in duration). Babies should be moni-tored with antepartum testing starting at 41 weeks. After41 weeks, there is an increasing risk that the placentacannot meet the growing baby’s needs for oxygen andnutrition . This may be reflected in decreased move-

ments of the baby, decreased amniotic fluid, and changesin the heart rate pattern of the baby.
Technology
The NST and CST use a technique called electronic
fetal monitoring to evaluate the heartbeat of the fetus.
The biophysical profile is an ultrasound examination.
NST
The NST is usually the first antepartum test used to

verify fetal well-being. It is based on the principle thatwhen the fetus moves, its heartbeat normally speeds up.The NST assesses fetal health through monitoring accel-erations of the heart rate in response to the baby’s ownmovements, i.e., in the absence of stress .
The mother lays down or sits, and an electronic fetal
monitor is placed on her abdomen to monitor the fetalheart rate. The doctor records the baby’s heartbeat on agraph or “tracing” to determine whether it demonstrates

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correct reactivity, or acceleration of the heart rate. To
record fetal movements on the tracing, the mother press-es a button every time she feels the baby move. If thebaby is inactive, the mother may be asked to rub herabdomen to “awaken” it. Sometimes an instrument isused to produce a loud noise to arouse the fetus (vibroa-coustic stimulation). The test usually takes between20–45 minutes.
A baby who is receiving enough oxygen should

move at least twice in a 20 minute period. The baby’sheart rate should increase at least 20 beats per minute forat least 20 seconds during these movements. The NST isthe simplest and cheapest antepartum test.
Biophysical profile
The biophysical profile is an ultrasound exam that

can add additional information to the NST. During thebiophysical profile, the examiner checks for variouscharacteristics of the baby to evaluate its overall health.These include: fetal movement, fetal tone, breathingmovements, and the amniotic fluid volume. Amnioticfluid volume is important because a decreased amountraises the possibility that the baby may be under stress.The five components of the test (NST is also included)are each given a score of 2 for normal (or present), 1 ifdecreased,

of 2 for normal (or present), 1 ifdecreased, and 0 for abnormal. The highest possiblescore is 10. The “modified” biophysical profile isanother option; this includes only the NST and amnioticfluid volume.

CST
The CST is like the NST, except that the fetus is
evaluated in response to contractions of the mother’suterus. Because it is a more complicated test, it is oftenused after an abnormal NST to confirm the results. Uter-ine contractions produce “stress” in the fetus becausethey temporarily stop the flow of blood and oxygen. TheCST is used to confirm that the fetus does not respond tothis stress by a decrease in the heart rate.
The CST is performed with the same equipment as

the NST. Maternal blood pressure and fetal heart rate arerecorded along with the onset, relative intensity, andduration of any spontaneous contractions. For an accu-rate test, the contractions should be of sufficient durationand frequency. If uterine activity does not occur natural-ly, a drug called oxytocin may be given to the motherintravenously (hence the test’s alternate name, the oxy-tocin challenge test) to provoke contractions. Anotheroption is self-stimulation of the mother’s

Anotheroption is self-stimulation of the mother’s nipples,because this releases natural oxytocin. The fetal heartrate is observed until, ideally, three moderate contrac-tions occur within 10 minutes.Preparation

The mother should eat just before the antepartum
tests to help stimulate fetal activity.
Risks
There are no appreciable risks from the NST or the
biophysical profile. Ultrasound used for the biophysicalprofile is painless and safe because it uses no harmfulradiation, and no evidence has been found that soundwaves cause any adverse effects on the mother or fetus.
The frequency of antepartum testing depends on the

reason for its use. All of the tests occasionally give incor-rect results, which may prompt an unnecessary earlydelivery or cesarean. Repeat testing is important to dou-ble-check any abnormal findings.
In general, “negative” or normal results on antepar-

tum testing provide reassurance that the baby is healthyand should remain so for perhaps a week, with no needfor immediate delivery. Unfortunately, the tests cannotguarantee that there are no problems, because falselynormal results can occur, though this is unusual. Even ifall test results are normal, it is important to realize thatthis does not guarantee a “perfect” baby.
The NST is normal (“reactive”) if two or more dis-

tinct fetal movements occur in association with appropri-ate accelerations of the fetal heart rate within 20 minutes.A biophysical profile score of 8-10 is considered reassur-ing. The CST is normal if the fetus shows no decelera-tions in heart rate in response to three uterine contrac-tions within 10 minutes.
A “positive” result suggests that the baby is not

receiving enough oxygen for some reason. However, it isquite possible that the test result was falsely abnormal.To confirm or monitor a suspected disorder, follow-uptesting with the same or an alternate test will probably beperformed at least weekly.
The NST is abnormal (“nonreactive”) if the fetal

heart rate fails to speed up by at least 20 beats per minuteat least two times during a 20-minute period. Abnormaldecreases in the heart rate (decelerations) are also a causefor concern.
A biophysical profile score of 6 is considered a
cause for concern and should be followed by further test-ing. Scores of 4 or less may require immediate deliveryof the fetus.

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Abnormal results on the CST include late decelera-
tions, or abnormal slowing of the fetal heart rate after theuterine contractions. This can suggest that the baby is notreceiving enough oxygen and may have difficulty with-standing the stress of labor and vaginal delivery. Cesare-
an section might be necessary so the baby can be spared
the stress of labor. With either NST or CST, a severedeceleration (a period of very slow heartbeat) can alsosuggest fetal distress.

The ultimate outcome will depend on the woman’s
individual situation. In some cases, delivery can be post-poned while medication is given to the mother (e.g., forhigh blood pressure) or the fetus (e.g., to speed up lungmaturity before delivery). Depending upon the readinessof the mother’s cervix, the doctor may decide to inducelabor. The extra-large fetus of a diabetic woman mayrequire cesarean delivery; severe preeclampsia also maynecessitate induction of labor or cesarean section. The

doctor will determine the most prudent course of action.
Resources
BOOKS
Illustrated Guide to Diagnostic Tests. Ed. J. A. Lewis. Spring-
house, PA: Springhouse Corp. 1994.
Johnson, Robert V . Mayo Clinic Complete Book of Pregnancy
& Baby’s First Year. New York: William Morrow and Co.,
Slupik, Ramona I. American Medical Association Complete
Guide to Women’s Health. New York: Random House,
1996.KEY TERMS
Amniotic fluid —The liquid that surrounds the

baby within the amniotic sac. Because it is com-posed mostly of fetal urine, a low amount of fluidcan indicate inadequate placental blood flow tothe fetus.
Deceleration —A decrease in the fetal heart rate
that can indicate inadequate blood flow throughthe placenta.
Oxytocin —A natural hormone that produces uter-
ine contractions.
Ultrasound —A procedure in which high-frequen-

cy sound waves are used to create a picture of thebaby, used alone or with antepartum tests.
Vibroacoustic stimulation —In the biophysical
profile, use of an artificial larynx to produce aloud noise to “awaken” the fetus.PERIODICALS
McMahon, Michael J., and Jeffrey A. Kuller. “Assessment of
the Post-term Pregnancy.” American Family Physician 54
(Aug. 1996): 631-636.
“Pregnancy—What to Expect When It’s Past Your Due Date.”

American Family Physician 54 (Aug. 1996): 641-642.
Smith-Levitin, Michelle, Boris Petrikovsky, and Elizabeth P.
Schneider. “Practical Guidelines for Antepartum FetalSurveillance.” American Family Physician 56 (15 Nov.
1997): 1981-1988.
12th Street, S.W., P.O. Box 96920, Washington, DC20090-6920. (202) 638-5577. <http://www.acog.com>.
National Institute of Child Health and Human Development.

Bldg 31, Room 2A32, MSC 2425, 31 Center Drive,Bethesda, MD 20892-2425. (800) 505-2742. <http://www.nichd.nih.gov/sids/sids.htm>.
Laura J. Ninger
Anthrax
Anthrax is a bacterial infection caused by Bacillus
anthracis that primarily affects livestock but that can
occasionally spread to humans, affecting either the skin,intestines, or lungs. In humans, the infection can often betreated, but it is almost always fatal in animals.
Anthrax is most often found in the agricultural

areas of South and Central America, southern and east-ern Europe, Asia, Africa, the Caribbean, and the MiddleEast. In the United States, anthrax is rarely reported,however, cases of animal infection with anthrax aremost often reported in Texas, Louisiana, Mississippi,Oklahoma, and South Dakota. The bacterium and itsassociated disease get their name from the Greek wordmeaning “coal” because of the characteristic coal-blacksore that is the hallmark of the most common form ofthe disease.

During the 1800s, in England and Germany, anthrax
was known either as “wool-sorter’s” or “ragpicker’s” dis-ease because workers contracted the disease from bacter-ial spores present on hides and in wool or fabric fibers.Spores are the small, thick-walled dormant stage of somebacteria that enable them to survive for long periods oftime under adverse conditions. The first anthrax vaccinewas perfected in 1881 by Louis Pasteur.

GALE ENCYCLOPEDIA OF MEDICINE 2 223AnthraxGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 223

The largest outbreak ever recorded in the United
States occurred in 1957 when nine employees of a goathair processing plant became ill after handling a contam-inated shipment from Pakistan. Four of the five patientswith the pulmonary form of the disease died. Other casesappeared in the 1970s when contaminated goatskindrumheads from Haiti were brought into this country assouvenirs. Today, anthrax is rare, even among cattle,largely because of widespread animal vaccination . How-

ever, some serious epidemics continue to occur amonganimal herds and in human settlements in developingcountries due to ineffective control programs.
There has been a great deal of recent concern that

the bacteria that causes anthrax may be used by somecountries as a type of biological warfare, since it is possi-ble to become infected simply by breathing in the spores.The largest-ever documented outbreak of human anthraxcontracted through spore inhalation occurred in Russia in1979, when anthrax spores were released from a militarylaboratory, causing a regional epidemic that killed 69 ofits 77 victims. Because the United States governmentconsiders anthrax to be of potential risk to soldiers,

anthrax to be of potential risk to soldiers, theDepartment of Defense has begun systematic vaccinationof all military personnel against anthrax, and othernations, such as Britain, are rapidly following suit.

Anthrax is caused by the bacterium Bacillus
anthracis , which produces spores that can remain dor-
mant for years in soil and on animal products, such ashides, wool, hair, or bones. The disease is often fatal tocattle, sheep, and goats, and their hides, wool, and bonesare often heavily contaminated.
Today, in humans, the disease is almost always an
occupational hazard, contracted by those who handleanimal hides (farmers, butchers, and veterinarians) or

sort wool. It is also possible to become infected withanthrax by eating meat from contaminated animals.There are no reports of the disease spreading from oneperson to another.
Symptoms vary depending on how the disease was
contracted, but the symptoms usually appear within oneweek of exposure.
Cutaneous anthrax
In humans, anthrax usually occurs when the bacteria

enter a cut or abrasion, causing a skin (cutaneous) infec-tion at the site. Cutaneous anthrax, as this infection iscalled, is the mildest form of the disease. At first, thebacteria cause an itchy, raised area like an insect bite.Within one to two days, inflammation occurs around theraised area, and a blister forms around an area of dyingtissue that becomes black in the center. Other symptomsmay include shivering and chills. In most cases the bacte-ria remain within the sore. If, however, they

remain within the sore. If, however, they spread to thenearest lymph node (or, in rare cases, escape into thebloodstream), the bacteria can cause a form of blood poi-

soning that rapidly proves fatal.
Inhalation anthrax
Inhaling the bacteria or bacterial spores can lead to a
rare, fatal form of anthrax known as pulmonary orinhalation anthrax that attacks the lungs and sometimesspreads to the brain. Inhalation anthrax begins with flu-like symptoms, namely fever ,fatigue ,headache , and
shortness of breath , but progresses to bronchitis , dur-
ing which time it becomes difficult to breathe, and final-ly, the patient enters a state of shock . This rare form of

anthrax is usually fatal, even if treated within one or twodays after the symptoms appear.
Intestinal anthrax
Intestinal anthrax is a rare, often-fatal form of the dis-
ease, caused by eating meat from an animal that died ofanthrax. Intestinal anthrax causes stomach and intestinalinflammation and sores or lesions (ulcers), much like thesores that appear on the skin in the cutaneous form ofanthrax. The first signs of the disease are nausea and

vomiting , loss of appetite, and fever, followed by abdomi-
nal pain, vomiting of blood, and severe bloody diarrhea .
Diagnosis
Anthrax is diagnosed by detecting B. anthracis in
samples taken from blood, skin lesions , or respiratory
secretions. The bacteria may be positively identifiedusing biochemical methods or using a technique where-
GALE ENCYCLOPEDIA OF MEDICINE 2 224Anthrax
Humans suffering from anthrax often develop ulcerating
nodules on the body. Custom Medical Stock Photo. Repro-

duced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 224

by, if present in the sample, the anthrax bacterium is
made to fluoresce. Blood samples will also indicate ele-vated antibody levels or increased amounts of a proteinproduced directly in response to infection with theanthrax bacterium. Additional DNA-based tests are alsocurrently being perfected.
Treatment
In the early stages, anthrax is curable by administering
high doses of penicillin, but in the advanced stages, it canbe fatal. Other commonly used antibiotics , such as ery-

thromycin, tetracycline, or chloramphenicol, are also effec-tive, particularly for those individuals who are allergic topenicillin. Although not proven, it is thought that newerantibiotics, like ciprofloxacin and some cephalosporins ,

may also prove effective. Although cutaneous anthrax maybe cured following a single dose of antibiotic, it is impor-tant to continue treatment so as to avoid potential seriouscomplications, such as inflammation of the membranescovering the brain and spinal cord ( meningitis ).
Prognosis
Untreated anthrax is often fatal, but death is far less

likely with appropriate care. Ten to twenty percent ofpatients will die from anthrax of the skin (cutaneousanthrax) if it is not properly treated. All patients withinhalation (pulmonary) anthrax will die if untreated.Intestinal anthrax is fatal 25-75% of the time.
Anthrax is relatively rare in the United States

because of widespread animal vaccination and practicesused to disinfect hides or other animal products. Forthose in high-risk professions, an anthrax vaccine isavailable that is 93% effective in protecting against infec-tion. To provide this immunity, an individual must begiven an initial course of three injections, given twoweeks apart, followed by booster injections at 6, 12, and18 months and an annual immunization thereafter.

Approximately 30% of those who have been vacci-
nated against anthrax may notice mild local reactions,such as a slight tenderness at the injection site. Someonewho has already had anthrax might have a more severelocal reaction upon vaccination. Infrequently, there maybe a severe local reaction with extensive swelling of theforearm, and only a very few vaccine recipients mayhave a more general flu-like reaction to the shot.
Other means of preventing the spread of infection

include carefully handling dead animals suspected ofhaving the disease and providing good ventilation whenprocessing hides, fur, wool, or hair. Whether this vaccineKEY TERMS
Bronchitis —Inflammation of the mucous mem-
brane of the bronchial tubes of the lung that canmake it difficult to breathe.

Cutaneous —Pertaining to the skin
Meningitis —Inflammation of the membranes cov-
ering the brain and spinal cord called themeninges.
Pulmonary —Having to do with the lungs or respi-
ratory system.
Spore —A dormant form assumed by some bacte-
ria, such as anthrax, that enable the bacterium tosurvive high temperatures, dryness, and lack ofnourishment for long periods of time. Under prop-er conditions, the spore may revert to the activelymultiplying form of the bacteria.

would protect against anthrax used as a biological
weapon is, as yet, unclear.
Anyone visiting a country where anthrax is common
or where herd animals are not often vaccinated shouldavoid contact with livestock or animal products andavoid eating meat that has not been properly preparedand cooked.
Resources
BOOKS
Infectious Disease. Ed. Barbara A. Bannister, et al. Oxford,
England: Blackwell Scientific, Inc., 1996.
Van De Graaff, Kent. Survey of Infectious and Parasitic Dis-

eases. New York: McGraw Hill, 1996.
Wilks, David, et. al. The Infectious Diseases Manual. Oxford,
England: Blackwell Scientific, Inc., 1995.
National Institute of Allergies and Infectious Diseases, Divi-
sion of Microbiology and Infectious Diseases. Building31, Room. 7A-50, 31 Center Drive MSC 2520, Bethesda,MD 20892. <http://www.niaid.nih.gov>.

World Health Organization, Division of Emerging and Other
Communicable Diseases Surveillance and Control.Avenue Appia 20, 1211 Geneva 27, Switzerland. (+00 4122) 791 21 11. <http://www.who.int>.
GALE ENCYCLOPEDIA OF MEDICINE 2 225AnthraxGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 225

OTHER
“Anthrax.” New York State Department of Health communica-
ble Disease Fact Sheet. <http://www.health.state.ny.us/
nysdoh/consumer/anthrax.htm>.
“Anthrax: Memo From a WHO Meeting.” World Health Orga-
nization. Bulletin of the World Health Organization, 74
(5)(Sept.-Oct. 1996):456-61.
“Bacterial Diseases.” Healthtouch Online Page. <http:www.
healthtouch.com>.
“Bacillus anthracis (Anthrax).” <http://web.bu.edu/COHIS/
infxns/bacteria/anthrax.htm>.

Centers for Disease Control. <http://www.cdc.gov/nccdphp/
ddt/ddthome.htm>.
Antiacne drugs
Antiacne drugs are medicines that help clear up pim-
ples, blackheads, whiteheads, and more severe forms ofacne .
Purpose
Different types of antiacne drugs are used for differ-

ent purposes. For example, lotions, soaps, gels, andcreams containing benzoyl peroxide or tretinoin may beused to clear up mild to moderately severe acne.Isotretinoin (Accutane) is prescribed only for verysevere, disfiguring acne.
Acne is a skin condition that occurs when pores or

hair follicles become blocked. This allows a waxymaterial, sebum, to collect inside the pores or follicles.Normally, sebum flows out onto the skin and hair toform a protective coating, but when it cannot get out,small swellings develop on the skin surface. Bacteriaand dead skin cells can also collect that can causeinflammation. Swellings that are small and notinflamed are whiteheads or blackheads. When theybecome inflamed, they turn into pimples. Pimples thatfill with pus are called pustules.

Acne cannot be cured, but acne drugs can help clear
the skin. Benzoyl peroxide and tretinoin work by mildlyirritating the skin. This encourages skin cells to sloughoff, which helps open blocked pores. Benzoyl peroxidealso kills bacteria, which helps prevent whiteheads andblackheads from turning into pimples. Isotretinoinshrinks the glands that produce sebum.Description
Benzoyl peroxide is found in many over-the-counter

acne products that are applied to the skin, such asBenoxyl, Clear By Design, Neutrogena Acne, PanOxyl,and some formulations of Clean & Clear, Clearasil, andOxy. Some benzoyl peroxide products are available with-out a physician’s prescription; others require a prescrip-tion. Tretinoin (Retin-A) is available only with a physi-cian’s prescription and comes in liquid, cream, and gelforms, which are applied to the skin. Isotretinoin (Accu-tane), which is taken by mouth in capsule form, is avail-able

is taken by mouth in capsule form, is avail-able only with a physician’s prescription. Only physicianswho have experience in diagnosing and treating severeacne, such as dermatologists, should prescribe isotretinoin.

anti-acne drug. These drugs usually come with writtendirections for patients and should be used only as direct-ed. Patients who have questions about how to use themedicine should check with a physician or pharmacist.
Patients who use isotretinoin usually take the medi-

cine for a few months, then stop for at least two months.Their acne may continue to improve even after they stoptaking the medicine. If the condition is still severe afterseveral months of treatment and a two-month break, thephysician may prescribe a second course of treatment.
Isotretinoin
Isotretinoin can cause serious birth defects , includ-
ing mental retardation and physical deformities. This
medicine should not be used during pregnancy . Women

who are able to bear children should not use isotretinoinunless they have very severe acne that has not cleared upwith the use of other anti-acne drugs. In that case, awoman who uses this drug must have a pregnancy testtwo weeks before beginning treatment and each monththey are taking the drug. Another pregnancy test must bedone one month after treatment ends. The woman mustuse an effective birth control method for one monthbefore treatment begins and must continue using itthroughout treatment

and must continue using itthroughout treatment and for one month after treatmentends. Women who are able to bear children and who wantto use this medicine should discuss this information withtheir health care providers. Before using the medicine,they will be asked to sign a consent form stating that theyunderstand the danger of taking isotretinoin during preg-nancy and that they agree to use effective birth control.

Do not donate blood to a blood bank while taking
isotretinoin or for 30 days after treatment with the drug
GALE ENCYCLOPEDIA OF MEDICINE 2 226Antiacne drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 226

ends. This will help reduce the chance of a pregnant
woman receiving blood containing isotretinoin, whichcould cause birth defects.
Isotretinoin may cause a sudden decrease in night
vision. If this happens, do not drive or do anything elsethat could be dangerous until vision returns to normal.Let the physician know about the problem.
This medicine may also make the eyes, nose, and

mouth dry. Ask the physician about using special eyedrops to relieve eye dryness. To temporarily relieve thedry mouth , chew sugarless gum, suck on sugarless
candy or ice chips, or use saliva substitutes, which comein liquid and tablet forms and are available without a pre-scription. If the problem continues for more than twoweeks, check with a physician or dentist. Mouth drynessthat continues over a long time may contribute to tooth

decay and other dental problems.
Isotretinoin may increase sensitivity to sunlight.
Patients being treated with this medicine should avoidexposure to the sun and should not use tanning beds, tan-ning booths, or sunlamps until they know how the drugaffects them.
In the early stages of treatment with isotretinoin,

some people’s acne seems to get worse before it startsgetting better. If the condition becomes much worse or ifthe skin is very irritated, check with the physician whoprescribed the medicine.
Benzoyl peroxide and tretinoin
When applying antiacne drugs to the skin, be careful
not to get the medicine in the eyes, mouth, or inside ofthe nose. Do not put the medicine on skin that is windburned, sunburned, or irritated, and do not apply it toopen wounds .

Because antiacne drugs such as benzoyl peroxide
and tretinoin irritate the skin slightly, avoid doing any-thing that might cause further irritation. Wash the facewith mild soap and water only two or three times a day,unless the physician says to wash it more often. Avoidusing abrasive soaps or cleansers and products that mightdry the skin or make it peel, such as medicated cosmet-
ics, cleansers that contain alcohol, or other acne productsthat contain resorcinol, sulfur or salicylic acid.

If benzoyl peroxide or tretinoin make the skin too
red or too dry or cause too much peeling, check with aphysician. Using the medicine less often or using aweaker strength may be necessary.
Tretinoin may increase sensitivity to sunlight. While

being treated with this medicine, avoid exposure to the sunand do not use tanning beds, tanning booths, or sunlamps.If it is not possible to avoid being in the sun, use a sun-screen with a skin protection factor (SPF) of at least 15 orwear protective clothing over the treated areas. The skinmay also become more sensitive to cold and wind. Peoplewho use this medicine should protect their skin from coldand wind until they know how the medicine affects them.

Benzoyl peroxide may discolor hair or colored fab-
rics.
People who have certain medical conditions or who are
taking certain other medicines may have problems if theyuse antiacne drugs. Before using these products, be sure tolet the physician know about any of these conditions:

to etretinate, isotretinoin, tretinoin, vitamin A prepara-tions, or benzoyl peroxide in the past should let his or herphysician know before using an antiacne drug. Thephysician should also be told about any allergies to
PREGNANCY. Women who are pregnant or who may
become pregnant should check with a physician beforeusing tretinoin or benzoyl peroxide. Isotretinoin causes

birth defects in humans and must not be used duringpregnancy.
BREASTFEEDING. No problems have been reported
in nursing babies whose mothers used tretinoin or ben-zoyl peroxide. Women who are breastfeeding babiesshould not take isotretinoin, however, as it may causeproblems in nursing babies.
GALE ENCYCLOPEDIA OF MEDICINE 2 227Antiacne drugs
Antiacne Drugs
Brand Name (Generic Name) Possible Common Side Effects Include:
Accutane (isotretinoin) Dry skin, dry mouth, conjunctivitis

Benzamycin Dry and itchy skinCleocin T (clindamycin phosphate) Dry skinDesquam-E (benzoyl peroxide) Itching, red and peeling skinErythromycin topical (A/T/S, erycette, t-stat) Burning, dry skin, hives, red and peeling skinMinocin (minocycline hydrochloride) Headache, hives, diarrhea, peeling skin, vomitingRetin-A (tretinoin) Darkening of the skin, blistering, crusted, or puffy skinGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 227

OTHER MEDICAL CONDITIONS. Before using anti-
acne drugs applied to the skin, people with any of thesemedical problems should make sure their physicians areaware of their conditions:
• eczema. Anti-acne drugs that are applied to the skin
may make this condition worse.
• sunburn or raw skin. Anti-acne drugs that are applied to
the skin may increase the pain and irritation of these
conditions.
In people with certain medical conditions, isotre-

tinoin may increase the amount of triglyceride (a fatty-substance) in the blood. This may lead to heart or bloodvessel problems. Before using isotretinoin, people withany of these medical problems should make sure theirphysicians are aware of their conditions:
• alcoholism or heavy drinking, now or in the past• diabetes (or family history of diabetes). Isotretinoin
may also change blood sugar levels.
• family history of high triglyceride levels in the blood• severe weight problems

USE OF CERTAIN MEDICINES. Using antiacne drugs
with certain other drugs may affect the way the drugswork or may increase the chance of side effects.
Minor discomforts such as dry mouth or nose, dry
eyes, dry skin, or itching usually go away as the body
adjusts to the drug and do not require medical attentionunless they continue or are bothersome.
Other side effects should be brought to a physicians
attention. These include:
• burning, redness, or itching of the eyes

• nosebleeds• signs of inflammation of the lips, such as peeling, burn-
ing, redness or pain
Bowel inflammation is not a common side effect,
but it may occur. If any of the following signs of bowelinflammation occur, stop taking isotretinoin immediatelyand check with a physician:
• pain in the abdomen• bleeding from the rectum• severe diarrhea
The most common side effects of antiacne drugs

applied to the skin are slight redness, dryness, peeling,KEY TERMS
Acne —A skin condition in which raised bumps,
pimples, and cysts form on the face, neck, shoul-ders and upper back.
Bacteria —Tiny, one-celled forms of life that cause
many diseases and infections.
Bowel —The intestine; a tube-like structure that
extends from the stomach to the anus. Some diges-tive processes are carried out in the bowel beforefood passes out of the body as waste.

Cyst—An abnormal sac or enclosed cavity in the
body, filled with liquid or partially solid material.
Eczema —Inflammation of the skin with itching
and a rash. The rash may have blisters that oozeand form crusts.
Pimple —A small, red swelling of the skin.
Psoriasis —A skin disease in which people have
itchy, scaly, red patches on the skin.
Pus—Thick, whitish or yellowish fluid that forms
in infected tissue.
Triglyceride —A substance formed in the body
from fat in the diet.

and stinging, and a warm feeling to the skin. These prob-
lems usually go away as the body adjusts to the drug anddo not require medical treatment.
Other side effects should be brought to a physician’s
attention. Check with a physician as soon as possible ifany of the following side effects occur:
• blistering, crusting or swelling of the skin
• severe burning or redness of the skin• darkening or lightening of the skin. (This effect will

eventually go away after treatment with an anti-acnedrug ends.)
• skin rash
Other side effects are possible with any type of anti-
acne drug. Anyone who has unusual symptoms whileusing anti-acne drugs should get in touch with his or herphysician.
Patients using antiacne drugs on their skin should
tell their physicians if they are using any other prescrip-tion or nonprescription (over-the-counter) medicine thatthey apply to the skin in the same area.

GALE ENCYCLOPEDIA OF MEDICINE 2 228Antiacne drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 228

Isotretinoin may interact with other medicines.
When this happens, the effects of one or both drugs maychange or the risk of side effects may be greater. Anyonewho takes isotretinoin should let the physician knowabout all other medicines he or she is taking and shouldask whether the possible interactions can interfere withdrug therapy. Among the drugs that may interact withisotretinoin are:
• etretinate (Tegison), used to treat severe psoriasis . Using

this medicine with isotretinoin increases side effects.
• tretinoin (Retin-A, Renova). Using this medicine with
isotretinoin increases side effects.
• vitamin A or any medicine containing vitamin A. Using
any vitamin A preparations with isotretinoin increasesside effects. Do not take vitamin supplements contain-ing vitamin A while taking isotretinoin.
• tetracyclines (used to treat infections). Using these medi-

cines with isotretinoin increases the chance of swellingof the brain. Make sure the physician knows if tetracy-cline is being used to treat acne or another infection.
Nancy Ross-FlaniganKEY TERMS

from fat in the diet.Antiangina drugs
Antiangina drugs are medicines that relieve the
symptoms of angina pectoris (severe chest pain ).
Purpose
The dull, tight chest pain of angina occurs when the

heart’s muscular wall is not getting enough oxygen. Byrelaxing the blood vessels, antiangina drugs reduce theheart’s work load and increase the amount of oxygen-rich blood that reaches the heart. These drugs come indifferent forms, and are used in three main ways:
• taken regularly over a long period, they reduce the
number of angina attacks.
• taken just before some activity that usually brings on an
attack, such as climbing stairs, they prevent attacks.

• taken when an attack begins, they relieve the pain and
pressure.
Not every form of antiangina drug can be used in
every way. Some work too slowly to prevent attacks thatare about to begin or to relieve attacks that have alreadystarted. These forms can be used only to reduce the num-ber of attacks. Be sure to understand how and when touse the type of antiangina drug that has been prescribed.
Antiangina drugs, also known as nitrates, come in

many different forms: tablets and capsules that are swal-lowed; tablets that are held under the tongue, inside thelip, or in the cheek until they dissolve; stick-on patches;ointment; and in-the-mouth sprays. Commonly usedantiangina drugs include isosorbide dinitrate (Isordil,Sorbitrate, and other brands) and nitroglycerin (Nitro-Bid, Nitro-Dur, Nitrolingual Spray, Nitrostat Tablets,Transderm-Nitro, and other brands). These medicines areavailable only with a physician’s prescription.

The recommended dosage depends on the type and
form of antiangina drug and may be different for differ-ent patients. Check with the physician who prescribedthe drug or the pharmacist who filled the prescription forthe correct dosage.
Always take antiangina drugs exactly as directed.
The medicine will not work if it is not taken correctly.
Do not stop taking this medicine suddenly after tak-
ing it for several weeks or more, as this could cause angi-

GALE ENCYCLOPEDIA OF MEDICINE 2 229Antiangina drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 229

na attacks to return. If it is necessary to stop taking the
drug, check with the physician who prescribed it forinstructions on how to taper down gradually.
Remember that some forms of antiangina drugs

work too slowly to relieve attacks that have already start-ed. Check with the physician who prescribed the medi-cine for instructions on how to use the type that has beenprescribed. Patients who are using slower-acting forms tomake attacks less frequent may want to ask their physi-cians to prescribe a fast-acting type to relieve attacks.Another method of treating the frequency of attacks is toincrease the dosage of the long-acting antiangina drug.Do this only with the approval of a physician.

These medicines make some people feel lighthead-
ed, dizzy, or faint when they get up after sitting or lyingdown. To lessen the problem, get up gradually and holdonto something for support if possible. Antiangina drugsmay also cause dizziness , lightheadedness, or fainting in
hot weather or when people stand for a long time orexercise . Use caution in all these situations. Drinking

alcohol while taking antiangina drugs may cause thesame problems. Anyone who takes this medicine shouldlimit the amount of alcohol consumed.
Because these drugs may cause dizziness, be careful
when driving, using machines, or doing anything elsethat could be dangerous.
If the person is taking the form of nitroglycerin that

is placed under the tongue and symptoms are not relievedwithin three doses taken about 5 minutes apart, the per-son should go to the hospital emergency room as soon aspossible. A heart attack may be in progress.
Some people develop tolerance to antiangina drugs
over time. That is, the drug no longer produces thedesired effects. Anyone who seems to be developing a
tolerance to this medicine should check with his or herphysician.
Anyone who has had unusual reactions to antiangina

drugs in the past should let his or her physician knowbefore taking the drugs again. The physician should alsobe told about any allergies to foods, dyes, preservatives,
Women who are pregnant or breastfeeding or who
may become pregnant should check with their physiciansbefore using antiangina drugs.
Older people may be especially sensitive to the
effects of antiangina drugs and thus more likely to haveside effects such as dizziness and lightheadedness.

Before using antiangina drugs, people with any of
these medical problems should make sure their physi-cians are aware of their conditions:
• recent heart attack or stroke
• kidney disease• liver disease• severe anemia
• overactive thyroid
• glaucoma• recent head injury
A common side effect is a headache just after taking

a dose of the medicine. These headaches usually becomeless noticeable as the body adjusts to the drug. Checkwith a physician if they are severe or they continue evenafter taking the medicine for a few weeks. Unless aphysician says to do so, do not change the dose to avoid
GALE ENCYCLOPEDIA OF MEDICINE 2 230Antiangina drugsAntiangina Drugs

Calan (calan SR, isoptin, isoptin SR, verelan) Constipation, dizziness, fatigue, headache, fluid retention, low
blood pressure, nausea
Cardene (nicardipine hydrochloride) Dizziness, headache, indigestion, nausea, rapid heartbeat,
sleepiness, swelling of feet, flushing
Cardizem (diltiazem hydrochloride) Dizziness, fluid retention, headache, nausea, rashCorgard (nadolol) Behaviorial changes, dizziness, drowsiness, tiredness

Imdur, Ismo, Monoket (isosorbide mononitrate) HeadacheIsordil (isosorbide dinitrate) Headache, dizziness, low blood pressureLopressor (metroprolol tartrate) Depression, diarrhea, itching, rash, tirednessNitro-Bid, Nitro-Dur, Nitrolingual Spray, Nitrostat Tables, Transderm-Nitro (nitroglycerin) Dizziness, flushing, headacheNorvasc (amlodipine besylate) Dizziness, fatigue, fluid retention, headache, palpitationsProcardia, Procardia XL, Adalat (nifedipine) Constipation, dizziness, hearburn, low

ness, nausea, swelling
Tenormin (atenolol) Dizziness, fatigue, nausea, slowed heartbeatGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 230

headaches. Other common side effects include dizziness,
lightheadedness, fast pulse, flushed face and neck, nau-sea or vomiting, and restlessness. These problems do notneed medical attention unless they do not go away orthey interfere with normal activities.
unusual symptoms after taking an antiangina drug shouldget in touch with his or her physician.
Antiangina drugs may interact with other medicines.

This may increase the risk of side effects or change theeffects of one or both drugs. Anyone who takes antiangi-na drugs should let the physician know all other medi-cines he or she is taking. Among the drugs that mayinteract with antiangina drugs are:
• other heart medicines• blood pressure medicines• aspirin• alcohol• ergot alkaloids used in migraine headaches
Antianxiety drugs
Antianxiety drugs are medicines that calm and relax

people with excessive anxiety , nervousness, or tension,
or for short term control of social phobia disorder or spe-cific phobia disorder.
Purpose
Antianxiety agents, or anxiolytics, may be used to
treat mild transient bouts of anxiety as well as more pro-nounced episodes of social phobia and specific phobia.Clinically significant anxiety is marked by severalKEY TERMS
Angina pectoris —A feeling of tightness, heavi-

ness, or pain in the chest, caused by a lack of oxy-gen in the muscular wall of the heart.symptoms. The patient experiences marked or persistent

fear of one or more social or performance situations inwhich he or she is exposed to unfamiliar people or pos-sible scrutiny by others, and may react in a humiliatingor embarrassing way. The exposure to the feared situa-tion produces an anxiety attack. Fear of these episodesof anxiety leads to avoidance behavior, which impairsnormal social functioning, including working or attend-ing classes. The patient is aware that these fears areunjustified.

In psychiatric practice, treatment of anxiety has
largely turned from traditional antianxiety agents, anxi-olytics, to antidepressant therapies. In current use, thebenzodiazepines , the best known class of anxiolytics,

have been largely supplanted by serotonin-specific reup-take inhibitors (SSRIs, citalopram, fluoxetine, fluvoxam-ine and others) which have a milder side effect profileand less risk of dependency. However, traditional anxi-olytics remain useful for patients who need a rapid onsetof action, or whose frequency of exposure to anxiety pro-voking stimuli is low enough to eliminate the need forcontinued treatment. While SSRIs may require three tofive weeks to show any effects, and must be taken

weeks to show any effects, and must be taken contin-uously, benzodiazepines may produce a response within30 minutes, and may be dosed on an as-needed basis.

lam (Xanax), and lorazepam (Ativan) are the appropriatechoice for treatment of mild anxiety and social phobia.Diazepam (Valium) is still widely used for anxiety, butits active metabolite, desmethyldiazepam, which has along half-life, may make this a poorer choice than otherdrugs in its class. Note that there is considerable varia-tion between individuals in metabolism of benzodi-azepines, so patient response may not be predictable. Asa class, benzodiazepines are used not only as anxiolytics,but

are used not only as anxiolytics,but also as sedatives, muscle relaxants , and in treatment

of epilepsy and alcoholism . The distinctions between
these uses are largely determined by onset and durationof action, and route of administration.
Buspirone (BuSpar), which is not chemically related

to other classes of central nervous system drugs, is also atraditional anxiolytic, although it is now consideredeither a third line or adjunctive agent for use after trialsof SSRIs and benzodiazepines. It is appropriate for use inpatients who have either failed trials of other treatments,or who should not receive benzodiazepines because of ahistory of substance abuse problems. Buspirone, in com-mon with antidepressants, requires a two to three weekperiod before there is clinical evidence of

weekperiod before there is clinical evidence of improvement,and must be continuously dosed to maintain its effects.

GALE ENCYCLOPEDIA OF MEDICINE 2 231Antianxiety drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 231

Benzodiazepines are controlled drugs under federal
law. Buspirone is not a controlled substance and has noestablished abuse potential.
Benzodiazepines should be administered 30 to 60
minutes before exposure to the anticipated stress .
Dosage should be individualized to minimize sedation .
The normal dose of alprazolam is 0.25–0.5 mg. Theusual dose of lorazepam is 2–3 mg. Doses may be repeat-ed if necessary.
Buspirone is initially dosed at 5 mg t.i.d. (3 times a

day.) Increase the dosage 5 mg/day, at intervals of two tothree days, as needed. Do not exceed 60 mg/day. Two tothree weeks may be required before a satisfactory responseis seen.
Benzodiazepines should not be used in patients with
psychosis , acute narrow angle glaucoma , or liver dis-

ease. The drugs can act as respiratory depressants andshould be avoided in patients with respiratory conditions.Benzodiazepines are potentially addictive and should notbe administered to patients with substance abuse disor-ders. Because benzodiazepines are sedative, they shouldbe avoided in patients who must remain alert. Their usefor periods over four months has not been documented.These drugs should not be used during the second andthird trimester of pregnancy , although use during the

first trimester appears to be safe. They should not betaken while breastfeeding. Consult specialized referencesfor use in children.
Buspirone is metabolized by the liver and excreted
by the kidney, and should be used with care in patientswith hepatic or renal disease. The drug is classified asschedule B during pregnancy, but should not be takenduring breastfeeding. Its use in children under the age of
18 years has not been studied.

The most common side effects of benzodiazepines are
secondary to their CNS effects and include sedation andsleepiness; depression; lethargy; apathy; fatigue ; hypoac-
tivity; lightheadedness; memory impairment; disorienta-tion; anterograde amnesia ; restlessness; confusion; crying
or sobbing; delirium ; headache ; slurred speech; aphonia;
dysarthria; stupor; seizures; coma ; syncope; rigidity;
tremor; dystonia; vertigo; dizziness ; euphoria; nervous-

ness; irritability; difficulty in concentration; agitation;inability to perform complex mental functions; akathisia;hemiparesis; hypotonia; unsteadiness; ataxia; incoordina-tion; weakness; vivid dreams; psychomotor retardation;“glassy-eyed” appearance; extrapyramidal symptoms;paradoxical reactions. Other reactions include changes inheart rate and blood pressure, changes in bowel function,severe skin rash and changes in genitourinary function.Other adverse effects have been reported.

Buspirone has a low incidence of side effects. Dizzi-
ness and drowsiness are the most commonly reportedadverse effects. Other CNS effects include dream distur-bances; depersonalization, dysphoria, noise intolerance,euphoria, akathisia, fearfulness, loss of interest, disasso-ciative reaction, hallucinations , suicidal ideation,
seizures; feelings of claustrophobia, cold intolerance,stupor and slurred speech, psychosis. Rarely, heart prob-lems, including congestive heart failure and myocardial

infarction, have been reported. Other adverse effectshave been reported.
The metabolism of alprazolam may be increased by:
cimetidine, oral contraceptives , disulfiram, fluoxetine,
GALE ENCYCLOPEDIA OF MEDICINE 2 232Antianxiety drugsAntianxiety Drugs
Atarax (hydroxyzine hydrochloride) Drowsiness, dry mouth

Ativan (lorazepam) Dizziness, excessive calm, weaknessBuSpar, Buspirone (buspirone hydrochloride) Dry mouth, dizziness, headache, fatigue, nauseaCentrax (pazepam) Decreased coordination, dizziness, drowsiness, fatigue, weaknessLibrium, Libritabs (chlordiazepoxide) Constipation, drowsiness, nausea, swellingMiltown, Equanil (meprobamate) Diarrhea, bruising, fever, headache, nausea, rash, slurred speechSerax (oxazepam) Dizziness, fainting, headache, liver problems, decreased coordination, nausea,

swelling, vertigo
Stelazine (trifluoperazine hydrochloride) Abnormal glucose in urine, allergic reactions, blurred vision, constipation, eye spasm s, fluid retention
and swelling
Tranxene, Tranxene-SD (clorazepate dipotassium) DrowsinessValium (diazepam) Decreased coordination, drowsiness, light-headednessGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 232

isoniazid, ketoconazole, metoprolol, propoxyphene, pro-
pranolol and valproic acid. The absorption of all benzo-diazepines is inhibited by concomitant use of antacids .
Benzodiazepines may increase blood devels of digoxin,and reduce the efficacy of levodopa. Other drug interac-tions have been reported.
Buspirone levels will be increased by concomitant

use of erythromycin, itraconazole, and nefazadone.Doses should be adjusted based on clinical response. Useof buspirone at the same time as mono-amine oxidaseinhibitors (MAOIs, phenelzine, tranycypromine) maycause severe blood pressure elevations. Use of buspironewith MAOIs should be avoided.
Antiarrhythmic drugs
Antiarrhythmic drugs are medicines that correct irreg-

ular heartbeats and slow down hearts that beat too fast.KEY TERMS
Anxiety —Worry or tension in response to real or
imagined stress, danger, or dreaded situations.Physical reactions, such as fast pulse, sweating,trembling, fatigue, and weakness may accompanyanxiety.
Epilepsy —A brain disorder with symptoms that
include seizures.
Panic disorder —An disorder in which people have

sudden and intense attacks of anxiety in certainsituations. Symptoms such as shortness of breath,sweating, dizziness, chest pain, and extreme fearoften accompany the attacks.
Phobia —An intense, abnormal, or illogical fear of
something specific, such as heights or open spaces.
Pregnancy category B —Animal studies indicate
no fetal risk, but no human studies; or adverseeffects in animals, but not in well-controlledhuman studies.

Pregnancy category C —No adequate human or
animal studies; or adverse fetal effects in animalstudies, but no available human data.
Seizure —A sudden attack, spasm, or convulsion.Purpose
Normally, the heart beats at a steady, even pace. The

pace is controlled by electrical signals that begin in one partof the heart and quickly spread through the whole heart. Ifsomething goes wrong with this control system, the resultmay be an irregular heartbeat, or an arrhythmia. Antiar-rhythmic drugs correct irregular heartbeats, restoring thenormal rhythm. If the heart is beating too fast, these drugswill slow it down. By correcting these problems, antiar-rhythmic drugs help the heart work more efficiently.

Antiarrhythmic drugs are available only with a
physician’s prescription and are sold in capsule (regularand extended release), tablet (regular and extended-release), and injectable forms. Commonly used antiar-rhythmic drugs are disopyramide (Norpace, NorpaceCR), procainamide (Procan SR, Pronestyl, Pronestyl-SR), and quinidine (Cardioquin, Duraquin, Quinidex,and other brands). Do not confuse quinidine with qui-

nine, which is a related medicine with different uses, suchas relieving leg cramps.
antiarrhythmic drug and other factors. Doses may be dif-ferent for different patients. Check with the physicianwho prescribed the drug or the pharmacist who filled theprescription for the correct dosage.
Always take antiarrhythmic drugs exactly as direct-
ed. Never take larger or more frequent doses.

with the physician who prescribed it. Stopping it sudden-ly could lead to a serious change in heart function.
Antiarrhythmic drugs work best when they are at

constant levels in the blood. To help keep levels constant,take the medicine in doses spaced evenly through the dayand night. Do not miss any doses. If taking medicine atnight interferes with sleep, or if it is difficult to remem-ber to take the medicine during the day, check with ahealth care professional for suggestions.
Persons who take these drugs should see their physi-

cian regularly. The physician will check to make sure themedicine is working as it should and will note anyunwanted side effects.
Some people feel dizzy, lightheaded, or faint when
using these drugs. This medicine may cause blurred
GALE ENCYCLOPEDIA OF MEDICINE 2 233Antiarrhythmic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 233

vision or other vision problems. Because of these possi-
ble problems, anyone who takes these drugs should notdrive, use machines or do anything else that might bedangerous until they have found out how the drugs affectthem. If the medicine does cause vision problems, waituntil vision is clear before driving or engaging in otheractivities that require normal vision.
Antiarrhythmic drugs make some people feel light-

headed, dizzy, or faint when they get up after sitting orlying down. To lessen the problem, get up gradually andhold onto something for support if possible.
Anyone taking this medicine should not drink alco-
hol without his or her physician’s approval.
Some antiarrhythmic drugs may change the results
of certain medical tests. Before having medical tests,anyone taking this medicine should alert the health careprofessional in charge.

Anyone who is taking antiarrhythmic drugs should
be sure to tell the health care professional in chargebefore having any surgical or dental procedures orreceiving emergency treatment.
Antiarrhythmic drugs may cause low blood sugar in
some people. Anyone who experiences symptoms of lowblood sugar should eat or drink a food that contains sugarand call a physician immediately. Signs of low bloodsugar are:
• anxiety• confusion
• nervousness
• shakiness• unsteady walk• extreme hunger
• headache

• headache
• nausea• drowsiness• unusual tiredness or weakness• fast heartbeat
• pale, cool skin
• chills• cold sweats
Antiarrhythmic drugs may cause dry mouth . To

temporarily relieve the discomfort, chew sugarless gum,suck on sugarless candy or ice chips, or use saliva substi-tutes, which come in liquid and tablet forms and areavailable without a prescription. If the problem continuesfor more than 2 weeks, check with a physician or dentist.Mouth dryness that continues over a long time may con-tribute to tooth decay and other dental problems.People taking antiarrhythmic drugs may sweat less,

which can cause the body temperature to rise. Anyonewho takes this medicine should be careful not to becomeoverheated during exercise or hot weather and should
avoid hot baths, hot tubs, and saunas. Overheating couldlead to heat stroke.
effects of antiarrhythmic drugs. This may increase therisk of certain side effects, such as dry mouth, difficulturination, and dizziness or lightheadedness.
The antiarrhythmic drug procainamide can cause

serious blood disorders. Anyone taking this medicineshould have regular blood counts and should check witha physician if any of the following symptoms occur:
• joint or muscle pain
• muscle weakness
• pain in the chest or abdomen
• tremors
• wheezing
• cough
• palpitations
• rash, sores, or pain in the mouth
• sore throat
• fever and chills
•diarrhea
• dark urine
• yellow skin or eyes
• unusual bleeding or bruising• dizziness

•hallucinations
• depression
People with certain medical conditions or who are tak-
ing certain other medicines may have problems if they takeantiarrhythmic drugs. Before taking these drugs, be sure tolet the physician know about any of these conditions:

to an antiarrhythmic drug in the past should let his or herphysician know before taking this type of medicineagain. Patients taking procainamide should let theirphysicians know if they have ever had an unusual orallergic reaction to procaine or any other “caine-type”medicine, such as xylocaine or lidocaine. Patients takingquinidine should mention any previous reactions to qui-

GALE ENCYCLOPEDIA OF MEDICINE 2 234Antiarrhythmic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 234

nine. The physician should also be told about any aller-
CONGESTIVE HEART DISEASE. Antiarrhythmic drugs
may cause low blood sugar, which can be a particularproblem for people with congestive heart disease. Any-one with congestive heart disease should be familiar withthe signs of low blood sugar (listed above) and shouldcheck with his or her physician about what to do if suchsymptoms occur.
DIABETES. Antiarrhythmic drugs may cause low

blood sugar, which can be a particular problem for peo-ple with diabetes. Anyone with diabetes should be famil-iar with the signs of low blood sugar (listed above) andshould check with his or her physician about what to doif such symptoms occur.
PREGNANCY. The effects of taking antiarrhythmic
drugs in pregnancy have not been studied in humans. In

studies of laboratory animals, this medicine increased therisk of miscarriage . In addition, some women who have
taken these drugs while pregnant have had contractionsof the uterus (womb). Women who are pregnant or whomay become pregnant should check with their physiciansbefore taking this medicine. Women who become preg-KEY TERMS

Arrhythmia —Abnormal heart rhythm.
Asthma —A disease in which the air passages of the
lungs become inflamed and narrowed.
Emphysema —A lung disease in which breathing
becomes difficult.
Glaucoma —A condition in which pressure in the

eye is abnormally high. If not treated, glaucomamay lead to blindness.
objects, sounds, or events that seems real. Hallucina-tions usually result from drugs or mental disorders.
Heat stroke —A severe condition caused by pro-

longed exposure to high heat. Heat stroke interfereswith the body’s temperature regulating abilities andcan lead to collapse and coma.Inflammation —Pain, redness, swelling, and heat
Myasthenia gravis —A chronic disease with symp-
toms that include muscle weakness and sometimesparalysis.

Prostate —A donut-shaped gland below the bladder
in men that contributes to the production of semen.
Tourette syndrome —A condition in which a person
has tics and other involuntary behavior, such asbarking, sniffing, swearing, grunting, and makinguncontrollable movements.

Tremor —Shakiness or trembling.
nant while taking this medicine should let their physi-
cians know right away.
BREASTFEEDING. Antiarrhythmic drugs pass into
breast milk. Women who are breastfeeding should checkwith their physicians before taking this medicine.
OTHER MEDICAL CONDITIONS. Before using antiar-
rhythmic drugs, people with any of these medical prob-lems should make sure their physicians are aware of theirconditions:
• heart disorders such as structural heart disease or inflam-

mation of the heart muscle
• congestive heart failure
• kidney disease
• diseases of the blood
• asthma or emphysema
• enlarged prostate or difficulty urinating
• low blood sugar
• psoriasis
•glaucoma
GALE ENCYCLOPEDIA OF MEDICINE 2 235Antiarrhythmic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 235

• myasthenia gravis
• systemic lupus erythematosus
USE OF CERTAIN MEDICINES. Taking antiarrhythmic
drugs with certain other drugs may affect the way thedrugs work or may increase the chance of side effects.
The most common side effects are dry mouth and

throat, diarrhea, and loss of appetite. These problemsusually go away as the body adjusts to the drug and donot require medical treatment. Less common side effects,such as dizziness, lightheadedness, blurred vision, dryeyes and nose, frequent urge to urinate, bloating, consti-
pation , stomach pain, and decreased sexual ability, also
may occur and do not need medical attention unless theydo not go away or they interfere with normal activities.

More serious side effects are not common, but may
occur. If any of the following side effects occur, checkwith the physician who prescribed the medicine as soonas possible:
• difficult urination• swollen or painful joints• pain when breathing• skin rash or itching
People who are especially sensitive to quinidine may
have a reaction to the first dose or doses. If any of theseside effects occur after taking quinidine, check with aphysician immediately:
• dizziness

• ringing in the ears• breathing problems• vision changes•f e v e r• headache
• skin rash
Other rare side effects may occur with any antiar-
rhythmic drug. Anyone who has unusual symptoms aftertaking antiarrhythmic drugs should get in touch with hisor her physician.
Antiarrhythmic drugs may interact with other medi-

cines. When this happens, the effects of one or both ofthe drugs may change or the risk of side effects may begreater. Anyone who takes antiarrhythmic drugs shouldlet the physician know all other medicines he or she istaking. Among the drugs that may interact with antiar-
rhythmic drugs are:
• other heart medicines, including other antiarrhythmic
drugs
• blood pressure medicine• blood thinners
• pimozide (Orap), used to treat Tourette’s syndrome

The list above does not include every drug that may
interact with antiarrhythmic drugs. Be sure to check witha physician or pharmacist before combining antiarrhyth-mic drugs with any other prescription or nonprescription(over-the-counter) medicine.
Antiasthmatic drugs
Antiasthmatic drugs are medicines that treat or pre-
vent asthma attacks.
Purpose
For people with asthma, the simple act of breathing

can be a struggle. Their airways become inflamed andblocked with mucus during asthma attacks, narrowing theopening through which air passes. This is not such a prob-lem when the person breathes in, because the airways nat-urally expand when a person takes a breath. The real prob-lem arises when the person with asthma tries to breatheout. The air cannot get out through the blocked airways, soit stays trapped in the lungs. With each new breath, theperson can take in only a little more air, so

theperson can take in only a little more air, so breathingbecomes shallow and takes more and more effort.

Asthma attacks can be caused by allergies to pollen,
dust, pets or other things, but people without knownallergies may also have asthma. Exercise ,stress , intense
emotions, exposure to cold, certain medicines and somemedical conditions also can bring on attacks.
The two main approaches to dealing with asthma are

avoiding substances and situations that trigger attacksand using medicines that treat or prevent the symptoms.With a combination of the two, most people with asthmacan find relief and live normal lives.
Three types of drugs are used in treating and pre-
venting asthma attacks:
GALE ENCYCLOPEDIA OF MEDICINE 2 236Antiasthmatic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 236

•Bronchodilators relax the smooth muscles that line the
airway. This makes the airways open wider, lettingmore air pass through them. These drugs are used main-ly to relieve sudden asthma attacks or to prevent attacksthat might come on after exercise. They may be takenby mouth, injected or inhaled.
•Corticosteroids block the inflammation that narrows

the airways. Used regularly, these drugs will help pre-vent asthma attacks. Those attacks that do occur will beless severe. However, corticosteroids cannot stop anattack that is already underway. These drugs may betaken by mouth, injected or inhaled.
• Cromolyn also is taken regularly to prevent asthma

attacks and may be used alone or with other asthmamedicines. It cannot stop an attack that already hasstarted. The drug works by preventing certain cells inthe body from releasing substances that cause allergicreactions or asthma symptoms. One brand of thisdrug, Nasalcrom, comes in capsule and nasal sprayforms and is used to treat hay fever and other aller-

gies. The inhalation form of the drug, Intal, is used forasthma. It comes in aerosol canisters, in capsules thatare inserted into an inhaler, and in liquid form that isused in a nebulizer.
Using antiasthmatic drugs properly is important.

Because bronchodilators provide quick relief, some peo-ple may be tempted to overuse them. However, withsome kinds of bronchodilators, this can lead to seriousand possibly life-threatening complications. In the longrun, patients are better off using bronchodilators only asdirected and also using corticosteroids, which eventually
will reduce their need for bronchodilators.
Patients who are using their antiasthmatic drugs cor-

rectly but feel their asthma is not under control shouldsee their physicians. The physician can either increasethe dose, switch to another medicine or add another med-icine to the regimen.
Corticosteroids are powerful drugs that may cause

serious side effects when used over a long time. However,these problems are much less likely with the inhalantforms than with the oral and injected forms. While theoral and injected forms generally should be used only forone to two weeks, the inhalant forms may be used forlong periods.
When used to prevent asthma attacks, cromolyn

must be taken as directed every day. The drug may takeas long as four weeks to start working. Unless told to doso by a physician, patients should not stop taking thedrug just because it does not seem to be working. Whensymptoms do begin to improve, patients should continuetaking all medicines that have been prescribed, unless aphysician directs otherwise.
Inhalant forms of antiasthmatic drugs may cause

dryness or irritation in the throat, dry mouth , or an
unpleasant taste in the mouth. To help prevent theseproblems, gargle and rinse the mouth or take a sip ofwater after each dose.
More serious side effects are not common when
these medicines are used properly. However, anyone who
GALE ENCYCLOPEDIA OF MEDICINE 2 237Antiasthmatic drugs
Antiasthmatic Drugs

AeroBid (aerobid-m, nasalide) Diarrhea, headache, nausea, sore throat
Alupent (metaproterenol sulfate) Cough, increased blood pressure and heart rate, nausea, upset stomachAtrovent (ipratropium bromide) Blurred vision, dry mouth, rash, headacheAzmacort (triamcinolone acetonide) Dry mouth, dry and irritated throatBeclovent Inhalation Aerosol, Beconase Dry mouth, fluid retention, rash, headache, nasal irritation and burning, watery eyes

AQ Nasal Spray, Beconase Inhalation Aerosol(beclomethasone dipropionate)
Brethine (terbutaline sulate) Difficulty in breathing, drowsiness, headache, increased heartbeat, vomitingDecadron Tables (dexamethasone) Blood clots, bruising, fluid retention, increased blood pressure, hivesDecadron Turbinaire/Respihaler Headache, nausea, coughing, irritated throat
(dexamethasone sodium phosphate)

Deltasone (orasone) Changes in behavior, mood and personality, may cause depression, fluid retention, increased blood pres-
sure

Intal (cromolyn sodium) Nausea, coughing and sneezing, irritated throatMedrol (methylprednisolone) Bruising, cataracts, increased blood pressure, stomach ulcer, rash, vertigoPediapred (prednisolone sodium phosphate) Loss of bone and muscle mass, dizziness, fluid retention, diabetes, peptic ulcerProvential (albuterol sulfate) Diarrhea, headache, heartburn, muscle cramps, nausea, ringing in the earsTheo-Dur (theophylline) Nausea, diarrhea, hair loss, decreased blood pressure, rash,

hair loss, decreased blood pressure, rash, sleepinessTilade (neodocromil sodium) Chest pain, headache, nausea, sore throatGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 237

has unusual or bothersome symptoms after taking an
antiasthmatic drug should get in touch with a physician.
Check with a physician or pharmacist before com-
bining antiasthmatic drugs with any other prescription ornonprescription (over-the-counter) medicine.
Antibacterial bath seeTherapeutic baths
Antibiotic-associated colitis
Antibiotic-associated colitis is an inflammation of

the intestines that sometimes occurs following antibiotictreatment and is caused by toxins produced by the bac-terium Clostridium difficile .
Antibiotic-associated colitis, also called antibiotic-
associated enterocolitis, can occur following antibiotictreatment. The bacteria Clostridia difficile are normally

found in the intestines of 5% of healthy adults, but peo-ple can also pick up the bacteria while they are in a hos-pital or nursing home. In a healthy person, harmless resi-dent intestinal bacteria compete with each other for foodand places to “sit” along the inner intestinal wall. Whenantibiotics are given, most of the resident bacteria areKEY TERMS
Asthma —A disease in which the air passages of
the lungs become inflamed and narrowed.

that usually develop in response to injury or ill-ness.
Inhalant —Medicine that is breathed into the
lungs.
Mucus —Thick fluid produced by the moist mem-
branes that line many body cavities and structures.
Nebulizer —A device that turns liquid forms of
medicine into a fine spray that can be inhaled.killed. With fewer bacteria to compete with, the normally
harmless Clostridia difficile grow rapidly and produce

toxins. These toxins damage the inner wall of theintestines and cause inflammation and diarrhea .
Although all antibiotics can cause this disease, it is
most commonly caused by clindamycin (Cleocin), ampi-cillin (Omnipen), amoxicillin (Amoxil, Augmentin, orWymox), and any in the cephalosporin class (such ascefazolin or cephalexin). Symptoms of the condition canoccur during antibiotic treatment or within four weeksafter the treatment has stopped.

In approximately half of cases of antibiotic-associated
colitis, the condition progresses to a more severe form ofcolitis called pseudomembranous enterocolitis in whichpseudomembranes are excreted in the stools. Pseudomem-branes are membrane-like collections of white blood cells,mucus, and the protein that causes blood to clot (fibrin)that are released by the damaged intestinal wall.
Antibiotic-associated colitis is caused by toxins pro-

duced by the bacterium Clostridium difficile after treat-
ment with antibiotics. When most of the other intestinalbacteria have been killed, Clostridium difficile grows
rapidly and releases toxins that damage the intestinalwall. The disease and symptoms are caused by these tox-ins, not by the bacterium itself.
Symptoms of antibiotic-associated colitis usually

begin four to ten days after antibiotic treatment hasbegun. The early signs and symptoms of this diseaseinclude lower abdominal cramps, an increased need topass stool, and watery diarrhea. As the disease progress-es, the patient may experience a general ill feeling,fatigue , abdominal pain , and fever . If the disease pro-

ceeds to pseudomembranous enterocolitis, the patientmay also experience nausea, vomiting, large amounts ofwatery diarrhea, and a very high fever (104-105°F/40-40.5°C). Complications of antibiotic-associated colitisinclude severe dehydration , imbalances in blood miner-
als, low blood pressure, fluid accumulation in deep skin
(edema ), enlargement of the large intestine (toxic mega-
colon), and the formation of a tear (perforation) in thewall of the large intestine.

Clostridium difficile is easily spread from person to
person in hospitals and nursing homes. The followingindividuals are most at-risk for developing this disease:
• the elderly
• severely ill individuals
• individuals with weakened or suppressed immune sys-
tems (immunocompromised)
GALE ENCYCLOPEDIA OF MEDICINE 2 238Antibiotic-associated colitisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 238

• individuals with poor hygiene
• individuals who have been hospitalized for a long peri-
od of time
The Clostridium difficile toxin is found in the stools
of persons older than 60 years of age 20-100 times morefrequently than in the stools of persons who are 10-20years old. As a result, the elderly are much more prone todeveloping antibiotic-associated colitis than youngerindividuals.
Diagnosis
Antibiotic-associated colitis can be diagnosed by the

symptoms and recent medical history of the patient, by alaboratory test for the bacterial toxin, and/or by using aprocedure called endoscopy.
If the diarrhea and related symptoms occurred after
the patient received antibiotics, antibiotic-associated col-itis may be suspected. A stool sample may be analyzedfor the presence of the Clostridium difficile toxin. This

toxin test is the preferred diagnostic test for antibiotic-associated colitis. One frequently used test for the toxininvolves adding the processed stool sample to a humancell culture. If the toxin is present in the stool sample, thecells die. It may take up to two days to get the resultsfrom this test. A simpler test, which provides results intwo to three hours, is also available. Symptoms and toxintest results are usually enough to diagnose the disease.

Another tool that may be useful in the diagnosis of
antibiotic-associated colitis, however, is a procedurecalled an endoscopy that involves inserting a thin, lightedtube into the rectum to visually inspect the intestinal lin-ing. Two different types of endoscopy procedures, thesigmoidoscopy and the colonoscopy , are used to view

different parts of the large intestine. These proceduresare performed in a hospital or doctor’s office. Patients aresedated during the procedure to make them more com-fortable and are allowed to go home after recoveringfrom the sedation .
Treatment
Diarrhea, regardless of the cause, is always treated

by encouraging the individual to replace lost fluids andprevent dehydration. One method to treat antibiotic-asso-ciated colitis is to simply stop taking the antibiotic thatcaused the disease. This allows the normal intestinal bac-teria to repopulate the intestines and inhibits the over-growth of Clostridium difficile . Many patients with mild

disease respond well to this and are free from diarrheawithin two weeks. It is important, however, to make surethat the original disease for which the antibiotics wereprescribed is treated.KEY TERMS
Colitis —Inflammation of the colon.
Edema —Fluid accumulation in a tissue.
Endoscopy —A procedure in which a thin, lighted
instrument is inserted into the interior of a holloworgan, such as the rectum and used to visuallyinspect the inner intestinal lining.

Fibrin —A fibrous blood protein vital to coagula-
tion and blood clot formation.
Rectum —The last part of the intestine. Stool pass-
es through the rectum and out through the analopening.
Toxic megacolon —Acute enlargement or dilation
of the large intestine.
Because of the potential seriousness of this disease,
most patients are given another antibiotic to control thegrowth of the Clostridium difficile , usually vancomycin

(Vancocin) or metronidazole (Flagyl or Protostat). Bothare designed to be taken orally four times a day for 10-14days. Upon finishing antibiotic treatment, approximately15-20% of patients will experience a relapse of diarrheawithin one to five weeks. Mild relapses can go untreatedwith great success, however, severe relapses of diarrhearequire another round of antibiotic treatment. Instead offurther antibiotic treatment, a cholestyramine resin(Questran or Prevalite) may be given. The bacterial

or Prevalite) may be given. The bacterial tox-ins produced in the intestine stick to the resin and arepassed out with the resin in the stool. Unfortunately,however, vancomycin also sticks to the resin, so thesetwo drugs cannot be taken at the same time. Serious dis-ease may require hospitalization so that the patient canbe monitored, treated, and rehydrated.

The goal of alternative treatment for antibiotic-asso-
ciated enterocolitis is to repopulate the intestinal envi-ronment with microorganisms that are normal andhealthy for the intestinal tract. These microorgansismsthen compete for space and keep the Clostridium difficile
from over-populating.
Several types of supplements can be used. Supple-
ments containing Lactobacillus acidophilus , the bacteria
commonly found in yogurt and some types of milk, Lacto-

bacillus bifidus , and Streptococcus faecium , are available
in many stores in powder, capsule, tablet, and liquid form.Acidophilus also acts as a mild antibiotic, which helps it to
GALE ENCYCLOPEDIA OF MEDICINE 2 239Antibiotic-associated colitisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 239

reestablish itself in the intestine, and all may aid in the
production of some B vitamins and vitamin K. These sup-
plements can be taken individually and alternated weeklyor together following one or more courses of antibiotics.
Prognosis
With appropriate treatment and replenishment of

fluids, the prognosis is generally excellent. One or morerelapses can occur. Very severe colitis can cause a tear(perforation) in the wall of the large intestine that wouldrequire major surgery. Perforation of the intestine cancause a serious abdominal infection. Antibiotic-associat-ed colitis can be fatal in people who are elderly and/orhave a serious underlying illness, such as cancer .

There are no specific preventative measures for this
disease. Good general health can reduce the chance ofdeveloping a bacterial infection that would requireantibiotic treatment and the chance of picking up theClostridia bacteria. Maintaining good general health can
also reduce the seriousness and length of the condition,should it develop following antibiotic therapy.
Resources
Fekety, R., and A. B. Shah. “Diagnosis and Treatment of

Clostridium difficile Colitis.” Journal of the American
Medical Association 269 (1993): 71+.
Kelly, Ciaran P., Charalabos Pothoulakis, and J. Thomas LaM-
ont. “Clostridium difficile Colitis.” The New England
Journal of Medicine 330 (27 Jan. 1994): 257+.KEY TERMS

of the large intestine.OTHER

Mayo Clinic Online. 5 Mar. 1998 <http://www.mayohealth.org>.
Antibiotic prophylaxis seeProphylaxis
Antibiotics
Antibiotics may be informally defined as the sub-
group of anti-infectives that are derived from bacterialsources and are used to treat bacterial infections. Otherclasses of drugs, most notably the sulfonamides , may be

effective antibacterials. Similarly, some antibiotics mayhave secondary uses, such as the use of demeclocycline(Declomycin, a tetracycline derivative) to treat the syn-drome of inappropriate antidiuretic hormone (SIADH)secretion. Other antibiotics may be useful in treating pro-tozoal infections.
Purpose
Antibiotics are used for treatment or prevention of
bacterial infection.
Classifications
Although there are several classification schemes for

antibiotics, based on bacterial spectrum (broad versus nar-row) or route of administration (injectable versus oral ver-sus topical), or type of activity (bactericidal vs. bacteriosta-tic), the most useful is based on chemical structure. Antibi-otics within a structural class will generally show similarpatterns of effectiveness, toxicity, and allergic potential.
PENICILLINS. The penicillins are the oldest class of

antibiotics, and have a common chemical structure whichthey share with the cephalopsorins. The two groups areclassed as the beta-lactam antibiotics, and are generallybacteriocidal—that is, they kill bacteria rather thaninhibiting growth. The penicillins can be further subdi-vided. The natural pencillins are based on the originalpenicillin G structure; penicillinase-resistant penicillins,notably methicillin and oxacillin, are active even in thepresence of the bacterial enzyme that inactivates

of the bacterial enzyme that inactivates mostnatural penicillins. Aminopenicillins such as ampicillinand amoxicillin have an extended spectrum of actioncompared with the natural penicillins; extended spectrum

GALE ENCYCLOPEDIA OF MEDICINE 2 240AntibioticsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 240

penicillins are effective against a wider range of bacteria.
These generally include coverage for Pseudomonas
aeruginaosa and may provide the penicillin in combina-
tion with a penicillinase inhibitor.
CEPHALOSPORINS. Cephalosporins and the closely

related cephamycins and carbapenems, like the pen-cillins, contain a beta-lactam chemical structure. Conse-quently, there are patterns of cross-resistance and cross-allergenicity among the drugs in these classes. The“cepha” drugs are among the most diverse classes ofantibiotics, and are themselves subgrouped into 1st, 2ndand 3rd generations. Each generation has a broader spec-trum of activity than the one before. In addition, cefox-itin, a cephamycin, is highly active against anaerobicbacteria,

is highly active against anaerobicbacteria, which offers utility in treatment of abdominalinfections. The 3rd generation drugs, cefotaxime, cefti-zoxime, ceftriaxone and others, cross the blood-brainbarrier and may be used to treat meningitis and

encephalitis . Cephalopsorins are the usually preferred
agents for surgical prophylaxis .
FLUROQUINOLONES. The fluroquinolones are syn-

thetic antibacterial agents, and not derived from bacteria.They are included here because they can be readily inter-changed with traditional antibiotics. An earlier, relatedclass of antibacterial agents, the quinolones, were notwell absorbed, and could be used only to treat urinarytract infections. The fluroquinolones, which are based onthe older group, are broad-spectrum bacteriocidal drugsthat are chemically unrelated to the penicillins or thecephaloprosins. They are well distributed into

thecephaloprosins. They are well distributed into bone tis-sue, and so well absorbed that in general they are aseffective by the oral route as by intravenous infusion.

TETRACYCLINES. Tetracyclines got their name
because they share a chemical structure that has fourrings. They are derived from a species of Streptomyces
bacteria. Broad-spectrum bacteriostatic agents, thetetracyclines may be effective against a wide varietyof microorganisms, including rickettsia and amebicparasites.
MACROLIDES. The macrolide antibiotics are derived
from Streptomyces bacteria, and got their name because

they all have a macrocyclic lactone chemical structure.Erythromycin, the prototype of this class, has a spectrumand use similar to penicillin. Newer members of thegroup, azithromycin and clarithyromycin, are particular-ly useful for their high level of lung penetration. Clar-ithromycin has been widely used to treat Helicobacter
pylori infections, the cause of stomach ulcers.
OTHERS. Other classes of antibiotics include the
aminoglycosides , which are particularly useful for their

effectiveness in treating Pseudomonas aeruginosa infec-tions; the lincosamindes, clindamycin and lincomycin,
which are highly active against anaerobic pathogens.There are other, individual drugs which may have utilityin specific infections.
Dosage varies with drug, route of administration,
pathogen, site of infection, and severity. Additional con-siderations include renal function, age of patient, andother factors. Consult manufacturers’ recommendationsfor dose and route.

All antibiotics cause risk of overgrowth by non-sus-
ceptible bacteria. Manufacturers list other major hazardsby class; however, the health care provider should revieweach drug individually to assess the degree of risk. Gen-erally, breastfeeding is not recommended while takingantibiotics because of risk of alteration to infant’s intesti-nal flora, and risk of masking infection in the infant.Excessive or inappropriate use may promote growth ofresistant pathogens.

Penicillins: Hypersensitivity may be common, and
cross allergenicity with cephalosporins has been reported.Penicillins are classed as category B during pregnancy .
Cephalopsorins: Several cephalopsorins and related
compounds have been associated with seizures. Cefmeta-zole, cefoperazone, cefotetan and ceftriaxone may be
GALE ENCYCLOPEDIA OF MEDICINE 2 241Antibiotics
A penicillin culture. (Photograph by P . Barber, Custom Medical

Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 241

associated with a fall in prothrombin activity and coagu-
lation abnormalities. Pseudomembranous colitis hasbeen reported with cephalosporins and other broad spec-trum antibiotics. Some drugs in this class may causerenal toxicity. Pregnancy category B.
Fluroquinolones: Lomefloxacin has been associated
with increased photosensitivity . All drugs in this class
have been associated with convulsions. Pregnancy cate-gory C.
Tetracyclines: Demeclocycline may cause increased

photosensitivity. Minocycline may cause dizziness . Do

not use tetracyclines in children under the age of eight,and specifically avoid during periods of tooth develop-ment. Oral tetracyclines bind to anions such as calciumand iron. Although doxycycline and minocycline may betaken with meals, patients must be advised to take othertetracycline antibiotics on an empty stomach, and not totake the drugs with milk or other calcium-rich foods.Expired tetracycline should never be administered. Preg-nancy category D. Use during pregnancy may

Preg-nancy category D. Use during pregnancy may causealterations in bone development.

Macrolides: Erythromycin may aggravate the weak-
ness of patients with myasthenia gravis . Azithromycin
has, rarely, been associated with allergic reactions,including angioedema, anaphylaxis , and dermatologicreactions, including Stevens-Johnson syndrome and
toxic epidermal necrolysis . Oral erythromycin may be

highly irritating to the stomach and when given by injec-tion may cause severe phlebitis. These drugs should beused with caution in patients with liver dysfunction.Pregnancy category B: Azithromycin, erythromycin.Pregnancy category C: Clarithromycin, dirithromycin,troleandomycin.
Aminoglycosides: This class of drugs causes kidney
and ototoxicity . These problems can occur even with

normal doses. Dosing should be based on renal function,with periodic testing of both kidney function and hear-ing. Pregnancy category D.
Recommended usage
To minimize risk of adverse reactions and develop-
ment of resistant strains of bacteria, antibiotics should berestricted to use in cases where there is either known or areasonable presumption of bacterial infection. The use ofantibiotics in viral infections is to be avoided. Avoid useof fluroquinolones for trivial infections.

In severe infections, presumptive therapy with a
broad-spectrum antibiotic such as a 3rd generationcephalosporin may be appropriate. Treatment should bechanged to a narrow spectrum agent as soon as the
GALE ENCYCLOPEDIA OF MEDICINE 2 242AntibioticsAntibiotic
Water entersCell deterioratesCell is destroyed
Different antibiotics destroy bacteria in different ways. Some short-circuit the processes by which bacteria receive energy.

Others disturb the structure of the bacterial cell wall, as shown in the illustration above. Still others interfere with the prod uc-
tion of essential proteins. (Illustration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 242

pathogen has been identified. After 48 hours of treat-
ment, if there is clinical improvement, an oral antibioticshould be considered.
Resources
Braffman-Miller, Judith. “Beware the Rise of Antibiotic-Resis-
tant Microbes.” USA Today (Magazine) 125 (March
1997): 56.
“Consumer Alert: Antibiotic Resistance Is Growing!” People’s
Medical Society Newsletter 16 (August 1997): 1.
Swartz, Morton N. “The Path of Least Resistance.” Harvard
Health Letter 20 (April 1995): 6.

Antibiotics, ophthalmic
Ophthalmic antibiotics are medicines that kill bac-
teria that cause eye infections.KEY TERMS
Meningitis —Inflammation of tissues that surround
the brain and spinal cord.
Microorganism —An organism that is too small to

be seen with the naked eye.
Organism —A single, independent unit of life,
such as a bacterium, a plant or an animal.
Pregnancy category —A system of classifying

drugs according to their established risks for useduring pregnancy. Category A: Controlled humanstudies have demonstrated no fetal risk. CategoryB: Animal studies indicate no fetal risk, but nohuman studies; or adverse effects in animals, butnot in well-controlled human studies. Category C:No adequate human or animal studies; or adversefetal effects in animal studies, but no availablehuman data. Category D: Evidence of fetal risk,but benefits outweigh risks. Category X: Evidenceof fetal risk.

risks. Category X: Evidenceof fetal risk. Risks outweigh any benefits.Purpose

Ophthalmic antibiotics are applied to the eye, or
under the eyelid, to treat eye infections caused by bacteria.
The medicine described here, tobramycin (Tobrex),
comes in the form of eye drops or ointment. It is avail-able only with a physician’s prescription.
The dosages given here are typical doses. Physicians

may adjust the number of doses per day, the timebetween doses, and the length of treatment with the med-icine, depending on the patient’s particular medical prob-lem. If the physician’s directions are different from thosegiven here, follow the physician’s directions.
Be sure to follow package directions for applying
drops or ointment properly.
Adults
EYE DROPS. For mild to moderate infections, use one
to two drops in the affected eye or eyes every four hours.

For severe infections, use two drops in the affected
eye or eyes every two hours until the condition improves.At that time, the physician will determine how much touse until the infection is completely cleared up.
OINTMENT. For mild to moderate infections,
squeeze a half-inch ribbon of ointment into the affectedeye or eyes two or three times a day. Do not let the tip ofthe ointment tube touch the eye.
For severe infections, squeeze a half-inch ribbon of

ointment into the affected eye or eyes every three to fourhours until the condition improves. At that time, thephysician will determine how much to use until theinfection is completely cleared up.
Children
The child’s physician should determine the proper
dose.
Use this drug as often as directed, for as long as

directed. Although the symptoms may have disap-peared, the infection may not clear up completely if thedrug is stopped too soon. Therefore, the medicationmay be prescribed for several days after the infectionappears to have cleared. However, it is just as importantto use the drug for only as long as directed. Using it for
GALE ENCYCLOPEDIA OF MEDICINE 2 243Antibiotics, ophthalmicGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 243

too long may lead to the growth of bacteria that do not
respond to the drug. These bacteria may then causeinfections that can be very difficult to treat. Make surethe physician or pharmacist specifies how long themedication is to be used.
Anyone who has had an allergic reaction to
tobramycin or any other ingredients of Tobrex should notuse this medicine. Be sure to tell the physician about anypast reactions to the drug or its ingredients.
Anyone who has an allergic reaction to tobramycin

should stop using it immediately and call a physician.
plan to become pregnant should check with their physi-cians before using tobramycin.
The main side effects of this medicine are itching ,
redness, and swelling of the eye or eyelid. Allergic reac-tions also are possible. If any of these symptoms occur,call the physician who prescribed the medicine.

Patients who are using any other prescription or non-
prescription (over-the-counter) medicines in their eyesshould check with their physicians before usingtobramycin.
Antibiotics, topical
Topical antibiotics are medicines applied to the skin
to kill bacteria.KEY TERMS
Ointment —A thick, spreadable substance that

contains medicine and is meant to be used on theskin, or, if it is specifically an ophthalmic, or “eye”ointment, in the eyePurpose
Topical antibiotics help prevent infections caused by
bacteria that get into minor cuts, scrapes, and burns .
Treating minor wounds with antibiotics allows quicker
healing. If the wounds are left untreated, the bacteria willmultiply, causing pain , redness, swelling, itching , and

oozing. Untreated infections can eventually spread andbecome much more serious.
Different kinds of topical antibiotics kill different
kinds of bacteria. Many antibiotic first-aid products con-tain combinations of antibiotics to make them effectiveagainst a broad range of bacteria.
When treating a wound, it is not enough to simply

apply a topical antibiotic. The wound must first be cleanedwith soap and water and patted dry. After the antibiotic isapplied, the wound should be covered with a dressing,such as a bandage or a protective gel or spray. For manyyears, it was thought that wounds heal best when exposedto the air. But now most experts say it is best to keepwounds clean and moist while they heal. The coveringshould still allow some air to reach the wound, however.

Some topical antibiotics are available without a pre-
scription and are sold in many forms, including creams,ointments, powders, and sprays. Some widely used topi-cal antibiotics are bacitracin, neomycin, mupirocin, andpolymyxin B. Among the products that contain one ormore of these ingredients are Bactroban (a prescriptionitem), Neosporin, Polysporin, and Triple Antibiotic Oint-ment or Cream.

topical antibiotic. Follow the directions on the packagelabel or ask a pharmacist for directions.
In general, topical antibiotics should be applied
within four hours after injury. Do not use more than therecommended amount and do not apply it more oftenthan three times a day. Do not apply the medicine overlarge areas of skin or on open wounds.
Many public health experts are concerned about

antibiotic resistance, a problem that can develop whenantibiotics are overused. Over time, bacteria develop newdefenses against antibiotics that once were effectiveagainst them. Because bacteria reproduce so quickly,these defenses can be rapidly passed on through genera-tions of bacteria until almost all are immune to the
GALE ENCYCLOPEDIA OF MEDICINE 2 244Antibiotics, topicalGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 244

faster than new antibiotics can be developed. To helpcontrol the problem, many experts advise people to usetopical antibiotics only for short periods, that is, until thewound heals, and only as directed. For the topical antibi-otic to work best, it should be used only to prevent infec-tion in a fresh wound, not to treat an infection that hasalready started. Wounds that are not fresh may need theattention of a physician to prevent complications such asblood poisoning .

Topical antibiotics are meant to be used only on the
skin and only for only a few days at a time. If the woundhas not healed in five days, stop using the antibiotic andcall a doctor.
Do not use topical antibiotics on large areas of skin
or on open wounds. These products should not be used totreat diaper rash in infants or incontinence rash in
adults.
Only minor cuts, scrapes, and burns should be treat-

ed with topical antibiotics. Certain kinds of injuries mayneed medical care and should not be self-treated withtopical antibiotics. These include:
• large wounds
• deep cuts
• cuts that continue bleeding
• cuts that may need stitches
• burns any larger than a few inches in diameter
• scrapes imbedded with particles that won’t wash away
• animal bites
• deep puncture wounds
• eye injuries
Never use regular topical antibiotics in the eyes.

Special antibiotic products are available for treating eyeinfections.
Although topical antibiotics control infections
caused by bacteria, they may allow fungal infections todevelop. The use of other medicines to treat the fungalinfections may be necessary. Check with the physician orpharmacist.
Some people may be allergic to one or more ingredi-
ents in a topical antibiotic product. If an allergic reactiondevelops, stop using the product immediately and call aphysician.

No harmful or abnormal effects have been reported
in babies whose mothers used topical antibiotics whilepregnant or nursing. However, pregnant women generallyare advised not to use any drugs during the first 3 monthsafter conception. A woman who is pregnant or breastfeed-KEY TERMS
Conception —The union of egg and sperm to form
a fetus.
Fungal —Caused by a fungus.
Fungus —A member of a group of simple organ-

isms that are related to yeast and molds.
Incontinence —The inability to control the bladder
or bowel.
ing or who plans to become pregnant should check with
her physician before using a topical antibiotic.
Unless a physician says to do so, do not use topical
antibiotics on children under two years of age.

The most common minor side effects are itching or
burning. These problems usually do not require medicaltreatment unless they do not go away or they interferewith normal activities.
If any of the following side effects occur, check with
a doctor as soon as possible:
• rash
• swelling of the lips and face
• sweating
• tightness or discomfort in the chest• breathing problems
• fainting or dizziness
• low blood pressure• nausea
• diarrhea
• hearing loss or ringing in the ears

• diarrhea
Other rare side effects may occur. Anyone who has
unusual symptoms after using a topical antibiotic shouldget in touch with the physician who prescribed or thepharmacist who recommedned the medication.
Using certain topical antibiotics at the same time as
hydrocortisone (a topical corticosteroid used to treat
GALE ENCYCLOPEDIA OF MEDICINE 2 245Antibiotics, topicalGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 245

inflammation) may hide signs of infection or allergic
reaction. Do not use these two medicines at the sametime unless told to do so by a health care provider.
Anyone who is using any other type of prescription
or nonprescription (over-the-counter) medicine on theskin should check with a doctor before using a topicalantibiotic.
Resources
Farley, Dixie. “Help for Cuts, Scrapes and Burns.” FDA Con-
sumer (May 1996):12.
Antibody screening seeBlood typing and

Anticancer drugs
Anticancer, or antineoplastic, drugs are used to treat
malignancies, cancerous growths. Drug therapy may beused alone, or in combination with other treatments suchas surgery or radiation therapy .
Purpose
Anticancer drugs are used to control the growth of
cancerous cells. Cancer is commonly defined as the

uncontrolled growth of cells, with loss of differentiationand commonly, with metastasis, spread of the cancer toother tissues and organs. Cancers are malignant growths.In contrast, benign growths remain encapsulated and growwithin a well-defined area. Although benign tumors maybe fatal if untreated, due to pressure on essential organs, asin the case of a benign brain tumor , surgery or radiation

are the preferred methods of treating growths which have awell defined location. Drug therapy is used when thetumor has spread, or may spread, to all areas of the body.
Several classes of drugs may be used in cancer treat-
ment, depending on the nature of the organ involved. Forexample, breast cancers are commonly stimulated byestrogens, and may be treated with drugs which inactivethe sex hormones. Similarly, prostate cancer may be

treated with drugs that inactivate androgens, the male sexhormone. However, the majority of antineoplastic drugsKEY TERMS
Cataract —Clouding of the lens of the eye, leading
to poor vision or blindness.
Impotent —Unable to achieve or maintain an
erection of the penis.
act by interfering with cell growth. Since cancerous cells

grow more rapidly than other cells, the drugs target thosecells which are in the process of reproducing themselves.As a result, antineoplastic drugs will commonly affectnot only the cancerous cells, but others cells that com-monly reproduce quickly, including hair follicles, ovariesand testis, and the blood-forming organs.
Newer approaches to antineoplastic drug therapy

have taken different approaches, including angigenesis—the inhibition of formation of blood vessels feeding thetumor and contributing to tumor growth. Although theseapproaches hold promise, they are not yet in common use.
Antineoplastic drugs may be divided into two class-

es: cycle specific and non-cycle specific. Cycle specificdrugs act only at specific points of the cell’s duplicationcycle, such as anaphase or metaphase, while non-cyclespecific drugs may act at any point in the cell cycle. Inorder to gain maximum effect, antineoplastic drugs arecommonly used in combinations.
Because antineoplastic agents do not target specific

cell types, they have a number of common adverse sideeffects. Hair loss is common due to the effects on hair fol-licles, and anemia, immune system impairment, and clot-ting problems are caused by destruction of the blood form-ing organs, leading to reduction in the number of red cells,white cells, and platelets. Because of the frequency andseverity of these side effects, it is common to administerchemotherapy in cycles, allowing time for recovery from

the drug effects before administering the next dose. Dosesare often calculated, not on the basis of weight, but ratherbased on blood counts, in order to avoid dangerous levelsof anemia (red cell depletion), neutropenia (white cell
deficiency), or thrombocytopenia (platelet deficiency.)
Nausea and vomiting are among the most common
adverse effects of cancer chemotherapy, and in somecases may be severe enough to cause dose reduction ordiscontinuation of treatment.

The health professional has many responsibilities in
dealing with patients undergoing chemotherapy. The
GALE ENCYCLOPEDIA OF MEDICINE 2 246Anticancer drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 246

patient must be well informed of the risks and benefits of
chemotherapy, and must be emotionally prepared for theside effects. These may be permanent, and youngerpatients should be aware of the high risk of sterility afterchemotherapy.
The patient must also know which side effects

should be reported to the practitioner, since manyadverse effects do not appear until several days after adose of chemotherapy. When chemotherapy is self-administered, the patient must be familiar with properuse of the drugs, including dose scheduling and avoid-ance of drug-drug and food-drug interactions.
Appropriate steps should be taken to minimize side

effects. These may include administration of antinause-ant medications to reduce nausea and vomiting, main-taining fluid levels to reduce drug toxicity, particularly tothe kidneys, or application of a scalp tourniquet to reduceblood flow to the scalp and minimize hair loss due todrug therapy.
Patients receiving chemotherapy are also at risk of
infections due to reduced white blood counts. While pro-phylactic antibiotics may be useful, the health care pro-

fessional should also be sure to use standard precautions,including gowns and gloves when appropriate. Patientsshould be alerted to avoid risks of viral contamination,
and live virus immunizations are contraindicated untilthe patient has fully recovered from the effects ofchemotherapy. Similarly, the patient should avoid contactwith other people who have recently had live virusimmunizations.
Other precautions which should be emphasized are

the risks to pregnant or nursing women. Because antineo-plastic drugs are commonly harmful to the fetus, womenof childbearing potential should be cautioned to use twoeffective methods of birth control while receiving cancerchemotherapy. This also applies if the woman’s malepartner is receiving chemotherapy. Breastfeeding shouldbe avoided while the mother is being treated.
Before prescribing or administering anticancer

drugs, health care providers should inquire whether thepatient has any of the following conditions:
•chickenpox or recent exposure to someone with chick-
enpox
• shingles (Herpes zoster)
• mouth sores
• current or past seizures
GALE ENCYCLOPEDIA OF MEDICINE 2 247Anticancer drugs
Anti Cancer Drugs
Generic (Brand Name) Clinical Uses Common Side Effects To Drug

Altretamine (Hexalen) Treatment of advanced ovarian cancer Bone marrow depression, nausea and vomiting
Asparaginase (Elspar) Commonly used in combination Liver, kidney, pancreas, CNS abnormalities
with other drugs; refractory acutelymphocytic leukemia
Bleomycin (Blenoxane) Lymphomas, Hodgkin’s disease, Hair loss, stomatitis, pulmonary toxicity,
testicular cancer hyperpigmentation of skin

Busulfan (Myleran) Chronic granulocytic leukemia Bone marrow depression, pulmonary toxicityCarboplatin (Paraplatin) Pallilation of ovarian cancer Bone marrow depression, nausea and vomitingCarmustine Hodgkin’s disease, brain Bone marrow depression, nausea and
tumors, multiple myeloma, vomiting, toxic damage to livermalignant melonoma
Chlorambucil (Leukeran) Chronic lymphocytic leukemia, Bone marrow depression,

non-Hodgkin’s lymphomas, breast excess uric acid in bloodand ovarian cancer
Cisplatin (Platinol) Treatment of bladder, ovarian, uterine, Renal toxicity and ototoxicity
testicular, head and neck cancers
Cladribine (Leustatin) Hairy cell leukemia Bone marrow depression, nausea and vomiting, feverCyclophosphamide (Cytoxan) Hodgkin’s disease, non-Hodgkin’s Bone marrow depression,

lymphomas, neuroblastoma. Often used hair loss, nausea and vomiting,with other drugs for breast, ovarian, and inflammation of the bladderlung cancers; acute lymphoblasticleukemia in children; multiple myeloma
Cytarabine (Cytosar-U) Leukemias occurring in adults and children Bone marrow depression, nausea and vomiting,
diarrhea, stomatitis

Dacarbazine (DTIC-Dome) Hodgkin’s disease, malignant melanoma Bone marrow depression, nausea and vomitingDiethylstilbestrol (DES) (Stilbestrol) Breast cancer in post-menopausal Hair loss, nausea and vomiting, edema,
women, prostate cancer excess calcium in blood; feminizing effects in men
Ethinyl estradiol (Estinyl) Advanced breast cancer in Excess calcium in blood, anorexia, edema,
post-menopausal women, prostate cancer nausea and vomiting; feminizing effects in men

Etoposide (VePesid) Acute leukemias, lymphomas, Bone marrow depression, nausea and vomiting, hair loss
testicular cancerGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 247

• head injury
• nerve or muscle disease• hearing problems• infection of any kind• gout• colitis• intestine blockage• stomach ulcer
• kidney stones
• kidney disease• liver disease• current or past alcohol abuse• immune system disease•cataracts or other eye problems
• high cholesterol
Other precautions
The anticancer drug methotrexate has additional pre-
cautions. Patients should be given advice on the effects ofsun exposure and the use of alcohol and pain relievers.Side effects
Tamoxifen

Tamoxifen
The anticancer drug tamoxifen (Nolvadex) increases
the risk of cancer of the uterus in some women. It alsocauses cataracts and other eye problems. Women takingthis drug may have hot flashes, menstrual changes, geni-tal itching , vaginal discharge, and weight gain. Men who
take tamoxifen may lose interest in sex or become impo-tent. Health care providers should keep in close contactwith patients to assess the individual risks associatedwith taking this powerful drug.

Other anticancer drugs
These side effects are not common, but could be a
sign of a serious problem. Health care providers shouldimmediately be consulted if any of the following occur:
• black, tarry, or bloody stools• blood in the urine• diarrhea• fever or chills• cough or hoarseness• wheezing or shortness of breath
GALE ENCYCLOPEDIA OF MEDICINE 2 248Anticancer drugsAnti Cancer Drugs (continued)

Floxuridine (FUDR) Cancers of the liver, pancreas, GI and See Cytarabine
biliary tract, head and neck tumors
Fludarabine (Fludara) Chronic lymphocytic leukemia Bone marrow depression, nausea and vomiting, feverFluorouracil (5–FU)(Adrucil) Breast, colon, pancreatic cancer, See Cytarabine
cancer of the rectum and stomach
Flutamide (Eulexin) Advanced prostate cancer Nausea and vomiting, hot flashes, diarrhea,
impotence, decreased libido, gynecomastia

Goserelin (Zoladex) Advanced prostate cancer Pain in bonesHydroxyurea (Hydrea) Chronic granulocytic leukemia, Bone marrow depression,
malignant melanoma gastrointestinal irritation
Idarubicin (Idamycin) Used in combination with other See Doxorubicin
antileukemic drugs, acutemyelogenous leukemia
Ifosfamide (Ifex) Germ cell testicular cancer Bone marrow depression, nausea and vomiting,
inflammation of the bladder

Leuprolide (Lupron) Advanced prostate cancer See GoserelinLevamisole (Ergamisol) Used in conjunction with Fluorouracil Diarrhea, dermatitis, nausea and vomiting
to treat colon cancer
Lomustine Brain tumors, Hodgkin’s disease Bone marrow depression, nausea and vomiting,
toxic damage to liver
Mechlorethamine (Mustargen) Lung cancer, Hodgkin’s disease and Bone marrow depression, nausea and vomiting
non-Hodgkin’s lymphomas

Medroxyprogesterone (Depo-Provera) Advanced uterine cancer May cause edemaMegestrol (Megace) Advanced uterine cancer, breast cancer Masculinizing effectsMelphalan (Alkeran) Multiple myeloma Bone marrow depression, nausea and vomitingMercaptopurine (Purinethol) Acute and chronic leukemias Bone marrow depression, nausea, excess uric acid in bloodMethotrexate (Mexate) Acute lymphoblastic leukemias in Bone marrow depression, diarrhea, nausea, stomatitis

children, bone cancer, choriocaricinomaof the testesGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 248

• sores in the mouth or on the lips
• unusual bleeding or bruising• swelling of the face
• red “pinpoint” spots on the skin
• redness, pain, or swelling at the place on the body
where an injectable anticancer drug is given
• pain in the side or lower back
• problems urinating or painful urination
• dizziness or faintness
• fast or irregular heartbeat
Other side effects do not need immediate care, but
should have medical attention. They are:
• joint pain
• skin rash

• skin rash
• hearing problems or ringing in the ears
• numbness or tingling in the fingers or toes
• trouble walking or balance problems
• swelling of the feet or lower legs
• unusual tiredness or weakness
• loss of taste• seizures
• agitation• headache
• dark urine• yellow eyes or skin• flushing of the face
In addition, there are other possible side effects that

do not need medical attention unless they persist or inter-fere with normal activities. These include changes inmenstrual period, itchy skin, nausea and vomiting, andloss of appetite.
unusual symptoms after taking anticancer drugs shouldcontact the physician who prescribed the medication.
Anticancer drugs may interact with a number of

other medicines. When this happens, the effects of one orboth of the drugs may change or the risk of side effectsmay be greater. The health care provider should be awareof all other prescription or non-prescription (over-the-counter) medicines a patient is taking. The primary careprovider should also be told if the patient has been treat-ed with radiation or has taken other anticancer drugs.

Anticholinergic drugs seeAntiparkinson
drugs
GALE ENCYCLOPEDIA OF MEDICINE 2 249Anticancer drugs
Anti Cancer Drugs (continued)
Mitomycin (Mutamycin) Bladder, breast, colon, lung, pancreas, Bone marrow depression, nausea and vomiting,
rectum cancers, head and neck cancer, diarrhea, stomatitis, possible tissue damagemalignant melanoma

Mitotane (Lysodren) Cancer of the adrenal cortex (inoperable) Damage to adrenal cortex, nausea, anorexiaMitoxantrone (Novantrone) Acute nonlymphocytic leukemia Cardiac arrhythmias, labored breating, nausea and
vomiting, diarrhea, fever, congestive heart failure
Paclitaxel (Taxol) Advanced ovarian cancer Bone marrow depression, hair loss, nausea and
vomiting, hypotension, allergic reactions, slow heartaction, muscle and joint pain

Pentastatin (Nipent) Hairy cell leukemia unresponsive Bone marrow depression, fever, skin rash,
to alpha-interferon liver damage, nausea and vomiting
Pipobroman (Vercyte) Chronic granulocytic leukemia Bone marrow depressionPlicamycin (Mithracin) Testucular tumors Toxicity/damage to bone marrow, kidneys, and liverPrednisone (Meticorten) Used in adjunct therapy for palliation of May be toxic to all body systems
symptoms in lymphomas, acute leukemiaHodgkin’s disease

Procarbazine (Matulane) Hodgkin’s disease Bone marrow depression, nausea and vomitingStreptozocin (Zanosar) Islet cell carcinoma of pancreas Nausea and vomiting, toxicity to kidneysTamoxifen (Nolvadex) Advanced breast cancer in post menopausal Nausea and vomiting, ocular toxicity, hot flashesTeniposide (Vumon) Acute lymphocytic leukemia in children See EtoposideVinblastine (Velban) Breast cancer, Hodgkin’s disease, Bone marrow depression, neurotoxicity
metastatic testicular cancer

Vincristine (Oncovin) Acute leukemia, Hodgkin’s Constipation, neurotoxicity, possible tissue necrosis
disease, lymphomasGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 249

Anticlotting drugs seeAnticoagulant and
antiplatelet drugs
Anticoagulant and
Anticoagulants are drugs used to prevent clot forma-
tion or to prevent a clot that has formed from enlarging.They inhibit clot formation by blocking the action ofclotting factors or platelets. Anticoagulant drugs fall intothree categories: inhibitors of clotting factor synthesis,inhibitors of thrombin and antiplatelet drugs.
Purpose
Anticoagulant drugs reduce the ability of the blood

to form clots. Although blood clotting is essential to pre-vent serious bleeding in the case of skin cuts, clots insidethe blood vessels block the flow of blood to major organsand cause heart attacks and strokes. Although these drugsare sometimes called blood thinners, they do not actuallythin the blood. Furthermore, this type of medication willnot dissolve clots that already have formed, although thedrug stops an existing clot from worsening. However,another type of drug, used in thrombolytic

dissolve existing clots.
Anticoagulant drugs are used for a number of condi-
tions. For example, they may be given to prevent bloodclots from forming after the replacement of a heart valveor to reduce the risk of a stroke or another heart attack

after a first heart attack. They are also used to reduce thechance of blood clots forming during open heart surgeryor bypass surgery. Low doses of these drugs may begiven to prevent blood clots in patients who must stay inbed for a long time after certain types of surgery.
Because anticoagulants affect the blood’s ability to

clot, they can increase the risk of severe bleeding andheavy blood loss. It is thus essential to take these drugsexactly as directed and to see a physician regularly aslong as they are prescribed.
Anticoagulant drugs, also called anticlotting drugs
or blood thinners, are available only with a physician’sprescription. They come in tablet and injectable forms.They fall into three groups:
• Inhibitors of clotting factor synthesis. These anticoagu-

lants inhibit the production of certain clotting factors inthe liver. One example is warfarin (brand name:coumadin).
• Inhibitors of thrombin. Thrombin inhibitors interfere
with blood clotting by blocking the activity of throm-bin. They include heparin, lepirudin (Refludan).
• Antiplatelet drugs. Antiplatelet drugs interact with
platelets, which is a type of blood cell, to blockplatelets from aggregating into harmful clots. Theyinclude: aspirin , ticlopidine (Ticlid), clopidogrel (Plav-

ix), tirofiban (Aggrastat), and eptifibatide (Integrilin).
anticoagulant drug and the medical condition for which itis prescribed. The prescribing physician or the pharmacistwho filled the prescription can provide information con-cerning the correct dosage. Usually, the physician willadjust the dose after checking the patient’s clotting time.
Anticoagulant drugs must be taken exactly as direct-

ed by the physician. Larger or more frequent dosesshould not be taken, and the drug should also not betaken for longer than prescribed. Taking too much of this
medication can cause severe bleeding. Anticoagulants

should also be taken on schedule. A record of each doseshould be kept as it is taken. If a dose is missed, it shouldbe taken as soon as possible followed by the regular doseschedule. However, a patient who forgets to take amissed dose until the next day should not take the misseddose at all and should not double the next dose, as thiscould lead to bleeding. A record of all missed dosesshould be kept for the prescribing physician who shouldbe informed at the scheduled visits.

Persons who take anticoagulants should see a physi-
cian regularly while taking these drugs, particularly atthe beginning of therapy. The physician will order peri-odic blood tests to check the blood’s clotting ability. Theresults of these tests will help the physician determinethe proper amount of medication to be taken each day.
Time is required for normal clotting ability to return

after anticoagulant treatment. During this period, patientsmust observe the same precautions they observed whiletaking the drug. The length of time needed for the bloodto return to normal depends on the type of anticoagulantdrug that was taken. The prescribing physician will adviseas to how long the precautions should be observed.
People who are taking anticoagulant drugs should

tell all physicians, dentists, pharmacists, and other med-ical professionals who provide medical treatments or ser-vices to them that they are taking such a medication.
GALE ENCYCLOPEDIA OF MEDICINE 2 250Anticoagulant and antiplatelet drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 250

They should also carry identification stating that they are
using an anticoagulant drug.
Other prescription drugs or over-the-counter medi-
cine—especially aspirin—should be not be taken withoutthe prescribing physician being informed.
Because of the risk of heavy bleeding, anyone who

takes an anticoagulant drug must take care to avoidinjuries. Sports and other potentially hazardous activitiesshould be avoided. Any falls, blows to the body or head,or other injuries should be reported to a physician, asinternal bleeding may occur without any obvious symp-toms. Special care should be taken in shaving and inbrushing and flossing the teeth. Soft toothbrushes shouldbe used and the flossing should be very gentle. Electricrazors should be used instead of a blade.

Alcohol can change the way anticoagulant drugs
affect the body. Anyone who takes this medicine shouldnot have more than one to two drinks at any time andshould not drink alcohol every day.
People with specific medical conditions or who are
taking certain other medicines can have problems if theytake anticoagulant drugs. Before taking these drugs, theprescribing physician should be informed about any ofthese conditions:

to anticoagulants in the past should let his or her physi-cian know before taking the drugs again. The physicianshould also be told about any allergies to beef, pork, or
other foods; dyes; preservatives; or other substances.
PREGNANCY. Anticoagulants may cause many seri-
ous problems if taken during pregnancy . Birth defects ,

severe bleeding in the fetus, and other problems thataffect the physical or mental development of the fetus ornewborn are possible. The mother may also experiencesevere bleeding if she takes anticoagulants during preg-nancy, during delivery, or even shortly after delivery.Women should not take start taking anticoagulants dur-ing pregnancy and should not become pregnant whiletaking it. Any woman who becomes pregnant or suspectsthat she has become pregnant while taking an anticoagu-lant should

pregnant while taking an anticoagu-lant should check with her physician immediately.

BREASTFEEDING. Some anticoagulant drugs may
pass into breast milk. Blood tests can be done on nursingbabies to see whether the drug is causing any problems.If it is, other medication may be prescribed to counteractthe effects of the anticoagulant drug.
coagulant drugs, people should inform their physicianabout anymedical problems they have. They should also

let the physician who prescribed the medicine know ifthey are being treated by any other medical physician ordentist. In addition, people who will be taking anticoagu-lant drugs should let their physician know if they haverecently had any of the following:
•fever lasting more than one to two days
• severe or continuing diarrhea
• heavy or unusual menstrual bleeding
• insertion of an intrauterine contraceptive device ( IUD)

• falls, injuries, or blows to the body or head• any type of surgery, including dental surgery• spinal anesthesia• radiation treatment
USE OF CERTAIN FOODS AND MEDICINES. Many
foods and drugs may affect the way the anticoagulantdrugs work or may increase the risk of side effects.
The most common minor side effects are bloating or
gas. These problems usually go away as the body adjuststo the drug and do not require medical treatment.

More serious side effects may occur, especially if
excessive anticoagulant is taken. If any of the followingside effects occur, a physician should be notified imme-diately:
• bleeding gums
• sores or white spots in the mouth or throat• unusual bruises or purplish areas on the skin
• unexplained nosebleeds
• unusually heavy bleeding or oozing from wounds
• unexpected or unusually menstrual bleeding• blood in the urine• cloudy or dark urine• painful or difficult urination or sudden decrease in

amount of urine
• black, tarry, or bloody stools
• coughing up blood
• vomiting blood or something that looks like coffee
grounds
• constipation•pain or swelling in the stomach or abdomen
• back pain• stiff, swollen, or painful joints
GALE ENCYCLOPEDIA OF MEDICINE 2 251Anticoagulant and antiplatelet drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 251

• painful, bluish or purplish fingers or toes
• puffy or swollen eyelids, face, feet, or lower legs
• changes in the color of the face• skin rash, itching , or hives
• severe or continuing headache
• sore throat and fever, with or without chills• breathing problems or wheezing
• tightness in the chest
• unusual tiredness or weakness• weight gain
In addition, patients taking anticoagulant drugs

should check with their physicians as soon as possible ifany of these side effects occur:
• nausea or vomiting
• diarrhea
• stomach pain or cramps
unusual symptoms while taking anticoagulant drugsshould get in touch with his or her physician.
Anticoagulants may interact with many other med-

ications. When this happens, the effects of one or bothof the drugs may change or the risk of side effects maybe increased. Anyone who takes anticoagulants should
inform the prescribing physician about other prescrip-tion or nonprescription (over-the-counter medicines) heKEY TERMS
Anticoagulant —Drug used to prevent clot forma-

tion or to prevent a clot that has formed fromenlarging. Anticoagulant drugs inhibit clot forma-tion by blocking the action of clotting factors orplatelets. Anticoagulant drugs fall into three groups:inhibitors of clotting factor synthesis, inhibitors ofthrombin and antiplatelet drugs.
Antiplatelet drug —Drug that inhibits platelets from
aggregating to form a plug. They are used to preventclotting and alter the natural course of atherosclerosis.

Atherosclerosis —Condition characterized by deposits
of fatty plaque in the arteries.Clot—A soft, semi-solid mass that forms when
blood gels.
Platelet —A small, disk-shaped body in the blood
that has an important role in blood clotting: theyform the initial plug at the rupture site of a bloodvessel.
Thrombin —Thrombin is a protein produced by the
body. It is a specific clotting factor that plays animportant role in the blood clotting process.
Thrombin inhibitor —Thrombin inhibitors are one

type of anticoagulant medication, used to help pre-vent formation of harmful blood clots in the bodyby blocking the activity of thrombin.
or she is taking—even aspirin, laxatives, vitamins, and
antacids.
Diet also affects the way anticoagulant drugs work

in the body. A normal, balanced diet should be followedevery day while taking such medication. No dietarychanges should be made without informing first the pre-scribing physician, who should also be told of any illnessor other condition interfering with the ability to eat nor-mally. Diet is a very important consideration because theamount of vitamin K in the body affects how anticoagu-lant drugs work. Dicoumarol and warfarin act by reduc-ing the effects of vitamin K. Vitamin K is found in

the effects of vitamin K. Vitamin K is found in meats,dairy products, leafy, green vegetables, and some multi-ple vitamins and nutritional supplements. For the drugs

to work properly, it is best to have the same amount ofvitamin K in the body all the time. Foods containing vita-min K in the diet should not be increased or decreasedwithout consulting with the prescribing physician. If thepatient takes vitamin supplements, he should check thelabel to see if it contains vitamin K. Because vitamin K isalso produced by intestinal bacteria, a severe case ofdiarrhea or the use of laxatives may also alter a person’s
vitamin K levels.

Anticonvulsant drugs
Anticonvulsant drugs are medicines used to prevent
or treat convulsions (seizures).
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Purpose
Anticonvulsant drugs are used to control seizures in
people with epilepsy. Epilepsy is not a single disease—itis a set of symptoms that may have different causes indifferent people. The common thread is an imbalance inthe brain’s electrical activity. This imbalance causesseizures that may affect part or all of the body and mayor may not cause a loss of consciousness. Anticonvulsantdrugs act on the brain to reduce the frequency and severi-ty of seizures.

Some cases of epilepsy are brought on by head
injuries, brain tumors or infections, or metabolic prob-lems such as low blood sugar. But in some people withepilepsy, the cause is not clear.
Anticonvulsant drugs are an important part of the
treatment program for epilepsy. Different kinds of drugsmay be prescribed for different types of seizures. In addi-tion to taking medicine, patients with epilepsy should getenough rest, avoid stress , and practice good health habits.

Some physicians believe that giving the drugs to
children with epilepsy may prevent the condition fromgetting worse in later life. However, others say the effectsare the same, whether treatment is started early or later inlife. Determining when treatment begins depends on thephysician and his assessment of the patient’s symptoms.
Physicians also prescribe certain anticonvulsant
drugs for other conditions, including bipolar disorder
and migraine headaches.

Anticonvulsant drugs may be divided into several
classes. The hydantoins include pheytoin (Dilantin) andmephenytoin (Mesantoin.) Ther succimides include etho-suximide (Zarontin)and methsuccimide (Celontin.) Thebenzodiazepines , which are better known for their use as

tranquilizers and sedatives, include clonazepam(Klonopin), clorazepate (Tranxene) and diazepam (Vali-um.) There are also a large number of other drugs whichare not related to larger groups. These include carba-mazepine (Tegretol), valproic acid (Depakote, Depak-ene) gabapentin (Neurontin), topiramate (Topamax), fel-bamate (Felbatol) and several others. Phenobarbital hasbeen used as an anticonvulsant, and is still useful forsome patients. The drugs are available only with a physi-cian’s

The drugs are available only with a physi-cian’s prescription and come in tablet, capsule, liquid,and “sprinkle” forms.

anticonvulsant, its strength, and the type of seizures forwhich it is being taken. Check with the physician whoprescribed the drug or the pharmacist who filled the pre-
scription for the correct dosage.
ing it for several weeks or more. Gradually tapering thedose may reduce the chance of withdrawal effects.
Do not change brands or dosage forms of this medi-

cine without checking with a pharmacist or physician. If aprescription refill does not look like the original medicine,check with the pharmacist who filled the prescription.
Patients on anticonvulsant drugs should see a physi-
cian regularly while on therapy, especially during thefirst few months. The physician will check to make surethe medicine is working as it should and will noteunwanted side effects. The physician may also need toadjust the dosage during this period.

Valproic acid can cause serious liver damage, espe-
cially in the first 6 months of treatment. Children are par-ticularly at risk, but anyone taking this medicine shouldsee their physician regularly for tests of liver function andshould be alert to symptoms of liver damage, such as yel-low skin and eyes, facial swelling, loss of appetite, gener-al feeling of illness, loss of appetite, and vomiting. If liverproblems are suspected, call a physician immediately.

Felbatol has caused serious liver damage and aplas-
tic anemia , a condition in which the bone marrow stops
producing blood cells. Patients taking this drug shouldhave regular blood counts, and should stop taking thedrug if there are too few red blood cells.
While taking anticonvulsant drugs, do not start or
stop taking any other medicines without checking with aphysician. The other medicines may affect the way theanticonvulsant medicine works.
Because anticonvulsant drugs work on the central

nervous system, they may add to the effects of alcoholand other drugs that slow down the central nervous sys-tem, such as antihistamines , cold medicine, allergy
medicine, sleep aids, other medicine for seizures, tran-quilizers, some pain relievers, and muscle relaxants .
Anyone taking anticonvulsant drugs should check withhis or her physician before drinking alcohol or taking anymedicines that slow the central nervous system.

Anticonvulsant drugs may interact with medicines
used during surgery, dental procedures, or emergencytreatment. These interactions could increase the chanceof side effects. Anyone who is taking anticonvulsantdrugs should be sure to tell the health care professional incharge before having any surgical or dental procedures orreceiving emergency treatment.
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Some people feel drowsy, dizzy, lightheaded, or less
alert when using these drugs, especially when they firstbegin taking them or when their dosage is increased.Anyone who takes anticonvulsant drugs should not drive,use machines or do anything else that might be danger-ous until they have found out how the drugs affect them.
Anticonvulsant drugs may affect the results of certain

medical tests. Before having medical tests, people whotake anticonvulsant drugs should make sure that the med-ical professional in charge knows what they are taking.
Children may be more likely to have certain side

effects from anticonvulsant drugs, such as behaviorchanges; tender, bleeding, or swollen gums; enlargedfacial features; and excessive hair growth. Problems withthe gums may be prevented by regularly brushing andflossing, massaging the gums, and having the teethcleaned every 3 months whether the patient is a child oran adult.
Children who take high doses of this medicine for a
long time may have problems in school.

anticonvulsant drugs. This may increase the chance ofside effects and overdoses.
taking certain other medicines can have problems if theytake anticonvulsant drugs. Before taking these drugs, besure to let the physician know about any of these condi-tions:

to anticonvulsant drugs or to tricyclic antidepressantssuch as imipramine (Tofranil) or desipramine (Nor-pramin) in the past should let his or her physician knowbefore taking the drugs again. The physician should alsobe told about any allergies to foods, dyes, preservatives,
PREGNANCY. Birth defects have been reported in
babies born to mothers who took anticonvulsant drugsduring pregnancy . Women who are pregnant or who

may become pregnant should check with their physiciansabout the safety of using anticonvulsant drugs duringpregnancy.
Some anticonvulsant drugs taken during pregnancy
may cause bleeding problems in the mother during deliv-ery and in the baby after delivery. This problem can beavoided by giving vitamin K to the mother during deliv-ery and to the baby after birth.
Pregnancy may affect the way the body absorbs anti-

convulsant drugs. Women who are prone to seizures mayhave more seizures during pregnancy, even though they
are taking their medicine regularly. If this happens, theyshould check with their physicians about whether thedose needs to be increased.
BREASTFEEDING. Some anticonvulsant drugs pass

into breast milk and may cause unwanted effects in babieswhose mothers take the medicine. Women who arebreastfeeding should check with their physicians aboutthe benefits and risks of using anticonvulsant drugs.
DIABETES. Anticonvulsant drugs may affect blood
sugar levels. Patients with diabetes who notice changesin the results of their urine or blood tests should checkwith their physicians.

convulsant drugs, people with any of these medical prob-lems should make sure their physicians are aware of theirconditions:
• liver disease• kidney disease
• heart or blood vessel disease• blood disease• brain disease• problems with urination• current or past alcohol abuse• behavior problems• diabetes mellitus•glaucoma
• porphyria• systemic lupus erythematosus
•fever higher than 101°F (38.3°C) for more than 24
hours

hours
USE OF CERTAIN MEDICINES. Taking anticonvulsant
The most common side effects are constipation ,
mild nausea or vomiting, and mild dizziness , drowsiness,
or lightheadedness. These problems usually go away asthe body adjusts to the drug and do not require medicaltreatment. Less common side effects, such as diarrhea ,

sleep problems, aching joints or muscles, increased sen-sitivity to sunlight, increased sweating, hair loss, enlarge-ment of facial features, excessive hair growth, muscletwitching, and breast enlargement in males also may
GALE ENCYCLOPEDIA OF MEDICINE 2 254Anticonvulsant drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 254

occur and do not need medical attention unless they per-
sist or are troublesome.
Other side effects may need medical attention. If any
of these side effects occur, check with a physician assoon as possible:
• clumsiness or unsteadiness
• slurred speech or stuttering• trembling
• unusual excitement, irritability, or nervousness
• uncontrolled eye movements
• blurred or double vision
• mood or mental changes• confusion
• increase in seizures

• bleeding, tender, or swollen gums• skin rash or itching
• enlarged glands in neck or armpits
• muscle weakness or pain•f e v e r
Other side effects are possible. Anyone who has
unusual symptoms after taking anticonvulsant drugsshould get in touch with his or her physician.
Some anticonvulsant drugs should not be taken
within two to three hours of taking antacids or medicine

for diarrhea. These medicines may make the anticonvul-sant drugs less effective. Ask the pharmacist or physicianfor more information.
Birth control pills may not work properly when anti-
convulsant drugs are being taken. To prevent pregnancy,ask the physician or pharmacist if additional methods ofbirth control should be used while taking anticonvulsantdrugs.
Anticonvulsant drugs may interact with many other

medicines. When this happens, the effects of one or bothof the drugs may change or the risk of side effects maybe greater. Anyone who takes anticonvulsant drugsshould let the physician know all other medicines he orshe is taking. Among the drugs that may interact withcertain anticonvulsant drugs are:
• airway opening drugs ( bronchodilators ) such as

aminophylline, theophylline (Theo-Dur and otherbrands), and oxtriphylline (Choledyl and other brands)
• medicines that contain calcium, such as antacids and
calcium supplementsKEY TERMS

Porphyria —A disorder in which porphyrins build
up in the blood and urine.
Porphyrin —A type of pigment found in living
things, such as chlorophyll which makes plantsgreen or hemoglobin which makes blood red.
Seizure —A sudden attack, spasm, or convulsion.
disease with many symptoms, including weakness,fatigue, joint pain, sores on the skin, and problemswith the kidneys, spleen, and other organs.

• blood thinning drugs
• caffeine• antibiotics such as clarithromycin (Biaxin), erythro-
mycins , and sulfonamides (sulfa drugs)
• disulfiram (Antabuse), used to treat alcohol abuse
• fluoxetine (Prozac)
• monoamine oxidase inhibitors (MAO inhibitors) such

as phenelzine (Nardil) or tranylcypromine (Parnate),used to treat conditions including depression andParkinson’s disease
• tricyclic antidepressants such as imipramine (Tofranil)
or desipramine (Norpramin)
• corticosteroids• acetaminophen (Tylenol)
• aspirin
• female hormones (estrogens)
• male hormones (androgens)
• cimetidine (Tagamet)
GALE ENCYCLOPEDIA OF MEDICINE 2 255Anticonvulsant drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 255

• central nervous system (CNS) depressants such as med-
icine for allergies, colds, hay fever, and asthma ; seda-
tives; tranquilizers; prescription pain medicine; musclerelaxants; medicine for seizures; sleep aids; barbitu-
rates ; and anesthetics
• alcohol• other anticonvulsant drugs

interact with anticonvulsant drugs. Be sure to check witha physician or pharmacist before combining anticonvul-sant drugs with any other prescription or nonprescription(over-the-counter) medicine.
Resources
Chadwick, David and Peter C. Rubin. “Case for Early Treat-
ment Is Not Established.” British Medical Journal 310
(January 21, 1995): 177.
Reynolds, E.H. “Do Anticonvulsant Drugs Alter the Natural

Course of Epilepsy? Treatment Should Be Started asEarly as Possible.” British Medical Journal 310 (January
21, 1995): 176.
American Epilepsy Society. 638 Prospect Avenue, Hartford,
CT 06105. (203) 232-4825.
Epilepsy Foundation of America. 4351 Garden City Drive,
#406, Landover, MD 20785. (800) 332-1000.
National Institute of Neurological Disorders and Stroke. P.O.
Box 5801, Bethesda, MD 20824. (301) 496-5751.
Antidepressant drugs

Antidepressant drugs are medicines that relieve
symptoms of depressive disorders .
Purpose
Depressive disorders may be either unipolar (depres-
sion alone) or bipolar (depression alternating with peri-ods of extreme excitation). The formal diagnosis requiresa cluster of symptoms, lasting at least two weeks. Thesesymptoms include, but are not limited to mood changes,insomnia or hypersomnia, and diminished interest in

daily activities. The symptoms are not caused by anymedical condition, drug side effect, or adverse life event.The condition is severe enough to cause clinically signif-icant distress or impairment in social, occupational, orother important areas of functioning.Secondary depression, depression caused by unfa-
vorable life events, is normally self limiting, and may bebest treated with cognitive/behavioral therapy rather thandrugs.
Antidepressant agents act by increasing the levels of

excitatory neurostransmitters. The main types of antide-pressant drugs in use today are:
• tricyclic antidepressants, such as amitriptyline (Elavil),
imipramine (Tofranil), nortriptyline (Pamelor)
•selective serotonin reuptake inhibitors (SSRIs or
serotonin boosters), such as fluoxetine (Prozac), parox-etine (Paxil), and sertraline (Zoloft)
•monoamine oxidase inhibitors (MAO inhibitors),
such as phenelzine (Nardil), and tranylcypromine (Par-nate)

• tetracyclic compounds and atypical antidepressants
which do not fall into any of the above categories
Selective serotonin reuptake inhibitors maintain lev-

els of the excitatory neurohormone serotonin in thebrain. They do not alter levels of norepinephrine. Thesehave become the drugs of choice for a variety of psychi-atric disorders, primarily because of their low incidenceof severe side effects as compared with other drugs inthis therapeutic class. SSRIs show similar actions andside effect profiles, but may vary in duration of action.
Tricyclic compounds, identified by their chemical

structure containing three carbon rings, are an older classof antidepressants. Although generally effective, theyhave a high incidence of anticholinergic effects, notablydry mouth and dry eyes, which can cause discomfort.

They also cause cardiac arrythmias. Because tricyclicsact on both serotonin and norepinephrine, they may havesome value in treatment of patients who fail to respond toSSRIs. Drugs in this class are often available at lowprices, which may be significant when cost is a majorfactor in treatment. They have also been found useful incontrol of some neurologic pain syndromes.
Tricyclic antidepressants are similar, but may vary in
severity of side effects, most notably the degree of seda-

tion and the extent of the anticholinergic effects.
Tetracyclic compounds and atypical antidepressants
are chemically distinct from both the major groups andeach other. Although maprotilene (no brand name, mar-keted in generic form only) and mirtazepine (Remeron)are similar in chemical structures, they differ in their bal-ance of activity on serotonine and norepinephrine levels.
Monoamine oxidase inhibitors (phenelzine [Nardil],
tranylcypromine [Parnate]) have largely been supplanted

GALE ENCYCLOPEDIA OF MEDICINE 2 256Antidepressant drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 256

in therapy because of their high risk of severe adverse
effects, most notably severe hypertension . They act by
inhibiting the enzyme monoamine oxidase, which isresponsible for the metabolism of the stimulatory neuro-hormones norepinephrine, epinephrine, dopamine, andserotonin. The MAOIs are normally reserved for patientswho are resistant to safer drugs. Two drugs, eldepryl(Carbex, used in treatment of Parkinson’s disease ) and
the herb, St. John’s wort , have some action against

monoamine oxidase B, and have shown some value asanti-depressants. They do not share the same risks as thenon-selective MAO inhibitors.
All antidepressant agents, regardless of their struc-
ture, have a slow onset of action, typically three to fiveweeks. Although adverse effects may be seen as early asthe first dose, significant therapeutic improvement isalways delayed. Similarly, the effects of antidepressantswill continue for a similar length of time after the drugshave been discontinued.

Dose varies with the specific drug and patient. Con-
sult specialized references.
Antidepressants have many significant cautions and
adverse effects. Although a few are listed here, specificreferences should be consulted for more complete infor-mation.
SSRIs. The most common side effect of SSRIs is exci-

tation and insomnia. Excitation has been reported in over20% of patients, and insomnia in 33%. Significant weightloss has been frequently reported, but most commonly inpatients who are already underweight. SSRIs may causesome sedation, and patients should be cautioned not to per-form tasks requiring alertness until they have evaluated the
effects of these drugs. SSRIs are pregnancy category C

drugs. Most SSRIs are excreted in breast milk, and therehave been anecdotal reports of somnolence in infantswhose mothers were taking SSRIs while breastfeeding.
Tricyclic antidepressants. Amoxepine (not marketed

by brand, generic available), although a tricyclic antide-pressant rather than a neuroleptic (major tranquilizer),displays some of the more serious effects of the neu-roleptics, including tardive dyskinesias (drug inducedinvoluntary movements) and neuroleptic malignant syn-drome, a potentially fatal syndrome whose symptomsinclude high fever , altered mental status, irregular pulse

or blood pressure, and changes in heart rate. Theseadverse effects have not been reported with other tri-cyclic antidepressants.
The most common adverse effects of tricyclic antide-
pressants are sedation and the anticholinergic effects,such as dry mouth, dry eyes, and difficult urination. Alter-ations in heartbeat are also common, and may progress tocongestive heart failure ,stroke , and sudden death .
Tricyclic antidepressants are in pregnancy categories

C or D, although there have been no formal studies of thedrugs on fetal development. There are no studies ofeffects on newborns, but some anecdotal reports of mal-formations have resulted from animal studies. The drugsare excreted in breast milk.
Monoamine oxidase inhibitors. The greatest risk

associated with these drugs is a hypertensive crisis whichmay be fatal and most often occurs when the drugs aretaken with interacting foods or drugs. More commonadverse reactions may include low blood pressure andslowing of heartbeat. Sedation and gastrointestinal distur-bances are also common. MAOIs are in pregnancy cate-gory C. Safety in breast feeding has not been established.
GALE ENCYCLOPEDIA OF MEDICINE 2 257Antidepressant drugs

Antidepressant Drugs
Desyrel (trazodone hydrochloride) Allergic skin reactions, blurred vision, decreased appetite, fluid retention, headache

Effexor (venlafaxine hydrochloride) Diarrhea, dizziness, gas, headache, insommia, rash, vomitingElavil (amitriptyline hydrochloride) Constipation, idzziness, high blood pressure, fever, nausea, rash, weight gain or lossNardil (phenelzine sulfate) Dry mouth, fatigue, headache, muscle spasms, tremorsNorpramin (desipramine hydrochloride) Blurred vision, cramps, hallucinations, hair loss, vomitingPamelor (nortriptyline hydrochloride) Diarrhea, fatigue, headache, decreased coordinationPaxil

fatigue, headache, decreased coordinationPaxil (paroxetine hydrochloride) Cold symptoms, drowsiness, nervousness, stomach painProzac (fluoxetine hydrochloride) Bronchitis, drowsiness, fatigue, nausea, tremorsSinequan (doxepin hydrochloride) Bruising, constipation, fluid retention, itching, increased heartbeatSurmontil (trimipramine maleate) Disorientation, flushing, headache, nausea, vomitingTofranil (imipramine hydrochloride) Bleeding sores, fever, hives, decreased coordinationTravil Asthma,

hives, decreased coordinationTravil Asthma, diarrhea, dizziness, fatigue, seizuresWellbutrin (bupropion hydrochloride) Agitation, dry mouth, headache, nausea, rashZoloft (sertraline) Diarrhea, fainting, gas, headache, nervousnessGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 257

Tetracyclics and atypicals. Because these drugs are
individual, there are no group patterns of adverse reac-tions. Consult specific references.
The antidepressants have many drug interactions,
some severe. Although a few are listed here, specific refer-ences should be consulted for more complete information.
SSRIs should not be administered with MAOIs.

Allow a wash-out period of about four weeks beforeswitching from one class of drugs to the other. Allow fiveweeks if switching from fluoxetine (Prozac) to an MAOI.
MAOIs have many interactions; however the best

known are those with foods containing the amino acid tyra-mine. These include aged cheese, chianti wine, and manyothers. Patients and providers should review the MAOI dietrestrictions before using or prescribing these drugs.Because of the severity of MAOI interactions, all additionsto the patient’s drug regimen should be reviewed with care.
Tricyclic compounds have many interactions, and

specialized references should be consulted. Specificallyavoid other drugs with anticholinergic effects. Tricyclicsshould not be taken with the antibiotics grepafloxacin
and sprafloxacin, since the combination may cause seri-ous heart arrythmias.KEY TERMS
Cognitive behavioral therapy —A type of psy-
chotherapy in which people learn to recognizeand change negative and self-defeating patterns ofthinking and behavior.

Depression —A mental condition in which people
feel extremely sad and lose interest in life. Peoplewith depression may also have sleep problemsand loss of appetite and may have trouble concen-trating and carrying out everyday activities.

drugs according to their established risks for useduring pregnancy. Category A: Controlled humanstudies have demonstrated no fetal risk. CategoryB: Animal studies indicate no fetal risk, but nohuman studies; or adverse effects in animals, butnot in well-controlled human studies. Category C:No adequate human or animal studies; or adversefetal effects in animal studies, but no availablehuman data. Category D: Evidence of fetal risk,Tricyclic compounds should not be taken with the

gastric acid inhibitor cimetidine (Tagamet), since thisincreases the blood levels of the tricyclic compound.Other acid inhibiting drugs do not share this interaction.
SSRIs interact with a number of other drugs which
act on the central nervous system. Use care in combiningthese drugs with major or minor tranquilizers, or withanti-epileptic agents such as phenytoin (Dilantin) or car-bamazepine (Tegretol).
Resources
“Treatment of Depression: Drugs Alone Are Not Enough.”

HealthFacts 20 (February 1995): 189.
Antidepressants, tricyclic
Tricyclic antidepressants are medicines that relieve
mental depression.
Purpose
Since their discovery in the 1950s, tricyclic antide-
pressants have been used to treat mental depression. Likeother antidepressant drugs , they reduce symptoms such

as extreme sadness, hopelessness, and lack of energy.Some tricyclic antidepressants are also used to treatbulimia, cocaine withdrawal, panic disorder , obsessive-
compulsive disorders, certain types of chronic pain , and
bed-wetting in children.
Named for their three-ring chemical structure, tri-

cyclic antidepressants work by correcting chemicalimbalances in the brain. But because they also affectother chemicals throughout the body, these drugs mayproduce many unwanted side effects.
Tricyclic antidepressants are available only with a

physician’s prescription and are sold in tablet, capsule,liquid, and injectable forms. Some commonly used tri-cyclic antidepressants are amitriptyline (Elavil),desipramine (Norpramin), imipramine (Tofranil), nor-triptyline (Pamelor), and protriptyline (Vivactil). Differ-ent drugs in this family have different effects, and physi-cians can choose the drug that best fits the patient’s symp-toms. For example, a physician might prescribe Elavil for

GALE ENCYCLOPEDIA OF MEDICINE 2 258Antidepressants, tricyclicGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 258

a person with depression who has trouble sleeping,
because this drug is more likely to make people feel calmand sleepy. Other tricyclic antidepressants might be moreappropriate for depressed people with low energy.
The recommended dosage depends on many factors,

including the patient’s age, weight, general health andsymptoms. The type of tricyclic antidepressant and itsstrength also must be considered. Check with the physi-cian who prescribed the drug or the pharmacist whofilled the prescription for the correct dosage.
Always take tricyclic antidepressants exactly as

directed. Never take larger or more frequent doses, anddo not take the drug for longer than directed. Do not stoptaking the medicine just because it does not seem to beworking. Several weeks may be needed for its effects tobe felt. Visit the physician as often as recommended sothat the physician can check to see if the drug is workingand to note for side effects.

ing it for several weeks or more. Gradually tapering thedose may be necessary to reduce the chance of withdraw-al symptoms.
Taking this medicine with food may prevent upset
stomach.
The effects of this medicine may continue for three
to seven days after patients stop taking it. All precautionsshould be observed during this period, as well asthroughout treatment with tricyclic antidepressants.
Some people feel drowsy, dizzy, or lightheaded, when

taking these drugs. The drugs may also cause blurredvision. Anyone who takes these drugs should not drive,use machines or do anything else that might be dangerousuntil they have found out how the drugs affect them.
Because tricyclic antidepressants work on the central
nervous system, they may add to the effects of alcoholand other drugs that cause drowsiness, such as antihista-
mines , cold medicine, allergy medicine, sleep aids, medi-

cine for seizures, tranquilizers, some pain relievers, andmuscle relaxants . Anyone taking tricyclic antidepres-
sants should check with his or her physician before drink-ing alcohol or taking any drugs that cause drowsiness.
ed, dizzy, or faint when they get up after sitting or lyingdown. To lessen the problem, get up gradually and holdonto something for support if possible.Tricyclic antidepressants may interact with medi-

cines used during surgery, dental procedures, or emer-gency treatment. These interactions could increase thechance of side effects. Anyone who is taking tricyclicantidepressants should be sure to tell the health care pro-fessional in charge before having any surgical or dentalprocedures or receiving emergency treatment.
These drugs may also change the results of medical
tests. Before having medical tests, anyone taking thismedicine should alert the health care professional incharge.

This medicine may increase sensitivity to sunlight.
Even brief exposure to sun can cause a severe sunburn
or a rash. While being treated with this tricyclic antide-pressants, avoid being in direct sunlight, especiallybetween 10 
A.M. and 3 P.M.; wear a hat and tightly woven
clothing that covers the arms and legs; use a sunscreenwith a skin protection factor (SPF) of at least 15; protectthe lips with a sun block lipstick; and do not use tanningbeds, tanning booths, or sunlamps.

Tricyclic antidepressants may cause dry mouth . To
temporarily relieve the discomfort, chew sugarless gum,suck on sugarless candy or ice chips, or use saliva substi-tutes, which come in liquid and tablet forms and areavailable without a prescription.
the effects of tricyclic antidepressants. This increasedsensitivity may increase the chance of side effects.

taking certain other medicines can have problems if theytake tricyclic antidepressants. Before taking these drugs,be sure to let the physician know about any of these con-ditions:

to tricyclic antidepressants or to carbamazepine (Tegre-tol), maprotiline (Ludiomil), or trazodone (Desyrel) inthe past should let his or her physician know before tak-ing tricyclic antidepressants. The physician should alsobe told about any allergies to foods, dyes, preservatives,
PREGNANCY. Problems have been reported in babies

whose mothers took tricyclic antidepressants just beforedelivery. Women who are pregnant or who may becomepregnant should check with their physicians about thesafety of using tricyclic antidepressants.
BREASTFEEDING. Tricyclic antidepressants pass into
breast milk and may cause drowsiness in nursing babieswhose mothers take the drugs. Women who are breast-

GALE ENCYCLOPEDIA OF MEDICINE 2 259Antidepressants, tricyclicGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 259

feeding should check with their physicians before using
tricyclic antidepressants.
DIABETES. Tricyclic antidepressants may affect
blood sugar levels. Diabetic patients who notice changesin blood or urine test results while taking this medicineshould check with their physicians.
OTHER MEDICAL CONDITIONS. Before using tri-
cyclic antidepressants, people with any of these medicalproblems should make sure their physicians are aware oftheir conditions:

• current or past alcohol or drug abuse• bipolar disorder (manic-depressive illness)
• schizophrenia
• seizures (convulsions)
• heart disease
• high blood pressure• kidney disease
• overactive thyroid• stomach or intestinal problems
• enlarged prostate
• problems urinating
•glaucoma
•asthma
USE OF CERTAIN MEDICINES. Taking tricyclic anti-
depressants with certain other drugs may affect the waythe drugs work or may increase the chance of sideeffects.

The most common side effects are dizziness ,
drowsiness, dry mouth, unpleasant taste, headache , nau-
sea, mild tiredness or weakness, increased appetite orcraving for sweets, and weight gain. These problemsusually go away as the body adjusts to the drug and donot require medical treatment. Less common side effects,such as diarrhea , vomiting, sleep problems, sweating,
and heartburn also may occur and do not need medical

attention unless they do not go away or they interferewith normal activities.
• blurred vision
• eye pain• confusion
• fainting• loss of balance• swallowing problems• difficulty speaking• mask-like face• shakiness or trembling
• nervousness or restlessness

• movement problems, such as shuffling walk, stiff arms
and legs, or slow movement
• decreased sexual ability• fast or irregular heartbeat• constipation• problems urinating
Some side effects may continue after treatment with
tricyclic antidepressants has ended. Check with a physi-cian if these symptoms occur:
• headache• nausea, vomiting, or diarrhea• sleep problems, including vivid dreams• unusual excitement, restlessness, or irritability

Life-threatening reactions, such as extrememly high
blood pressure, may occur when tricyclic antidepressantsare taken with other antidepressants called monoamineoxidase (MAO) inhibitors (such as Nardil and Parnate).Do not take tricyclic antidepressants within 2 weeks oftaking a MAO inhibitor. However, a patient can take anMAO inhibitor immediately after tricyclic antidepressanttherapy is stopped by the physician. 
Tricyclic antidepressants may interact with many

other medicines. When this happens, the effects of one orboth of the drugs may change or the risk of side effectsmay be greater. Anyone who takes tricyclic antidepres-sants should let the physician know all other medicineshe or she is taking. Among the drugs that may interactwith tricyclic antidepressants are:
• Central nervous system (CNS) depressants such as
medicine for allergies, colds, hay fever , and asthma;

sedatives; tranquilizers; prescription pain medicine;muscle relaxants; medicine for seizures; sleep aids;barbiturates ; and anesthetics.
• Diet pills
GALE ENCYCLOPEDIA OF MEDICINE 2 260Antidepressants, tricyclicGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 260

• amphetamines
• medicine for overactive thyroid
• cimetidine (Tagamet)• other antidepressant drugs, including MAO inhibitors
(such as Nardil and Parnate) and antidepressants thatraise serotonin levels (such as Prozac and Zoloft)
• blood pressure medicines such as clonidine (Catapres)
and guanethidine monosulfate (Ismelin)
• disulfiram (Antabuse), used to treat alcohol abuse• major tranquilizers such as thioridazine (Mellaril) and
chlorpromazine (Thorazine)

• antianxiety drugs such as chlordiazepoxide (Librium)
and alprazolam (Xanax)
• antiseizure medicines such as carbamazaepine (Tegre-
tol) and phenytoin (Dilantin)KEY TERMS
Bulimia —An eating disorder in which a person
binges on food and then induces vomiting, uses lax-atives, or goes without food for some time.

condition. Chronic conditions often develop gradu-ally and involve slow changes.
Delusion —An abnormal mental state characterized
by the acceptance of something as true that is actu-ally false or unreal, such as the belief that one isJesus Christ.
Depression —A mental condition in which a person

feels extremely sad and loses interest in life. A per-son with depression may also have sleep problemsand loss of appetite and may have trouble concen-trating and carrying out everyday activities.

Obsessive-compulsive disorder —An anxiety disor-
der in which a person cannot prevent himself fromdwelling on unwanted thoughts, acting on urges, or
performing repetitious rituals, such as washing hishands or checking to make sure he turned off thelights.
Panic disorder —An disorder in which a person has

sudden and intense attacks of anxiety in certain sit-uations. Symptoms such as shortness of breath,sweating, dizziness, chest pain, and extreme fearoften accompany the attacks.
Prostate —A donut-shaped gland in males below
the bladder that contributes to the production ofsemen.
Schizophrenia —A severe mental disorder in which

a person loses touch with reality and may haveillogical thoughts, delusions, hallucinations, behav-ioral problems and other disturbances.
Serotonin —A natural chemical found in the brain
and other parts of the body, that carries signalsbetween nerve cells.

interact with tricyclic antidepressants. Be sure to checkwith a physician or pharmacist before combining tri-cyclic antidepressants with any other prescription or non-prescription (over-the-counter) medicine.
Antidiabetic drugs

Antidiabetic drugs are medicines that help control
blood sugar levels in people with diabetes mellitus
(sugar diabetes).
Purpose
Diabetes may be divided into type I and type II, for-
merly termed juvenile onset or insulin-dependent, and
GALE ENCYCLOPEDIA OF MEDICINE 2 261Antidiabetic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 261

maturity onset or non insulin-dependent. Type I is caused
by a deficiency of insulin production, while type II ischaracterized by insulin resistance.
Treatment of type I diabetes is limited to insulin
replacement, while type II diabetes is treatable by a num-ber of therapeutic approaches. Many cases of insulinresistance are asymptomatic due to normal increases ininsulin secretion, and others may be controlled by dietand exercise . Drug therapy may be directed towards

increasing insulin secretion, increasing insulin sensitivi-ty, or increasing insulin penetration of the cells.
Antidiabetic drugs may be subdivided into six groups:
insulin, sufonylureas, alpha-glucosidase inhibitors,biguanides, meglitinides, and thiazolidinediones.
Insulin (Humulin, Novolin) is the hormone responsi-

ble for glucose utilization. It is effective in both types ofdiabetes, since, even in insulin resistance, some sensitivi-ty remains and the condition can be treated with largerdoses of insulin. Most insulins are now produced byrecombinant DNA techniques, and are chemically identi-cal to natural human insulin. Isophane insulin suspen-sion, insulin zinc suspension, and other formulations areintended to extend the duration of action of insulin, andpermit glucose control over longer periods of

Sulfonylureas (chlorpropamide [Diabinese], tolaza-
mide [Tolinase], glipizide [Glucotrol] and others) act byincreasing insulin release from the beta cells of the pan-crease. Glimepiride (Amaryl), a member of this class,appears to have a useful secondary action in increasinginsulin sensitivity in peripheral cells.
Alpha-glucosidase inhibitors (acarbose [Precose],

miglitol [Glyset]) do not enhance insulin secretion.Rather, they inhibit the conversion of disaccharides andcomplex carbohydrates to glucose. This mechanism doesnot prevent conversion, but only delays it, reducing thepeak blood glucose levels. Alpha-glucosidase inhibitorsare useful for either monotherapy or in combination ther-apy with sulfonylureas or other hypoglycemic agents.
Metformin (Glucophage) is the only available mem-

ber of the biguanide class. Metformin decreases hepaticglucose production, decreases intestinal absorption ofglucose and increases peripheral glucose uptake and uti-lization. Metformin may be used as monotherapy, or incombination therapy with a sulfonylurea.
There are two members of the meglitinide class:

repaglinide (Prandin) and nateglitinide (Starlix). Themechanism of action of the meglitinides is to stimulateinsulin production. This activity is both dose dependentand dependent on the presence of glucose, so that thedrugs have reduced effectiveness in the presence of low

blood glucose levels. The meglitinides may be used alone,or in combination with metformin. The manufacturerwarns that nateglitinide should not be used in combina-tion with other drugs which enhance insulin secretion.
Rosiglitazone (Avandia) and pioglitazone (Actos)

and the members of the thiazolidinedione class. They actby both reducing glucose production in the liver, andincreasing insulin dependent glucose uptake in musclecells. They do not increase insulin production. Thesedrugs may be used in combination with metoformin or asulfonylurea.
Dosage must be highly individualized for all antidia-

betic agents and is based on blood glucose levels whichmust be taken regularly. Review specific literature.
Insulin. The greatest short term risk of insulin is
hypoglycemia , which may be the result of either a direct
overdose or an imbalance between insulin injection andlevel of exercise and diet. This may also occur in thepresence of other conditions which reduce the glucoseload, such as illness with vomiting and diarrhea . Treat-

ment is with glucose in the form of glucose tablets or liq-uid, although severe cases may require intravenous thera-py. Allergic reactions and skin reactions may also occur.Insulin is classified as category B in pregnancy , and is

considered the drug of choice for glucose control duringpregnancy. Insulin glargine (Lantus), an insulin analogwhich is suitable for once-daily dosing, is classified ascategory C, because there have been reported changes inthe hearts of newborns in animal studies of this drug. Thereports are essentially anecdotal, and no cause and effectrelationship has been determined. Insulin is not recom-mended during breast feeding because either low of highdoses of insulin may inhibit milk production.

highdoses of insulin may inhibit milk production. Insulinadministered orally is destroyed in the GI tract, and rep-resents no risk to the newborn.

Sulonylureas. All sulfonylurea drugs may cause
hypoglycemia. Most patients become resistant to thesedrugs over time, and may require either dose adjustmentsor a switch to insulin. The list of adverse reactions isextensive, and includes central nervous system problemsand skin reactions, among others. Hematologic reactions,although rare, may be severe and include aplastic ane-
mia and hemolytic anemia . The administration of oral

hypoglycemic drugs has been associated with increasedcardiovascular mortality as compared with treatmentwith diet alone or diet plus insulin. The sulfonylureas areclassified as category C during pregnancy, based on ani-
GALE ENCYCLOPEDIA OF MEDICINE 2 262Antidiabetic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 262

mal studies, although glyburide has not shown any harm
to the fetus and is classified as category B. Because theremay be significant alterations in blood glucose levelsduring pregnancy, it is recommended that patients beswitch to insulin. These drugs have not been fully studiedduring breast feeding, but it is recommended thatbecause their presence in breast milk might cause hypo-glycemia in the newborn, breastfeeding be avoided whiletaking sulfonylureas.

Alpha-glucosidase inhibitors are generally well tol-
erated, and do not cause hypoglycemia. The most com-mon adverse effects are gastrointestinal problems,including flatulence, diarrhea, and abdominal pain .

These drugs are classified as category B in pregnancy.Although there is no evidence that the drugs are harmfulto the fetus, it is important that rigid blood glucose con-trol be maintained during pregnancy, and pregnantwomen should be switched to insulin. Alpha-glucosidaseinhibitors may be excreted in small amounts in breastmilk, and it is recommended that the drugs not be admin-istered to nursing mothers.
Metformin causes gastrointestinal reactions in about

a third of patients. A rare, but very serious, reaction tometformin is lactic acidosis, which is fatal in about 50%of cases. Lactic acidosis occurs in patients with multiplemedical problems, including renal insufficiency. The riskmay be reduced with careful renal monitoring, and care-ful dose adjustments to metformin. Metformin is catego-ry B during pregnancy. There have been no carefullycontrolled studies of the drug during pregnancy, but thereis no evidence of fetal harm from animal studies.

no evidence of fetal harm from animal studies. It isimportant that rigid blood glucose control be maintainedduring pregnancy, and pregnant women should beswitched to insulin. Animal studies show that metforminis excreted in milk. It is recommended that metforminnot be administered to nursing mothers.

Meglitinides. These drugs are generally well tolerat-
ed, with an adverse event profile similar to placebo. Thedrugs are classified as category C during pregnancy,based on fetal abnormalities in rabbits given about 40times the normal human dose. It is important that rigidblood glucose control be maintained during pregnancy,

and pregnant women should be switched to insulin. It isnot known whether the meglitinides are excreted inhuman milk, but it is recommended that these drugs notbe given to nursing mothers.
Thiazolidinediones. These drugs are generally well

tolerated, however they are structurally related to an ear-lier drug, troglitazone, which was associated with liverfunction problems. It is strongly recommended that allpatients treated with pioglitazone or rosiglitazone haveregular liver function monitoring. The drugs are classi-fied as pregnancy category C, based on evidence of inhi-bition of fetal growth in rats given more than four timesthe normal human dose. It is important that rigid bloodglucose control be maintained during pregnancy,

control be maintained during pregnancy, andpregnant women should be switched to insulin. It is notknown whether the thiazolidinediones are excreted inhuman milk, however they have been identified in themilk of lactating rats. It is recommended that these drugsnot be administered to nursing mothers.

The sulfonylureas have a particularly long list of
drug interactions, several of which may be severe.Review specific literature for these drugs.
The actions of oral hypoglycemic agents may be
strengthened by highly protein bound drugs, includingNSAIDs, salicylates, sulfonamides , chloramphenicol,
coumarins, probenecid, MAOIs, and beta blockers .
Review the specific literature of each drugs for pos-
sible drug-drug or food-drug interactions.
Resources

Resources
Hingley, Audrey. “Diabetes Demands a Trial of Treatments.”
FDA Consumer 31 (May-June 1997): 33.
American Diabetes Association. ADA National Service Center,
1660 Duke Street, Alexandria, V A 22314. (800)232-3472.<http://www.diabetes.org>.
GALE ENCYCLOPEDIA OF MEDICINE 2 263Antidiabetic drugs
Antidiabetic Drugs
Brand Name(Generic Name) Possible Common Side Effects Include:
Diabinese (chlorpropamide) Diarrhea, nausea, loss of appetite

Glucotrol (glipizide) Dizziness, fatigue, headache, nervousness*Insulin Mild allergic reactions, decreased blood pressure, rash, shortness of breathMicronase (glyburide) Nausea, heartburn, bloatingorinase (tolbutamide) Nausea, heartburn, bloating
*Insulin is the generic name for several brands which may be animal-based, human-based, or synthetic.GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 263

National Diabetes Information Clearinghouse. 1 Information
Way, Bethesda, MD 20892-3560. (301)654-3327. ndic@info.niddk.nih.gov.
OTHER
eases. <http://www.niddk.nih.gov>.
Antidiarrheal drugs
Antidiarrheal drugs are medicines that relieve diarrhea .KEY TERMS
Blood sugar —The concentration of glucose in the
blood.
Glucose —A simple sugar that serves as the body’s
main source of energy.

Hormone —A substance that is produced in one
part of the body, then travels through the blood-stream to another part of the body where it has itseffect.
Metabolism —All the physical and chemical
changes that occur in cells to allow growth andmaintain body functions. These include processesthat break down substances to yield energy andprocesses that build up other substances necessaryfor life.

risks. Category X: Evidenceof fetal risk. Risks outweigh any benefits.

Salicylates —A group of drugs that includes aspirin
and related compounds. Salicylates are used torelieve pain, reduce inflammation, and lower fever.
Antidiarrheal drugs help control diarrhea and some

of the symptoms that go along with it. An average,healthy person has anywhere from three bowel move-ments a day to three a week, depending on that person’sdiet. Normally the stool (the material that is passed in abowel movement) has a texture something like clay. Withdiarrhea, bowel movements may be more frequent, andthe texture of the stool is thin and sometimes watery.
Diarrhea is not a disease, but a symptom of some other

problem. The symptom may be caused by eating or drink-ing food or water that is contaminated with bacteria, virus-es, or parasites, or by eating something that is difficult todigest. People who have trouble digesting lactose (milksugar), for example, may get diarrhea if they eat dairyproducts. Some cases of diarrhea are caused by stress ,
while others are brought on by taking certain medicines.
Antidiarrheal drugs work in several ways. The drug

loperamide, found in Imodium A-D, for example, slowsthe passage of stools through the intestines. This allowsmore time for water and salts in the stools to beabsorbed back into the body. Adsorbents, such as atta-pulgite (found in Kaopectate) pull diarrhea-causing sub-stances from the digestive tract. However, they may alsopull out substances that the body needs, such asenzymes and nutrients. Bismuth subsalicylate, the ingre-dient in Pepto-Bismol, decreases the secretion of fluidinto the

decreases the secretion of fluidinto the intestine and inhibits the activity of bacteria. Itnot only controls diarrhea, but relieves the cramps thatoften accompany diarrhea.

These medicines come in liquid, tablet, caplet, and
chewable tablet forms and can be bought without aphysician’s prescription.
The dose depends on the type of antidiarrheal drug.
Read and follow the directions on the product label. Forquestions about dosage, check with a physician or phar-macist. Never take larger or more frequent doses, and donot take the drug for longer than directed.
Diarrhea usually improves within 24-48 hours. If the

problem lasts longer or if it keeps coming back, diarrheacould be a sign of a more serious problem. Anyone whohas any of the symptoms listed below should get medicalattention as soon as possible:
• diarrhea that lasts more than two days or gets worse
GALE ENCYCLOPEDIA OF MEDICINE 2 264Antidiarrheal drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 264

•f e v e r
• blood in the stool• vomiting• cramps or tenderness in the abdomen• Signs of dehydration , such as decreased urination,
dizziness or lightheadedness, dry mouth , increased
thirst, or wrinkled skin
Do not use antidiarrheal drugs for more than two
days unless told to do so by a physician.
Severe, long-lasting diarrhea can lead to dehydra-
tion. In such cases, lost fluids and salts, such as calcium,sodium, and potassium, must be replaced.
People older than 60 should not use attapulgite

(Kaopectate, Donnagel, Parepectolin), but may use otherkinds of antidiarrheal drugs. However, people in this agegroup may be more likely to have side effects, such assevere constipation , from bismuth subsalicylate. Ask the
pharmacist for more information.
Bismuth subsalicylate may cause the tongue or the

stool to temporarily darken. This is harmless. However,do not confuse this harmless darkening of the stool withthe black, tarry stools that are a sign of bleeding in theintestinal tract.
Children with flu or chicken pox should not be given
bismuth subsalicylate. It can lead to Reye’s syndrome ,a

life-threatening condition that affects the liver and centralnervous system. To be safe, never give bismuth subsalicy-late to a child under 16 years without consulting a physi-cian. Children may have unpredictable reactions to otherantidiarrheal drugs. Loperamide should not be given to chil-dren under six years and attapulgite should not be given tochildren under three years unless directed by a physician.
Anyone who has a history of liver disease or who

has been taking antibiotics should check with his or her
physician before taking the antidiarrheal drug lop-eramide. A physician should also be consulted beforeanyone with acute ulcerative colitis or anyone who has
been advised to avoid constipation uses the drug.
Loperamide should not be used by people whose
diarrhea is caused by certain infections, such as salmo-nella or shigella. To be safe, check with a physicianbefore using this drug.

Anyone who has a medical condition that causes
weakness should check with a physician about the bestway to treat diarrhea.
Before taking antidiarrheal drugs, be sure to let the
physician know about any of these conditions:ALLERGIES. Anyone who has had unusual reactions
to aspirin or other drugs containing salicylates should

check with a physician before taking bismuth subsalicy-late. Anyone who has developed a rash or other unusualreactions after taking loperamide should not take thatdrug again without checking with a physician. The physi-cian should also be told about any allergies to foods,
dyes, preservatives, or other substances.
PREGNANCY AND BREASTFEEDING. Women who are

pregnant or breastfeeding should check with their physi-cians before using antidiarrheal drugs. They should alsoask advice on how to replace lost fluids and salts.
OTHER MEDICAL CONDITIONS. Before using
antidiarrheal drugs, people with any of these medicalproblems should make sure their physicians are aware oftheir conditions:
• dysentery• gout• hemophilia or other bleeding problems
• stomach ulcer• severe colitis

USE OF CERTAIN MEDICINES. Taking antidiarrheal
The most common side effects of attapulgite are con-

stipation, bloating, and fullness. Bismuth subsalicylatemay cause ringing in the ears, but that side effect is rare.Possible side effects from loperamide include skin rash,constipation, drowsiness, dizziness, tiredness, dry mouth,nausea, vomiting, and swelling, pain , and discomfort in

the abdomen. Some of these symptoms are the same asthose that occur with diarrhea, so it may be difficult to tellif the medicine is causing the problems. Children may bemore sensitive than adults to certain side effects of lop-eramide, such as drowsiness and dizziness.
Other rare side effects may occur with any antidiar-
rheal medicine. Anyone who has unusual symptoms aftertaking an antidiarrhea drug should get in touch with hisor her physician.

Attapulgite can decrease the effectiveness of other
medicines taken at the same time. Changing the times atwhich the other medicines are taken may be necessary.
GALE ENCYCLOPEDIA OF MEDICINE 2 265Antidiarrheal drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 265

Check with a physician or pharmacist to work out the
proper dose schedule.
Bismuth subsalicylate should not be taken with

aspirin or any other medicine that contains salicylate.This drug may also interact with other drugs, such asblood thinners (warfarin, for example), methotrexate, theantigout medicine probenecid, and the antidiabetes drugtolbutamide. In addition, bismuth subsalicylate mayinteract with any drug that interacts with aspirin. Anyonetaking these drugs should check with a physician or phar-macist before taking bismuth subsalicylate.

Antidiuretic hormone (ADH)
test
Antidiuretic hormone (ADH) test, also called the
Vasopressin test, is a test for the antidiuretic hormone,which is released from the pituitary gland and acts on thekidneys to increase their reabsorption of water into theblood.
Purpose
An ADH test is used to aid in the diagnosis of dia-
betes insipidus or the syndrome of inappropriate ADH
called SIADH.
Certain drugs can either increase or decrease ADH

levels. Drugs that increase ADH levels include aceta-KEY TERMS
Colitis —Inflammation of the colon (large bowel).
Dehydration —Excessive loss of water from the
body.
Nutrient —A food substance that provides energy

or is necessary for growth and repair. Examples ofnutrients are vitamins, minerals, carbohydrates,fats, and proteins.minophen ,barbiturates , cholinergic agents, estrogen,
nicotine, oral hypoglycemia agents, some diuretics
(e.g., thiazides), cyclophosphamide, narcotics, and tri-cyclic antidepressants. Drugs that decrease ADH levelsinclude alcohol, beta-adrenergic agents, morphine antag-onists, and phenytoin (Dilantin).

The purpose of ADH is to control the amount of
water reabsorbed by the kidneys. Water is continuallybeing taken into the body in food and drink, as well asbeing produced by chemical reactions in cells. Water isalso continually lost in urine, sweat, feces, and in thebreath as water vapor. ADH release helps maintain theoptimum amount of water in the body when there is anincrease in the concentration of the blood serum or adecrease in blood volume. Physical stress , surgery, and

high levels of anxiety can also stimulate ADH.
Various factors can affect ADH production, thereby

disturbing the body’s water balance. For example, alcoholconsumption reduces ADH production by direct action onthe brain, resulting in a temporarily increased productionof urine. This may also occur in diabetes insipidus, whenthe pituitary gland produces insufficient ADH, or rarely,when the kidneys fail to respond to ADH. The reverseeffect of water retention can result from temporarilyincreased ADH production after a major operation oraccident. Water retention may also be caused by thesecretion

retention may also be caused by thesecretion of ADH by some tumors, especially of the lung.

The test requires collection of a blood sample. The
patient must be fasting (nothing to eat or drink) for 12
hours, be adequately hydrated, and limit physical activityfor 10-12 hours before the test.
Risks
ADH normal ranges are laboratory-specific but can

range from 1-5 pg/ml or 1.5 ng/L (SI units).
Patients who are dehydrated, who have a decreased
amount of blood in the body (hypovolemia), or who areundergoing severe physical stress (e.g., trauma, pain or
GALE ENCYCLOPEDIA OF MEDICINE 2 266Antidiuretic hormone (ADH) testGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 266

prolonged mechanical ventilation) may exhibit increased
ADH levels. Patients who are overly hydrated or whohave an increased amount of blood in the body (hyperv-olemia) may have decreased ADH levels.
Other conditions that cause increased levels include
SIADH, central nervous system tumors or infection, orpneumonia .
Resources
BOOKS

Antiemetic drugs seeAntinausea drugs
Antiepileptic drugs seeAnticonvulsant drugs
Antifungal drugs, systemic
Systemic antifungal drugs are medicines taken by
mouth or by injection to treat deep infections caused by afungus.
Purpose
Systemic antifungal drugs are used to treat infec-
tions in various parts of the body that are caused by aKEY TERMS
Diabetes insipidus —A metabolic disorder in

which the pituitary gland produces inadequateamounts of antidiuretic hormone (ADH) or thekidneys are unable to respond to release of thehormone. Primary symptoms are excessive urina-tion and constant thirst.
Pituitary gland —The pituitary gland is sometimes

referred to as the “master gland.” As the most impor-tant of the endocrine glands (glands which releasehormones directly into the bloodstream), it regulatesand controls not only the activities of otherendocrine glands but also many body processes.fungus. A fungus is an organism that can be either one-

celled or filamentous. Unlike a plant, which makes itsown food, or an animal, which eats plants or other ani-mals, a fungus survives by invading and living off otherliving things. Fungi thrive in moist, dark places, includ-ing some parts of the body.
Fungal infections can either be systemic, meaning

that the infection is deep, or topical (dermatophytic),meaning that the infection is superficial and occurs on theskin. Additionally, yeast infections can affect the mucousmembranes of the body. Fungal infections on the skin areusually treated with creams or ointments (topical antifun-gal drugs). However, systemic infections, yeast infectionsor topical infections that do not clear up after treatmentwith creams or ointments may need to be treated with sys-temic antifungal drugs. These drugs are

with sys-temic antifungal drugs. These drugs are used, for example,to treat common fungal infections such as tinea ( ring-

worm ), which occurs on the skin or candidiasis (a yeast
infection, also known as trush), which can occur in thethroat, in the vagina, or in other parts of the body. They arealso used to treat other deep fungal infections such ashistoplasmosis ,blastomycosis , and aspergillosis , which

can affect the lungs and other organs. They are sometimesused to prevent or treat fungal infections in people whoseimmune systems are weakened, such as bone marrow ororgan transplant patients and people with AIDS .
Antifungal drugs are categorized depending on their
route or site of action, their mechanism of action andtheir chemical nature.
Systemic antifungal drugs, such as capsofungin (Can-

cidas), flucytosine, fluconazole (Diflucan), itraconazole(Sporanox), ketoconazole (Nizoral), and miconazole(Monistat I.V .) are available only by prescription. They areavailable in tablet, capsule, liquid, and injectable forms.

antifungal drug and the nature and extent of fungal infec-tion being treated. Doses may also be different for differ-ent patients. The prescribing physician or the pharmacistcan provide dosage information. Systemic antifungaldrugs must be taken exactly as directed. Itraconazole andketoconazole should be taken with food.
Fungal infections can take a long time to clear up, so

it may be necessary to take the medication for severalmonths, or even for a year or longer. It is very importantto keep taking the medicine for as long as the physiciansays to take it, even if symptoms seem to improve. If thedrug is stopped too soon, the symptoms may return.
GALE ENCYCLOPEDIA OF MEDICINE 2 267Antifungal drugs, systemicGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 267

Systemic antifungal drugs work best when their
amount is kept constant in the body, meaning that theyhave to be taken regularly, at the same time every day,and without missing any doses.
Patients taking the liquid form of ketoconazole

should use a specially marked medicine spoon or othermedicine measuring device to make sure they take thecorrect amount. A regular household teaspoon may nothold the right amount of medicine. Ask the pharmacistsabout ways to accurately measure the dose of these drugs.
If symptoms do not improve within a few weeks, the
prescribing physician should be informed.
While taking this medicine, regular medical visits

should be scheduled. The physician needs to keep check-ing for side effects throughout the antifungal therapy.
Some people feel drowsy or dizzy while taking sys-
temic antifungal drugs. Anyone who takes these drugsshould not drive, use machines or do anything else thatmight be dangerous until they have found out how thedrugs affect them.
Liver problems, stomach problems and other prob-

lems may occur in people who drink alcohol while takingsystemic antifungal drugs. Alcohol and prescription ornonprescription (over-the-counter) drugs that containalcohol should be avoided while taking antifungal drugs.(Medicines that may contain alcohol include some cough
syrups, tonics, and elixirs.) Alcohol should be avoidedfor at least a day after taking an antifungal drug.
The antifungal drug ketoconazole may make the

eyes unusually sensitive to light. Wearing sunglasses andavoiding exposure to bright light may help.
taking certain other medicines can have problems if theytake systemic antifungal drugs. Before taking thesedrugs, the prescribing physician should be informedabout any of the following conditions:
ALLERGIES. Anyone who has had unusual reactions to

systemic antifungal drugs in the past should let his or herphysician know about the problem before taking the drugsagain. The physician should also be told about any aller-
PREGNANCY. In laboratory studies of animals, sys-
temic antifungal drugs have caused birth defects and

other problems in the mother and fetus. Studies have notbeen done on pregnant women, so it is not knownwhether these drugs cause similar effects in people.Women who are pregnant or who plan to become preg-
nant should check with their physicians before takingsystemic antifungal drugs. Any woman who becomespregnant while taking these drugs should let her physi-cian know immediately.
BREASTFEEDING. Systemic antifungal drugs pass

into breast milk. Women who are breastfeeding shouldcheck with their physicians before using systemic anti-fungal drugs.
OTHER MEDICAL CONDITIONS. People who have

medical conditions that deplete stomach acid (achlorhy-dria) or decrease stomach acid (hypochlorhydria) should besure to inform their physicians about their condition beforethey use a systemic antifungal drug. These drugs are notactive in their natural form, but must be converted to theactive form by an acid. If these is not enough stomach acid,the drugs will be ineffective. For people with insufficientstomach acid, it may help to take the medicine with anacidic drink, such as a cola. The

medicine with anacidic drink, such as a cola. The patient’s health careprovider can suggest the best way to take the medicine.

Before using systemic antifungal drugs, people with
any of these medical problems should also make suretheir physicians are aware of their conditions:
• current or past alcohol abuse• liver disease
USE OF CERTAIN MEDICINES. Taking systemic anti-
fungal drugs with certain other drugs may affect the waythe drugs work or may increase the chance of sideeffects.
Fluconazole
Although rare, severe allergic reactions to this medi-

cine have been reported. Call a physician immediately ifany of these symptoms develop after taking fluconazole(Diflucan):
• hives, itching , or swelling
• breathing or swallowing problems
• sudden drop in blood pressure•diarrhea
• abdominal pain
Ketoconazole
Ketoconazole has caused anaphylaxis (a life-threat-
ening allergic reaction) in some people after their firstdose. This is a rare reaction.

GALE ENCYCLOPEDIA OF MEDICINE 2 268Antifungal drugs, systemicGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 268

Systemic antifungal drugs in general
Systemic antifungal drugs may cause serious and
possibly life-threatening liver damage. Patients who takethese drugs should have liver function tests before they
start taking the medicine and as often as their physicianrecommends while they are taking it. The physicianshould be notified immediately if any of these symptomsdevelop:
• nausea or vomiting• yellow skin or eyes• unusual fatigue
• pale stools

The most common minor side effects of systemic
antifungal drugs are constipation , diarrhea, nausea,
vomiting, headache , drowsiness, dizziness , and flushing

of the face or skin. These problems usually go away asthe body adjusts to the drug and do not require medicaltreatment. Less common side effects, such as menstrualproblems in women, breast enlargement in men, anddecreased sexual ability in men also may occur and donot need medical attention unless they do not improve ina reasonable amount of time.

occur. If any of the following side effects occur, checkwith the physician who prescribed the medicine immedi-ately:
• skin rash or itching
• high blood pressure• pain, redness, or swelling at site of injection (for inject-
able miconazole)Other rare side effects are possible. Anyone who has
unusual symptoms after taking systemic antifungal drugsshould get in touch with his or her physician.

Serious and possibly life-threatening side effects can
result if the oral forms of itraconazole or ketoconazole orthe injectable form of miconazole are taken with certaindrugs. Do not take those types of systemic antifungaldrugs with any of the following drugs unless the physi-cian approves of the therapy:
• cisapride (Propulsid)• antacids
• theophylline-containing anti-wheezing medications
Taking an acid blocker such as cimetidine (Taga-

met), famotidine (Pepcid), nizatidine (Axid), omeprazole(Prilosec), or ranitidine (Zantac) at the same time as asystemic antifungal drug may prevent the antifungal drugfrom working properly. For best results, take the acidblocker at least 2 hours after taking the antifungal drug.
In addition, systemic antifungal drugs may interact

with many other medicines. When this happens, theeffects of one or both of the drugs may change or the riskof side effects may be greater. Anyone who takes sys-
temic antifungal drugs should inform the prescribingphysician about all other prescription and nonprescrip-tion (over-the-counter) medicines he or she is taking.Among the drugs that may interact with systemic anti-fungal drugs are:
• acetaminophen (Tylenol)
• birth control pills• male hormones (androgens)

GALE ENCYCLOPEDIA OF MEDICINE 2 269Antifungal drugs, systemic
Antifungal Drugs
Diflucan (fluconazole) Nausea, diarrhea, headache, vomiting

Femstat (butoconazole nitrate) Vaginal discharge or burning, soreness, swellingGris-PEG, Grisactin, Fulvicin P/G (griseofulvin) Rash, hives, diarrhea, fatigue, oral thrushGyne-Lotrimin, Mycelex-7 (clotrimazole) Burning sensation, hives, itching/irritated skin, swellingLoprox (ciclopiroz olamine) This drug rarely causes side effectsLotrisone Blistering, hives, itching/irritated skin, swellingMonistat (miconazole nitrate) Burning sensation, headaches, hives, rash, vaginal itchingMycolog-II

headaches, hives, rash, vaginal itchingMycolog-II Burning, blistering, rash, itching/peeling of skinNizoral (ketoconazole) Nausea, vomitingOxistat (oxiconazole nitrate) Burning, cracked skin, rash, itchingSpectazole Cream (econazole nitrate) Burning, itchingSporanox (itraconazole) Headache, diarrhea, increased blood pressure, feverGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 269

• medicine for other types of infections
• antidepressants
• antihistamines
• muscle relaxants• medicine for diabetes, such as tolbutamide (Orinase),
glyburide (DiaBeta), and glipizide (Glucotrol)
• blood-thinning medicine, such as warfarin (Coumadin)
interact with systemic antifungal drugs. Be sure to checkwith a physician or pharmacist before combining sys-temic antifungal drugs with any other medicine.

Antifungal drugs, topical
Topical antifungal drugs are medicines applied to
the skin to treat skin infections caused by a fungus.
Purpose
Dermatologic fungal infections are usually
described by their location on the body: tinea pedis(infection of the foot), tinea unguium (infection of thenails), tinia capitis (infection of the scalp.) Three types offungus are involved in most skin infections: Trichophy-

ton, Epidermophyton, and Microsporum. Mild infectionsKEY TERMS
Elixir —A sweetened liquid that contains alcohol,
water, and medicine.
Fungus —A unicellular to filamentous organism
that causes parasitic infections.
Ointment —A thick substance that contains medi-
cine and is meant to be spread on the skin, or if anophthalmic ointment, in the eye.
Systemic —A term used to describe a medicine

that has effects throughout the body, as opposed totopical drugs that work on the skin. Most medi-cines that are taken by mouth or by injection aresystemic drugs.are usually susceptible to topical therapy, however severe
or resistant infections may require systemic treatment.
There are a large number of drugs currently avail-

able in topical form for fungal infections. Other than theimidazoles, (miconazole [Micatin, Miconazole], clotri-mazole [Lotrimin], econazole [Spectazole], ketoconazole[Nizoral], oxiconazole [Oxistat], sulconazole [Exel-derm]) and the allylamine derivatives (butenafine [Men-tax], naftifine [Naftin], terbinafine [Lamisil]), the drugsin this therapeutic class are chemically distinct from eachother. All drugs when applied topically have a good mar-gin of safety, and most show a high degree of

mar-gin of safety, and most show a high degree of effective-ness. There are no studies comparing drugs on which tobase a recommendation for drugs of choice. Althoughsome of the topical antifungals are available over-the-counter, they may be as effective as prescription drugsfor this purpose.

Traditional antifungal drugs such as undecylinic
acid (Cruex, Desenex) and gentian violet (also known ascrystal violet) remain available, but have a lower curerate (complete eradication of fungus) than the neweragents and are not recommended. Tolnaftate (Tinactin)has a lower cure rate than the newer drugs, but may beused prophylactically to prevent infection.
All drugs are applied topically. Consult individual
product information for specific application recommen-dations.

form may be as important as proper drug selection. Con-sider factors such as presence or absence of hair on theaffected area, and type of skin to which the medication isto be applied. Thin liquids may preferable for applicationto hairy areas, creams for the hands and face, and oint-ments may be preferable for the trunk and legs. Otherdosage forms available include shampoos and sprays.Ciclopirox and triacetin are available in formulations fortopical treatment of nail fungus as well as skin

treatment of nail fungus as well as skin infections(ciclopirox as Penlac Nail Lacquer and triacetin as Ony-Clear Nail).

Most topical antifungal drugs require four weeks of
treatment. Infections in some areas, particularly thespaces between toes, may take up to six weeks for cure.
Most topical antifungal agents are well tolerated.
The most common adverse effects are localized irritationcaused by the vehicle or its components. This may
GALE ENCYCLOPEDIA OF MEDICINE 2 270Antifungal drugs, topicalGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 270

include redness, itch, and a burning sensation. Some
direct allergic reactions are possible.
Topical antifungal drugs should only be applied in
accordance with labeled uses. They are not intended orophthalmic (eye) or otic (ear) use. Application to mucousmembranes should be limited to appropriate formulations.
The antifungal drugs have not been evaluated for
safety in pregnancy and lactation on topical application

under the pregnancy risk category system. Although sys-temic absorption is probably low, review specific refer-ences. Gentian violet is labeled with a warning againstuse in pregnancy.
Topical antifungal drugs have no recognized drug-
drug or food-drug interactions.
Antigas agents
Antigas agents are medicines that relieve the uncom-
fortable symptoms of too much gas in the stomach andintestines.
Purpose
Excess gas can build up in the stomach and

intestines for a number of reasons. Eating high-fiberKEY TERMS
Cream —A spreadable substance, similar to an
ointment, but not as thick. Creams may be moreappropriate than ointments for application toexposed skin areas such as the face and hands.
contains medicine and is meant to be used on theskin, or if a vaginal preparation, in the vagina.
Opthalmic —Pertaining to the eye.
Otic—Pertaining to the ear.

Topical —A term used to describe medicine that
has effects only in a specific area, not throughoutthe body, particularly medicine that is put directlyon the skin.foods, such as beans, grains, and vegetables is one

cause. Some people unconsciously swallow air whenthey eat, drink, chew gum, or smoke cigarettes, whichcan lead to uncomfortable amounts of gas in the diges-tive system. Surgery and certain medical conditions,such as irritable colon, peptic ulcer, and diverticulosis,can also lead to gas build-up. Certain intestinal parasitescan contribute to the production of severe gas - theseparasites need to be treated separately with specialdrugs. Abdominal pain , pressure, bloating, and flatu-

lence are signs of too much gas. Antigas agents helprelieve the symptoms by preventing the formation of gaspockets and breaking up gas that already is trapped inthe stomach and intestines.
Antigas agents are sold as capsules, liquids, and

tablets (regular and chewable) and can be bought withouta physician’s prescription. Some commonly used brandsare Gas-X, Flatulex, Mylanta Gas Relief, Di-Gel, andPhazyme. The ingredient that helps relieve excess gas issimethicone. Simethicone does not relieve acid indiges-
tion, but some products also contain antacids for that
purpose. Check the label of the product or ask the phar-macist for more information.

Check the product container for dosing informa-
tion. Typically, the doses should be taken after mealsand at bedtime. Chewable forms should be chewedthoroughly.
Check with a physician before giving this medicine
to children under age 12 years.
Some anti-gas medicines may contain sugar, sodi-

um, or other ingredients. Anyone who is on a special dietor is allergic to any foods, dyes, preservatives, or othersubstances should check with his or her physician orpharmacist before using any of these products.
Anyone who has had unusual reactions to sime-
thicone—the active ingredient in antigas medicines—should check with his or her physician before takingthese drugs.
No common or serious side effects have been report-

ed in people who use this medicine. However, anyonewho has unusual symptoms after taking an antigas agentshould get in touch with his or her physician.
GALE ENCYCLOPEDIA OF MEDICINE 2 271Antigas agentsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 271

Antigas agents are not known to interact with any
other drugs.
Antigastroesophageal reflux
drugs
These drugs are used to treat gastroesophageal
reflux, the backward flow of stomach contents into theesophagus.
Purpose
The drug discussed here, cisapride (Propulsid), is
used to treat nighttime heartburn resulting from gas-

troesophageal reflux disease (GERD). In this condition,food and stomach juices flow backward from the stom-ach into the esophagus, the part of the digestive tractthrough which food passes on its way from the mouth tothe stomach. Normally, a muscular ring called the loweresophageal sphincter (LES) opens to allow food into thestomach and then closes to prevent the stomach’s con-tents from flowing back into the esophagus. In peoplewith GERD, this muscular ring is either weak or it relax-es at the

ring is either weak or it relax-es at the wrong times. The main symptom is heartburn—a burning sensation centered behind the breastbone andspreading upward toward the neck and throat.

Cisapride works by strengthening the lower
esophageal sphincter and making the stomach emptymore quickly. This shortens the amount of time that theesophagus comes in contact with the stomach contents.KEY TERMS
Digestive tract —The stomach, intestines, and
other parts of the body through which food passes.
Diverticulosis —A condition in which the colon
(large intestine) develops a number of outpouch-ings or sacs.
Flatulence —Excess gas in the digestive tract.

Irritable colon —An intestinal disorder often
accompanied by abdominal pain and diarrhea.Other drugs, such as H2-blockers are sometimes pre-
scribed to reduce the amount of acid in the stomach.
Cisapride is available only with a physician’s pre-
scription. Cisapride is sold in tablet and liquid forms.
The dose depends on the patient. The average dose

for adults and children age 12 and over is 5-20 mg takentwo to four times a day. The medicine should be taken 15minutes before meals and at bedtime. For children under12, the dose is based on body weight and should bedetermined by the child’s physician.
This medicine is effective in treating only nighttime
heartburn, not daytime heartburn.
Cisapride may increase the effects of alcohol and
tranquilizers.

Cisapride has caused dangerous irregular heartbeats
in a few people who took it with other medicines. Any-one who takes this drug should let the physician know allother medicines he or she is taking. Patients with heartproblems should check with their physicians before tak-ing cisapride.
Anyone who has bleeding, blockage, or leakage in

the stomach or intestines should not take cisapride. Cis-apride should not be used by anyone who has had anunusual reaction to the drug in the past. In addition, peo-ple with any of the following medical problems shouldmake sure their physicians are aware of their conditions:
• epilepsy or history of seizures• kidney disease
The effects of taking cisapride during pregnancy

have not been fully studied. Women who are pregnant orplan to become pregnant should check with their physi-cians before taking Cisapride. The drug passes intobreast milk and may affect nursing babies. Women whoare breastfeeding and need to take this medicine shouldcheck with their physicians. Avoiding breastfeedingwhile taking the drug may be necessary.
The most common side effects are abdominal pain ,

bloating, gas, diarrhea ,constipation , nausea, upper res-
piratory infections, inflammation of the nasal passages
GALE ENCYCLOPEDIA OF MEDICINE 2 272Antigastroesophageal reflux drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 272

and sinuses, headache , and viral infections. Other side
effects may occur. Anyone who has unusual or trouble-some symptoms after taking this drug should get in touchwith his or her physician.
Cisapride may interact with a variety of other medi-

cines. When this happens, the effects of one or both ofthe drugs may change or the risk of side effects may begreater. Anyone who takes Cisapride should let thephysician know all other medicines he or she is taking.Among the drugs that may interact with cisapride are:
• antifungal drugs such as ketoconazole (Nizoral),
miconazole (Monistat), and fluconazole (Diflucan)
• antibiotics such as clarithromycin (Biaxin) and ery-
thromycin (E-Mycin, ERYC)
• blood-thinners such as warfarin (Coumadin)

• H2-blockers such as cimetidine (Tagamet) and raniti-
dine (Zantac)
• tranquilizers such as chlordiazepoxide (Librium), diaz-
epam (Valium), and alprazolam (Xanax)
interact with cisapride. Be sure to check with a physician orpharmacist before combining cisapride with any other pre-scription or nonprescription (over-the-counter) medicine.
Resources

Resources
National Digestive Diseases Information Clearinghouse. 2 Infor-
mation Way, Bethesda, MD 20892-3570. (800) 891-5389.<http://www.niddk.nih.gov/health/digest/nddic.htm>.
Pediatric/Adolescent Gastroesophageal Reflux Association,
Inc. P.O. Box 1153, Germantown, MD 20875-1153. (301)601-9541. <http://www.reflux.org>.
OTHER
GERD Information Resource Center. <http://www.gerd.com>.
Pharmaceutical Information Network. GERD Information Cen-

ter. <http://pharminfo.com/disease/gerd/gerd_info.html>.
Esophagus —The part of the digestive tract
between the pharynx and the stomach. (The phar-ynx is the space just behind the mouth.)
that usually develop in response to injury or illness.Antihelminthic drugs
Antihelminthic drugs are used to treat parasitic
infestations.
Purpose
Parasitic infestations are caused by protozoa or

worms gaining entry into the body. Most of these organ-isms cause infections by being ingested in the form ofeggs or larvae, usually present on contaminated food orclothing, while others gain entry through skin abrasions.Common parasitic infestations include amebiasis ,malar-
ia,giardiasis , hookworm, pinworm, threadworm, whip-

worm and tapeworm infestations. Once in the body, para-sitic worms may go unnoticed if they cause no severesymptoms. However, if they multiply rapidly and spread toa major organ, they can cause very serious and even life-threatening conditions. Antihelminthic drugs are pre-scribed to treat these infestations. They function either bydestroying the worms on contact or by paralyzing them, orby altering the permeability of their plasma membranes.The dead worms then pass out of the body in the

scription and are available as liquids, tablets or capsules.Some commonly used antihelminthics include: albenda-zole (Albenza), mebendazole (Vermox), niclosamide(Niclocide), oxamniquine (Vansil), praziquantel (Biltri-cide), pyrantel (Antiminth), pyantel pamoate (Antiminth)and thiabendazole (Mintezol). Some types of parasiticinfestations are rarely seen in the United States, thus, thecorresponding antihelminthic drugs are not widely dis-tributed and need to be obtained from the United

and need to be obtained from the United StatesCenter for Disease Control (CDC) when required. Theseinclude for example bitional and ivermectin, used to treatonchocerciasis infestations. Other antihelminthic drugs,such as diethylcarbamazepine citrate (Hetrezan), usedfor treatment of roundworms and other parasites, is sup-plied directly by its manufacturer when needed.

cific parasites, some are also toxic. Before treatment, theparasites must therefore be identified using tests that lookfor parasites, eggs or larvae in feces, urine, blood, sputum,or tissues. Thus, niclosamide is used against tapeworms,but will not be effective for the treatment of pinworm orroundworm infestations, because it acts by inhibiting ATPproduction in tapeworm cells. Thiabendazole (Mintezole)is the drug usually prescribed for treatment of thread-worm, but a similar drug, mebendazole

GALE ENCYCLOPEDIA OF MEDICINE 2 273Antihelminthic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 273

better on whipworm by disrupting the microtubules of this
worm. Praziquantel is another drug that acts by alteringthe membrane permeability of the worms.
Dosage is established depending on the patient’s
general health status and age, the type of antihelminthicdrug used, and the type of parasitic infestation beingKEY TERMS
Amebiasis —Parasitic infestation caused by amebas,
especially by Entamoeba histolytica.
Colitis —Inflammation of the colon (large intestine).

Feces —The solid waste that is left after digestion.
Feces form in the intestines and leave the bodythrough the anus.
Flukes —Parasite worms that look like leeches. They
usually have one or more suckers for attaching tothe digestive mucosa of the host. Liver flukes infestthe liver, destroying liver tissue and impairing bileproduction and drainage.
Giardiasis —Parasitic infestation caused by a flagel-
late protozoan of the genus Giardia, especially byG. lamblia.

objective reality. Imaginary objects, sounds, andevents are perceived as real.
Hookworm —Parasitic intestinal infestation caused
by any of several parasitic nematode worms of thefamily Ancylostomatidae. These worms have strongbuccal hooks that attach to the host’s intestinal lining.
Larva —The immature, early form of an organism
that at birth or hatching is not like its parent and hasto undergo metamorphosis before assuming adultfeatures.

Malaria —Disease caused by the presence of sporo-
zoan parasites of the genus Plasmodium in the redblood cells, transmitted by the bite of anophelinemosquitoes, and characterized by severe and recur-ring attacks of chills and fever).
Microtubules —Slender, elongated anatomical
channels in worms.
Nematode —Roundworm.
Organism —A single, independent life form, such as
a bacterium, a plant or an animal.Parasite —An organism that lives in or with another

organism, called the host, in parasitism, a type ofassociation characterized by the parasite obtainingbenefits from the host, such as food, and the hostbeing injured as a result.
Parasitic —Of, or relating to a parasite.
Pinworm —Enterobius vermicularis, a nematode
worm of the family Oxyuridae that causes parasiticinfestation of the intestines and cecum. Pinworm isendemic in both temperate and tropical regions andcommon especially in school age children.

Onchocerciasis —Parasitic infestation caused by fil-
amentous worms of the genus Onchocerca, espe-cially O. volvulus, that is found in tropical Americaand is transmitted by several types of blackflies.
Protozoan —Any unicellular or multicellular organ-
ism containing nuclei and organelles (eukaryotic) ofthe subkingdom Protozoa.
Roundworm —Any round-bodied unsegmented
worm as distinguished from a flatworm. Also calleda nematode, they look similar to the common earth-worm.

Tapeworm —Flat and very long (up to 30 meters)
intestinal parasitic worms, similar to a long piece oftape. Common tapeworms include: T. saginata (beeftapeworm), T. solium (pork tapeworm) D. latum(fish tapeworm), H. Nana (dwarf tapeworm) and E.granulosus (dog tapeworm). General symptoms arevague abdominal discomfort, nausea, vomiting,diarrhea and weight loss.
Threadworm —Any long, thin nematode worm.
Trematode —Any parasitic flatworm of the class
Trematoda, as the liver fluke.

Whipworm —A nematode worm of the family
Trichuridae with a body that is thick at one end andvery long and slender at the other end.
treated. The number of doses per day, the time between
doses, and the length of treatment will also depend onthese factors.
Antihelminthic drugs must be taken exactly as

directed to completely rid the body of the parasitic infes-tation, and for as long as directed. A second round oftreatment may be required to ensure that the infection hascompletely cleared.
GALE ENCYCLOPEDIA OF MEDICINE 2 274Antihelminthic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 274

Some antihelminthic drugs work best when ingested
along with fatty foods, such as milk or ice cream. Oraldrugs should be taken with water during or after meals.The prescribing physician should be informed if thepatient has a low-fat or other special diet.
Some antihelminthic drugs, such as praziquantel,
come in chewable form. These tablets should not bechewed or kept in the mouth, but should swallowed wholebecause their bitter taste may cause gagging or vomiting.

Antihelminthic drugs sometimes need to be taken
with other medications. For example, steroids such asprednisone are also prescribed together with the anti-helminthic drug for tapeworm to reduce the inflamma-tion that the worm may cause.
When required, pre- or post-treatment purges are
also performed with magnesium or sodium sulfate.
Regular medical visits are recommended for people

affected by parasitic infestations. The physician monitorswhether the infection is clearing or not and also keepstrack of unwanted side effects. The prescribing physicianshould be informed if symptoms do not disappear or ifthey get worse.
Hookworm or whipworm infections are also treated
with iron supplements along with the antihelminthic pre-scription.
Some types of parasitic infestations (e.g. pinworms)

can be passed from one person to another. It is then oftenrecommended that everyone in the household of aninfected person be asked to also take the prescribed anti-helminthic drug.
Risks
People with the following medical conditions may
have adverse reactions to antihelminthic drugs. The pre-scribing physician should accordingly be informed if anyof these conditions are present:
•Allergies . Anyone who has had adverse reactions to

antihelminthic drugs should inform the prescribingphysician before taking the drugs again. The physicianshould also be informed about any other pre-existingallergies.
• Ulcers. Antihelminthic drugs are also contraindicated
for persons diagnosed with ulcers of the digestive tract,especially ulcerative colitis .
•Pregnancy . There is research evidence reporting that
some antihelminthic drugs cause birth defects or mis-
carriage in animal studies. No human birth defects have

been reported, but antihelminthic drugs are usually notrecommended for use during pregnancy. Pregnant women
should accordingly inform the prescribing physician.
• Breastfeeding. Some antihelminthic drugs can pass into
breast milk. Breastfeeding may have to be discontinueduntil the antihelminthic treatment has ended and breast-feeding mothers must also inform the prescribingphysician.
• Other risk conditions. Any of the following medical

conditions should also be reported to the prescribingphysician: Crohn’s disease , liver disease, kidney dis-
ease and worm cysts in the eyes.
Common side effects of antihelminthic drugs include
dizziness , drowsiness, headache , sweating, dryness of the

mouth and eyes, and ringing in the ears. Anyone takingthese drugs should accordingly avoid driving, operatingmachines or other activities that may be dangerous untilthey know how they are affected by the drugs. Side effectsusually wear off as the body adjusts to the drug and do notusually require medical treatment. Thiabendazole maycause the urine to have an unusual odor that can last for aday after the last dose. Other side effects of antihelminthicdrugs, such as loss of appetite, diarrhea ,

ing, or abdominal cramps are less common. If they occur,they are usually mild and do not require medical attention.
More serious side effects, such as fever , chills, con-
fusion, extreme weakness, hallucinations , severe diar-
rhea, nausea or vomiting, skin rashes ,low back pain ,
dark urine, blurred vision, seizures, and jaundice have

been reported in some cases. The patient’s physicianshould be informed immediately if any should develop.As a rule, anyone who has unusual symptoms after start-ing treatment with antihelminthic drugs should notify theprescribing physician.
Antihelminthic drugs may interact with each other

or with other drugs, whether prescribed or not. For exam-ple, it has been reported that use of the antihelminthicdrugs pyrantel and piperazine together lowers the effi-ciency of pyrantel. Similarly, combining a given anti-helminthic drug with another medication may increasethe risk of side effects from either drug.
Antihemorrhoid drugs
Antihemorrhoid drugs are medicines that reduce the

swelling and relieve the discomfort of hemorrhoids
(swellings in the area around the anus).
GALE ENCYCLOPEDIA OF MEDICINE 2 275Antihemorrhoid drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 275

Purpose
Hemorrhoids are bulges in the veins that supply
blood to the skin and membranes of the area around theanus. They may form for various reasons. Frequent heavylifting, sitting for long periods, or straining to have bowelmovements may put stress on anal tissues, which can lead
to hemorrhoids. Some women develop hemorrhoids dur-ing pregnancy as the expanding uterus puts pressure on

the anal tissues. The strain of labor and delivery can alsocause hemorrhoids or make existing hemorrhoids worse.Hemorrhoids sometimes result from certain medicalproblems, such as tumors pressing on the lower bowel.
The main symptoms of hemorrhoids are bleeding
from the rectum, especially after a bowel movement, anditching , burning, pain , and general discomfort in the

anal area. Over-the-counter antihemorrhoid products canrelieve many of these symptoms. The products containcombinations of four main types of ingredients:
• local anesthetics, such as benzocaine, lidocaine and
tetracaine, to temporarily relieve the pain
• vasoconstrictors, such as epinephrine base, epinephrine
hydrochloride, ephedrine sulfate and phenylephrinehydrochloride that reduce swelling and relieve itchingand discomfort by tightening blood vessels

• astringents (drying agents), such as witch hazel,
calamine, and zinc oxide. These help shrink hemor-rhoids by pulling water out of the swollen tissue. This,in turn, helps relieve itching, burning, and irritation.
• protectants, such as cocoa butter, lanolin, glycerin, min-
eral oil, and shark liver oil which soothe irritated tissuesand form a protective barrier to prevent further irrita-tion
Antihemorrhoid drugs are available as creams, oint-

ments and suppositories. Most can be bought without aphysician’s prescription.
Follow package instructions for using these prod-
ucts. Do not use more than the recommended amount ofthis medicine every day. For explanations or furtherinformation about how to use antihemorrhoid drugs,check with a physician or pharmacist.
Do not use antihemorrhoid drugs for more than
seven days in a row. If the problem gets worse or doesnot improve, check with a physician.KEY TERMS

Anus —The opening at the end of the intestine
through which solid waste (stool) passes as itleaves the body.
Rectum —The end of the intestine closest to the
anus.
Uterus —A hollow organ in a female in which a
fetus develops until birth.
If rectal bleeding continues, check with a physician.
This could be a sign of a condition that needs medicalattention.
Side effects are rare, however, if a rash or any other
sign of an allergic reaction occurs, stop using the medicine.

Some antihemorrhoid drugs should not be used by
people who are taking or have recently taken monoamine
oxidase inhibitors (MAO inhibitors), such as phenelzine
(Nardil) or tranylcypromine (Parnate), used to treat condi-tions including depression and Parkinson’s disease .

Anyone who is not sure if he or she has taken this type ofdrug should check with a physician or pharmacist beforeusing an antihemorrhoid drug. People who are takingantidepressants or medicine for high blood pressure alsoshould not use certain antihemorrhoid drugs. Check witha pharmacist for a list of drugs that may interact with spe-cific antihemorrhoid drugs.
Antihistamines are drugs that block the action of

histamine (a compound released in allergic inflammatoryreactions) at the H
1receptor sites, responsible for imme-
diate hypersensitivity reactions such as sneezing anditching . Members of this class of drugs may also be used
for their side effects, including sedation and antiemesis
(prevention of nausea and vomiting ).
GALE ENCYCLOPEDIA OF MEDICINE 2 276AntihistaminesGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 276

Purpose
Antihistamines provide their primary action by
blocking histamine H1at the receptor site. They have no

effect on rate of histamine release, nor do they inactivatehistamine. By inhibiting the activity of histamine, theycan reduce capillary fragility, which produces the erythe-ma, or redness, associated with allergic reactions. Theywill also reduce histamine-induced secretions, includingexcessive tears and salivation. Additional effects varywith the individual drug used. Several of the older drugs,called first-generation antihistamines, bind non-selec-tively to H

1receptors in the central nervous system as
well as to peripheral receptors, and can produce sedation,inhibition of nausea and vomiting, and reduction ofmotion sickness . The second-generation antihistamines
bind only to peripheral H
1receptors, and reduce allergic
response with little or no sedation.
The first-generation antihistamines may be divided

into several chemical classes. The side effect profile,which also determines the uses of the drugs, will vary bychemical class. The alkylamines include brompheni-ramine (Dimetapp) and chlorpheniramine (Chlor-Trime-ton.) These agents cause relatively little sedation, and areused primarily for treatment of allergic reactions. Promet-hazine (Phenergan), in contrast, is a phenothiazine, chem-ically related to the major tranquilizers, and while it isused for treatment of allergies , may also be used

sedative, the relieve anxiety prior to surgery, as an anti-
nauseant, and for control of motion sickness. Diphenhy-dramine (Benadryl) is chemically an ethanolamine, and inDANIELE BOVET (1907–1992)
A gifted researcher in therapeutic chemistry,

Daniele Bovet was born in Neuchatel, Switzerland, oneof four children of a professor of experimental educa-tion. Bovet studied zoology and comparative anatomyat the University of Geneva, receiving his doctor of sci-ence degree in 1929. He then joined the Pasteur Insti-tute in Paris, becoming director of the Laboratory ofTherapeutic Chemistry in 1936.
Bovet investigated histamine, thought to cause aller-

gy symptoms. No antagonist of histamine was known, soBovet—with his research student Anne-Marie Staub—began studying substances that blocked hormones simi-lar to histamine. By 1937 he had produced the first anti-histamine, thymoxydiethylamine. Since this substancewas too toxic for human use, Bovet and Staub performedthousands more experiments seeking less toxic antihista-mines. This work formed the basis for the developmentof subsequent clinically useful antihistamines.

addition to its role in reducing allergic reactions, may be
used as a nighttime sedative, for control of drug-inducedParkinsonism, and, in liquid form, for control of coughs.Consult more detailed references for further information.
The second generation antihistamines have no cen-

tral action, and are used only for treatment of allergicreactions. These are divided into two chemical classes.Cetirizine (Zyrtec) is a piperazine derivative, and has aslight sedative effect. Loratidine (Claritin) and fexofena-dine (Allegra) are members of the piperadine class andare essentially non-sedating.
Dosage varies with drug, patient and intended use.
Consult more detailed references for further information.

When used for control of allergic reactions, antihista-
mines should be taken on a regular schedule, rather than onan as-needed basis, since they have no effect on histamineitself, nor on histamine already bound to the receptor site.
Efficacy is highly variable from patient to patient. If
an antihistamine fails to provide adequate relief, switchto a drug from a different chemical class. Individualdrugs may be effective in no more than 40% of patients,and provide 50% relief of allergic symptoms.

GALE ENCYCLOPEDIA OF MEDICINE 2 277Antihistamines
KEY TERMS
Allergen —A substance that causes an allergy.
Anaphylaxis —A sudden, life-threatening allergic
reaction.
Histamine —A chemical released from cells in the
immune system as part of an allergic reaction.

risks. Category X: Evidenceof fetal risk. Risks outweigh any benefits.GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 277

The frequency and severity of adverse effects will
vary between drugs. Not all adverse reactions will applyto every member of this class.
Central nervous system reactions include drowsi-
ness, sedation, dizziness , faintness, disturbed coordina-
tion, lassitude, confusion, restlessness, excitation,tremor, seizures, headache ,insomnia , euphoria, blurred
vision, hallucinations , disorientation, disturbing

dreams/nightmares, schizophrenic-like reactions, weak-ness, vertigo, hysteria , nerve pain , and convulsions.
Overdoses may cause involuntary movements. Otherproblems have been reported.
Gastrointestinal problems include increased appetite,
decreased appetite, nausea, vomiting, diarrhea , and con-
stipation .
Hematologic reactions are rare, but may be severe.
These include anemia, or breakdown of red blood cells;reduced platelets; reduced white cells; and bone marrowfailure.

A large number of additional reactions have been
reported. Not all apply to every drug, and some reactionsmay not be drug related. Some of the other adverse effectsare chest tightness; wheezing ; nasal stuffiness; dry
mouth , nose and throat; sore throat ; respiratory depres-
sion; sneezing; and a burning sensation in the nose.
When taking antihistamines during pregnancy ,

Chlorpheniramine (Chlor-Trimeton), dexchlorpheni-ramine (Polaramine), diphenhydramine (Benadryl),brompheniramine (Dimetapp), cetirizine (Zyrtec), cypro-heptadine (Periactin), clemastine (Tavist), azatadine (Opti-mine), loratadine (Claritin) are all listed as category B.Azelastine (Astelin), hydroxyzine (Atarax), promethazine(Phenergan) are category C.Regardless of chemical class of the drug, it is recom-

mended that mothers not breast feed while taking antihis-tamines.
Contraindications
The following are absolute or relative contraindica-
tions to use of antihistamines. The significance of thecontraindication will vary with the drug and dose.
• glaucoma
• hyperthyroidism (overactive thyroid)
• ulcers or other stomach problems• stomach or intestinal blockage
• bladder obstruction
• diabetes

• diabetes
Drug interactions will vary with the chemical class
of antihistamine. In general, antihistamines will increasethe effects of other sedatives, including alcohol.
Monoamine oxidase inhibitor antidepressants (phe-
nelzine [Nardil], tranylcypromine [Parnate]) may prolongand increase the effects of some antihistamines. Whenused with promethazine (Phenergan) this may causereduced blood pressure and involuntary movements.
Resources

Resources
Allergy and Asthma Network. 3554 Chain Bridge Road, Suite
200. (800) 878-4403.
GALE ENCYCLOPEDIA OF MEDICINE 2 278AntihistaminesAntihistamines
*Atarax (hydroxyzine hydrochloride) Drowsiness, dry mouth

Benadryl (diphenhydramine hydrochloride) Dizziness, sleepiness, upset stomach, decreased coordinationHismanal (astemiozole) Drowsiness, dry mouth, fatigue, weight gainPBZ-SR (tripelennamine hydrochloride) Dizziness, drowsiness, dry mouth and throat, chest congestion, decreased coordina-
tion, upset stomach
Periactin (cyproheptadine hydrochloride) Chest congestion, dizziness, fluttery heartbeat, loss of appetite, hives, sleepiness, v ision
problems

problems
Phenergan (promethazine hydrochloride) Changes in blood pressure, dizziness, blurred vision, nausea, rashPolaramine (dexchlorpheniramine maleate) DrowinessSeldane, Seldane-D (terfenadine) Upset stomach, nausea, drowiness, headache, fatigueTavist (clemastine fumarate) Decreased coordination, dizziness, upset stomachTrinalin Repetabs (azatadine maleate, pseudoephedrine sulfate) Abdominal cramps, chest pain, dry mouth, headache

*Also used in the treatment of anxietyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 278

American Academy of Allergy and Immunology. 611 East
Wells Street, Milwaukee, WI 53202. (800)822-2762.
Asthma and Allergy Foundation of America. 1125 15th Street
NW, Suite 502, Washington, DC 20005. (800)727-8462.
Antihyperlipidemic drugs seeCholesterol-
reducing drugs
Antihypertensive drugs
Antihypertensive drugs are medicines that help
lower blood pressure.
Purpose
The overall class of antihypertensive agents lowers

blood pressure, although the mechanisms of action varygreatly. Within this therapeutic class, there are severalsubgroups. There are a very large number of drugs used tocontrol hypertension , and the drugs listed below are rep-
resentatives, but not the only members of their classes.
The calcium channel blocking agents, also called

slow channel blockers or calcium antagonists, inhibit themovement of ionic calcium across the cell membrane.This reduces the force of contraction of muscles of theheart and arteries. Although the calcium channel block-
ersare treated as a group, there are four different chemi-

cal classes, leading to significant variations in the activi-ty of individual drugs. Nifedipine (Adalat, Procardia) hasthe greatest effect on the blood vessels, while verapamil(Calan, Isoptin) and diltiazem (Cardizem) have a greatereffect on the heart muscle itself.
Peripheral vasodilators such as hydralazine
(Apresoline), isoxuprine (Vasodilan), and minoxidil
(Loniten) act by relaxing blood vessels.
There are several groups of drugs which act by reduc-

ing adrenergic nerve stimulation, the excitatory nervestimulation that causes contraction of the muscles in thearteries, veins, and heart. These drugs include the beta-adrenergic blockers and alpha/beta adrenergic blockers.There are also non-specific adrenergic blocking agents.
Beta-adrenergic blocking agents include propranolol

(Inderal), atenolol (Tenormin), and pindolol (Visken).Propranolol acts on the beta-adrenergic receptors any-where in the body, and has been used as a treatment foremotional anxiety and rapid heart beat. Atenolol andacebutolol (Sectral) act specifically on the nerves of the
heart and circulation.
There are two alpha/beta adrenergic blockers,
labetolol (Normodyne, Trandate) and carvedilol (Coreg).These work similarly to the beta blockers .
Angiotensin-converting enzyme inhibitors (ACE

inhibitors) act by inhibiting the production of angiotensinII, a substance that both induces constriction of bloodvessels and retention of sodium, which leads to waterretention and increased blood volume. There are 10 ACEinhibitors currently marketed in the United States,including captopril (Capoten), benazepril (Lotensin),enalapril (Vasotec), and quinapril (Acupril). The primarydifference between these drugs is their onset and dura-tion of action.

The ACE II inhibitors, losartan (Cozaar), candesar-
tan (Atacand), irbesartan (Avapro), telmisartan(Micardis), valsartan (Diovan) and eprosartan (Teveten)directly inhibit the effects of ACE II rather than blockingits production. Their actions are similar to the ACEinhibitors, but they appear to have a more favorable sideeffect and safety profile.
In addition to these drugs, other classes of drugs

have been used to lower blood pressure, most notably thethiazide diuretics . There are 12 thiazide diuretics mar-

keted in the United States, including hydrochlorothiazide(Hydrodiuril, Esidrex), indapamide (Lozol), polythiazide(Renese), and hydroflumethiazide (Diucardin). Thedrugs in this class appear to lower blood pressurethrough several mechanisms. By promoting sodium lossthey lower blood volume. At the same time, the pressureof the walls of blood vessels, the peripheral vascularresistance, is lowered. Thiazide diuretics are commonlyused as the first choice for reduction of mild hyperten-sion, and may

for reduction of mild hyperten-sion, and may be used in combination with other antihy-pertensive drugs.

Recommended dosage varies with patient, drug,
severity of hypertension, and whether the drug is beingused alone or in combination with other drugs. Consultspecialized references for further information.
Because of the large number of classes and individ-
ual drugs in this group, consult specialized references forcomplete information.
Peripheral vasodilators may cause dizziness and

orthostatic hypotension—a rapid lowering of blood pres-sure when the patient stands up in the morning. Patients
GALE ENCYCLOPEDIA OF MEDICINE 2 279Antihypertensive drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 279

taking these drugs must be instructed to rise from bed
slowly. Pregnancy risk factors for this group are gener-
ally category C. Hydralazine has been shown to causecleft palate in animal studies, but there is no human dataavailable. Breastfeeding is not recommended.
ACE inhibitors are generally well tolerated, but
may rarely cause dangerous reactions including laryn-gospasm and angioedema. Persistent cough is a com-

mon side effect. ACE inhibitors should not be used inpregnancy. When used in pregnancy during the secondand third trimesters, angiotension-converting inhibitors(ACEIs) can cause injury to and even death in the devel-
oping fetus. When pregnancy is detected, discontinuethe ACE inhibitor as soon as possible. Breastfeeding isnot recommended.ACE II inhibitors are generally well tolerated and do

not cause cough. Pregnancy risk factor is category C dur-ing the first trimester and category D during the secondand third trimesters. Drugs that act directly on the renin-angiotensin system can cause fetal and neonatal morbidi-ty and death when administered to pregnant women. Sev-eral dozen cases have been reported in patients who weretaking ACE inhibitors. When pregnancy is detected, dis-continue AIIRAs as soon as possible. Breast feeding isnot recommended.

Thiazide diuretics commonly cause potassium deple-
tion. Patients should have potassium supplementationeither through diet, or potassium supplements. Pregnancyrisk factor is category B (chlorothiazide, chlorthalidone,hydrochlorothiazide, indapamide, metolazone) or catego-
GALE ENCYCLOPEDIA OF MEDICINE 2 280Antihypertensive drugsAntihypertensive Drugs
Accupril (quinapril hydrochloride) Headache, dizziness

Aldatazide Diarrhea, fever, headache, decreased coordinationAldactone (spironolactone) Cramps, drowsiness, stomach disordersAldomet (methyldopa) Fluid retention, headache, weak feelingAltace (ramipril) Headache, coughCalan, Calan SR (verapamil hydrochloride) Constipation, fatigue, decreased blood pressureCapoten (captopril) Decreased sense of taste, decreased blood pressure tiching, rashCardene (nicardipine Hydrochloride) Dizziness, headache, indigestion and nausea, increased heartbeatCardizem

and nausea, increased heartbeatCardizem (diltiazem hydrochloride) Dizziness, fluid retention, headache, nausea, skin rashCardura (doxazosin mesylate) Dizziness, fatigue, drowsiness, headacheCatapres Dry mouth, drowsiness, dizziness, constipationCorgard (nadolol) Behaviorial changes, dizziness, decreased heartbeat, tirednessCorzide Dizziness, decreased heartbeat, fatigue, cold hands and feetDiuril (chlorothiazide) Cramps, constipation or diarrhea, dizziness, fever, increased glocose level in

dizziness, fever, increased glocose level in urineDyazide Blurred vision, muscle and abdominal pain, fatigueDynaCirc (isradipine) Chest pain, fluid retention, headache, fatigueHydroDIURIL (hydrochlorothiazide) Upset stomach, headache, cramps, loss of appetiteHygroton (chlorthalidone) Anemia, constipation or diarrhea, cramps, itchingHytrin (terazosin hydrochloride) Dizziness, labored breathing, nausea, swellingInderal (propranolol hydrochloride) Constipation or diarrhea, tingling sensation,

Constipation or diarrhea, tingling sensation, nausea and vomitingInderide Blurred vision, cramps, fatigue, loss of appetiteLasix (furosemide) Back and muscle pain, indigestion, nauseaLopressor (metoprolol tartrate) Diarrhea, itching/rash, tirednessLotensin (benazepril hydrochloride) Nausea, dizziness, fatigue, headacheAlozol (indapamide) Anxiety, headache, loss of energy, muscle crampsMaxzide Cramps, labored breathing, drowsiness, irritated stomachMinipress (prazosin hdrochloride) Headache,

(prazosin hdrochloride) Headache, nausea, weakness, dizzinessModuretic Diarrhea, fatigue, itching, loss of appetiteMonopril (fosinopril sodium) Nausea and vomiting, headache, coughNormodyne (labetalol hydrochloride) Fatigue, nausea, stuffy nosePlendil (felodipine) Pain in back, chest, muscles, joints, and abdomen, itching, dry mouth, respiratory problemsProcardia, Procardia X (nifedipine) Swelling, constipation, decreased blood pressure, nausea, fatigueSectral (acebutolol hydrochloride)

nausea, fatigueSectral (acebutolol hydrochloride) Constipation or diarrhea, gas, chest and joint painSer-Ap-Es Blurred vision, cramps, muscle pain, dizzinessTenex (guanfacine hydrochloride) Headache, constipation, dry mouth, weaknessTenoretic Decreased heartbeat, fatigue, nauseaTenormin (atenolol) Nausea, fatigue, dizzinessVeseretic Diarrhea, muscle cramps, rashVasotec (enalapril maleate) Chest pain, blurred vision, constipation or diarrhea, hives, nauseaVisken (pindolol) Muscle cramps, labored

nauseaVisken (pindolol) Muscle cramps, labored breathing, nausea, fluid retentionWytensin (guanabenz acetate) Headache, drowsiness, dizzinessZaroxolyn (metolazone) Constipation or diarrhea, chest pain, spasms, nauseaZestoretic (lisinopril hydrochlorothiazide) Fatigue, headache, dizzinessZestril (lisinopril) Labored breathing, abdominal and chest pain, nausea, decreased blood pressureGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 280

ry C (bendroflumethiazide, benzthiazide, hydroflumethi-
azide, methyclothiazide, trichlormethiazide). Routine useduring normal pregnancy is inappropriate. Thiazides arefound in breast milk. Breastfeeding is not recommended.
Beta blockers may cause a large number of adverse

reactions including dangerous heart rate abnormalities.Pregnancy risk factor is category B (acebutolol, pindolol,sotalol) or category C (atenolol, labetalol, esmolol, meto-prolol, nadolol, timolol, propranolol, penbutolol, carte-olol, bisoprolol). Breastfeeding is not recommended.
Consult specific drug references.
Samuel Uretsky, PharmDKEY TERMS
Adrenergic —Activated by adrenalin (norepineph-

rine), loosely applied to the sympathetic nervoussystem responses.
Angioedema —An allergic skin disease character-
ized by patches of circumscribed swelling involv-ing the skin and its subcutaneous layers, themucous membranes, and sometimes the viscera—called also angioneurotic edema, giant urticaria,Quincke’s disease, or Quincke’s edema.
Arteries —Blood vessels that carry blood away from
the heart to the cells, tissues, and organs of the body.

Laryngospasm— Spasmodic closure of the larynx.

Sympathetic nervous system —The part of the
autonomic nervous system that is concerned espe-cially with preparing the body to react to situa-tions of stress or emergency; it contains chieflyadrenergic fibers and tends to depress secretion,decrease the tone and contractility of smooth mus-cle, and increase heart rate.Anti-hyperuricemic drugs
Anti-hyperuricemic drugs are used to treat hyper-
uricemia, the state of having too much uric acid in theblood.
Purpose

Purpose
Anti-hyperuricemic drugs decrease the levels of uric
acid in the blood, either by increasing the rate at whichuric acid is excreted in the urine, or by preventing theformation of excess uric acid.
Before taking any medication, patients should notify

their physician of all other medications that they are cur-rently taking. Patients should also notify their physicianof any health problems they are currently experiencing.Patients must notify physicians if they have kidney prob-lems, since this might affect the type of drug adminis-tered. Patients must also notify their physician if they areallergic to any of the medications used to treat acute orlong-term gout . Since all of these factors contribute to

the disease, patients suffering from gout should attemptto lose weight, avoid excess alcohol consumption, andavoid foods high in purines, such as asparagus, sardines,lobster, avocado, and peas.
Gout and hyperuricemia
Persons with high levels of uric acid (hyper-

uricemia) may experience gout. Commonly gout occursin males in their 40s and 50s. Gout is defined by theattacks of (arthritic) painful, reddened joints, and is oftenaccompanied by hard lumps in the painful joints. Themost common joint affected is the big toe. Kidney
stones , and/or poor kidney function may also be associ-

ated with hyperuricemia, but may not be considered goutif the patient does not have painful joints. In persons withgout (and associated symptoms), uric acid forms crystals,which then cause the aforementioned symptoms.Although uric acid levels must be high in order forpatients to have crystals form, and therefore have gout,most persons with high uric acid levels don’t ever havesymptoms. Thus, recent criteria for use of anti-hyper-uricemic agents suggest that patients who have neverexperienced

suggest that patients who have neverexperienced symptoms of gout should not receive drugtherapy, unless their hyperuricemia is associated withcancer (may lead to kidney damage) or certain rare

GALE ENCYCLOPEDIA OF MEDICINE 2 281Anti-hyperuricemic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 281

genetic disorders (McGill, Rheumatologist, University of
Sydney, Australia, 2000).
Acute gout attacks
When patients experience acute attacks of gout, drugs

that lower the levels of uric acid can cause an acute goutattack or cause an attack to become more severe. Thus,drugs that lower uric acid levels and are used to treat goutin the long term are not used in the short term. Medica-tions used in acute gout attacks include non-steroidal anti-inflammatory drugs (such as indomethacin), colchicine,and corticosteroids . Colchicine causes side effects in a

large number of individuals (usually diarhhea). The mostimportant factor in the effective treatment of gout may notbe the drug used, but how quickly it is administered afteran acute attack has begun.
Long-term treatment
Long-term treatment of gout or hyperuricemia usu-

ally involves one of four drugs: allopurinol, probenicid,sulphinpyrazone, or benzbromarone (as of this printingin 2001, benzbromarone is not available for use in theUnited States). While allopurinol decreases the amountof uric acid that is produced (and may help prevent acuteattacks of gout), the other drugs all increase the rate atwhich uric acid is excreted in the urine. As previouslymentioned, lowering the concentration of uric acid cancause gout attacks. Thus, patients taking these

gout attacks. Thus, patients taking these medica-tions should have the dose slowly increased (and uricacid levels slowly lowered) to prevent acute attacks ofgout. Patients may also be treated with colchicine or non-steroidal anti-inflammatory drugs to prevent acuteattacks of gout (corticosteroids are not used in this sce-nario because over the long term corticosteroids havedeleterious side effects).

Michael V Zuck, PhD
Anti-insomnia drugs
Anti-insomnia drugs are medicines that help people
fall asleep or stay asleep.
Purpose
Physicians prescribe anti-insomnia drugs for short-

term treatment of insomnia—a sleep problem in whichpeople have trouble falling asleep or staying asleep orwake up too early and can’t go back to sleep. These drugsshould be used only for occasional treatment of tempo-rary sleep problems and should not be taken for more thana week or two at a time. People whose sleep problems lastlonger than this should see a physician. Their sleep prob-lems could be a sign of another medical problem.
The anti-insomnia drug described here, zolpidem

(Ambien), is a classified as a central nervous system(CNS) depressant. CNS depressants are medicines thatslow the nervous system. Physicians also prescribe medi-cines in the benzodiazepine family, such as flurazepam(Dalmane), quazepam (Doral), triazolam (Halcion), esta-zolam (ProSom), and temazepam (Restoril), for insom-
nia. Benzodiazepine drugs are described in the essay on
antianxiety drugs . Zaleplon (Sonata) is another anti-

insomnia drug that is not related to other drugs with thesame effect. The barbiturates , such as pentobarbital
(Nembutal) and secobarbital (Seconal) are no longercommonly used to treat insomnia because they are toodangerous if they are taken in overdoses. For patientswith mild insomnia, some antihistamines , such as
diphenhydramine (Benadryl) or hydroxyzine (Atarax)may be used, since these also cause sleepiness.
Zolpidem is available only with a physician’s pre-

scription and comes in tablet form.
The recommended dose for adults is 5-10 mg just
before bedtime. The medicine works quickly, often within20 minutes, so it should be taken right before going to bed.
For older people and others who may be more sensi-
tive to the drug’s effects, the recommended startingdosage is 5 mg just before bedtime.
Never take more than 10 mg of zolpidem in one 24-
hour period. Overdoses can lead to excessive sleepinessor coma.

Zolpidem may be taken with food or on an empty
stomach, but it may work faster when taken on an emptystomach. Check with a physician or pharmacists forinstructions on how to take the medicine.
Zolpidem is meant only for short-term treatment of

insomnia. If sleep problems last more than seven to 10days, check with a physician. Longer-lasting sleep prob-lems could be a sign of another medical problem. Also,this drug may lose its effectiveness when taken everynight for more than a few weeks.
GALE ENCYCLOPEDIA OF MEDICINE 2 282Anti-insomnia drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 282

Some people feel drowsy, dizzy, confused, light-
headed, or less alert the morning after they have takenzolpidem. The medicine may also cause clumsiness,unsteadiness, double vision, or other vision problems thenext day. For these reasons, anyone who takes thesedrugs should not drive, use machines or do anything elsethat might be dangerous until they have found out howzolpidem affects them.
This medicine has caused cause behavior changes in

some people, similar to those seen in people whosebehavior changes when they drink alcohol. Examplesinclude giddiness and rage. More extreme changes, suchas confusion, agitation, and hallucinations , also are pos-
sible. Anyone who starts having strange or unusualthoughts or behavior while taking this medicine shouldget in touch with his or her physician.
Zolpidem and other sleep medicines may cause a

special type of temporary memory loss, in which the per-son does not remember what happens between the timethey take the medicine and the time its effects wear off.This is usually not a problem, because people go to sleepright after taking the medicine and stay asleep until itseffects wear off. But it could be a problem for anyonewho has to wake up before getting a full night’s sleep(seven to eight hours). In particular, travelers should nottake this medicine on airplane flights of less than

this medicine on airplane flights of less than sevento eight hours.

Because zolpidem works work on the central ner-
vous system, it may add to the effects of alcohol andother drugs that slow down the central nervous system,such as antihistamines, cold medicine, allergy medicine,medicine for seizures, tranquilizers, some pain relievers,
and muscle relaxants . Zolpidem may also add to the

effects of anesthetics, including those used for dentalprocedures. The combined effects of zolpidem and alco-hol or other CNS depressants (drugs that slow the centralnervous system) can be very dangerous, leading tounconsciousness or even death . People who take zolpi-

dem should not drink alcohol and should check with theirphysicians before taking any other CNS depressant. Any-one who shows signs of an overdose or of the effects ofcombining zolpidem drugs with alcohol or other drugsshould have immediate emergency help. Warning signs
include severe drowsiness, severe nausea or vomiting,breathing problems, and staggering.
Anyone who takes zolpidem for more than one to

two weeks should not stop taking it without first check-ing with a physician. Stopping the drug abruptly maycause rebound insomnia; increased difficulty fallingasleep for the first one of two nights after the drug hasbeen discontinued. In rare cases, withdrawal symptoms,such as vomiting, cramps, and unpleasant feelings mayoccur. Gradual tapering may be necessary.

zolpidem. This may increase the chance of side effects,such as confusion, and may also increase the risk offalling.
In people with breathing problems, zolpidem may
worsen the symptoms.
People with certain other medical conditions or who
are taking certain other medicines can have problems ifthey take zolpidem. Before taking this medicine, be sureto let the physician know about any of these conditions:

to zolpidem in the past should let his or her physicianknow before taking the drugs again. The physicianshould also be told about any allergies to foods, dyes,
preservatives, or other substances.
become pregnant should check with their physiciansabout the safety of using zolpidem during pregnancy .
BREASTFEEDING. Women who are breastfeeding
should check with their physicians before using zolpi-dem.

OTHER MEDICAL CONDITIONS. Before using zolpi-
dem, people with any of these medical problems shouldmake sure their physicians are aware of their conditions:
• chronic lung diseases ( emphysema ,asthma , or chron-
ic bronchitis)
GALE ENCYCLOPEDIA OF MEDICINE 2 283Anti-insomnia drugs
Anti-Insomnia Drugs
Ambien (zolpidem tartrate) Daytime drowsiness, dizziness, headache

Dalmane (flurazepam hydrochloride) Decreased coordination, lightheadedness, dizzinessDoral (quazepam) Daytime drowsiness, headache, dry mouth, fatigueHalcion (triazolam) Decreased coordination, chest pain, memory impairmentProSom (estazolam) Dizziness, headache, nausea, weaknessRestoril (temazepam) Dizziness, fatigue, nausea, headache, sluggishnessGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 283

• current or past alcohol or drug abuse
• depression• sleep apnea
USE OF CERTAIN MEDICINES. Taking zolpidem with
certain other drugs may affect the way the drugs work ormay increase the chance of side effects.
The most common minor side effects are daytime
drowsiness or a “drugged” feeling, vision problems,memory problems, nightmares or unusual dreams, vom-iting, nausea, abdominal or stomach pain, diarrhea ,dry

mouth ,headache , and general feeling of discomfort or
illness. These problems usually go away as the bodyadjusts to the drug and do not require medical treatment.
Patients who take zolpidem may notice side effects

for several weeks after they stop taking the drug. Theyshould check with their physicians if these or other trou-blesome symptoms occur:
• agitation, nervousness, feelings of panic
• uncontrolled crying
• worsening of mental or emotional problems
• seizures• tremors
• lightheadedness
• sweating
• flushing
• nausea or abdominal or stomach cramps
• muscle cramps

unusual symptoms after taking zolpidem should get intouch with his or her physician.
Zolpidem may interact with other medicines. When
this happens, the effects of one or both of the drugs mayKEY TERMS
Bronchitis —Inflammation of the air passages of
the lungs.

Sleep apnea —A condition in which a person tem-
porarily stops breathing during sleep.
change or the risk of side effects may be greater. Anyone

who takes zolpidem should let the physician know allother medicines he or she is taking. Among the drugs thatmay interact with zolpidem are:
• other central nervous system (CNS) depressants such as
sedatives; tranquilizers; prescription pain medicine;muscle relaxants; medicine for seizures; barbiturates;and anesthetics.
• the major tranquilizer chlorpromazine (Thorazine).

and amitriptyline (Elavil)
Anti-itch drugs
Anti-itch drugs are medicines taken by mouth or by
injection to relieve itching .
Purpose
The medicine described here, hydroxyzine, is a type
of antihistamine used to relieve itching caused by allergic
GALE ENCYCLOPEDIA OF MEDICINE 2 284Anti-itch drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 284

reactions. An allergic reaction occurs when the body is
unusually sensitive to some substance, such as pollen,dust, mold, or certain foods or medicine. The body reactsby releasing a chemical called histamine that causes itch-ing and other symptoms, such as sneezing and wateryeyes. Antihistamines reduce the symptoms by blocking
the effects of histamine.
Hydroxyzine is also prescribed for anxiety and to help
people relax before or after having general anesthesia.

Anti-itch drugs, also called antipruritic drugs, are
available only with a physician’s prescription and come intablet and injectable forms. Some commonly used brandsof the anti-itch drug hydroxyzine are Atarax and Vistaril.
When prescribed for itching, the usual dosage for

adults is 25 mg, three to four times a day. For childrenover six years of age, the usual dosage 50-100 mg perday, divided into several small doses. The usual dosagefor children under six years of age is 50 mg per day,divided into several small doses.
The dosage may be different for different people.

Check with the physician who prescribed the drug or thepharmacist who filled the prescription for the correctdosage, and take the medicine exactly as directed.
This medicine should not be used for more than four
months at a time because its effects can wear off. See aphysician regularly while taking the medicine to deter-mine whether it is still needed.
Hydroxyzine may add to the effects of alcohol and

other drugs that slow down the central nervous system,such as other antihistamines, cold medicine, allergy medi-cine, sleep aids, medicine for seizures, tranquilizers, somepain relievers, and muscle relaxants . Anyone taking
hydroxyzine should not drink alcohol and should checkwith his or her physician before taking any of the above.
Some people feel drowsy or less alert when using

this medicine. Anyone who takes it should not drive, usemachines, or do anything else that might be dangerousuntil they have found out how the drugs affect them.
Anyone who has had unusual reactions to hydrox-
yzine in the past should let his or her physician knowbefore taking the medicine again. The physician shouldalso be told about any allergies to foods, dyes, preserva-
tives, or other substances.KEY TERMS

Anesthesia —Treatment with medicine that causes
a loss of feeling, especially pain. Local anesthesianumbs only part of the body; general anesthesiacauses loss of consciousness.
Antihistamine —Medicine that prevents or relieves
allergy symptoms.
A woman who is pregnant or who may become
pregnant should check with her physician before takingthis medicine. In studies of laboratory animals, hydrox-yzine has caused birth defects when taken during preg-

nancy . Although the drug’s effects on pregnant women
have not been fully studied, physicians advise againsttaking it in early pregnancy.
should also check with their physicians before usinghydroxyzine. The medicine may pass into breast milkand may cause problems in nursing babies whose moth-ers take it.
The most common side effect, drowsiness, usually

goes away as the body adjusts to the drug. If it does not,reducing the dosage may be necessary. Other sideeffects, such as dry mouth , also may occur and do not
need medical attention unless they continue.
• twitches or tremors
• convulsions (seizures)

Hydroxyzine may interact with other medicines.
When this happens, the effects of one or both of thedrugs may change or the risk of side effects may begreater. Anyone who takes hydroxyzine should let thephysician know all other medicines he or she is taking.Among the drugs that may interact with hydroxyzine are:
• barbiturates such as phenobarbital and secobarbital
(Seconal)
• opioid (narcotic) pain medicines such as meperidine

(Demerol) and oxycodone (Percocet)
GALE ENCYCLOPEDIA OF MEDICINE 2 285Anti-itch drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 285

• non-narcotic pain medicines such as acetaminophen
(Tylenol) and ibuprofen (Motrin, Advil)
The list above may not include every drug that inter-
acts with hydroxyzine. Be sure to check with a physicianor pharmacist before combining hydroxyzine with anyother prescription or nonprescription (over-the-counter)medicine.
Antimalarial drugs
Antimalarial drugs are medicines that prevent or
treat malaria .
Purpose
Antimalarial drugs treat or prevent malaria, a disease

that occurs in tropical, subtropical, and some temperateregions of the world. The disease is caused by a parasite,Plasmodium , which belongs to a group of one-celled

organisms known as protozoa. The only way to getmalaria is to be bitten by a certain type of mosquito thathas bitten someone who has the disease.Thanks to mos-quito control programs, malaria has been eliminated inthe United States, almost all of Europe, and large parts ofCentral and South America. However, mosquito controlhas not worked well in other parts of the world, andmalaria continues to be a major health problem in partsof Africa, Southeast Asia, Latin America, Haiti, theDominican

Asia, Latin America, Haiti, theDominican Republic, and some Pacific Islands. Everyyear, some 30,000 Americans and Europeans who travelto these areas get malaria. People planning to travel tothe tropics are often advised to take antimalarial drugsbefore, during, and after their trips, to help them avoidgetting the disease and bringing it home with them.These drugs kill Plasmodium or prevent its growth.

In recent years, some strains of Plasmodium have
become resistant to antimalarial drugs, and medicalresearchers have stepped up efforts to develop a malariavaccine. In early1997, researchers reported encouragingresults from a small study of one vaccine and planned totest the vaccine in Africa.
Antimalarial drugs are available only with a physi-

cian’s prescription. They come in tablet, capsule, andinjectable forms. Among the commonly used antimalari-al drugs are chloroquine (Aralen), mefloquine (Lariam),primaquine, pyrimethamine (Daraprim), and quinine.
Recommended dosage depends on the type of anti-

malarial drug, its strength, and the form in which it isbeing used (such as tablet or injection). The dosage mayalso be different for different people. Check with thephysician who prescribed the drug or the pharmacist whofilled the prescription for the correct dosage. Always takethis medicine exactly as directed, and keep taking it forthe full time of treatment. If the drug is being taken totreat malaria, do not stop taking it just because symptomsbegin to improve. Symptoms may return if the

to improve. Symptoms may return if the drug isstopped too soon. Never take larger or more frequentdoses than the physician has ordered, and do not take thedrug for longer than directed.

Travelers taking this medicine to prevent malaria may
be told to take it for one to two weeks before their trip andfor 4 weeks afterward, as well as for the whole time theyare away. It is important to follow these directions.
Antimalarial drugs work best when they are taken on

a regular schedule. When taken once a week to preventmalaria, they should be taken on the same day everyweek. When taken daily or several times a day to treatmalaria, they should be taken at the same time every day.Doses should not be missed or skipped.
Some antimalarial drugs should be taken with meals
or with milk to prevent upset stomach. Others must betaken with a full glass of water. Be sure to follow direc-tions for the best way to take the drug that is prescribed.

Antimalarial drugs may cause lightheadedness,
dizziness , blurred vision and other vision changes. Any-
one who takes these drugs should not drive, use machinesor do anything else thatmight be dangerous until theyhave found out how the drugs affect them.
The antimalarial drug mefloquine (Lariam) has
received attention because of reports that it causes panicattacks, hallucinations ,anxiety , depression, paranoia ,

and other mental and mood changes, sometimes lastingfor months after the last dose. A study published in 1996in the British Medical Journal noted that about one in 140

travelers who take the drug may have mental or moodchanges severe enough to interfere with normal activities.This compares to about one in 1,100 patients who havesuch reactions to the antimalarial drug chloroquine. Any-one who has unexplained anxiety, depression, restless-ness, confusion, or other troubling mental or moodchanges after taking mefloquine should call a physician
GALE ENCYCLOPEDIA OF MEDICINE 2 286Antimalarial drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 286

right away. Switching to a different antimalarial drug may
be an alternative and can allow the side effects to stop.
Anyone taking antimalarial drugs to prevent malaria
who develops a fever or flu-like symptoms while taking
the medicine or within two to three months after travel-ing to an area where malaria is common should call aphysician immediately.
If the medicine is being taken to treat malaria, and
symptoms stay the same or get worse, check with thephysician who prescribed the medicine.

Patients who take this medicine over a long time
need to have a physician check them periodically forunwanted side effects.
Babies and children are especially sensitive to the
antimalarial drug chloroquine. Not only are they morelikely to have side effects from the medicine, but they arealso at greater risk of being harmed by an overdose. Asingle 300-mg tablet could kill a small child. Keep this
medicine out of the reach of children. Use safety vials.

taking certain other medicines can have problems ifthey take antimalarial drugs. Before taking these drugs,be sure to let the physician know about any of theseconditions:
ALLERGIES. Anyone who has had unusual reac-
tions to antimalarial drugs or related medicines in thepast should let his or her physician know before takingthe drugs again. The physician should also be toldabout any allergies to foods, dyes, preservatives, or

other substances.
PREGNANCY. In laboratory animal studies, some
antimalarial drugs cause birth defects . But it is also
risky for a pregnant woman to get malaria. Untreatedmalaria can cause premature birth, stillbirth , and mis-
carriage . When given in low doses to prevent malaria,

antimalarial drugs have not been reported to cause birthdefects in humans. If possible, pregnant women shouldavoid traveling to areas where they could get malaria. Iftravel is necessary, women who are pregnant or who maybecome pregnant should check with their physiciansabout the use of antimalarial drugs.
BREASTFEEDING. Some antimalarial drugs pass into

breast milk. Although no problems have been reported innursing babies whose mothers took antimalarial drugs,babies and young children are particularly sensitive tosome of these drugs. Women who are breastfeedingshould check with their physicians before using anti-malarial drugs.OTHER MEDICAL CONDITIONS. Before using anti-

malarial drugs, people who have any of these medicalproblems (or have had them in the past) should makesure their physicians are aware of their conditions:
• blood disease
• nerve or brain disease or disorder, including seizures
(convulsions)
• past or current mental disorder
• stomach or intestinal disease
• deficiency of the enzyme glucose-6-phosphate dehy-
drogenase (G6PD), which is important in the break-down of sugar in the body

• deficiency of the enzyme nicotinamide adenine dinu-
cleotide (NADH) methemoglobin reductase
• heart disease• family or personal history of the genetic condition fav-
ism (a hereditary allergic condition)
• family or personal history of hemolytic anemia , a con-
dition in which red blood cells are destroyed
• purpura
• hypoglycemia (low blood sugar)
• blackwater fever (a serious complication of one type of
malaria)
• myasthenia gravis (a disease of the nerves and muscles)

USE OF CERTAIN MEDICINES. Taking antimalarial
High doses of the antimalarial drug pyrimethamine

may cause blood problems that caninterfere with healingand increase the risk of infection. People taking this drugshould be careful not to injure their gums when brushingor flossing their teeth or using toothpicks. If possible,dental work should be postponed until treatment is com-plete and the blood has returned to normal.
The most common side effects of antimalarial drugs
are diarrhea , nausea or vomiting, stomach cramps or

pain , loss of appetite, headache ,itching , difficulty con-
centrating, dizziness, lightheadedness, and sleep prob-lems. These problems usually go away as the bodyadjusts to the drug and do not require medical treatment.Less common side effects, such as hair loss or loss ofcolor in the hair; skin rash; or blue-black discoloration ofthe skin, fingernails, or inside of the mouth also may
GALE ENCYCLOPEDIA OF MEDICINE 2 287Antimalarial drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 287

occur and do not need medical attention unless they are
long-lasting.
occur. If any of the following side effects occur, check withthe physician who prescribed the medicine immediately:
• blurred vision or any other vision changes
• hallucinations• anxiety
• weakness or unusual tiredness• unusual bruising or bleeding
• hearing loss or ringing or buzzing in the ears

• fever, with or without sore throat
• slow heartbeat
• pain in the back or legs• dark urine
• pale skin
• taste changes• soreness, swelling, or burning sensation in the tongue
unusual symptoms after taking anantimalarial drugshould get in touch with his or her physician.
Some antimalarial drugs may interact with other

medicines. When this happens, the effects of one or bothof the drugs may change or the risk of side effects maybe greater. Anyone who takes antimalarial drugs shouldlet the physician know all other medicines he or she istaking. Among the drugs that interact with some anti-malarial drugs are:
• beta blockers such as atenolol (Tenormin), propranolol
(Inderal), and metoprolol (Lopressor)
• calcium channel blockers such as diltiazem (Cardizem),

nicardipene (Cardene), and nifedipine (Procardia)
• other antimalarial drugs• quinidine, used to treat abnormal heart rhythms
• antiseizure medicines such as vaproic acid derivatives
(Depakote or Depakene)
• oral typhoid vaccine• diabetes medicines taken by mouth
• sulfonamides (sulfa drugs)
• vitamin KKEY TERMS
Hypoglycemia —Abnormally low levels of glucose
in the blood.
Organism —An individual of some type of life

form, such as a plant or an animal.
Parasite —An organism that lives and feeds in or
on another organism (the host) and does nothingto benefit the host.
Protozoa —Animal-like, one-celled organisms,
some of which cause diseases in people.
Purpura —A spotty or patchy purplish rash caused
by bleeding under the surface of the skin.
• anticancer drugs

• medicine for overactive thyroid• antiviral drugs such as zidovudine (Retrovir)
The list above does not include every medicine that
may interact with every antimalarial drug. Be sure tocheck with a physician or pharmacist before combiningan antimalarial drug with any other prescription or non-prescription (over-the-counter) medicine.
Resources
Schmidt, Elizabeth B. “The Road to Illville.” Harvard Health
Letter 19 (Nov. 1993): 6.
OTHER

OTHER
“Should You Take Lariam?” Travel Health Information Page.
<http://travelhealth.com/lariam.htm>.
Antimicrobial agents seeAntibiotics
Antimigraine drugs
Antimigraine drugs are medicines used to prevent or
reduce the severity of migraine headaches.
GALE ENCYCLOPEDIA OF MEDICINE 2 288Antimigraine drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 288

Purpose
Migraine headaches usually cause a throbbing pain
on one side of the head. Nausea, vomiting, dizziness ,

increased sensitivity to light and sound, and other symp-toms may accompany the pain. The attacks may last forseveral hours or for a day or more and may come as oftenas several times a week. Some people who get migraineheadaches have warning signals before the headachesbegin, such as restlessness, tingling in an arm or leg, orseeing patterns of flashing lights. This set of signals iscalled an aura. The antimigraine drugs discussed in thissection are meant to be taken as soon as the pain

are meant to be taken as soon as the pain begins,to relieve the pain and other symptoms. Other types ofdrugs, such as antiseizure medicines, antidepressants,calcium channel blockers and beta blockers , are some-

times prescribed to prevent attacks in people with verysevere or frequent migraines.
Migraine is thought to be caused by electrical and

chemical imbalances in certain parts of the brain. Theseimbalances affect the blood vessels in the brain—firsttightening them up, then widening them. As the blood ves-sels widen, they stimulate the release of chemicals thatincrease sensitivity to pain and cause inflammation andswelling. Antimigraine drugs are believed to work by cor-recting the imbalances and by tightening the blood vessels.
Examples of drugs in this group are ergotamine

(Cafergot), naratriptan (Amerge), sumatriptan (Imitrex),rizatriptan (Maxalt) and zolmitriptan (Zomig). Methy-sergide maleate (Sansert) may be used by patients whoseheadaches are not controlled by other drugs, while somepatients do well on other drugs. For example, combina-tions or ergotamine and caffeine may be very effective.
The caffeine acts by constricting blood vessels to relievethe headache . Sometimes, an analgesic such as aceta-

minophen , caffeine, and a barbiturate which acts as a
sedative, are combined, as in Fioricet and similar com-pounds. These medicines are available only with a physi-cian’s prescription and come in several forms. Ergota-mine is available as tablets and rectal suppositories;sumatriptan as tablets, injections, and nasal spray; andzolmitriptan as tablets.
Antimigraine drugs are used to treat headaches once
they have started. These drugs should not be taken to pre-vent headaches.

Recommended dosage depends on the type of drug.
Typical recommended dosages for adults are given belowfor each type of drug.Ergotamine
Take at the first sign of a migraine attack. Patients
who get warning signals (aura) may take the drug as soonas they know a headache is coming.
TABLETS. No more than six tablets for any single
attack.
No more than 10 tablets per week.
SUPPOSITORIES. No more than two suppositories
for any single attack.

No more than five suppositories per week.
Naratriptan
Take as soon as pain or other migraine symptoms
begin. Also effective if taken any time during an attack.Do not take the drug until the pain actually starts as notall auras result in a migraine.
TABLETS. Usual dose is one 1-mg tablet taken with
water or other liquid.
Doses of 2.5-mg may be used, but they may cause
more side effects.
If the headache returns or if there is only partial

response, the dose may be repeated once after four hours,for a maximum dose of 5 mg in a 24-hour period. Largerdoses do not seem to offer any benefit.
Sumatriptan
TABLETS. Usual dose is one 25-mg tablet, taken with

Doses should be spaced at least two hours apart.Anyone with liver disease should consult with a
physician for proper dosing.
INJECTIONS. No more than 6 mg per dose, injected
under the skin.
No more than two 6-mg injections per day. These
doses should be taken at least 1 hour apart.
Zolmitriptan
Take as soon as symptoms begin.
TABLETS. Usual dose is 1-5 mg. Additional doses
may be taken at two-hour intervals.
No more than 10 mg per 24-hour period.

GALE ENCYCLOPEDIA OF MEDICINE 2 289Antimigraine drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 289

General dosage advice
Always take antimigraine drugs exactly as directed.
Never take larger or more frequent doses, and do not takethe drug for longer than directed.
If possible, lie down and relax in a dark, quiet room
for a few hours after taking the medicine.
These drugs should be used only to treat the type of
headache for which they were prescribed. Patients shouldnot use them for other headaches, such as those causedby stress or too much alcohol, unless directed to do so by

a physician.
Anyone whose headache is unlike any previous
headache should check with a physician before taking thesedrugs. If the headache is far worse than any other, emer-gency medical treatment should be sought immediately.
Taking too much of the antimigraine drug ergota-
mine (Cafergot), can lead to ergot poisoning . Symptoms
include headache, muscle pain, numbness, coldness, andunusually pale fingers and toes. If not treated, the condi-tion can lead to gangrene (tissue death ).

Sumatriptan (Imitrex), naratriptan (Amerge), riza-
triptan (Maxalt) and zolmitriptan (Zomig) may interactwith ergotamine. These drugs should not be taken within24 hours of taking any drug containing ergotamine.
Some antimigraine drugs work by tightening blood

vessels in the brain. Because these drugs also affectblood vessels in other parts of the body, people withcoronary heart disease, circulatory problems, or highblood pressure should not take these medicines unlessdirected to do so by their physicians.

are taking certain other medicines can have problems if theytake antimigraine drugs. Before taking these drugs, be sureto let the physician know about any of these conditions:
to ergotamine, caffeine, sumatriptan, zolmitriptan, orother antimigraine drugs in the past should let his or her
physician know before taking the drugs again. The physi-cian should also be told about any allergies to foods,

PREGNANCY. Women who are pregnant should not
take ergotamine (Cafergot). The effects of other antimi-graine drugs during pregnancy have not been well stud-
ied. Any woman who is pregnant or plans to becomepregnant should let her physician know before an antimi-graine drug is prescribed.
BREASTFEEDING. Some antimigraine drugs can pass

into breast milk and may cause serious problems in nurs-ing babies. Women who are breastfeeding should checkwith their physicians about whether to stop breastfeedingwhile taking the medicine.
antimigraine drugs, people with any of these medicalproblems should make sure their physicians know abouttheir conditions:

• coronary heart disease• angina (crushing chest pain)• circulatory problems or blood vessel disease• high blood pressure• liver problems• kidney problems• any infection• eye problems
USE OF CERTAIN MEDICINES. Taking antimigraine
drugs certain other drugs may affect the way the drugswork or may increase the chance of side effects.
The most common side effects are fluid retention,

flushing; high blood pressure; unusually fast or slowheart rate; numbness; tingling; itching ; nausea; vomit-
ing; weakness; neck or jaw pain and stiffness; feelings oftightness, heaviness, warmth, or coldness; sore throat ;
and discomfort of the mouth and tongue.
GALE ENCYCLOPEDIA OF MEDICINE 2 290Antimigraine drugsAntimigraine Drugs

Cafergot Nausea, increased blood pressure, fluid retention, numbness, increased heart rate, tingling sensation
Imitrex (sumatriptan succinate) Burning, flushing, neck pain, inflammation at injection site, sore throat, tingling sensationInderal (propranolol hydrochloride) Constipation or diarrhea, headache, nausea, rashMidrin Dizziness, rashGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 290

More serious side effects are not common, but they
may occur. If any of the following side effects occur, calla physician immediately:
• bluish tinge to the skin• cold arms and legs• signs of gangrene, such as coldness, dryness, and a
shriveled or black appearance of a body part
• drowsiness
• shortness of breath or wheezing
• skin rash• swelling of the eyelids or face
Other side effects may occur with any antimigraine

drug. Anyone who has unusual symptoms after taking thismedicine should get in touch with his or her physician.
Antimigraine drugs may interact with other medicines.
When this happens, the effects of one or both of the drugsmay change, or the risk of side effects may be greater. Any-one who takes these drugs should let the physician know allother medicines he or she is taking. Among the drugs thatmay interact with antimigraine drugs are:

• beta blockers such as atenolol (Tenormin) and propra-
nolol (Inderal)
• drugs that tighten blood vessels such as epinephrine
(EpiPen) and pseudoephedrine (Sudafed)
• nicotine such as cigarettes or Nicoderm, Habitrol, and
other smoking-cessation drugs
• certain antibiotics , such as erythromycin and clar-
ithromycin (Biaxin)
• monoamine oxidase inhibitors such as phenelzine
(Nardil) and tranylcypromine (Parnate)
• certain antidepressants, such as sertraline (Zoloft), flu-

oxetine (Prozac), and paroxetine (Paxil)
• fluvoxamine (Luvox), prescribed for obsessive compul-
sive disorder or chronic pain
Remember naratriptan, sumatriptan, rizatriptan and
zolmitriptan may interact with ergotamine. These drugsshould not be taken within 24 hours of taking any drugcontaining ergotamine.
Resources
BOOKS
Duckro, Paul N., William D. Richardson, and Janet E. Mar-
shall. Taking Control of Your Headaches: How to Get theKEY TERMS
Aura —A set of warning symptoms, such as seeing

flashing lights, that some people have 10-30 min-utes before a migraine attack.
Treatment You Need . New York, NY: The Guilford Press,
1995.
American Council for Headache Education (ACHE). 19 Man-
tua Road, Mt. Royal, NJ 08061. (800) 255-2243. <http://www.achenet.org>.
National Headache Foundation. 428 W. St. James Place, Chica-

go, IL 60614. (800) 843-2256. <http://www.headaches.org>. 
Box 5801, Bethesda, MD 20824. (800) 352-9424. <http://www.ninds.nih.gov>.
Antimyocardial antibody test
Testing for antimyocardial antibodies is done when
evaluating a person for heart damage or heart disease.
Purpose
Antimyocardial antibodies are autoantibodies. Nor-

mal antibodies are special proteins built by the body as adefense against foreign material entering the body.Autoantibodies are also proteins built by the body, butinstead of attacking foreign material, they inappropriate-ly attack the body’s own cells. Antimyocardial antibodiesattack a person’s heart muscle, or myocardium.
This test may be done on a person who recently had
trauma to the heart, such as heart surgery or a myocardialinfarction ( heart attack ). It also may be done on some-

one with heart disease, such as cardiomyopathy orrheumatic fever .
Although the presence of antimyocardial antibodies
does not diagnose heart damage or disease, there is aconnection between the presence of these antibodies anddamage to the heart. The amount of damage, however,cannot be predicted by the amount of antibodies.
GALE ENCYCLOPEDIA OF MEDICINE 2 291Antimyocardial antibody testGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 291

These antibodies usually appear after heart surgery
or the beginning of disease, but they may be presentbefore surgery or the onset of disease. In 30% of peoplewith myocardial infarction and 70% of people havingheart surgery, antimyocardial antibodies will appear with-in two to three weeks and stay for three to eight weeks.
A 5-10 mL sample of venous blood is drawn from the

patient’s arm in the region of the inner elbow. Antimyocar-dial antibodies are detected by combining a patient’sserum (clear, thin, sticky fluid in blood) with cells fromanimal heart tissue, usually that of a monkey. Antimyocar-dial antibodies in the serum bind to the heart tissue cells. Afluorescent dye is then added to the mixture. This dye willattach to any antibodies and heart tissue cells boundtogether. The final mixture is studied under a microscopethat is designed to show fluorescence.

microscopethat is designed to show fluorescence. If fluorescent cellsare seen under the microscope, the test is positive.

When the test is positive, the next step is to find out
how much antibody is present. The patient’s serum isdiluted, or titered, and the test is done again. The serum isthen further diluted and the test repeated until the serum isso dilute that fluorescence is no longer seen. The last dilu-tion that showed fluorescence is the titer reported.
No fasting or special prepartion is needed. Before
the test is done it should be explained to the patient.
Aftercare

Aftercare
site after the blood is drawn or the person may feel dizzyor faint. Pressure to the puncture site until the bleedingstops reduces bruising. Warm packs on the puncture siterelieve discomfort.
Antimyocardial antibodies are not normally seen in
healthy individuals.
A positive result means that antimyocardial antibod-

ies are present and that heart disease or damage is likely.Further testing may be needed as other autoantibodiescould also be present, causing a false abnormal test.
Resources
BOOKS
Clinical Diagnosis and Management by Laboratory Methods.
19th ed. Ed. John B. Henry. Philadelphia: W. B. SaundersCo., 1996.KEY TERMS
Antibody —A special protein built by the body as a
defense against foreign material entering the body.
Antimyocardial antibody —An autoantibody that

attacks a person’s own heart muscle, or myocardi-um.
Autoantibody —An antibody that attacks the body’s
own cells or tissues.
Myocardial infarction —A block in the blood sup-
ply to the heart, resulting in what is commonlycalled a heart attack.
Myocardium —The muscular middle layer of the
heart.
Titer —A dilution of a substance with an exact
known amount of fluid. For example, one part ofserum diluted with four parts of saline is a titerof 1:4.

Antinausea drugs
Antinausea drugs are medicines that control nausea—

a feeling of sickness or queasiness in the stomach with anurge to vomit. These drugs also prevent or stop vomiting.Drugs that control vomiting are called antiemetic drugs.
Purpose
The drug described here, prochlorperazine (Com-
pazine), controls both nausea and vomiting . Prochlor-
perazine is also sometimes prescribed for symptoms ofmental disorders, such as schizophrenia .
Prochlorperazine is available only with a physician’s

prescription. It is sold in syrup, capsule, tablet, injection,and suppository forms.
GALE ENCYCLOPEDIA OF MEDICINE 2 292Antinausea drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 292

To control nausea and vomiting in adults, the usual
dose is:
• tablets: one 5-mg or 10-mg tablet three to four times a
day
• extended-release capsules: one 15-mg capsule first
thing in the morning or one 10-mg capsule every 12hours
• suppository: 25 mg, twice a day• syrup: 5-10 mg three to four times a day• injection: 5-10 mg injected into a muscle three to four
times a day
Doses for children must be determined by a physician.

Prochlorperazine may cause a movement disorder
called tardive dyskinesia . Signs of this disorder are
involuntary twitches and muscle spasms in the face andbody and jutting or rolling movements of the tongue. Thecondition may be permanent. Older people, especiallywomen, are particularly at risk of developing this prob-lem when they take prochlorperazine.
Some people feel drowsy, dizzy, lightheaded, or

less alert when using this medicine. The drug may alsocause blurred vision, and movement problems. Forthese reasons, anyone who takes this drug should notdrive, use machines or do anything else that might bedangerous until they have found out how the drugaffects them.
Prochlorperazine makes some people sweat less,

which can allow the body to overheat. The drug mayalso make the skin and eyes more sensitive to the sun.People who are taking prochlorperazine should try toavoid extreme heat and exposure to the sun. Whengoing outdoors, they should wear protective clothing, ahat, a sunscreen with a skin protection factor (SPF) ofat least 15, and sunglasses that block ultraviolet (UV)light. Saunas, sunlamps, tanning booths, tanning beds,hot baths, and hot tubs should be avoided while takingthis medicine. Anyone

be avoided while takingthis medicine. Anyone who must be exposed to extremeheat while taking the drug should check with his or her

physician.
This medicine adds to the effects of alcohol and
other drugs that slow down the central nervous system,such as antihistamines , cold and flu medicines, tran-
quilizers, sleep aids, anesthetics, some pain medicines,
and muscle relaxants . Do not drink alcohol while tak-
ing prochlorperazine, and check with the physician whoprescribed the drug before combining it with any othermedicines.

with the physician who prescribed it. Stopping the drugsuddenly can dizziness , nausea, vomiting, tremors , and
other side effects. When stopping the medicine, it may benecessary to taper down the dose gradually.
Prochlorperazine may cause false pregnancy tests.
Women who are pregnant (or planning to become
pregnant) or breast feeding should check with theirphysicians before using this medicine.
Before using prochlorperazine, people with any of

• previous sensitivity or allergic reaction to prochlorper-
azine
• glaucoma• brain tumor
• intestinal blockage
• abnormal blood conditions, such as leukemia
• exposure to pesticides.
Many side effects are possible with this drug,
including, but not limited to, constipation , dizziness,

drowsiness, decreased sweating, dry mouth , stuffy nose,
movement problems, changes in menstrual period,increased sensitivity to sun, and swelling or pain inbreasts. Anyone who has unusual or troublesome symp-toms after taking prochlorperazine should get in touchwith his or her physician.
GALE ENCYCLOPEDIA OF MEDICINE 2 293Antinausea drugs
Antinausea Drugs

Compazine (phochlorperazine) Involuntary muscle spasms, dizziness, jitteriness, puckering of the mouth
Phenergan (promethazine hydrochloride) Dizziness, dry mouth, nausea and vomiting, rashReglan (metoclopramide hydrochloride) Fatigue, drowsiness, restlessnessTigan (trimethobenzamide hydrochloride) Blurred vision, diarrhea, cramps, headacheZofan (ondansetron hydrochloride) Constipation, headache, fatigue, abdominal painGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 293

Prochlorperazine may interact with other medicines.

When this happens, the effects of one or both of thedrugs may change or the risk of side effects may begreater. Among the drugs that may interact withprochlorperazine are antiseizure drugs such as phenytoin(Dilantin) and carbamazepine (Tegretol), anticoagulantssuch as warfarin (Coumadin), and drugs that slow thecentral nervous system such as alprazolam (Xanax),diazepam (Valium), and secobarbital (Seconal). Notevery drug that interacts with prochlorperazine is listedhere. Be sure to check with a

is listedhere. Be sure to check with a physician or pharmacistbefore taking any other prescription or nonprescription(over-the-counter) drug with Prochlorperazine.

Antinuclear antibody test
The antinuclear antibody (ANA) test is a test done
early in the evaluation of a person for autoimmune orrheumatic disease, particularly systemic lupus erythe-
matosus (SLE).
Purpose
In autoimmune diseases, the body makes antibodies
that work against its own cells or tissues. Rheumatic dis-eases (diseases that affect connective tissue, includingthe joints, bone, and muscle) are also associated withKEY TERMS

Anesthetic —Medicine that causes a loss of feel-
ing, especially pain. Some anesthetics also cause aloss of consciousness.
and the nerves throughout the body.
Spasm —Sudden, involuntary tensing of a muscle
or a group of muscles.
Tranquilizer —Medicine that has a calming effect
and is used to treat anxiety and mental tension.these antibodies. Autoantibodies are proteins built by the

body, but instead of guarding against foreign material(including bacteria, viruses, and fungi) as normal anti-bodies do, they attack the body’s own cells.
Autoimmune and rheumatic diseases can be difficult
to diagnose. People with the same disease can have verydifferent symptoms. A helpful strategy in the diagnosisof these diseases is to find and identify an autoantibodyin the person’s blood.
The antinuclear antibody test looks for a group of

autoantibodies that attack substances found in the center(nucleus) of all cells. It is useful as a screen for manyautoantibodies associated with diseases that affect theentire body (systemic diseases).
This test is particularly useful when diagnosing a

person with symptoms of SLE, an illness that affectsmany body organs and tissues. If the test is negative, it isunlikely that the person has SLE; if the test is positive,more tests are done to confirm whether the person hasSLE or another related disease. Other diseases, such asscleroderma ,Sjögren’s syndrome ,Raynaud’s disease ,
rheumatoid arthritis , and autoimmune hepatitis, often
have a positive test for antinuclear antibodies.
Five to 10 mL of blood is needed for this test. The

antinuclear antibody test is done by adding a person’sserum to commercial cells mounted on a microscopeslide. If antinuclear antibodies are in the serum, they bindto the nuclei of cells on the slide. Next, a second anti-body is added to the mixture. This antibody is “tagged”with a fluorescent dye so that it can be seen. The secondantibody attaches to any antibodies and cells boundtogether and, because of the fluorescent “tag,” the areaswith antinuclear antibodies seem to glow, or fluoresce,when

antibodies seem to glow, or fluoresce,when the slide is viewed under an ultraviolet microscope.

If fluorescent cells are seen, the test is positive.
When positive, the serum is diluted, or titered, and thetest done again. These steps are repeated until the serumis so dilute it no longer gives a positive result. The lastdilution that shows fluorescence is the titer reported.
The pattern of fluorescence within the cells gives the
physician clues as to what the disease might be. The testresult includes the titer and the pattern.
This test is also called the fluorescent antinuclear

antibody test or FANA. Results are available within oneto three days.
No special preparations or diet changes are required
before a person undergoes an antinuclear antibody test.
GALE ENCYCLOPEDIA OF MEDICINE 2 294Antinuclear antibody testGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 294

Aftercare
site or the person may feel dizzy or faint. Pressure to thepuncture site until the bleeding stops reduces bruising.Warm packs relieve discomfort.
Normal results will be negative, showing no antinu-
clear antibodies.
A positive test in a person with symptoms of an

autoimmune or rheumatic disease helps the physicianmake a diagnosis. More than 95% of people with SLEhave a positive ANA test. Scleroderma has a 60-71%positive rate; Sjögren’s disease, 50-60%, and rheumatoidarthritis, 25-30%.
Several factors must be considered when interpret-

ing a positive test. Diseases other than autoimmune dis-eases can cause autoantibodies. Some healthy peoplehave a positive test. More testing is done after a positivetest to identify individual autoantibodies associated withthe various diseases.
Resources
BOOKS
Antibody —A special protein built by the immune

system as a defense against foreign material enter-ing the body.
Antinuclear antibodies —Autoantibodies that
attack substances found in the center, or nucleus,of all cells.
Autoimmune disease —Disease in which the body
makes antibodies against its own cells or tissues.

known amount of fluid. For example, one part ofserum diluted with four parts of saline is a titerof 1:4.Lehman, Craig A. Saunders Manual of Clinical Laboratory

Slater, Cindi S., Roger B. Davis, and Robert H. Shmerling.
“Antinuclear Antibody Testing. A Study of Clinical Utili-ty.”Archives of Internal Medicine (July 1996): 1421-1425.
Ward, Michael M. “Laboratory Testing for Systemic Rheumat-
ic Diseases.” Postgraduate Medicine (Feb. 1998): 93-100.
Antiparkinson drugs

Antiparkinson drugs are medicines that relieve the
symptoms of Parkinson’s disease and other forms of
parkinsonism.
Purpose
Antiparkinson drugs are used to treat symptoms of

parkinsonism, a group of disorders that share four mainsymptoms: tremor or trembling in the hands, arms, legs,jaw, and face; stiffness or rigidity of the arms, legs, andtrunk; slowness of movement (bradykinesia); and poorbalance and coordination. Parkinson’s disease is the mostcommon form of parkinsonism and is seen more fre-quently with advancing age. Other forms of the disordermay result from viral infections, environmental toxins,carbon monoxide poisoning , and the effects of treat-

ment with antipsychotic drugs .
The immediate cause of Parkinson’s disease or
Parkinsonian-like syndrome is the lack of the neurotrans-mitter dopamine in the brain. Drug therapy may take sev-eral forms, including replacement of dopamine, inhibitionof dopamine metabolism to increase the effects of thedopamine already present, or sensitization of dopaminereceptors. Drugs may be used singly or in combination.
Levodopa (Larodopa) is the mainstay of Parkinson’s

treatment. The drug crosses the blood-brain barrier, and isconverted to dopamine. The drug may be administeredalone, or in combination with carbidopa (Lodosyn) which
GALE ENCYCLOPEDIA OF MEDICINE 2 295Antiparkinson drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 295

inhibits the enzyme responsible for the destruction of lev-
odopa. The limitation of levodopa or levodopa-carbidopatherapy is that after approximately two years of treatment,the drugs cease to work reliably. This has been termed the“on-off phenomenon.” Additional treatment strategieshave been developed to retard the progression of Parkin-sonism, or to find alternative approaches to treatment.
Anticholinergic drugs reduce some of the symptoms

of Parkinsonism, and reduce the reuptake of dopamine,thereby sustaining the activity of the natural neurohor-mone. They may be effective in all stages of the disease.All drugs with anticholinergic properties, the naturallyoccurring belladonna alkaloids (atropine, scopolamine,hyoscyamine), some antihistamines with anticholinergic

properties, and synthetics such as benztropin (Cogentin),procyclidine (Kemadrin) and biperiden (Akineton) aremembers of this group. Although the anticholinergicdrugs have only limited activity against Parkinson’s dis-ease, they are useful in the early stages, and may beadjuncts to levodopa as the disease progresses.
Amantadine (Symmetrel), was developed for pre-
vention of influenza virus infection, but has anti-Parkin-
sonian properties. Its mechanism of action is not known.

Bromocriptine (Parlodel) is a prolactin inhibitor,
which is used for a variety of indications includingamenorrhea/galactorrhea, female infertility , and
acromegaly. It appears to work by direct stimulation ofthe dopamine receptors. Bromocriptine is used as a lateadjunct to levodopa therapy, and may permit reduction inlevodopa dosage. Pergolide (Permax) is similar tobromocriptine, but has not been studied as extensively inParkinson’s disease.
Entacapone (Comtan) appears to act by maintaining

levels of dopamine through enzyme inhibition. It is usedas an adjunct to levodopa was the patient is beginning toexperience the on-off effect. Tolcapone (Tasmar) is asimilar agent, but has demonstrated the potential forinducing severe liver failure. As such, tolcapone isreserved for cases where all other adjunctive therapieshave failed or are contraindicated.Selegeline (Carbex, Eldepryl) is a selective

monoamine oxidase B (MAO-B) inhibitor, however itsmechanism of action in Parkinsonism is unclear, sinceother drugs with MAO-B inhibition have failed to showsimilar anti-Parkinsonian effects. Selegeline is used pri-marily as an adjunct to levodopa, although some studieshave indicated that the drug may be useful in the earlystages of Parkinsonism, and may delay the progressionof the disease.
Pramipexole (Mirapex) and ropinirole (Requip) are

believed to act by direct stimulation of the dopamine recep-tors in the brain. They may be used alone in early Parkison’sdisease, or as adjuncts to levodopa in advanced stages.
Dosages of anti-Parkinsonian medications must be
highly individualized. All doses must be carefully titrat-ed. Consult specific references.
There are a large number of drugs and drug classes

used to treat Parkinson’s disease, and individual refer-ences should be consulted.
The anticholinergics have a large number of adverse
effects, all related to their primary mode of activity. Theircardiovascular effects include tachycardia, palpitations ,
hypotension , postural hypotension, and mild bradycar-
dia. They may also cause a wide range of central nervoussystem effects, including disorientation, confusion,memory loss, hallucinations , psychoses, agitation, ner-

vousness, delusions ,delirium ,paranoia , euphoria,
excitement, lightheadedness, dizziness ,headache , list-
lessness, depression, drowsiness, weakness, and giddi-ness. Dry mouth , dry eyes and gastrointestinal distress
are common problems. Sedation has been reported with
some drugs in this group, but this may be beneficial inpatients who suffer from insomnia . Pregnancy risk fac-

tor is C. Because anticholinergic drugs may inhibit milkproduction, their use during breastfeeding is not recom-mended. Patients should be warned that anticholinergic
GALE ENCYCLOPEDIA OF MEDICINE 2 296Antiparkinson drugsAntiparkinson Drugs
Artane (trihexyphenidyl hydrochloride) Dry mouth, nervousness, blurred vision, nausea

Benadryl (diephenhydramine hydrochloride) Dizziness, sleepiness, upset stomach, decreased coordinationCogentin (benztropine mesylate) Constipation, dry mouth, nausea and vomiting, rashEldepryl (selegiline hydrochloride) Abdominal and back pain, drowsiness, decreased coordinationParlodel (bromocriptine mesylate) Constipation, decreased blood pressure, abdominal crampsSinemet CR Involuntary body movements, confusion, nausea, hallucinationsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 296

medications will inhibit perspiration, and so exercise
during periods of high temperature should be avoided.
Levodopa has a large number of adverse effects.
Anorexia, loss of appetite, occurs in roughly half thepatients using this drug. Symptoms of gastrointestinalupset, such as nausea and vomiting , have been reported
in 80% of cases. Other reported effects include increasedhand tremor; headache; dizziness; numbness; weaknessand faintness; bruxism ; confusion; insomnia; nightmares;

hallucinations and delusions; agitation and anxiety ;
malaise; fatigue and euphoria. Levodopa has not been list-
ed under the pregnancy risk factor schedules, but shouldbe used with caution. Breastfeeding is not recommended.
Amantadine is generally well tolerated, but may cause
dizziness and nausea. It is classified as pregnancy scheduleC. Since amantadine is excreted in breast milk, breastfeed-ing while taking amantidine is not recommended.
Pergolide and bromocriptine have been generally

well tolerated. Orthostatic hypotension are common
problems, and patients must be instructed to risk slowlyfrom bed. This problem can be minimized by low initialdoses with small dose increments. Hallucinations may bea problem. Bromocriptine has not been evaluated forpregnancy risk, while pergolide is category B. Since bothKEY TERMS
Anorexia —Lack or loss of appetite.
Anticholigerginc —An agent that blocks the

parasympathetic nerves and their actions.
Bradykinesia —Extremely slow movement.
Bruxism —Compulsive grinding or clenching of the
teeth, especially at night.
Carbon monoxide —A colorless, odorless, highly
poisonous gas.

longed exposure to high heat. Heat stroke interfereswith the body’s temperature regulating abilities andcan lead to collapse and coma.Parkinsonism —A group of conditions that all have
these typical symptoms in common: tremor, rigidity,slow movement, and poor balance and coordination.

according to their established risks for use duringpregnancy. Category A: Controlled human studieshave demonstrated no fetal risk. Category B: Animalstudies indicate no fetal risk, but no human studies;or adverse effects in animals, but not in well-con-trolled human studies. Category C: No adequatehuman or animal studies; or adverse fetal effects inanimal studies, but no available human data. Cate-gory D: Evidence of fetal risk, but benefits outweighrisks. Category X: Evidence of fetal risk.

Category X: Evidence of fetal risk. Risks out-weigh any benefits.

Spasm —Sudden, involuntary tensing of a muscle or
a group of muscles.
drugs may inhibit lactation , breastfeeding while taking
these drugs is not recommended.
Pramipexole and ropinirole cause orthostatic

hypotension, hallucinations and dizziness. The two drugsare in pregnancy category C. In animals, ropinirole hasbeen shown to have adverse effects on embryo-fetaldevelopment, including teratogenic effects, decreasedfetal body weight, increased fetal death and digital mal-
formation. Because these drugs inhibit prolactin secre-tion, they should not be taken while breastfeeding.
The most common side effects are associated with

the central nervous system, and include dizziness, light-headedness, mood changes and hallucinations. Gastroin-testinal problems, including nausea and vomiting, arealso common.
All anti-Parkinsonian regimens should be carefully
reviewed for possible drug interactions. Note that combi-nation therapy with anti-Parkinsonian drugs is, in itself,use of additive and potentiating interactions between

GALE ENCYCLOPEDIA OF MEDICINE 2 297Antiparkinson drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 297

drugs, and so careful dose adjustment is needed whenev-
er a drug is added or withdrawn.
Resources
American Parkinson Disease Association. 60 Bay Street, Suite
401, Staten Island, NY 10301. (800) 223-2732.
Box 5801, Bethesda, MD 20824. (800) 352-9424.
National Parkinson Foundation, Inc. 1501 N.W. 9th Avenue,
Miami, FL 33136-1494. (800) 327-4545.
Antiplatelet drugs seeAnticoagulant and

Antiprotozoal drugs
Antiprotozoal drugs are medicines that treat infec-
tions caused by protozoa.
Purpose
Antiprotozoal drugs are used to treat a variety of dis-
eases caused by protozoa. Protozoa are animal-like, one-celled animals, such as amoebas. Some are parasites thatcause infections in the body. African sleeping sickness ,
giardiasis ,amebiasis ,Pneumocystis carinii pneumonia

(PCP), and malaria are examples of diseases caused by
protozoa.
Antiprotozoal drugs come in liquid, tablet, and
injectable forms and are available only with a doctor’sprescription. Some commonly used antiprotozoal drugsare metronidazole (Flagyl), eflornithine (Ornidyl), fura-zolidone (Furoxone), hydroxychloroquine (Plaquenil),iodoquinol (Diquinol, Yodoquinol, Yodoxin), and pen-tamidine (Pentam 300).

antiprotozoal drug, its strength, and the medical problemfor which it is being used. Check with the physician whoprescribed the drug or the pharmacist who filled the pre-scription for the correct dosage. Always take antiproto-zoal drugs exactly as directed.Precautions
Some people feel dizzy, confused, lightheaded, or

less alert when using these drugs. The drugs may alsocause blurred vision and other vision problems. For thesereasons, anyone who takes these drugs should not drive,use machines or do anything else that might be danger-ous until they have found out how the drugs affect them.
The antiprotozoal drug furazolidone may cause very

dangerous side effects when taken with certain foods orbeverages. Likewise, metronidazole (Flagyl) can causeserious liver damage if taken with alcohol. Check withthe physician who prescribed the drug or the pharmacistwho filled the prescription for a list of products to avoidwhile taking these medicines.
Anyone who has ever had unusual reactions to

antiprotozoal drugs or related medicines should let his orher physician know before taking the drugs again. Thephysician should also be told about any allergies to
Some antiprotozoal drugs may cause problems with

the blood. This can increase the risk of infection orexcessive bleeding. Patients taking these drugs shouldbecareful not to injure their gums when brushing or floss-ing their teeth or using a toothpick. They shouldcheckwith the physician before having any dentalwork done.Care should also be taken to avoidcuts from razors, nailclippers, or kitchen knives, orhousehold tools. Anyonewho has any of these symptoms while taking antiproto-zoal drugs should call the physician immediately:

• fever or chills
• signs of cold or flu
• signs of infection, such as redness, swelling, or inflam-
mation
• unusual bruising or bleeding• black, tarry stools
• blood in urine or stools
• pinpoint red spots on the skin
• unusual tiredness or weakness.
Anyone taking this medicine should also check with
a physician immediately if any of these symptoms occur:
• blurred vision or other vision changes
• skin rash, hives , or itching
• swelling of the neck• clumsiness or unsteadiness

• numbness, tingling, pain , or weakness in the hands or
feet
• decrease in urination
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Children are especially sensitive to the effects of some
antiprotozoal drugs. Never give this medicine to a child
unless directed to do so by a physician, and always keepthis medicine out of the reach of children. Use safety vials.
The effects of antiprotozoal drugs on pregnant
women have not been studied. However, in experimentswith pregnant laboratory animals, some antiprotozoaldrugs cause birth defects or death of the fetus. Women

who are pregnant or who plan to become pregnantshould check with their physicians before takingantiprotozoal drugs. Mothers who are breastfeedingshould also check with their physicians about the safetyof taking these drugs.
Before using antiprotozoal drugs, people with any of
• anemia or other blood problems
• heart disease• low blood pressure
• diabetes

• diabetes
• hypoglycemia (low blood sugar)• liver disease• stomach or intestinal disease
• nerve or brain disease or disorder, including convul-
sions (seizures)
• psoriasis (a skin condition)
• hearing loss• deficiency of the enzyme glucose-6-phosphate dehy-
drogenase (G6PD)
• eye or vision problems
The most common side effects are diarrhea , nausea,

vomiting, and stomach pain. These problems usually goaway as the body adjusts to the drug and do not requiremedical treatment.
unusual symptoms after taking an antiprotozoal drugshould get in touch with his or her physician.
Antiprotozoal drugs may interact with other medi-

cines. When this happens, the effects of one or both ofthe drugs may change or the risk of side effects may begreater. Anyone who takes antiprotozoal drugs should letKEY TERMS
Amebiasis —An infection caused by an ameba,
which is a type of protozoan.
Giardiasis —A condition in which the intestines
are infected with Giardia lamblia , a type of proto-
zoan.

Pneumocystis carinii pneumonia —A severe lung
infection caused by a parasitic protozoan. The dis-ease mainly affects people with weakenedimmune systems, such as people with AIDS.
the physician know all other medicines he or she is tak-

ing. Among the drugs that may interact with antiproto-zoal drugs are:
• alcohol
• anticancer drugs• medicine for overactive thyroid
• antiviral drugs such as zidovudine (Retrovir)
• antibiotics• medicine used to relieve pain or inflammation• amphetamine• diet pills (appetite suppressants)
as phenelzine (Nardil) and tranylcypromine (Parnate),used to treat conditions including depression andParkinson’s disease

• tricyclic antidepressants such as amitriptyline (Elavil)
and imipramine (Tofranil)
• decongestants such as phenylephrine (Neo-Synephrine)
and pseudoephedrine (Sudafed)
• other antiprotozoal drugs
may interact with an antifungal drug. Be sure to checkwith a physician or pharmacist before combining anti-fungal drugs with any other prescription or nonprescrip-tion (over-the-counter) medicine.

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Antipruritic drugs seeAnti-itch drugs
Antipsychotic drugs
Antipsychotic drugs are a class of medicines used to
treat psychosis and other mental and emotional condi-
tions.
Purpose
Psychosis is defined as “a serious mental disorder
(as schizophrenia ) characterized by defective or lost
contact with reality often with hallucinations or delu-

sions.” Psychosis is an end-stage condition arising from avariety of possible causes. Anti-psychotic drugs controlthe symptoms of psychosis, and in many cases are effec-tive in controlling the symptoms of other disorders thatmay lead to psychosis, including bipolar mood disorder(formerly termed manic-depressive), in which the patientcycles from severe depression to feelings of extremeexcitation. This class of drugs is primarily composed ofthe major tranquilizers; however, lithium carbonate,

major tranquilizers; however, lithium carbonate, adrug that is largely specific to bipolar mood disorder, iscommonly classified among the antipsychotic agents.

The antipsychotic agents may be divided by chemi-
cal class. The phenothiazines are the oldest group, andinclude chlorpromazine (Thorazine), mesoridazine (Ser-entil), prochlorperazine (Compazine), and thioridazine(Mellaril). These drugs are essentially similar in actionand adverse effects. They may also be used as anti-emet-ics, although prochlorperazine is the drug most oftenused for this indication.
The phenylbutylpiperadines are haloperidol (Haldol)

and pimozide (Orap). They find primary use in control ofTourette’s syndrome. Haloperidol has been extremelyuseful in controlling aggressive behavior.
The debenzapine derivatives, clozapine (Clozaril),
loxapine (Loxitane), olanzapine (Zyprexa) and quetiap-ine (Seroquel), have been effective in controlling psy-chotic symptoms that have not been responsive to otherclasses of drugs.
The benzisoxidil group is composed of resperidone

(Resperidal) and ziprasidone (Geodon). Resperidone hasbeen found useful for controlling bipolar mood disorder,while ziprasidone is used primarily as second-line treat-ment for schizophrenia.In addition to these drugs, the class of antipsychotic
agents includes lithium carbonate (Eskalith, Lithonate),which is used for control of bipolar mood disorder, andthiothixene (Navane), which is used in the treatment ofpsychosis.

Dose varies with the drug, condition being treated,
and patient response. See specific references.
Neuroleptic malignant syndrome (NMS). NMS is a

rare, idiosyncratic combination of extra-pyramidal symp-toms (EPS), hyperthermia, and autonomic disturbance.Onset may be hours to months after drug initiation, butonce started, proceeds rapidly over 24 to 72 hours. It ismost commonly associated with haloperidol, long-actingfluphenazine, but has occurred with thiothixene, thiori-dazine, and clozapine, and may occur with other agents.NMS is potentially fatal, and requires intensive sympto-matic treatment and immediate discontinuation of

treatment and immediate discontinuation of neu-roleptic treatment. There is no established treatment.Most patients who develop NMS will have the sameproblem if the drug is restarted.

syndrome of involuntary movements that may appear inpatients treated with neuroleptic drugs. Although preva-lence of TD appears highest among the elderly, especial-ly women, it is impossible to predict which patients arelikely to develop the syndrome. Both the risk of develop-ing TD and the likelihood that it will become irreversibleare increased with higher doses and longer periods oftreatment. The syndrome can develop after short treat-ment periods at low doses. Anticholinergic agents

periods at low doses. Anticholinergic agents mayworsen these effects. Clozapine has occasionally beenuseful in controlling the TD caused by other antipsychot-ic drugs.

Agranulocytosis has been associated with clozapine.
This is a potentially fatal reaction, but can be preventedwith careful monitoring of the white blood count . There
are no well-established risk factors for developing agran-ulocytosis, and so all patients treated with this drug mustfollow the clozapine Patient Management System. Formore information, call 1-800-448-5938.
Anticholinergic effects, particularly dry mouth ,

have been reported with all of the phenothiazines, andcan be severe enough to cause patients to discontinuetheir medication.
Photosensitization is a common reaction to chlor-
promazine. Patients must be instructed to use precautionswhen exposed to sunlight.
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Lithium carbonate commonly causes increased fre-
quency of urination.
Antipsychotic drugs are pregnancy category C.

(Clozapine is category B.) The drugs in this class appearto be generally safe for occasional use at low doses dur-ing pregnancy, but should be avoided near time of deliv-ery. Although the drugs do not appear to be teratogenic,when used near term, they may cross the placenta andhave adverse effects on the newborn infant, includingcausing involuntary movements. There is no informationabout safety in breast feeding.

As a class, the antipsychotic drugs have a large num-
ber of potential side effects, many of them serious. Spe-cific references should be consulted.
Because the phenothiazines have anticholinergic
effects, they should not be used in combination withother drugs that may have similar effects.
Because the drugs in this group may cause hypoten-
sion, or low blood pressure, they should be used with
extreme care in combination with blood pressure-lower-ing drugs.

The antipsychotic drugs have a large number of drug
interactions. Consult specific references.
Samuel D. Uretsky, PharmD
Antipsychotic drugs, atypical
The atypical antipsychotic agents, sometimes called
the “novel” antipsychotic agents are a group of drugswhich are different chemically from the older drugs usedto treat psychosis . The “conventional” antipsychotic
drugs are classified by their chemical structures as the

phenothiazines, thioxanthines (which are chemicallyvery similar to the phenothiazines), butyrophenones,diphenylbutylpiperadines and the indolones. All of theatypical antipsychotic agents are chemically classified asdibenzepines. They are considered atypical or novel

because they have different side effects from the conven-tional antipsychotic agents. The atypical drugs are farless likely to cause extra-pyrammidal side-effects(EPS),drug induced involuntary movements, than are the olderdrugs. The atypical antipsychotic drugs may also beeffective in some cases that are resistant to older drugs.
The drugs in this group are clozapine (Clozaril),
loxapine (Loxitane), olanzapine (Zyprexa), and quetiap-ine (Seroquel).
Purpose

Purpose
The antipsychotic drugs are used to treat severe
emotional disorders. Although there may be differentnames for these disorders, depending on severity andhow long the symptoms last, psychotic disorders allcause at least one of the following symptoms:
• delusions
• disorganized speech• grossly disorganized or catatonic behavior
Loxapine has also been used to treat anxiety with
The recommended dose depends on the drug, the

patient, and the condition being treated. The normalpractice is to start each patient at a low dose, and gradu-ally increase the dose until a satisfactory response isachieved. The odse should be held at the lowest level thatgives satisfactory results.
GALE ENCYCLOPEDIA OF MEDICINE 2 301Antipsychotic drugs, atypical
Antipsychotic Drugs

Clozaril (clozapine) Seizures, agranulocytosis, dizziness, increased blood pressure

Compazine (prochlorperazine) Involuntary muscle spasms, dizziness, jitteriness, puckering of the mouthHaldol (haloperidol) Involuntary muscle spasms, blurred vision, dehydration, headache, puckering of the mouthMellaril (thioridazine) Involuntary muscle spasms, constipation and diarrhea, sensitivity to lightNavane (thiothixene) Involuntary muscle spasms, dry mouth, rash, hivesRisperdal (risperidone) Involuntary muscle spasms, abdominal and chest pain, fever, headacheStelazine (trifluoperazine

pain, fever, headacheStelazine (trifluoperazine hydrochloride) Involuntary muscle spasms, drowsiness, fatigueThorazine (chlorpromazine) Involuntary muscle spasms, labored breathing, fever, puckering of the mouthTriavil Involuntary muscle spasms, disorientation, excitability, lightheadednessGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 301

Clozapine usually requires doses between 300 and
600 milligrams a day, but some people require as muchas 900 milligrams/day. Doses higher than 900 mill-grams/day are not recommended.
Loxapine is usually effective at doses of 60-100 mil-
ligrams/day, but may be used in doses as high as 250mg/day if needed.
Olanzapine doses vary with the condition being
treated. The usual maximum dose is 20 milligrams/day.
Quetiapine may be dosed anywhere from 150-750 mil-

ligrams/day, depending on how well the patient responds.
Although the atypical antipsychotics are generally

safe, clozapine has been associated with severe agranulo-cytosis, a shortage of white blood cells. For this reason,people who may be treated with clozapine should haveblood counts before starting the drug, blood counts everyweek for as long as they are using clozapine, and bloodcounts every week for the first four weeks after they stoptaking clozapine. If there is any evidence of a drop in thewhite blood count while using clozapine, the drug
should be stopped.

Atypical antipsychotics should not be used in
patients with liver damage, brain or circulatory prob-lems, or some types of blood problems.
Allergies
People who have had an allergic reaction to one of
the atypical antipsychotics should not use that medica-tion again. However, sometimes it is possible to use adifferent drug from the same group safely.
Pregnancy
The atypical antipsychotics have not been proved
safe in pregnancy . They should be used only when

clearly needed and when potential benefits outweighpotential hazards to the fetus. These drugs have not beenreported in human milk.
Although the atypical antipsychotics are less likely to
cause involuntary movements than the older antipsychoticdrugs, they still have a large number of adverse effects.The following list is not complete. Review each drug indi-vidually for a full list of possible adverse effects.

• chest pain• high blood pressure• low blood pressure
• fast heart beatKEY TERMS
Anxiety —An abnormal and overwhelming sense
of apprehension and fear often marked by physio-logical signs (as sweating, tension, and increasedpulse), by doubt concerning the reality and natureof the threat, and by self-doubt about one’s capac-ity to cope with it.
Delusions —A false belief regarding the self or per-
sons or objects outside the self that persists despitethe facts.

Depression —A state of being depressed marked
especially by sadness, inactivity, difficulty withthinking and concentration, a significant increase ordecrease in appetite and time spent sleeping, feel-ings of dejection and hopelessness, and sometimessuicidal thoughts or an attempt to commit suicide.
Glucocorticoid —Any of a group of corticosteroids

(as hydrocortisone or dexamethasone) that areanti-inflammatory and immunosuppressive, andthat are used widely in medicine (as in the allevia-tion of the symptoms of rheumatoid arthritis).
Psychosis —A serious mental disorder character-
ized by defective or lost contact with reality oftenwith hallucinations or delusions.
• aggitation
• memory loss
• confusion• dizziness
• tiredness
• headache• sleep disturbances
• stuttering
• dry skin• nausea

• constipation
•f e v e r• weight gain
• visual disturbances
Taking atypical antipsychotic medications with cer-
tain other drugs may affect the way the drugs work ormay increase the chance of side effects. While takingantipsychotic drugs, do not take any other prescription or
GALE ENCYCLOPEDIA OF MEDICINE 2 302Antipsychotic drugs, atypicalGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 302

nonprescription (over-the-counter) drugs without first
checking with a physician.
Because the atypical antipsychotics may cause low-
ering of blood pressure, care should be used when thesedrugs are taken at the same time as other drugs whichlower blood pressure.
Quetiapine has many interactions. Doses should be
carefully adjusted when quetiapine is used with keto-conazole, itraconazole, fluconazole, erythromycin, car-bamazepine, barbiturates , rifampin or glucocorticoids

including prednisone, dexamethasone and methylpred-nisolone.
These drugs will also require dose adjustments when
used with antiparkinson drugs .
Resources
BOOKS
Brain Basics: An Integrated Biological Approach to Under-
standing and Assessing Human Behavior. Phoenix: Bio-
logical-Psychiatry-Institute, June 1999.
Contemporary Treatment of Psychosis: Healing Relationships
in the “Decade of the Brain. ” Northvale: Jason-Aronson-
Publishers, May 1996.

McDougle, C. J. “A double-blind, placebo-controlled study of
risperidone addition in serotonin reuptake inhibitor-refrac-tory obsessive-compulsive disorder.” Archives of General
Psychiatry (August 2000): 794.
Samuel David Uretsky, PharmD
Antiretroviral drugs
Antiretroviral drugs inhibit the reproduction of

retroviruses—viruses composed of RNA rather thanDNA. The best known of this group is HIV , humanimmunodeficiency virus, the causative agent of AIDS .
Purpose
Antiretroviral agents are virustatic agents which
block steps in the replication of the virus. The drugs arenot curative; however continued use of drugs, particular-ly in multi-drug regimens, significantly slows diseaseprogression.

although only two steps in the viral replications processare blocked. Nucleoside analogs, or nucleoside reversetranscriptase inhibitors (NRTIs), such as didanosine (ddI,Videx), lamivudine (3TC, Epivir), stavudine (d4T, Zerit),zalcitabine (ddC, Hivid), and zidovudine (AZT, Retrovir),act by inhibiting the enzyme reverse transcriptase.Because a retrovirus is composed of RNA, the virus mustmake a DNA strand in order to replicate itself. Reversetranscriptase is an enzyme that is essential to making

is an enzyme that is essential to making theDNA copy. The nucleoside reverse transcriptaseinhibitors are incorporated into the DNA strand. This is afaulty DNA molecule which is incapable of reproducing.

The non-nucleoside reverse transcriptase in-
hibitors (NNRTIs), such as delavirdine (Rescriptor),
loviride, and nevirapine (Viramune) act by bindingdirectly to the reverse transcriptase molecule, inhibitingits activity.
Protease inhibitors , such as indinavir (Crixivan),

nelfinavir (Viracept), ritonavir (Norvir), and saquinavir(Invirase) act on the enzyme protease, which is essentialfor the virus to break down the proteins in infected cells.Without this essential step, the virus produces immaturecopies of itself, which are non-infectious.
Because HIV mutates readily, the virus can develop

resistance to single drug therapy. However, treatmentwith drug combinations appears to produce a durableresponse. Proper treatment appears to slow the progres-sion of HIV infections and reduce the frequency ofopportunistic infections.
Doses must be individualized based on the patient,
and use of interacting drugs. The optimum combinationsof antiretroviral drugs have not been determined, nor isthere agreement on the stage of infection at which to starttreatment.

Although the antiretroviral drugs fall into three
groups, each drug has a unique pattern of adverse effectsand drug interactions. Since the drugs are used in variouscombinations, the frequency and severity of adverseeffects will vary with the combination. Although mostdrug combinations show a higher rate of adverse eventsthat single drug therapy, some patterns are not pre-dictable. For example, indinavir has been reported tocause insomnia in 3% of patients, however, when used

in combination with zidovudine, only 1.5% of patientscomplained of sleep difficulties.
The most severe adverse effects associated with the
protease inhibitors are renal and hepatic toxicity. Patientshave also reported a syndrome of abdominal distention
GALE ENCYCLOPEDIA OF MEDICINE 2 303Antiretroviral drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 303

and increased body odor, which may be socially limiting.
Hemophilic patients have reported increased bleedingtendencies while taking protease inhibitors. The drugsare pregnancy category B. There have been no con-
trolled studies of safety in pregnancy. HIV-infectedmothers are advised not to breast feed in order to preventtransmission of the virus to the newborn.
The nucleoside reverse transcriptase inhibitors have

significant levels of toxicity. Lactic acidosis in theabsence of hypoxemia and severe hepatomegaly withsteatosis have been reported with zidovudine and zal-citabine, and are potentially fatal. Rare cases of hepaticfailure, considered possibly related to underlying hepati-
tis B and zalcitabine monotherapy, have been reported.
Abacavir has been associated with fatal hypersensi-
tivity reactions. Didanosine has been associated withsevere pancreatitis . Nucleoside reverse transcriptase

inhibitors are pregnancy category C. There is limitedinformation regarding safety during pregnancy. Zidovu-dine has been used during pregnancy to reduce the risk ofHIV infection to the infant. HIV-infected mothers areadvised not to breastfeed in order to prevent transmissionof the virus to the newborn.
Efavirenz has been associated with a high frequency

of skin rash, 27% in adults and 40% in children. Nevirap-ine has been associated with severe liver damage andskin reactions. All of the non-nucleoside reverse tran-scriptase inhibitors are pregnancy category C, based onanimal studies.KEY TERMS
Antiviral drugs —Medicines that cure or control
virus infections.
Bioavailability —A measure of the amount of drug
that is actually absorbed from a given dose.
Immune system —The body’s natural defenses
against disease and infection.

Insomnia —A sleep disorder characterized by
inability to either fall asleep or to stay asleep.
Mutates —Undergoes a spontaneous change in the
make-up of genes or chromosomes.
Pancreas —A gland located beneath the stomach.

The pancreas produces juices that help break downfood and secretes insulin that helps the body usesugar for energy.Pregnancy category —A system of classifying drugs

Retrovirus —A virus composed of ribonucleic acid
(RNA) instead of deoxynucleic acid (DNA).
Virus —A tiny, disease-causing particle that can
reproduce only in living cells.
Because of the high risk of viral resistance develop-

ment, antiretroviral agents should be used in combina-tion. If one drug in the group must be discontinued, it isrecommended that all antiretroviral therapy be discontin-ued until a multi-drug regimen can be resumed. The non-nucleoside reverse transcriptase inhibitors particularlyshould not be used alone.
Because of the high frequency of drug interactions
associated with AIDS therapy, specialized referencesshould be consulted.
Saquinavir is marketed in both hard and soft gelatin

capsules. Because saquinavir in the hard gelatin capsuleformulation (Invirase) has poor bioavailability, it is rec-ommended that this formulation only be used in combi-nation with other drugs which interact to raise saquinavirblood levels. Saquinavir soft gelatin capsules (Fortovase)are the preferred dosage form of this drug.
Resources
Lipsky, James J. “Antiretroviral Drugs for AIDS.” The Lancet
348 (September 21, 1996): 800.
Williams, Ann B. “New Horizons: Antiretroviral Therapy in

1997.” Journal of the Association of Nurses in AIDS Care
8 (July-August 1997): 26.
Project Inform. 205 13th Street, #2001, San Francisco, CA
94103. (415) 558-8669. <http://www.projinf.org>.
GALE ENCYCLOPEDIA OF MEDICINE 2 304Antiretroviral drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 304

OTHER
AIDS Clinical Trials Information Service website and tele-
phone information line. Sponsored by Centers for DiseaseControl and Prevention, Food and Drug Administration,National Institute of Allergy and Infectious Diseases, andNational Library of Medicine. 800-TRIALS-A (800-874-2572). <http://actis.org>.
HIV/AIDS Treatment Information Service website and tele-

phone information line. Sponsored by Agency for HealthCare Policy and Research, Centers for Disease Controland Prevention, Health Resources and Services Adminis-tration, Indian Health Service, National Institutes ofHealth, and Substance Abuse and Mental Health ServicesAdministration. 800-HIV-0440 (800-448-0440). <http://www.hivatis.org>.
Project Inform National HIV/AIDS Treatment Hotline. 800-
822-7422.
Antirheumatic drugs

Antirheumatic drugs are drugs used to treat rheuma-
toid arthritis .
Purpose
Rheumatoid arthritis is a progressive form of arthritis
that has devastating effects on joints and general health. Itis classified as an auto-immune disease, because the dis-ease is caused by the body’s own immune system actingagainst the body itself. Symptoms include painful, stiff,swollen joints, fever ,fatigue , and loss of appetite.
In recent years, there has been a change in attitude

concerning the treatment of rheumatoid arthritis. Physi-cians now use Disease Modifying Anti-Rheumatic Drugs(DMARDs) early in the history of the disease and areless inclined to wait for crippling stages before resortingto the more potent drugs. Fuller understanding of theside-effects of non-steroidal anti-inflammatory drugs(NSAIDs) has also stimulated reliance on other types ofantirheumatic drugs.
The major classes of antirheumatic drugs include:

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs.
Drugs belonging to this class bring symptomatic reliefof both inflammation and pain, but have a limited effect
on the progressive bone and cartilage loss associatedwith rheumatoid arthritis. They act by slowing thebody’s production of prostaglandins. Common NSAIDsinclude: ibuprofen (Motrin, Nuprin or Advil), naproxen(Naprosyn, Aleve) and indomethacin(Indocin).

•Corticosteroids . These drugs are very powerful anti-
inflammatory agents. They are the synthetic analogs ofcortisone, produced by the body. Corticosteroids areused to reduce inflammation and suppress activity ofthe immune system. The most commonly prescribedare prednisone and dexamethasone.
• Disease Modifying Anti-Rheumatic Drugs (DMARDs).

DMARDs influence the disease process itself and do notonly treat symptoms, hence their name. DMARDs alsohave anti-inflammatory effects, and most were borrowedfrom the treatment of other diseases, such as cancer and
malaria . Antimalarials DMARDs include chloroquine

(Aralen) and hydroxychloroquine (Plaquenil). PowerfulDMARDs include: methotrexate (Rheumatrex), sul-fasalazine, cyclosporine, azathioprine (Imuran) andcyclophosphamide (Cytoxan), azathioprine, sulfasalazine,penicillamine, and organic gold compounds such asaurothioglucose (Solganol), gold sodium thiomalate(Aurolate) and auranofin (Ridaura).
• Slow-Acting Antirheumatic Drugs (SAARDs). SAARDs

are a special class of DMARDs and the effect of thesedrugs is slow acting and not so quickly apparent as thatof the NSAIDs. Examples are hydroxychloroquine andaurothioglucose.
• Immunosuppresive cytotoxic drugs. This class of drugs

is used if treatment with NSAIDs and SAARDs haveno effect. Immunosuppresive drugs have a stabilizingeffect on the immune system. Since the inflammationassociated with chronic arthritis is due to malfunctionsof the immune system, use of this class of drugs hasbeen shown to be beneficial for the treatment ofrheumatoid arthritis as well. Examples are: methotrex-ate, mechlorethamine, cyclophosphamide, chlorambu-cil, and azathioprine.

The prescribing physician or the pharmacist provideinformation for the correct dosage. The drugs must betaken exactly as directed.
When taking methotrexate for rheumatoid arthritis,
it should be taken only once or twice a week as pre-
scribed, not every day. Taking it every day can lead to a
fatal overdose.
Many antirheumatic drugs such as, for example, aza-
thioprine (Imuran) and methotrexate (Rheumatrex), are very

GALE ENCYCLOPEDIA OF MEDICINE 2 305Antirheumatic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 305

powerful drugs. They are usually prescribed in severe cases,
when all other treatments have failed. Thus, they may haveserious side effects, so it is important to be monitored close-ly by a physician while taking any of these drugs.
Hydroxychloroquine (Plaquenil) may cause vision
problems. Anyone taking it should see an ophthalmolo-gist (a physician who specializes in treating eyes) for athorough eye examination every six months.
Methotrexate and penicillamine may cause birth

defects . Women taking these drugs must stop taking
them during pregnancy and for several months before a
planned pregnancy. Methotrexate may also cause lungdamage or fertility problems and should not be taken byKEY TERMS
Anti-inflammatory drugs —A class of drugs that
lower inflammation and that includes NSAIDs andcorticosteroids.
Arthritis —A painful condition that involves inflam-
mation of one or more joints.

Conception —The union of egg and sperm to form a
fetus.
Corticosteroids —A class of drugs that are synthetic
versions of the cortisone produced by the body.They rank among the most powerful anti-inflamma-tory agents.
Cortisone —Glucocorticoid produced by the adren-
al cortex in response to stress. Cortisone is a steroidand has anti-inflammatory and immunosuppressiveproperties.
Cytotoxic drugs —Drugs that function by destroying
cells.

cells.
Disease Modifying Anti-Rheumatic Drugs
(DMARDs) —A class of drugs that function by.
Inflammation —A process occurring in body tissues,
characterized by increased circulation and theaccumulation of white blood cells. Inflammationalso occurs in disorders such as arthritis and causesharmful effects.
Inflammatory —Pertaining to inflammation.
Immune response —Physiological response of the
body controlled by the immune system thatinvolves the production of antibodies to fight off

specific foreign substances or agents (antigens).
Immune system —The sum of the defence mecha-
nisms of the body that protects it against foreignsubstances and organisms causing infection.
Immunosuppressive —Any agent that suppresses the
immune response of an individual.
Immunosuppresive cytotoxic drugs —A class of
drugs that function by destroying cells and sup-pressing the immune response.
Methotrexate —A drug that interferes with cell

growth and is used to treat rheumatoid arthritis aswell as various types of cancer. Side-effects mayinclude mouth sores, digestive upsets, skin rashes,and hair loss.
Non steroidal —Not containing steroids or corti-
sone. Usually refers to a class of drugs called NonSteroidal Anti-Inflammatory Drugs (NSAID).
Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) —

A class of drugs that is used to relieve pain, andsymptoms of inflammation, such as ibuprofen andketoprofen.
Osteoarthritis —A form of arthritis that occurs
mainly in older people and involves the gradualdegeneration of the cartilage of the joints.
Prostaglandins —Prostaglandins are produced by
the body and are responsible for inflammation fea-tures, such as swelling, pain, stiffness, redness andwarmth.

anyone with serious kidney or liver disease or by anyone
who drinks alcohol.
Azathioprine may cause birth defects if either the man
or woman is using it at the time of conception. Anyonewho uses this drug and is sexually active should consultwith a physician about an effective birth control method.
Other common side effects of antirheumatic drugs
include abdominal cramps, diarrhea ,dizziness , loss of
appetite, headache , nausea, vomiting, fever and chills,

and mouth sores. A variety of other side effects mayoccur. Anyone who has unusual symptoms while takingantirheumatic drugs should notify the treating physician.
The gold compounds may cause serious blood prob-
lems by reducing the ability of the blood forming organs toproduce blood cells. These drugs may decrease the number
GALE ENCYCLOPEDIA OF MEDICINE 2 306Antirheumatic drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 306

of white blood cells, red blood cells, or both. Patients tak-
ing these drugs should have regular blood counts.
Entanercept (Enbrel) may also cause blood prob-
lems, and some patients who received this drug havedeveloped eye problems and multiple sclerosis . It is not
certain whether these reactions were caused by entaner-cept, but multiple sclerosis has been seen in patients tak-ing other drugs which act against tumor necrosis factor.

Antirheumatic drugs may interact with a variety of
other medicines or other antirheumatic drugs. When thishappens, the effects of one or both of the drugs maychange, or the risk of side effects may be greater. Anyonewho takes this type of drug should inform the prescribingphysician about any other medication he or she is taking.Among the drugs that may interact with antirheumaticdrugs are phenytoin (Dilantin), aspirin , sulfa drugs such

as Bactrim and Gantrisin, tetracycline and some otherantibiotics and cimetidine (Tagamet). NSAIDs such as
ibuprofen (Motrin, Advil) are also known to interact withother classes of antirheumatic drugs.
Resources
Arthritis Foundation. 1300 W. Peachtree St., Atlanta, GA
Antiseptics
An antiseptic is a substance which inhibits the

growth and development of microorganisms. For practi-cal purposes, antiseptics are routinely thought of as topi-cal agents, for application to skin, mucous membranes,and inanimate objects, although a formal definitionincludes agents which are used internally, such as the uri-nary tract antiseptics.
Purpose
Antiseptics are a diverse class of drugs which are

applied to skin surfaces or mucous membranes for theiranti-infective effects. This may be either bacteriocidal orbacteriostatic. Their uses include cleansing of skin andwound surfaces after injury, preparation of skin surfacesprior to injections or surgical procedures, and routine disin-fection of the oral cavity as part of a program of oralhygiene . Antiseptics are also used for disinfection of inani-
mate objects, including instruments and furniture surfaces.

Commonly used antiseptics for skin cleaning include
benzalkonium chloride, chlorhexidine, hexachlorophine,iodine compounds, mercury compounds, alcohol andhydrogen peroxide. Other agents which have been usedfor this purpose, but have largely been supplanted bymore effective or safer agents, include boric acid andvolatile oils such as methyl salicylate (oil of wintergreen.)
Chlorhexidine shows a high margin of safety when

applied to mucous membranes, and has been used in oralrinses and preoperative total body washes.
Benzalkonium chloride and hexachlorophine are used

primarily as hand scrubs or face washes. Benzalkonium mayalso find application is a disinfecting agent for instruments,and in low concentration as a preservative for drugs includ-ing ophthalmic solutions. Benzalkonium chloride is inacti-vated by organic compounds, including soap, and must notbe applied to areas which have not been fully rinsed.
Iodine compounds include tincture of iodine and

povidone iodine compounds. Iodine compounds have thebroadest spectrum of all topical anti-infectives, with actionagainst bacteria, fungi, viruses, spores, protozoa, andyeasts. Iodine tincture is highly effective, but its alcoholiccomponent is drying and extremely irritating when appliedto abraided (scraped or rubbed) skin. Povidone iodine, anorganic compound, is less irritating and less toxic, but notas effective. Povidone iodine has been used for handscrubs and disinfection of surgical sites.

handscrubs and disinfection of surgical sites. Aqueous solu-tions of iodine have also been used as antiseptic agents,but are less effective than alcoholic solutions and less con-venient to use that the povidone iodine compounds.

Hydrogen peroxide acts through the liberation of
oxygen gas. Although the antibacterial activity of hydro-gen peroxide is relatively weak, the liberation of oxygenbubbles produces an effervescent action, which may beuseful for wound cleansing through removal of tissuedebris. The activity of hydrogen peroxide may bereduced by the presence of blood and pus. The appropri-ate concentration of hydrogen peroxide for antiseptic useis 3%, although higher concentrations are available.

Thimerosol (Mersol) is a mercury compound with
activity against bacteria and yeasts. Prolonged use mayresult in mercury toxicity.
Dosage varies with product and intended use. Con-
sult individualized references.
Precautions vary with individual product and use.
Consult individualized references.
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Hypersensitivity reactions should be considered
with organic compounds such as chlorhexidine, benza-lkonium and hexachlorophine.
Skin dryness and irritation should be considered with
all products, but particularly with those containing alcohol.
Systemic toxicity may result from ingestion of
iodine containing compounds or mercury compounds.
Chlorhexidine should not be instilled into the ear.

There is one anecdotal report of deafness following use ofchlorhexidine in a patient with a perforated eardrum .
Safety in pregnancy and breastfeeding have not been
reported, however there is one anecdotal report of aninfant developing slowed heartbeat apparently related tomaternal use of chlorhexidine.
Iodine compounds should be used sparingly during
pregnancy and lactation due to risk of infant absorption
of iodine with alterations in thyroid function.

Antiseptics are not known to interact with any other
medicines. However, they should not be used togetherwith any other topical cream, solution, or ointment.
Resources
Antispasmodic drugs
Antispasmodic drugs relieve cramps or spasms of
the stomach, intestines, and bladder.KEY TERMS
Antibiotic —A medicine used to treat infections.

Mucous membrane —The moist lining of a body
cavity or structure, such as the mouth or nose.
Residue —Traces that remain after most of the rest
of the material is gone.Purpose
Antispasmodic drugs have been used to treat stom-

ach cramps. Traditionally, they were used to treat stom-ach ulcers, but for this purpose they have largely beenreplaced by the acid inhibiting compoundsa, the H-2receptor blockers such as cimetidine and ranitidine andthe proton pump inhibtors such as omeprazole, lansopra-zole and rabetazole.
Most of the drugs used for this purpose as “anti-

cholinergics”, since they counteract the effects of theneurohormone acetylcholine. Some of these drugs arederived from the plant belladonna, also known as DeadlyNightshade. There is also a group of drugs with similaractivity, but not taken from plant sources. The anti-cholingergics decrease both the movements of the stom-ach and intestine, and also the secretions of stomach acidand digestive enzymes. They may be used for other pur-poses including treatment of Parkinson’s Disease , and

bladder urgency. Because these drugs inhibit secretions,they cause dry mouth and dry eyes because of reduced
salivation and tearing. Dicyclomine is an antispasmodicwith very lettle effect on secretions. It is used to treatirritable bowel syndrome .
Dicyclomine is available only with a prescription
and is sold as capsules, tablets (regular and extended-release forms), and syrup.
The usual dosage for adults is 20 mg, four times a

day. However, the physician may recommend starting ata lower dosage and gradually increasing the dose toreduce the chance of unwanted side effects.
The dosage for children depends on the child’s age.
Check with the child’s physician for the correct dosage.
Dicyclomine makes some people sweat less, which
allows the body to overheat and may lead to heat prostra-tion ( fever and heat stroke ). Anyone taking this drug

should try to avoid extreme heat. If that is not possible,check with the physician who prescribed the drug. If heatprostration occurs, stop taking the medicine and call aphysician immediately.
This medicine can cause drowsiness and blurred or
double vision. People who take this drug should notdrive, use machines, or do anything else that might bedangerous until they have found out how the medicineaffects them.

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Dicyclomine should not be given to infants or chil-
dren unless the physician decides the use of this drug isnecessary. Diclyclomine should not be used by womenwho are breast feeding. Women who are pregnant or planto become pregnant should check with their physiciansbefore using this drug.
Anyone with the following medical conditions
should not take dicyclomine unless directed to do so by aphysician:
• previous sensitivity or allergic reaction to dicyclomine

• glaucoma• myasthenia gravis• blockage of the urinary tract, stomach, or intestines• severe ulcerative colitis
• reflux esophagitis
In addition, patients with these conditions should
check with their physicians before using dicyclomine:
• heart problems• enlarged prostate gland• hiatal hernia
• autonomic neuropathy (a nerve disorder)
• hyperthyroidism
The most common side effects are dizziness , drowsi-

ness, lightheadedness, nausea, nervousness, blurredvision, dry mouth, and weakness. Other side effects mayoccur. Anyone who has unusual symptoms after takingdicyclomine should get in touch with his or her physician.
Dicyclomine may interact with other medicines.
When this happens, the effects of one or both of thedrugs may change or the risk of side effects may begreater. Among the drugs that may interact with Dicy-clomine are:
• antacids such as Maalox

• antihistamines such as clemastine fumarate (Tavist)• bronchodilators (airway opening drugs) such as albu-
terol (Proventil, Ventolin)
• corticosteroids such as prednisone (Deltasone)
as phenelzine (Nardil) and tranylcypromine (Parnate)
• tranquilizers such as diazepam (Valium) and alprazo-
lam (Xanax)KEY TERMS
Heat stroke —A serious condition that results from

exposure to extreme heat. The body loses its abili-ty to cool itself. Severe headache, high fever, andhot, dry skin may result. In severe cases, a personwith heat stroke may collapse or go into a coma.
Hiatal hernia —A condition in which part of the
stomach protrudes through the diaphragm.
Hyperthyroidism —Secretion of excess thyroid
hormones by the thyroid gland.

Myasthenia gravis —A condition in which certain
muscles weaken and may become paralyzed.
Reflux esophagitis —Inflammation of the lower
esophagus caused by the backflow of stomachcontents.
or a group of muscles
Ulcerative colitis —Long-lasting and repeated
inflammation of the colon with the developmentof sores.

interact with dicyclomine. Be sure to check with a physi-cian or pharmacist before combining dicyclomine withany other prescription or nonprescription (over-the-counter) medicine.
Antistreptolysin O titer (ASO) see
Streptococcal antibody tests
Antithrombin III deficiency see
Hypercoagulation disorders
Antituberculosis drugs
Antituberculosis drugs are medicines used to treat
tuberculosis , an infectious disease that can affect the
lungs and other organs.

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Purpose
Tuberculosis is a disease caused by Mycobacterium
tuberculae, a bacteria that is passed between peoplethrough the air. The disease can be cured with properdrug therapy, but because the bacteria may become resis-tant to any single drug, combinations of antituberculosisdrugs are used to treat tuberculosis (TB) are normallyrequired for effective treatment. At the start of the 20thCentury, tuberculosis was the most common cause ofdeath in the United States, but was laregly eliminated

with better living conditions. It is most common in areasof crowding and poor ventilation, suich as crowdedurban areas and prisons. In some areas, the AIDS epi-
demic has been accompanied by an increase in the preva-lence of tuberculosis.
Some antituberculosis drugs also are used to treat or
prevent other infections such as Mycobacterium avium
complex (MAC), which causes disease throughout thebodies of people with AIDS or other diseases of theimmune system.

Antituberculosis drugs are available only with a
physician’s prescription and come in tablet, capsule, liq-uid and injectable forms. Some commonly used antitu-berculosis drugs are cycloserine (Seromycin), ethambu-tol (Myambutol), ethionamide (Trecator-SC), isoniazid(Nydrazid, Laniazid), pyrazinamide, rifabutin(Mycobutin), and rifampin (Rifadin, Rimactane).

antituberculosis drug and may be different for differentpatients. Check with the physician who prescribed themedicine or the pharmacist who filled the prescriptionfor the proper dosage. The physician may graduallyincrease the dosage during treatment. Be sure to followthe physician’s orders. Patients who are infected withHIV must usually take larger combinations of drugs for alonger period of time than is needed for patients with anunimpaired immune system.

Some antituberculosis drugs must be taken with
other drugs. If they are taken alone, they may encouragethe bacteria that cause tuberculosis to become resistant todrugs used to treat the disease. When the bacteria becomeresistant, treating the disease becomes more difficult.
To clear up tuberculosis completely, antituberculosis

drugs must be taken for as long as directed. This maymean taking the medicine every day for a year or two oreven longer. Symptoms may improve very quickly aftertreatment with this medicine begins. However, they may
come back if the medicine is stopped too quickly. Do notstop taking the medicine just because symptoms improve.
Because people may neglect to take their medication

for tuberculosis, it is common to have tuberculosis centersdevelop a program of Directly Observed Therapy (DOT.)In these programs, patients come to the hospital or clinic,and take their medication in front of an observer. Theseprograms may be annoying to the patients, but are justi-fied by the risks to public health if tuberculosis germswhich have become resistant to drugs were to be spread.
Cycloserine works best when it is at constant levels

in the blood. To help keep levels constant, take the medi-cine in doses spaced evenly through the day and night.Do not miss any doses. If taking medicine at night inter-feres with sleep, or if it is difficult to remember to takethe medicine during the day, check with a health careprofessional for suggestions.
Do not take antacids that contain aluminum, such as
Maalox, within 1 hour of taking isoniazid, as this maykeep the medicine from working.

Seeing a physician regularly while taking antituber-
culosis drugs is important. The physician will check tomake sure the medicine is working as it should and willwatch for unwanted side effects. These visits also willhelp the physician know if the dosage needs to bechanged.
Symptoms should begin to improve within a few
weeks after treatment begins with antituberculosis drugs.If they do not, or if they become worse, check with aphysician.

Some people feel drowsy, dizzy, confused, or less
alert when using these drugs. Some may also causevision changes, clumsiness, or unsteadiness. Because ofthese possible problems, anyone who takes antitubercu-losis drugs should not drive, use machines, or do any-thing else that might be dangerous until they have foundout how the medicine affects them.
Daily doses of pyridoxine (vitamin B
6) may lessen

or prevent some side effects of ethionamide or isoniazid.If the physician who prescribed the medicine recom-mends this, be sure to take the pyridoxine every day.
Certain kinds of cheese (such as Swiss and Cheshire)
and fish (such as tuna and skipjack) may cause an unusualreaction in people taking isoniazid. Symptoms of thisreaction include fast or pounding heartbeat, sweating or ahot feeling, chills or a clammy feeling, headache , light-

headedness, and red or itchy skin. This reaction is very
GALE ENCYCLOPEDIA OF MEDICINE 2 310Antituberculosis drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 310

rare. However, if any of these symptoms occur, check
with a physician as soon as possible.
Rifabutin and rifampin will make saliva, sweat, tears,
urine, feces, and skin turn reddish orange to reddish brown.This is nothing to worry about. However, the discoloredtears may permanently stain soft contact lenses (but nothard contact lenses). To avoid ruining contact lenses, do notwear soft contacts while taking these medicines.
Rifampin may temporarily lower the number of

white blood cells. Because the white blood cells areimportant in fighting infection, this effect increases thechance of getting an infection. This drug also may lowerthe number of platelets that play an important role inclotting. To reduce the risk of bleeding and infection inthe mouth while taking this medicine, be especially care-ful when brushing and flossing the teeth. Check with aphysician or dentist for suggestions on how to keep theteeth and mouth clean without causing injuries. Put

and mouth clean without causing injuries. Put offany dental work until blood counts return to normal.

Rifampin may affect the results of some medical tests.
Before having medical tests, anyone taking this medicineshould alert the health care professional in charge.
People who have certain medical conditions may
have problems if they take antituberculosis drugs. Forexample:
• cycloserine or isoniazid may increase the risk of
seizures (convulsions) in people with a history ofseizures.
• the dosage of cycloserine may need to be adjusted for
people with kidney disease.

• ethambutol or pyrazinamide may cause or worsen
attacks of gout in people who are prone to having them.
• ethambutol may cause or worsen eye damage.
• diabetes may be harder to control in patients who take
ethionamide.
• isoniazid may cause false results on some urine sugar
tests, and pyrazinamide may cause false results on urineketone tests. Diabetic patients who either of these medi-cines should discuss the possibility of false test resultswith their physicians.

• people with liver disease or a history of alcohol abuse
may be more likely to develop hepatitis when takingisoniazid and are more likely to have side effects thataffect the liver when taking rifampin.
• in people with kidney disease, ethambutol, ethion-
amide, or isoniazid may be more likely to cause sideeffects.
• side effects are also more likely in people with liver dis-
ease who take pyrazinamide.Before taking antituberculosis drugs, be sure to let

the physician know about these or any other medicalproblems.
In laboratory tests of pregnant animals, high doses of
some antituberculosis drugs have caused birth defects
and other problems in the fetus or newborn. However,pregnant women with tuberculosis need to take antituber-culosis drugs to clear up their disease. Knowing that manywomen have had healthy babies after taking these drugsduring pregnancy may be reassuring. Pregnant women

who need to take this medicine and are worried about birthdefects or other problems should talk to their physicians.
Anyone who has had unusual reactions to antituber-
culosis drugs or to niacin should let his or her physicianknow before taking any antituberculosis drug. The physi-cian should also be told about any allergies to foods,
Patients who are on special diets , such as low-sodi-

um or low-sugar diets, should make sure their physiciansknow. Some antituberculosis medicines may containsodium, sugar, or alcohol.
Cycloserine
In some people, this medicine causes depression and
thoughts of suicide. If this happens, check with a physi-cian immediately. Switching to another medicine willusually stop these troubling thoughts and feelings. Alsolet the physician know immediately about any other moodor mental changes; such as nervousness, nightmares, anx-

iety, confusion, or irritability; and about symptoms such
as muscle twitches, convulsions, or speech problems.
Headache is a common side effect that usually goes
away as the body adjusts to this medicine. This problemdoes not need medical attention unless it continues or itinterferes with everyday life.
Ethambutol
This medicine may cause eye pain or vision
changes, including loss of vision or changes in colorvision. Check with a physician immediately if any ofthese problems develop.

In addition, anyone who has any of these symptoms
while taking ethambutol should check with a physicianimmediately:
• painful or swollen joints, especially in the knee, ankle,
or big toe
• a tight, hot sensation in the skin over painful or swollen
joints
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• chills
Other side effects may occur but do not need med-
ical attention unless they are bothersome or they do notgo away as the body adjusts to the medicine. Theseinclude: headache, confusion, nausea and vomiting ,
stomach pain, and loss of appetite.
Ethionamide
Check with a physician immediately if eye pain,
blurred vision, or other vision changes occur while tak-ing this medicine.
Symptoms such as unsteadiness, clumsiness and

pain, numbness, tingling, or burning in the hands or feetcould be the first signs of nerve problems that maybecome more serious. If any of these symptoms occur,check with a physician immediately. Other side effectsthat should be brought to a physician’s attention immedi-ately include yellow eyes or skin and mood or mentalchanges such as depression or confusion.
Less serious side effects such as dizziness , nausea or

vomiting, appetite loss, sore mouth, or metallic taste mayalso occur. These problems usually go away as the bodyadjusts to the medicine. They do not need medical atten-tion unless they continue or they interfere with normalactivities.
Isoniazid
This medicine may cause serious liver damage,

especially in people over 40 years of age. However, tak-ing medicine for tuberculosis is very important for peo-ple with the disease. Anyone who has tuberculosis andhas been advised to take this drug should thoroughly dis-cuss treatment options with his or her physician.
Recognizing the early signs of liver and nerve dam-
age can help prevent the problems from getting worse. Ifany of these symptoms occur, check with a physicianimmediately:

• pain, numbness, tingling, or burning in the hands and
feet
• loss of appetite• vomiting
This medicine may also cause less serious side
effects such as diarrhea and stomach pain. These usual-
ly go away as the body adjusts to the medicine and do notneed medical attention unless they continue.
If eye pain, blurred vision, or other vision changes
occur while taking this medicine, check with a physicianimmediately.Pyrazinamide

Check with a physician immediately if pain in the
joints occurs.
Rifabutin
Check with a physician immediately if a skin rash
occurs.
Nausea and vomiting are other possible side effects
of this medicine. These problems usually go away as thebody adjusts to the medicine. If they do not, check with aphysician.
Rifampin
Stop taking rifampin and check with a physician

immediately if any of the following symptoms occur.These symptoms could be early signs of problems thatmay become more serious. Getting prompt medicalattention could prevent them from getting worse.
while taking rifampin should check with a physicianimmediately:
•f e v e r
• chills
• shivering

•f e v e r
• chills
• headache• dizziness
• itching
• skin rash or redness
• muscle and bone pain
Other side effects, such as diarrhea and stomach
pain, may occur with this medicine, but should go awayas the body adjusts to the drug. Medical treatment is notnecessary unless these problems continue.
Other side effects may occur with any antituberculo-
sis drug. Anyone who has unusual symptoms while tak-ing an antituberculosis drug should get in touch with hisor her physician.

Taking cycloserine and ethionamide together may
increase the risk of seizures and other nervous systemproblems. These and other side effects also are more
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likely in people who drink alcohol while taking cycloser-
ine. To avoid these problems, do not drink alcohol while
taking cycloserine and check with a physician before
combining cycloserine and ethionamide.
Drinking alcohol regularly may prevent isoniazid
from working properly and may increase the chance ofliver damage. Anyone taking this medicine should strict-ly limit the use of alcohol. Check with a health care pro-fessional for advice on the amount of alcohol that maysafely be used.

Many drugs may interact with isoniazid or rifampin,
increasing the chance of liver damage or other sideeffects. Among these drugs are acetaminophen
(Tylenol), birth control pills and other drugs that containfemale hormones, and the antiseizure drugs divalproex(Depakote) and valproic acid (Depakene). For a com-plete list of drugs that may have this effect, check with apharmacist.
Isoniazid may also decrease the effects of the anti-

fungal drug ketoconazole (Nizoral) and the antitubercu-losis drug rifampin (Rifadin).
Rifampin may make many drugs less effective.
Among the drugs that may be affected are diabetes medi-cines taken by mouth (oral hypoglycemics), digitalisheart drugs, many antifungal drugs, and birth controlpills. Because it makes birth control pills less effective,taking rifampin may increase the chance of becomingKEY TERMS

Feces —(Also called stool.) The solid waste that is left
after food is digested. Feces form in the intestinesand pass out of the body through the anus.
Gout —A disease in which uric acid, a waste prod-
uct that normally passes out of the body in urine,collects in the joints and the kidneys. This causesarthritis and kidney stones.

Microorganism —An organism (life form) that is
too small to be seen with the naked eye.
Platelets —Disk-shaped bodies in the blood that
are important in clotting.
Seizure —A sudden attack, spasm, or convulsion.pregnant. Women who take this medicine along with
birth control pills should use an additional form of birthcontrol. For a complete list of drugs that may be affectedby rifampin, check with a pharmacist.
Using rifabutin with the antiretroviral drug zidovu-

dine (AZT, Retrovir) may make the zidovudine less effec-tive. Consult with a physician if both drugs are prescribed.
Not every drug that may interact with an antituber-
culosis drug is listed here. Be sure to check with a physi-cian or pharmacist before combining an antituberculosisdrug with any other prescription or nonprescription(over-the-counter) medicine.
Resources
Cornwall, Janet. “Tuberculosis: A Clinical Problem of Interna-

tional Importance.” The Lancet (August 30, 1997): 660.
Antiulcer drugs
Antiulcer drugs are a class of drugs, exclusive of the
antibacterial agents, used to treat ulcers in the stomachand the upper part of the small intestine.
Purpose
Recurrent gastric and duodenal ulcers are caused by
Helicobacter pylori infections, and are treated with com-

bination treatments that incorporate antibiotic therapywith gastric acid suppression. Additionally, bismuthcompounds have been used. The primary class of drugsused for gastric acid suppression are the proton pumpinhibitors, omeprazole, lansoprazole, pantoprazole andrabeprazole. The H-2 receptor blocking agents, cimeti-dine, f amotidine, nizatidine, and ranitidine have been used

for this purpose, but are now more widely used for mainte-nance therapy after treatment with the proton pumpinhibitors. Sucralfate, which acts by forming a protectivecoating over the ulcerate lesion, is also used in ulcer treat-ment and may be appropriate for patients in whom otherclasses of drugs are not indicated, or those whose gastriculcers are caused by non-steroidal anti-inflammatorydrugs (NSAIDs) rather than H. pylori infections.

The proton pump inhibitors block the secretion of
gastric acid by the gastric parietal cells. The extent of inhi-
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bition of acid secretion is dose related. In some cases, gas-
tric acid secretion is completely blocked for over 24 hourson a single dose. In addition to their role in treatment ofgastric ulcers, the proton pump inhibitors are used to treatsyndromes of excessive acid secretion (Zollinger-EllisonSyndrome) and gastroesophageal reflux disease (GERD).
Histamine H-2 receptor blockers stop the action of

histamine on the gastric parietal cells, inhibiting the secre-tion of gastric acid. These drugs are less effective than theproton pump inhibitors, but may achieve a 75–79% reduc-tion in acid secretion. Higher rates of acid inhibition maybe achieved when the drug is administered by the intra-venous route. The H-2 receptor blockers may also be usedto treat heartburn and hypersecretory syndromes. When
given before surgery, the H-2 receptor blockers are usefulin prevention of aspiration pneumonia .

Sucralfate (Carafate), a substituted sugar molecule
with no nutritional value, does not inhibit gastric acid, butrather, reacts with existing stomach acid to form a thickcoating that covers the surface of an ulcer, protecting theopen area from further damage. A secondary effect is toact as an inhibitor of the digestive enzyme pepsin. Sucral-fate does not bind to the normal stomach lining. The drughas been used for prevention of stress ulcers, the type

seen in patients exposed to physical stress such as burns
and surgery. It has no systemic effects.
The doses of the proton pump inhibitors and H-2
receptor blockers vary depending on the drug and condi-tion being treated. Consult individual references.
The dose of sucralfate for acute ulcer therapy is 1
gram four times a day. After the ulcer has healed, mainte-nance treatment may continue at 1 gram two times daily.

The proton pump inhibitors are generally well toler-
ated, and the most common adverse effects are diarrhea ,itching , skin rash, dizziness and headache . Muscle

aches and a higher than normal rate of respiratory infec-tions are among the other adverse reactions reported.Omeprazole has an increased rate of fetal deaths in ani-mal studies. It is not known if these drugs are excreted inhuman milk, but because of reported adverse effects toinfants in animal studies, it is recommended that protonpump inhibitors not be used by nursing mothers.
The H-2 receptor blockers vary widely in their

adverse effects. Although they are generally well tolerat-ed, cimetidine may cause confusion in elderly patients,and has an antiandrogenic effect that may cause sexual
dysfunction in males. Famotidine has been reported to
cause headache in 4.7% of patients. It is advisable thatmothers not take H-2 receptor blockers while nursing.
Sucralfate is well tolerated. It is poorly absorbed,
and its most common side effect is constipation in 2% of

patients. Diarrhea, nausea, vomiting, gastric discomfort,indigestion , flatulence, dry mouth , rash, pruritus (itch-
ing), back pain , headache, dizziness, sleepiness, and ver-
tigo have been reported, as well as rare allergic respons-es. Because sucralfate releases small amounts of alu-minum into the system, it should be used with caution inpatients with renal insufficiency. There is no informationavailable about sucralfate’s safety in breastfeeding.

Proton pump inhibitors may increase the pH of the
stomach. This will inactivate some antifungal drugs thatrequire an acid medium for effectiveness, notable itra-conazole and ketoconazole.
H-2 receptor blocking agents have a large number of
drug interactions. Consult individualized references.
Sucralfate should not be used with aluminum con-
taining antacids , because of the risk of increased alu-

minum absorption. Sucralfate may inhibit absorption andreduce blood levels of anticoagulants, digoxin, quinidine,ketoconazole, quinolones and phenytoin.
GALE ENCYCLOPEDIA OF MEDICINE 2 314Antiulcer drugsAntiulcer Drugs
Axid (nitzatidine) Diarrhea, headache, nausea and vomiting, sore throat

Carafate (sucralfate) Constipation, insomnia, hives, upset stomach, vomitingCytotec (misoprostol) Cramps, diarrhea, nausea, gas, headache, menstrual disorders (including 
heavy bleeding and severe cramping)

Pepcid (famotidine) Constipation or diarrhea, dizziness, fatigue, feverPrilosec (omeprazole) Nausea and vomiting, headache, diarrhea, abdominal painTagamet (cimetidine) Headache, breast development in men, depression and disorientationZantac (ranitidine hydrochloride) Headache, constipation or diarrhea, joint painGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 314

Resources
Digestive Disease National Coalition. 507 Capitol Court NE,
Suite 200, Washington, DC 20003. (202) 544-7497.
National Digestive Diseases Information Clearinghouse. 2
Information Way, Bethesda, MD 20892-3570.nddic@aerie.com. <http://www.niddk.nih.gov/Brochures/NDDIC.htm>.
OTHER
Duodenal Ulcer Fact sheet . Johns Hopkins Health Information
Adult Health Advisor. Available at <http://csi.intelihealth.com>.

PharmInfoNet’s Digestive Disease Center. <http://pharminfo.
com/disease.gastro.html>.
Stomach and Duodenal Ulcers. Fact sheet. National Institute of
Diabetes and Digestive and Kidney Diseases, January1995 (NIH Publication No. 95-38).
Stomach Ulcer (Gastric Ulcer). Fact sheet. Johns Hopkins
Health Information Adult Health Advisor. Available onwebsite at <http://csi.intelihealth.com>.
Antibiotic —Medicine used to treat infections.

Gastrointestinal tract —The stomach, small intes-
tine and large intestine.
Hypersecretory —Excessive production of a bodily

secretion. The most common hypersecretory syn-drome of the stomach is Zollinger-Ellison Syn-drome, a syndrome consisting of fulminatingintractable peptic ulcers, gastric hypersecretion andhyperacidity, and the occurrence of gastrinomas ofthe pancreatic cells of the islets of Langerhans.
Mucous —Thick fluid produced by the moist mem-

Nonsteroidal anti-inflammatory drug (NSAID) —
A type of medicine used to relieve pain, swelling,and other symptoms of inflammation, such asibuprofen or ketoprofen.Antiviral drugs
Antiviral drugs are medicines that cure or control
Purpose
Antivirals are used to treat infections caused by

viruses. Unlike antibacterial drugs, which may cover awide range of pathogens, antiviral agents tend to be nar-row in spectrum, and have limited efficacy.
Exclusive of the antiretroviral agents used in HIV
(AIDS ) therapy, there are currently only 11 antiviral

drugs available, covering four types of virus. Acyclovir(Zovirax), famciclovir (Famvir), and valacyclovir (Val-trex) are effective against herpesvirus, including herpeszoster and herpes genitalis. They may also be of value ineither conditions caused by herpes, such as chickenpox
and shingles . These drugs are not curative, but may
reduce the pain of a herpes outbreak and shorten the
period of viral shedding.
Amantadine (Symmetrel), oseltamivir (Tamiflu),

rimantidine (Flumadine), and zanamivir (Relenza) areuseful in treatment of influenza virus. Amantadine,
rimantadine, and oseltamivir may be administeredthroughout the flu season as preventatives for patientswho cannot take influenza virus vaccine.
Cidofovir (Vistide), foscarnet (Foscavir), and ganci-

clovir (Cytovene) have been beneficial in treatment ofcytomegalovirus in immunosupressed patients, primarilyHIV-positive patients and transplant recipients. Ribavirin(Virazole) is used to treat respiratory syncytial virus. Incombination with interferons, ribavirin has shown someefficacy against hepatitis C , and there have been anecdo-
tal reports of utility against other types of viral infections.
As a class, the antivirals are not curative, and must be

used either prophylactically or early in the developmentof an infection. Their mechanism of action is typically toinactivate the enzymes needed for viral replication. Thiswill reduce the rate of viral growth, but will not inactivethe virus already present. Antiviral therapy must normallybe initiated within 48 hours of the onset of an infection toprovide any benefit. Drugs used for influenza may beused throughout the influenza season in high risk patients,or within 48 hours of exposure to a

risk patients,or within 48 hours of exposure to a known carrier. Anti-herpetic agents should be used at the first signs of an out-break. Anti-cytomegaloviral drugs must routinely be usedas part of a program of secondary prophylaxis (mainte-

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nance therapy following an initial response) in order to
prevent reinfection in immunocompromised patients.
Dosage varies with the drug, patient age and condi-
tion, route of administration, and other factors. See spe-cific references.
Ganciclovir is available in intravenous injection, oral

capsules, and intraoccular inserts. The capsules should bereserved for prophylactic use in organ transplant patients,or for HIV infected patients who cannot be treated withthe intravenous drug. The toxicity profile of this drugwhen administered systemically includes granulocytope-nia, anemia and thrombocytopenia . The drug is in preg-
nancy category C, but has caused significant fetal abnor-
malities in animal studies including cleft palate and organdefects. Breast feeding is not recommended.

Cidofovir causes renal toxicity in 53% of patients.
Patients should be well hydrated, and renal functionshould be checked regularly. Other common adverseeffects are nausea and vomiting in 65% or patients,
asthenia in 46% and headache and diarrhea , both
reported in 27% of cases. The drug is category C in preg-nancy, due to fetal abnormalities in animal studies.Breast feeding is not recommended.
Foscarnet is used in treatment of immunocompro-

mised patients with cytomegalovirus infections and inacyclovir-resistant herpes simples virus. The primaryhazard is renal toxicity. Alterations in electrolyte levelsmay cause seizures. Foscarnet is category C during preg-nancy. The drug has caused skeletal abnormailities indeveloping fetuses. It is not known whether foscarnet isexcreted in breast milk, however the drug does appear inbreast milk in animal studies.

hazards of the two drugs are very similar. They are gener-ally well tolerated, but nausea and headache are commonadverse effects. They are both pregnancy category B.Although there have been no reports of fetal abnormali-ties attributable to either drug, the small number of report-ed cases makes it impossible to draw conclusions regard-ing safety in pregnancy. Acyclovir is found in breast milk,but no adverse effects have been reported in the newborn.Famciclovir is similar in actions and adverse

Ribavirin is used by aerosol for treatment of hospital-
ized infants and young children with severe lower respira-tory tract infections due to respiratory syncytial virus(RSV). When administered orally, the drug has been usedin adultys to treat other viral diseases including acute andKEY TERMS
Asthenia —Muscle weakness.
Cytomegalovirus (CMV) —A type of virus that
attacks and enlarges certain cells in the body. Thevirus also causes a disease in infants.

Herpes simplex —A virus that causes sores on the
lips (cold sores) or on the genitals (genital herpes).
HIV—Acronym for human immunodeficiency
virus, the virus that causes AIDS.
Parkinsonism —A group of conditions that all have
these typical symptoms in common: tremor, rigidi-ty, slow movement, and poor balance and coordi-nation.

drugs according to their established risks for useduring pregnancy. Category A: Controlled humanstudies have demonstrated no fetal risk. CategoryB: Animal studies indicate no fetal risk, but nohuman studies, or adverse effects in animals, butnot in well-controlled human studies. Category C:No adequate human or animal studies, or adversefetal effects in animal studies, but no availablehuman data. Category D: Evidence of fetal risk,but benefits outweigh risks. Category X: Evidenceof fetal risk.

Prophylactic —Guarding from or preventing the
spread or occurrence of disease or infection.
Retrovirus —A group of viruses that contain RNA
and the enzyme reverse transcriptase. Many virus-es in this family cause tumors. The virus that caus-es AIDS is a retrovirus.
Shingles —An disease caused by an infection with
the Herpes zoster virus, the same virus that causeschickenpox. Symptoms of shingles include painand blisters along one nerve, usually on the face,chest, stomach, or back.

Virus —A tiny, disease-causing structure that can
reproduce only in living cells and causes a varietyof infectious diseases.
chronic hepatitis, herpes genitalis, measles , and Lassa
fever , however there is relatively little information about
these uses. In rare cases, initiation of ribavirin therapy hasled to deterioration of respiratory function in infants.Careful monitoring is essential for safe use.
The anti-influenza drugs are generally well tolerat-

ed. Amantadine, which is also used for treatment of
GALE ENCYCLOPEDIA OF MEDICINE 2 316Antiviral drugsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 316

Parkinsonism, may show more frequent CNS effects,
including sedation and dizziness . Rapid discontinuation
of amantidine may cause an increase in Parkinsoniansymptoms in patients using the drug for that purpose. Allare schedule C for pregnancy. In animal studies, theyhave caused fetal malformations in doses several timeshigher than the normal human dose. Use caution inbreast feeding.
Consult specific references for information on drug
interactions.

Use particular caution in HIV-positive patients,
since these patients are commonly on multi-drug regi-mens with a high frequency of interactions. Ganciclovirshould not be used with other drugs which cause hemato-logic toxicity, and cidofovir should not be used withother drugs that may cause kidney damage.
Resources
Gray, Mary Ann. “Antiviral Medications.” Orthopaedic Nurs-
ing15 (November-December 1996): 82.
Anxiety

Anxiety
Anxiety is a multisystem response to a perceived

threat or danger. It reflects a combination of biochemicalchanges in the body, the patient’s personal history andmemory, and the social situation. As far as we know, anxi-ety is a uniquely human experience. Other animals clearlyknow fear, but human anxiety involves an ability, to usememory and imagination to move backward and forwardin time, that animals do not appear to have. The anxietythat occurs in post-traumatic syndromes indicates thathuman memory is a much more complicated mental

memory is a much more complicated mental func-tion than animal memory. Moreover, a large portion ofhuman anxiety is produced by anticipation of futureevents. Without a sense of personal continuity over time,people would not have the “raw materials” of anxiety.

It is important to distinguish between anxiety as a
feeling or experience, and an anxiety disorder as a psy-chiatric diagnosis. A person may feel anxious withouthaving an anxiety disorder. Also a person facing a clearand present danger or a realistic fear is not usually con-sidered to be in a state of anxiety. In addition, anxietyfrequently occurs as a symptom in other categories ofpsychiatric disturbance.
Although anxiety is a commonplace experience that

everyone has from time to time, it is difficult to describeconcretely because it has so many different potential caus-es and degrees of intensity. Doctors sometimes categorizeanxiety as an emotion or an affect depending on whether itis being described by the person having it (emotion) or byan outside observer (affect). The word emotion is general-

ly used for the biochemical changes and feeling state thatunderlie a person’s internal sense of anxiety. Affect is used
to describe the person’s emotional state from an observer’sperspective. If a doctor says that a patient has an anxiousaffect, he or she means that the patient appears nervous oranxious, or responds to others in an anxious way (forexample, the individual is shaky, tremulous, etc.).
Although anxiety is related to fear, it is not the same

thing. Fear is a direct, focused response to a specific eventor object, and the person is consciously aware of it. Mostpeople will feel fear if someone points a loaded gun atthem or if they see a tornado forming on the horizon. Theyalso will recognize that they are afraid. Anxiety, on theother hand, is often unfocused, vague, and hard to pindown to a specific cause. In this form it is called free-float-ing anxiety. Sometimes anxiety being experienced in thepresent may stem from an event or

in thepresent may stem from an event or person that producedpain and fear in the past, but the anxious individual is not

consciously aware of the original source of the feeling. Itis anxiety’s aspect of remoteness that makes it hard forpeople to compare their experiences of it. Whereas mostpeople will be fearful in physically dangerous situations,and can agree that fear is an appropriate response in thepresence of danger, anxiety is often triggered by objects orevents that are unique and specific to an individual. Anindividual might be anxious because of a unique meaningor memory being stimulated by present

meaningor memory being stimulated by present circumstances, notbecause of some immediate danger. Another individuallooking at the anxious person from the outside may betruly puzzled as to the reason for the person’s anxiety.

Anxiety can have a number of different causes. It is
a multidimensional response to stimuli in the person’senvironment, or a response to an internal stimulus (forexample, a hypochondriac’s reaction to a stomach rum-bling) resulting from a combination of general biologicaland individual psychological processes.
Physical
In some cases, anxiety is produced by physical respons-
es to stress , or by certain disease processes or medications.

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vous system of human beings is “hard-wired” to respondto dangers or threats. These responses are not subject toconscious control, and are the same in humans as inlower animals. They represent an evolutionary adaptationto the animal predators and other dangers with which allanimals, including primitive humans, had to cope. Themost familiar reaction of this type is the so-called “fight-or-flight” reaction. This response is the human organ-ism’s automatic “red alert” in a life-threatening

automatic “red alert” in a life-threatening situation.It is a state of physiological and emotional hyperarousalmarked by high muscle tension and strong feelings offear or anger. When a person has a fight-or-flight reac-tion, the level of stress hormones in their blood rises.They become more alert and attentive, their eyes dilate,their heartbeat increases, their breathing rate increases,and their digestion slows down, allowing more energy tobe available to the muscles.

nervous system called the autonomic nervous system, orANS. The ANS is controlled by the hypothalamus, a spe-cialized part of the brainstem that is among a group ofstructures called the limbic system. The limbic systemcontrols human emotions through its connections toglands and muscles; it also connects to the ANS and“higher” brain centers, such as parts of the cerebral cor-tex. One problem with this arrangement is that the limbicsystem cannot tell the difference between a realisticphysical

tell the difference between a realisticphysical threat and an anxiety-producing thought or idea.The hypothalamus may trigger the release of stress hor-mones by the pituitary gland, even when there is noexternal and objective danger. A second problem iscaused by the biochemical side effects of too many “falsealarms” in the ANS. When a person responds to a realdanger, his or her body gets rid of the stress hormones byrunning away or by fighting. In modern life, however,people often have

In modern life, however,people often have fight-or-flight reactions in situations inwhich they can neither run away nor lash out physically.As a result, their bodies have to absorb all the biochemi-cal changes of hyperarousal, rather than release them.These biochemical changes can produce anxious feel-ings, as well as muscle tension and other physical symp-toms associated with anxiety. They may even producepermanent changes in the brain, if the process occursrepeatedly. Moreover, chronic

the process occursrepeatedly. Moreover, chronic physical disorders, such ascoronary artery disease , may be worsened by anxiety,

as chronic hyperarousal puts undue stress on the heart,stomach, and other organs.
DISEASES AND DISORDERS. Anxiety can be a symp-
tom of certain medical conditions. Some of these dis-eases are disorders of the endocrine system, such asCushing’s syndrome (overproduction of cortisol by the
adrenal cortex), and include over- or underactivity of thethyroid gland. Other medical conditions that can produce
anxiety include respiratory distress syndrome ,mitral

valve prolapse , porphyria, and chest pain caused by
inadequate blood supply to the heart ( angina pectoris).
MEDICATIONS AND SUBSTANCE USE. Numerous
medications may cause anxiety-like symptoms as a sideeffect. They include birth control pills; some thyroid orasthma drugs; some psychotropic agents; occasionally,
local anesthetics; corticosteroids ; antihypertensive
drugs ; and nonsteroidal anti-inflammatory drugs (like
flurbiprofen and ibuprofen).

Although people do not usually think of caffeine as
a drug, it can cause anxiety-like symptoms when con-sumed in sufficient quantity. Patients who consume caf-feine rich foods and beverages, such as chocolate, cocoa,coffee, tea, or carbonated soft drinks (especially colabeverages), can sometimes lower their anxiety symptomssimply by reducing their intake of these substances.
Withdrawal from certain prescription drugs, primari-

ly beta blockers and corticosteroids, can cause anxiety.
Withdrawal from drugs of abuse, including LSD ,
cocaine , alcohol, and opiates, can also cause anxiety.
Learned associations
Some aspects of anxiety appear to be unavoidable

byproducts of the human developmental process.Humans are unique among animals in that they spend anunusually long period of early life in a relatively helplesscondition, and a sense of helplessness can lead to anxi-ety. The extended period of human dependency on adultsmeans that people may remember, and learn to antici-pate, frightening or upsetting experiences long beforethey are capable enough to feel a sense of mastery overtheir environment. In addition, the fact that anxiety dis-

orders often run in families indicates that children can
learn unhealthy attitudes and behaviors from parents, aswell as healthy ones. Also, recurrent disorders in familiesmay indicate that there is a genetic or inherited compo-nent in some anxiety disorders. For example, there hasbeen found to be a higher rate of anxiety disorders(panic) in identical twins than in fraternal twins.
CHILDHOOD DEVELOPMENT AND ANXIETY. Re-

searchers in early childhood development regard anxietyin adult life as a residue of childhood memories ofdependency. Humans learn during the first year of lifethat they are not self-sufficient and that their basic sur-vival depends on the care of others. It is thought that thisearly experience of helplessness underlies the most com-mon anxieties of adult life, including fear of powerless-ness and fear of being unloved. Thus, adults can be madeanxious by symbolic threats to their sense of

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and/or significant relationships, even though they are no
longer helpless children.
SYMBOLIZATION. The psychoanalytic model gives

considerable weight to the symbolic aspect of humananxiety; examples include phobic disorders, obsessions,compulsions, and other forms of anxiety that are highlyindividualized. The length of the human maturationprocess allows many opportunities for children and ado-lescents to connect their experiences with certain objectsor events that can bring back feelings in later life. Forexample, a person who was frightened as a child by a tallman wearing glasses may feel panicky years later bysomething

glasses may feel panicky years later bysomething that reminds him of that person or experiencewithout consciously knowing why.

internal conflicts. According to his theory, people feelanxious when they feel torn between desires or urgestoward certain actions, on the one hand, and moralrestrictions, on the other. In some cases, the person’sanxiety may attach itself to an object that represents theinner conflict. For example, someone who feels anxiousaround money may be pulled between a desire to stealand the belief that stealing is wrong. Money becomes asymbol for the inner conflict between doing what is con-sidered

inner conflict between doing what is con-sidered right and doing what one wants.

PHOBIAS. Phobias are a special type of anxiety
reaction in which the person’s anxiety is concentrated ona specific object or situation that the person then tries toavoid. In most cases, the person’s fear is out of all pro-portion to its “cause.” Prior to the Diagnostic and Statis-
tical Manual of Mental Disorders, 4th edition (DSM-IV),

these specific phobias were called simple phobias. It isestimated that 10-11% of the population will develop aphobia in the course of their lives. Some phobias, such asagoraphobia (fear of open spaces), claustrophobia (fear
of small or confined spaces), and social phobia, areshared by large numbers of people. Others are less com-mon or unique to the patient.
Social and environmental stressors
Anxiety often has a social dimension because

humans are social creatures. People frequently reportfeelings of high anxiety when they anticipate and, there-fore, fear the loss of social approval or love. Social phobiais a specific anxiety disorder that is marked by high levelsof anxiety or fear of embarrassment in social situations.
Another social stressor is prejudice. People who

belong to groups that are targets of bias are at higher riskfor developing anxiety disorders. Some experts think, forexample, that the higher rates of phobias and panic dis-
order among women reflects their greater social and
economic vulnerability.Some controversial studies indicate that the increase

in violent or upsetting pictures and stories in newsreports and entertainment may raise the anxiety level ofmany people. Stress and anxiety management programsoften suggest that patients cut down their exposure toupsetting stimuli.
Anxiety may also be caused by environmental or
occupational factors. People who must live or workaround sudden or loud noises, bright or flashing lights,chemical vapors, or similar nuisances, which they cannotavoid or control, may develop heightened anxiety levels.

Existential anxiety
Another factor that shapes human experiences of
anxiety is knowledge of personal mortality. Humans arethe only animals that appear to be aware of their limitedlife span. Some researchers think that awareness ofdeath influences experiences of anxiety from the time
that a person is old enough to understand death.
Symptoms of anxiety
In order to understand the diagnosis and treatment of
anxiety, it is helpful to have a basic understanding of itssymptoms.

SOMATIC. The somatic or physical symptoms of
anxiety include headaches, dizziness or lightheadedness,
nausea and/or vomiting, diarrhea , tingling, pale com-
plexion, sweating, numbness, difficulty in breathing, andsensations of tightness in the chest, neck, shoulders, orhands. These symptoms are produced by the hormonal,muscular, and cardiovascular reactions involved in thefight-or-flight reaction.
BEHAVIORAL. Behavioral symptoms of anxiety

include pacing, trembling, general restlessness, hyper-ventilation, pressured speech, hand wringing, or fingertapping.
COGNITIVE. Cognitive symptoms of anxiety include
recurrent or obsessive thoughts, feelings of doom, mor-bid or fear-inducing thoughts or ideas, and confusion, orinability to concentrate.
EMOTIONAL. Feeling states associated with anxiety

include tension or nervousness, feeling “hyper” or“keyed up,” and feelings of unreality, panic, or terror.
DEFENSE MECHANISMS. In psychoanalytic theory,
the symptoms of anxiety in humans may arise from oractivate a number of unconscious defense mechanisms.Because of these defenses, it is possible for a person tobe anxious without being consciously aware of it orappearing anxious to others. These psychological defens-es include:

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• Repression. The person pushes anxious thoughts or
ideas out of conscious awareness.
• Displacement. Anxiety from one source is attached to a
different object or event. Phobias are an example of themechanism of displacement in psychoanalytic theory.
• Rationalization. The person justifies the anxious feel-
ings by saying that any normal person would feel anx-ious in their situation.
• Somatization. The anxiety emerges in the form of phys-

ical complaints and illnesses, such as recurrentheadaches, stomach upsets, or muscle and joint pain.
• Delusion formation. The person converts anxious feel-
ings into conspiracy theories or similar ideas withoutreality testing. Delusion formation can involve groupsas well as individuals.
Other theorists attribute some drug addiction to the

desire to relieve symptoms of anxiety. Most addictions,they argue, originate in the use of mood-altering sub-stances or behaviors to “medicate” anxious feelings.
Diagnosis
The diagnosis of anxiety is difficult and complex

because of the variety of its causes and the highly personal-ized and individualized nature of its symptom formation.There are no medical tests that can be used to diagnoseanxiety by itself. When a doctor examines an anxiouspatient, he or she will first rule out physical conditions anddiseases that have anxiety as a symptom. Apart from theseexclusions, the physical examination is usually inconclu-

sive. Some anxious patients may have their blood pressureor pulse rate affected by anxiety, or may look pale or per-spire heavily, but others may appear physically completelynormal. The doctor will then take the patient’s medication,dietary, and occupational history to see if they are takingprescription drugs that might cause anxiety, if they areabusing alcohol or mood-altering drugs, if they are con-suming large amounts of caffeine, or if their workplace isnoisy or dangerous. In most cases,

workplace isnoisy or dangerous. In most cases, the most importantsource of diagnostic information is the patient’s psycholog-ical and social history. The doctor may administer a briefpsychological test to help evaluate the intensity of thepatient’s anxiety and some of its features. Some tests thatare often given include the Hamilton Anxiety Scale and theAnxiety Disorders Interview Schedule (ADIS). Many doc-tors will check a number of chemical factors in the blood,such as the level of thyroid

factors in the blood,such as the level of thyroid hormone and blood sugar.

Treatment
Not all patients with anxiety require treatment, but
for more severe cases, treatment is recommended.Because anxiety often has more than one cause and is

experienced in highly individual ways, its treatment usu-ally requires more than one type of therapy. In addition,there is no way to tell in advance how patients willrespond to a specific drug or therapy. Sometimes the doc-tor will need to try different medications or methods oftreatment before finding the best combination for theparticular patient. It usually takes about six to eightweeks for the doctor to evaluate the effectiveness of atreatment regimen.

Medications are often prescribed to relieve the phys-
ical and psychological symptoms of anxiety. Most agentswork by counteracting the biochemical and muscularchanges involved in the fight-or-flight reaction. Somework directly on the chemicals in the brain that arethought to underlie the anxiety.
ANXIOLYTICS. Anxiolytics are sometimes called
tranquilizers. Most anxiolytic drugs are either benzodi-
azepines or barbiturates . Barbiturates, once commonly

used, are now rarely used in clinical practice. Barbitu-rates work by slowing down the transmission of nerveimpulses from the brain to other parts of the body. Theyinclude such drugs as phenobarbital (Luminal) and pen-tobarbital (Nembutal). Benzodiazepines work by relax-ing the skeletal muscles and calming the limbic system.They include such drugs as chlordiazepoxide (Librium)and diazepam (Valium). Both barbiturates and benzodi-azepines are potentially habit-forming and may causewithdrawal

potentially habit-forming and may causewithdrawal symptoms, but benzodiazepines are far lesslikely than barbiturates to cause physical dependency.Both drugs also increase the effects of alcohol andshould never be taken in combination with it.

meprobamate (Equanil), which is now rarely used, andbuspirone (BuSpar), a new type of anxiolytic that appearsto work by increasing the efficiency of the body’s ownemotion-regulating brain chemicals. Buspirone has sever-al advantages over other anxiolytics. It does not causedependence problems, does not interact with alcohol, anddoes not affect the patient’s ability to drive or operatemachinery. However, buspirone is not effective againstcertain types of anxiety, such as panic disorder.

ANTIDEPRESSANTS AND BETA-BLOCKERS. For some
anxiety disorders, such as obsessive-compulsive disor-
derand panic type anxiety, a type of drugs used to treat
depression, selective serotonin reuptake inhibitors
(SSRIs; such as Prozac and Paxil), are the treatment ofchoice. Because anxiety often coexists with symptoms ofdepression, many doctors prescribe antidepressant med-ications for anxious/depressed patients. While SSRIs are

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more common, antidepressants are sometimes pre-
scribed, including tricyclic antidepressants such asimipramine (Tofranil) or monoamine oxidase inhibitors
(MAO inhibitors) such as phenelzine (Nardil).
Beta-blockers are medications that work by blocking

the body’s reaction to the stress hormones that arereleased during the fight-or-flight reaction. They includedrugs like propranolol (Inderal) or atenolol (Tenormin).Beta-blockers are sometimes given to patients with post-traumatic anxiety symptoms. More commonly, the beta-blockers are given to patients with a mild form of socialphobic anxiety, such as fear of public speaking.
Psychotherapy
Most patients with anxiety will be given some form of

psychotherapy along with medications. Many patientsbenefit from insight-oriented therapies, which aredesigned to help them uncover unconscious conflicts anddefense mechanisms in order to understand how theirsymptoms developed. Patients who are extremely anxiousmay benefit from supportive psychotherapy, which aims atsymptom reduction rather than personality restructuring.
Two newer approaches that work well with anxious
patients are cognitive-behavioral therapy (CBT), and

relaxation training. In CBT, the patient is taught to identifythe thoughts and situations that stimulate his or her anxi-ety, and to view them more realistically. In the behavioralpart of the program, the patient is exposed to the anxiety-provoking object, situation, or internal stimulus (like arapid heart beat) in gradual stages until he or she is desen-sitized to it. Relaxation training, which is sometimescalled anxiety management training, includes breathingexercises and similar techniques

breathingexercises and similar techniques intended to help thepatient prevent hyperventilation and relieve the muscletension associated with the fight-or-flight reaction. BothCBT and relaxation training can be used in group therapy

as well as individual treatment. In addition to CBT, sup-port groups are often helpful to anxious patients, becausethey provide a social network and lessen the embarrass-ment that often accompanies anxiety symptoms.
Psychosurgery
Surgery on the brain is very rarely recommended for

patients with anxiety; however, some patients with severecases of obsessive- compulsive disorder (OCD) havebeen helped by an operation on a part of the brain that isinvolved in OCD. Normally, this operation is attemptedafter all other treatments have failed.
Alternative treatments for anxiety cover a variety of
approaches. Meditation and mindfulness training arethought beneficial to patients with phobias and panic disor-
der. Hydrotherapy is useful to some anxious patients

because it promotes general relaxation of the nervous sys-tem. Yoga , aikido, t’ai chi , and dance therapy help patients
work with the physical, as well as the emotional, tensionsthat either promote anxiety or are created by the anxiety.
Homeopathy and traditional Chinese medicine

approach anxiety as a symptom of a systemic disorder.Homeopathic practitioners select a remedy based onother associated symptoms and the patient’s general con-stitution. Chinese medicine regards anxiety as a blockageof qi, or vital force, inside the patient’s body that is most
likely to affect the lung and large intestine meridian flow.The practitioner of Chinese medicine chooses acupunc-
ture point locations and/or herbal therapy to move the qi

and rebalance the entire system in relation to the lungand large intestine.
Aromatherapy using essential oils can also be ben-
eficial in treating patients with anxiety. The oils godirectly to the brain via the olfactory nerve (which con-trols smell) and can have direct affect on calming the ner-vous system.
Prognosis
The prognosis for resolution of anxiety depends on

the specific disorder and a wide variety of factors,including the patient’s age, sex, general health, living sit-uation, belief system, social support network, andresponses to different anxiolytic medications and formsof therapy.
Humans have significant control over thoughts, and,

therefore, may learn ways of preventing anxiety bychanging irrational ideas and beliefs. Humans also havesome power over anxiety arising from social and envi-ronmental conditions. Other forms of anxiety, however,are built into the human organism and its life cycle, andcannot be prevented or eliminated.
Resources
BOOKS
“Anxiety Disorders.” In Diagnostic and Statistical Manual of

Clark, R. Barkley. “Psychosocial Aspects of Pediatrics & Psy-
chiatric Disorders.” In Current Pediatric Diagnosis &
Treatment , ed. William W. Hay Jr., et al. Stamford: Apple-
ton & Lange, 1997.
GALE ENCYCLOPEDIA OF MEDICINE 2 321AnxietyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 321

Doctor, Ronald M., and Ada P. Kahn. The Encyclopedia of Pho-
bias, Fears, and Anxieties. New York: Facts On File, 1989.
Gaylin, Willard. Feelings: Our Vital Signs. New York: Ballan-
tine Books, 1979.

Rebecca J. FreyKEY TERMS
Affect —An observed emotional expression or
response. In some situations, anxiety would beconsidered an inappropriate affect.
Anxiolytic —A type of medication that helps to
relieve anxiety.
Autonomic nervous system (ANS) —The part of

the nervous system that supplies nerve endings inthe blood vessels, heart, intestines, glands, andsmooth muscles, and governs their involuntaryfunctioning. The autonomic nervous system isresponsible for the biochemical changes involvedin experiences of anxiety.
Endocrine gland —A ductless gland, such as the
pituitary, thyroid, or adrenal gland, that secretes itsproducts directly into the blood or lymph.

Free-floating anxiety —Anxiety that lacks a defi-
nite focus or content.
Hyperarousal —A state or condition of muscular
and emotional tension produced by hormonesreleased during the fight-or-flight reaction.
Hypothalamus —A portion of the brain that regu-
lates the autonomic nervous system, the release ofhormones from the pituitary gland, sleep cycles,and body temperature.
Limbic system —A group of structures in the brain

that includes the hypothalamus, amygdala, andhippocampus. The limbic system plays an impor-tant part in regulation of human moods and emo-tions. Many psychiatric disorders are related tomalfunctioning of the limbic system.
Phobia —In psychoanalytic theory, a psychologi-
cal defense against anxiety in which the patientdisplaces anxious feelings onto an external object,activity, or situation.Anxiety disorders

The anxiety disorders are a group of mental distur-
bances characterized by anxiety as a central or core symp-tom. Although anxiety is a commonplace experience, noteveryone who experiences it has an anxiety disorder. Anx-iety is associated with a wide range of physical illnesses,medication side effects, and other psychiatric disorders.
The revisions of the Diagnostic and Statistical Man-
ual of Mental Disorders (DSM) that took place after

1980 brought major changes in the classification of theanxiety disorders. Prior to 1980, psychiatrists classifiedpatients on the basis of a theory of causality that definedanxiety as the outcome of unconscious conflicts in thepatient’s mind. DSM-III (1980), DSM-III-R (1987), and
DSM-IV (1994) introduced and refined a new classifica-

tion that took into consideration recent discoveries aboutthe biochemical and post-traumatic origins of some typesof anxiety. The present definitions are based on the exter-nal and reported symptom patterns of the disorders ratherthan on theories about their origins.
Anxiety disorders are the most common form of

mental disturbance in the United States population. It isestimated that 28 million persons suffer from an anxietydisorder every year. These disorders are a serious prob-lem for the entire society because of their interferencewith patients’ work, schooling, and family life. They alsocontribute to the high rates of alcohol and substanceabuse in the United States. Anxiety disorders are an addi-tional problem for health professionals because the phys-ical symptoms of anxiety frequently bring people

symptoms of anxiety frequently bring people to pri-mary care doctors or emergency rooms.

DSM-IV defines twelve types of anxiety disorders in
the adult population. They can be grouped under sevenheadings:
• Panic disorders with or without agoraphobia . The
chief characteristic of panic disorder is the occurrence

of panic attacks coupled with fear of their recurrence.In clinical settings, agoraphobia is usually not a disor-der by itself, but is typically associated with some formof panic disorder. Patients with agoraphobia are afraidof places or situations in which they might have a panicattack and be unable to leave or to find help. About25% of patients with panic disorder develop obsessive-
compulsive disorder (OCD).
•Phobias . These include specific phobias and social

phobia. A phobia is an intense irrational fear of a spe-
GALE ENCYCLOPEDIA OF MEDICINE 2 322Anxiety disordersGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 322

cific object or situation that compels the patient to
avoid it. Some phobias concern activities or objects thatinvolve some risk (for example, flying or driving) butmany are focused on harmless animals or other objects.Social phobia involves a fear of being humiliated,judged, or scrutinized. It manifests itself as a fear ofperforming certain functions in the presence of others,such as public speaking or using public lavatories.
• Obsessive-compulsive disorder (OCD). This disorder is

marked by unwanted, intrusive, persistent thoughts orrepetitive behaviors that reflect the patient’s anxiety orattempts to control it. It affects between 2-3% of thepopulation and is much more common than was previ-ously thought.
•Stress disorders. These include post-traumatic stress
disorder (PTSD) and acute stress disorder . Stress dis-
orders are symptomatic reactions to traumatic events inthe patient’s life.
•Generalized anxiety disorder (GAD). GAD is the

most commonly diagnosed anxiety disorder and occursmost frequently in young adults.
• Anxiety disorders due to known physical causes. These
include general medical conditions or substance abuse.
• Anxiety disorder not otherwise specified. This last cate-
gory is not a separate type of disorder, but is included tocover symptoms that do not meet the specific DSM-IV
criteria for other anxiety disorders.
All DSM-IV anxiety disorder diagnoses include a

criterion of severity. The anxiety must be severe enoughto interfere significantly with the patient’s occupationalor educational functioning, social activities or close rela-tionships, and other customary activities.
The anxiety disorders vary widely in their frequency

of occurrence in the general population, age of onset,family patterns, and gender distribution. The stress disor-ders and anxiety disorders caused by medical conditionsor substance abuse are less age- and gender-specific.Whereas OCD affects males and females equally, GAD,panic disorder, and specific phobias all affect womenmore frequently than men. GAD and panic disorders aremore likely to develop in young adults, while phobiasand OCD can begin in childhood.

Anxiety disorders in children and adolescents
DSM-IV defines one anxiety disorder as specific to
children, namely, separation anxiety disorder. This disor-der is defined as anxiety regarding separation from homeor family that is excessive or inappropriate for the child’sage. In some children, separation anxiety takes the formof school avoidance.Children and adolescents can also be diagnosed with
panic disorder, phobias, generalized anxiety disorder,and the post- traumatic stress syndromes.

The causes of anxiety include a variety of individual
and general social factors, and may produce physical,cognitive, emotional, or behavioral symptoms. Thepatient’s ethnic or cultural background may also influ-ence his or her vulnerability to certain forms of anxiety.Genetic factors that lead to biochemical abnormalitiesmay also play a role.
Anxiety in children may be caused by suffering from
abuse, as well as by the factors that cause anxiety in adults.
Diagnosis

Diagnosis
The diagnosis of anxiety disorders is complicated by
the variety of causes of anxiety and the range of disor-ders that may include anxiety as a symptom. Manypatients who suffer from anxiety disorders have featuresor symptoms of more than one disorder. Patients whoseanxiety is accounted for by another psychic disorder,such as schizophrenia or major depression, are not diag-

nosed with an anxiety disorder. A doctor examining ananxious patient will usually begin by ruling out diseasesthat are known to cause anxiety and then proceed to takethe patient’s medication history, in order to exclude sideeffects of prescription drugs. Most doctors will ask aboutcaffeine consumption to see if the patient’s dietary habits
are a factor. The patient’s work and family situation willalso be discussed. Laboratory tests for blood sugar andthyroid function are also common

Diagnostic testing for anxiety
There are no laboratory tests that can diagnose anxi-

ety, although the doctor may order some specific tests torule out disease conditions. Although there is no psychi-atric test that can provide definite diagnoses of anxiety dis-orders, there are several short-answer interviews or symp-tom inventories that doctors can use to evaluate the inten-sity of a patient’s anxiety and some of its associated fea-tures. These measures include the Hamilton Anxiety Scaleand the Anxiety Disorders Interview Schedule (ADIS).
Treatment

Treatment
For relatively mild anxiety disorders, psychotherapy
alone may suffice. In general, doctors prefer to use a com-bination of medications and psychotherapy with moreseverely anxious patients. Most patients respond better toa combination of treatment methods than to either med-
GALE ENCYCLOPEDIA OF MEDICINE 2 323Anxiety disordersGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 323

ications or psychotherapy in isolation . Because of the
variety of medications and treatment approaches that areused to treat anxiety disorders, the doctor cannot predictin advance which combination will be most helpful to aspecific patient. In many cases the doctor will need to trya new medication or treatment over a six- to eight-weekperiod in order to assess its effectiveness. Treatment trialsdo not necessarily mean that the patient cannot be helpedor that the doctor is incompetent.

diagnose, there are several reasons why it is important forpatients with severe anxiety symptoms to get help. Anxi-ety doesn’t always go away by itself; it often progresses topanic attacks, phobias, and episodes of depression.Untreated anxiety disorders may eventually lead to a diag-nosis of major depression, or interfere with the patient’seducation or ability to keep a job. In addition, many anx-ious patients develop addictions to drugs or alcohol whenthey try to “medicate” their symptoms.

whenthey try to “medicate” their symptoms. Moreover, sincechildren learn ways of coping with anxiety from their par-ents, adults who get help for anxiety disorders are in a bet-ter position to help their families cope with factors thatlead to anxiety than those who remain untreated.

approaches. Meditation and mindfulness training are
thought beneficial to patients with phobias and panic disor-der. Hydrotherapy is useful to some anxious patients

approach anxiety as a symptom of a systemic disorder.Homeopathic practitioners select a remedy based on otherassociated symptoms and the patient’s general constitution.Chinese medicine regards anxiety as a blockage of qi,o r
vital force, inside the patient’s body that is most likely toaffect the lung and large intestine meridian flow. The practi-tioner of Chinese medicine chooses acupuncture point

locations and/or herbal therapy to move the qi and rebalancethe entire system in relation to the lung and large intestine.
Prognosis
The prognosis for recovery depends on the specific
disorder, the severity of the patient’s symptoms, the spe-KEY TERMS

Agoraphobia —Abnormal anxiety regarding public
places or situations from which the patient maywish to flee or in which he or she would be help-less in the event of a panic attack.
Compulsion —A repetitive or ritualistic behavior
that a person performs to reduce anxiety. Compul-sions often develop as a way of controlling or“undoing” obsessive thoughts.
Obsession —A repetitive or persistent thought,
idea, or impulse that is perceived as inappropriateand distressing.

Panic attack —A time-limited period of intense
fear accompanied by physical and cognitivesymptoms. Panic attacks may be unexpected ortriggered by specific cues.
cific causes of the anxiety, and the patient’s degree of
control over these causes.
Anxiety is an unavoidable feature of human exis-

tence. However, humans do have some power over theirreactions to anxiety- provoking events and situations.Cognitive therapy and meditation or mindfulness trainingappear to be beneficial in helping people lower theirlong-term anxiety levels.
Resources
BOOKS

Doctor, Ronald M., and Ada P. Kahn. The Encyclopedia of
Phobias, Fears, and Anxieties. New York: Facts On File,
1989.

1989.
Nemiah, John C. “Psychoneurotic Disorders.” In The New Har-
vard Guide to Psychiatry , ed. Armand M. Nicholi Jr.
Cambridge, MA: The Belknap Press of Harvard Universi-ty Press, 1988.
GALE ENCYCLOPEDIA OF MEDICINE 2 324Anxiety disordersGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 324

“Psychiatric Disorders: Anxiety Neurosis.” In The Merck Manu-
Anxiolytics seeAntianxiety drugs
Aortic aneurysm
An aneurysm is an abnormal bulging or swelling of
a portion of a blood vessel. The aorta, which can developthese abnormal bulges, is the large blood vessel that car-ries oxygen-rich blood away from the heart to the rest ofthe body.

The aorta carries oxygen-rich blood to the body, and
is therefore called an artery. Because the aorta is anartery, its walls are made of up three layers; a thin innerlayer, a muscular middle layer (that gives the vessel itsflexibility under pressure from the filling blood), and afiber-like outer layer that gives the vessel strength to notburst when the heart pumps blood to the body.
Aortic aneurysms occur when a weakness develops

in part of the wall of the aorta; three basic types are usual-ly found. If all three layers of the vessel are affected andweakness develops along an extended area of the vessel,the weakened area will appear as a large, bulging regionof blood vessel; this is called a fusiform aneurysm. Ifweakness develops between the inner and outer layers ofthe aortic wall, a bulge results as blood from the interiorof the vessel is pushed around the damaged region in thewall and collects between these layers.

in thewall and collects between these layers. This is called adissecting aneurysm because one layer is “dissected” orseparated from another. If damage occurs to only the mid-dle (muscular) layer of the vessel, a sack-like bulge canform; therefore, this is a saccular aneurysm.

Aortic aneurysms occur in different portions of the
aorta, which begins in the chest (at the heart) and travelsdownward through the abdomen. Aneurysms found inthe region of the aorta within the chest are called thoracicaortic aneurysms. Aneurysms that occur in the part of theaorta within the abdomen are called abdominal aorticaneurysms.
Thoracic aortic aneurysms do not usually produce

any noticeable symptoms. However, as the aneurysmbecomes larger, chest, shoulder, neck, lower back, orabdominal pain can result. Abdominal aortic aneurysms
occur more often in men, and these aneurysms can causepain in the lower back, hips, and abdomen. A painfulabdominal aortic aneurysm usually means that theaneurysm could burst very soon.
Most abdominal aortic aneurysms are caused by
atherosclerosis , a condition caused when fat (mostly

cholesterol) carried in the blood builds up in the innerwall of the aorta. As more and more fat attaches to theaortic wall, the wall itself becomes abnormally weak andoften results in an aneurysm or bulge.
Aortic aneurysms are also caused by a breakdown of
the muscular middle layer of the artery wall, by highblood pressure, by direct injury to the chest, and althoughrare, by bacteria that can infect the aorta.
GALE ENCYCLOPEDIA OF MEDICINE 2 325Aortic aneurysm

Surgery being performed to correct aortic aneurysm. (Cus-
tom Medical Stock Photo. Reproduced by permission.)
An aneurysm in progress. An aneurysm is an abnormal
bulging or swelling of a portion of a blood vessel. (Custom
Medical Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 325

Diagnosis
Silent, stable aneurysms are often detected when a
person has an x ray as part of a routine examination orfor other medical reasons. Otherwise, when chest,abdominal, or back pain is severe, aortic aneurysm issuspected and x-ray (radiographic) studies can confirmor rule out that condition.
Treatment
Aortic aneurysms are potentially life-threatening con-

ditions. Small aneurysms should be monitored for their rateof growth and large aneurysms require consideration for asurgical repair. The most common method of surgicalrepair is to cut out the bulging section of artery wall andsew a Dacron fiber material into its place in the vessel wall.
Prognosis
Only 1-2% of people die from having surgical repair
of an aortic aneurysm. However, if the aneurysm isuntreated and eventually ruptures, less than half of the

people with ruptured aneurysms will survive. The chal-lenge for the physician is to decide when or if to do thepreventive surgery.
Aneuryms can develop in people with atherosclerosis.
High blood pressure can also lead to this condition. Althoughno definite prevention exists, lifestyle and dietary changesthat help lower blood pressure and the amount of fat in theblood stream may slow the development of aneurysms.
Resources
BOOKS

Resources
BOOKS
“Aneurysms and Other Vascular Disorders.” In Cardiovascular
Diseases and Disorders Sourcebook , ed. Karen Bellenir
and Peter D. Dresser. Detroit: Omnigraphics, Inc., 1995.
Dzau, Victor J., and Mark A.Creager. “Diseases of the Aorta.”
In Harrison’s Principles of Internal Medicine , ed. Antho-
ny S. Fauci, et al. New York: McGraw Hill, 1997.
GALE ENCYCLOPEDIA OF MEDICINE 2 326Aortic aneurysm
Aortic 
aneurysmAortaSubclavian arteryCarotid artery
HeartHepatic artery
Messentric artery

Iliac arteryRenal arteryPulmonary artery
Liver
Kidney
Aortic aneurysms occur when a weakness develops in a part of the wall of the aorta.The aorta is the large blood vessel that
carries oxygen-rich blood away from the heart to the rest of the body. (Illustration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 326

KEY TERMS
Atherosclerosis —The accumulation of fat on the
inner wall of an artery. This fat is largely made upof cholesterol being carried in the blood.
Dacron —A synthetic polyester fiber used to surgi-
cally repair damaged sections of blood vessel walls.
Lindsay, Joseph L., Michael E. DeBakey, and Arthur C. Beall.
“Diagnosis and Treatment of Diseases of the Aorta.” InHurst’s The Heart , ed. Robert C. Schlant, et al. New York:
McGraw Hill, 1994.

van der Vleit, J. Adam, and Albert P. M. Boll. “Abdominal Aor-
tic Aneurysm.” The Lancet 349 (22 Mar. 1997): 863.
American Heart Association. 7320 Greenville Ave. Dallas, TX
75231. (214) 373-6300. <http://www.americanheart.org>.
Dominic De Bellis, PhD
Aortic dissection

Aortic dissection is a rare, but potentially fatal, con-
dition in which blood passes through the inner lining andbetween the layers of the aorta. The dissecting aorta usu-ally does not burst, but has an abnormal second channelwithin it.
A defect in the inner lining of the aorta allows an

opening or tear to develop. The aorta is the main artery ofthe body and is an area of high blood pressure. When adefect develops, blood pressure can force the tear to openand allow blood to pass through. Since the blood is underpressure, it eventually splits (dissecting) the middle layerof the blood vessel, creating a new channel for blood.The length of the channel grows over time and can resultin the closing off of connection points to other arteries.This can lead to heart attack , strokes,

arteries.This can lead to heart attack , strokes, abdominal pain ,

and nerve damage. Blood may leak from the dissectionand collect in the chest an around the heart.A second mechanism leading to aortic dissection is
medial hemorrhage. A medial hemorrhage occurs in themiddle layer of the blood vessel and spills through theinner lining of the aorta wall. This opening then allowsblood from the aorta to enter the vessel wall and begin adissection. Approximately 2,000 cases of aortic dissec-tion occur yearly in the United States.

Aortic dissection is caused by a deterioration of the
inner lining of the aorta. There are a number of condi-tions that predispose a person to develop defects of theinner lining, including high blood pressure, Marfan’s dis-ease, Ehlers-Danlos syndrome , connective tissue dis-

eases, and defects of heart development which begin dur-ing fetal development. A dissection can also occur acci-dentally following insertion of a catheter, trauma, orsurgery. The main symptom is sudden, intense pain. Thepain can be so intense as to immobilize the patient andcause him to fall to the ground. The pain is frequentlyfelt in both the chest and in the back, between the shoul-der blades. The extent of the pain is proportional to thelength of the dissection.
Diagnosis

Diagnosis
The pain experienced by the patient is the first symp-

tom of aortic dissection and is unique. The pain is usuallydescribed by the patient as “tearing, ripping, or stabbing.”This is in contrast to the pain associated with heartattacks. The patient frequently has a reduced or absentpulse in the extremities. A murmur may be heard if thedissection is close to the heart. An enlarged aorta will usu-ally appear in the chest x rays and ultrasound exams ofmost patients. The use of a blood dye in angiogramsand/or CT scans ( computed tomography scans ) will

in diagnosing and visualizing the dissection.
Treatment
Because of the potentially fatal nature of aortic dis-
section, patients are treated immediately. Drugs areadministered to reduce the blood pressure and heart rate.If the dissection is small, drug therapy alone may beused. In other cases, surgery is performed. In surgery,damaged sections of the aorta are removed and a synthet-ic graft is often used to reconstruct the damaged vessel.
Prognosis

Prognosis
Depending on the nature and extent of the dissection,
death can occur within a few hours of the start of a dis-
section. Approximately 75% of untreated people die with-
GALE ENCYCLOPEDIA OF MEDICINE 2 327Aortic dissectionGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 327

in two weeks of the start of a dissection. Of those who are
treated, 40% survive more than 10 years. Patients are usu-ally given long term treatment with drugs to reduce theirblood pressure, even if they have had surgery.
Resources
BOOKS

Braunwald, E. Heart Disease. Philadelphia: W. B. Saunders
Co., 1997.
Aortic incompetence seeAortic valve
insufficiency
Aortic regurgitation seeAortic valve
Aortic stenosis seeAortic valve stenosis
Aortic valve insufficiency
The aortic valve separates the left ventricle of the

heart (the heart’s largest pumping chamber) from theaorta, the large artery that carries oxygen-rich blood outof the left ventricle to the rest of the body. In aortic valveinsufficiency, the aortic valve becomes leaky, causingblood to flow backwards into the left ventricle.
Aortic valve insufficiency occurs when this valve

cannot properly close after blood that is leaving theheart’s left ventricle enters the aorta. With each contrac-tion of the heart more and more blood flows back into theKEY TERMS
Dissection —A cut or divide.
Hemorrhage —A large discharge of blood, profuse
bleeding.left ventricle, causing the ventricle to become overfilled.

This larger-than-normal amount of blood that collects inthe left ventricle puts pressure on the walls of the heart,causing the heart muscle to increase in thickness (hyper-trophy). If this thickening continues, the heart can be per-manently damaged.
Aortic valve insufficiency is also know as aortic
valve regurgitation because of the abnormal reversed flowof blood leaking through the poorly functioning valve.
The faulty working of the aortic valve can be caused

by a birth defect; by abnormal widening of the aorta (whichcan be caused by very high blood pressure and a variety ofother less common conditions); by various diseases thatcause large amounts of swelling (inflammation) in differentareas of the body, like rheumatic fever ; and, although
rarely, by the sexually transmitted disease, syphilis .
About 75% of people with aortic valve insufficiency

are men. Rheumatic (inflammatory) diseases have beenthe main cause of this condition in both men and women.
Aortic valve insufficiency can remain unnoticed for
10 to 15 years. In cases of severe insufficiency a personmay notice a variety of symptoms, including an uncom-fortable pounding of the heart when lying down, a veryrapid or hard heart beat ( palpitations ),shortness of
breath , chest pain , and if untreated for very long times,
swelling of the liver, ankles, and belly.
Diagnosis

Diagnosis
A poorly functioning or insufficient aortic valve can
be identified when a doctor listens to the heart during aphysical examination . A chest x ray , an electrocardio-
gram (ECG, an electrical printout of the heart beats), aswell as an echocardiogram (a test that uses sound wavesto create an image of the heart and its valves), can furtherevaluate or confirm the condition.
Treatment
Aortic insufficiency is usually corrected by having

the defective valve surgically replaced. However, such anoperation is done in severe cases. Before the conditionworsens, certain drugs can be used to help manage thiscondition.
Drugs that remove water from the body, drugs that
lower blood pressure, and drugs that help the heart beatmore effectively can each be used for this condition.Reducing the amount of salt in the diet also helps lowerthe amount of fluid the body holds and can help the heartto work more efficiently as well.

GALE ENCYCLOPEDIA OF MEDICINE 2 328Aortic valve insufficiencyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 328

In cases of a severely malfunctioning valve that has
been untreated for a long time, surgery is the treatment ofchoice, especially if the heart is not functioning normal-ly. Human heart valves can be replaced with man-madevalves or with valves taken from pig hearts.
Prognosis
Although drug treatment can help put off the need
for surgical valve replacement, it is important to replacethe faulty valve before the heart muscle itself is damagedbeyond recovery.
Resources
BOOKS

Resources
BOOKS
Braunwald, Eugene. “Valvular Heart Disease.” In Harrison’s
al. New York: McGraw Hill, 1997.
“Heart Valve Surgery.” In Cardiovascular Diseases and Disor-
ders Sourcebook , ed. Karen Bellenir and Peter D. Dresser.
Detroit: Omnigraphics, Inc., 1995.
Carabello, Blase A., and Fred A. Crawford Jr. “Valvular Heart
Disease.” New England Journal of Medicine 337 (3 July
1997): 32-41.

Condos Jr., William R. “Decade-old Heart Drug May Have a
New Use.” San Diego Business Journal 18 (21 July 1997):
24.KEY TERMS
Rheumatic fever —A disease believed to be
caused by a bacterium named group A streptococ-cus. This bacterium causes a sore “strep throat”and can also result in fever. Infection by this bac-terium can also damage the heart and its valves,but how this takes place is not clearly understood.

Aortic valve stenosis
When aortic valve stenosis occurs, the aortic valve,
located between the aorta and left ventricle of the heart,is narrower than normal size.

A normal aortic valve, when open, allows the free
flow of blood from the left ventricle to the aorta.When the valve narrows, as it does with stenosis,blood flow is impeded. Because it is more difficult forblood to flow through the valve, there is increasedstrain on the heart. This can cause the left ventricle toenlarge and malfunction, resulting in reduced bloodsupply to the heart muscle and body, as well as fluidbuild up in the lungs.

Aortic valve stenosis can occur because of a birth
defect in the formation of the valve. Calcium depositsmay form on the valve with aging , causing the valve to
become stiff and narrow. Stenosis can also occur as aresult of rheumatic fever . Mild aortic stenosis may pro-
duce no symptoms at all. The most common symptoms,depending on the severity of the disease, are chest pain ,
blackouts, and difficulty breathing.
GALE ENCYCLOPEDIA OF MEDICINE 2 329Aortic valve stenosis

Normal
blood flowDiseased valve
Blood backflow
A human heart with a diseased valve that doesn’t open and
close properly, allowing blood to backflow to the heart.(Illustration by Argosy, Inc.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 329

Diagnosis
Using a stethoscope, a physician may hear a murmur
and other abnormal heart sounds. An ECG, also called anelectrocardiogram, records the electrical activity of theheart. This technique and chest x ray can show evidence
that the left ventricle is enlarged. An x ray can also revealcalcium deposits on the valve, as well as congestion inthe lungs. Echocardiography can pick up thickening of

the valve, heart size, and whether or not the valve isworking properly. This is a procedure in which high fre-quency sound waves harmlessly bounce off organs in thebody. Cardiac catheterization , in which a contrast dye
is injected in an artery using a catheter, is the key tool toconfirm stenosis and gauge its severity.
Treatment
Treatment depends on the symptoms and how the

heart’s function is affected. The valve can be opened with-out surgery by using a balloon catheter, but this is often atemporary solution. The procedure involves inserting adeflated balloon at the end of a catheter through the arteriesto the valve. Inflating the balloon should widen the valve. Insevere stenosis, heart valve replacement is recommended,

most often involving open-heart surgery. The valve can bereplaced with a mechanical valve, a valve from a pig, or bymoving the patient’s other heart valve (pulmonary) into theposition of the aortic valve and then replacing the pul-monary valve with an mechanical one. Anyone with aorticstenosis needs to take antibiotics (amoxicillin, ery-
thromycin, or clindamycin) before dental and some othersurgical procedures, to prevent a heart valve infection.
Prognosis

Prognosis
The prognosis for aortic valve stenosis depends on
the severity of the disease. With surgical repair, the dis-KEY TERMS
Aorta —The largest artery in the body, which
moves blood from the left ventricle to the rest ofthe body.
ECG—Also called an electrocardiogram, it records
Echocardiogram —A procedure in which high fre-
quency sound waves harmlessly bounce off organsin the body providing an image so one can deter-mine their structure and function.

Cardiac catheterization —A procedure in which
dye is injected through a tube or catheter into anartery to more easily observe valves or blood ves-sels seen on an x ray.
Left ventricle —One of the lower chambers of the
heart, which pumps blood to the aorta.
Murmur —An abnormal heart sound that can
reflect a valve dysfunction.
Rheumatic fever —A bacterial infection that often
causes heart inflammation.
Pulmonary valve —The valve located between the

pulmonary artery and the right ventricle, whichbrings blood to the lungs.
ease is curable. Patients suffering mild stenosis can usu-

ally lead a normal life; a minority of the patients progressto severe disease. Anyone with moderate stenosis shouldavoid vigorous physical activity. Most of these patientsend up suffering some kind of coronary heart diseaseover a 10 year period. Because it is a progressive disease,moderate and severe stenosis will be treated ultimatelywith surgery. Severe disease, if left untreated, leads todeath within 2 to 4 years once the symptoms start.
There is no way to prevent aortic stenosis.

Resources
BOOKS
Bender, Jeffrey R. “Heart Valve Disease.” In Yale University
School of Medicine Heart Book , ed. Barry L. Zaret, et al.
New York: Hearst Books, 1992.
Braunwald, E. “Aortic Stenosis.” In Heart Disease: A Textbook
of Cardiovascular Medicine. Philadelphia: W. B. Saunders
Co., 1997.
McGoon, Michael D. “Aortic Stenosis.” In Mayo Clinic Heart
Book. New York: William Morrow and Co., 1993.

GALE ENCYCLOPEDIA OF MEDICINE 2 330Aortic valve stenosis
A close-up view of a calcified stenosis of the aortic valve.
(Custom Medical Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 330

OTHER
“Aortic Stenosis.” Ochsner Heart and Vascular Institute.
<http://www.ochsner.org/pedcard/as.htm>.
Rahimtoola, Aly. “Aortic Stenosis.” Loyola University Health
System Page. <http://www.luhs.org>.
Apgar testing
Apgar testing is the assessment of the newborn rat-

ing color, heart rate, stimulus response, muscle tone, andrespirations on a scale of zero to two, for a maximumpossible score of 10. It is performed twice, first at oneminute and then again at five minutes after birth.
Purpose
Apgar scoring was originally developed in the 1950s

by the anesthesiologist Virginia Apgar to assist practi-tioners attending a birth in deciding whether or not anewborn was in need of resuscitation. Using a scoringmethod fosters consistency and standardization amongdifferent practitioners. A February 2001 study publishedin the New England Journal of Medicine investigated

whether Apgar scoring continues to be relevant.Researchers concluded that “The Apgar scoring systemremains as relevant for the prediction of neonatal sur-vival today as it was almost 50 years ago”.
The five areas are scored as follows:
• Appearance, or color: 2 if the skin is pink all over; 1 for
acrocyanosis , where the trunk and head are pink, but

the arms and legs are blue; and 0 if the whole body isblue. Newborns with naturally darker skin color willnot be pink. However, pallor is still noticeable, espe-cially in the soles and palms. Color is related to theneonate’s ability to oxygenate its body and extremities,and is dependent on heart rate and respirations. A per-fectly healthy newborn will often receive a score of 9because of some blueness in the hands and feet.
• Pulse (heart rate): 2 for a pulse of 100+ beats per minute

(bpm); 1 for a pulse below 100 bpm; 0 for no pulse.Heart rate is assessed by listening with a stethoscope tothe newborn’s heart and counting the number of beats.
• Grimace, or reflex irritability: 2 if the neonate coughs,
sneezes, or vigorously cries in response to a stimulusKEY TERMS
Acrocyanosis —A slight cyanosis, or blueness of

the hands and feet of the neonate is considerednormal. This impaired ability to fully oxygenatethe extremities is due to an immature circulatorysystem which is still in flux.
Amniotic fluid —The protective bag of fluid that
surrounds the fetus while growing in the uterus.
Neonate —A term referring to the newborn infant,
from birth until one month of age.
Neonatologist —A physician who specializes in
problems of newborn infants.

Pallor —Extreme paleness in the color of the skin.
(such as the use of nasal suctioning, stroking the back
to assess for spinal abnormalities, or having the foottapped); 1 for a slight cry or grimace in response to thestimulus; 0 for no response.
• Activity, or muscle tone: 2 for vigorous movements of
arms and legs; 1 for some movement; 0 for no move-ment, limpness.
• Respirations: 2 for visible breathing and crying; 1 for

slow, weak, irregular breathing; 0 for apnea, or nobreathing. A crying newborn can adequately oxygenateits lungs. Respirations are best assessed by watchingthe rise and fall of the neonate’s abdomen, as infants arediaphragmatic breathers.
The combined first letters in these five areas spell
Apgar.
No preparation is needed to perform the test. How-

ever, while being born the neonate may receive nasal andoral suctioning to remove mucus and amniotic fluid. Thismay be done when the head of the newborn is safely out,while the mother rests before she continues to push.
Aftercare
Since the test is primarily observational in nature, no
aftercare is needed. However, the test may flag the needfor immediate intervention or prolonged observation.
The maximum possible score is 10, the minimum is

zero. It is rare to receive a true 10, as some acrocyanosis in
GALE ENCYCLOPEDIA OF MEDICINE 2 331Apgar testingGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 331

cause for concern. Most infants score between 7 and 10.These infants are expected to have an excellent outcome.A score of 4, 5, or 6 requires immediate intervention, usu-ally in the form of oxygen and respiratory assistance, orperhaps just suctioning if breathing has been obstructed bymucus. While suctioning is being done, a source of oxy-gen may be placed near, but not over the newborn’s noseand mouth. This form of oxygen is referred to as blow-by .

A score in the 4-6 range indicates that the neonate is hav-ing some difficulty adapting to extrauterine life. This maybe due to medications given to the mother during a diffi-cult labor, or at the very end of labor, when these medica-tions have an exaggerated effect on the neonate.
With a score of 0-3, the newborn is unresponsive,

apneic, pale, limp and may not have a pulse. Interven-tions to resuscitate will begin immediately. The test isrepeated at five minutes after birth and both scores aredocumented. Should the resuscitation effort continue intothe five-minute time period, interventions will not stop inorder to perform the test. The one-minute score indicatesDR. VIRGINIA APGAR (1909–1974)

the need for intervention at birth. It addresses survivaland prevention of birth-related complications resultingfrom inadequate oxygen supply. Poor oxygenation maybe due to inadequate neurological and/or chemical con-trol of respiration. The five-minute score appears to havea more predictive value for morbidity and normal devel-opment, although research studies on this are inconsis-tent in their conclusions.
Resources
BOOKS
Doenges, Marilynn E., and Mary Frances Moorhouse.

Feinbloom, Richard I. Pregnancy, Birth and the Early Months.
Cambridge, MA: Perseus Publishing, 2000.
Pillitteri, Adele. Maternal & Child Nursing; Care of the Child-
bearing and Childrearing Family. 3rd Edition. Philadel-
phia: Lippincott, 1999.
Spencer, Paula. Parenting: Guide to Pregnancy and Childbirth.
New York: Ballantine Books, 1998.
Casey, B. M., D. D. McIntire, and K. J. Leveno. “The Continu-

ing Value of Apgar Score for the Assessment of NewbornInfants”. New England Journal of Medicine 344(February
15, 2000): 467-71.
GALE ENCYCLOPEDIA OF MEDICINE 2 332Apgar testingAs one of very few female medical students at

Columbia University College of Physicians and Surgeonsin New York during the early 1930s and one of the firstwomen to graduate from its medical school, Apgar knewthat her goal of becoming a surgeon would not beachieved easily in a male-dominated profession. Reluc-tantly, she switched her medical specialty to anesthesiol-ogy, she embraced her new field with typical intelligenceand energy. At this time, anesthesiology was a relativelynew field, having been left by the doctors mostly to

field, having been left by the doctors mostly to theattention of nurses. Apgar realized immediately howmuch in need of scientifically trained personnel was thissignificant part of surgery, and she set out to make anes-thesiology a separate medical discipline. By 1937, shehad become the fiftieth physician to be certified as ananesthesiologist in the United States. The following yearshe was appointed director of anesthesiology at theColumbia-Presbyterian Medical Center, becoming thefirst woman to

Medical Center, becoming thefirst woman to head a department at that institution.

As the attending anesthesiologist who assisted in the
delivery of thousands of babies during these years, Apgarrealized that infants had died from respiratory or circulato-ry complications that early treatment could have prevent-ed. Apgar decided to bring her considerable research skillsto this childbirth dilemma, and her careful study resultedin her publication of the Apgar Score System in 1952.
(AP/Wide World Photos. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 332

OTHER
Apgar, Virginia. A Proposal for a New Method of Evaluation of
the Newborn Infant. <http://www.apgarfamily.com/
Apgar_Paper.html>.
The National Childbirth Trust. <http://www.nctpregnancy
andbabycare.com>.
PregnancyWeekly.com <http://www.pregnancyweekly.com>.
Esther Csapo Rastegari, RN, BSN, EdM
Aphasia
Aphasia is condition characterized by either partial

or total loss of the ability to communicate verbally orusing written words. A person with aphasia may havedifficulty speaking, reading, writing, recognizing thenames of objects, or understanding what other peoplehave said. Aphasia is caused by a brain injury, as mayoccur during a traumatic accident or when the brain isdeprived of oxygen during a stroke . It may also be
caused by a brain tumor , a disease such as Alzheimer’s,
or an infection, like encephalitis . Aphasia may be tem-

porary or permanent. Aphasia does not include speechimpediments caused by loss of muscle control.
To understand and use language effectively, an indi-

vidual draws upon word memory—stored information onwhat certain words mean, how to put them together, andhow and when to use them properly. For a majority ofpeople, these and other language functions are located inthe left side (hemisphere) of the brain. Damage to thisside of the brain is most commonly linked to the devel-opment of aphasia. Interestingly, however, left-handedpeople appear to have language areas in both the left andright hemispheres of the brain and, as a result, maydevelop

of the brain and, as a result, maydevelop aphasia from damage to either side of the brain.

United States. Approximately 500,000 individuals sufferstrokes each year, and 20% of these individuals developsome type of aphasia. Other causes of brain damageinclude head injuries, brain tumors, and infection. Abouthalf of the people who show signs of aphasia have whatis called temporary or transient aphasia and recover com-pletely within a few days. An estimated one millionAmericans suffer from some form of permanent aphasia.As yet, no connection between aphasia and age, gender,or race has

between aphasia and age, gender,or race has been found.Aphasia is sometimes confused with other conditions

that affect speech, such as dysarthria and apraxia. Thesecondition affect the muscles used in speaking rather thanlanguage function itself. Dysarthria is a speech distur-bance caused by lack of control over the muscles used inspeaking, perhaps due to nerve damage. Speech apraxia isa speech disturbance in which language comprehensionand muscle control are retained, but the memory of howto use the muscles to form words is not.
Aphasia can develop after an individual sustains a

brain injury from a stroke, head trauma, tumor, or infec-tion, such as herpes encephalitis. As a result of this injury,the pathways for language comprehension or productionare disrupted or destroyed. For most people, this meansdamage to the left hemisphere of the brain. (In 95 to 99%of right-handed people, language centers are in the lefthemisphere, and up to 70% of left-handed people alsohave left-hemisphere language dominance.) According tothe traditional classification scheme, each form of

traditional classification scheme, each form of aphasiais caused by damage to a different part of the left hemi-sphere of the brain. This damage affects one or more of thebasic language functions: speech, naming (the ability toidentify an object, color, or other item with an appropriateword or term), repetition (the ability to repeat words,phrases, and sentences), hearing comprehension (the abili-ty to understand spoken language), reading (the ability tounderstand written words and their

(the ability tounderstand written words and their meaning), and writing(the ability to communicate and record events with text).

The traditional classification scheme includes eight
types of aphasia:
• Broca’s aphasia, also called motor aphasia, results from
damage to the front portion or frontal lobe of the lan-guage-dominant area of the brain. Individuals withBroca’s aphasia may be completely unable to use speech(mutism ) or may be able to use single-word statements

or even full sentences, though these sentences mayrequire a great deal of effort to construct. Small words,such as conjunctions (and, or, but) and articles (the, an,a), may be omitted, leading to a “telegraph” quality intheir speech. Hearing comprehension is usually notaffected, so they are able to understand other people’sspeech and conversation and can follow commands.Often, they may experience weakness on the right side oftheir bodies, which can make it difficult to write. Read-ing ability

can make it difficult to write. Read-ing ability is impaired, and they may have difficulty find-ing the right word when speaking. Individuals withBroca’s aphasia may become frustrated and depressedbecause they are aware of their language difficulties.

• Wernicke’s aphasia is caused by damage to the side
portion or temporal lobe of the language-dominant area
GALE ENCYCLOPEDIA OF MEDICINE 2 333AphasiaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 333

in long, uninterrupted sentences; however, the wordsused are frequently unnecessary or even made-up. Theyhave a great deal of difficulty understanding other peo-ple’s speech, sometimes to the point of being unable tounderstand spoken language at all. Reading ability isdiminished, and although writing ability is retained,what is written may be abnormal. No physical symp-toms, such as the right-sided weakness seen withBroca’s aphasia, are typically observed. Also, in con-trast to Broca’s aphasia,

observed. Also, in con-trast to Broca’s aphasia, individuals with Wernicke’saphasia are not aware of their language errors.

• Global aphasia is caused by widespread damage to the
language areas of the left hemisphere. As a result, allbasic language functions are affected, but some areasmay be more affected than others. For example, an indi-vidual may have difficulty speaking but may be able towrite well. The individual may experience weaknessand loss of feeling on the right side of their body.
• Conduction aphasia, also called associative aphasia, is

rather uncommon. Individuals with conduction aphasiaare unable to repeat words, sentences, and phrases.Speech is fairly unbroken, although individuals may

frequently correct themselves and words may beskipped or repeated. Although able to understand spo-ken language, it may also be difficult for the individualwith conduction aphasia to find the right word todescribe a person or object. The impact of this condi-tion on reading and writing ability varies. As with othertypes of aphasia, right-sided weakness or sensory lossmay be present.
• Anomic or nominal aphasia primarily influences an

individual’s ability to find the right name for a personor object. As a result, an object may be described ratherthan named. Hearing comprehension, repetition, read-ing, and writing are not affected, other than by thisinability to find the right name. Speech is fluent, exceptfor pauses as the individual tries to recall the rightname. Physical symptoms are variable, and some indi-viduals have no symptoms of one-sided weakness orsensory loss.

guage areas of the left hemisphere outside the primarylanguage areas. There are three types of aphasia:transcortical motor aphasia, transcortical sensory apha-sia, and mixed transcortical aphasia. All of the transcor-tical aphasias are distinguished from other types by theindividual’s ability to repeat words, phrases, or sen-tences. Other language functions may also be impairedto varying degrees, depending on the extent and partic-ular location of brain damage.

As researchers continue to learn more about the
brain’s structure and function, new types of aphasia arebeing recognized. One newly recognized type of aphasia,subcortical aphasia, mimics the symptoms of other tradi-tional types of aphasia but involves language disordersthat are not typical. This type of aphasia is associatedwith injuries to areas of the brain typically not identifiedwith language and language processing.
Diagnosis
Following brain injury, an initial bedside assessment is

made to determine whether language function has beenaffected. If the individual experiences difficulty communi-cating, attempts are made to determine whether this diffi-culty arises from impaired language comprehension or animpaired ability to speak. A typical examination involveslistening to spontaneous speech and evaluating the individ-ual’s ability to recognize and name objects, comprehendwhat is heard, and repeat sample words and phrases. Theindividual may also be asked to read text aloud

may also be asked to read text aloud and explainwhat the passage means. In addition, writing ability is eval-uated by having the individual copy text, transcribe dictatedtext, and write something without prompting.

GALE ENCYCLOPEDIA OF MEDICINE 2 334Aphasia Broca's areaWernicke's area
Broca’s aphasia results from damage to the frontal lobe of

the language-dominant area of the brain. Individuals withBroca’s aphasia may become mute or may be able to usesingle-word statements or full sentences, although it mayrequire great effort.Wernicke’s aphasia is caused by damageto the temporal lobe of the language-dominant area of thebrain. People with this condition speak in long, uninterrupt-ed sentences, but the words used are often unnecessary andunintelligible. (Illustration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03

A speech pathologist or neuropsychologist may be
asked to conduct more extensive examinations using in-depth, standardized tests. Commonly used tests include theBoston Diagnostic Aphasia Examination, the Western Apha-sia Battery, and possibly, the Porch Index of Speech Ability.
The results of these tests indicate the severity of the

aphasia and may also provide information regarding theexact location of the brain damage. This more extensivetesting is also designed to provide the information neces-sary to design an individualized speech therapy program.Further information about the location of the damage isgained through the use of imaging technology, such asmagnetic resonance imaging (MRI) and computed
tomography scans (CT).
Treatment
Initially, the underlying cause of aphasia must be

treated or stabilized. To regain language function, thera-KEY TERMS
Anomic aphasia —A condition characterized by
either partial or total loss of the ability to recall thenames of persons or things as a result of a stroke,head injury, brain tumor, or infection.
Broca’s aphasia —A condition characterized by either

partial or total loss of the ability to express oneself,either through speech or writing. Hearing compre-hension is not affected. This condition may resultfrom a stroke, head injury, brain tumor, or infection.
Computed tomography (CT) —An imaging tech-
nique that uses cross-sectional x rays of the body tocreate a three-dimensional image of the body’sinternal structures.
Conduction aphasia —A condition characterized by

the inability to repeat words, sentences, or phrasesas a result of a stroke, head injury, brain tumor, orinfection.
Frontal lobe —The largest, most forward-facing part
of each side or hemisphere of the brain.
Global aphasia —A condition characterized by

either partial or total loss of the ability to communi-cate verbally or using written words as a result ofwidespread injury to the language areas of thebrain. This condition may be caused by a stroke,head injury, brain tumor, or infection. The exact lan-guage abilities affected vary depending on the loca-tion and extent of injury.Hemisphere —One of the two halves or sides-the
left and the right-of the brain.

Magnetic resonance imaging (MRI) —An imaging
technique that uses a large circular magnet andradio waves to generate signals from atoms in thebody. These signals are used to construct images ofinternal structures.
Subcortical aphasia —A condition characterized by

either partial or total loss of the ability to communi-cate verbally or using written words as a result ofdamage to non language-dominated areas of thebrain. This condition may be caused by a stroke,head injury, brain tumor, or infection.
Temporal lobe —The part of each side or hemi-
sphere of the brain that is on the side of the head,nearest the ears.
Transcortical aphasia —A condition characterized

by either partial or total loss of the ability to com-municate verbally or using written words that doesnot affect an individual’s ability to repeat words,phrases, and sentences.
Wernicke’s aphasia —A condition characterized by
either partial or total loss of the ability to under-stand what is being said or read. The individualmaintains the ability to speak, but speech may con-tain unnecessary or made-up words.

py must begin as soon as possible following the injury.
Although there are no medical or surgical procedurescurrently available to treat this condition, aphasia result-ing from stroke or head injury may improve through the
use of speech therapy. For most individuals, however, theprimary emphasis is placed on making the most ofretained language abilities and learning to use othermeans of communication to compensate for lost lan-guage abilities.

Speech therapy is tailored to meet individual needs,
but activities and tools that are frequently used includethe following:
•Exercise and practice. Weakened muscles are exercised
by repetitively speaking certain words or making facialexpressions, such as smiling.
• Picture cards. Pictures of everyday objects are used to
improve word recall and increase vocabulary. The
GALE ENCYCLOPEDIA OF MEDICINE 2 335AphasiaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 335

names of the objects may also be repetitively spoken
aloud as part of an exercise and practice routine.
• Picture boards. Pictures of everyday objects and activi-
ties are placed together, and the individual points tocertain pictures to convey ideas and communicate withothers.
• Workbooks. Reading and writing exercises are used to
sharpen word recall and regain reading and writingabilities. Hearing comprehension is also redevelopedusing these exercises.

• Computers. Computer software can be used to improve
speech, reading, recall, and hearing comprehension by,for example, displaying pictures and having the indi-vidual find the right word.
Prognosis
The degree to which an individual can recover lan-

guage abilities is highly dependent on how much braindamage occurred and the location and cause of the origi-nal brain injury. Other factors include the individual’sage, general health, motivation and willingness to partici-pate in speech therapy, and whether the individual is leftor right handed. Language areas may be located in boththe left and right hemispheres in left-handed individuals.Left-handed individuals are, therefore, more likely todevelop aphasia following brain injury, but because

aphasia following brain injury, but because theyhave two language centers, may recover more fullybecause language abilities can be recovered from eitherside of the brain. The intensity of therapy and the timebetween diagnosis and the start of therapy may alsoaffect the eventual outcome.

Because there is no way of knowing when a stroke,
traumatic head injury, or disease will occur, very littlecan be done to prevent aphasia. The extent of recovery,however, in some cases, can be affected by an individ-ual’s willingness to cooperate and participate in speechtherapy directly following the injury.
Resources
BOOKS
Goodglass, Harold. Understanding Aphasia. San Diego: Acad-
emic Press, 1993.
Kirshner, Howard S., ed. Handbook of Neurological Speech

and Language Disorders. New York: Marcel Dekker, Inc.,
1995.
LaPointe, Leonard L., ed. Aphasia and Related Neurogenic
Language Disorders. 2nd ed. New York: Thieme, 1997.
Lyon, Jon G., and Marianne B. Simpson. Coping with Aphasia.
San Diego: Singular Publishing Group, 1998.ORGANIZATIONS
National Aphasia Association. 156 5th Ave., Suite 707, New
York, NY 10010. (800) 922-4622. <http://www.aphasia.org>.
National Institute on Deafness and Other Communication Dis-

orders. National Institutes of Health, 31 Center Drive,MSC 2320, Bethesda, MD USA 20892-2320. (800) 241-1044. <http://www.nidcd.nih.gov>.
Apheres seeTransfusion
Aplastic anemia is a disorder in which the bone mar-
row greatly decreases or stops production of blood cells.
The bone marrow (soft tissue which is located with-

in the hard outer shell of the bones) is responsible for theproduction of all the types of blood cells. The matureforms of these cells include red blood cells, which carryoxygen throughout the body; white blood cells, whichfight infection; and platelets, which are involved in clot-ting. In aplastic anemia, the basic structure of the marrowbecomes abnormal, and those cells responsible for gener-ating blood cells (hematopoietic cells) are greatlydecreased in number or absent. These

are greatlydecreased in number or absent. These hematopoieticcells are replaced by large quantities of fat.

Yearly, aplastic anemia strikes about 5-10 people in
every one million. Although aplastic anemia strikes bothmales and females of all ages, there are two age groupsthat have an increased risk. Both young adults (between15-30 years of age) and the elderly (over the age of 60)have higher rates of aplastic anemia than the generalpopulation. While the disorder occurs worldwide, youngadults in Asia have a higher disease rate than do popula-tions in North America and Europe.

Aplastic anemia falls into three basic categories,
based on the origin of its cause: idiopathic, acquired, andhereditary.
In about 60% of cases, aplastic anemia is considered
to be idiopathic, meaning that the cause of the disorder isunknown.
GALE ENCYCLOPEDIA OF MEDICINE 2 336Aplastic anemiaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 336

Acquired aplastic anemia refers to those cases where
certain environmental factors and physical conditionsseem to be associated with development of the disease.Acquired aplastic anemia can be associated with:
• exposure to drugs, especially anti-cancer agents, antibi-
otics , anti-inflammatory agents, seizure medications,
and antithyroid drugs (drugs given to stop the function-ing of an overactive thyroid)
• exposure to radiation• chemical exposure (especially to the organic solvent

benzene and certain insecticides)
• infection with certain viruses (especially those causing
viral hepatitis, as well as Epstein-Barr virus, par-vovirus, and HIV , the virus which can cause AIDS )
• pregnancy• certain other disorders, including a disease called parox-
ysmal nocturnal hemoglobinuria, an autoimmune reac-tion called graft-vs-host disease (which occurs when thebody’s immune system attacks and destroys the body’sown cells), and certain connective tissue diseases

Hereditary aplastic anemia is relatively rare, but
does occur in Fanconi’s anemia, Shwachman-Diamondsyndrome, and dyskeratosis congenita.
Symptoms of aplastic anemia tend to be those of
other anemias , including fatigue , weakness, tiny red-

dish-purple marks (petechiae) on the skin (evidence ofpinpoint hemorrhages into the skin), evidence of abnor-mal bruising, and bleeding from the gums, nose, intes-tine, or vagina. The patient is likely to appear pale. If theanemia progresses, decreased oxygen circulating in theblood may lead to an increase in heart rate and the sud-den appearance of a new heart murmur.
Diagnosis
The blood count in aplastic anemia will reveal low

numbers of all formed blood cells. Red blood cells willappear normal in size and coloration, but greatlydecreased in number. Cells called reticulocytes (veryyoung red blood cells, which are usually produced ingreat numbers by the bone marrow in order to compen-sate for a severe anemia) will be very low in number.Platelets and white blood cells will also be decreased innumber, though normal in structure.
A sample of the patient’s bone marrow will need to

be removed by needle (usually from the hip bone) andexamined under a microscope. If aplastic anemia is pre-sent, this examination will reveal very few or nohematopoietic cells, and replacement with fat.Treatment
The first step in the treatment of aplastic anemia

involves discontinuing exposure to any substance thatmay be causing the disorder. Although it would seem thatblood transfusions would be helpful in this disease, infact, they only serve as a temporary help, and may com-plicate future attempts at bone marrow transplantation .
The most successful treatment for aplastic anemia is

bone marrow transplantation. To do this, a marrow donor(often a sibling) must be identified. There are a number oftissue markers which must be examined to determinewhether a bone marrow donation is likely to be compatiblewith the patient’s immune system. Compatibility is neces-sary to avoid complications, including the destruction ofthe donor marrow by the patient’s own immune system.
Patients who cannot undergo bone marrow trans-

plant can be treated with a number of agents, includingantithymocyte globulin (ATG), cyclophosphamide,steroids, and cyclosporine. These agents all have thepotential to cause a number of troublesome side-effects.Furthermore, not all patients respond fully to theseagents. Still, even among those patients who do have agood response, many later suffer a relapse (return) ofaplastic anemia.
Prognosis
Aplastic anemia is a life-threatening illness. Without

vival depends on how severe the disease is at diagnosis,which type of treatment a patient is eligible for, and whatkind of response their body has to that treatment. Theworst-prognosis type of aplastic anemia is one associatedwith very low numbers of a particular type of whiteblood cell. These patients have a high chance of dyingfrom overwhelming bacterial infections. In fact, 80% ofall patients treated with blood transfusions alone diewithin 18 months to two years. Patients who undergobone

18 months to two years. Patients who undergobone marrow transplantation have a 60-90% chance ofbeing cured of the disease.

Resources
BOOKS
Castro-Malaspina, Hugo, and Richard J. O’Reilly. “Aplastic
Anemia and Myelodysplastic Syndromes.” In Harrison’s
Doney, Kristine, et al. “Primary Treatment of Acquired Aplas-
tic Anemia: Outcomes with Bone Marrow Transplantationand Immunosuppressive Therapy.” Annals of Internal
Medicine 126 (15 Jan. 1997): 107+.

GALE ENCYCLOPEDIA OF MEDICINE 2 337Aplastic anemiaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 337

Young, Neal. “Aplastic Anaemia.” The Lancet 346 (22 July
1995): 228+.
Young, Neal, and Jaroslaw Maciejewski. “The Pathophysiolo-
gy of Acquired Aplastic Anemia.” The New England Jour-
nal of Medicine 336 (8 May 1997): 1365+.
Aplastic Anemia Foundation of America. P.O. Box 613, Annapo-
lis, MD 21404. (800) 747-2820. <http://www.aplastic.org>.
Aplastic crisis seeFifth disease
Appendectomy
Appendectomy is the surgical removal of the appen-

dix. The appendix is a worm-shaped hollow pouchattached to the cecum, the beginning of the large intestine.
Purpose
Appendectomies are performed to treat appendici-
tis, an inflamed and infected appendix.
Since appendicitis occurs most commonly in males
between the ages of 10-14 and in females between the agesKEY TERMS
Bone marrow —A substance found in the cavities

of bones, especially the long bones and the ster-num (breast bone). The bone marrow containsthose cells which are responsible for the produc-tion of the blood cells (red blood cells, whiteblood cells, and platelets).
Bone marrow transplant —A procedure in which a
quantity of bone marrow is extracted through aneedle from a donor, and then passed into apatient to replace the patient’s diseased or absentbone marrow.

Hematopoietic cells —Those cells which are
lodged within the bone marrow, and which areresponsible for producing the cells which circulatein the blood (red blood cells, white blood cells,and platelets).of 15-19, appendectomy is most often performed during this
time. The diagnosis of appendicitis is most difficult in thevery young (less than two years of age) and in the elderly.
Appendectomy is considered a major surgical opera-

tion. Therefore, a general surgeon must perform thisoperation in the operating room of a hospital. An anes-thesiologist is also present during the operation to admin-ister an anesthetic. Most often the anesthesiologist uses ageneral anesthetic technique whereby patients are put tosleep and made pain free by administering drugs in the
vein or by agents inhaled through a tube placed in thewindpipe. Occasionally a spinal anesthetic may be used.

After the patient is anesthetized, the general surgeon
can remove the appendix either by using the traditionalopen procedure (in which a 2-3 [5-7.6 cm] in incision ismade in the abdomen) or via laparoscopy (in which four
1 in [2.5 cm] incisions are made in the abdomen).
Traditional open appendectomy
When the surgeon uses the open approach, he makes

an incision in the lower right section of the abdomen. Mostincisions are less than 3 in (7.6 cm) in length. The surgeonthen identifies all of the organs in the abdomen and exam-ines them for other disease or abnormalities. The appendixis located and brought up into the wounds . The surgeon

separates the appendix from all the surrounding tissue andits attachment to the cecum and then removes it. The sitewhere the appendix was previously attached, the cecum, isclosed and returned to the abdomen. The muscle layersand then the skin are sewn together.
Laproscopic appendectomy
When the surgeon conducts a laproscopic appendec-

tomy, four incisions, each about 1 in (2.5 cm) in length,are made. One incision is near the umbilicus, or navel,and one is between the umbilicus and the pubis. Twoother incisions are smaller and are in the right side of thelower abdomen. The surgeon then passes a camera andspecial instruments through these incisions. With the aidof this equipment, the surgeon visually examines theabdominal organs and identifies the appendix. Similarly,the appendix is freed from all of its attachments

appendix is freed from all of its attachments andremoved. The place where the appendix was formerlyattached, the cecum, is stitched. The appendix isremoved through one of the incisions. The instrumentsare removed and then all of the incisions are closed.

Studies and opinions about the relative advantages
and disadvantages of each method are divided. A skilledsurgeon can perform either one of these procedures in
GALE ENCYCLOPEDIA OF MEDICINE 2 338AppendectomyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 338

(LA) always takes longer than traditional appendectomy(TA). The increased time required to do a LA increasesthe patient’s exposure to anesthetics, which increases therisk of complications. The increased time requirementalso escalates fees charged by the hospital for operatingroom time and by the anesthesiologist. Since LA alsorequires specialized equipment, the fees for its use alsoincreases the hospital charges. Patients with either opera-tion have similar pain medication needs, begin

have similar pain medication needs, begin eatingdiets at comparable times, and stay in the hospital equiv-

alent amounts of time. LA is of special benefit in womenin whom the diagnosis is difficult and gynecological dis-ease (such as endometriosis ,pelvic inflammatory dis-
ease, ruptured ovarian follicles, ruptured ovarian cysts ,

and tubal pregnancies) may be the source of pain and notappendicitis. If LA is done in these patients, the pelvicorgans can be more thoroughly examined and a definitivediagnosis made prior to removal of the appendix. Mostsurgeons select either TA or LA based on the individualneeds and circumstances of the patient.
Insurance plans do cover the costs of appendectomy.
Fees are charged independently by the hospital and thephysicians. Hospital charges include fees for operating

and recovery room use, diagnostic and laboratory testing,as well as the normal hospital room charges. Surgicalfees vary from region to region and range between $250-$750. The anesthesiologist’s fee depends upon the healthof the patient and the length of the operation.
Once the diagnosis of appendicitis is made and the

decision has been made to perform an appendectomy, thepatient undergoes the standard preparation for an operation.This usually takes only one to two hours and includes sign-ing the operative consents, patient identification proce-dures, evaluation by the anesthesiologist, and moving thepatient to the operating suites of the hospital. Occasionally,if the patient has been ill for a prolonged period of time orhas had protracted vomiting, a delay of few to several hoursmay be necessary to give the

few to several hoursmay be necessary to give the patient fluids and antibiotics .

Aftercare
Recovery from an appendectomy is similar to other
operations. Patients are allowed to eat when the stomach
GALE ENCYCLOPEDIA OF MEDICINE 2 339Appendectomy
Large intestine
Appendix
Swollen and
inflamed appendixRectum
Cecum
Cecum
A traditional open appendectomy. After the surgeon makes an incision in the lower right section of the abdomen, he/she
pulls the appendix up, separates it from the surrounding tissue and its attachment to the cecum, and then removes it. (Illus-

tration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 339

meal is a clear liquid diet—broth, juice, soda pop, andgelatin. If patients tolerate this meal, the next meal usuallyis a regular diet. Patients are asked to walk and resume theirnormal physical activities as soon as possible. If TA wasdone, work and physical education classes may be restrict-ed for a full three weeks after the operation. If a LA wasdone, most patients are able to return to work and strenuousactivity within one to three weeks after the operation.
Risks

Risks
Certain risks are present when any operation requires
a general anesthetic and the abdominal cavity is opened.Pneumonia and collapse of the small airways ( atelecta-
sis) often occurs. Patients who smoke are at a greater risk
for developing these complications. Thrombophlebitis ,
or inflammation of the veins, is rare but can occur if thepatient requires prolonged bed rest. Bleeding can occurbut rarely is a blood transfusion required. Adhesions

(abnormal connections to abdominal organs by thinfibrous tissue) is a known complication of any abdominalprocedure such as appendectomy. These adhesions canlead to intestinal obstruction which prevents the normalflow of intestinal contents. Hernia is a complication of
any incision, However, they are rarely seen after appen-dectomy because the abdominal wall is very strong in thearea of the standard appendectomy incision.
The overall complication rate of appendectomy

depends upon the status of the appendix at the time it isremoved. If the appendix has not ruptured the complicationrate is only about 3%. However, if the appendix has rup-tured the complication rate rises to almost 59%. Woundinfections do occur and are more common if the appendici-tis was severe, far advanced, or ruptured. An abscess may
form in the abdomen as a complication of appendicitis.
Occasionally, an appendix will rupture prior to its

removal, spilling its contents into the abdominal cavity.Peritonitis or a generalized infection in the abdomen

will occur. Treatment of peritonitis as a result of a rup-tured appendix includes removal of what remains of theappendix, insertion of drains (rubber tubes that promotethe flow of infection inside the abdomen to outside of thebody), and antibiotics. Fistula formation (an abnormalconnection between the cecum and the skin) rarelyoccurs. It is only seen if the appendix has a broad attach-ment to the cecum and the appendicitis is far advancedcausing destruction of the cecum itself.

Most patients feel better immediately after an opera-
tion for appendicitis. Many patients are discharged fromthe hospital within 24 hours after the appendectomy.KEY TERMS
Abscess —A collection of pus buried deep in the
tissues or in a body cavity.
Anesthesiologist —A physician who has special
training and expertise in the delivery of anesthetics.
Anesthetics —Drugs or methodologies used to
make a body area free of sensation or pain.

Cecum —The beginning of the large intestine and
the place where the appendix attaches to theintestinal tract.
General surgeon —A physician who has special
training and expertise in performing a variety ofoperations.
Pelvic organs —The organs inside of the body that
are located within the confines of the pelvis. Thisincludes the bladder and rectum in both sexes andthe uterus, ovaries, and fallopian tubes in females.

Pubis —The anterior portion of the pelvis located
in the anterior abdomen.
Thrombophlebitis —Inflammation of the veins,
usually in the legs, which causes swelling and ten-derness in the affected area.
Umbilicus —The navel.
Others may require a longer stay—three to five days.
Almost all patients are back to their normal activitieswithin three weeks.
The mortality rate of appendicitis has dramatically

decreased over time. Currently, the mortality rate is esti-mated at one to two per 1,000,000 cases of appendicitis.
Death is usually due to peritonitis, intra abdominal
abscess or severe infection following rupture.
The complications associated with undiagnosed, mis-

diagnosised, or delayed diagnosis of appendectomy arevery significant. The diagnosis is of appendicitis is diffi-cult and never certain. This has led surgeons to perform anappendectomy any time that they feel appendicitis is thediagnosis. Most surgeons feel that in approximately 20%of their patients, a normal appendix will be removed.Rates much lower than this would seem to indicate that thediagnosis of appendicitis was being frequently missed.
Resources
BOOKS

Resources
BOOKS
Schwartz, Seymour I. “Appendix.” In Principles of Surgery ,e d .
Seymour Schwartz, et al. New York: McGraw-Hill, 1994.
GALE ENCYCLOPEDIA OF MEDICINE 2 340AppendectomyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 340

Silen, William. “Acute Appendicitis.” In Harrison’s Principles
of Internal Medicine , ed. Anthony S. Fauci, et al. New
York: McGraw-Hill, 1997.
McCall, J. L., K. Sharples, and F. Jafallah. “Systematic Review
of Randomized Controlled Trial Comparing Laproscopicwith Open Appendectomy.” British Journal of Surgery 84,
no. 8 (Aug. 1997): 1045-1950.
Minne, L., et al. “Laproscopic Vs Open Appendectomy.
Prospective Randomized Study of Outcomes.” Archives of
Surgery 132 (July 1997): 708-711.

OTHER
“Appendectomy.” ThriveOnline. <http://thriveonline.oxygen.
com>.
“The Appendix.” Mayo Clinic Online. <http://www.mayo
health.org>.
Mary Jeanne Krob, MD, FACS
Appendicitis
Appendicitis is an inflammation of the appendix,

which is the worm-shaped pouch attached to the cecum,the beginning of the large intestine. The appendix has noknown function in the body, but it can become diseased.Appendicitis is a medical emergency, and if it is leftuntreated the appendix may rupture and cause a poten-tially fatal infection.
Appendicitis is the most common abdominal emer-

gency found in children and young adults. One person in15 develops appendicitis in his or her lifetime. The inci-dence is highest among males aged 10-14, and amongfemales aged 15-19. More males than females developappendicitis between puberty and age 25. It is rare in the
elderly and in children under the age of two.
The hallmark symptom of appendicitis is increasing-
ly severe abdominal pain . Since many different condi-

tions can cause abdominal pain, an accurate diagnosis ofappendicitis can be difficult. A timely diagnosis is impor-tant, however, because a delay can result in perforation,or rupture, of the appendix. When this happens, theinfected contents of the appendix spill into the abdomen,potentially causing a serious infection of the abdomencalled peritonitis .
Other conditions can have similar symptoms, espe-

cially in women. These include pelvic inflammatorydisease , ruptured ovarian follicles, ruptured ovarian
cysts , tubal pregnancies, and endometriosis . Various
forms of stomach upset and bowel inflammation mayalso mimic appendicitis.
The treatment for acute (sudden, severe) appendici-
tis is an appendectomy , surgery to remove the appendix.

Because of the potential for a life-threatening rupturedappendix, persons suspected of having appendicitis areoften taken to surgery before the diagnosis is certain.
The causes of appendicitis are not well understood,
but it is believed to occur as a result of one or more ofthese factors: an obstruction within the appendix, thedevelopment of an ulceration (an abnormal change in tis-sue accompanied by the death of cells) within the appen-
dix, and the invasion of bacteria.

Under these conditions, bacteria may multiply with-
in the appendix. The appendix may become swollen andfilled with pus (a fluid formed in infected tissue, consist-ing of while blood cells and cellular debris), and mayeventually rupture. Signs of rupture include the presenceof symptoms for more than 24 hours, a fever , a high
white blood cell count, and a fast heart rate. Very rarely,
GALE ENCYCLOPEDIA OF MEDICINE 2 341Appendicitis

An extracted appendix. (Photograph by Lester V. Bergman,
Corbis Images. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 341

the inflammation and symptoms of appendicitis may dis-
appear but recur again later.
The distinguishing symptom of appendicitis is pain

beginning around or above the navel. The pain, whichmay be severe or only achy and uncomfortable, eventual-ly moves into the right lower corner of the abdomen.There, it becomes more steady and more severe, andoften increases with movement, coughing, and so forth.The abdomen often becomes rigid and tender to thetouch. Increasing rigidity and tenderness indicates anincreased likelihood of perforation and peritonitis.
Loss of appetite is very common. Nausea and vom-

iting may occur in about half of the cases and occasion-
ally there may be constipation or diarrhea . The temper-
ature may be normal or slightly elevated. The presence ofa fever may indicate that the appendix has ruptured.
Diagnosis
A careful examination is the best way to diagnose

appendicitis. It is often difficult even for experiencedphysicians to distinguish the symptoms of appendicitisfrom those of other abdominal disorders. Therefore, veryspecific questioning and a thorough physical examina-
tion are crucial. The physician should ask questions,

such as where the pain is centered, whether the pain hasshifted, and where the pain began. The physician shouldpress on the abdomen to judge the location of the painand the degree of tenderness.
The typical sequence of symptoms is present in about

50% of cases. In the other half of cases, less typical pat-terns may be seen, especially in pregnant women, olderpatients, and infants. In pregnant women, appendicitis iseasily masked by the frequent occurrence of mild abdom-inal pain and nausea from other causes. Elderly patientsmay feel less pain and tenderness than most patients,thereby delaying diagnosis and treatment, and leading torupture in 30% of cases. Infants and young children oftenhave diarrhea, vomiting, and fever in addition to

While laboratory tests cannot establish the diagno-
sis, an increased white cell count may point to appendici-tis. Urinalysis may help to rule out a urinary tract infec-
tion that can mimic appendicitis.
Patients whose symptoms and physical examination

are compatible with a diagnosis of appendicitis are usual-ly taken immediately to surgery, where a laparotomy(surgical exploration of the abdomen) is done to confirmthe diagnosis. In cases with a questionable diagnosis,other tests, such as a computed tomography scan (CT)may be performed to avoid unnecessary surgery. Anultrasound examination of the abdomen may help toidentify an inflamed appendix or other condition thatwould explain the symptoms. Abdominal x-rays are not

of much value except when the appendix has ruptured.
Often, the diagnosis is not certain until an operation is
done. To avoid a ruptured appendix, surgery may be recom-mended without delay if the symptoms point clearly toappendicitis. If the symptoms are not clear, surgery may bepostponed until they progress enough to confirm a diagnosis.
When appendicitis is strongly suspected in a woman
of child-bearing age, a diagnostic laparoscopy (an

examination of the interior of the abdomen) is sometimesrecommended before the appendectomy in order to besure that a gynecological problem, such as a rupturedovarian cyst, is not causing the pain. In this procedure, alighted viewing tube is inserted into the abdomenthrough a small incision around the navel.
A normal appendix is discovered in about 10-20% of

patients who undergo laparotomy, because of suspectedappendicitis. Sometimes the surgeon will remove a nor-mal appendix as a safeguard against appendicitis in thefuture. During the surgery, another specific cause for thepain and symptoms of appendicitis is found for about30% of these patients.
Treatment
The treatment of appendicitis is an immediate

appendectomy. This may be done by opening theabdomen in the standard open appendectomy technique,or through laparoscopy. In laparoscopy, a smaller inci-sion is made through the navel. Both methods can suc-cessfully accomplish the removal of the appendix. It isnot certain that laparoscopy holds any advantage overopen appendectomy. When the appendix has ruptured,patients undergoing a laparoscopic appendectomy mayhave to be switched to the open appendectomy procedurefor the successful management

procedurefor the successful management of the rupture. If a rup-tured appendix is left untreated, the condition is fatal.

Prognosis
Appendicitis is usually treated successfully by appen-
dectomy. Unless there are complications, the patient shouldrecover without further problems. The mortality rate incases without complications is less than 0.1%. When anappendix has ruptured, or a severe infection has developed,the likelihood is higher for complications, with slowerrecovery, or death from disease. There are higher rates ofperforation and mortality among children and the elderly.

Appendicitis is probably not preventable, although
there is some indication that a diet high in green vegeta-bles and tomatoes may help prevent appendicitis.
GALE ENCYCLOPEDIA OF MEDICINE 2 342AppendicitisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 342

Resources
BOOKS
Carter, David C. “The Acute Abdomen.” In Diseases of the
Gastrointestinal Tract and Liver , ed. David J.C. Shear-
man, et al. New York: Churchill Livingstone, 1997.
Mulholland, Michael W. “Approach to the Patient with Acute
Abdomen.” In Textbook of Gastroenterology , ed. Tadataka
Yamada, et al. Philadelphia: J. B. Lippincott, 1995.

Van Der Meer, Antonia. “Do You Know the Warning Signs of
Appendicitis?” Parents Magazine , Apr. 1997, 49.
Wagner J. M., et al. “Does This Patient Have Appendicitis?”
The Journal of the American Medical Association 276
(1996): 1589-1594.
Caroline Andrews Helwick
Appendix removal seeAppendectomy
Applied kinesiology
Applied kinesiology (AK) is the study of muscles

and the relationship of muscle strength to health. Itincorporates a system of manual muscle testing andtherapy. AK is based on the theory that an organ dys-function is accompanied by a specific muscle weakness.Diseases are diagnosed through muscle-testing proce-dures and then treated. AK is not the same as kinesiolo-gy, or biomechanics, which is the scientific study ofmovement.KEY TERMS
Appendectomy (or appendicectomy) —Surgical

removal of the appendix.
Appendix —The worm-shaped pouch attached to
the cecum, the beginning of the large intestine.
Laparotomy —Surgical incision into the loin,
between the ribs and the pelvis, which offers sur-geons a view inside the abdominal cavity.
Peritonitis —Inflammation of the peritoneum,
membranes lining the abdominal pelvic wall.Purpose
AK is not designed for crisis medicine. For example,

betes, heart disease, or infections. This therapy isdesigned to be a part of a holistic approach to preventivemedicine. The goals of AK are to (1) restore normalnerve function, (2) achieve normal endocrine, immune,digestive, and other internal organ functions, (3) inter-vene early in degenerative processes to prevent or delaypathological conditions, and to (4) restore postural bal-ance, correct gait (walking) impairment, and improverange of motion.
Origins

Origins
AK is based on principles of functional neurology,
anatomy, physiology, biomechanics, and biochemistry aswell as principles from Chinese medicine, acupuncture ,

and massage. It was developed from traditional kinesiolo-gy in 1964 by George G. Goodheart, a chiropractor fromDetroit, Michigan. He observed that each large musclerelates to a body organ. A weakness in a muscle may meanthat there is a problem in the associated organ. Goodheartfound that by treating the muscle and making it strongagain, he was able to improve the function of the organ aswell. For example, if a particular nutritional supplementwas given to a patient, and the muscle tested

given to a patient, and the muscle tested strong, it wasthe correct supplement for the patient. If the muscleremained weak, it was not. Other methods of treatmentcan be evaluated in a similar manner. Goodheart alsofound that painful nodules (small bumps) may be associat-ed with a weak muscle. By deeply massaging the muscle,he was able to improve its strength. Goodheart’s findingsin 1964 led to the origin and insertion treatment, the firstmethod developed in AK. Other diagnostic and

firstmethod developed in AK. Other diagnostic and therapeuticprocedures were developed for various reflexes describedby other chiropractors and doctors. Goodheart incorporat-ed acupuncture meridian therapy into AK after reading thewritings of Felix Mann, M.D.

that incorporates feedback from the body. He said that“applied kinesiology is based on the fact that the bodylanguage never lies.” He felt that the body’s muscleswere indicators of disharmony. Once muscle weaknesshas been ascertained, the problem may be solved in avariety of ways. If a practitioner approaches the problemcorrectly, he believed, making the proper and adequatediagnosis and treatment, the outcome is satisfactory bothto the doctor and to the patient.

According to AK, each muscle in the body relates to
a specific meridian or energy pathway (acupuncture
GALE ENCYCLOPEDIA OF MEDICINE 2 343Applied kinesiologyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 343

lines) in the body. These meridians also relate to organs
or glands, allowing the muscles to provide informationabout organ or gland function and energy. The five areasof diagnosis and therapy for the applied kinesiologist are(1) the nervous system, (2) the lymphatic system, (3) thevascular (blood vessel) system, (4) the cerebrospinal sys-tem, and (5) the meridian system.
The first part of AK is muscle testing, which is used

to help diagnose what part of the body is functioningabnormally. Muscle testing involves putting the bodyinto a position that requires a certain muscle to remaincontracted, and then applying pressure against the mus-cle. The testing does not measure strength but is meant toreveal stresses and imbalances in the body through thetension in the muscle. The test evaluates the ability of acontrolling system (like the nervous system) to adapt themuscle to meet the changing pressure of the

themuscle to meet the changing pressure of the examiner’stest. AK practitioners also examine structural factorssuch as posture, gait, and range of motion. Some chiro-GEORGE GOODHEART (1918– )

gan, in 1918 and became a second-generation doctor ofchiropractic. He graduated from the National College ofChiropractic in 1939 and is recognized as the founderand developer of Applied Kinesiology. After he joinedthe U.S. Air Force as an aviation cadet in World War II,he received a promotion to major at the age of 22. Hewas the youngest ever to attain that rank. He served inactive duty from 1941-1946 and continued as a mem-ber of the Air Force Reserve until the mid-1950s.

Dr. Goodheart held numerous positions of distinc-
tion during his career, including director of the NationalChiropractic Mutual Insurance Company and directorfor the International College of Applied Kinesiology-U.S.A. He also lectured and taught throughout the Unit-ed States, Japan, Europe, and Australia; and he was theofficial doctor of chiropractic for the Lake Placed WinterOlympic Games in 1980. He contributes to a variety oftrade publications on a regular basis.

Achievement Award from the International College ofKinesiology. Earlier, in 1987 he was honored with theLeonardo da Vinci Award from the Institute for theAchievement of Human Potential, and he was cited forhis research by Logan and Palmer Colleges of Chiro-practic. He represented the State of Michigan as a dele-gate to the American Chiropractic Association and wasa fellow at the International College of Chiropractic. Heresides with his wife, JoAnn in Grosse Pointe Woods,Michigan, where he

JoAnn in Grosse Pointe Woods,Michigan, where he enjoys skiing and tennis.practors use AK to help them evaluate the success of

spinal adjustment. A leg muscle is tested for strength orweakness to determine whether the adjustments made areappropriate.
According to AK, common internal causes of mus-
cle weakness include:
• dysfunction of nerve supply (nerve interference
between spine and muscles)
• impairment of lymphatic drainage
• reduction of blood supply• abnormal pressure in cerebral fluid affecting nerve-to-
muscle relationships
• blockage of an acupuncture meridian
• imbalance of chemicals

• dysfunction of organs or glands• excesses or deficiencies in nutrition
Physiological reactions to chemicals, including
those associated with nutrition and allergies , may also be

evaluated using AK. The AK protocol for testing chemi-cal compounds is to place the substance on the patient’stongue so that he tastes the material, and the normalchemical reactions of ingestion begin. In some cases, thesubstances are inhaled through the nose. The AK practi-tioner then tests the associated muscle-organ pattern todetermine where or if there is a strength or weakness.The patient does not need to swallow the substance for achange in strength or weakness to be identified. David

in strength or weakness to be identified. David S.Walther, a diplomate of the International College ofApplied Kinesiology, has indicated that “it is possiblethat the central nervous system, recognizing the com-pound being ingested, relays information to the organsand glands preparing for use of the compound. If thecompound is recognized as beneficial, the energy patternis immediately enhanced, influencing not only the organor gland, but also the associated muscle.”

AK has been used as a diagnostic health tool for a
variety of conditions.
Bone health
• neck/low back pain and sciatica
• whiplash• frozen shoulder
Joint health
• carpal tunnel syndrome• arthritis (including rheumatoid arthritis)• sports injuries
Muscle health
• tennis elbow
GALE ENCYCLOPEDIA OF MEDICINE 2 344Applied kinesiologyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 344

• heel spurs
• wound healing
• intermittent claudication (pain on walking)
• restless legs• cramps
Vascular system health
• aching varicose veins
• palpitations• high blood pressure
Nervous system health
• migraine and other headaches• trigeminal neuralgia and other face pains
• Bell’s palsy
• anxiety
• depression• fears• addictions (like smoking)
• claustrophobia
• Meniere’s disorder• neuralgia (severe, throbbing pain)
• travel sickness

• fatigue• phantom limb pain• paralysis of leg or arm after a stroke
Respiratory system health
• hay fever• rhinitis (inflammed nasal passages)
•asthma
• bronchitis• emphysema (lung disease)
Urinary system health
• cystitis (bladder inflammation), especially in the elderly
• early prostate enlargement• non-specific urethritis (inflammation of tube from the
bladder)
• bedwetting
Reproductive organ health
• menstrual pains• irregular or excessive menstrual activity

• pelvic pains and endometriosis
• menopausal flushes• painful, nodular breasts
• preparation for childbirth• vaginal pain• post herpetic ( shingles ) pain
• impotence and infertility
Skin health
• pain after operations• painful, prominent scars• wrinkles or bagginess of face• acne• psoriasis and eczema (skin diseases)
• boils
• excessive perspiration• hemorrhoids• canker sores• itching
Immune system health
• recurring tonsillitis (inflammed tonsils)
• persisting weakness after a severe illness

Sensory organ health
• tinnitus (ringing ears)• tired eyes• retinitis pigmentosa and pterygium retinitis (diseases of
the retina)
Digestive system health
• colitis or other bowel inflammations• ulcers• diarrhea• obesity
The second part of AK involves the treatment phase.

Goodheart and other practitioners of AK have adaptedmany treatment methods for the problems that are diag-nosed with muscle testing. Examples of treatment meth-ods include special diets , dietary supplements, chiro-
practic manipulation, osteopathic cranial techniques,
acupuncture/meridian therapies, acupressure , deep mus-

cle massage, and nervous system coordination proce-dures. For example, an AK practitioner might treat asth-ma by looking for weaknesses in specific lower back andleg muscles that share a connection with the adrenalglands. The practitioner will strengthen these musclesand help the adrenal gland produce bronchodilators ,
chemicals that relax or open air passages in the lungs.
GALE ENCYCLOPEDIA OF MEDICINE 2 345Applied kinesiologyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 345

in conjunction with other standard diagnostic methods byprofessionals trained in clinical diagnosis. Most practi-tioners of AK are chiropractors, but naturopaths, medicaldoctors, dentists, osteopaths, nutritionists, physical thera-pists, massage therapists, podiatrists, psychiatrists, andnurse practitioners are also involved. In 1991, 37.2% of4,835 full-time chiropractors in the United States whoresponded to a survey by the National Board of Chiro-practic Examiners (NBCE) said they used AK in

Examiners (NBCE) said they used AK in theirpractice. Subsequent NBCE surveys indicated that 31%of chiropractors in Canada, 60% in Australia, and 72% inNew Zealand use AK.

Most practitioners of AK utilize a holistic approach
and evaluate a person from a triad-based health perspec-tive. Generally, chiropractors approach health and heal-ing from a structural basis, medical doctors generallyfrom a chemical basis, and psychiatrists and psycholo-gists from a mental or emotional basis. Applied kinesiol-ogists attempt to work with all three areas of health, andin some cases, include a spiritual dimension.
The use of AK is often included in insurance cover-

age if the policy covers chiropractor benefits. The cost ofthe AK examination is similar to the costs of other chiro-practic practices.
AK should only by used by trained professionals

with the necessary expertise to perform specific andaccurate tests. The AK examination should be combinedwith a standard physical diagnosis, which often includeslaboratory tests, x rays, health and dietary history, andother special tests. An AK examination should enhance astandard diagnosis, not replace it. The total diagnosticwork-up should be used to determine the final diagnosis.
The use of manual muscle testing to evaluate nutri-

tion is particularly a problem if it is done by a lay nutri-tion sales person as a tool to sell his/her product. The per-son should have the educational background to evaluatenutritional needs as well as have a high level of knowl-edge in the use of proper muscle testing techniques.
If AK is performed by a trained practitioner with the
appropriate educational background, side effects fromthe muscle-testing procedures should be minimal.

AK is a tool that is used by many health care pro-
fessionals, and especially by chiropractors. A literaturereview published in 1999 by researchers from the

School of Medicine at the University of North Carolinaat Chapel Hill and the Foundation for Allied Conserva-tive Therapies Research in Chapel Hill stated that,although AK appears to be a promising methodology,there is a lack of research results relevant to clinicalpractice and outcomes of AK care. They found thislack of results surprising, since cost, satisfaction, uti-lization, and changes in symptoms are the importantresults of clinical practice. In addition, they determinedthat some studies

In addition, they determinedthat some studies that were supposed to be an evalua-tion of AK procedures did not actually use clinicalpractices and principles of AK. However, from studiesadhering to AK principles and employing standardizedtraining by well-trained practitioners, they did statethere was some evidence that AK is an objectively veri-fiable phenomenon. They suggested that “future stud-ies of AK should focus on outcomes of care, includingsymptoms, function, costs, and safety. Only

function, costs, and safety. Only well-designed studies that account for the individual natureof AK diagnosis and treatment and preserve the properclinical context of AK treatment will be informative.Understanding the individual components of theprocess of AK treatment remains important. Studiesaddressing validation of isolated AK procedures needto meet the methodological challenges of studyingappropriate subjects that reflects the current recog-nized practice and understanding of AK. Further

practice and understanding of AK. Further evalu-ation of the basic physiologic phenomena involved andcorrelation of AK manual muscle test results will alsoadvance understanding of this diagnostic and therapeu-tic system.”

Resources
BOOKS
Holdway, Anne. Kinesiology: Muscle Testing and Energy Bal-
ancing for Health and Well-Being. Rockport, MA: Ele-
ment, 1997.
Valentine, Tom, Carol Valentine, and D.P. Hetrick. Applied
Kinesiology. Rochester, VT: Healing Arts Press, 1989.
International College of Applied Kinesiology. 6405 Metcalf
Ave., Suite 503, Shawnee Mission, KS 66202. 913-384-5336. <http://www.icakusa.com and <http://www.icak.com>.
APSGN seeAcute poststreptococcal

APTT seePartial thromboplastin time
Arachnodactyly seeMarfan syndrome
GALE ENCYCLOPEDIA OF MEDICINE 2 346Applied kinesiologyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 346

Arbovirus encephalitis
Encephalitis is a serious inflammation of the brain.
Arbovirus encephalitis is caused by a virus from theArbovirus group. The term arbovirus stands for Arthro-
pod-borne virus because these viruses are passed to
humans by members of the phylum Arthropoda (whichincludes insects and spiders).
Of the huge number of arboviruses known to exist,

about 80 types are responsible for human disease. Inaddition to the virus, there are usually two other types ofliving creatures involved in the cycle leading to humandisease. When large quantities of virus are present in anarthropod (often a tick or mosquito), the viruses arepassed to a bird or small mammal when the arthropodattempts to feed on the blood of that creature. The virusthrives within the new host, sometimes causing illness,sometimes not. More ticks or mosquitoes are infectedwith the

More ticks or mosquitoes are infectedwith the virus when they feed on the host’s blood. Even-tually, a tick or mosquito bites a human, and the virus ispassed along. Just a few types of arboviruses cycle onlybetween arthropods and humans, with no intermediatestop in a bird or small mammal.

Because the arboviruses require an arthropod to pass
them along to humans, the most common times of yearfor these illnesses include summer and fall, when mos-quitoes and ticks are most prevalent. Damp environmentsfavor large populations of mosquitoes, and thus alsoincrease the risk of arbovirus infections.
The major causes of arbovirus encephalitis include

the members of the viral families alphavirus (causingEastern equine encephalitis, Western equine encephalitis,and Venezuelan equine encephalitis), flavivirus (respon-sible for St. Louis encephalitis, Japanese encephalitis ,
Tick-borne encephalitis, Murray Valley encephalitis,Russian spring-summer encephalitis, and Powassan), andbunyavirus (causing California encephalitis).
In the United States, the most important types of

arbovirus encephalitis include Western equine encephali-tis (WEE), Eastern equine encephalitis (EEE), St. Louisencephalitis, and California encephalitis. WEE strikesyoung infants in particular, with a 5% chance of death

from the illness. Of those who survive, about 60% sufferpermanent brain damage. EEE strikes infants and chil-dren, with a 20% chance of death, and a high rate of per-manent brain damage among survivors. St. Louisencephalitis tends to strike adults older than 40 years ofage, and older patients tend to have higher rates of deathand long-term disability from the infection. Californiavirus primarily strikes 5-18 year olds, with a lowerdegree of permanent brain damage.

Encephalitis occurs because specific arboviruses
have biochemical characteristics which cause them to beparticularly attracted to the cells of the brain and thenerves. The virus causes cell death and inflammation,with fever and swelling within the brain and nerves. The
membranous coverings of the brain and spinal cord (themeninges) may also become inflamed, a condition calledmeningitis . The brain is swollen, and patches of bleed-

ing occur throughout the brain and spinal cord.
Patients with encephalitis suffer from headaches,
fever, nausea and vomiting , stiff neck, and sleepiness.
As the disease progresses, more severe symptoms devel-op, including tremors , confusion, seizures, coma , and
paralysis . Loss of function occurs when specific nerve
areas are damaged and/or killed.
Diagnosis
Early in the disease, laboratory testing of blood may

reveal the presence of the arbovirus. The usual techniqueused to verify the presence of arbovirus involves injectingthe patient’s blood into the brain of a newborn mouse,then waiting to see if the mouse develops encephalitis.Diagnosis is usually based on the patient’s symptoms,history of tick or mosquito bites, and knowledge that thepatient has been in an area known to harbor the arbovirus.
Treatment
Treatment is mostly supportive, meaning it is direct-

ed at improving the symptoms, but does not shorten thecourse of the illness. The main concerns of treatmentinvolve lowering fever, treating pain , avoiding dehydra-
tion or other chemical imbalances, and decreasing
swelling in the brain with steroids.
Prognosis
Prognosis depends on the particular type of

arbovirus causing disease, and on the age and priorhealth status of the patient. Death rates range all the wayup to 20% for arbovirus encephalitis, and the rates oflifelong effects due to brain damage reach 60% for sometypes of arboviruses.
Prevention involves avoiding contact with arthro-
pods which carry these viruses. This means wearing

GALE ENCYCLOPEDIA OF MEDICINE 2 347Arbovirus encephalitisGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 347

appropriate insect repellents, and dressing properly in
areas known to be infested. Insecticides and the avoid-ance of collections of standing water (which are goodbreeding ground for arthropods) is also effective atdecreasing arthropod populations.
There are immunizations available against EEE and
WEE. These have primarily been used to safeguard labo-ratory workers who have regular exposure to these viruses.
Resources
BOOKS
Ray, C. George. “Arthropod-Borne and Other Zoonotic Virus-

es.” In Sherris Medical Microbiology: An Introduction to
Infectious Diseases. 3rd ed. Ed. Kenneth J. Ryan. Nor-
walk, CT: Appleton & Lange, 1994.
Stoffman, Phyllis. The Family Guide to Preventing and Treat-
ing 100 Infectious Diseases. New York: John Wiley &
Sons, 1995.
ARDS seeAdult respiratory distress
syndrome
Aromatherapy
Aromatherapy is the therapeutic use of plant-

derived, aromatic essential oils to promote physical andpsychological well-being. It is sometimes used in combi-nation with massage and other therapeutic techniques aspart of a holistic treatment approach.
Purpose
Aromatherapy offers diverse physical and psycho-

logical benefits, depending on the essential oil or oilcombination and method of application used. Some com-mon medicinal properties of essential oils used in aro-matherapy include: analgesic, antimicrobial, antiseptic,KEY TERMS
Arthropods —A phylum name referring to certain
insects (including mosquitoes and ticks) and spiders.
Encephalitis —A condition in which the brain swells.anti-inflammatory, astringent, sedative, antispasmodic,

expectorant, diuretic, and sedative. Essential oils areused to treat a wide range of symptoms and conditions,including, but not limited to, gastrointestinal discomfort,skin conditions, menstrual pain and irregularities, stress-
related conditions, mood disorders , circulatory prob-
lems, respiratory infections, and wounds .
Origins
Aromatic plants have been employed for their heal-

ing, preservative, and pleasurable qualities throughoutrecorded history in both the East and West. As early as1500 
B.C. the ancient Egyptians used waters, oils,
incense, resins, and ointments scented with botanicals fortheir religious ceremonies.
There is evidence that the Chinese may have recog-
nized the benefits of herbal and aromatic remedies muchearlier than this. The oldest known herbal text, ShenNung’s Pen Ts’ao (c. 2700-3000 
B.C.) catalogs over 200

botanicals. Ayurveda, a practice of traditional Indianmedicine that dates back over 2,500 years, also used aro-matic herbs for treatment.
The Romans were well-known for their use of fra-
grances. They bathed with botanicals and integratedthem into their state and religious rituals. So did theGreeks, with a growing awareness of the medicinal prop-erties of herbs, as well. Greek physician and surgeonPedanios Dioscorides, whose renown herbal text De
Materia Medica (60

Materia Medica (60 
A.D.) was the standard textbook for
Western medicine for 1,500 years, wrote extensively onthe medicinal value of botanical aromatics. The Medica
contained detailed information on over 500 plants and4,740 separate medicinal uses for them, including anentire section on aromatics.
Written records of herbal distillation are found as early
as the first century 
A.D., and around 1000 A.D., the noted

Arab physician and naturalist Avicenna described the distil-lation of rose oil from rose petals, and the medicinal prop-erties of essential oils in his writings. However, it wasn’tuntil 1937, when French chemist René-Maurice Gattefossépublished Aromatherapie: Les Huiles essentielles, hor-
mones végé tales , that aromatherapie, or aromatherapy, was

introduced in Europe as a medical discipline. Gattefossé,who was employed by a French perfumeur, discovered thehealing properties of lavender oil quite by accident whenhe suffered a severe burn while working and used the clos-est available liquid, lavender oil, to soak it in.
In the late 20th century, French physician Jean Valnet
used botanical aromatics as a front line treatment forwounded soldiers in World War II. He wrote about his use

GALE ENCYCLOPEDIA OF MEDICINE 2 348AromatherapyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 348

of essential oils and their healing and antiseptic properties,
in his 1964 book Aromatherapie, traitement des maladies
par les essences des plantes , which popularized the use of
essential oils for medical and psychiatric treatment through-out France. Later, French biochemist Mauguerite Maurypopularized the cosmetic benefits of essential oils, and in1977 Robert Tisserand wrote the first English languagebook on the subject, The Art of Aromatherapy , which intro-

duced massage as an adjunct treatment to aromatherapy andsparked its popularity in the United Kingdom.
In aromatherapy, essential oils are carefully selected
for their medicinal properties. As essential oils areabsorbed into the bloodstream through application to theskin or inhalation, their active components trigger certainpharmalogical effects (e.g., pain relief).
In addition to physical benefits, aromatherapy has

strong psychological benefits. The volatility of an oil, orthe speed at which it evaporates in open air, is thought tobe linked to the specific psychological effect of an oil. Asa rule of thumb, oils that evaporate quickly are consid-ered emotionally uplifting, while slowly-evaporating oilsare thought to have a calming effect.
Essential oils commonly used in aromatherapy treat-
ment include:
• Roman chamomile ( Chamaemelum nobilis ). An anti-

inflammatory and analgesic. Useful in treating otitis
media (earache), skin conditions, menstrual pains, and
• Clary sage ( Salvia sclarea ). This natural astringent is
not only used to treat oily hair and skin, but is also saidto be useful in regulating the menstrual cycle, improv-ing mood, and controlling high blood pressure. Clarysage should not be used by pregnant women.
• Lavender ( Lavandula officinalis ). A popular aromather-

apy oil which mixes well with most essential oils,lavender has a wide range of medicinal and cosmeticapplications, including treatment of insect bites, burns ,
respiratory infections, intestinal discomfort, nausea,migraine, insomnia , depression, and stress .
• Myrtle ( Myrtus communis ). Myrtle is a fungicide, dis-
infectant, and antibacterial. It is often used in steamaromatherapy treatments to alleviate the symptoms ofwhooping cough ,bronchitis , and other respiratory
infections.

• Neroli (bitter orange), ( Citrus aurantium ). Citrus oil
extracted from bitter orange flower and peel and used totreat sore throat , insomnia, and stress and anxiety-
related conditions.
• Sweet orange ( Citrus sinensis ). An essential oil used to
treat stomach complaints and known for its reportedability to lift the mood while relieving stress.• Peppermint ( Mentha piperita ). Relaxes and soothes the

stomach muscles and gastrointestinal tract. Pepper-mint’s actions as an anti-inflammatory, antiseptic, andantimicrobial also make it an effective skin treatment,and useful in fighting cold and flu symptoms.
• Rosemary ( Rosmarinus officinalis ). Stimulating essen-
tial oil used to treat muscular and rheumatic com-plaints, as well as low blood pressure, gastrointestinalproblems, and headaches.
• Tea tree ( Melaleuca alternifolia ). Has bactericidal,

virucidal, fungicidal, and anti-inflammatory propertiesthat make it a good choice for fighting infection. Rec-ommended for treating sore throat and respiratoryinfections, vaginal and bladder infections, wounds, anda variety of skin conditions.
• Ylang ylang ( Cananga odorata ). A sedative essential oil
sometimes used to treat hypertension and tachycardia.
Essential oils contain active agents that can have

potent physical effects. While some basic aromatherapyhome treatments can be self-administered, medical aro-matherapy should always be performed under the guid-ance of an aromatherapist, herbalist, massage therapist,nurse, or physician.
Inhalation
The most basic method of administering aromather-
apy is direct or indirect inhalation of essential oils. Sev-eral drops of an essential oil can be applied to a tissue or
GALE ENCYCLOPEDIA OF MEDICINE 2 349Aromatherapy

Aromatic substancesNasal cavityOlfactory bulb
Olfactory
neuronsLimbic system of the brain
As a holistic therapy, aromatherapy is believed to benefit
both the mind and body. Here, the aromatic substancesfrom a flower stimulates the olfactory bulb and neurons.Thedesired emotional response (such as relaxation) is activat-ed from the limbic system of the brain. (Illustration by Elec-

tronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 349

essential oil can also be added to a bowl of hot water andused as a steam treatment. This technique is recommend-ed when aromatherapy is used to treat respiratory and/orskin conditions. Aromatherapy steam devices are alsoavailable commercially. A warm bath containing essen-tial oils can have the same effect as steam aromatherapy,with the added benefit of promoting relaxation. Whenused in a bath, water should be lukewarm rather than hotto slow the evaporation of the oil.

Essential oil diffusers, vaporizers, and light bulb
rings can be used to disperse essential oils over a largearea. These devices can be particularly effective in aro-matherapy that uses essential oils to promote a healthierhome environment. For example, eucalyptus and tea treeoil are known for their antiseptic qualities and are fre-quently used to disinfect sickrooms, and citronella andgeranium can be useful in repelling insects.
Direct application

Because of their potency, essential oils are diluted in

a carrier oil or lotion before being applied to the skin toprevent an allergic skin reaction. The carrier oil can be avegetable or olive based one, such as wheat germ or avo-cado. Light oils, such as safflower, sweet almond, grape-seed, hazelnut, apricot seed, or peach kernel, may beabsorbed more easily by the skin. Standard dilutions ofessential oils in carrier oils range from 2–10%. However,some oils can be used at higher concentrations, and oth-ers should be diluted further for safe and

oth-ers should be diluted further for safe and effective use.The type of carrier oil used and the therapeutic use of theapplication may also influence how the essential oil ismixed. Individuals should seek guidance from a health-care professional and/or aromatherapist when diluting

essential oils.
Massage is a common therapeutic technique used in
conjunction with aromatherapy to both relax the bodyand thoroughly administer the essential oil treatment.Essential oils can also be used in hot or cold compressesand soaks to treat muscle aches and pains (e.g., lavenderand ginger). As a sore throat remedy, antiseptic andsoothing essential oils (e.g., tea tree and sage) can bethoroughly mixed with water and used as a gargle ormouthwash.
Internal use

Some essential oils can be administered internally in
tincture, infusion, or suppository form to treat certainsymptoms or conditions; however, this treatment shouldnever be self-administered. Essential oils should only betaken internally under the supervision of a qualifiedhealthcare professional.
As non-prescription botanical preparations, the

essential oils used in aromatherapy are typically not paidfor by health insurance. The self-administered nature ofthe therapy controls costs to some degree. Aromatherapytreatment sessions from a professional aromatherapistare not covered by health insurance in most cases,although aromatherapy performed in conjunction withphysical therapy, nursing, therapeutic massage, or othercovered medical services may be. Individuals shouldcheck with their insurance provider to find out abouttheir specific

The adage “You get what you pay for” usually
applies when purchasing essential oils, as bargain oils are
GALE ENCYCLOPEDIA OF MEDICINE 2 350AromatherapyAromatherapy Oils
Name Description Conditions treated
Bay laurel Antiseptic, diuretic,sedative, etc. Digestive problems, bronchitis, common cold, influenza, and scabies and
lice. CAUTION: Don’t use if pregnant.

Clary sage Relaxant, anticonvulsive, antiinflammatory, and antiseptic Menstrual and menopausal symptoms, burns, eczema, and anxie ty. CAU-
TION: Don’t use if pregnant.
Eucalyptus Antiseptic, antibacterial, astringent, Boils, breakouts, cough, common cold, influenza, and
expectorant, and analgesic sinusitis. CAUTION: Not to be taken orally.

Chamomile Sedative, antiinflammatory, antiseptic, and pain reliever Hay fever, burns, acne, arthritis, digestive problems, sunbur n, and men-
strual an menopausal symptoms.
Lavender Analgesic, antiseptic, calming/soothing Headache, depression, insomnia, stress, sprains, and nausea.Peppermint Pain reliever Indigestion, nausea, headache, motion sickness, and muscle pain.Rosemary Antiseptic, stimulant, and diuretic Indigestion, gas, bronchitis, fluid retention, and influenza. CAUTION: Don’t

use if pregnant or have epilepsy or hypertension.
Tarragon Diuretic, laxative, antispasmodic, and stimulant Menstrual and menopausal symptoms, gas, and indigestion. CAUTION:
Don’t use if pregnant.
Tea tree Antiseptic and soothing Common cold, bronchitis, abscesses, acne, vaginitis, and burns.Thyme Stimulant, antiseptic, antibacterial, and antispasmodic Cough, laryngitis, diarrhea, gas, and intestinal worms. CAUTION: Do n’t

use if pregnant or have hypertension.GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 350

often adulterated, diluted, or synthetic. Pure essential oils
can be expensive; and the cost of an oil will vary depend-ing on its quality and availability.
Preparations
The method of extracting an essential oil varies by

plant type. Common methods include water or steam dis-tillation and cold pressing. Quality essential oils shouldbe unadulterated and extracted from pure botanicals.Many aromatherapy oils on the market are syntheticand/or diluted, contain solvents, or are extracted frombotanicals grown with pesticides or herbicides. To ensurebest results, essential oils should be made from pureorganic botanicals and labeled by their full botanicalname. Oils should always be stored dark bottles out ofdirect

Before using essential oils on the skin, individuals
should perform a skin patch test by applying a smallamount of the diluted oil behind the wrist and covering itwith a bandage or cloth for up to 12 hours. If redness orirritation occurs, the oil should be diluted further and asecond skin test performed, or it should be avoided alto-gether. Individuals should never apply undiluted essen-tial oils to the skin unless advised to do so by a trainedhealthcare professional.

Individuals should only take essential oils internally
under the guidance and close supervision of a health-careprofessional. Some oils, such as eucalyptus, wormwood,KEY TERMS
Antiseptic —Inhibits the growth of microorganisms.
Bactericidal —An agent that destroys bacteria (e.g.,
Staphylococci aureus, Streptococci pneumoniae,Escherichia coli, Salmonella enteritidis).
Carrier oil —An oil used to dilute essential oils for
use in massage and other skin care applications.

Contact dermatitis —Skin irritation as a result of
contact with a foreign substance.
Essential oil —A volatile oil extracted from the
leaves, fruit, flowers, roots, or other components ofa plant and used in aromatherapy, perfumes, andfoods and beverages.
Holistic —A practice of medicine that focuses on
the whole patient, and addresses the social, emo-tional, and spiritual needs of a patient as well as
their physical treatment.

Phototoxic —Causes a harmful skin reaction when
exposed to sunlight.
Remedy antidote —Certain foods, beverages, pre-
scription medications, aromatic compounds, andother environmental elements that counteract theefficacy of homeopathic remedies.
Steam distillation —A process of extracting essential
oils from plant products through a heating andevaporation process.
Volatile —Something that vaporizes or evaporates
quickly when exposed to air.

and sage, should never be taken internally. Many essen-
tial oils are highly toxic and should never be used at all inaromatherapy. These include (but are not limited to) bit-ter almond, pennyroyal, mustard, sassafras, rue, andmugwort.
Citrus-based essential oils, including bitter and
sweet orange, lime, lemon, grapefruit, and tangerine, arephototoxic, and exposure to direct sunlight should beavoided for at least four hours after their application.

Other essential oils, such as cinnamon leaf, black
pepper, juniper, lemon, white camphor, eucalyptus bluegum, ginger, peppermint, pine needle, and thyme can beextremely irritating to the skin if applied in high enoughconcentration or without a carrier oil or lotion. Cautionshould always be exercised when applying essential oilstopically. Individuals should never apply undilutedessential oils to the skin unless directed to do so by atrained healthcare professional and/or aromatherapist.

Individuals taking homeopathic remedies should
avoid black pepper, camphor, eucalyptus, and pepper-mint essential oils. These oils may act as a remedy anti-dote to the homeopathic treatment.
Children should only receive aromatherapy treat-
ment under the guidance of a trained aromatherapist orhealthcare professional. Some essential oils may not beappropriate for treating children, or may require addi-tional dilution before use on children.
Certain essential oils should not be used by pregnant

or nursing women or by people with specific illnesses orphysical conditions. Individuals suffering from any
GALE ENCYCLOPEDIA OF MEDICINE 2 351AromatherapyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 351

chronic or acute health condition should inform their
healthcare provider before starting treatment with anyessential oil.
Asthmatic individuals should not use steam inhala-
tion for aromatherapy, as it can aggravate their condition.
Essential oils are flammable, and should be kept
away from heat sources.
Side effects vary by the type of essential oil used.
Citrus-based essential oils can cause heightened sensitivi-ty to sunlight. Essential oils may also cause contact der-

matitis , an allergic reaction characterized by redness and
irritation. Anyone experiencing an allergic reaction to anessential oil should discontinue its use and contact theirhealthcare professional for further guidance. Individualsshould do a small skin patch test with new essential oilsbefore using them extensively (see “Preparations” above).
The antiseptic and bactericidal qualities of some

essential oils (such as tea tree and peppermint) and theirvalue in fighting infection has been detailed extensivelyin both ancient and modern medical literature.
Recent research in mainstream medical literature

has also shown that aromatherapy has a positive psycho-logical impact on patients, as well. Several clinical stud-ies involving both post-operative and chronically ill sub-jects showed that massage with essential oils can behelpful in improving emotional well-being, and conse-quently, promoting the healing process.
Today, the use of holistic aromatherapy is widely

accepted in Europe, particularly in Great Britain, whereit is commonly used in conjunction with massage as botha psychological and physiological healing tool. In theUnited States, where aromatherapy is often misunder-stood as solely a cosmetic treatment, the mainstreammedical community has been slower to accept it.
Resources
BOOKS
Lawless, Julia. The Complete Illustrated Guide To Aromathera-
py.Rockport, MA: Element Books Ltd, 1997.

Schnaubelt, Kurt. Medical Aromatherapy: Healing With Essen-
tial Oils. Berkeley, CA: Frog Ltd, 1999.
National Association of Holistic Aromatherapy. 836 Hanley
Industrial Court, St. Louis, MO 63144. 888-ASK-NAHA.<http://www.naha.org>.
Paula Ford-MartinArrhythmias
An arrhythmia is an abnormality in the heart’s rhythm,

or heartbeat pattern. The heartbeat can be too slow, too fast,have extra beats, skip a beat, or otherwise beat irregularly.
Arrhythmias are deviations from the normal cadence

of the heartbeat, which cause the heart to pump improp-erly. The normal heartbeat starts in the right atrium,where the heart’s natural pacemaker (the sinus node)sends an electrical signal to the center of the heart to theatrioventricular node. The atrioventricular node thensends signals into the main pumping chamber to makethe ventricle contract. Arrhythmias occur when the heart-beat starts in a part of the heart other than the sinus node,an abnormal rate or rhythm develops in the sinus node,

rate or rhythm develops in the sinus node, ora heart conduction “block” prevents the electrical signalfrom traveling down the normal pathway.

More than four million Americans have arrhythmias,
most of which are harmless. Middle-aged adults common-ly experience arrhythmias. As people age, the probabilityof experiencing an arrhythmia increases. Arrhythmiasoften occur in people who do not have heart disease. Inpeople with heart disease, it is usually the heart diseasewhich is dangerous, not the arrhythmia. Arrhythmias oftenoccur during and after heart attacks. Some types ofarrhythmias, such as ventricular tachycardia , are serious

and even life threatening. In the United States, arrhythmiasare the primary cause of sudden cardiac death , account-
ing for more than 350,000 deaths each year.
Slow heart rates (less than 60 beats per minute) are

called bradycardias, while fast heart rates (more than 100beats per minute) are called tachycardias. Bradycardiacan result in poor circulation of blood, and, hence, a lackof oxygen throughout the body, especially the brain.Tachycardias also can compromise the heart’s ability topump effectively because the ventricles do not haveenough time to completely fill.
Arrhythmias are characterized by their site of origin:

the atria or the ventricles. Supraventricular arrhythmiasoccur in the upper areas of the heart and are less seriousthan ventricular arrhythmias. Ventricular fibrillation is
the most serious arrhythmia and is fatal unless medicalhelp is immediate.
In many cases, the cause of an arrhythmia is
unknown. Known causes of arrhythmias include heart
GALE ENCYCLOPEDIA OF MEDICINE 2 352ArrhythmiasGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 352

disease, stress ,caffeine , tobacco, alcohol, diet pills, and
decongestants in cough and cold medicines.
Symptoms of an arrhythmia include a fast heartbeat,
pounding or fluttering chest sensations, skipping a heart-beat, “flip-flops,” dizziness , faintness, shortness of
breath , and chest pains.
Diagnosis
Examination with a stethoscope, electrocardio-

grams, and electrophysiologic studies is used to diagnosearrhythmias. Sometimes arrhythmias can be identified bylistening to the patient’s heart through a stethoscope, but,since arrhythmias are not always present, they may notoccur during the physical exam.
An electrocardiogram (ECG) shows the heart’s
activity and may reveal a lack of oxygen from poor circu-lation ( ischemia ). Electrodes covered with conducting

jelly are placed on the patient’s chest, arms, and legs.They send impulses of the heart’s activity through anelectrical activity monitor (oscilloscope) to a recorderthat traces them on paper. The test takes about 10 min-utes and is performed in a physician’s office. Anothertype of ECG, commonly known as the exercisestress
test, measures how the heart and blood vessels respond

to exertion while the patient is exercising on a treadmillor a stationary bike. This test is performed in a physi-cian’s office or an exercise laboratory and takes 15-30minutes. Other types of ECGs include 24-hour ECGmonitoring and transtelephonic monitoring. In 24-hourECG (Holter) monitoring, the patient wears a small,portable tape recorder connected to disks on his/her chestthat record the heart’s rhythm during daily activities.Transtelephonic monitoring can identify arrhythmias thatoccur

monitoring can identify arrhythmias thatoccur infrequently. Similar to Holter monitoring ,

transtelephonic monitoring can continue for days orweeks, and it enables patients to send the ECG via tele-phone to a monitoring station when an arrhythmia is felt,or the patient can store the information in the recorderand transmit it later.
Electrophysiologic studies are invasive procedures
performed in a hospital to identify the origin of seriousarrhythmias and responses to various treatments. Theyinvolve cardiac catheterization , in which catheters

tipped with electrodes are passed from a vein in the armor leg through the blood vessels into the heart. The elec-trodes record impulses in the heart, highlighting wherethe arrhythmia starts. During the procedure, physicianscan test the effects of various drugs by provoking anarrhythmia through the electrodes and trying differentdrugs. The procedure takes one to three hours, duringwhich the patient is awake but mildly sedated. Localanesthetic is injected at the catheter insertion

Many arrhythmias do not require any treatment. For
serious arrhythmias, treating the underlying heart diseasesometimes controls the arrhythmia. In some cases, thearrhythmia itself is treated with drugs, electrical shock ( car-
dioversion ), automatic implantable defibrillators, artificial
pacemakers ,catheter ablation , or surgery. Supraventricu-
lar arrhythmias often can be treated with drug therapy. Ven-tricular arrhythmias are more complex to treat.

Drug therapy can manage many arrhythmias, but
finding the right drug and dose requires care and can takesome time. Common drugs for suppressing arrhythmiasinclude beta-blockers, calcium channel blockers , quini-

dine, digitalis preparations, and procainamide. Becauseof their potential serious side effects, stronger, desensi-tizing drugs are used only to treat life-threateningarrhythmias. All of the drugs used to treat arrhythmiashave possible side effects, ranging from mild complica-tions with beta-blockers and calcium channel blockers tomore serious effects of desensitizing drugs that can, para-doxically, cause arrhythmias or make them worse.Response to drugs is usually measured by ECG, Holtermonitor,

drugs is usually measured by ECG, Holtermonitor, or electrophysiologic study.

In emergency situations, cardioversion or defibrilla-
tion (the application of an electrical shock to the chest
wall) is used. Cardioversion restores the heart to its nor-mal rhythm. It is followed by drug therapy to preventrecurrence of the arrhythmia.
Artificial pacemakers that send electrical signals to

make the heart beat properly can be implanted under theskin during a simple operation. Leads from the pacemak-er are anchored to the right side of the heart. Pacemakersare used to correct bradycardia and are sometimes usedafter surgical or catheter ablation.
Automatic implantable defibrillators correct life-

threatening ventricular arrhythmias by recognizing themand then restoring a normal heart rhythm by pacing theheart or giving it an electric shock. They are implantedwithin the chest wall without major surgery and storeinformation for future evaluation by physicians. Auto-matic implantable defibrillators have proven to be moreeffective in saving lives than drugs alone. They often areused in conjunction with drug therapy.
Ablation, a procedure to alter or remove the heart

tissue causing the arrhythmia in order to prevent a recur-rence, can be performed through a catheter or surgery.Supraventricular tachycardia can be treated successfullywith ablation. Catheter ablation is performed in acatheterization laboratory with the patient under seda-
tion. A catheter equipped with a device that maps the
heart’s electrical pathways is inserted into a vein and is
GALE ENCYCLOPEDIA OF MEDICINE 2 353ArrhythmiasGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 353

threaded into the heart. High-frequency radio waves are
then used to remove the pathway(s) causing the arrhyth-mia. Surgical ablation is similar in principle but it is per-formed in a hospital, using a cold probe instead of radiowaves to destroy tissue. Ablation treatments are usedwhen medications fail.
Maze surgery treats atrial fibrillation by making

multiple incisions through the atrium to allow electricalimpulses to move effectively. This is often recommendedfor patients who have not responded to drugs or car-dioversion.
Since some arrhythmias can be life threatening, a
conventional medical doctor should always be consultedfirst. Acupuncture can correct an insignificant number

(1.5%) of atrial fibrillation cases. For new, minor arrhyth-mias, acupuncture may be effective in up to 70% of cases,but this figure may not differ much from placebo therapy.Both western and Chinese herbal remedies are also usedin the treatment of arrhythmias. Since hawthorn ( Cratae-
gus laevigata ) dilates the blood vessels and stimulates the

heart muscle, it may help to stabilize arrhythmias. It isgentle and appropriate for home use, unlike foxglove(Digitalis purpurea ), an herb whose action on the heart is
too potent for use without supervision by a qualified prac-titioner. Homeopathic practitioners may prescribe reme-dies such as Lachesis and aconite or monkshood ( Aconi-
tum napellus ) to treat mild arrhythmias.
Prognosis
Advances in diagnostic techniques, new drugs, and

medical technology have extended the lives of manypatients with serious arrhythmias. Diagnostic techniquesenable physicians to accurately identify arrhythmias,while new drugs, advances in pacemaker technology, thedevelopment of implantable defibrillators, and progressin ablative techniques offer effective treatments for manytypes of arrhythmia.
Some arrhythmias can be prevented by managing

stress, controlling anxiety , and avoiding caffeine, alco-
hol, decongestants, cocaine , and cigarettes.
Resources
BOOKS
American Heart Association. American Heart Association
Guide to Heart Attack Treatment, Recovery, and Preven-tion. New York: Time Books, 1996.
DeBakey, Michael E., and Antonio M. Gotto Jr. “Arrhythmias”
and “Controlling Arrhythmias: Pacemakers, Ablation, andKEY TERMS
Bradycardia —A slow heart rate. Bradycardia is

one of the two types of arrhythmia
Electrocardiogram —A test which uses electric sen-
sors placed on the body to monitor the heartbeat.
Electrophysiology study —A test using cardiac
catheterization to stimulate an electrical current toprovoke an arrhythmia. The test identifies the ori-gin of arrhythmias and is used to test the effective-ness of antiarrhythmic drugs.
Tachycardia —A fast heart rate. Tachycardia is one
of the two types of arrhythmia.

Surgery.” In The New Living Heart. Holbrook, MA:
Adams Media Corporation, 1997.
Notelovitz, Morris, and Diane Tonnessen. “Other Cardiovascu-
lar Conditions.” In The Essential Heart Book for Women.
New York: St. Martin’s Press, 1996.
Texas Heart Institute. “Arrhythmias.” In Texas Heart Institute
Heart Owner’s Handbook. New York: John Wiley & Sons,
1996.

National Heart, Lung and Blood Institute. PO Box 30105,
Texas Heart Institute. Heart Information Service. PO Box 20345,
Houston, TX 77225-0345. <http://www.tmc.edu/thi>.
OTHER
“The Correction of Abnormal Heart Rhythms.” Health World
Online. 3 Mar. 1998 <http://www.health.net/library/books>.
“Implanted Defibrillators Save More Lives Than Drugs.” Mayo

Clinic Online. 26 Feb. 1998. 3 Mar. 1998 <http://www.
mayohealth.org>.
Arterial blood gas analysis seeBlood gas
analysis
Arterial embolism
An embolus is a blood clot, bit of tissue or tumor,
gas bubble, or other foreign body that circulates in theblood stream until it becomes stuck in a blood vessel.
GALE ENCYCLOPEDIA OF MEDICINE 2 354Arterial embolismGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 354

When a blood clot develops in an artery and remains
in place, it is called a thrombosis. If all or part of theblockage breaks away and lodges in another part of theartery, it is called an embolism . Blockage of an artery in
this manner can be the result of a blood clot, fat cells, oran air bubble.
When an embolus blocks the flow of blood in an

artery, the tissues beyond the plug are deprived of normalblood flow and oxygen. This can cause severe damageand even death of the tissues involved.
Emboli can affect any part of the body. The most
common sites are the legs and feet. When the brain isaffected, it is called a stroke . When the heart is involved,
it is called a heart attack or myocardial infarction (MI).
A common cause of embolus is when an artery

whose lining has become thickened or damaged, usuallywith age, allows cholesterol to build up more easily thannormal on the artery wall. If some of the cholesterolbreaks off, it forms an embolus. Emboli also commonlyform from blood clots in a heart that has been damagedfrom heart attack or when the heart contracts abnormallyfrom arterial fibrillation.
Other known causes are fat cells that enter the blood

after a major bone fracture, infected blood cells, cancer
cells that enter the blood stream, and small gas bubbles.
Symptoms of an embolus can begin suddenly or build
slowly over time, depending on the amount of blockedblood flow.
If the embolus is in an arm or leg, there will be mus-
cle pain , numbness or tingling, pale skin color, lower
temperature in the limb, and weakness or loss of musclefunction. If it occurs in an internal organ, there is usuallypain and/or loss of the organ’s function.

Diagnosis
The following tests can be used to confirm the pres-
ence of an arterial embolism:
• Electrocardiogram, also known as an EKG or ECG. For
this test, patches that detect electrical impulses from theheart are attached to the chest and extremities. The infor-mation is displayed on a monitor screen or a paper tapein the form of waves. Reduced blood and oxygen supplyto the heart shows as a change in the shape of the waves.
• Noninvasive vascular tests. These involve measuring

blood pressure in various parts of the body and compar-ing the results from each location. When there is aKEY TERMS
Arterial fibrillation —An arrhythmia; chaotic quiv-
ering of the arteries.
Thrombosis —A blockage in a blood vessel that
builds and remains in one place.
decrease in blood pressure beyond what is normal
between two points, a blockage is presumed to be present.
•Angiography . In this procedure, a colored liquid mate-

rial (a dye, or contrast material) that can be seen with xrays is injected into the blood stream through a smalltube called a catheter. As the dye fills the arteries, theyare easily seen on x ray motion pictures. If there is ablockage in the artery, it shows up as a sudden cut off inthe movement of contrast material. Angiography is anexpensive procedure and does carry some risk. Thecatheter may cause a blood clot to form, blocking bloodflow. There is also the risk of poking the catheterthrough

is also the risk of poking the catheterthrough the artery or heart muscle. Some people maybe allergic to the dye. The risk of any of these injuriesoccurring is small.

Treatment
Arterial embolism can be treated with medication or
surgery, depending on the extent and location of theblockage.
Medication to dissolve the clot is usually given
through a catheter directly into the affected artery. If theembolus was caused by a blood clot, medications thatthin the blood will help reduce the risk of anotherembolism.
A surgeon can remove an embolus by making an

incision in the artery above the blockage and, using acatheter inserted past the embolus, drag it out through theincision.
If the condition is severe, a surgeon may elect to
bypass the blocked vessel by grafting a new vessel in itsplace.
Prognosis
An arterial embolism is serious and should be treat-

ed promptly to avoid permanent damage to the affectedarea. The outcome of any treatment depends on the loca-tion and seriousness of the embolism. New arterialemboli can form even after successful treatment of thefirst event.
GALE ENCYCLOPEDIA OF MEDICINE 2 355Arterial embolismGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 355

Prevention may include diet changes to reduce cho-
lesterol levels, medications to thin the blood, and practic-ing an active, healthy lifestyle.
Resources
BOOKS
McGoon, Michael D., ed. Mayo Clinic Heart Book: The Ulti-
mate Guide to Heart Health. New York: William Morrow
and Co., Inc., 1993.
OTHER
“Arterial Embolism.” HealthAnswers.com. <http://www.heal

thanswers.com>.
Dorothy Elinor Stonely
Arteriogram seeAngiography
Arteriography seeAngiography
Arteriosclerosis seeAtherosclerosis
Arteriovenous fistula
An arteriovenous fistula is an abnormal channel or
passage between an artery and a vein.
An arteriovenous fistula is a disruption of the normal

blood flow pattern. Normally, oxygenated blood flows tothe tissue through arteries and capillaries. Following therelease of oxygen in the tissues, the blood returns to theheart in veins. An arteriovenous fistula is an abnormal con-nection of an artery and a vein. The blood bypasses the cap-illaries and tissues, and returns to the heart. Arterial bloodhas a higher blood pressure than veins and causes swellingof veins involved in a fistula. Although both the artery andthe vein retain their normal

both the artery andthe vein retain their normal connections, the new openingbetween the two will cause some arterial blood to shuntinto the vein because of the blood pressure difference.

There are two types of arteriovenous fistulas, congen-
ital and acquired. A congenital arteriovenous fistula is onethat formed during fetal development. It is a birth defect.KEY TERMS
Congenital —Present at the time of birth.
In congenital fistulas, blood vessels of the lower extremity

are more frequently involved than other areas of the body.Congenital fistulas are not common. An acquired arteri-ovenous fistula is one that develops after a person is born.It usually occurs when an artery and vein that are side-by-side are damaged and the healing process results in thetwo becoming linked. After catheterizations, arteriovenousfistulas may occur as a complication of the arterial punc-ture in the leg or arm. Fistulas also form without apparentcause. In the case of patients on

without apparentcause. In the case of patients on hemodialysis, physiciansperform surgery to create a fistula. These patients receivemany needle sticks to flush their blood through dialysismachines and for routine blood analysis testing. The veinsused may scar and become difficult to use. Surgery is usedto connect an artery and vein so that arterial blood pressureand flow rate widens the vein and decreases the chance ofblood clots forming inside the vein.

The main symptoms of arteriovenous fistulas near
the surface of the skin are bulging and discolored veins.In some cases, the bulging veins can be mistaken forvaricose veins . Other fistulas can cause more serious
problems depending on their location and the blood ves-sels involved.
Diagnosis
Using a stethoscope, a physician can detect the

sound of a pulse in the affected vein (bruit). The sound isa distinctive to-and-fro sound. Dye into the blood can betracked by x ray to confirm the presence of a fistula.
Treatment
Small arteriovenous fistulas can be corrected by

surgery. Fistulas in the brain or eye are very difficult totreat. If surgery is not possible or very difficult, injectiontherapy may be used. Injection therapy is the injection ofsubstances that cause the blood to clot at the site of theinjection. In the case of an arteriovenous fistula, theblood clot should stop the passage of blood from theartery to the vein. Surgery is usually used to correctacquired fistulas once they are diagnosed.
Resources

Resources
BOOKS
GALE ENCYCLOPEDIA OF MEDICINE 2 356Arteriovenous fistulaGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 356

Co., 1997.
Arteriovenous malformations
Arteriovenous malformations are blood vessel

defects that occur before birth when the fetus is growingin the uterus (prenatal development). The blood vesselsappear as a tangled mass of arteries and veins. They donot possess the capillary (very fine blood vessels) bedwhich normally exists in the common area where thearteries and veins lie in close proximity (artery-veininterface). An arteriovenous malformation (A VM) mayhemorrhage, or bleed, leading to serious complicationsthat can be life-threatening.

arteries and veins. Normally, arteries carry oxygenatedblood to the body’s tissues through progressively smallerblood vessels. The smallest are capillaries, which form aweb of blood vessels (the capillary bed) through thebody’s tissues. The arterial blood moves through tissuesby these tiny pathways, exchanging its load of oxygenand nutrients for carbon dioxide and other waste productsproduced by the body cells (cellular wastes). The blood iscarried away by progressively larger blood vessels,

away by progressively larger blood vessels, theveins. A VMs lack a capillary bed and arterial blood ismoved (shunted) directly from the arteries into the veins.

A VMs can occur anywhere in the body and have been
found in the arms, hands, legs, feet, lungs, heart, liver, andkidneys. However, 50% of these malformations are locat-ed in the brain, brainstem, and spinal cord. Owing to thepossibility of hemorrhaging, such A VMs carry the risk ofstroke ,paralysis , and the loss of speech, memory, or
vision. An A VM that hemorrhages can be fatal.
Approximately three of every 100,000 people have a

cerebral A VM and roughly 40-80% of them will experi-ence some bleeding from the abnormal blood vessels atsome point. The annual risk of an A VM bleeding is esti-mated at about 1-4%. After age 55, the risk of bleedingdecreases. Pre-existing high blood pressure or intensephysical activity do not seem to be associated with A VMhemorrhage, but pregnancy and labor could cause a rup-

ture or breaking open of a blood vessel. An A VM hemor-rhage is not as dangerous as an aneurysmal rupture. (Ananeurysm is a swollen, blood filled vessel where thepressure of the blood causes the wall to bulge outward.)There is an approximate 10% fatality rate associated withA VM hemorrhage, compared to a 50% fatality rate forruptured aneurysms.
Although A VMs are congenital defects, meaning a

person is born with them, they are rarely discoveredbefore age 20. A genetic link has been proposed for someA VMs, but studies are only suggestive, not positive. Themajority of A VMs are discovered in people age 20-40.Medical researchers estimate that the malformations arecreated during days 45-60 of fetal development. A sec-ond theory suggests that A VMs are primitive structuresthat are left over from the period when fetal blood circu-lating systems began to develop.

are abnormally fragile. The arteries that feed into themalformation are unusually swollen and thin walled.They lack the usual amount of smooth muscle tissue andelastin, a fibrous connective tissue. These blood vesselscommonly accumulate deposits of calcium salts andhyalin. The venous part of the malformation receivesblood directly from the artery. Without the interveningcapillary bed, the veins receive blood at a higher pressurethan they were designed to handle. This part of the mal-formation

to handle. This part of the mal-formation is also swollen (dilated) and thin walled. Thereis a measurable risk of an aneurysm forming near anA VM, increasing the threat of hemorrhage, brain dam-age, and death . Approximately 10-15% of A VMs are

accompanied by saccular aneurysms, a type of aneurysmthat looks like a small sac attached to the outer wall ofthe blood vessel.
GALE ENCYCLOPEDIA OF MEDICINE 2 357Arteriovenous malformations
Arteriovenous malformations. (Custom Medical Stock Photo.
Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 357

there is often an abnormal proliferation of capillariesnext to the defect. These blood vessels feed into the mal-formation, causing it to grow larger in some cases. As theA VM receives more blood through this “steal,” adjacentbrain tissue does not receive enough. These areas showabnormal nerve cell growth, cell death, and deposits ofcalcium in that area (calcification). Nerve cells within themalformation may demonstrate abnormal growth and arebelieved to be nonfunctional.

Most people do not realize that they have an A VM
unless it hemorrhages enough to produce symptoms.Small A VMs are more likely to hemorrhage. If a hemor-rhage occurs, it produces a sudden, severe headache .

The headache may be focused in one specific area or itmay be more general. It can be mistaken for a migrainein some cases. The headache is accompanied by othersymptoms, such as vomiting, a stiff neck, sleepiness,lethargy, confusion, irritability, or weakness anywhere inthe body. Seizures occur in about a quarter of A VMcases. A person may experience decreased, double, orblurred vision. Hemorrhaging from an A VM is generallyless dangerous than hemorrhaging from an aneurysm,with a survival rate

Other symptoms occur less frequently, but some-
times appear alongside major symptoms such as the sud-den severe headache. Additional warning signs of ableeding A VM are impaired speech or smell, fainting ,
facial paralysis, a drooping eyelid, dizziness , and ringing
or buzzing in the ears.
Although large A VMs are less likely to hemorrhage,

they can induce symptoms based on their mass alone.Large A VMs exert pressure against brain tissue, causeabnormal development in the surrounding brain tissue,and slow down or block blood flow. Hydrocephalus ,a

swelling of brain tissue caused by accumulated fluids,may develop. The warning signs associated with a largenon-bleeding A VM are similar to the symptoms of asmall malformation that is bleeding. Unexplainedheadaches, seizures, dizziness, and neurological symp-toms, such as sensory changes, are signals that demandmedical attention.
Diagnosis
Based on the clinical symptoms such as severe
headache and neurological problems, and after a com-plete neurologic exam , a computed tomography scan

(CT) of the head will be done. In some cases, a whoosh-ing sound from arteries in the neck or over the eye or jaw(called a bruit), can be heard with a stethoscope. The CTscan will reveal whether there has been bleeding in the
brain and can identify A VMs larger than 1 inch (2.5 cm).Magnetic resonance imaging (MRI) is also used to

identify an A VM. A lumbar puncture, or spinal tap, mayfollow the MRI or CT scan. A lumbar puncture involvesremoving a small amount of cerebrospinal fluid from thelower part of the spine. Blood cells or blood breakdownproducts in the cerebrospinal fluid indicate bleeding.
To pinpoint where the blood is coming from, a cere-
bral angiography is done. This procedure uses x rays to

map out the blood vessels in the brain, including the ves-sels that feed into the malformation. The informationgained from angiography complements the MRI andhelps distinguish the precise location of the A VM.
Treatment
Neurosurgeons consider several factors before

deciding on a treatment option. There is some debateover whether or not to treat A VMs that have not rup-tured and are not causing any symptoms. The risks andbenefits of proceeding with treatment need to be mea-sured on an individual basis, taking into account factorssuch as the person’s age and general health, as well asthe A VM’s size and location. Several treatment optionsare available, both for symptomatic or asymptomaticA VMs. These treatment options may be used alone or incombination.

it from causing future problems. Both small and largeA VMs can be handled in surgery. Surgery is recommend-ed for superficial A VMs, but may be too dangerous fordeep or very large A VMs. Unless it is an emergency situ-ation, an A VM that has hemorrhaged is treated conserva-tively for several weeks. Conservative treatment consistsof managing the immediate symptoms and allowing thepatient’s condition to stabilize. Surgery requires generalanesthesia and a longer period of recuperation than

and a longer period of recuperation than anyother treatment option.

Radiation
Radiation is particularly useful to treat small (under

1 in) malformations that are deep within the brain. Ioniz-ing radiation is directed at the malformation, destroyingthe A VM without damaging the surrounding tissue. Radi-ation treatment is accomplished in a single session and itis not necessary to open the skull. However, success canonly be measured over the course of the following twoyears. A year after the procedure, 50-75% of treatedA VMs are completely blocked; two years after radiationtreatment, the percentage increases to 85-95%.

GALE ENCYCLOPEDIA OF MEDICINE 2 358Arteriovenous malformationsGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 358

Embolization
Embolization involves plugging up access to the mal-

formation. This technique does not require opening theskull to expose the brain and can be used to treat deepA VMs. Using x-ray images as a guide, a catheter isthreaded through the artery in the thigh (femoral artery) tothe affected area. The patient remains awake during theprocedure and medications can be administered to pre-vent discomfort. The blood vessel leading into the A VMis assessed for its importance to the rest of the brainbefore a balloon or other blocking agent is inserted via

a balloon or other blocking agent is inserted via thecatheter. The block chokes off the blood supply to themalformation. There may be a mild headache or nauseaassociated with the procedure, but patients may resumenormal activities after leaving the hospital. At least two tothree embolization procedures are usually necessary atintervals of two to six weeks. At least a three-day hospitalstay is associated with each embolization.

and neurological changes may be permanent in another10-30% cases of A VM rupture. If an A VM bleeds once, itis about 20% likely to bleed again in the next year. Astime passes from the initial hemorrhage, the risk for fur-ther bleeding drops to about 3-4%. If the A VM has notbled, it is possible, but not guaranteed, that it never will.Untreated A VMs can grow larger over time and rarely goaway by themselves. Once an A VM is removed and a per-KEY TERMS

Aneurysm —A weak point in a blood vessel where
the pressure of the blood causes the vessel wall tobulge outwards.
Angiography —A mapping of the brain’s blood
vessels, using x-ray imaging.
Capillary bed —A dense network of tiny blood ves-
sels that enables blood to fill a tissue or organ.
Hydrocephalus —Swelling of the brain caused by
an accumulation of fluid.
Lumbar puncture —A diagnostic procedure in

which a needle is inserted into the lower spine towithdraw a small amount of cerebrospinal fluid.This fluid is examined to assess trauma to the brain.
Saccular aneurysm —A type of aneurysm that
resembles a small sack of blood attached to theouter surface of a blood vessel by a thin neck.son has recovered from the procedure, there should be no
further symptoms associated with that malformation.
Resources
BOOKS

Resources
BOOKS
Camarate, P. J., and R. C. Heros. “Arteriovenous Malforma-
tions of the Brain.” In Neurological Surgery. V ol. 2.
Philadelphia: W. B. Saunders Co., 1996.
Henning, Mast. “Risk of Spontaneous Hemorrhage after Diag-
nosis of Cerebral Arteriovenous Malformation.” The
Lancet 350 (11 Oct. 1997): 1065.
American Chronic Pain Association. PO Box 850, Rocklin, CA
95677-0850. (916) 632-0922. <http://members.tripod.com/~widdy/ACPA.html>.

Arteriovenous Malformation Support Group. 168 Six Mile
Canyon Road, Dayton, NV 89403. (702) 246-0682.
National Chronic Pain Outreach Association, Inc. P.O. Box
274, Millboro, V A 24460. (540) 997-5004.
Arthritis seeJuvenile arthritis;
Osteoarthritis; Psoriatic arthritis;Rheumatoid arthritis
Arthrocentesis seeJoint fluid analysis
Arthrogram seeArthrography
Arthrography
Arthrograpy is a procedure involving multiple x rays of

a joint using a fluoroscope, or a special piece of x-ray equip-ment which shows an immediate x-ray image. A contrastmedium (in this case, a contrast iodine solution) injectedinto the joint area helps highlight structures of the joint.
Purpose
Frequently, arthrography is ordered to determine the
cause of unexplained joint pain . This fluoroscopic proce-

dure can show the internal workings of specific jointsand outline soft tissue structures. The procedure mayalso be conducted to identify problems with the liga-ments, cartilage, tendons, or the joint capsule of the hip,shoulder, knee, ankle or wrist. An arthrography proce-dure may locate cysts in the joint area, evaluate problemswith the joint’s arrangement and function, or indicate the
GALE ENCYCLOPEDIA OF MEDICINE 2 359ArthrographyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 359

need for joint replacement (prostheses). The most com-
monly studied joints are the knee and shoulder.
Patients who are pregnant or may be pregnant
should not have this procedure unless the benefits of thefindings outweigh the risk of radiation exposure. Patientswho are known to be allergic to iodine need to discussthis complication with their physician. Patients who havea known allergy to shellfish are more likely to be allergicto iodine contrast.

Arthrograpy may be referred to as “joint radiography”

or “x rays of the joint.” The term arthrogram may be usedinterchangeably with arthrography. The joint area will becleaned and a local anesthetic will be injected into the tis-sues around the joint to reduce pain. Next, if fluids are pre-sent in the joint, the physician may suction them out (aspi-rate) with a needle. These fluids may be sent to a laborato-ry for further study. Contrast agents are then injected intothe joint through the same location by attaching the aspi-rating needle to a

location by attaching the aspi-rating needle to a syringe containing the contrast medium.The purpose of contrast agents in x-ray procedures is tohelp highlight details of areas under study by making themopaque. Agents for arthrography are generally air andwater-soluble dyes, the most common containing iodine.Air and iodine may be used together or independently.After the contrast agent is administered, the site of injec-tion will be sealed and the patient may be asked to movethe joint around to

patient may be asked to movethe joint around to distribute the contrast.

Before the contrast medium can be absorbed by the
joint itself, several films will be quickly taken under theguidance of the fluoroscope. The patient will be asked tomove the joint into a series of positions, keeping still

between positioning. Sometimes, the patient will experiencesome tingling or discomfort during the procedure, which isnormal and due to the contrast. Following fluoroscopictracking of the contrast, standard x rays of the area may alsobe taken. The entire procedure will last about one hour.
It is important to discuss any known sensitivity to

local anesthetics or iodine prior to this procedure. Aphysician should explain the procedure and the risksassociated with contrast agents and ask the patient to signan informed consent. If iodine contrast will be adminis-tered, the patient may be instructed not to eat before theexam. The timeframe of fasting may extend from only
90 minutes prior to the exam up to the night before.There is no other preparation necessary.
Aftercare
The affected joint should be rested for approximate-

ly 12 hours following the procedure. The joint may bewrapped in an elastic bandage and the patient shouldreceive instructions on the care and changing of the ban-dage. Noises in the joint such as cracking or clicking arenormal for a few days following arthrography. Thesenoises are the result of liquid in the joints. Swelling mayalso occur and can be treated with application of ice orcold packs. A mild pain reliever can be used to lessenpain in the first few days. However, if any of these

in the first few days. However, if any of these symp-toms persist for more than a few days, patients areadvised to contact their physician.

Risks
In some patients iodine can cause allergic reactions,
ranging from mild nausea to severe cardiovascular ornervous system complications. Since the contrast dye isput into a joint, rather than into a vein, allergic reactionsare rare. Facilities licensed to perform contrast examsshould meet requirements for equipment, supplies andstaff training to handle a possible severe reaction. Infec-tion or joint damage are possible, although not frequent,complications of arthrography.

A normal arthrography exam will show proper
placement of the dye or contrast medium throughout thejoint structures, joint space, cartilage and ligaments.
The abnormal placement of dye may indicate
rheumatoid arthritis , cysts, joint dislocation, rupture of
GALE ENCYCLOPEDIA OF MEDICINE 2 360Arthrography
An x-ray image of the knees of a patient with cysts caused

by rheumatoid arthritis.The cysts appear as dark areas justbelow the knee joints. (Custom Medical Stock Photo. Repro-
duced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 360

the rotator cuff, tears in the ligament and other condi-
tions. The entire lining of the joint becomes opaque fromthe technique, which allows the radiologist to see abnor-malities in the intricate workings of the joint. In the caseof recurrent shoulder dislocations, arthrography resultscan be used to evaluate damage. Patients with hip pros-theses may receive arthrography to evaluate properplacement or function of their prostheses.
Resources
BOOKS

Resources
BOOKS
Juhl, John H., and Andrew B. Crummy. Paul and Juhl’s Essen-
tials of Radiologic Imaging. Philadelphia: J. B. Lippincott
Co., 1993.
American College of Radiology. 1891 Preston White Drive,
Reston, V A 22091. (800) 227-5463. <http://www.acr.org>.
Teresa Norris, RN
Arthroplasty
Arthroplasty is surgery to relieve pain and restore

range of motion by realigning or reconstructing a joint.KEY TERMS
Aspirate —Remove fluids by suction, often through
a needle.
Contrast (agent, medium) —A substance injected
into the body that illuminates certain structuresthat would otherwise be hard to see on the radi-ograph(film).
Fluoroscope —A device used in some radiology
procedures that provides immediate images andmotion on a screen much like those seen at airportbaggage security stations.

Radiologist —A medical doctor specially trained in
radiology (x ray) interpretation and its use in thediagnosis of diseases and injuries.
X ray —A form of electromagnetic radiation with
shorter wavelengths than normal light. X rays canpenetrate most structures.Purpose
The goal of arthroplasty is to restore the function of a

stiffened joint and relieve pain. Two types of arthroplasticsurgery exist. Joint resection involves removing a portionof the bone from a stiffened joint, creating a gap betweenthe bone and the socket, to improve the range of motion.Scar tissue eventually fills the gap. Pain is relieved andmotion is restored, but the joint is less stable.
Interpositional reconstruction is surgery to reshape

the joint and add a prosthetic disk between the two bonesforming the joint. The prosthesis can be made of plasticand metal or from body tissue such as fascia and skin.When interpositional reconstruction fails, total joint
replacement may be necessary. Joint replacement is also
called total joint arthroplasty.
In recent years, joint replacement has become the oper-

ation of choice for most knee and hip problems. Elbow,shoulder, ankle, and finger joints are more likely to be treat-ed with joint resection or interpositional reconstruction.
Arthroplasty is performed on people suffering from
severe pain and disabling joint stiffness that result fromosteoarthritis or rheumatoid arthritis . Joint resection,

rather than joint replacement, is more likely to be per-formed on people with rheumatoid arthritis, especiallywhen the elbow joint is involved. Total joint replacementis usually reserved for people over the age of 60.
If both the bone and socket of a joint are damaged,
joint replacement is usually the preferred treatment.
Arthroplasty is performed under general or regional

anesthesia in a hospital, by an orthopedic surgeon. Cer-tain medical centers specialize in joint surgery and tendto have higher success rates than less specialized centers.
In joint resection, the surgeon makes an incision at

the joint, then carefully removes minimum amount ofbone necessary to allow free motion. The more bone thatremains, the more stable the joint. Ligament attachmentsare preserved as much as possible. In interpositionalreconstruction, both bones of the joint are reshaped, anda disk of material is placed between the bones to preventtheir rubbing together. Length of hospital stay dependson which joint is treated, but is normally only a few days.

Prior to arthroplasty, all the standard preoperative
blood and urine tests are performed. The patient meets
GALE ENCYCLOPEDIA OF MEDICINE 2 361ArthroplastyGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 361

with the anesthesiologist to discuss any special condi-
tions that affect the administration of anesthesia.
Aftercare
Patients who have undergone arthroplasty must be
careful not to over stress or destabilize the joint. Physical
therapy is begun immediately. Antibiotics are given to
prevent infection.
Risks
Joint resection and interpositional reconstruction do

not always produce successful results, especially inpatients with rheumatoid arthritis. Repeat surgery or totaljoint replacement may be necessary. As with any majorsurgery, there is always a risk of an allergic reaction toanesthesia or that blood clots will break loose andobstruct the arteries.
Most patients recover with improved range of
motion in the joint and relief from pain.
Resources
BOOKS
“Joint Replacement.” In Everything You Need to Know About

Medical Treatments. Springhouse, PA: Springhouse Corp.,
1996.
OTHER
“Darrach’s Procedure.” Wheeless’Textbook of Orthopaedics
Page. <http://www.medmedia.com/ooa1/119.htm>.
Arthroscopic surgery
Arthroscopic surgery is a procedure to visualize,
diagnose, and treat joint problems. The name is derivedKEY TERMS
Fascia —Thin connective tissue covering or sepa-
rating the muscles and internal organs of the body.
Rheumatoid arthritis —A joint disease of unknown

origins that may begin at an early age, causingdeformity and loss of function in the joints.from the Greek words arthron, which means joint, and
skopein, which means to look at.
Purpose
Arthroscopic surgery is used to identify, monitor,

and diagnose joint injuries and disease; or to removebone or cartilage or repair tendons or ligaments. Diag-nostic arthroscopic surgery is performed when medicalhistory, physical exam, x rays, and other tests such asMRIs or CTs don’t provide a definitive diagnosis.
Diagnostic arthroscopic surgery should not be per-
formed unless conservative treatment does not fix theproblem.
In arthroscopic surgery, an orthopedic surgeon uses

an arthroscope, a fiber-optic instrument, to see the insideof a joint. After making an incision about the size of abuttonhole in the patient’s skin, a sterile sodium chloridesolution is injected to distend the joint. The arthroscope,an instrument the size of a pencil, is then inserted into thejoint. The arthroscope has a lens and a lighting systemthrough which the structures inside the joint are transmit-ted to a miniature television camera attached to the endof the arthroscope. The surgeon

to the endof the arthroscope. The surgeon uses irrigation and suc-tion to remove blood and debris from the joint beforeexamining it. Other incisions may be made in order tosee other parts of the joint or to insert additional instru-ments. Looking at the interior of the joint on the televi-sion screen, the surgeon can then determine the amountor type of injury and, if necessary, take a biopsy speci-men or repair or correct the problem. Arthroscopicsurgery can be used to remove floating bits of

can be used to remove floating bits of cartilageand treat minor tears and other disorders. When the pro-cedure is finished, the arthroscope is removed and thejoint is irrigated. The site of the incision is bandaged.

Arthroscopic surgery is used to diagnose and treat
joint problems, most commonly in the knee, but also in theshoulder, elbow, ankle, wrist, and hip. Some of the mostcommon joint problems seen with an arthroscope are:
• inflammation in the knee, shoulder, elbow, wrist, or ankle• injuries to the shoulder (rotator cuff tendon tears,

impingement syndrome, and recurrent dislocations),knee (cartilage tears, wearing down of or injury to thecartilage cushion, and anterior cruciate ligament tearswith instability), and wrist ( carpal tunnel syndrome )
• loose bodies of bone and/or cartilage in the knee, shoul-
der, elbow, ankle, or wrist
GALE ENCYCLOPEDIA OF MEDICINE 2 362Arthroscopic surgeryGEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 362

Corrective arthroscopic surgery is performed with
instruments that are inserted through additional inci-sions. Arthritis can sometimes be treated with arthro-scopic surgery. Some problems are treated with a combi-nation of arthroscopic and standard surgery.
Also called arthroscopy , the procedure is per-

formed in a hospital or outpatient surgical facility. Thetype of anesthesia (local, spinal, or general) and thelength of the procedure depends on the joint operated onand the complexity of the suspected problem. Arthro-scopic surgery rarely takes more than an hour. Mostpatients who have arthroscopic surgery are released thatsame day; some patients stay in the hospital overnight.
Considered the most important orthopedic develop-

ment in the 20th century, arthroscopic surgery is widelyused. The use of arthroscopic surgery on famous athleteshas been well publicized. It is estimated that 80% oforthopedic surgeons practice arthroscopic surgery.Arthroscopic surgery was initially a diagnostic tool usedprior to open surgery, but as better instruments and tech-niques were developed, it began to be used to actuallytreat a variety of joint problems. New techniques current-ly under development are likely to lead to other

under development are likely to lead to other jointsbeing treated with arthroscopic surgery in the future.

Recently, lasers were introduced in arthroscopic surgeryand other new energy sources are being explored. Lasersand electromagnetic radiation can repair rather than resectinjuries and may be more cost effective than instruments.
Before the procedure, blood and urine studies and x
rays of the joint will be conducted.
Aftercare
Immediately after the procedure, the patient will

spend several hours in the recovery room. An ice packwill be put on the joint that was operated on for up to 48hours after the procedure. Pain medicine, prescription or

non-prescription, will be given. The morning after thesurgery, the dressing can be removed and replaced byadhesive strips. The patient should call his/her doctorupon experiencing an increase in pain, swelling, redness,drainage or bleeding at the site of the surgery, signs ofinfection ( headache , muscle aches, dizziness ,fever ), or
nausea or vomiting.
GALE ENCYCLOPEDIA OF MEDICINE 2 363Arthroscopic surgery
CameraTelescope

An arthroscope uses optical fibers to form an image of the damged cartilage, which it sends to a television monitor that
helps the surgeon perform surgery. (Illustration by Argosy Inc.)GEM - 0001 to 0432 - A  10/22/03 1:42 PM  Page 363

It takes several days for the puncture wounds to
heal, and several weeks for the joint to fully recover.Many patients can resume their daily activities, includinggoing back to work, within a few days of the procedure.A rehabilitation program, including physical therapy,
may be suggested to speed recovery and improve thefuture functioning of the joint.
Risks
Complications are rare in arthroscopic surgery,

occurring in less than 1% of patients. These includeinfection and inflammation, blood vessel clots, damageto blood vessels or nerves, and instrument breakage.
Resources
BOOKS
Andrews, James R, and Laura A. Timmerman. Diagnostic and
Operative Arthroscopy. Philadelphia: W. B. Saunders Co.,
1997.
Brillhart, Allen T., ed. Arthroscoic Laser Surgery: Clinical
Applications. New York: Springer-Verlag, 1995.

Oxford Medical Publications. Oxford Textbook of Sports Medi-
cine. New York: Oxford Medical Publications, 1994.
“Arthroscopic Knee Surgery.” Harvard Women’s Health Watch
4 (Dec. 1996): 4.
Pierce, Michael W. “Arthroscopic Surgery.” Scientific Ameri-
can276 (Feb. 1997): 108.
“Should You Be Scoped?” Prevention (Aug. 1997): 82.
Wilkinson, Todd. “Pop, Crackle, Snap.” Women’s Sports & Fit-
ness (Apr. 1998): 68.
OTHER

OTHER
“Arthroscopy.” American Academy of Orthopaedic Surgeons.
15 Apr. 1998. <http://www.aos.org/ wordhtml/pat_educ/arthrosc.htm>.KEY TERMS
Joint—The point where bones meet. Arthroscopic
surgery is used on joint problems.
Laser —A device that concentrates electromagnet-
ic radiation into a narrow beam and treats tissuequickly without heating surrounding areas.
Orthopedics —The medical specialty that deals

with preserving, restoring, and developing formand function in the extremities, spine, and otherstructures using medical, surgical, and physicalmethods. Arthroscopic surgery is performed byorthopedic surgeons.“Arthroscopy.” ThriveOnline. 15 Apr. 1998. <http://thrive
“Knee Arthroscopy.” The Center for Orthopaedics and Sports
Medicine. 15 Apr. 1998. <http://www.arthro scopy.com/spo4002.htm>.
Arthroscopy

Arthroscopy is the examination of a joint, specifical-
ly, the inside structures. The procedure is performed byinserting a specifically designed illuminated device intothe joint through a small incision. This instrument iscalled an arthroscope. The procedure of arthroscopy isprimarily associated with the process of diagnosis. How-ever, when actual repair is performed, the procedure iscalled arthroscopic surgery .
Purpose

ize in treating disorders of the bones and related structures(orthopedics) to help diagnose joint problems. Oncedescribed as essential for those who primarily care for ath-letic injuries, arthroscopy is now a technique commonlyused by orthopedic surgeons for the treatment of patients ofall ages. This procedure is most commonly used to diagnoseknee and shoulder problems, although the elbow, hip, wrist,and ankle may also be examined with an arthroscope.

A joint is a complex system. Within a joint, ligaments
attach bones to other bones, tendons attach muscles tobones, cartilage lines and helps protect the ends of bones,and a special fluid (synovial fluid) cushions and lubricatesthe structures. Looking inside the joint allows the doctorsto see exactly which structures are damaged. Arthroscopyalso permits earlier diagnosis of many types of joint prob-lems which had been difficult to detect in previous years.

Most arthroscopic procedures today are performed
in same-day surgery centers where the patient is admittedjust before surgery. A few hours following the procedure,the patient is allowed to return home, although usuallysomeone else must drive. Depending on the type of anes-thesia used, the patient may be told not to eat for severalhours before arriving. Before the procedure, the anesthe-siologist will ask if the patient has any known allergies

to local or general anesthetics. Airway obstruction isalways possible in any patient who receives a general
GALE ENCYCLOPEDIA OF MEDICINE 2 364ArthroscopyGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 364

anesthesia. Because of this, oxygen, suction, and moni-
toring equipment must be available. The patient’s cardiacstatus should always be monitored in the event that anycardiac abnormalities arise during the arthroscopy.
The arthroscope is an instrument used to look direct-

ly into the joint. It contains magnifying lenses and glass-coated fibers that send concentrated light into the joint. Acamera attached to the arthroscope allows the surgeon tosee a clear image of the joint. This image is then trans-ferred to a monitor located in the operating room at thetime of the arthroscopy. This video technology is alsoimportant for documentation of the arthroscopic proce-dure. For example, if the surgeon decides after the arthro-scopic examination that a conventional

the arthro-scopic examination that a conventional approach to sur-gically expose or “open” the joint (arthrotomy) must beused, a good photographic record will be useful when thesurgeon returns to execute the final surgical plan.The procedure requires the surgeon to make several

small incisions (portals) through the skin’s surface intothe joint. Through one or two of the portals, a large-boreneedle, called a cannula, is attached to tubing and insertedinto the joint. The joint is inflated with a sterile salinesolution to expand the joint and ensure clear arthroscopicviewing. Often, following a recent traumatic injury to ajoint, the joint’s natural fluid may be cloudy, making inte-rior viewing of the joint difficult. In this condition, a con-stant flow of the saline

In this condition, a con-stant flow of the saline solution is necessary. This inflowof saline solution may be through the cannula with theoutflow through the arthroscope, or the positions may bereversed. The arthroscope is placed through one of theportals to view and evaluate the condition of the joint.

Before an arthroscopy can take place, the surgeon
completes a thorough medical history and evaluation.Important for the accuracy of this diagnostic procedure, a
GALE ENCYCLOPEDIA OF MEDICINE 2 365Arthroscopy
Arthroscope
Superolateral Superomedial
Common entry sites for the arthroscopeInferomedial
CentralMedial Lateral
Inferolateral
Arthroscopy is primarily used to help diagnose joint problems.This procedure, most commonly associated with knee and

shoulder problems, allows accurate examination and diagnosis of damaged joint ligaments, surfaces, and other related jointstructures.The illustration above indicates the most common entry sites, or portals, in knee arthroscopy. (Illustration by Elec-
tronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 365

medical history and evaluation may discover other disor-
ders of the joint or body parts, proving the procedureunnecessary. This is always an important preliminary step,because pain can often be referred to a joint from another
area of the body. Anatomical models and pictures are use-ful aids to explain to the patient the proposed arthroscopyand what the surgeon may be looking at specifically.
Proper draping of the body part is important to pre-

vent contamination from instruments used in arthroscopy,such as the camera, light cords, and inflow and outflowdrains placed in the portals. Draping packs used inarthroscopy include disposable paper gowns and drapeswith adhesive backing. The surgeon may also place atourniquet above the joint to temporarily block blood flowto the area during the arthroscopic exam.
General or local anesthesia may be used during

arthroscopy. Local anesthesia is usually used because itreduces the risk of lung and heart complications andallows the patient to go home sooner. The local anesthet-ic may be injected in small amounts in multiple locationsin skin and joint tissues in a process called infiltration. Inother cases, the anesthetic is injected into the spinal cordor a main nerve supplying the area. This process is calleda “block,” and it blocks all sensation below the maintrunk of the nerve. For example, a femoral

maintrunk of the nerve. For example, a femoral block anes-thetizes the leg from the thigh down (its name comesfrom femur, the thighbone). Most patients are comfort-able once the skin, muscles, and other tissues around thejoint are numbed by the anesthetic; however, somepatients are also given a sedative if they express anxiety

about the procedure. (It’s important for the patient toremain still during the arthroscopic examination.)
General anesthesia, in which the patient becomes
unconcious, may be used if the procedure may be unusu-ally complicated or painful. For example, people whohave relatively “tight” joints may be candidates for gen-eral anesthesia because the procedure may take longerand cause more discomfort.
Aftercare
The portals are closed by small tape strips or stitches

and covered with dressings and a bandage. The patientspends a short amount of time in the recovery room afterarthroscopy. Most patients can go home after about anhour in the recovery room. Pain medication may be pre-scribed for a short period; however, many patients findvarious over-the-counter pain relievers sufficient.
Following the surgical procedure, the patient needs

to be aware of the signs of infection, which include red-ness, warmth, excessive pain, and swelling. The risk ofinfection increases if the incisions become wet too earlyfollowing surgery. Because of this, it is good practice to
cover the joint with plastic (for example, a plastic bag)while showering after arthroscopy.
The use of crutches is commonplace after arthro-
scopy, with progression to independent walking on an “astolerated” basis by the patient. Generally, a rehabilitation

program, supervised by a physical therapist, follows short-ly after the arthroscopy to help the patient regain mobilityand strength of the affected joint and limb.
Risks
The incidence of complications is low compared to
the high number of arthroscopic procedures performedevery year. Possible complications include infection,swelling, damage to the tissues in the joint, blood clots inthe leg veins ( thrombophlebitis ), leakage of blood into

the joint (hemarthrosis), blood clots that move to the lung(pulmonary embolus), and injury to the nerves aroundthe joint.
The goal of arthroscopy is to diagnose a joint prob-

lem causing pain and/or restrictions in normal joint func-tion. For example, arthroscopy can be a useful tool inlocating a tear in the joint surface of the knee or locatinga torn ligament of the shoulder. Arthroscopic examina-tion is often followed by arthroscopic surgery performedto repair the problem with appropriate arthroscopic tools.The final result is to decrease pain, increase joint mobili-ty, and thereby improve the overall quality of thepatient’s activities of daily living.

Less optimal results that may require further treat-
ment include adhesive capsulitis. In this condition, thejoint capsule that naturally forms around the jointbecomes thickened, forming adhesions. This results in astiff and less mobile joint. This problem is frequentlycorrected by manipulation and mobilization of the jointwith the patient placed under general anesthesia.
Resources
BOOKS
Casscells, Ward S. Arthroscopy: Diagnostic and Surgical Prac-

tice. Philadelphia: Lea and Febiger, 1984.
McGinty, John B. “Complications of Arthroscopy and Arthro-
scopic Surgery.” In Arthroscopic Surgery , ed. Serge J.
Parisien. New York: McGraw Hill, 1988.
Parisien, Serge J., and Dzenis Peteris. “Development of Mod-
ern Arthroscopic Techniques, Fundamentals of Endo-scopes, Basic Equipment for Diagnosis of Surgery.” In
GALE ENCYCLOPEDIA OF MEDICINE 2 366ArthroscopyGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 366

Arthroscopic Surgery , ed. Serge J. Parisien. New York:
McGraw Hill, 1988.
Scott, Norman W. Arthroscopy of the Knee. Philadelphia: W. B.
Saunders Co., 1990.
Smith, Genevieve L., and Phyllis E. Davis. Medical Terminolo-
gy: A Programmed Text. New York: John Wiley and Sons,
Inc., 1988.
Glassman, Scott. “Advances in Treating Shoulder Injuries.”
Advanced Magazine for Physical Therapists , Dec. 1997,
10-12.
Mattson, Patricia, and Thomas Moore. “Preoperative and Post-

operative Management of Lower Extremity Surgery.”Orthopaedic Physical Therapy Clinics of North America(Mar. 1993): 87-92.
Artificial insemination seeInfertility
therapies
Art therapy
Art therapy, sometimes called creative arts therapy
or expressive arts therapy, encourages people to expressand understand emotions through artistic expression andthrough the creative process.
Purpose
Art therapy provides the client-artist with critical

insight into emotions, thoughts, and feelings. Key bene-fits of the art therapy process include:
• Self-discovery. At its most successful, art therapy trig-
gers an emotional catharsis.KEY TERMS
Hemarthrosis —A condition of blood within a
joint.
Pulmonary embolus —Blockage of an artery of the
lung by foreign matter such as fat, tumor, tissue, ora clot originating from a vein.
Thrombophlebitis —Inflamation of a vein with the

formation of a thrombus or clot.• Personal fulfillment. The creation of a tangible reward
can build confidence and nurture feelings of self-worth.Personal fulfillment comes from both the creative andthe analytical components of the artistic process.
• Empowerment. Art therapy can help people visually
express emotions and fears that they cannot expressthrough conventional means, and can give them somesense of control over these feelings.

• Relaxation and stress relief. Chronic stress can be
harmful to both mind and body. Stress can weaken anddamage the immune system, can cause insomnia and
depression, and can trigger circulatory problems (likehigh blood pressure and irregular heartbeats). Whenused alone or in combination with other relaxationtechniques such as guided imagery , art therapy can
effectively relieve stress.
• Symptom relief and physical rehabilitation . Art thera-

py can also help patients cope with pain . This therapy
can promote physiological healing when patients iden-tify and work through anger, resentment, and otheremotional stressors. It is often prescribed to accompanypain control therapy for chronically and terminally illpatients.
Origins
Humans have expressed themselves with symbols

throughout history. Masks, ritual pottery, costumes, otherobjects used in rituals, cave drawings, Egyptian hiero-glyphics, and Celtic art and symbols are all visualrecords of self-expression and communication throughart. Art has also been associated spiritual power, andartistic forms such as the Hindu and Buddhist mandalaand Native American sand painting are considered pow-erful healing tools.
In the late nineteenth century, French psychiatrists

Ambrose Tardieu and Paul-Max Simon both publishedstudies on the similar characteristics of and symbolism inthe artwork of the mentally ill. Tardieu and Simonviewed art therapy as an effective diagnostic tool to iden-tify specific types of mental illness or traumatic events.Later, psychologists would use this diagnostic aspect todevelop psychological drawing tests (the Draw-A-Mantest, the Draw-A-Person Questionnaire [DAP.Q]) andprojective personality tests involving visual symbolrecognition

tests involving visual symbolrecognition (e.g., the Rorschach Inkblot Test, the The-

matic Apperception Test [TAT], and the Holtzman
Inkblot Test [HIT]).
The growing popularity of milieu therapies at psy-
chiatric institutions in the twentieth century was animportant factor in the development of art therapy in the
GALE ENCYCLOPEDIA OF MEDICINE 2 367Art therapyGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 367

United States. Milieu therapies (or environmental thera-
py) focus on putting the patient in a controlled therapeu-tic social setting that provides the patient with opportuni-ties to gain self-confidence and interact with peers in apositive way. Activities that encourage self-discoveryand empowerment such as art, music, dance, and writingare important components of this approach.
Educator and therapist Margaret Naumburg was a

follower of both Freud and Jung, and incorporated art intopsychotherapy as a means for her patients to visualize andrecognize the unconscious. She founded the WaldenSchool in 1915, where she used students’ artworks in psy-chological counseling. She published extensively on thesubject and taught seminars on the technique at New YorkUniversity in the 1950s. Today, she is considered thefounder of art therapy in the United States.

In the 1930s, Karl, William, and Charles Menninger
introduced an art therapy program at their Kansas-basedpsychiatric hospital, the Menninger Clinic. The Men-ninger Clinic employed a number of artists in residencein the following years, and the facility was also consid-ered a leader in the art therapy movement through the1950s and 60s. Other noted art therapy pioneers whoemerged in the 50s and 60s include Edith Kramer, HannaYaxa Kwiatkowska (National Institute of Mental Health),and Janie Rhyne.

psychology, encourages self-discovery and emotionalgrowth. It is a two part process, involving both the cre-ation of art and the discovery of its meaning. Rooted inFreud and Jung’s theories of the subconscious andunconscious, art therapy is based on the assumption thatvisual symbols and images are the most accessible andnatural form of communication to the human experience.Patients are encouraged to visualize, and then create, thethoughts and emotions that they cannot talk about. Theresulting

that they cannot talk about. Theresulting artwork is then reviewed and its meaning inter-preted by the patient.

The “analysis” of the artwork produced in art thera-
py typically allows patients to gain some level of insightinto their feelings and lets them to work through theseissues in a constructive manner. Art therapy is typicallypracticed with individual, group, or family psychothera-py (talk therapy). While a therapist may provide criticalguidance for these activities, a key feature of effective arttherapy is that the patient/artist, not the therapist, directsthe interpretation of the artwork.

Art therapy can be a particularly useful treatment
tool for children, who frequently have limited languageskills. By drawing or using other visual means to expresstroublesome feelings, younger patients can begin toaddress these issues, even if they cannot identify or labelthese emotions with words. Art therapy is also valuable
for adolescents and adults who are unable or unwilling totalk about thoughts and feelings.
Beyond its use in mental health treatment, art thera-

py is also used with traditional medicine to treat organicdiseases and conditions. The connection between mentaland physical health is well documented, and art therapycan promote healing by relieving stress and allowing thepatient to develop coping skills.
Art therapy has traditionally centered on visual

mediums, like paintings, sculptures, and drawings. Somemental healthcare providers have now broadened the def-inition to include music, film, dance, writing, and othertypes of artistic expression.
Art therapy is often one part of a psychiatric inpatient
or outpatient treatment program, and can take place inindividual or group therapy sessions. Group art therapy

sessions often take place in hospital, clinic, shelter, andcommunity program settings. These group therapy ses-sions can have the added benefits of positive social inter-action, empathy, and support from peers. The client-artistcan learn that others have similar concerns and issues.
Before starting art therapy, the therapist may have an

introductory session with the client-artist to discuss arttherapy techniques and give the client the opportunity toask questions about the process. The client-artist’s comfortwith the artistic process is critical to successful art therapy.
The therapist ensures that appropriate materials and

space are available for the client-artist, as well as an ade-quate amount of time for the session. If the individualartist is exploring art as therapy without the guidance of atrained therapist, adequate materials, space, and time arestill important factors in a successful creative experience.
The supplies used in art therapy are limited only by

the artist’s (and/or therapist’s) imagination. Some of thematerials often used include paper, canvas, poster board,assorted paints, inks, markers, pencils, charcoals, chalks,fabrics, string, adhesives, clay, wood, glazes, wire, bend-able metals, and natural items (like shells, leaves, etc.).Providing artists with a variety of materials in assortedcolors and textures can enhance their interest in theprocess and may result in a richer, more diverse explo-ration of their emotions in the resulting

explo-ration of their emotions in the resulting artwork. Appro-priate tools such as scissors, brushes, erasers, easels, sup-ply trays, glue guns, smocks or aprons, and cleaningmaterials are also essential.

An appropriate workspace should be available for
the creation of art. Ideally, this should be a bright, quiet,comfortable place, with large tables, counters, or other
GALE ENCYCLOPEDIA OF MEDICINE 2 368Art therapyGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 368

suitable surfaces. The space can be as simple as a kitchen
or office table, or as fancy as a specialized artist’s studio.
The artist should have adequate time to become

comfortable with and explore the creative process. Thisis especially true for people who do not consider them-selves “artists” and may be uncomfortable with the con-cept. If performed in a therapy group or one-on-one ses-sion, the art therapist should be available to answer gen-eral questions about materials and/or the creativeprocess. However, the therapist should be careful not toinfluence the creation or interpretation of the work.

Art materials and techniques should match the age
and ability of the client. People with impairments, suchas traumatic brain injury or an organic neurological con-dition, may have difficulties with the self-discovery por-tion of the art therapy process depending on their level offunctioning. However, they may still benefit from arttherapy through the sensory stimulation it provides andthe pleasure they get from artistic creation.

While art is accessible to all (with or without a ther-
apist to guide the process), it may be difficult to tap thefull potential of the interpretive part of art therapy with-out a therapist to guide the process. When art therapy ischosen as a therapeutic tool to cope with a physical con-dition, it should be treated as a supplemental therapy andnot as a substitute for conventional medical treatments.
A wide body of literature supports the use of art

therapy in a mental health capacity. And as the mind-body connection between psychological well-being andphysical health is further documented by studies in thefield, art therapy gains greater acceptance by mainstreammedicine as a therapeutic technique for organic illness.
Resources
BOOKS
Fausek, Diane. A Practical Guide to Art Therapy. Binghamton,
New York: Haworth Press, 1997.
Ganim, Barbara. Art and Healing: Using expressive art to heal

your body, mind, and spirit. New York: Three Rivers
Press, 1999.
Malchiodi, Cathy A. The Art Therapy Sourcebook. Los Ange-
les: Lowell House, 1998.
McNiff, Shaun. Art as Medicine: Creating a Therapy of the
Imagination. Boston: Shambhala, 1992.
American Art Therapy Association.1202 Allanson Rd.,
Mundelein, IL 60060-3808. 888-290-0878 or 847-949-KEY TERMS
Catharsis —Therapeutic discharge of emotional
tension by recalling past events.
Mandala —A design, usually circular, that appears

in religion and art. In Buddhism and Hinduism,the mandala has religious ritual purposes andserves as a yantra (a geometric emblem or instru-ment of contemplation).
Organic illness —A physically, biologically based
illness.
6064. Fax: 847-566-4580. arttherapy@ntr.net. <http://
www.arttherapy.org>.
Asbestosis
Asbestosis is chronic, progressive inflammation of
the lung. It is not contagious.

Asbestosis is a consequence of prolonged exposure
to large quantities of asbestos, a material once widelyused in construction, insulation, and manufacturing.When asbestos is inhaled, fibers penetrate the breathingpassages and irritate, fill, inflame, and scar lung tissue. Inadvanced asbestosis,, the lungs shrink, stiffen, andbecome honeycombed (riddled with tiny holes).
Legislation has reduced use of asbestos in the United

States, but workers who handle automobile brake shoelinings, boiler insulation, ceiling acoustic tiles, electricalequipment, and fire-resistant materials are still exposedto the substance. Asbestos is used in the production ofpaints and plastics. Significant amounts can be releasedinto the atmosphere when old buildings or boats arerazed or remodeled.
Asbestosis is most common in men over 40 who

have worked in asbestos-related occupations. Smokers orheavy drinkers have the greatest risk of developing thisdisease. Between 1968 and 1992, more than 10,000Americans over the age of 15 died as a result of asbesto-sis. Nearly 25% of those who died lived in California or
GALE ENCYCLOPEDIA OF MEDICINE 2 369AsbestosisGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 369

New Jersey, and most of them had worked in the con-
struction or shipbuilding trades.
Occupational exposure is the most common cause of
asbestosis, but the condition also strikes people whoinhale asbestos fiber or who are exposed to waste prod-ucts from plants near their homes. Family members candevelop the disease as a result of inhaling particles ofasbestos dust that cling to workers’ clothes.
It is rare for asbestosis to develop in anyone who

hasn’t been exposed to large amounts of asbestos on aregular basis for at least 10 years. Symptoms of the dis-ease do not usually appear until 15–20 years after initialexposure to asbestos.
The first symptom of asbestosis is usually shortness
of breath following exercise or other physical activity.
The early stages of the disease are also characterized by adry cough and a generalized feeling of illness.
As the disease progresses and lung damage increas-

es, shortness of breath occurs even when the patient is atrest. Recurrent respiratory infections and coughing upblood are common. So is swelling of the feet, ankles, orhands. Other symptoms of advanced asbestosis includechest pain , hoarseness, and restless sleep. Patients who
have asbestosis often have clubbed (widened and thick-ened) fingers. Other potential complications includeheart failure , collapsed (deflated) lung, and pleurisy
(inflammation of the membrane that protects the lung).

Diagnosis
Screening of at-risk workers can reveal lung inflamma-
tion and lesions characteristic of asbestosis. Patients’ med-ical histories can identify occupations, hobbies, or other sit-
uations likely to involve exposure to asbestos fibers.
X rays can show shadows or spots on the lungs or an

indistinct or shaggy outline of the heart that suggests thepresence of asbestosis. Blood tests are used to measureconcentrations of oxygen and carbon dioxide. Pulmonaryfunction tests can be used to assess a patient’s ability toinhale and exhale, and a computed tomography scan(CT) of the lungs can show flat, raised patches associatedwith advanced asbestosis.
Treatment
The goal of treatment is to help patients breathe

more easily, prevent colds and other respiratory infec-tions, and control complications associated withadvanced disease. Ultrasonic, cool-mist humidifiers orcontrolled coughing can loosen bronchial secretions.
Regular exercise helps maintain and improve lung
capacity. Although temporary bed rest may be recom-mended, patients are encouraged to resume their regularactivities as soon as they can.
Antibiotics may be prescribed to combat infection.

Aspirin or acetominophen (Tylenol) can relieve minor
discomfort and bronchodilators that are swallowed or
inhaled can relax and widen breathing passages.
Diuretics (drugs that increase urine production and
excretion) or digitalis glycoside ( Digitalis purpurea ) are
prescribed for some patients. Others may need to usesupplemental oxygen or use less salt.
Anyone who develops symptoms of asbestosis

should see a family physician or lung disease specialist.A doctor should be notified if someone who has beendiagnosed with asbestosis:
• coughs up blood
• continues to lose weight
• is short of breath• has chest pain• develops a sudden fever of 101°F (38.3°C) or higher
• develops unfamiliar, unexplained symptoms
Prognosis
Asbestosis can’t be cured, but its symptoms can be

controlled. Doctors don’t know why the health of somepatients deteriorates and the condition of others remainthe same, but believe the difference may be due to vary-ing exposures of asbestos. People with asbestosis whosmoke, particularly those who smoke more than onepack of cigarettes each day, are at increased risk for
GALE ENCYCLOPEDIA OF MEDICINE 2 370Asbestosis
Micrograph of asbestos fibers embedded in lung tissue.

(Photograph by Dr. E. Walker, Custom Medical Stock Photo.Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 370

developing lung cancer and should be strongly advised
to quit smoking .
Workers in asbestosis-related industries should have
regular x rays to determine whether their lungs arehealthy. A person whose lung x ray shows a shadowshould eliminate asbestos exposure even if no symptomsof the condition have appeared.
Anyone who works with asbestos should wear a pro-

tective mask or a hood with a clean-air supply and obeyrecommended procedures to control asbestos dust. Any-one who is at risk of developing asbestosis should:
• not smoke• be vaccinated against influenza and pneumonia
• exercise regularly to maintain cardiopulmonary fitness• avoid crowds and people who have respiratory infec-
tions
A person who has asbestosis should exercise regu-
larly, relax, and conserve energy whenever necessary.
Resources

Resources
BOOKS
Burton, George G., John E. Hodgkin, and Jeffrey J. Ward, eds.
Respiratory Care: A Guide to Clinical Practice. 4th ed.
Philadelphia: Lippincott, 1997.
Farzan, Sattar. A Concise Handbook of Respiratory Diseases.
4th ed. Stamford: Appleton & Lange, 1997.
American Lung Association. 1740 Broadway, New York, NY
10019. (800) 586-4872. <http://www.lungusa.org>.

OTHER
“Asbestosis.” ThriveOnline. 1 May 1998. <http://thriveonline.
“1996 World Report: Asbestosis Mortality.” Centers for Dis-
ease Control. 1 May 1998. <http://www.cdc.gov/hiosh/w7asbt9.html>.
Maureen HaggertyKEY TERMS
Asbestos —A silicate (containing silica) mineral
that occurs in a variety of forms; it is characterizedby a fibrous structure and resistance to fire.Ascariasis seeRoundworm infections

Ascending cholangitis seeCholangitis
Ascending contrast phlebography see
Venography
Ascites
Ascites is an abnormal accumulation of fluid in the
abdomen.
Rapidly developing (acute) ascites can occur as a
complication of trauma, perforated ulcer, appendicitis ,

or inflammation of the colon or other tube-shaped organ(diverticulitis). This condition can also develop whenintestinal fluids, bile, pancreatic juices, or bacteriainvade or inflame the smooth, transparent membrane thatlines the inside of the abdomen (peritoneum). However,ascites is more often associated with liver disease andother long-lasting (chronic) conditions.
Types of ascites
Cirrhosis , which is responsible for 80% of all

instances of ascites in the United States, triggers a seriesof disease-producing changes that weaken the kidney’sability to excrete sodium in the urine.
Pancreatic ascites develops when a cyst that has
thick, fibrous walls (pseudocyst) bursts and permits pan-creatic juices to enter the abdominal cavity.
Chylous ascites has a milky appearance caused by

lymph that has leaked into the abdominal cavity.Although chylous ascites is sometimes caused by trau-ma, abdominal surgery, tuberculosis , or another peri-
toneal infection, it is usually a symptom of lymphoma orsome other cancer .
Cancer causes 10% of all instances of ascites in the

United States. It is most commonly a consequence of dis-ease that originates in the peritoneum (peritoneal carci-nomatosis) or of cancer that spreads (metastasizes) fromanother part of the body.
Endocrine and renal ascites are rare disorders.
Endocrine ascites, sometimes a symptom of an endocrinesystem disorder, also affects women who are taking fer-tility drugs. Renal ascites develops when blood levels ofalbumin dip below normal. Albumin is the major protein

GALE ENCYCLOPEDIA OF MEDICINE 2 371AscitesGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 371

in blood plasma. It functions to keep fluid inside the
blood vessels.
Causes
The two most important factors in the production of
ascites due to chronic liver disease are:
• Low levels of albumin in the blood that cause a change
in the pressure necessary to prevent fluid exchange(osmotic pressure). This change in pressure allows fluidto seep out of the blood vessels.
• An increase in the pressure within the branches of the

portal vein that run through liver (portal hypertension ).
Portal hypertension is caused by the scarring thatoccurs in cirrhosis. Blood that cannot flow through theliver because of the increased pressure leaks into theabdomen and causes ascites.
Other conditions that contribute to ascites develop-
• hepatitis• heart or kidney failure• inflammation and fibrous hardening of the sac that con-
tains the heart (constrictive pericarditis )Persons who have systemic lupus erythematosus

but do not have liver disease or portal hypertension occa-sionally develop ascites. Depressed thyroid activitysometimes causes pronounced ascites, but inflammationof the pancreas ( pancreatitis ) rarely causes significant
accumulations of fluid.
Symptoms
Small amounts of fluid in the abdomen do not usual-
ly produce symptoms. Massive accumulations may cause:
• rapid weight gain
• abdominal discomfort and distention
• shortness of breath• swollen ankles
Diagnosis

Diagnosis
Skin stretches tightly across an abdomen that con-
tains large amounts of fluid. The navel bulges or lies flat,and the fluid makes a dull sound when the doctor taps theabdomen. Ascitic fluid may cause the flanks to bulge.
Physical examination generally enables doctors to
distinguish ascites from pregnancy , intestinal gas, obe-
sity, or ovarian tumors. Ultrasound or computed tomog-
raphy scans (CT) can detect even small amounts of

fluid. Laboratory analysis of fluid extracted by insertinga needle through the abdominal wall (diagnostic para-
centesis ) can help identify the cause of the accumulation.
Treatment
Reclining minimizes the amount of salt the kidneys
absorb, so treatment generally starts with bed rest and alow-salt diet. Urine-producing drugs ( diuretics ) may be

prescribed if initial treatment is ineffective. The weightand urinary output of patients using diuretics must becarefully monitored for signs of :
• hypovolemia (massive loss of blood or fluid)
• azotemia (abnormally high blood levels of nitrogen-
bearing materials)
• potassium imbalance• high sodium concentration. If the patient consumes
more salt than the kidneys excrete, increased doses ofdiuretics should be prescribed
Moderate-to-severe accumulations of fluid are treat-

ed by draining large amounts of fluid (large-volumeparacentesis) from the patient’s abdomen. This procedureis safer than diuretic therapy. It causes fewer complica-tions and requires a shorter hospital stay.
Large-volume paracentesis is also the preferred
treatment for massive ascites. Diuretics are sometimes
GALE ENCYCLOPEDIA OF MEDICINE 2 372Ascites
A computed tomography (CT) scan of an axial section

through the abdomen, showing ascites. At right is the liveroccupying much of the abdomen; the stomach and spleenare also seen. Around these organs is fluid giving rise tothis condition. (Custom Medical Stock Photo. Reproduced by
permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 372

used to prevent new fluid accumulations, and the proce-
dure may be repeated periodically.
Dietary alterations, focused on reducing salt intake,
should be a part of the treatment. In less severe cases,herbal diuretics like dandelion ( Taraxacum officinale ) can
help eliminate excess fluid and provide potassium. Potas-sium-rich foods like low-fat yogurt, mackerel, cantaloupe,and baked potatoes help balance excess sodium intake.
Prognosis

Prognosis
The prognosis depends upon the condition that is
causing the ascites. Carcinomatous ascites has a very badprognosis. However, salt restriction and diuretics cancontrol ascites caused by liver disease in many cases.
Therapy should also be directed towards the under-
lying disease that produces the ascites. Cirrhosis shouldbe treated by abstinence from alcohol and appropriatediet. The new interferon agents maybe helpful in treatingchronic hepatitis.

Modifying or restricting use of salt can prevent most
cases of recurrent ascites.KEY TERMS
Computed tomography scan (CT) —An imaging
technique in which cross-sectional x rays of thebody are compiled to create a three-dimensionalimage of the body’s internal structures.
Interferon —A protein formed when cells are
exposed to a virus. Interferon causes other nonin-fected cells to develop translation inhibitory protein(TIP). TIP blocks viruses from infecting new cells.

Paracentesis —A procedure in which fluid is
drained from a body cavity by means of a catheterplaced through an incision in the skin.
Systemic lupus erythematosus —An inflammatory
disease that affects many body systems, includingthe skin, blood vessels, kidneys, and nervous sys-tem. It is characterized, in part, by arthritis, skinrash, weakness, and fatigue.
Ultrasonography —A test using sound waves to

measure blood flow. Gel is applied to a hand-heldtransducer that is pressed against the patient’sbody. Images are displayed on a monitor.Resources
BOOKS
tion. Whitehouse Station, NJ: Merck Research Laborato-
ries, 1997.
New Choices in Natural Healing. Ed. Bill Gottlieb, et al.

Emmaus, PA: Rodale Press, 1995.
Jaffe, D. L., R. T. Chung, and L. S. Friedman. “Management of
portal hypertension and its complications.” The Medical
Clinics of North America 80 (1996): 1021-34.
American Liver Foundation. 1425 Pompton Ave., Cedar Grove,
NJ 07009. (800) 223-0179. <http://www.liverfoundation.org>.
OTHER
“Hepatic and Liver Disorders.” The Meck Page. 20 Apr. 1998.
<http://www.merck.com>.
Ascorbic acid deficiency seeScurvy

ASD seeAtrial septal defect
Asian American health seeMinority health
Asian flu seeInfluenza
Aspartate aminotransferase test
The Aspartate aminotransferase test measures levels
of AST, an enzyme released into the blood when certainorgans or tissues, particularly the liver and heart, areinjured. Aspartate aminotransferase (AST) is also knownas serum glutamic oxaloacetic transaminase (SGOT).
Purpose
The determination of AST levels aids primarily in

the diagnosis of liver disease. In the past, the AST testwas used to diagnose heart attack (myocardial infarc-
tion or MI) but more accurate blood tests have largelyreplaced it for cardiac purposes.
AST is determined by analysis of a blood sample,
usually from taken from a venipuncture site at the bendof the elbow.
GALE ENCYCLOPEDIA OF MEDICINE 2 373Aspartate aminotransferase testGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 373

kidney, pancreas, spleen, lung, red blood cells, and braintissue. When disease or injury affects these tissues, thecells are destroyed and AST is released into the blood-stream. The amount of AST is directly related to thenumber of cells affected by the disease or injury, but thelevel of elevation depends on the length of time that theblood is tested after the injury. Serum AST levelsbecome elevated eight hours after cell injury, peak at 24-36 hours, and return to normal in three to seven days.

and return to normal in three to seven days. Ifthe cellular injury is chronic (ongoing), AST levels willremain elevated.

tion has formerly been in the diagnosis of a heart attack,or MI. AST can assist in determining the timing andextent of a recent MI, although it is less specific than cre-atine phosphokinase (CPK), CKMB, myglobin, tro-ponins, and lactic dehydrogenase (LDH). Assuming nofurther cardiac injury occurs, the AST level rises within6-10 hours after an acute attack, peaks at 12-48 hours,and returns to normal in three to four days. Myocardialinjuries such as angina (chest pain ) or pericarditis

(inflammation of the pericardium, the membrane aroundthe heart) do not increase AST levels.
AST is also a valuable aid in the diagnosis of liver
disease. Although not specific for liver disease, it canbe used in combination with other enzymes to monitorthe course of various liver disorders. Chronic, silenthepatitis ( hepatitis C ) is sometimes the cause of elevat-

ed AST. In alcoholic hepatitis, caused by excessivealcohol ingestion, AST values are usually moderatelyelevated; in acute viral hepatitis, AST levels can rise toover 20 times normal. Acute extrahepatic (outside theliver) obstruction (e.g. gallstone), produces AST levelsthat can quickly rise to 10 times normal, and then rapid-ly fall. In cases of cirrhosis , the AST level is related to

the amount of active inflammation of the liver. Determi-nation of AST also assists in early recognition of toxichepatitis that results from exposure to drugs toxic to theliver, like acetaminophen and cholesterol lowering
medications.
Other disorders or diseases in which the AST deter-
mination can be valuable include acute pancreatitis ,
muscle disease, trauma, severe burn, and infectious
mononucleosis .
The physician may require discontinuation of any

drugs that might affect the test. These types include suchdrugs as antihypertensives (for treatment of high bloodpressure), coumarin-type anticoagulants (blood-thinningdrugs), digitalis, erythromycin (an antibiotic), oral con-KEY TERMS
Cirrhosis —Disease of the liver caused by chronic
damage to its cells.
Myocardial infarction —Commonly known as a

heart attack. Sudden death of part of the heartmuscle, characterized, in most cases, by severe,unremitting chest pain.
traceptives , and opiates, among others. The patient may
also need to cut back on strenuous activities temporarily,because exercise can also elevate AST for a day or two.
Risks

Normal ranges for the AST are laboratory-specific,
but can range from 3-45 units/L (units per liter).
Striking elevations of AST (400-4000 units/L) are
found in almost all forms of acute hepatic necrosis, suchas viral hepatitis and carbon tetrachloride poisoning . In

alcoholics, even moderate doses of the analgesic aceta-minophen have caused extreme elevations (1,960-29,700units/L). Moderate rises of AST are seen in jaundice ,
cirrhosis, and metastatic carcinoma. Approximately 80%of patients with infectious mononucleosis show eleva-tions in the range of 100-600 units/L.
Resources
BOOKS

Asperger’s syndrome seePervasive
developmental disorders
Aspergilloma seeAspergillosis
GALE ENCYCLOPEDIA OF MEDICINE 2 374Aspartate aminotransferase testGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 374

Aspergillosis
Aspergillosis refers to several forms of disease
caused by a fungus in the genus Aspergillus . Aspergillo-
sis fungal infections can occur in the ear canal, eyes,nose, sinus cavities, and lungs. In some individuals, theinfection can even invade bone and the membranes thatenclose the brain and spinal cord ( meningitis ).
Aspergillosis is primarily an infection of the lungs

caused by the inhalation of airborne spores of the fungusAspergillus . Spores are the small particles that most
fungi use to reproduce. Although virtually everyone isexposed to this fungus in their daily environment, itrarely causes disease. When Aspergillus does cause dis-

ease, however, it usually occurs in those individuals withweakened immune systems (immunocompromised) orwho have a history of respiratory ailments. Because itdoes not present distinctive symptoms, aspergillosis isgenerally thought to be underdiagnosed and underre-ported. Furthermore, many patients with the more severeforms of aspergillosis tend to have multiple, complexhealth problems, such as AIDS or a blood disorder like
leukemia, which can further complicate diagnosis andtreatment.

Once considered particularly rare, the incidence of
reported aspergillosis has risen somewhat with the devel-opment of more sophisticated methods of diagnosis andadvances made in other areas of medicine, such as withthe increased use of certain chemotherapeutic and corti-costeroid drugs that are extremely useful in treating vari-ous types of cancer but that decrease the individual’s
immune response, making them more susceptible toother diseases like aspergillosis.

Our advanced ability to perform tissue and organ
transplants has also increased the number of people vul-nerable to fungal infections. Transplant recipients, partic-ularly those receiving bone marrow or heart transplants,are highly susceptible to Aspergillus , which may be cir-
culating in the hospital air.
Aspergillosis can be a serious, potentially deadly
threat for two primary reasons:
• Aspergillosis usually occurs in those individuals who

are already ill or have weakened immune systems, suchas patients who have undergone chemotherapy for
cancer.
• None of the currently available antifungal drugs are
reliably effective against Aspergillus .Causes and symptoms
Aspergillus is a fungus that is found almost everywhere,

but particularly in soil, water, decaying vegetation, andstored grain. The fungus has also been cultured from ventila-tion systems and may be stirred up during building renova-tions. The species most commonly identified in patients withconfirmed disease are A. fumigatus and A. flavus .
Airborne Aspergillus spores enter the body primarily

through inhalation but can also lodge in the ear or eye.Normally functioning immune systems are generally ableto cope without consequent development of aspergillosis.
It is important to make distinctions between the vari-
ous forms of aspergillosis, as the treatment and prognosisvaries considerably among types. Aspergillosis as a diag-nosis refers to three general forms:
• Allergic bronchopulmonary aspergillosis (ABPA) is
seen in patients with long-standing asthma , particular-

ly in patients taking oral corticosteroids for a long
period of time. This is usually the least serious andmost treatable form.
• Aspergilloma refers to the mass formed when fungal
spores settle into or colonize areas of the lung that havebeen pitted and scarred as a result of tuberculosis or
prior pneumonia . There are several available treatments,
although the success rate varies with each treatment.
• Invasive fungal infection refers to rare cases in which

the fungus spreads throughout the body via the bloodstream and invades other organ systems. Once estab-lished, invasive fungal infections are extremely difficultto cure and, as a result, the associated death rate is
extremely high.
Aspergillus infection of the ear (called otomycosis),
can produce itching and a discharge, sometimes noticed
as a spot on the pillow. Fungal infection of the cornea ofthe eye in a susceptible person can result in blindness, ifnot diagnosed and treated promptly.

Diagnosis
Aspergillosis can be quite difficult to diagnose
because the symptoms, such as coughing and wheezing ,
if present at all, are common to many respiratory disor-ders. Furthermore, blood and sputum cultures are notvery helpful. The presence of Aspergillus is so common,

even in asthmatics, that a positive culture alone is insuffi-cient for a diagnosis. Other, potentially more useful,screening tools include examining the sample obtainedafter repeatedly washing the bronchial tubes of the lungwith water (bronchial lavage), but examining a tissuesample (biopsy) is the most reliable diagnostic tool.Researchers are currently attempting to develop a practi-
GALE ENCYCLOPEDIA OF MEDICINE 2 375AspergillosisGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 375

cal, specific, and rapid blood test that would confirm
Aspergillus infection.
Signs of ABPA include a worsening of bronchial
asthma accompanied by a low-grade fever . Brown flecks
or clumps may be seen in the sputum. Pulmonary func-tion tests may show decreased blood flow, suggesting anobstruction within the lungs. Elevated blood levels of anantibody produced in response to Aspergillus and of cer-
tain immune system cells may indicate a specific aller-gic-type immune system response.

A fungal mass (aspergilloma) in the lung usually
does not produce clear symptoms and is generally diag-nosed when seen on chest x rays. However, 70% or moreof patients spit up blood from the lungs ( hemoptysis ) at
least once, and this may become repetitive and serious.Hemoptysis, then, is another indication that the patientmay be suffering from an aspergilloma.
In patients with lowered immune systems who are at

risk for developing invasive aspergillosis, the physicianmay use a combination of blood culture with visual diag-
nostic techniques, such as computed tomography scans
(CT) and radiography, to arrive at a likely diagnosis.
Treatment
The treatment method selected depends on the form
of aspergillosis. ABPA can usually be treated with manyof the same drugs used to treat asthma, such as systemic

steroids. Long-term therapy may be required, however, toprevent recurrence. Antifungal agents are not recom-mended in the treatment of ABPA. In cases of aspergillo-ma, it may become necessary to surgically remove orreduce the size of a fungal mass, especially if the patientcontinues to spit up blood. In aspergillosis cases affectingthe nose and nasal sinuses, surgery may also be required.
In non-ABPA cases, the use of antifungal drugs may

be indicated. In such cases, amphotericin B (Fungizone)is the first-line therapy. The prescribed dose will dependon the patient’s condition but usually begins with a smalltest dose and then escalates. Less than one-third ofpatients are likely to respond to amphotericin B, and itsside effects often limit its use. For patients who do notrespond to oral amphotericin B, another option is a dif-ferent formulation of the same drug called liposomalamphotericin B.

For patients who fail to respond or who cannot toler-
ate amphotericin B, another drug called itraconazole(Sporanox), given 400-600 mg daily, has also beenapproved. Treatment generally lasts about 3 months. Giv-ing itraconazole can produce adverse reactions if pre-scribed in combination with certain other drugs byincreasing the concentrations of both drugs in the bloodand creating a potentially life-threatening situation. Evenantacids can significantly affect itraconazole levels. As a

result, drug levels must be continually monitored toensure that absorption is occurring at acceptable levels.
Two other methods of treatment are being studied:

direct instillation of an antifungal agent into the lungsand administration of antifungals using a nebulizer.Instilling or injecting amphotericin B or itraconazoledirectly into the lung cavity or into the fungal ball(aspergilloma) itself has been helpful in stoppingepisodes of hemoptysis, but not in preventing futurerecurrences. Furthermore, many patients with aspergillo-mas are poor risks for surgery because their lung func-tion is already compromised. As a result, instillation of afungal

compromised. As a result, instillation of afungal agent should only be considered in those whohave significant hempotysis.

A popular method of treating some respiratory dis-
orders is to add a liquid drug to another carrier liquid andaerosolize or produce a fine mist that can be inhaled intothe lungs through a device called a nebulizer. However,this has not yet been shown to improve the patient’s con-dition in cases of aspergillosis, possibly because the drugis not reaching the aspergilloma.
At this point, preventative therapy for aspergillosis is

not suggested for susceptible individuals, primarilybecause overuse of the drugs used to fight fungal infec-tions may lead to the development of drug-resistant
GALE ENCYCLOPEDIA OF MEDICINE 2 376Aspergillosis
Aspergillus
Aspergillosis is an infection of the lungs caused by inhala-
tion of airborne spores of the fungus Aspergillus .(Illustra-
tion by Electronic Illustrators Group).GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 376

aspergillosis against which current antifungal drugs are
no longer effective.
Prognosis
The likelihood of recovery from aspergillosis depends
on any underlying medical conditions, the patient’s gener-al health, and the specific type of aspergillosis. If the prob-lem is based on an allergic response, as in ABPA, thepatient will likely respond well to systemic steroids.
Patients who require lung surgery , especially those

who have problems with coughing up blood, have a mortal-ity rate of about 7-14%, and complications or recurrencemay result in a higher overall death rate. However, by treat-ing aspergilloma with other, non-surgical methods, that riskrises to 26%, making surgery a better option in some cases.
Unfortunately, the prognosis for the most serious

form, invasive aspergillosis, is quite poor, largely becausethese patients have little resilience due to their underlyingdisorders. Death rates have ranged from about 50% insome studies to as high as 95% for bone-marrow recipientsand patients with AIDS. The course of the illness can berapid, resulting in death within a few months of diagnosis.
Fungal infection by Aspergillus presents a major

challenge, particularly in the patient with a suppressedimmune system (immunocompromised). Hospitals andgovernment health agencies continually seek ways tominimize exposure for hospitalized patients. Practicalsuggestions are minimal but include moving leaf pilesaway from the house. Unfortunately, overall avoidance ofthis fungus is all but impossible because it is present inthe environment virtually everywhere. Research effortsare being directed at enhancing patients’ resistance toAspergillus

at enhancing patients’ resistance toAspergillus rather than trying to eliminate exposure to

the fungus. Given the growing number of people withimmune disorders or whose immune systems have beensuppressed in the course of treating another disease,research and clinical trials for new antifungal agents willbe increasingly important in the future.
Resources
BOOKS
Bonadio, G. R. Air Pollution of Humans With Bacteria, Fun-
gus, and Molds in Homes, Offices, and Hospitals: Index ofNew Information With Author & Subjects. ABBE Publish-
ers Association of Washington, DC, 1995.

Greenberger, P. A. “Immunologic Aspects of Lung Diseases
and Cystic Fibrosis.” The Journal of the American Med-
ical Association 278 (10 Dec. 1997):1924-1930.KEY TERMS
Aspergilloma —A ball or mass made of Aspergillus
fungi that can form in the lungs of patients withsuppressed immune systems.
Bronchial lavage —A procedure that involves

repeatedly washing the inside of the bronchialtubes of the lung.
Hemoptysis —Spitting up blood from the lungs or
sputum stained with blood.
Immunocompromised —A state in which the
immune system is suppressed or not functioningproperly.
ering the brain and spinal cord, called themeninges.
Nebulizer —A device that produces an extremely
fine mist that is readily inhalable.

Spores —The small, thick-walled reproductive
structures of fungi.
Sputum —Mucus and other matter coughed up
from the airways.
American College of Allergy, Asthma, and Immunology. 85
West Algonquin Road, Suite 550, Arlington Heights, IL60005. <http://allergy.mcg.edu>.
OTHER
“Lung, Allergic and Immune Diseases: Mold Allergy: Preven-
tion Techniques.” National Jewish Medical and Research.<http://nationaljewish.org/main.html>.

Office of Rare Diseases (ORD) at National Institutes of Health,
Bldg. 31,1BO3, Bethesda, MD 20892-2082. (301) 402-4336 <http://rarediseases.info.nih.gov/ord>.
Jill S. Lasker
Aspirin
Aspirin is a medicine that relieves pain and reduces
fever .
GALE ENCYCLOPEDIA OF MEDICINE 2 377AspirinGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 377

Purpose
Aspirin is used to relieve many kinds of minor aches
and pains—headaches, toothaches, muscle pain, men-strual cramps, the joint pain from arthritis, and achesassociated with colds and flu. Some people take aspirindaily to reduce the risk of stroke ,heart attack , or other
heart problems.
Aspirin—also known as acetylsalicylic acid—is sold

over the counter and comes in many forms, from thefamiliar white tablets to chewing gum and rectal supposi-tories. Coated, chewable, buffered, and extended releaseforms are available. Many other over-the-counter medi-cine contain aspirin. Alka-Seltzer Original EffervescentAntacid Pain Reliever, for example, contains aspirin forpain relief and sodium bicarbonate to relieve acid indi-
gestion ,heartburn , and sour stomach.
Aspirin belongs to a group of drugs called salicy-

lates. Other members of this group include sodium salicy-late, choline salicylate, and magnesium salicylate. Thesedrugs are more expensive and no more effective thanaspirin. However, they are a little easier on the stomach.Aspirin is quickly absorbed into the bloodstream and pro-vides quick and relatively long-lasting pain relief. Aspirinalso reduces inflammation. Researchers believe theseeffects come about because aspirin blocks the productionof pain-producing chemicals called prostaglandins.

In addition to relieving pain and reducing inflamma-
tion, aspirin also lowers fever by acting on the part of thebrain that regulates temperature. The brain then signalsthe blood vessels to widen, which allows heat to leavethe body more quickly.
Adults
TO RELIEVE PAIN OR REDUCE FEVER. one to two
tablets every three to four hours, up to six times per day.
TO REDUCE THE RISK OF STROKE. one tablet four
times a day or two tablets twice a day.

TO REDUCE THE RISK OF HEART ATTACK. Check with
a physician for the proper dose and number of times perweek aspirin should, if at all, be taken.
Children
Check with a physician.
Aspirin—even children’s aspirin—should never be
given to children or teenagers with flu-like symptoms orchickenpox . Aspirin can cause Reye’s syndrome , a life-

threatening condition that affects the nervous system andliver. As many as 30% of children and teenagers whodevelop Reye’s syndrome die. Those who survive mayhave permanent brain damage.
Check with a physician before giving aspirin to a
child under 12 years for arthritis, rheumatism, or anycondition that requires long-term use of the drug.
No one should take aspirin for more than 10 days in

a row unless told to do so by a physician. Anyone withfever should not take aspirin for more than 3 days with-out a physician’s consent. Do not to take more than therecommended daily dosage.
People in the following categories should not use
aspirin without first checking with their physician:
• Pregnant women. Aspirin can cause bleeding problems
in both the mother and the developing fetus. Aspirincan also cause the infant’s weight to be too low at birth.

• Women who are breastfeeding. Aspirin can pass into
breast milk and may affect the baby.
• People with a history of bleeding problems.• People who are taking blood-thinning drugs, such as
warfarin (Coumadin).
• People with a history of ulcers.• People with a history of asthma ,nasal polyps , or both.
These people are more likely to be allergic to aspirin.
• People who are allergic to fenoprofen, ibuprofen, indo-

methacin, ketoprofen, meclofenamate sodium, naprox-en, sulindac, tolmetin, or the orange food-coloring tar-trazine. They may also be allergic to aspirin.
• People with AIDS or AIDS-related complex who are
taking AZT (zidovudine). Aspirin can increase the riskof bleeding in these patients.
• People taking certain other drugs (discussed in Interac-
tions).
• People with liver damage or severe kidney failure.
Aspirin should not be taken before surgery, as it can

increase the risk of excessive bleeding. Anyone who isscheduled for surgery should check with his or her sur-geon to find out how long before surgery to avoid takingaspirin.
Aspirin can cause stomach irritation. To reduce the
likelihood of that problem, take aspirin with food or milkor drink a full 8-oz glass of water with it. Taking coatedor buffered aspirin can also help. Be aware that drinkingalcohol can make the stomach irritation worse.
Stop taking aspirin immediately and call a physician

if any of these symptoms develop:
GALE ENCYCLOPEDIA OF MEDICINE 2 378AspirinGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 378

• hearing loss
•dizziness
• stomach pain that does not go away
Do not take aspirin that has a vinegary smell. That is
a sign that the aspirin is too old and ineffective. Flushsuch aspirin down the toilet.
Because aspirin can increase the risk of excessive
bleeding, do not take aspirin daily over long periods—toreduce the risk of stroke or heart attack, for example—unless advised to do so by a physician.
The most common side effects include stomachache,

heartburn, loss of appetite, and small amounts of blood inKEY TERMS
Diuretic —Medicine that increases the amount of
urine produced and relieves excess fluid buildupin body tissues. Diuretics may be used in treatinghigh blood pressure, lung disease, premenstrualsyndrome, and other conditions.
NSAIDs —Nonsteroidal anti-inflammatory drugs.

Drugs such as ketoprofen and ibuprofen whichrelieve pain and reduce inflammation.
Polyp —A lump of tissue protruding from the lining
of an organ, such as the nose, bladder, or intes-tine. Polyps can sometimes block the passages inwhich they are found.
Prostaglandin —A hormonelike chemical produced
in the body. Prostaglandins have a wide variety ofeffects, and may be responsible for the productionof some types of pain and inflammation.

Reye’s syndrome —A life-threatening disease that
affects the liver and the brain and sometimesoccurs after a viral infection, such as flu or chick-enpox. Children or teenagers who are givenaspirin for flu or chickenpox are at increased riskof developing Reye’s syndrome.
Rhinitis —Inflammation of the membranes inside
the nose.

and related compounds. Salicylates are used torelieve pain, reduce inflammation, and lower fever.stools. Less common side effects are rashes ,hives , fever,
vision problems, liver damage, thirst, stomach ulcers,and bleeding. People who are allergic to aspirin or thosewho have asthma, rhinitis , or polyps in the nose may
have trouble breathing after taking aspirin.
Aspirin may increase, decrease, or change the

effects of many drugs. Aspirin can make drugs such asmethotrexate (Rheumatrex) and valproic acid (Depakote,Depakene) more toxic. If taken with blood-thinningdrugs, such as warfarin (Coumadin) and dicumarol,aspirin can increase the risk of excessive bleeding.Aspirin counteracts the effects of other drugs, such asangiotensin-converting enzyme (ACE) inhibitors andbeta blockers , which lower blood pressure, and medi-

cines used to treat gout (probenecid and sulfinpyrazone).
Blood pressure may drop unexpectedly and cause faint-
ingor dizziness if aspirin is taken along with nitroglyc-
erin tablets. Aspirin may also interact with diuretics , dia-
betes medicines, other nonsteroidal anti-inflammatory
drugs (NSAIDs), seizure medications, and steroids.
Anyone who is taking these drugs should ask his or herphysician whether they can safely take aspirin.
Resources

Resources
“How to Give Medicine to Children” (Includes related article
on health risks of aspirin for children). FDA Consumer
(Jan./Feb. 1996): 6.
“The Miracle Drug in Your Medicine Cabinet.” American
Health (Jan./Feb. 1996): 67.
“No Aspirin, Please.” Current Health (Dec. 1992): 12.
“What’s the Best Pain Reliever? Depends on Your Pain.” Con-
sumer Reports , May 1996, 62.
AST seeAspartate aminotransferase test
Astemizole seeAntihistamines
Asthma

Asthma
Today asthma is viewed as a chronic (long-lasting)
inflammatory disease of the airways. In those susceptibleto asthma, this inflammation causes the airways to nar-row periodically. This, in turn, produces wheezing and
breathlessness, sometimes to the point where the patient
GALE ENCYCLOPEDIA OF MEDICINE 2 379AsthmaGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 379

gasps for air. Obstruction to air flow either stops sponta-
neously or responds to a wide range of treatments, butcontinuing inflammation makes the airways hyper-responsive to stimuli such as cold air, exercise , dust
mites, pollutants in the air, and even stress and anxiety .
About 10 million Americans have asthma, and the

number seems to be increasing. Between 1982-92, therate actually rose by 42%. Not only is asthma becomingmore frequent, but it also is a more severe disease thanbefore, despite modern drug treatments. In the same 10-year period, the death rate from asthma in the United
States increased by 35%.
The changes that take place in the lungs of asth-

matic persons makes the airways (the “breathing tubes,”or bronchi and the smaller bronchioles ) hyper-reactive

to many different types of stimuli that don’t affecthealthy lungs. In an asthma attack, the muscle tissue inthe walls of bronchi go into spasm, and the cells liningthe airways swell and secrete mucus into the air spaces.Both these actions cause the bronchi to become nar-rowed (bronchoconstriction). As a result, an asthmaticperson has to make a much greater effort to breathe inair and to expel it.
Cells in the bronchial walls, called mast cells,

release certain substances that cause the bronchial mus-cle to contract and stimulate mucus formation. Thesesubstances, which include histamine and a group ofchemicals called leukotrienes, also bring white bloodcells into the area, which is a key part of the inflammato-ry response. Many patients with asthma are prone toreact to such “foreign” substances as pollen, house dustmites, or animal dander; these are called allergens. Onthe other hand, asthma affects many patients who are not“allergic”

Asthma usually begins in childhood or adolescence,
but it also may first appear during adult years. While thesymptoms may be similar, certain important aspects ofasthma are different in children and adults.
Child-onset asthma
When asthma does begin in childhood, it often does

so in a child who is likely, for genetic reasons, to becomesensitized to common “allergens” in the environment(atopic person). When these children are exposed tohouse-dust mites, animal proteins, fungi, or other poten-tial allergens, they produce a type of antibody that isintended to engulf and destroy the foreign materials. Thishas the effect of making the airway cells sensitive to par-ticular materials. Further exposure can lead rapidly to anasthmatic response. This condition of atopy is

at least one-third and as many as half of the general pop-ulation. When an infant or young child wheezes duringviral infections, the presence of allergy (in the child itselfor a close relative) is a clue that asthma may well contin-ue throughout childhood.
Adult-onset asthma
Allergenic materials may also play a role when
adults become asthmatic. Asthma can actually start atany age and in a wide variety of situations. Many adultswho are not allergic do have such conditions as sinusitis

or nasal polyps , or they may be sensitive to aspirin and
related drugs. Another major source of adult asthma isexposure at work to animal products, certain forms ofplastic, wood dust, or metals.
In most cases, asthma is caused by inhaling an aller-

gen that sets off the chain of biochemical and tissuechanges leading to airway inflammation, bronchocon-striction, and wheezing. Because avoiding (or at leastminimizing) exposure is the most effective way of treat-ing asthma, it is vital to identify which allergen or irritantis causing symptoms in a particular patient. Once asthmais present, symptoms can be set off or made worse if thepatient also has rhinitis (inflammation of the lining of

the nose) or sinusitis. When, for some reason, stomachacid passes back up the esophagus (acid reflux), this canalso make asthma worse. A viral infection of the respira-tory tract can also inflame an asthmatic reaction. Aspirinand a type of drug called beta-blockers, often used totreat high blood pressure, can also worsen the symptomsof asthma.
The most important inhaled allergens giving rise to
attacks of asthma are:

• animal dander• mites in house dust• fungi (molds) that grow indoors• cockroach allergens
• pollen
• occupational exposure to chemicals, fumes, or particles
of industrial materials in the air
Inhaling tobacco smoke, either by smoking or being

near people who are smoking, can irritate the airwaysand trigger an asthmatic attack. Air pollutants can have asimilar effect. In addition, there are three important fac-tors that regularly produce attacks in certain asthmaticpatients, and they may sometimes be the sole cause ofsymptoms. They are:
GALE ENCYCLOPEDIA OF MEDICINE 2 380AsthmaGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 380

• inhaling cold air (cold-induced asthma)
• exercise-induced asthma (in certain children, asthma is
caused simply by exercising)
• stress or a high level of anxiety
Wheezing is often very obvious, but mild asthmatic
attacks may be confirmed when the physician listens tothe patient’s chest with a stethoscope. Besides wheezingand being short of breath, the patient may cough and
may report a feeling of “tightness” in the chest. Childrenmay have itching on their back or neck at the start of an

attack. Wheezing is often loudest when the patientbreathes out, in an attempt to expel used air through thenarrowed airways. Some asthmatics are free of symp-toms most of the time but may occasionally be short ofbreath for a brief time. Others spend much of their days(and nights) coughing and wheezing, until properly treat-ed. Crying or even laughing may bring on an attack.Severe episodes are often seen when the patient gets aviral respiratory tract infection or is exposed to a heavyload of an

infection or is exposed to a heavyload of an allergen or irritant. Asthmatic attacks may lastonly a few minutes or can go on for hours or even days (acondition called status asthmaticus).

very anxious, sit upright, lean forward, and use the mus-cles of the neck and chest wall to help breathe. Thepatient may be able to say only a few words at a timebefore stopping to take a breath. Confusion and a bluishtint to the skin are clues that the oxygen supply is muchtoo low, and that emergency treatment is needed. In asevere attack that lasts for some time, some of the airsacs in the lung may rupture so that air collects withinthe chest. This makes it even harder to breathe in

chest. This makes it even harder to breathe in enoughair. Almost always, even patients with the most severeattacks will recover completely.

Diagnosis
Apart from listening to the patient’s chest, the exam-
iner should look for maximum chest expansion whiletaking in air. Hunched shoulders and contracting neckmuscles are other signs of narrowed airways. Nasalpolyps or increased amounts of nasal secretions are oftennoted in asthmatic patients. Skin changes, like atopic
dermatitis or eczema, are a tipoff that the patient has
allergic problems.
Inquiring about a family history of asthma or aller-

giescan be a valuable indicator of asthma. The diagnosis
may be strongly suggested when typical symptoms andsigns are present. A test called spirometry measures howrapidly air is exhaled and how much is retained in thelungs. Repeating the test after the patient inhales a drugthat widens the air passages (a bronchodilator) will showwhether the airway narrowing is reversible, which is a

very typical finding in asthma. Often patients use a relat-ed instrument, called a peak flow meter, to keep track ofasthma severity when at home.
Often, it is difficult to determine what is triggering

asthma attacks. Allergy skin testing may be used,although an allergic skin response does not always meanthat the allergen being tested is causing the asthma. Also,the body’s immune system produces antibody to fight offthe allergen, and the amount of antibody can be mea-sured by a blood test. This will show how sensitive thepatient is to a particular allergen. If the diagnosis is stillin doubt, the patient can inhale a suspect allergen whileusing a spirometer to detect airway narrowing.

a spirometer to detect airway narrowing. Spirome-try can also be repeated after a bout of exercise if exer-cise-induced asthma is a possibility. A chest x ray will

help rule out other disorders.
Treatment
Patients should be periodically examined and have
their lung function measured by spirometry to make surethat treatment goals are being met. These goals are to pre-vent troublesome symptoms, to maintain lung function asclose to normal as possible, and to allow patients to pur-sue their normal activities including those requiring exer-tion. The best drug therapy is that which controls asthmat-ic symptoms while causing few or no side-effects.
Drugs

Drugs
METHYLXANTHINES. The chief methylxanthine drug
is theophylline. It may exert some anti-inflammatoryeffect, and is especially helpful in controlling nighttimesymptoms of asthma. When, for some reason, a patientcannot use an inhaler to maintain long-term control, sus-tained-release theophylline is a good alternative. Theblood levels of the drug must be measured periodically,as too high a dose can cause an abnormal heart rhythm orconvulsions.
BETA-RECEPTOR AGONISTS. These drugs, which are

bronchodilators , are the best choice for relieving sudden
attacks of asthma and for preventing attacks from beingtriggered by exercise. Some agonists, such as albuterol,act mainly in lung cells and have little effect on otherorgans, such as the heart. These drugs generally start act-ing within minutes, but their effects last only four to sixhours (although longer-acting forms are being devel-oped). They may be taken by mouth, inhaled, or injected.

STEROIDS. These drugs, which resemble natural
body hormones, block inflammation and are extremelyeffective in relieving symptoms of asthma. Whensteroids are taken by inhalation for a long period, asthma
GALE ENCYCLOPEDIA OF MEDICINE 2 381AsthmaGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 381

attacks become less frequent as the airways become less
sensitive to allergens. This is the strongest medicine forasthma, and can control even severe cases over the longterm and maintain good lung function. Steroids cancause numerous side-effects, however, including bleed-ing from the stomach, loss of calcium from bones,cataracts in the eye, and a diabetes-like state. Patients

using steroids for lengthy periods may also have prob-lems with wound healing, may gain weight, and may suf-fer mental problems. In children, growth may be slowed.Besides being inhaled, steroids may be taken by mouthor injected, to rapidly control severe asthma.
LEUKOTRIENE MODIFIERS. Leukotriene modifiers

are a new type of drug that can be used in place ofsteroids, for older children or adults who have a milddegree of asthma that persists. They work by counteract-ing leukotrienes, which are substances released by white
blood cells in the lung that cause the air passages to con-strict and promote mucus secretion.
OTHER DRUGS. Cromolyn and nedocromil are anti-

inflammatory drugs that are often used as initial treatmentto prevent asthmatic attacks over the long term in children.They can also prevent attacks when given before exerciseor when exposure to an allergen cannot be avoided. Theseare safe drugs but are expensive, and must be taken regular-ly even if there are no symptoms. Anti-cholinergic drugs,such as atropine, are useful in controlling severe attackswhen added to an inhaled beta-receptor agonist. They helpwiden the airways and suppress mucus

If a patient’s asthma is caused by an allergen that
cannot be avoided and it has been difficult to controlsymptoms by drugs, immunotherapy may be worth try-
GALE ENCYCLOPEDIA OF MEDICINE 2 382Asthma
In normal bronchioles the airway
is open and unobstructed.
During an attack, the bronchioles of an
asthma sufferer are constricted by bandsof muscle around them. They may befurther obstructed by increased mucusproduction and tissue inflammation.

A comparison of normal bronchioles and those of an asthma sufferer. (Illustration by Hans & Cassady.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 382

ing. Typically, increasing amounts of the allergen are
injected over a period of three to five years, so that thebody can build up an effective immune response. Thereis a risk that this treatment may itself cause the airwaysto become narrowed and bring on an asthmatic attack.Not all experts are enthusiastic about immunotherapy,although some studies have shown that it does reduceasthmatic symptoms caused by exposure to house-dustmites, ragweed pollen, and cats.
Managing asthmatic attacks

A severe asthma attack should be treated as quickly
as possible. It is most important for a patient suffering anacute attack to be given extra oxygen. Rarely, it may benecessary to use a mechanical ventilator to help thepatient breathe. A beta-receptor agonist is inhaled repeat-edly or continuously. If the patient does not respondpromptly and completely, a steroid is given. A course ofsteroid therapy, given after the attack is over, will make arecurrence less likely.

Maintaining control
Long-term asthma treatment is based on inhaling a

beta-receptor agonist using a special inhaler that meters thedose. Patients must be instructed in proper use of an inhalerto be sure that it will deliver the right amount of drug. Onceasthma has been controlled for several weeks or months, itis worth trying to cut down on drug treatment, but this mustbe done gradually. The last drug added should be the first tobe reduced. Patients should be seen every one to sixmonths, depending on the frequency of attacks.

makes for minimal delay and helps the patient to gain asense of control over the disease. All patients should betaught how to monitor their symptoms so that they willknow when an attack is starting, and those with moderateor severe asthma should know how to use a flow meter.They should also have a written “action plan” to follow ifsymptoms suddenly become worse, including how toadjust their medication and when to seek medical help. Ifmore intense treatment is necessary, it should be contin-ued

treatment is necessary, it should be contin-ued for several days. Over-the-counter “remedies” shouldbe avoided. When deciding whether a patient should behospitalized, the past history of acute attacks, severity ofsymptoms, current medication, and whether good supportis available at home all must be taken into account.

Referral to an asthma specialist should be considered if:
• there has been a life-threatening asthma attack or
severe, persistent asthma
• treatment for three to six months has not met its goals
• some other condition, such as nasal polyps or chronic
lung disease, is complicating asthma• special tests, such as allergy skin testing or an allergen
challenge, are needed
• intensive steroid therapy has been necessary
Special populations
INFANTS AND YOUNG CHILDREN. It is especially

important to closely watch the course of asthma in youngpatients. Treatment is cut down when possible and ifthere is no clear improvement, some other treatmentshould be tried. If a viral infection leads to severe asth-matic symptoms, steroids may help. The health careprovider should write out an asthma treatment plan forthe child’s school. Asthmatic children often need med-ication at school to control acute symptoms or to preventexercise- induced attacks. Proper management will usu-ally allow a

attacks. Proper management will usu-ally allow a child to take part in play activities. Only as alast resort should activities be limited.

THE ELDERLY. Older persons often have other types of
obstructive lung disease, such as chronic bronchitis or
emphysema . This makes it important to know to what

extent the symptoms are caused by asthma. Giving steroidsfor two to three weeks can help determine this. Side-effectsfrom beta-receptor agonist drugs (including a speedingheart and tremor) may be more common in older patients.These patients may benefit from receiving an anti-choliner-gic drug, along with the beta-receptor agonist. If theo-phylline is given, the dose should be limited, as olderpatients are less able to clear this drug from their blood.Steroids should be avoided, as they often

blood.Steroids should be avoided, as they often make elderlypatients confused and agitated. Steroids may also furtherweaken the bones.

best drug or combination of drugs is found, and they areable to lead relatively normal lives. More than half ofaffected children stop having attacks by the time theyreach 21 years of age. Many others have less frequentand less severe attacks as they grow older. Urgent mea-sures to control asthma attacks and ongoing treatment toprevent attacks are equally important. A small minorityof patients will have progressively more trouble breath-ing and they run a risk of going into respiratory failure

and they must receive intensive treatment.
Minimizing exposure to allergens
There are a number of ways to cut down exposure to
the common allergens and irritants that provoke asthmat-ic attacks, or to avoid them altogether:
GALE ENCYCLOPEDIA OF MEDICINE 2 383AsthmaGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 383

• If the patient is sensitive to a family pet, remove the
animal or at least keep it out of the bedroom (with thebedroom door closed). Keep the pet away from carpetsand upholstered furniture. Remove all feathers.
• To reduce exposure to house dust mites, remove wall-
to-wall carpeting, keep the humidity down, and use spe-cial pillow and mattress covers. Cut down on stuffedtoys, and wash them each week in hot water.
• If cockroach allergen is causing asthma attacks, kill the

roaches (using poison, traps, or boric acid rather thanchemicals). Take care not to leave food or garbageexposed.
• Keep indoor air clean by vacuuming carpets once or
twice a week (with the patient absent), avoid usinghumidifiers, and do use air conditioning during warmweather (so that the windows can be closed).
• Avoid exposure to tobacco smoke.
• Do not exercise outside when air pollution levels are
high.
• When asthma is related to exposure at work, take all

precautions, including wearing a mask and, if neces-sary, arrange to work in a safer area.
Resources
BOOKS
Gershwin, M. Eric, E. L. Klinglhofer. Asthma: Stop Suffering,
Start Living. 2nd ed. Reading, MA: Addison-Wessey Pub-
lishing Co., l992.KEY TERMS
Allergen —A foreign substance, such as mites in
house dust or animal dander which, wheninhaled, causes the airways to narrow and pro-duces symptoms of asthma.
Atopy —A state that makes persons more likely to

develop allergic reactions of any type, includingthe inflammation and airway narrowing typical ofasthma.
Hypersensitivity —The state where even a tiny
amount of allergen can cause the airways to con-strict and bring on an asthmatic attack.
Spirometry —A test using an instrument called a

spirometer that shows how difficult it is for anasthmatic patient to breathe. Used to determinethe severity of asthma and to see how well it isresponding to treatment.Haas, Francois, and Sheila S Haas. The Essential Asthma
Book: A Manual for Asthmatics of All Ages. New York:
Ivy Books, 1987.
Asthma and Allergy Foundation of America. 1233 20th Street,
NW, Suite 402, Washington, DC 20036. (800) 727-8462.<http://www.aafa.org>.

Mothers of Asthmatics, Inc. 3554 Chain Bridge Road, Suite
200, Fairfax, V A 22030. (800) 878-4403.
National Asthma Education Program. 4733 Bethesda Ave.,
Suite 350, Bethesda, MD 20814. 301-495-4484.
National Jewish Medical and Research Center. 1400 Jackson
St., Denver, CO 80206. 800-222-LUNG.
Astigmatism
Astigmatism is the result of an inability of the
cornea to properly focus an image onto the retina. Theresult is a blurred image.

The cornea is the outermost part of the eye. It is a

transparent layer that covers the colored part of the eye(iris), pupil, and lens. The cornea bends light and helps tofocus it onto the retina where specialized cells (photoreceptors) detect light and transmit nerve impulses viathe optic nerve to the brain where the image is formed.The cornea is dome shaped. Any incorrect shaping of thecornea results in an incorrect focusing of the light thatpasses through that part of the cornea. The bending oflight is called refraction and focusing problems

is called refraction and focusing problems with thecornea are called diseases of refraction or refractive dis-orders. Astigmatism is an image distortion that resultsfrom an improperly shaped cornea. Usually the cornea isspherically shaped, like a baseball. However, in astigma-tism the cornea is elliptically shaped, more like a foot-ball. There is a long meridian and a short meridian.These two meridians generally have a constant curvatureand are generally perpendicular to each other

are generally perpendicular to each other (regularastigmatism). Irregular astigmatism may have more thantwo meridians of focus and they may not be 90° apart. Apoint of light, therefore, going through an astigmaticcornea will have two points of focus, instead of one nicesharp image on the retina. This will cause the person tohave blurry vision. What the blur looks like will dependupon the amount and the direction of the astigmatism. Aperson with nearsightedness ( myopia ) or farsightedness

GALE ENCYCLOPEDIA OF MEDICINE 2 384AstigmatismGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 384

(hyperopia ) may see a dot as a blurred circle. A person
with astigmatism may see the same dot as a blurred ovalor frankfurter-shaped blur.
Some cases of astigmatism are caused by problems

in the lens of the eye. Minor variations in the curvature ofthe lens can produce minor degrees of astigmatism(lenticular astigmatism). In these patients, the cornea isusually normal in shape. Infants, as a group, have theleast amount of astigmatism. Astigmatism may increaseduring childhood, as the eye is developing.
The main symptom of astigmatism is blurring. Peo-

ple can also experience headaches and eyestrain. Parentscan notice that a child may have astigmatism when thechild can see some part of a pattern or picture more clear-ly than others. For example, lines going across may seemclearer than lines going up and down.
Regular astigmatism can be caused by the weight of

the upper eyelid resting on the eyeball creating distortion,surgical incisions in the cornea, trauma or scarring to thecornea, the presence of tumors in the eyelid, or a develop-mental factor. Irregular astigmatism can be caused by scar-ring or keratoconus. Keratoconus is a condition in whichthe cornea thins and becomes cone shaped. It usuallyoccurs around puberty and is more common in women.

Although the causes of keratoconus are unknown, it maybe hereditary or a result of chronic eye rubbing, as in peo-ple with allergies . The center of the cone may not be in

line with the center of the cornea. Diabetes can play a rolein the development of astigmatism. High blood sugar lev-els can cause shape changes in the lens of the eye. Thisprocess usually occurs slowly and, often, is only noticedwhen the diabetic has started treatment to control theirblood sugar. The return to a more normal blood sugarallows the lens to return to normal and this change issometimes noticed by the patient as farsightedness.Because of this, diabetics should wait until their

of this, diabetics should wait until their bloodsugar is under control for at least one month to allowvision to stabilize before being measured for eyeglasses.

variety of tests can be used to detect astigmatism duringthe eye exam. The patient may be asked to describe theastigmatic dial, a series of lines that radiate outward froma center. People with astigmatism will see some of thelines more clearly than others. One diagnostic instrumentused is the keratometer. This measures the curvature ofthe central cornea. It measures the amount and directionof the curvature. A corneal topographer can measure alarger area of the cornea. It can measure the central

and mid-periphery of the cornea. A keratoscope projectsa series of concentric light rings onto the cornea. Mis-shapen areas of the cornea are revealed by noting areasof the light pattern that do not appear concentric on thecornea. Because these instruments are measuring thecornea, it is also important to have a refraction in case thelens is also contributing to the astigmatism. The refrac-tion measures the optics or visual status of the eye andthe result is the eyeglass prescription. The

andthe result is the eyeglass prescription. The refraction iswhen the patient is looking at an eye chart and the doctoris putting different lenses in front of the patient’s eyesand asks which one looks better.

Treatment
Astigmatism can be treated by the use of cylindrical
lenses. They can be in eyeglasses or contact lenses. Theunit of measure describing the power of the lens system orlens is called the diopter (D). The lenses are shaped tocounteract the shape of the sections of cornea that are caus-ing the difficulty. Because the correction is in one direction,it is written in terms of the axis the correction is in. On aprescription, for example, it may say -1.00D /H11003180°.

GALE ENCYCLOPEDIA OF MEDICINE 2 385Astigmatism
Cornea
LensLightRetina
Horizontal line out of focus
Astigmatism corrected by lensLight
Astigmatism can be treated by the use of cylindrical lenses.
The lenses are shaped to counteract the shape of the sec-tions of the cornea that are causing the difficulty. (Illustration
by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 385

Cylinders correct astigmatism, minus spheres correct
myopia, and plus spheres correct hyperopia.
There is some debate as to whether people with very

small amounts of astigmatism should be treated. Gener-ally, if visual acuity is good and the patient experiencesno overt symptoms, treatment is not necessary. Whentreating larger amounts of astigmatism, or astigmatismfor the first time, the doctor may not totally correct theastigmatism. The cylindrical correction in the eyeglassesmay make the floor appear to tilt, thus making it difficultfor the patient at first. Generally, the doctor will placelenses in a trial frame to allow the patient to

in a trial frame to allow the patient to try the pre-scription at the exam. It may take a week or so to getused to the glasses, however, if the patient is having aproblem they should contact their doctor, who mightwant to recheck the prescription.

Contact lenses that are used to correct astigmatism
are called toric lenses. When a person blinks, the contactlens rotates. In toric lenses, it is important for the lens toreturn to the same position each time. Lenses have thinzones, or cut-off areas (truncated), or have other ways torotate and return to the correct position. Soft toric lensesare available in a variety of prescriptions, materials, andeven in tints. Patients should ask their doctors about thepossibility of toric lenses.

In 1997, the Food and Drug Administration (FDA)
approved laser treatment of astigmatism. Patients consid-ering this should make sure the surgeon has a lot of expe-rience in the procedure and discuss the possible sideeffects or risks with the doctor. In the case of kerato-conus, a corneal transplant is performed if the astigma-tism can not be corrected with hard contact lenses.
Prognosis
Astigmatism is a condition that may be present at

birth. It may also be acquired if something is distorting thecornea. Vision can generally be corrected with eyeglassesKEY TERMS
Meridian —A section of a sphere. For example, lon-
gitude or latitude on the globe. Or, on a clock, asection going through 12:00-6:00 or 3:00-9:00, etc.
Refraction —The turning or bending of light waves

as the light passes from one medium or layer toanother. In the eye it means the ability of the eyeto bend light so that an image is focused onto theretina.or contact lenses. The major risks of surgery (aside from
the surgical risks) are over and under correction of theastigmatism. There is no cure for over correction. Undercorrection can be solved by repeating the operation.
Resources
BOOKS

Resources
BOOKS
Albert, D. M., and F. A. Jakobiec. Principles and Practice of
Ophthalmology. New York: W. B. Saunders Co., 1994.
Aston-Patterning
Aston-Patterning is an integrated system of move-

ment education, bodywork, ergonomic adjustments, andfitness training that recognizes the relationship betweenthe body and mind for well being. It helps people whoseek a remedy from acute or chronic pain by teaching
them to improve postural and movement patterns.
Purpose
Aston-Patterning assists people in finding more effi-

cient and less stressful ways of performing the simplemovements of everyday life to dissipate tension in thebody. This is done through massage, alteration of theenvironment, and fitness training.
Seeking to solve movement problems, Aston-Pat-
terning helps make the most of their own unique bodytypes rather than trying to force them to conform to anideal. Unlike Rolfing , it doesn’t strive for linear symme-

try. Rather it works with asymmetry in the human bodyto develop patterns of alignment and movement that feelright to the individual. Aston also introduced the idea ofworking in a three-dimensional spinal pattern.
Aston-Patterning sessions have four general compo-
nents. They are:
• A personal history that helps the practitioner assess the
client’s needs.
• Pre-testing, in which the practitioner and the client explore
patterns of movement and potential for improvement.

GALE ENCYCLOPEDIA OF MEDICINE 2 386Aston-PatterningGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 386

• Movement education and bodywork, including mas-
sage, myofacial release, and arthrokinetics, to helprelease tension and make new movement patterns easier.
• Post-testing, when pre-testing movements are repeated,
allowing the client to feel the changes that have takenplace and integrate them into daily life.
Aston-Patterning requires more participation from

the client than many bodywork techniques. The massageaspect of Aston-Patterning is designed around a three-dimensional, non-compressive touch that releases pat-terns of tension in the body. It is gentler than Rolfing.Myokinetics uses touch to release tension in the face andneck. Arthrokinetics addresses tension at bones andjoints. This massage is accompanied by education abouthow new movement patterns may be established.

In addition to Aston-Patterning sessions, clients are
also helped to examine their environment for factors, suchas seating or sleeping arrangements, that may limit theirbody function and introduce tension. Finally, they maychoose to participate in the Aston fitness training programthat includes loosening techniques based on self-massage,toning, stretching, and cardiovascular fitness.KEY TERMS
Rolfing —Developed by Dr. Ida Rolf (1896–1979),

rolfing is a systematic approach to relieving stresspatterns and dysfunctions in the body’s structurethrough the manipulation of the highly pliant myofa-cial (connective) tissue. It assists the body in reorga-nizing its major segments into vertical alignment.
No special preparation need be taken.
No special precautions are necessary when partici-
pating.
No undesirable side effects are reported. Usually

clients report a diminution of tension, improved bodymovement, and an enhanced feeling of well being.
Aston-Patterning is an outgrowth of Rolfing, which

has been shown to be of benefit in a limited number ofcontrolled studies. Little controlled research has been doneon the either benefits or limitations of Aston-Patterning. Itsclaims have been neither proven nor disproved, althoughanecdotally many clients report relief from pain and ten-sion and also improved body movement.
Resources
The Aston Training Center. P. O. Box 3568, Incline Village,
NV 89450. 775-831-8228. Astonpat@aol.com <http://www.aston-patterning.com>.

Astrocytoma seeBrain tumor
Ataxia-telangiectasia
Ataxia-telangiectasia (A-T), also called Louis-Bar
syndrome, is a rare, genetic neurological disorder of child-
GALE ENCYCLOPEDIA OF MEDICINE 2 387Ataxia-telangiectasia
JUDITH ASTON
Judith Aston was born in Long Beach, California.

She graduated from University of California at Los Ange-les with a B.A. and a M.F.A. in dance. Her interest inmovement arose from working as a dancer. In 1963Aston established her first movement education pro-gram for dancers, actors, and athletes at Long BeachCity College.
Five years later, while recovering from injuries sus-

tained during two consecutive automobile accidents,Aston met Ida Rolf, the developer of Rolfing. Astonbegan working for Rolf, teaching a movement educationprogram called Rolf-Aston Structural Patterning thatemphasized using the body with minimum effort andmaximum precision.
In time, Rolf and Aston’s views on movement

diverged, and the partnership was dissolved in 1977.Aston formed her own company called the Aston Para-digm Corporation in Lake Tahoe, California. This com-pany provides training and certification for Aston practi-tioners. She also began exploring how environmentalconditions affect body movement, foreshadowing theergonomic movement in the workplace that developedin the 1990s. Over time, Aston has expanded her move-ment work to include a fitness program for older adults.Today, Judith Aston

program for older adults.Today, Judith Aston serves as director of Aston ParadigmCorporation.GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 387

hood that progressively destroys part of the motor control
area of the brain, leading to a lack of balance and coordina-tion. A-T also affects the immune system and increases therisk of leukemia and lymphoma in affected individuals.
The disorder first appeared in the medical literature in

the mid-1920s, but was not named specifically until 1957.The name is a combination of two recognized abnormali-ties: ataxia (lack of muscle control) and telangiectasia(abnormal dilatation of capillary vessels that often result intumors and red skin lesions ). However, A-T involves more
than just the sum of these two findings. Other associatedA-T problems include immune system deficiencies,extreme sensitivity to radiation, and blood cancers.
Medical researchers initially suspected that multiple

genes (the units responsible for inherited features) wereinvolved. However, in 1995, mutations in a single largegene were identified as causing A-T. Researchers namedthe gene ATM for A-T, mutated. Subsequent researchrevealed that ATM has a significant role in regulating celldivision. The symptoms associated with A-T reflect themain role of the AT gene, which is to induce several cellu-lar responses to DNA damage, such as preventing damagedDNA from being reproduced. When the AT gene is

from being reproduced. When the AT gene is mutatedinto ATM, the signaling networks are affected and the cellno longer responds correctly to minimize the damage.

world wide, with an estimated frequency of between1/40,000 and 1/100,000 live births. But it is believed thatmany A-T cases, particularly those who die at a youngage, are never properly diagnosed. Therefore, this diseasemay actually be much more prevalent. According to theA-T Project Foundation, an estimated 1% (2.5 million inthe United States) of the general population carries defec-tive A-T genes. Carriers of one copy of this gene do notdevelop A-T, but have a significantly increased risk

A-T, but have a significantly increased risk ofcancer . This makes the A-T gene one of the most impor-

tant cancer-related genes identified to date.
The ATM gene is autosomal recessive, meaning the
disease occurs only if a defective gene is inherited fromboth parents. Infants with A-T initially often appear veryhealthy. At around age two, ataxia and nervous systemabnormalities becomes apparent. The root cause of A-T-associated ataxia is cell death in the brain, specifically

the large branching cells of the nervous system (Purkin-je’s cells) which are located in the cerebellum. A toddlerbecomes clumsy, loses balance easily and lacks musclecontrol. Speech becomes slurred and more difficult, andthe symptoms progressively worsen. Between ages twoand eight, telangiectases, or tiny, red “spider” veins,
appear on the cheeks and ears and in the eyes.
By age 10-12, children with A-T can no longer control

their muscles. Immune system deficiencies become com-mon, and affected individuals are extremely sensitive toradiation. Immune system deficiencies vary between indi-viduals but include lower-than-normal levels of proteinsthat function as antibodies (immunoglobulins) and whiteblood cells (blood cells not containing “iron” proteins). Thethymus gland, which aids in development of the body’simmune system, is either missing or has developed abnor-mally. Intelligence is normal, but growth may be

Intelligence is normal, but growth may be retardedowing to immune system or hormonal deficiencies. Indi-viduals with A-T are also sometimes afflicted with dia-betes, prematurely graying hair, and difficulty swallowing.As the children grow older, the immune system becomesweaker and less capable of fighting infection. In the laterstages, recurrent respiratory infections and blood cancers,such as leukemia or lymphoma, are common.

Diagnosis
Diagnosis relies on recognizing the hallmarks of A-
T: progressive ataxia and telangiectasia. However, thismay be difficult as ataxia symptoms do appear prior totelangiectasia symptoms by several years. Other symp-toms can vary between individuals; for example, 70% ofindividuals with A-T have a high incidence of respiratoryinfection, 30% do not. The identification of the ATMgene raises hopes that screening, and perhaps treatment,may be possible.
Treatment

focuses on managing the individual’s multiple symp-toms. Physical therapy and speech therapy can help thepatient adjust to ataxia. Injections of gamma globulin, orextracts of human blood that contain antibodies, are usedto strengthen the weakened immune system. High-dosevitamin administrations may also be prescribed.Research continues in many countries to find effectivetreatments. Individuals and families living with this dis-order may benefit from attending support groups.
Prognosis

Prognosis
A-T is a fatal condition. Children with A-T become
physically disabled by their early teens and typically dieby their early 20s, usually from the associated blood can-cers and malignancies. In very rare cases, individualswith A-T may experience slower progression and aslightly longer life span, surviving into their 30s. A-Tcarriers have a five-fold higher risk than non-carriers ofdeveloping certain cancers, especially breast cancer .

GALE ENCYCLOPEDIA OF MEDICINE 2 388Ataxia-telangiectasiaGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 388

Medical researchers are investigating methods for
screening individuals who may be carriers of the defec-tive gene. Prenatal testing for A-T is possible but notdone routinely, because commercial screening tests haveyet to be developed.
Resources
Lavin, Martin F., and Yosef Shiloh. “The Genetic Defect in
Ataxia-Telangiectasia.” Annual Review of Immunology 15
(1997): 177.
A-T Children’s Project. 1 W. Camino Real, Suite 212, Boca

Raton, FL 33432-5966. (561) 395-2621 or (800) 543-5728. <http://www.med.jhu.edu/ataxia/.
A-T Medical Research Foundation. 5241 Round Meadow Rd.,
Hidden Hills, CA 91302. (818) 704-8146.
A-T Project. 3002 Enfield Rd., Austin, TX 78703. (512) 472-
3417.KEY TERMS
Angioma —A tumor (such as a hemangioma or lym-
phangioma) that mainly consists of blood vessels orlymphatic vessels.
Antibody —Any of a large number of proteins pro-

duced by specialized blood cells after stimulationby an antigen and that act specifically against theantigen in an immune response.
Antigen —Any substance (such as a toxin or
enzyme) capable of stimulating an immuneresponse in the body.
Ataxia —The inability to control voluntary muscle
movement, most frequently resulting from disordersin the brain or spinal cord.
Autosomal —Relating to any of the chromosomes

except for X and Y, the sex chromosomes.
Cerebellum —The part of the brain responsible for
coordination of voluntary movements.
Gamma-globulin —An extract of human blood that
contains antibodies.
Immune response —A response from the body to an

antigen that occurs when the antigen is identified asforeign and that induces the production of antibod-ies and lymphocytes capable of destroying the anti-gen or making it harmless.Immunoglobulin —A protein in the blood that is the
component part of an antibody.
Leukemia —A cancer of blood cells characterized

by the abnormal increase in the number of whiteblood cells in the tissues. There are many types ofleukemias and they are classified according to thetype of white blood cell involved.
Lymphoma —A blood cancer in which lymphocytes,
a variety of white blood cells, grow at an unusuallyrapid rate.
Mutation —Any change in the hereditary material of
genes.
Purkinje’s cells —Large branching cells of the ner-
vous system.

Recessive —Producing little or no phenotypic effect
when occurring in heterozygous condition with acontrasting allele.
Telangiectases —Spidery red skin lesions caused by
dilated blood vessels.
Telangiectasia —Abnormal dilation of capillary
blood vessels leading to the formation of telangiec-tases or angiomas.
Thymus —A gland located in the front of the neck
that coordinates the development of the immunesystem.
The Ataxia-Telangiectasia Society of the United Kingdom,

<http://www.atsociety.org.uk>.
National Ataxia Foundation. 2600 Fernbrook Ln., Suite 119,
Minneapolis, MN 55447- 4752. (61) 553-0020. <http://www.ataxia.org/>.
Fairfield, CT 06812- 1783. (203) 746-6518 or (800) 999-6673.
Ataxia seeMovement disorders
Atelectasis
Atelectasis is a collapse of lung tissue affecting part
or all of one lung. This condition prevents normal oxy-gen absoption to healthy tissues.

GALE ENCYCLOPEDIA OF MEDICINE 2 389AtelectasisGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 389

age) of the airways that affects tiny air scas called alve-oli. Alveoli are very thin-walled and contain a rich bloodsupply. They are important for lung function, since theirpurpose is the exchange of oxygen and carbon dioxide.When the airways are blocked by a mucous “plug,” for-eign object, or tumor, the alveoli are unable to fill withair and collapse of lung tissue can occur in the affectedarea. Atelectasis is a potential complication followingsurgery, especially in individuals who have

especially in individuals who have undergonechest or abdominal operations resulting in associatedabdominal or chest pain during breathing. Congenital

atelectasis can result from a failure of the lungs toexpand at birth. This congenital condition may be local-ized or may affect all of both lungs.
Causes of atelectasis include insufficient attemps at

respiration by the newborn, bronchial obstruction, orabsence of surfactant (a substance secreted by alveolithat maintains the stability of lung tissue by reducing thesurface tension of fluids that coat the lung). This lack ofsurfactant reduces the surface area available for effectivegas exchange causing it to collapse if severe. Pressure onthe lung from fluid or air can cause atelectasis as well asobstruction of lung air passages by thick mucus resultingfrom various infections and lung

mucus resultingfrom various infections and lung diseases. Tumors andinhaled objects can also cause obstruction of the airway,

leading to atelectasis.
Anyone undergoing chest or abdominal surgery

using general anesthesia is at risk to develop atelectasis,since breathing is often shallow after surgery to avoidpain from the surgical incision. Any significant decreasein airflow to the alveoli contributes to pooling of secre-tions, which in turn can cause infection. Chest injuriescausing shallow breathing, including fractured ribs, cancause atelectasis. Common symptoms of atelectasisinclude shortness of breath and decreased chest wall

expansion. If atelectasis only afects a small area of thelung, symptoms are ususally minimal. If the conditionaffects a large area of the lung and develops quickly, theindividual may turn blue (cyanotic) or pale, have extremeshortness of breath, and feel a stabbing pain on theaffected side. Fever and increased heart rate may be pre-
sent if infection accompanies atelectasis.
Diagnosis
To diagnose atelectasis, a doctor starts by recording
the patient’s symptoms and performing a thorough phys-

ical examination . When the doctor listens to the lungs
through a stethoscope (ausculation), diminished orbronchial breath sounds may be heard. By tapping on thechest (percussion) while listening through the stetho-scope, the doctor can often tell if the lung is collapsed. Achest x ray that shows an airless area in the lung con-
firms the diagnosis of atelectasis. If an obstruction of theairways is suspected, a computed tomography scan (CT)or bronchoscopy may be performed to locate the cause

of the blockage.
Treatment
If atelectasis is due to obstruction of the airway, the
first step in treatment is to remove the cause of the block-age. This may be done by coughing, suctioning, or bron-choscopy. If a tumor is the cause of atelectasis, surgerymay be necessary to remove it. Antibiotics are commonly

used to fight the infection that often accompanies atelec-tasis. In cases where recurrent or long-lasting infection isdisabling or where significant bleeding occurs, the affect-ed section of the lung may be surgically removed.
Prognosis
If atelectasis is caused by a thick mucus “plug” or

inhaled foreign object, the patient usually recovers com-pletely when the blockage is removed. If it is caused by atumor, the outcome depends on the nature of the tumorinvolved. If atelectasis is a result of surgery, other post-oper-ative conditions and/or complications affect the prognosis.
GALE ENCYCLOPEDIA OF MEDICINE 2 390Atelectasis
A computed tomography (CT) scan through a patient’s

chest.The collapsed lung appears at the right of the image.(Photo Researchers, Inc. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 390

When recovering from surgery, frequent reposi-
tioning in bed along with coughing and deep breathingare important. Coughing and breathing deeply everyone to two hours after any surgical operation with gen-eral anesthesia is recommended. Breathing exercisesand the use of breathing devices, such as an incentivespirometer, may also help prevent atelectasis.Although smokers have a higher risk of developingatelectasis following surgery, stopping smoking six to

eight weeks before surgery can help reduce the risk.Increasing fluid intake during respiratory illness orafter surgery (by mouth or intravenously) helps lungsecretions to remain loose. Increasing humidity mayalso be beneficial.
Postural drainage techniques can be learned from a
respiratory therapist or physical therapist and are a usefultool for anyone affected with a respiratiory illness thatcould cause atelectasis. Because foreign objects block-

ing the airway can cause atelectasis, it is very importantto keep small objects that might be inhaled away fromyoung children.
Resources
BOOKS
Banasik, Jacquelyn L. “Restrictive Pulmonary Disorders.” In
Perspectives on Pathophysiology. Ed. Lee-Ellen C. Cop-
ogy.East Norwalk, CT: Appleton & Lange, 1991.KEY TERMS
Alveoli —Tiny air sacs in the lungs where gas

exchange takes place between alveolar air and pul-monary blood within the capillaries
Bronchial —Relating to the air passages to and from
the lungs including the bronchi and the bronchi-oles.
Bronchoscopy —A procedure in which a hollow,
flexible tube is inserted into the airway to allowvisual examination of the larynx, trachea, bronchi,and bronchioles. It is also used to collect specimensfor biopsy or culturing and to remove airwayobstructions.

Incentive spirometer —A breathing device that pro-
vides feedback on performance to encourage deepbreathing.Mucus —A thin, slippery film secreted by the
mucous membranes and glands.
Postural drainage —Techniques to help expel excess
mucus by specific poistions of the body (thatdecrease the effects of gravity) combined with man-ual percussion and vibration over various parts ofthe lung.
Surfactant —A substance secreted by the alveoli in

the lungs that reduces the surface tension of lungfluids, allowing gas exchange and helping maintainthe elasticity of lung tissue.
Tumor —An abnormal growth of tissue resulting
from uncontrolled, progressive multiplication ofcells.
Atenolol seeBeta blockers
Atherectomy
Atherectomy is a non-surgical procedure to open

blocked coronary arteries or vein grafts by using a deviceon the end of a catheter to cut or shave away atheroscle-rotic plaque (a deposit of fat and other substances thataccumulate in the lining of the artery wall).
Purpose
Atherectomy is performed to restore the flow of
oxygen-rich blood to the heart, to relieve chest pain , and

to prevent heart attacks. It may be done on patients withchest pain who have not responded to other medical ther-apy and on certain of those who are candidates for bal-loon angioplasty (a surgical procedure in which a bal-
loon catheter is used to flatten plaque against an arterywall) or coronary artery bypass graft surgery . It is
GALE ENCYCLOPEDIA OF MEDICINE 2 391AtherectomyGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 391

sometimes performed to remove plaque that has built up
after a coronary artery bypass graft surgery.
Atherectomy should not be performed when the
plaque is located where blood vessels divide into branch-es, when plaque is angular or inside an angle of a bloodvessel, on patients with weak vessel walls, on ulceratedor calcium-hardened lesions, or on blockages throughwhich a guide wire won’t pass.
Atherectomy uses a rotating shaver or other device

placed on the end of a catheter to slice away or destroyplaque. At the beginning of the procedure, medications tocontrol blood pressure, dilate the coronary arteries, andprevent blood clots are administered. The patient isawake but sedated. The catheter is inserted into an arteryin the groin, leg, or arm, and threaded through the bloodvessels into the blocked coronary artery. The cuttinghead is positioned against the plaque and activated, andthe plaque is ground up or suctioned out.The types of

plaque is ground up or suctioned out.The types of atherectomy are rotational, directional,

and transluminal extraction. Rotational atherectomy uses ahigh speed rotating shaver to grind up plaque. Directionalatherectomy was the first type approved, but is no longercommonly used; it scrapes plaque into an opening in oneside of the catheter. Transluminal extraction coronaryatherectomy uses a device that cuts plaque off vessel wallsand vacuums it into a bottle. It is used to clear bypass grafts.
Performed in a cardiac catheterization lab, atherec-

tomy is also called removal of plaque from the coronaryarteries. It can be used instead of, or along with, balloonangioplasty. Atherectomy is successful about 95% of thetime. Plaque forms again in 20-30% of patients.
The day before atherectomy, the patient takes med-
ication to prevent blood clots and may be asked to batheand shampoo with an antiseptic skin cleaner.
Aftercare
After the procedure, the patient spends several days

in the hospital’s cardiac monitoring area. For at least 20
GALE ENCYCLOPEDIA OF MEDICINE 2 392Atherectomy
In this digitized ultrasound of a blood vessel, C is the catheter, D is the dissection, and F is the artherosclerotic flap. (Custom
Medical Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 392

minutes, pressure is applied to a dressing on the insertion
site. For the first hour, an electrocardiogram and closemonitoring are conducted; vital signs are checked every15 minutes. Pain medication is then administered. Thepuncture site is checked once an hour or more. For mostof the first 24 hours, the patient remains in bed.
Risks
Chest pain is the most common complication of

atherectomy. Other common complications are injury tothe blood vessel lining, plaque that re-forms, blood clots(hematoma), and bleeding at the site of insertion. Moreserious but less frequent complications are blood vesselholes, blood vessel wall tears, or reduced blood flow tothe heart.
Resources
BOOKS
Current Medical Diagnosis and Treatment, 1998. 37th ed. Ed.

DeBakey Michael E, and Antonio M. Gotto Jr. “Therapeutic
Procedures.” In The New Living Heart. Holbrook, MA:
Texas Heart Institute. “Coronary Artery Disease, Angina, and
Heart Attacks.” In Texas Heart Institute Heart Owner’s
Handbook. New York: John Wiley & Sons, 1996.
Bittl, John A., and Patricia Thomas. “Beyond the Balloon.”
Harvard Health Letter 21, no. 3 (Jan. 1996): 4.KEY TERMS
Atherosclerotic plaque —A deposit of fat and

other substances that accumulate in the lining ofthe artery wall.
Balloon angioplasty —A surgical procedure in
which a balloon catheter is used to flatten plaqueagainst an artery wall.
Coronary arteries —The two main arteries that

provide blood to the heart. The coronary arteriessurround the heart like a crown, coming out of theaorta, arching down over the top of the heart, anddividing into two branches. These are the arterieswhere coronary artery disease occurs.
Hematoma —A localized collection of blood, usu-
ally clotted, due to a break in the wall of bloodvessel.ORGANIZATIONS

OTHER
“Atherectomy.” American Heart Association. 1997. 30 Mar.
1998 <http://www.americanheart.org>.
Atherectomy seeAngioplasty
Atherosclerosis
Atherosclerosis is the build up of a waxy plaque on
the inside of blood vessels. In Greek, athere means gruel ,

and skleros means hard. Atherosclerosis is often called
arteriosclerosis. Arteriosclerosis (from the Greek arteria,
meaning artery ) is a general term for hardening of the
arteries. Arteriosclerosis can occur in several forms,including atherosclerosis.
Atherosclerosis, a progressive process responsible

for most heart disease, is a type of arteriosclerosis orhardening of the arteries. An artery is made up of severallayers: an inner lining called the endothelium, an elasticmembrane that allows the artery to expand and contract,a layer of smooth muscle, and a layer of connective tis-sue. Arteriosclerosis is a broad term that includes a hard-ening of the inner and middle layers of the artery. It canbe caused by normal aging , by high blood pressure, and

by diseases such as diabetes. Atherosclerosis is a type ofarteriosclerosis that affects only the inner lining of anartery. It is characterized by plaque deposits that blockthe flow of blood.
Plaque is made of fatty substances, cholesterol,

waste products from the cells, calcium, and fibrin, astringy material that helps clot blood. The plaque forma-tion process stimulates the cells of the artery wall to pro-duce substances that accumulate in the inner layer. Fatbuilds up within these cells and around them, and theyform connective tissue and calcium. The inner layer ofthe artery wall thickens, the artery’s diameter is reduced,and blood flow and oxygen delivery are decreased.Plaques can rupture or crack open, causing the

can rupture or crack open, causing the suddenformation of a blood clot (thrombosis). Atherosclerosis

GALE ENCYCLOPEDIA OF MEDICINE 2 393AtherosclerosisGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 393

can cause a heart attack if it completely blocks the
blood flow in the heart (coronary) arteries. It can cause astroke if it completely blocks the brain (carotid) arteries.
Atherosclerosis can also occur in the arteries of the neck,kidneys, thighs, and arms, causing kidney failure or gan-
grene and amputation .
Atherosclerosis can begin in the late teens, but it

usually takes decades to cause symptoms. Some peopleexperience rapidly progressing atherosclerosis duringtheir thirties, others during their fifties or sixties. Athero-sclerosis is complex. Its exact cause is still unknown. It isthought that atherosclerosis is caused by a response todamage to the endothelium from high cholesterol , high
blood pressure, and cigarette smoking . A person who has

all three of these risk factors is eight times more likely todevelop atherosclerosis than is a person who has none.Physical inactivity, diabetes, and obesity are also risk
factors for atherosclerosis. High levels of the amino acidhomocysteine and abnormal levels of protein-coated fatscalled lipoproteins also raise the risk of coronary artery
disease . These substances are the targets of much current

research. The role of triglycerides, another fat that circu-lates in the blood, in forming atherosclerotic plaques isunclear. High levels of triglycerides are often associatedwith diabetes, obesity, and low levels of high-densitylipoproteins (HDL cholesterol). The more HDL (“good”)cholesterol, in the blood, the less likely is coronary arterydisease. These risk factors are all modifiable. Non-modi-fiable risk factors are heredity, sex, and age.
Risk factors that can be changed:

• Cigarette/tobacco smoke—Smoking increases both the
chance of developing atherosclerosis and the chance ofdying from coronary heart disease. Second hand smokemay also increase risk.
• High blood cholesterol—Cholesterol, a soft, waxy sub-

stance, comes from foods such as meat, eggs, and otheranimal products and is produced in the liver. Age, sex,heredity, and diet affect cholesterol. Total blood choles-terol is considered high at levels above 240 mg/dL andborderline at 200-239 mg/dL. High-risk levels of low-density lipoprotein (LDL cholesterol) begin at 130-159mg/dL.
• High triglycerides—Most fat in food and in the body

takes the form of triglycerides. Blood triglyceride lev-els above 400 mg/dL have been linked to coronaryartery disease in some people. Triglycerides, however,are not nearly as harmful as LDL cholesterol.• High blood pressure—Blood pressure of 140 over 90 or
higher makes the heart work harder, and over time, bothweakens the heart and harms the arteries.
• Physical inactivity—Lack of exercise increases the risk
of atherosclerosis.
• Diabetes mellitus—The risk of developing atheroscle-

rosis is seriously increased for diabetics and can belowered by keeping diabetes under control. Most dia-betics die from heart attacks caused by atherosclerosis.
• Obesity—Excess weight increases the strain on the
heart and increases the risk of developing atherosclero-sis even if no other risk factors are present.
Risk factors that cannot be changed:
• Heredity—People whose parents have coronary artery

disease, atherosclerosis, or stroke at an early age are atincreased risk. The high rate of severe hypertension
among African-Americans puts them at increased risk.
• Sex—Before age 60, men are more likely to have heart
attacks than women are. After age 60, the risk is equalamong men and women.
• Age—Risk is higher in men who are 45 years of age and
older and women who are 55 years of age and older.
Symptoms differ depending upon the location of the
atherosclerosis.

• In the coronary (heart) arteries: Chest pain, heart attack,
or sudden death .
• In the carotid (brain) arteries: Sudden dizziness , weak-
ness, loss of speech, or blindness.
• In the femoral (leg) arteries: Disease of the blood ves-
sels in the outer parts of the body ( peripheral vascular
disease ) causes cramping and fatigue in the calves
when walking.
• In the renal (kidney) arteries: High blood pressure that
is difficult to treat.
Diagnosis

Diagnosis
Physicians may be able to make a diagnosis of athero-
sclerosis during a physical exam by means of a stetho-scope and gentle probing of the arteries with the hand (pal-pation). More definite tests are electrocardiography ,
echocardiography or ultrasonography of the arteries (for
example, the carotids), radionuclide scans, and angiogra-
phy.
An electrocardiogram shows the heart’s activity. Elec-

trodes covered with conducting jelly are placed on thepatient’s body. They send impulses of the heart to arecorder. The test takes about 10 minutes and is performedin a physician’s office. Exercise electrocardiography ( stress
test) is conducted while the patient exercises on a treadmill
GALE ENCYCLOPEDIA OF MEDICINE 2 394AtherosclerosisGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 394

or a stationary bike. It is performed in a physician’s office or
an exercise laboratory and takes 15-30 minutes.
Echocardiography, cardiac ultrasound, uses sound

waves to create an image of the heart’s chambers andvalves. A technician applies gel to a hand-held transduc-er, presses it against the patient’s chest, and images aredisplayed on a monitor. This technique cannot evaluatethe coronary arteries directly. They are too small and arein motion with the heart. Severe coronary artery disease,however, may cause abnormal heart motion that isdetected by echocardiography. Performed in a cardiologyoutpatient diagnostic laboratory, the test takes

diagnostic laboratory, the test takes 30-60minutes. Ultrasonography is also used to assess arteriesof the neck and thighs.Radionuclide angiography and thallium (or ses-

tamibi) scanning enable physicians to see the blood flowthrough the coronary arteries and the heart chambers.Radioactive material is injected into the bloodstream. Adevice that uses gamma rays to produce an image of theradioactive material (gamma camera) records pictures ofthe heart. Radionuclide angiography is usually performedin a hospital’s nuclear medicine department and takes 30-60 minutes. Thallium scanning is usually done after anexercise stress test or after injection of a vasodilator,

drug to enlarge the blood vessels, like dipyridamole (Per-santine). Thallium is injected, and the scan is done thenand again four hours (and possibly 24 hours) later. Thalli-um scanning is usually performed in a hospital’s nuclearmedicine department. Each scan takes 30-60 minutes.
GALE ENCYCLOPEDIA OF MEDICINE 2 395Atherosclerosis
The result is a fibrous

The result is a fibrous 
lesion, made up in partof muscle cells, proteins, and collagen, that has at its center a pool of lipids and dead cells. Blood flow can be very nearly cut off by the blockage.
When the arterial lining becomes 
separated over the growing mass of foam cells, platelets are attracted to the site and begin the process of clot formation.PlateletsHigh cholesterol levels,

high blood pressure, diabetes, obesity, viruses,cigarette smoking, etc., cause injuries to the lining of the artery, creating areas where higher levels of lipidsare trapped.
Further injury is inflicted by foam cells
attempting to remove lipids back to thelungs, liver, spleen and lymph nodesby again passing through the lining ofthe artery.Monocyte Lining of
arteryMuscle
T -cell
Monocytes (the largest of the 
white blood cells) and T -cells are attracted to the injury.

Foam cellMonocytes, which become 
macrophages when they leave the bloodstream, and T -cells penetrate the lining of the artery.The macrophages soak up lipids, becoming large foam cells and distorting the inner surface of the artery. Blood flow becomesrestricted.
The progression of atherosclerosis. (Illustration by Hans & Cassady.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 395

tic method and the only one that requires entering thebody (invasive procedure). A cardiologist inserts acatheter equipped with a viewing device into a blood ves-sel in the leg or arm and guides it into the heart. Thepatient has been given a contrast dye that makes the heartvisible to x rays. Motion pictures are taken of the con-trast dye flowing though the arteries. Plaques and block-ages, if present, are well defined. The patient is awakebut has been given a sedative. Coronary angiography

has been given a sedative. Coronary angiography isperformed in a cardiac catheterization laboratory and

takes from 30 minutes to two hours.
Treatment
Treatment includes lifestyle changes, lipid-lowering
drugs, percutaneous transluminal coronary angioplasty ,
and coronary artery bypass surgery. Atherosclerosisrequires lifelong care.
Patients who have less severe atherosclerosis may

achieve adequate control through lifestyle changes anddrug therapy. Many of the lifestyle changes that preventdisease progression—a low-fat, low-cholesterol diet, los-ing weight (if necessary), exercise, controlling bloodpressure, and not smoking—also help prevent the disease.
Most of the drugs prescribed for atherosclerosis seek

to lower cholesterol. Many popular lipid-lowering drugscan reduce LDL-cholesterol by an average of 25-30%when combined with a low-fat, low-cholesterol diet.Lipid-lowering drugs include bile acid resins, “statins”(drugs that effect HMG-CoA reductase, an enzyme thatcontrols the processing of cholesterol), niacin, and fibricacid derivatives such as gemfibrozil (Lobid). Aspirin
helps prevent thrombosis and a variety of other medica-tions can be used to treat the effects of atherosclerosis.

bypass surgery are invasive procedures that improveblood flow in the coronary arteries. Percutaneous translu-minal coronary angioplasty (coronary angioplasty) is anon-surgical procedure in which a catheter tipped with aballoon is threaded from a blood vessel in the thigh intothe blocked artery. The balloon is inflated, compresses theplaque to enlarge the blood vessel, and opens the blockedartery. Coronary angioplasty is performed by a cardiolo-gist in a hospital and generally requires a

in a hospital and generally requires a hospital stay ofone or two days. It is successful about 90% of the time,but for one-third of patients the artery narrows again with-in six months. It can be repeated and a “stent” may beplaced in the artery to help keep it open (see below).

In coronary artery bypass surgery (bypass surgery),
a detour is built around the blockage with a healthy veinor artery, which then supplies oxygen-rich blood to theheart. It is major surgery appropriate for patients with

blockages in two or three major coronary arteries orseverely narrowed left main coronary arteries, and forthose who have not responded to other treatments. It isperformed in a hospital under general anesthesia anduses a heart-lung machine. About 70% of patients experi-ence full relief; about 20% partial relief.
Three other semi-experimental surgical procedures
may be used to treat atherosclerosis. In atherectomy ,a

cardiologist shaves off and removes strips of plaque fromthe blocked artery. In laser angioplasty, a catheter with alaser tip is inserted to burn or break down the plaque. Ametal coil called a stent may be permanently implantedto keep a blocked artery open.
Alternative therapies that focus on diet and lifestyle
can help prevent, retard, or reverse atherosclerosis. Herbaltherapies that may be helpful include: hawthorn ( Cratae-

gus laevigata ), notoginseng root ( Panax notoginseng ),
garlic ( Allium sativum ), ginger ( Zingiber officinale ), hot
red or chili peppers, yarrow ( Achillea millefolium ), and
alfalfa ( Medicago sativum ). Relaxation techniques
including yoga ,meditation ,guided imagery ,biofeed-
back , and counseling and other “talking” therapies may

also be useful to prevent or slow the progress of the dis-ease. Dietary modifications focus on eating foods that arelow in fats (especially saturated fats), cholesterol, sugar,and animal proteins and high in fiber and antioxidants(found in fresh fruits and vegetables). Liberal use ofonions and garlic is recommended, as is eating raw andcooked fish, especially cold-water fish like salmon.Smoking, alcohol, and stimulants like coffee should beavoided. Chelation therapy , which uses anticoagulant

drugs and nutrients to dissolve plaque and flush it throughthe kidneys, is controversial. Long-term remedies can beprescribed by specialists in ayurvedic medicine , which
combines diet, herbal remedies, relaxation and exercise,and homeopathy , which treats a disease with small doses
of a drug that causes the symptoms of the disease.
Prognosis
Atherosclerosis can be successfully treated but not

cured. Recent clinical studies have shown that athero-sclerosis can be delayed, stopped, and even reversed byaggressively lowering LDL cholesterol. New diagnostictechniques enable physicians to identify and treat athero-sclerosis in its earliest stages. New technologies and sur-gical procedures have extended the lives of many patientswho would otherwise have died. Research continues.
GALE ENCYCLOPEDIA OF MEDICINE 2 396AtherosclerosisGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 396

A healthy lifestyle—eating right, regular exercise,
maintaining a healthy weight, not smoking, and control-ling hypertension—can reduce the risk of developingatherosclerosis, help keep the disease from progressing,and sometimes cause it to regress.
• Eat right-A healthy diet reduces excess levels of LDL

cholesterol and triglycerides. It includes a variety offoods that are low in fat and cholesterol and high infiber; plenty of fruits and vegetables; and limited sodi-um. Fat should comprise no more than 30%, and saturat-ed fat no more than 8-10%, of total daily caloriesaccording to the American Heart Association. Choles-terol should be limited to about 300 milligrams per dayand sodium to about 2,400 milligrams. The “FoodGuide” Pyramid developed by the U.S. Departments ofAgriculture and Health

by the U.S. Departments ofAgriculture and Health and Human Services providesdaily guidelines: 6-11 servings of bread, cereal, rice, andpasta; 3-5 servings of vegetables; 2-4 servings of fruit;2-3 servings of milk, yogurt, and cheese; and 2-3 serv-ings of meat, poultry, fish, dry beans, eggs, and nuts.Fats, oils, and sweets should be used sparingly. Mono-unsaturated oils, like olive and rapeseed (Canola) aregood alternatives to use for cooking.

pressure, help control weight, and increase HDL(“good”) cholesterol. It may keep the blood vesselsmore flexible. Moderate to intense aerobic exerciselasting about 30 minutes (or three 10-minute exerciseperiods) four or more times per week is recommended,according to the Centers for Disease Control and Pre-vention and the American College of Sports Medicine.Aerobic exercise includes walking, jogging, andcycling, active gardening, climbing stairs, or briskhousework. A physician should be

stairs, or briskhousework. A physician should be consulted beforeexercise if a person has atherosclerosis or is atincreased risk for it.

• Maintain a desirable body weight—Losing weight can
help reduce total and LDL cholesterol, reduce triglyc-erides, and boost HDL cholesterol. It may also reduceblood pressure. Eating right and exercising are two keycomponents in maintaining a desirable body weight.
• Do not smoke or use tobacco—Smoking has many

adverse effects on the heart but quitting can repairdamage. Ex-smokers face the same risk of heart dis-ease as non-smokers within five to 10 years of quitting.Smoking is the worst thing a person can do to theirheart and lungs.
• Seek treatment for hypertension—High blood pressure
can be controlled through lifestyle changes—reducingsodium and fat, exercising, managing stress, quittingKEY TERMS
Arteriosclerosis —Hardening of the arteries. It

includes atherosclerosis, but the two terms areoften used synonymously.
Cholesterol —A fat-like substance that is made by
the human body and eaten in animal products.Cholesterol is used to form cell membranes andprocess hormones and vitamin D. High choles-terol levels contribute to the development of ath-erosclerosis.
HDL Cholesterol —About one-third or one-fourth

of all cholesterol is high-density lipoprotein cho-lesterol. High levels of HDL, nicknamed “good”cholesterol, decrease the risk of atherosclerosis.
LDL Cholesterol —Low-density lipoprotein choles-
terol is the primary cholesterol molecule. Highlevels of LDL, nicknamed “bad” cholesterol,increase the risk of atherosclerosis
Plaque —A deposit of fatty and other substances
that accumulates in the lining of the artery wall.

Triglyceride —A fat that comes from food or is
made from other energy sources in the body. Ele-vated triglyceride levels contribute to the develop-ment of atherosclerosis.
smoking, and drinking alcohol in moderation—and
medication. Drugs that provide effective treatment are:diuretics , beta-blockers, sympathetic nerve inhibitors,
vasodilators , angiotensin converting enzyme

inhibitors, and calcium antagonists. Hypertension usu-ally has no symptoms so it must be checked to beknown. Like cholesterol, hypertension is called a“silent killer”.
Resources
BOOKS
American Heart Association. “The Power of Prevention.” In
American Heart Association and American Cancer Society.
Living Well, Staying Well. New York: American Heart

Association and American Cancer Society, 1996.
“Atherosclerosis.” In The Complete Family Guide to Alterna-
tive Medicine , ed. C. Norman Shealy. New York: Barnes
& Noble Books, 1996.
“Basic Mechanisms of Atherosclerosis.” In Cardiovascular
Medicine , ed. J. T. Willerson and J. Cohn. New York:
GALE ENCYCLOPEDIA OF MEDICINE 2 397AtherosclerosisGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 397

Athlete’s foot fungus on bottom of patient’s foot. (Custom
Medical Stock Photo. Reproduced by permission.)DeBakey Michael E., and Antonio M. Gotto Jr. “Atherosclero-
sis.” In The New Living Heart. Holbrook, MA: Adams
Media Corporation, 1997.
The Editors of Time-Life Books. “Atherosclerosis.” In The
Alternative Advisor: The Complete Guide to NaturalTherapies and Alternative Treatments. Alexandria, V A:
Time-Life Books, 1997.

Heart Attacks” and “Diseases of the Peripheral Arteriesand Veins.” In Texas Heart Institute Heart Owner’s Hand-
book. New York: John Wiley & Sons, 1996.
“Landmark Study Shows Heart Disease Prevention Must Start
Early.” The Nation’s Health (Mar. 1997): 13.
Morgan, Peggy. “What Your Heart Wishes You Knew About
Cholesterol.” Prevention , Sept. 1997, 96.

Athetosis seeMovement disorders
Athlete’s foot
A common fungus infection between the toes in

which the skin becomes itchy and sore, cracking andpeeling away. Athlete’s foot (also known as tinea pedis orfoot ringworm ) can be treated, but it can be tenacious
and difficult to clear up completely.
Athlete’s foot is a very common condition of itchy,

peeling skin on the feet. In fact, it’s so common that mostpeople will have at least one episode at least once in theirlives. It’s less often found in women and children underage 12. (Symptoms that look like athlete’s foot in youngchildren most probably are caused by some other skincondition).
Because the fungi grow well in warm, damp areas,

they flourish in and around swimming pools, showers,and locker rooms. Tinea pedis got its common namebecause the infection was common among athletes whooften used these areas.
Athlete’s foot is caused by a fungal infection that
most often affects the fourth and fifth toe webs. Trichophy-
ton rubrum ,T. mentagrophytes , and Epidermophyton floc-
cosum , the fungi that cause athlete’s foot, are unusual in

that they live exclusively on dead body tissue (hair, theouter layer of skin, and nails). The fungus grows best inmoist, damp, dark places with poor ventilation. The prob-lem doesn’t occur among people who usually go barefoot.
Many people carry the fungus on their skin. Howev-

er, it will only flourish to the point of causing athlete’sfoot if conditions are right. Many people believe athlete’sfoot is highly contagious, especially in public swimmingpools and shower rooms. Research has shown, however,that it is difficult to pick up the infection simply by walk-ing barefoot over a contaminated damp floor. Exactlywhy some people develop the condition and others don’tis not well understood.
Sweaty feet, tight shoes, synthetic socks that don’t

absorb moisture well, a warm climate, and not drying thefeet well after swimming or bathing, all contribute to theovergrowth of the fungus.
Symptoms of athlete’s foot include itchy, sore skin
on the toes, with scaling, cracking, inflammation, andblisters. Blisters that break, exposing raw patches of tis-sue, can cause pain and swelling. As the infection
spreads, itching and burning may get worse.
If it’s not treated, athlete’s foot can spread to the

soles of the feet and toenails. Stubborn toenail infectionsmay appear at the same time, with crumbling, scaling andthickened nails, and nail loss. The infection can spreadfurther if patients scratch and then touch themselves else-
GALE ENCYCLOPEDIA OF MEDICINE 2 398Athlete’s footGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 398

where (especially in the groin or under the arms). It’s also
possible to spread the infection to other parts of the bodyvia contaminated bed sheets or clothing.
Diagnosis
Not all foot rashes are athlete’s foot, which is why a
physician should diagnose the condition before anyremedies are used. Using nonprescription products on arash that is not athlete’s foot could make the rash worse.
A dermatologist can diagnose the condition by
physical examination and by examining a preparation

of skin scrapings under a microscope. This test, called aKOH preparation, treats a sample of tissue scraped fromthe infected area with heat and potassium hydroxide(KOH). This treatment dissolves certain substances inthe tissue sample, making it possible to see the fungiunder the microscope.
Treatment
Athlete’s foot may be resistant to medication and

should not be ignored. Simple cases usually respond wellto antifungal creams or sprays (clotrimazole, ketocona-zole, miconazole nitrate, sulconazole nitrate, or tolnaf-tate). If the infection is resistant to topical treatment, thedoctor may prescribe an oral antifungal drug.
Untreated athlete’s foot may lead to a secondary
bacterial infection in the skin cracks.
A footbath containing cinnamon has been shown to

slow down the growth of certain molds and fungi, and issaid to be very effective in clearing up athlete’s foot. Tomake the bath:• heat four cups of water to a boil
• add eight to 10 broken cinnamon sticks
• reduce heat and simmer five minutes
• remove and let the mixture steep for 45 minutes until
lukewarm
• soak feet
Other herbal remedies used externally to treat ath-

lete’s foot include: a foot soak or powder containinggoldenseal ( Hydrastis canadensis ); tea tree oil ( Melaleu-
caspp.); or calendula ( Calendula officinalis ) cream to
help heal cracked skin.
Prognosis
Athlete’s foot usually responds well to treatment,

but it is important to take all medication as directed by adermatologist, even if the skin appears to be free of fun-gus. Otherwise, the infection could return. The toenailinfections that may accompany athlete’s foot, however,are typically very hard to treat effectively
Good personal hygiene and a few simple precautions
can help prevent athlete’s foot. To prevent spread of ath-lete’s foot:
• wash feet daily

• dry feet thoroughly (especially between toes)• avoid tight shoes (especially in summer)• wear sandals during warm weather
• wear cotton socks and change them often if they get
damp
• don’t wear socks made of synthetic material• go barefoot outdoors when possible
• wear bathing shoes in public bathing or showering
areas
• use a good quality foot powder• don’t wear sneakers without socks• wash towels, contaminated floors, and shower stalls

well with hot soapy water if anyone in the family hasathlete’s foot
Resources
BOOKS
Donahue, Peggy Jo. Relief from Chronic Skin Problems. New
York: Dell Publishing, 1992.
Orkin, Milton, Howard Maibach, and Mark Dahl. Dermatol-
ogy.Norwalk, CT: Appleton & Lange, 1991.
ing 100 Infectious Illnesses. New York: John Wiley &
GALE ENCYCLOPEDIA OF MEDICINE 2 399Athlete’s foot

Athlete’s foot fungus on toes of patient. (Custom Medical
Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 399

Thompson, June, et al. Mosby’s Clinical Nursing. St. Louis:
Mosby, 1998.
American Podiatric Medical Association. 9312 Old George-
town Road, Bethesda, MD 20814-1698. (301) 571-9200.<http://www.apma.org>.
Athletic heart syndrome
Athletic heart syndrome is the adaptation of an ath-
lete’s heart in response the physiologic stresses of strenu-ous physical training. It can be difficult to distinguish asignificant medical condition from an athletic heart.

especially the left ventricle. Enlargement increases thecardiac output, the amount of blood pumped with eachbeat of the heart. The exact type of adaptation dependson the nature of the physical demand. There are twotypes of demand, static and dynamic. Static demandinvolves smaller groups of muscles under extreme resis-tance for brief period. An example is weight lifting.Dynamic training involves larger groups of muscles atlower resistance for extended periods of time. Examplesare aerobic

for extended periods of time. Examplesare aerobic training and tennis. Cardiac enlargement isassociated with dynamic training. The heart’s response tostatic training is hypertrophy, thickening of the musclewalls of the heart. As the wall of the heart adapts, thereare changes in the electrical conducting system of theheart. Because of the larger volume of blood beingpumped with each heart beat, the heart rate when at restdecreases below the normal level for nonathletes.

Sudden unexpected death (SUD) is the death of an
athlete, usually during or shortly after physical activity.Often, there is no warning that the person will experienceSUD, although in some cases, warning signs appearwhich cause the person to seek medical advice. Impor-tantly, cases of death occurring during physical activityare not caused by athletic heart syndrome, but by undiag-nosed heart disorders.
Athletic heart syndrome is the consequence of a nor-

mal adaptation by the heart to increased physical activity.The changes in the electrical conduction system of theheart may be pronounced and diagnostic, but should notcause problems. In the case of SUD, other heart prob-lems are involved. In 85-97% of the cases of SUD, anunderlying structural defect of the heart has been noted.
Diagnosis
The changes in the heart beat caused by the electri-

cal conduction system of the heart are detectable on anelectrocardiogram. Many of the changes seen in athleticheart syndrome mimic those of various heart diseases.Careful examination must be made to distinguish heartdisease from athletic heart syndrome.
Prognosis
The yearly rate for occurrence of SUD in people less
than 35 years of age is less than seven incidents per100,000. Of all SUD cases, only about 8% are exercise

related. On a national basis, this means that each yearapproximately 25 athletes experience SUD. In personsover age 35, the incidence of SUD is approximately 55 in100,000, with only 3% of the cases occurring duringexercise.
Resources
BOOKS
Co., 1997.
Gibler, W. B., and T. P. Aufderheide. Emergency Cardiac Care.
St. Louis: Mosby, 1994.

Atkins diet
The Atkins diet is a high-protein, high-fat, and very
low-carbohydrate regimen. It emphasizes meat, cheese,and eggs, while discouraging foods such as bread, pasta,fruit, and sugar. It is a form of ketogenic diet.
Purpose
The primary benefit of the diet is rapid and substan-

tial weight loss. By restricting carbohydrate intake, thebody will burn more fat stored in the body. Since there areno limits on the amount of calories or quantities of foodsallowed on the diet, there is little hunger between meals.According to Atkins, the diet can alleviate symptoms of
GALE ENCYCLOPEDIA OF MEDICINE 2 400Athletic heart syndromeGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 400

conditions such as fatigue , irritability, headaches, depres-
sion, and some types of joint and muscle pain.
The regimen is a low-carbohydrate, or ketogenic

diet, characterized by initial rapid weight loss, usuallydue to water loss. Drastically reducing the amount of car-bohydrate intake causes liver and muscle glycogen loss,which has a strong but temporary diuretic effect. Long-term weight loss occurs because with a low amount ofcarbohydrate intake, the body burns stored fat for energy.
The four-step diet starts with a two-week induction

program designed to rebalance an individual’s metabo-lism. Unlimited amounts of fat and protein are allowedbut carbohydrate intake is restricted to 15-20 grams perday. Foods allowed include butter, oil, meat, poultry, fish,eggs, cheese, and cream. The daily amount of carbohy-drates allowed equals about three cups of salad vegeta-bles, such as lettuce, cucumbers, and celery.
The second stage is for ongoing weight loss. It

allows 15-40 grams of carbohydrates a day. When theindividual is about 10 pounds from their desired weight,
they begin the pre-maintenance phase. This graduallyadds one to three servings a week of high carbohydratefoods, such as a piece of fruit or slice of whole-wheatbread. When the desired weight is reached, the mainte-nance stage begins. It allows 40-60 grams of carbohy-drates per day.
Opinion from the general medical community

remains mixed on the Atkins diet, but is generally unfa-vorable. There have been no significant long-term scien-tific studies on the diet. A number of leading medical andhealth organizations, including the American MedicalAssociation, American Dietetic Association (ADA), andthe American Heart Association oppose it. It is drastical-ly different than the dietary intakes recommended by theU.S. Department of Agriculture and the National Insti-tutes of Health. Much of the opposition is because

of Health. Much of the opposition is because thediet is lacking in some vitamins and nutrients, and

because it is high in fat. In a hearing before the U.S. Con-gress on February 24, 2000, an ADA representativecalled the Atkins diet “hazardous” and said it lacked sci-entific credibility.
GALE ENCYCLOPEDIA OF MEDICINE 2 401Atkins diet
DR. ROBERT C. ATKINS (1930– )
Dr. Robert C. Atkins graduated from the University
of Michigan in 1951 and received his medical degreefrom Cornell University Medical School in 1955 with aspecialty in cardiology. As an internist and cardiologist

he developed the Atkins Diet in the early 1970s. The dietis a ketogenic diet—a high protein, high fat, and verylow carbohydrate regimen resulting in ketosis. It empha-sizes meat, cheese, and eggs, while discouraging foodssuch as bread, pasta, fruit, and sugar. It first came to pub-lic attention in 1972 with the publication of Dr. Atkins’
Diet Revolution . The book quickly became a bestseller

but unlike most other fad diet books, this one hasremained popular. At last count, it had been reprinted 28times and sold more than 10 million copies worldwide.Since then, Atkins has authored a number of other bookson his diet theme, including Dr. Atkins’ New Diet Revo-
lution (1992), Dr. Atkins’ Quick and Easy New Diet
Cookbook (1997), and The Vita-Nutrient Solution:
Nature’s Answer to Drugs (1998).
Atkins has seen about 60,000 patients in his more

than 30 years of practice. He has also appeared on numer-ous radio and television talk shows, has his own syndicat-ed radio program, Your Health Choices , and authors the
monthly newsletter Dr. Atkins’ Health Revelations . Atkins

has received the World Organization of Alternative Medi-cine’s Recognition of Achievement Award and beennamed the National Health Federation’s Man of the Year.He is director of the Atkins Center for ComplementaryMedicine which he founded in the early 1980s. The centeris located at 152 E. 55th St., New York, NY 10022.
(AP/Wide World Photos. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 401

No advance preparation is needed to go on the diet.
However, as with most diets , it is generally considered
appropriate to consult with a physician and to have aphysical evaluation before starting such a nutritional reg-imen. The evaluation should include blood tests to deter-mine levels of cholesterol, triglycerides, glucose, insulin,and uric acid. A glucose tolerance test is also recom-mended.
Adherence to the Atkins diet can result in vitamin

and mineral deficiencies. In his books, Atkins recom-mends a wide-range of nutritional supplements, includ-ing a multi-vitamin. Among his recommendations,Atkins suggests the following daily dosages: 300-600micrograms (mcg) of chromium picolinate, 100-400 mil-ligrams (mg) of pantetheine, 200 mcg of selenium, and450-675 mcg of biotin.
The diet is not recommended for lacto-ovo vegetari-

ans, since it cannot be done as successfully without pro-tein derived from animal products. Also, vegans cannotfollow this diet, since a vegan diet is too high in carbohy-drates, according to Atkins. Instead, he recommends veg-etarians with a serious weight problem give up vegetari-
anism , or at least include fish in their diet.
According to Atkins, the diet causes no adverse side

effects. Many health care professionals disagree. In a factsheet for the Healthcare Reality Check Web site(http://www.hcrc.org), Ellen Coleman, a registered dieti-cian and author, said the diet may have serious sideeffects for some people. She said complications associat-ed with the diet include ketosis, dehydration , electrolyte
loss, calcium depletion, weakness, nausea, and kidneyproblems. “It is certainly riskier for overweight individu-als with medical problems such as heart disease, hyper-

tension , kidney disease, and diabetes than it is for over-
weight people with no health problems,” she said.
People with diabetes taking insulin are at risk of
becoming hypoglycemic if they do not eat appropriatecarbohydrates. Also, persons who exercise regularly may
experience low energy levels and muscle fatigue fromlow carbohydrate intake.
Resources
BOOKS
Atkins, Dr. Robert C. Dr. Atkins’ New Diet Revolution. New
York City: Avon Books. 1992.KEY TERMS

Biotin —A B complex vitamin, found naturally in
yeast, liver, and egg yolks.
Carbohydrates —Neutral compounds of carbon,
hydrogen, and oxygen found in sugar, starches,and cellulose.
Hypertension —Abnormally high arterial blood
pressure, which if left untreated can lead to heartdisease and stroke.
Ketogenic diet —A diet that supplies an abnormal-
ly high amount of fat, and small amounts of carbo-hydrates and protein.

Ketosis —An abnormal increase in ketones in the
body, usually found in people with uncontrolleddiabetes mellitus.
Pantetheine —A growth factor substance essential
in humans, and a constituent of coenzyme A.
Triglycerides —A blood fat lipid that increases the
risk for heart disease.
Atkins, Dr. Robert C. Dr. Atkins’Vita-Nutrient Solution: Nature’s
Answer to Drugs. New York: Simon & Schuster. 1998.
Atkins, Dr. Robert C. Dr. Atkins’ Health Revolution: How

Complementary Medicine Can Extend Your Life. New
York: Bantam Books. 1990.
Atkins, Dr. Robert C. Dr. Atkins’Age-Defying Diet Revolution.
New York: St. Martin’s Press. 1999.
Atkins, Dr. Robert C. Dr. Atkins’ Diet Revolution: The High
Calorie Way to Stay Thin Forever. New York: Bantam
Books. 1989.
Alger, Alexandra. “Meat’s Neat.” Forbes (Aug. 11, 1997): 129.
Carroll, Joanne. “The Ketogenic Diet: A Practical Guide for
Caregivers.” Journal of the American Dietetic Association

(March 1998): 316-321.
Cray, Dan, et al. “The Low-Carb Diet Craze.” Time (Nov. 1,
1999): 72-79.
Gotthardt, Melissa Meyers. “The New Low-Carb Diet Craze.”
Cosmopolitan (Feb. 2000): 148.
Hammock, Delia. “Dr. Atkins’ New Diet Revolution.” Good
Housekeeping (June 1997): 127.
Howe, Maggy. “Excess Pounds.” Country Living (Nov. 1995):
60-61.
Merrell, Woodson. “How I Became a Low-Carb Believer.”
Time (Nov. 1, 1999): 80.
Turner, Richard. “The Trendy Diet That Sizzles.” Newsweek
Sept. 6, 1999): 60.

GALE ENCYCLOPEDIA OF MEDICINE 2 402Atkins dietGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 402

OTHER
Atkins Center for Complementary Medicine. 152 E. 55th St.,
New York, NY 10022. 212-758-2110. <http://www.atkinscenter.com>.
Atopic dermatitis
Eczema is a general term used to describe a variety
of conditions that cause an itchy, inflamed skin rash.Atopic dermatitis , a form of eczema, is a non-conta-
gious disorder characterized by chronically inflamedskin and sometimes intolerable itching .
Atopic dermatitis refers to a wide range of diseases

that are often associated with stress and allergic disor-
ders that involve the respiratory system, like asthma and
hay fever . Although atopic dermatitis can appear at any
age, it is most common in children and young adults.Symptoms usually abate before the age of 25 and do notaffect the patient’s general health.
About one in ten babies develop a form of atopic

dermatitis called infantile eczema. Characterized by skinthat oozes and becomes encrusted, infantile eczema mostoften occurs on the face and scalp. The condition usuallyimproves before the child’s second birthday, and medicalattention can keep symptoms in check until that time.
When atopic dermatitis develops after infancy,

inflammation, blistering, oozing, and crusting are lesspronounced. The patient’s sores become dry, turn fromred to brownish-gray, and skin may thicken and becomescaly. In dark-skinned individuals, this condition cancause the complexion to lighten or darken. Itching asso-ciated with this condition is usually worst at night. It canbe so intense that patients scratch until their sores bleed,sometimes causing scarring and infection.

Atopic dermatitis affects about 3% of the population
of the United States, and about 80% of the people whohave the condition have one or more relatives with thesame condition or a similar one. Symptoms tend to bemost severe in females. Atopic dermatitis can erupt onany part of the skin, and crusted, thickened patches onthe fingers, palms, or the soles of the feet can last foryears. In teenagers and young adults, atopic dermatitisoften appears on one or more of the following areas:

• elbow creases
• backs of the knees• ankles
• wrists
• face• neck• upper chest• palms and between the fingers
While allergic reactions often trigger atopic dermati-

tis, the condition is thought to be the result of an inherit-ed over-active immune system or a genetic defect thatcauses the skin to lose abnormally large amounts ofmoisture. The condition can be aggravated by a cycle thatdevelops in which the skin itches, the patient scratches,the condition worsens, the itching worsens, the patientscratches, etc. This cycle must be broken by relieving theitching to allow the skin time to heal. If the skin becomes

GALE ENCYCLOPEDIA OF MEDICINE 2 403Atopic dermatitis
A close-up view of atopic dermatitis in the crook of the
elbow of a 12-year-old patient. (Custom Medical Stock Photo.
Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 403

broken, there is also a risk of developing skin infections
which, if not recognized and treated promptly, canbecome more serious.
Symptoms of atopic dermatitis include the following:
• an itchy rash and dry, thickened skin on areas of the
body where moisture can be trapped
• continual scratching
• chronic fatigue , caused when itching disrupts sleep
An individual is more at-risk for developing the con-

dition if there is a personal or family history of atopicdermatitis, hay fever, asthma, or other allergies . Expo-
sure to any of the following can cause a flare-up:
• hot or cold temperatures
• wool and synthetic fabrics• detergents, fabric softeners, and chemicals• use of drugs that suppress immune-system activity
Certain foods, such as peanuts, cow’s milk, eggs,

and fish, can trigger symptoms of atopic dermatitis. Asmall percentage of patients with atopic dermatitis findthat their symptoms worsen after having been exposed todust, feather pillows, rough-textured fabrics, or othermaterials to which dust adheres.
Diagnosis
Diagnosis of atopic dermatitis is usually based on

the patient’s symptoms and personal and family healthhistory. Skin tests do not generally provide reliable infor-mation about this condition.
Treatment
Atopic dermatitis cannot be cured, but the severity
and duration of symptoms can be controlled. A dermatol-ogist should be consulted when symptoms first appear,and is likely to recommend warm baths to loosenencrusted skin, followed by applications of petroleumjelly or vegetable shortening to prevent the skin’s naturalmoisture from escaping.

Externally applied (topical) steroids or preparations
containing coal tar can relieve minor itching, but coal tarhas an unpleasant odor, stains clothes, and may increaseskin-cancer risk. Excessive use of steroid creams inyoung children can alter growth. Pregnant women shouldnot use products that contain coal tar. Topical steroids cancause itching, burning, acne , permanent stretch marks,

and thinning and spotting of the skin. Applying topicalsteroids to the area around the eyes can cause glaucoma .
Oral antihistamines , such as diphenhydramine
(Benadryl), can relieve symptoms of allergy-related atopicdermatitis. More concentrated topical steroids are recom-mended for persistent symptoms. A mild tranquilizer maybe prescribed to reduce stress and help the patient sleep,and antibiotics are used to treat secondary infections.
Cortisone ointments should be used sparingly, and

strong preparations should never be applied to the face,groin, armpits, or rectal area. Regular medical monitor-ing is recommended for patients who use cortisonesalves or lotions to control wide-spread symptoms. Oralcortisone may be prescribed if the patient does notrespond to other treatments, but patients who take themedication for more than two weeks have a greater-than-average risk of developing severe symptoms when thetreatment is discontinued.

Allergy shots rarely improve atopic dermatitis and
sometimes aggravate the symptoms. Since food allergiesmay trigger atopic dermatitis, the doctor may suggest
GALE ENCYCLOPEDIA OF MEDICINE 2 404Atopic dermatitis
Infant Adult
Atopic dermatitis can erupt on any part of the skin. In

infants, it often appears on the face, scalp, and knees, whileit develops on the elbows, neck, back of the knees, andankles in adults. (Illustration by Electronic Illustrators Group.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 404

eliminating certain foods from the diet if other treatments
prove ineffective.
If symptoms are extremely severe, ultraviolet light

therapy may be prescribed, and a wet body wrap recom-mended to help the skin retain moisture. This technique,used most often with children, involves sleeping in awarm room while wearing wet pajamas under dry cloth-ing, rain gear, or a nylon sweatsuit. The patient’s face maybe covered with wet gauze covered by elastic bandages,and his hands encased in wet socks covered by dry ones.
A physician should be notified if the condition is

widespread or resists treatment, or the skin oozes,becomes encrusted, or smells, as this may indicate aninfection.
Alternative therapies can sometimes bring relief or
resolution of atopic dermatitis when conventional thera-pies are not helping. If the condition becomes increas-ingly widespread or infected, a physician should be con-sulted.
Helpful alternative treatments for atopic dermatitis
may include:
• Taking regular brisk walks, followed by bathing in

warm water sprinkled with essential oil of lavender(Lavandula officinalis ); lavender oil acts as a nerve
relaxant for the whole body including the skin
• Supplementing the diet daily with zinc, fish oils, vita-
min A, vitamin E, and evening primrose oil ( Oenothera
biennis )—all good sources of nutrients for the skin
• Reducing or eliminating red meat from the diet• Eliminating or rotating potentially allergic foods such
as cow’s milk, peanuts, wheat, eggs, and soy

• Implementing stress reduction techniques in daily life.
Herbal therapies also can be helpful in treating
atopic dermatitis. Western herbal remedies used in thetreatment of this condition include burdock ( Arctium
lappa ) and Ruta (Ruta graveolens ). Long-term herbal
therapy requires monitoring and should be guided by anexperienced practitioner.
Other alternative techniques that may be useful in
the treatment of atopic dermatitis include:

• Acupressure ( acupuncture without needles) to relieve
tension that may trigger a flare
• Aromatherapy, using essential oils like lavender, thyme
(Thymus vulgaris ), jasmine ( Jasminum officinale ) and
chamomile ( Matricaria recutita ) in hot water, to add a
soothing fragrance to the airKEY TERMS
Corticosteroid —A steroid hormone produced by
the adrenal gland or as a synthetic compoundthat reduces inflammation, redness, rashes, andirritation.

Dermatitis —Inflammation of the skin.
• Shiatsu massage and reflexology , performed by
licensed practitioners, to alleviate symptoms by restor-ing the body’s natural balance
• Homeopathy, which may temporarily worsen symp-
toms before relieving them, and should be supervisedby a trained alternative healthcare professional
• Hydrotherapy, which uses water, ice, liquid, and steam,
to stimulate the immune system
• Juice therapy to purify the liver and relieve bowel con-
gestion

gestion
• Yoga to induce a sense of serenity.
Prognosis
Atopic dermatitis is unpredictable. Although symp-
toms occur less often with age and sometimes disappearaltogether, they can recur without warning. Atopic der-matitis lowers resistance to infection and increases therisk of developing cataracts . Sixty percent of patients
with atopic dermatitis will experience flares and remis-sions throughout their lives.
Research has shown that babies weaned from breast

milk before they are four months old are almost threetimes more likely than other babies to develop recurrenteczema. Feeding eggs or fish to a baby less than one yearold can activate symptoms, and babies should be shieldedfrom such irritants as mites, molds, pet hair, and smoke.
Possible ways to prevent flare-ups include the fol-
lowing:
• eliminate activities that cause sweating
• lubricate the skin frequently

• avoid wool, perfumes, fabric softeners, soaps that dry
the skin, and other irritants
• avoid sudden temperature changes.
A doctor should be notified whenever any of the fol-
lowing occurs:
• fever or relentless itching develop during a flare
GALE ENCYCLOPEDIA OF MEDICINE 2 405Atopic dermatitisGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 405

• an unexplained rash develops in someone who has a
personal or family history of eczema or asthma
• inflammation does not decrease after seven days of
treatment with an over-the-counter preparation contain-ing coal tar or steroids
• a yellow, tan, or brown crust or pus-filled blisters appear
on top of an existing rash
• a person with active atopic dermatitis comes into con-
tact with someone who has cold sores, genital herpes ,
or another viral skin disease
Resources
BOOKS

Resources
BOOKS
Atrial ectopic beats
Atrial ectopic beats (AEB) refers to a contraction of

the upper heart chamber which occurs before it would beexpected. Atrial ectopic beats are also known as prema-ture atrial beats, premature atrial complex (PAC), or atri-al extrasystole.
An AEB is usually a harmless disturbance in the
normal rhythm of the heart. It can occur only occasional-ly, in a regular pattern, or several may occur in sequenceand then disappear. Most often, the person is unaware ofthe event.
As people age, extra beats tend to happen more fre-

quently even in perfectly healthy individuals. AEB maybe triggered or increased by stress ,caffeine ,smoking ,
and some medicines. Cold remedies containing ephedrineor pseudoephedrine have been known to increase the inci-dence of atrial ectopic beats. AEB may also be the resultof an enlarged atria, lung disease, or the result of reducedblood supply to that area of the heart.If a person is aware of the event, the first symptom

of AEB is usually a feeling that the heart has skipped ormissed a beat. This is often accompanied by a feelingthat the heart is thumping or pounding in the chest. Thethumping or pounding is caused by the fact that whenthere is an AEB, the pause before the next beat is usuallylonger than normal. The next beat must be stronger thanusual to pump the accumulated blood out of the chamber.
Diagnosis
Diagnosis of AEB is often suspected on the basis of

the patient’s description of the occurrence. An electrocar-diogram (ECG) can confirm the diagnosis. An ECGshows the heart beat as three wave forms. The first waveis called P, the second is called QRS, and the last is T. Anatrial ectopic beat will show up on the ECG as a P wavethat occurs closer than usual to the preceding T wave.
Treatment
Atrial ectopic beats do not usually require treatment.

If treatment is necessary because the beats occur fre-quently and cause intolerable discomfort, the doctor mayprescribe medication.
Prognosis
Occasional AEB usually have no significance. If
they increase in frequency, they can lead to atrial tachy-cardia or fibrillation and to a decrease in cardiac output.
AEB cannot usually be prevented. Aggravating fac-
tors can be addressed, like excessive stimulants, anduncontrolled pulmonary disorders.
Resources
BOOKS

Resources
BOOKS
Atrial extrasystole seeAtrial ectopic beats
GALE ENCYCLOPEDIA OF MEDICINE 2 406Atrial ectopic beatsGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 406

Atrial fibrillation and flutter
Atrial fibrillation and flutter are abnormal heart
rhythms in which the atria, or upper chambers of the heart,are out of sync with the ventricles, or lower chambers ofthe heart. In atrial fibrillation, the atria “quiver” chaotical-ly and the ventricles beat irregularly. In atrial flutter, theatria beat regularly and faster than the ventricles.
Atrial fibrillation and flutter are two types of cardiac

arrhythmias , irregularities in the heart’s rhythm. Nearly
2 million Americans have atrial fibrillation, according tothe American Heart Association. It is the most commonchronic arrhythmia. Atrial flutter is less common, butboth of these arrhythmias can cause a blood clot to formin the heart. This can lead to a stroke or a blockage car-
ried by the blood flow (an embolism ) anywhere in the
body’s arteries. Atrial fibrillation is responsible for about15% of strokes.

The atria are the heart’s two small upper chambers. In
atrial fibrillation, the heart beat is completely irregular.The atrial muscles contract very quickly and irregularly;the ventricles, the heart’s two large lower chambers, beatirregularly but not as fast as the atria. When the atria fibril-late, blood that is not completely pumped out can pool andform a clot. In atrial flutter, the heart beat is usually veryfast but steady. The atria beat faster than the ventricles.

Atrial fibrillation often occurs in people with various
types of heart disease. Atrial fibrillation may also resultfrom an inflammation of the heart’s covering ( pericardi-
tis), chest trauma or surgery, pulmonary disease, and cer-
tain medications. Atrial fibrillation is more common inolder people; about 10% of people over the age of 75have it. Atrial flutter and fibrillation usually occur in peo-ple with hypertensive or coronary heart disease and othertypes of heart disorders.

In most cases, the cause of atrial fibrillation and flut-
ter can be found, but often it cannot. Causes of theseheart beat abnormalities include:
• many types of heart disease
•stress and anxiety
•caffeine
• alcohol• tobacco• diet pills• some prescription and over-the-counter medications
• open heart surgery
Symptoms, when present, include:
• a fluttering feeling in the chest
• a pulse that feels like the heart is skipping, racing, jump-
ing, or is irregular

• low energy• a faint or dizzy feeling• pressure or discomfort in the chest
• shortness of breath
• anxiety.
Diagnosis
A doctor can sometimes hear these arrhythmias
using an instrument (a stethoscope) to listen to thesounds within the chest. Atrial fibrillation and flutter areusually diagnosed through electrocardiography
(EKGs), an exercisestress test , a 24-hour Holter EKG

monitor, or a telephone cardiac monitor. An EKG showsthe heart’s activity and may reveal a lack of oxygen(ischemia ). Electrodes covered with conducting jelly are

placed on the patient’s chest, arms, and legs. The elec-trodes send impulses of the heart’s activity through amonitor (called an oscilloscope) to a recorder that tracesthe pattern of the impulses onto paper. The test takesabout 10 minutes and is performed in a doctor’s office.The exercise stress test measures how the heart and bloodvessels respond to work when the patient is exercising ona treadmill or a stationary bike. This test is performed ina doctor’s office within an exercise laboratory

ina doctor’s office within an exercise laboratory and takes15-30 minutes.

In 24-hour EKG (Holter) monitoring, the patient
wears a small, portable tape recorder connected to diskson his/her chest that record the heart’s rhythm duringnormal activities. An EKG called transtelephonic moni-toring identifies arrhythmias that occur infrequently.Like Holter monitoring , transtelephonic monitoring

continues for days or weeks and enables patients to sendthe EKG via telephone to a monitoring station when anarrhythmia is felt, or to store the information in therecorder and transmit it later. Doctors can also use high-frequency sound waves ( echocardiography ) to deter-
mine the structure and function of the heart. This diag-nostic method is often helpful to evaluate for underlyingheart disease.
Treatment
Atrial fibrillation and flutter are usually treated with

medications and/or electrical shock ( cardioversion ). In
GALE ENCYCLOPEDIA OF MEDICINE 2 407Atrial fibrillation and flutterGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 407

some cases, removal of a small portion of the heart (abla-
tion), implantation of a pacemaker or a cardioverterdefibrillator, or maze surgery is needed.
If the heart rate cannot be quickly controlled, electri-
cal cardioversion may be used. Cardioversion, the elec-tric shock to the chest wall, is usually performed emer-gencies. This device briefly suspends the heart’s activityand allows it to return to a normal rhythm.
Ablation destroys the heart tissue that causes the

arrhythmia. The tissue can be destroyed by catheteriza-tion or surgery. Radiofrequency catheter ablation , per-
formed in a cardiac catheterization laboratory, can

cure atrial flutter and control the heart rate in atrial fib-rillation. The patient is awake but sedated. A thin tubecalled a catheter is inserted into a vein and is threadedinto the heart. At the end of the catheter, a device mapsthe electrical pathways of the heart. A cardiologist, adoctor specializing in the heart, uses this map to identifythe pathway(s) causing the arrhythmia, and then elimi-nates it (them) with bursts of high-frequency radiowaves. Surgical ablation is performed in an

radiowaves. Surgical ablation is performed in an operatingroom under general anesthesia. Computerized mappingtechniques are combined with a cold probe to destroyarrhythmia-causing tissue. Ablation is generally suc-cessful. When ablation is used for atrial fibrillation, it isusually followed by implantation of a pacemaker as wellas drug therapy.

size of a matchbox that is surgically implanted near thecollarbone to regulate the heart beat. Lead wires thread-ed to the right side of the heart supply electrical energyto pace the atria and ventricles. The implantable car-dioverter defibrillator is a treatment for serious arrhyth-mias. The battery-powered device senses an abnormalheart rhythm and automatically provides electricalshock(s). The shock(s) suspends heart activity and thenallows the heart to initiate a normal rhythm. Wire

the heart to initiate a normal rhythm. Wire elec-trodes on the device are attached to the heart. Some ofthe electrodes are attached to the outside of the heartand some are attached to the inside of the heart throughveins. The newest implantable cardioverter defibrilla-tors can be implanted in the chest wall and do notrequire open chest surgery. These devices weigh lessthan 10 oz and generally last seven or eight years. Animplantable cardioverter defibrillator is usually usedwith drug therapy,

defibrillator is usually usedwith drug therapy, but the amount medication isreduced. In maze surgery, often the last resort, surgeonscreate a maze of stitches (sutures) that help the heart’selectrical impulses travel effectively.

Most of the drugs used for treatment have poten-
tial side effects and should be carefully monitored bya doctor. The goal of treatment is to control the rateand rhythm of the heart and to prevent the formation
of blood clots. If the arrhythmia is caused by heartdisease, the heart disease will also be treated. TheAmerican Heart Association recommends aggressivetreatment.
A digitalis drug, most commonly digoxin, is usually
prescribed to control the heart rate. Digitalis drugs slow

the heart’s electrical impulses, helping to restore the nor-mal rate and rhythm. These drugs also increase the abili-ty of the heart’s muscular layer to contract and pumpproperly. Beta-blockers and calcium channel blockers
can also be used for this purpose. Beta-blockers slow thespeed of electrical impulses through the heart. Some cal-cium channel blockers dampen the heart’s response toerratic electrical impulses.
To prevent blood clots, aspirin or warfarin

(Coumadin) is administered. Warfarin, however, haspotential bleeding side effects, especially in olderpatients. Amiodarone is fairly efffective for atrial flutter.This drug is often able to maintain the heart’s properrhythm and can also help control the heart rate when theflutter occurs.
Prognosis
Patients with atrial fibrillation and flutter can live a

normal life for many years as long as the arrhythmia iscontrolled and serious blood clots are prevented.
Atrial fibrillation and flutter can sometimes be pre-
vented when the cause can be identified and controlled.Depending on the cause, prevention could include:
• treating the underlying heart disease• reducing stress and anxiety
• reducing or stopping consumption of caffeine, alcohol,
or tobacco; and/or
• discontinuing diet pills or other medications (over-the-

counter or prescription)
Resources
BOOKS
DeBakey, Michael E., and Antonio M. Gotto Jr. The New Liv-
ing Heart. Holbrook, MA: Adams Media Corporation,
1997.
Falk, Rodney H., and Philip J. Podrid, eds. Atrial Fibrillation:
Mechanisms and Management. 2nd ed. New York: Lippin-
cott-Raven, 1997.

GALE ENCYCLOPEDIA OF MEDICINE 2 408Atrial fibrillation and flutterGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 408

1996.
Waldo, Albert L., and Paul Touboul, eds. Atrial Flutter:
Advances in Mechanisms and Management. Armonk, NY:
Futura Publishing Co., Inc., 1996.
Kosinski, Daniel, et al. “Catheter Ablation for Atrial Flutter
and Fibrillation: An Effective Alternative to Medical Ther-apy.” Postgraduate Medicine 103, no. 1 (Jan. 1998): 103-
110.

110.
OTHER
“Atrial Fibrillation” and “Management of Patients with Atrial

Fibrillation.” American Heart Association. 1997. 30 Mar.1998 <http://www.americanheart.org>.
“Facts About Arrhythmias/Rhythm Disorders.” National Insti-
tutes of Health. 30 Mar. 1998 <http://www.nhlbi.nih.gov/nhlbi/cardio/other/gp/arrhyth.htm>.
“Understanding Your Arrythmia.” Deborah Heart and Lung
Center. 30 Mar. 1998 <http://www/deborah.org/consumer/arr_atrial.html>.
Atrial flutter seeAtrial fibrillation and flutterKEY TERMS
Arrhythmia —A variation in the normal rhythm of

the heart beat. Atrial fibrillation and flutter are twotypes of arrhythmia.
Atria —The two small upper chambers of the heart
that receive blood from the lungs and the body.
Stroke —A brain attack caused by a sudden disrup-
tion of blood flow to the brain, in this casebecause of a blood clot.
Ventricles —The two large lower chambers of the
heart that pump blood to the lungs and to the restof the body.Atrial septal defect

An atrial septal defect is an abnormal opening in the
wall separating the left and right upper chambers (atria)of the heart.
During the normal development of the fetal heart,

there is an opening in the wall (the septum) separatingthe left and right upper chambers of the heart. Normally,this opening closes before birth, but if it does not, thechild is born with a hole between the left and right atria.This abnormal opening is called an atrial septal defectand causes blood from the left atrium to flow into theright atrium.
Different types of atrial septal defects can occur, and

they are classified according to where in the separatingwall they are found. The most commonly found atrialseptal defect occurs in the middle of the atrial septumand accounts for about 70% of all atrial septal defects.Abnormal openings can form in the upper and lowerparts of the atrial septum as well.
Abnormal openings in the atrial septum occur dur-

ing fetal development and are twice as common infemales as in males. These abnormalities can go unno-ticed if the opening is small, producing no abnormalsymptoms. If the defect is big, large amounts of bloodflowing from the left to the right atrium will cause theright atrium to swell to hold the extra blood.
People born with an atrial septal defect can have no

symptoms through their twenties, but by age 40, mostpeople with this condition have symptoms that caninclude shortness of breath , rapid abnormal beating of
the atria (atrial fibrillation), and eventually heart failure .
Diagnosis
Atrial septal defects can be identified by various
methods. Abnormal changes in the sound of the heartbeats can be heard when a doctor listens to the heart witha stethoscope. In addition, a chest x ray , an electrocar-

diogram (ECG, an electrical printout of the heartbeats),and an echocardiogram (a test that uses sound waves toform a detailed image of the heart) can also be used toidentify this condition.
An atrial septal defect can also be diagnosed by using
a test called cardiac catheterization . This test involves
GALE ENCYCLOPEDIA OF MEDICINE 2 409Atrial septal defectGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 409

inserting a very thin tube (catheter) into the heart’s cham-
bers to measure the amount of oxygen present in theblood within the heart. If the heart has an openingbetween the atria, oxygen-rich blood from the left atriumenters the right atrium. Through cardiac catheterization,doctors can detect the higher-than-normal amount of oxy-gen in the heart’s right atrium, right ventricle, and thelarge blood vessels that carry blood to the lungs, wherethe blood would normally subsequently get its oxygen.

Treatment
Atrial septal defects often correct themselves without
medical treatments by the age of two. If this dose not hap-pen, surgery is done by sewing the hole closed, or bysewing a patch of Dacron material or a piece of the sac thatsurrounds the heart (the pericardium), over the opening.
Some patients can have the defect fixed by having an
clam-shaped plug placed over the opening. This plug is aman-made device that is put in place through a catheterinserted into the heart.
Prognosis

Prognosis
Individuals with small defects can live a normal life,
but larger defects require surgical correction. Less than1% of people younger than 45 years of age die from cor-rective surgery. Five to ten percent of patients can diefrom the surgery if they are older than 40 and have otherheart-related problems. When an atrial septal defect iscorrected within the first 20 years of life, there is anexcellent chance for the individual to live normally.
Resources
BOOKS

Resources
BOOKS
“Congenital Heart Disease.” In Texas Heart Institute Heart
Owner’s Handbook. New York: John Wiley & Sons, Inc.,
Cardiac catheterization —A test that involves hav-
ing a tiny tube inserted into the heart through ablood vessel.
cally repair damaged sections of heart muscle andblood vessel walls.
Echocardiogram —A test that uses sound waves to

generate an image of the heart, its valves, andchambers.“If Your Child Has A Congenital Heart Defect.” In Cardiovas-
cular Diseases and Disorders Sourcebook , ed. Karen Bel-
lenir and Peter D. Dresser. Detroit: Omnigraphics, Inc.,1995.
Friedman, William F., and John S. Child. “Congenital Heart
Disease in the Adult.” In Harrison’s Principles of Internal
Medicine , ed. Anthony S. Fauci, et al. New York: McGraw
Hill, 1997.

Nugent, Elizabeth W., et al. “The Pathology, Pathophysiology,
Recognition, and Treatment of Congenital Heart Disease.”In Hurst’s The Heart , ed. Robert C. Schlant, et al. New
York: McGraw Hill, 1994.
Atrioventricular block seeHeart block
Attapulgite seeAntidiarrheal drugs
Attention-deficit/hyperactivity
disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) is
a developmental disorder characterized by distractibility,hyperactivity, impulsive behaviors, and the inability toremain focused on tasks or activities.
ADHD, also known as hyperkinetic disorder (HKD)

outside of the United States, is estimated to affect 3-9%of children, and afflicts boys more often than girls.Although difficult to assess in infancy and toddlerhood,signs of ADHD may begin to appear as early as age twoor three, but the symptom picture changes as adolescenceapproaches. Many symptoms, particularly hyperactivity,diminish in early adulthood, but impulsivity and inatten-tion problems remain with up to 50% of ADHD individu-als throughout their adult life.

Children with ADHD have short attention spans,
becoming easily bored and/or frustrated with tasks.Although they may be quite intelligent, their lack of focusfrequently results in poor grades and difficulties in school.ADHD children act impulsively, taking action first andthinking later. They are constantly moving, running,climbing, squirming, and fidgeting, but often have troublewith gross and fine motor skills and, as a result, may be

GALE ENCYCLOPEDIA OF MEDICINE 2 410Attention-deficit/hyperactivity disorder (ADHD)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 410

physically clumsy and awkward. Their clumsiness may
extend to the social arena, where they are sometimesshunned due to their impulsive and intrusive behavior.
The causes of ADHD are not known. However, it
appears that heredity plays a major role in the develop-ment of ADHD. Children with an ADHD parent or sib-ling are more likely to develop the disorder themselves.Before birth, ADHD children may have been exposed topoor maternal nutrition , viral infections, or maternal

substance abuse. In early childhood, exposure to lead orother toxins can cause ADHD-like symptoms. Traumaticbrain injury or neurological disorders may also triggerADHD symptoms. Although the exact cause of ADHD isnot known, an imbalance of certain neurotransmitters,the chemicals in the brain that transmit messagesbetween nerve cells, is believed to be the mechanismbehind ADHD symptoms.
A widely publicized study conducted by Dr. Ben
Feingold in the early 1970s suggested that allergies to

certain foods and food additives caused the characteristichyperactivity of ADHD children. Although some chil-dren may have adverse reactions to certain foods that canaffect their behavior (for example, a rash might tem-porarily cause a child to be distracted from other tasks),carefully controlled follow-up studies have uncovered nolink between food allergies and ADHD. Another popular-ly held misconception about food and ADHD is that theconsumption of sugar causes hyperactive behavior.Again,

of sugar causes hyperactive behavior.Again, studies have shown no link between sugar intakeand ADHD. It is important to note, however, that a nutri-tionally balanced diet is important for normal develop-ment in allchildren.

Psychologists and other mental health professionals
typically use the criteria listed in the Diagnostic and Sta-
tistical Manual of Mental Disorders, Fourth Edition(DSM-IV) as a guideline for determining the presence of
ADHD. For a diagnosis of ADHD, DSM-IV requires the
presence of at least six of the following symptoms ofinattention, or six or more symptoms of hyperactivityand impulsivity combined:
Inattention:
• fails to pay close attention to detail or makes careless

mistakes in schoolwork or other activities
• has difficulty sustaining attention in tasks or activities• does not appear to listen when spoken to• does not follow through on instructions and does not
finish tasks
• has difficulty organizing tasks and activities• avoids or dislikes tasks that require sustained mental
effort (e.g., homework)
• is easily distracted
• is forgetful in daily activities
Hyperactivity:

• fidgets with hands or feet or squirms in seat• does not remain seated when expected to• runs or climbs excessively when inappropriate (in ado-
lescence and adults, feelings of restlessness)
• has difficulty playing quietly
• is constantly on the move
• talks excessively
Impulsivity:
• blurts out answers before the question has been com-
pleted
• has difficulty waiting for his or her turn
• interrupts and/or intrudes on others

DSM-IV also requires that some symptoms develop

before age seven, and that they significantly impair func-tioning in two or more settings (e.g., home and school)for a period of at least six months. Children who meet thesymptom criteria for inattention, but not for hyperactivi-ty/impulsivity are diagnosed with Attention-Deficit/Hyperactivity Disorder, Predominantly Inattentive Type,commonly called ADD. (Young girls with ADHD maynot be diagnosed because they have mainly this subtypeof the disorder.)
Diagnosis

Diagnosis
The first step in determining if a child has ADHD is
to consult with a pediatrician. The pediatrician can makean initial evaluation of the child’s developmental maturi-ty compared to other children in his or her age group.The physician should also perform a comprehensivephysical examination to rule out any organic causes of
ADHD symptoms, such as an overactive thyroid orvision or hearing problems.
If no organic problem can be found, a psychologist,

psychiatrist, neurologist, neuropsychologist, or learningspecialist is typically consulted to perform a comprehen-sive ADHD assessment. A complete medical, family,social, psychiatric, and educational history is compiledfrom existing medical and school records and frominterviews with parents and teachers. Interviews mayalso be conducted with the child, depending on his orher age. Along with these interviews, several clinicalinventories may also be used, such as the Conners Rat-ing Scales

also be used, such as the Conners Rat-ing Scales (Teacher’s Questionnaire and Parent’s Ques-

GALE ENCYCLOPEDIA OF MEDICINE 2 411Attention-deficit/hyperactivity disorder (ADHD)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 411

tionnaire), Child Behavior Checklist (CBCL), and the
Achenbach Child Behavior Rating Scales. These inven-tories provide valuable information on the child’s behav-ior in different settings and situations. In addition, theWender Utah Rating Scale has been adapted for use indiagnosing ADHD in adults.
It is important to note that mental disorders such as
depression and anxiety disorder can cause symptoms

similar to ADHD. A complete and comprehensive psy-chiatric assessment is critical to differentiate ADHDfrom other possible mood and behavioral disorders.Bipolar disorder , for example, may be misdiagnosed, as
ADHD.
Public schools are required by federal law to offer
free ADHD testing upon request. A pediatrician can alsoprovide a referral to a psychologist or pediatric specialistfor ADHD assessment. Parents should check with theirinsurance plans to see if these services are covered.
Treatment

ications, is the treatment approach of choice to alleviateADHD symptoms. Psychostimulants, such as dextroam-phetamine (Dexedrine), pemoline (Cylert), and methyl-phenidate (Ritalin) are commonly prescribed to controlhyperactive and impulsive behavior and increase atten-tion span. They work by stimulating the production ofcertain neurotransmitters in the brain. Possible sideeffects of stimulants include nervous tics, irregular heart-beat, loss of appetite, and insomnia . However, the med-

ications are usually well-tolerated and safe in most cases.
In children who don’t respond well to stimulant ther-
apy, tricyclic antidepressants such as desipramine (Nor-pramin, Pertofane) and amitriptyline (Elavil) are fre-quently recommended. Reported side effects of thesedrugs include persistent dry mouth ,sedation , disorien-

tation, and cardiac arrhythmia (particularly withdesipramine). Other medications prescribed for ADHDtherapy include buproprion (Wellbutrin), an antidepres-sant; fluoxetine (Prozac), an SSRI antidepressant; andcarbamazepine (Tegretol, Atretol), an anticonvulsantdrug. Clonidine (Catapres), an antihypertensive medica-tion, has also been used to control aggression and hyper-activity in some ADHD children, although it should not

be used with Ritalin. A child’s response to medicationwill change with age and maturation, so ADHD symp-toms should be monitored closely and prescriptionsadjusted accordingly.
Behavior modification therapy uses a reward system

to reinforce good behavior and task completion and canbe implemented both in the classroom and at home. Atangible reward such as a sticker may be given to the childevery time he completes a task or behaves in an accept-able manner. A chart system may be used to display thestickers and visually illustrate the child’s progress. Whena certain number of stickers are collected, the child maytrade them in for a bigger reward such as a trip to the zooor a day at the beach. The reward system stays in

a day at the beach. The reward system stays in placeuntil the good behavior becomes ingrained.

A variation of this technique, cognitive-behavioral
therapy , works to decrease impulsive behavior by get-
ting the child to recognize the connection betweenthoughts and behavior, and to change behavior by chang-ing negative thinking patterns.
Individual psychotherapy can help an ADHD child
build self-esteem, give them a place to discuss their wor-ries and anxieties, and help them gain insight into theirbehavior and feelings. Family therapy may also be ben-

eficial in helping family members develop coping skillsand in working through feelings of guilt or anger parentsmay be experiencing.
ADHD children perform better within a familiar,

consistent, and structured routine with positive reinforce-ments for good behavior and real consequences for bad.Family, friends, and caretakers should all be educated onthe special needs and behaviors of the ADHD child.Communication between parents and teachers is espe-cially critical to ensuring an ADHD child has an appro-priate learning environment.
A number of alternative treatments exist for ADHD.

Although there is a lack of controlled studies to provetheir efficacy, proponents report that they are successfulin controlling symptoms in some ADHD patients. Someof the more popular alternative treatments include:
GALE ENCYCLOPEDIA OF MEDICINE 2 412Attention-deficit/hyperactivity disorder (ADHD)Drugs Used To Treat ADHD
Cylert (pemoline) Insomnia

Dexedrine (dextroamphetamine sulfate) Excessive stimulation, restlessnessRitalin (methylphenidate hydrochloride) Insomnia, nervousness, loss of appetiteGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 412

• EEG (electroencephalograph) biofeedback . By mea-
suring brainwave activity and teaching the ADHDpatient which type of brainwave is associated withattention, EEG biofeedback attempts to train patients togenerate the desired brainwave activity.
• Dietary therapy. Based in part on the Feingold food

allergy diet, dietary therapy focuses on a nutritionalplan that is high in protein and complex carbohydratesand free of white sugar and salicylate-containing foodssuch as strawberries, tomatoes, and grapes.
• Herbal therapy. Herbal therapy uses a variety of natur-
al remedies to address the symptoms of ADHD, suchas ginkgo ( Gingko biloba ) for memory and mental
sharpness and chamomile ( Matricaria recutita ) extract

for calming. The safety of herbal remedies has notbeen demonstrated in controlled studies. For example,it is known that gingko may affect blood coagulation,but controlled studies have not yet evaluated the risk ofthe effect.
• Homeopathic medicine. This is probably the most effec-

tive alternative therapy for ADD and ADHD because ittreats the whole person at a core level. Constitutionalhomeopathic care is most appropriate and requires con-sulting with a well-trained homeopath who has experi-ence working with ADD and ADHD individuals.
Prognosis
Untreated, ADHD negatively affects a child’s social

and educational performance and can seriously damagehis or her sense of self-esteem. ADHD children haveimpaired relationships with their peers, and may belooked upon as social outcasts. They may be perceived asslow learners or troublemakers in the classroom. Siblingsand even parents may develop resentful feelings towardsthe ADHD child.KEY TERMS
Conduct disorder —A behavioral and emotional

disorder of childhood and adolescence. Childrenwith a conduct disorder act inappropriately,infringe on the rights of others, and violate soci-etal norms.
Nervous tic —A repetitive, involuntary action, such
as the twitching of a muscle or repeated blinking.
Oppositional defiant disorder —A disorder char-
acterized by hostile, deliberately argumentative,and defiant behavior towards authority figures.Some ADHD children also develop a conduct disor-

der problem. For those adolescents who have both
ADHD and a conduct disorder, up to 25% go on to devel-op antisocial personality disorder and the criminal behav-ior, substance abuse, and high rate of suicide attempts thatare symptomatic of it. Children diagnosed with ADHDare also more likely to have a learning disorder, a mooddisorder such as depression, or an anxiety disorder.
Approximately 70-80% of ADHD patients treated

with stimulant medication experience significant relieffrom symptoms, at least in the short-term. Approximate-ly half of ADHD children seem to “outgrow” the disor-der in adolescence or early adulthood; the other half willretain some or all symptoms of ADHD as adults. Withearly identification and intervention, careful compliancewith a treatment program, and a supportive and nurturinghome and school environment, ADHD children canflourish socially and academically.
Resources
BOOKS

Resources
BOOKS
Alexander-Roberts, Colleen. The ADHD Parenting Handbook:
Practical Advice for Parents from Parents. Dallas: Taylor
Publishing Co., 1994.
Manual of Mental Disorders. 4th ed. Washington, DC:
American Psychiatric Press, Inc., 1994.
Hallowell, Edward M., and John J. Ratey. Driven to Distrac-
tion. New York: Pantheon Books, 1994.
Kennedy, Patricia, Leif Terdal, and Lydia Fusetti. The Hyper-

active Child Book. New York: St. Martin’s Press, 1993.
Maxmen, Jerrold S., and Nicholas G. Ward. “Disorders Usually
First Diagnosed in Infancy, Childhood, or Adolescence.”In Essential Psychopathology and Its Treatment. 2nd ed.
New York: W. W. Norton, 1995.
Osman, Betty B. Learning Disabilities and ADHD: A Family
Guide to Living and Learning Together. New York: John
Wiley & Sons, 1997.
Glicken, Anita D. “Attention Deficit Disorder and the Pediatric

Patient: A Review.” Physician Assistant 21, no. 4 (Apr.
1997):101-11.
Hallowell, Edward M. “What I’ve Learned from A.D.D.” Psy-
chology Today 30, no. 3 (May/June 1997): 40-6.
Swanson, J. M., et al. “Attention-deficit Hyperactivity Disorder
and Hyperkinetic Disorder.” The Lancet 351 (7 Feb.
1997): 429-33.
American Academy of Child and Adolescent Psychiatry.
(AACAP). 3615 Wisconsin Ave. NW, Washington, DC20016. (202) 966-7300. <http://www.aacap.org>.

Children and Adults with Attention Deficit Disorder
(CH.A.D.D.). 8181 Professional Place, Suite 201, Planta-tion, FL 33317. (800) 233-4050. <http://www.chadd.org>.
GALE ENCYCLOPEDIA OF MEDICINE 2 413Attention-deficit/hyperactivity disorder (ADHD)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 413

The National Attention Deficit Disorder Association. (ADDA).
9930 Johnnycake Ridge Road, Suite 3E, Mentor, OH44060. (800) 487-2282. <http://www.add.org>.
Attention deficit disorder seeAttention-
deficit/Hyperactivity disorder (ADHD)
Atypical mycobacterial infections see
Mycobacterial infections, atypical
Atypical pneumonia seeMycoplasma
infections
Audiometry
Audiometry is the testing of a person’s ability to

hear various sound frequencies. The test is performedwith the use of electronic equipment called an audiome-ter. This testing is usually administered by a trained tech-nician called an audiologist.
Purpose
Audiometry testing is used to identify and diagnose
hearing loss . The equipment is used in health screening

programs, for example in grade schools, to detect hearingproblems in children. It is also used in the doctor’s office orhospital audiology department to diagnose hearing prob-lems in children, adults, and the elderly. With correct diag-nosis of a person’s specific pattern of hearing impairment,the right type of therapy, which might include hearing aids ,
corrective surgery, or speech therapy, can be prescribed.
Testing with audiometry equipment is simple and

painless. No special precautions are required.
A trained audiologist (a specialist in detecting hear-
ing loss) uses an audiometer to conduct audiometry test-ing. This equipment emits sounds or tones, like musicalnotes, at various frequencies, or pitches, and at differingvolumes or levels of loudness. Testing is usually done ina soundproof testing room.
The person being tested wears a set of headphones

that blocks out other distracting sounds and delivers atest tone to one ear at a time. At the sound of a tone, thepatient holds up a hand or finger to indicate that thesound is detected. The audiologist lowers the volume andrepeats the sound until the patient can no longer detect it.This process is repeated over a wide range of tones orfrequencies from very deep, low sounds, like the lowestnote played on a tuba, to very high sounds, like the ping-ing of a triangle. Each ear is tested

the ping-ing of a triangle. Each ear is tested separately. It is notunusual for levels of sensitivity to sound to differ fromone ear to the other.

A second type of audiometry testing uses a headband
rather than headphones. The headband is worn with smallplastic rectangles that fit behind the ears to conduct soundthrough the bones of the skull. The patient being testedsenses the tones that are transmitted as vibrations throughthe bones to the inner ear. As with the headphones, thetones are repeated at various frequencies and volumes.
The results of the audiometry test may be recorded

on a grid or graph called an audiogram. This graph isgenerally set up with low frequencies or tones at one endand high ones at the other end, much like a piano key-board. Low notes are graphed on the left and high noteson the right. The graph also charts the volume of thetones used; from soft, quiet sounds at the top of the chartto loud sounds at the bottom. Hearing is measured inunits called decibels. Most of the sounds associated withnormal speech patterns are generally spoken in the rangeof

patterns are generally spoken in the rangeof 20-50 decibels. An adult with normal hearing candetect tones between 0-20 decibels.

Speech audiometry is another type of testing that
uses a series of simple recorded words spoken at variousvolumes into headphones worn by the patient being test-ed. The patient repeats each word back to the audiologistas it is heard. An adult with normal hearing will be ableto recognize and repeat 90-100% of the words.
GALE ENCYCLOPEDIA OF MEDICINE 2 414Audiometry
An audiologist conducting a hearing test. (Custom Medical

Stock Photo. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 414

The ears may be examined with an otoscope prior to
audiometry testing to determine if there are any block-ages in the ear canal due to ear wax or other material.
A person with normal hearing will be able to recog-

nize and respond to all of the tone frequencies adminis-tered at various volumes in both ears by the audiometrytest. An adult with normal hearing can detect a range oflow and high pitched sounds that are played as softly asbetween nearly 0-20 decibels. Normal speech is general-ly spoken in the range of 20-50 decibels.
Audiometry test results are considered abnormal if

there is a significant or unexplained difference betweenthe levels of sound heard between the two ears, or if theperson being tested is unable to hear in the normal rangeof frequencies and volume. The pattern of responses dis-played on the audiogram can be used by the audiologistto identify if a significant hearing loss is present and ifthe patient might benefit from hearing aids or correctivesurgery.
Resources
BOOKS
“Clinical Evaluation of Complaints Referable to the Ears.” In

The Merck Manual. 17th ed. Ed. Robert Berkow. Rahway
NJ: Merck & Co., Inc., 1996.
“Pure-Tone Audiometry.” In The Yale University Patient’s
Guide to Medical Tests , ed. Barry L. Zaret, et al. Boston:
Houghton Mifflin Co., 1997.KEY TERMS
Audiogram —A chart or graph of the results of a
hearing test conducted with audiographic equip-ment. The chart reflects the softest (lowest volume)sounds that can be heard at various frequencies orpitches.
Decibel —A unit of measure for expressing the

loudness of a sound. Normal speech is typicallyspoken in the range of about 20-50 decibels.
Otoscope —A hand-held instrument with a tiny
light and a funnel-shaped attachment called anear speculum, which is used to examine the earcanal and eardrum.ORGANIZATIONS
American Academy of Audiology. 8201 Greensboro Drive,
Suite 300, McLean, V A 22102. (703) 610-9022. <http://audiology.org>.
Audiology Awareness Campaign. 3008 Millwood Ave., Colum-

bia, SC 29205. (800) 445-8629.
OTHER
“How to Read Your Hearing Test.” Hearing Alliance of Ameri-
ca.<http://www.earinfo.com>.
“Understanding Your Audiogram.” The League for the Hard of
Hearing. <http://www.lhh.org>.
Auditory integration training
Auditory integration training, or AIT, is one specific
type of music/auditory therapy based upon the work ofFrench otolaryngologists Dr. Alfred Tomatis and Dr. GuyBerard.
Origins

Origins
The premise upon which most auditory integration
programs are based is that distortion in how things areheard contributes to commonly seen behavioral or learningdisorders in children. Some of these disorders includeattention deficit/hyperactive disorder (ADHD), autism ,
dyslexia, and central auditory processing disorders(CAPD). Training the patient to listen can stimulate cen-tral and cortical organization.
Auditory integration is one facet of what audiolo-

gists call central auditory processing. The simplest defin-ition of central auditory processing, or CAP, is Universi-ty of Buffalo Professor of Audiology Jack Katz’s, whichis: “What we do with what we hear.” Central auditoryintegration is actually the perception of sound, includingthe ability to attend to sound, to remember it, retaining itin both the long- and short-term memory, to be able tolisten to sound selectively, and to localize it.
Guy Berard developed one of the programs com-

monly used. Berard’s auditory integration training con-sists of twenty half-hour sessions spent listening to musi-cal sounds via a stereophonic system. The music is ran-dom, with filtered frequencies, and the person listensthrough earphones. These sound waves vibrate and exer-cise structures in the middle ear. This is normally done insessions twice a day for 10 days.

GALE ENCYCLOPEDIA OF MEDICINE 2 415Auditory integration trainingGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 415

Alfred Tomatis is also the inventor of the Electronic
Ear. This device operates through a series of filters, andreestablishes the dominance of the right ear in hearing. Thebasis of Tomatis’ work is a series of principles that follow:
• The most important purpose of the ear is to adapt sound
waves into signals that charge the brain.
• Sound is conducted via both air and bone. It can be
considered something that nourishes the nervous sys-tem, either stimulating or destimulating it.

• Just as seeing is not the same as looking, hearing is not
the same as listening. Hearing is passive. Listening isactive.
• A person’s ability to listen affects all language develop-
ment for that person. This process influences everyaspect of self-image and social development.
• The capacity to listen can be changed or improved
through auditory stimulation using musical and vocalsounds at high frequencies.ALFRED TOMATIS (1920– )
• Communication begins in the womb. As early as the

beginning of the second trimester, fetuses can hearsounds. These sounds literally cause the brain and ner-vous system of the baby to develop.
A quartet of CAP defects have been identified that
can unfavorably alter how each person processes sound.Among these are:
• Phonetic decoding, a problem that occurs when the
brain incorrectly decodes what is being heard. Soundsare unrecognizable, often because the person speakingtalks too fast.

• Tolerance-fading memory, a condition with little or
poor tolerance for background sounds.
• Auditory integration involves a person’s ability to put
together things heard with things seen. Characteristical-
GALE ENCYCLOPEDIA OF MEDICINE 2 416Auditory integration training
Internationally renowned French otolaryngologist,

psychologist, educator and inventor Alfred Tomatis per-ceived the importance of sound and hearing early in hiscareer. He took his degree as a Doctor of Medicine fromthe University of Paris and specialized in ear, nose andthroat medicine. The son of two opera singers, Tomatisearly in his career treated some of his parents’ fellow

opera singers. From these experiences with the sound ofmusic, he developed the principle that has come to beknown as the Tomatis Effect, i.e. that the human voice canonly sing what it hears.
Tomatis has been called the Einstein of the ear. It was

his research that made the world aware that the ears of aninfant in utero are already functioning at four and halfmonths of age. Just as the umbilical cord provides nour-ishment to the unborn infant’s body, Tomatis postulatedthat the sound of the mother’s voice is also a nutrientheard by the fetus. This sound literally charges and stimu-lates the growth of the brain.
Tomatis took this further, into the realm of language.

Tomatis concluded that the need to communicate and tobe understood are among our most basic needs. He was apioneer in perceiving that language problems convert intosocial problems for people. “Language is what character-izes man and makes him different from other creatures,”Tomatis is quoted as saying. The techniques he developedto teach people how to listen effectively are international-ly respected tools used in the treatment of autism, atten-tion-deficit disorder, and other learning

His listening program, the invention of the Electronic
Ear, and his work with the therapeutic use of sound andmusic for the past fifty years have made Tomatis arguablythe best known and most successful ear specialist in theworld. There are more than two hundred Tomatis Centersworldwide, treating a vast variety of problems related tothe ability to hear.
(Photograph by V. Brynner. Gamma Liaison. Reproduced by
permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 416

ly there are long response delays and trouble with
phonics, or recognizing the symbols for sounds.
• The fourth problem area, often called auditory organi-
zation, overlaps the previous three. It is characterizedby disorganization in handling auditory and other infor-mation.
Certain audiological tests are carried out to see if the
person has a CAP problem, and if so, how severe it is.Other tests give more specific information regarding thenature of the CAP problem. They include:

• Puretone air-conduction threshold testing, which mea-
sures peripheral hearing loss. If loss is found, thenbone-conduction testing, or evaluation of the vibrationof small bones in the inner ear, is also carried out.
• Word discrimination scores (WDS) determines a per-
son’s clarity in hearing ideal speech. This is done bypresenting 25–50 words at 40 decibels above the per-son’s average sound threshold in each ear. Test scoresequal the percentage of words heard correctly.

• Immittance testing is made up of two parts, assessing
the status of, and the protective mechanisms of the mid-dle ear.
• Staggered sporadic word (SSW) testing delivers 40
compound words in an overlapping way at 50 decibelsabove threshold to each ear of the person being tested.This test provides expanded information that makes itpossible to break down CAP problems into the fourbasic types.
• Speech in noise discrimination (SN) testing is similar to

Staggered Sporadic Word testing except that other noiseis also added and the percentage correct in quiet is com-pared with that correct when there is added noise.
• Phonemic synthesis (PS) determines serious learning
problems. The types of errors made in sounding outwritten words or associating written letters with thesounds they represent help in determining the type andseverity of CAP problems.
Purpose
Upon completion of an auditory integration training

program, the person’s hearing should be capable of per-ceiving all frequencies at, or near, the same level. Totalimprovement from this therapy, in both hearing andbehavior, can take up to one year.
Auditory integration training is based upon newly
learned information about the brain. Though brain struc-tures and connections are predetermined, probably byheredity, another factor called plasticity also comes into

play. Learning, we now know, continues from birth todeath. Plasticity is the ability of the brain to actuallychange its structuring and connections through theprocess of learning.
Problems with auditory processing are now viewed

as having a wide–reaching ripple effect on our society. Itis estimated that 30–40% of children starting school havelanguage-learning skills that can be described as poor.CAP difficulties are a factor in several different learningdisabilities. They affect not only academic success, butalso nearly every aspect of societal difficulties. Oneexample to illustrate this is a 1989 University of Buffalostudy where CAP problems were found to be present in asurprising 97% of youth inmates in an upstate

in asurprising 97% of youth inmates in an upstate New Yorkcorrections facility.

Resources
BOOKS
Katz, Jack, Ph.D., Wilma Laufer Gabbay, M.S., Deborah S.
Ungerleider, M.A., and Lorin Wilde, M.S. Handbook of
Clinical Audiology. Waverly Press, Inc., 1985.
Katz, Jack, Ph.D. “Central Auditory Processing Evaluation.”
(1996).
Masters, M. Gay. “Speech and Language Management of
CAPD.” (1996).
Musiek, Frank, Ph.D. “Auditory Training: An Eclectic
Approach.” American Journal of Audiology (1995).
OTHER
Cooper, Rachel. “What is Auditory Integration Training?”

<http://www.vision3d.com/adhd/>. (December 2000).
Dejean, Valerie. About the Tomatis Method,1997. Tomatis
Auditory Training Spectrum Center, Bethseda, MD.
Masters, M. Gay and Jack Stecker Katz, N.A. Central Auditory
Processing Disorders: Characteristic Difficulties.Miniseminar, 1994.
The Spectrum Center. “Auditory Integration and Alfred Toma-
tis.” <http://listeningtraining.com/>. (December 2000).
Australia antigen-associated hepatitis see
Hepatitis B
Autism

Autism
Autism is a severe disorder of brain function marked
by problems with social contact, intelligence and lan-
GALE ENCYCLOPEDIA OF MEDICINE 2 417Auditory integration trainingGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 417

guage, together with ritualistic or compulsive behavior
and bizarre responses to the environment.
Autism is a lifelong disorder that interferes with the

ability to understand what is seen, heard, and touched.This can cause profound problems in personal behaviorand in the ability to relate to others. A person withautism must learn how to communicate normally andhow to relate to people, objects and events. However,not all patients suffer the same degree of impairment.There is a full spectrum of symptoms, which can rangefrom mild to severe.
Autism occurs in as many as one or two per 1,000

children. It is found four times more often in boys (usual-ly the first-born) and occurs around the world in all racesand social backgrounds. Autism usually is evident in thefirst three years of life, although in some children it’shard to tell when the problem develops. Sometimes thecondition isn’t diagnosed until the child enters school.
While a person with autism can have symptoms

ranging from mild to severe, about 10% have an extraor-dinary ability in one area, such as in mathematics, mem-ory, music, or art. Such children are known as “autisticsavants” (formerly known as “idiot savants.”).
Autism is a brain disorder that affects the way the

brain uses or transmits information. Studies have foundabnormalities in several parts of the brain that almostcertainly occurred during fetal development. The prob-lem may be centered in the parts of the brain responsiblefor processing language and information from the senses.
There appears to be a strong genetic basis for

autism. Identical twins are more likely to both beaffected than twins who are fraternal (not geneticallyidentical). In a family with one autistic child, thechance of having another child with autism is about 1in 20, much higher than in the normal population.Sometimes, relatives of an autistic child have mildbehaviors that look very much like autism, such asrepetitive behaviors and social or communication prob-lems. Research also has found that some emotional dis-orders (such as manic

that some emotional dis-orders (such as manic depression) occur more often infamilies of a child with autism.

At least one group of researchers has found a link
between an abnormal gene and autism. The gene may bejust one of at least three to five genes that interact insome way to cause the condition. Scientists suspect that afaulty gene or genes might make a person vulnerable todevelop autism in the presence of other factors, such as achemical imbalance, viruses or chemicals, or a lack of
oxygen at birth.
In a few cases, autistic behavior is caused by a dis-
ease such as:

•rubella in the pregnant mother
• tuberous sclerosis
•fragile X syndrome
• encephalitis
• untreated phenylketonuria .
The severity of the condition varies between individ-
uals, ranging from the most severe (extremely unusual,repetitive, self- injurious, and aggressive behavior) tovery mild, resembling a personality disorder with somelearning disability.
Profound problems with social interaction are the

most common symptoms of autism. Infants with the dis-order won’t cuddle; they avoid eye contact and don’tseem to want or need physical contact or affection. Theymay become rigid or flaccid when they are held, cry whenpicked up, and show little interest in human contact. Sucha child doesn’t smile or lift his arms in anticipation ofbeing picked up. He forms no attachment to parents norshows any normal anxiety toward strangers. He doesn’t

learn typical games of childhood, such as peek-a-boo.
Language problems
The child with autism may not speak at all; if he
does, it is often in single words. He may endlessly repeatwords or phrases that are addressed to him and mayreverse pronouns (“You go sleep” instead of “I want togo to sleep”).
Restricted interests and activity
Usually a child with autism has many problems

playing normally. He probably won’t act out adultrolesduring play time, and instead of enjoying fantasy play, hemay simply repeatedly mimic the actions of someoneelse. Bizarre behavior patterns are very common amongautistic children and may include complex rituals,screaming fits, rhythmic rocking, arm flapping, fingertwiddling, and crying without tears. Autistic childrenmay play with their own saliva, feces or urine.They maybe self-destructive, biting their own hands, gouging attheir eyes,

biting their own hands, gouging attheir eyes, pulling their hair, or banging their head.

Sensory problems
The sensory world poses a real problem to many
autistic children, who seem overwhelmed by their ownsenses. A child with autism may ignore objects or
GALE ENCYCLOPEDIA OF MEDICINE 2 418AutismGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 418

become obsessed with them, continually watching the
object or the movement of his fingers over it. Many ofthese children may react to sounds by banging their heador flapping fingers. Some high-functioning autistic adultswho have written books about their childhood experi-ences report that sounds were often excruciatinglypainful to them, forcing them to withdraw from theirenvironment or try to cope by withdrawing into their ownworld of sensation and movement.
Intellectual problems

Most autistic children appear to be moderately mental-
ly retarded. They may giggle or cry for no reason, have nofear of real danger, but exhibit terror of harmless objects.
Diagnosis
There is no medical test for autism. Because the

symptoms of autism are so varied, the condition may goundiagnosed for some time (especially in those with mildcases or if other handicaps are also present). It may beconfused with other diseases, such as fragile X syndrome,tuberous sclerosis, and untreated phenylketonuria.Autism is diagnosed by observing the child’s behav-

ior, communication skills, and social interactions. Med-ical tests should rule out other possible causes of autisticsymptoms. Criteria that mental health experts use todiagnose autism include:
• problems with developing friendships• problems with make-believe or social play
• endlessly repeated words or strings of words
• difficulty in carrying on a conversation• obsessions with rituals or restricted patterns• preoccupation with parts of objects

but not enough to be diagnosed with the “classical” formof the condition. Children who have autistic behavior butno problems with language may be diagnosed with“Asperger syndrome.” Children who seem normal at firstbut who begin to show autistic behavior as they get oldermight be diagnosed with “childhood disintegrative disor-der” (CDD). These problems are sometimes called “autis-tic spectrum disorders.” It is also important to rule outother problems that seem similar to autism.

GALE ENCYCLOPEDIA OF MEDICINE 2 419Autism
This autistic child is encouraged to interact with the guinea pig in an effort to improve his social interaction. (Helen B. Senisi.
Photo Researchers, Inc. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 419

Treatment
There is no cure for autism. Treatments are aimed at
reducing specific symptoms. Because the symptoms varyso widely from one person to the next, there is not a sin-gle approach that works for every person. A spectrum ofinterventions include training in music, listening, vision,speech and language, and senses. Special diets and med-
ications may also be prescribed.
Studies show that people with autism can improve

significantly with proper treatment. A child with autismcan learn best with special teachers in a structured pro-gram that emphasizes individual instruction. The twomost-often studied types of treatment are:
Educational or behavioral treatment
Typically, behavioral techniques are used to help the

child respond and decrease symptoms. This mightinclude positive reinforcement (food and rewards) toboost language and social skills. This training includesstructured, skill-oriented instruction designed to boostsocial and language abilities. Training needs to begin asearly as possible, since early intervention appears toinfluence brain development.
Most experts believe that modern treatment is most
effective when carried out at home, although treatmentKEY TERMS

Antidepressants —A type of medication that is used
to treat depression; it is also sometimes used to treatautism.
Asperger syndrome —Children who have autistic
behavior but no problems with language.
Encephalitis —A rare inflammation of the brain
caused by a viral infection. It has been linked to thedeveloment of autism.
Fragile X syndrome —A genetic condition related to
the X chromosome that affects mental, physical andsensory development.
Major tranquilizers —The family of drugs that

includes the psychotropic or neuroleptic drugs,sometimes used to help autistic people. They carrysignificant risk of side effects, including Parkinson-ism and movement disorders, and should be pre-scribed with caution.
Opiate blockers —A type of drug that blocks theeffects of natural opiates in the system. This makes
some people, including some people with autism,appear more responsive to their environment.

Phenylketonuria (PKU) —An enzyme deficiency
present at birth that disrupts metabolism and causesbrain damage. This rare inherited defect may belinked to the development of autism.
Rubella —Also known as German measles. When a
woman contracts rubella during pregnancy, herdeveloping infant may be damaged. One of theproblems that may result is autism.
Stimulants —A class of drugs, including Ritalin, used

to treat people with autism. They may make childrencalmer and better able to concentrate, but they alsomay limit growth or have other side effects.
Tuberous sclerosis —A genetic disease that causes
skin problems, seizures, and mental retardation. Itmay be confused with autism.
may also take place in a psychiatric hospital, specialized
school, or day care program.
Medication
No single medication has yet proved highly effective

for the major features of autism. However, a variety ofdrugs can control self-injurious, aggressive, and other ofthe more difficult behaviors. Drugs also can controlepilepsy, which afflicts up to 20% of people with autism.
Five types of drugs are sometimes prescribed to help
the behavior problems of people with autism:
• stimulants, such as methylphenidate (Ritalin)• antidepressants, such as fluroxamine (Luvox)
• opiate blockers, such as naltrexone (ReVia)
• antipsychotics• tranquilizers

Today, most experts recommend a complex treat-
ment regimen that begins early and continues through theteenage years. Behavioral therapies are used in conjunc-tion with medications.
Many parents report success with megavitamin ther-
apy. Some studies have shown that vitamin B6improves
GALE ENCYCLOPEDIA OF MEDICINE 2 420AutismGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 420

eye contact and speech and lessens tantrum behavior. Vit-
amin B6causes fewer side effects than other medications
and is considered safe when used in appropriate doses.However, not many health practitioners advocate its usein the treatment of autism, citing that the studies showingits benefit were flawed.
DMG (dimethylglycine)
This compound, available in many health food stores,

is legally classified as a food, not a vitamin or drug. Someresearchers claim that it improves speech in children withautism. Those who respond to this treatment will usuallydo so within a week. Again, many doctors do not feel thatthe studies are adequate to promote this treatment.
Exercise
One researcher found that vigorous exercise (20
minutes or longer, three or four days a week) seems todecrease hyperactivity, aggression, self-injury and otherautistic symptoms.
Prognosis

Prognosis
While there is no cure, with appropriate treatment
the negative behaviors of autism may improve. Earliergenerations placed autistic children in institutions; today,even severely disabled children can be helped in a lessrestrictive environment to develop to their highest poten-tial. Many can eventually become more responsive toothers as they learn to understand the world around them,and some can lead nearly normal lives.
People with autism have a normal life expectancy.

Some people with autism can handle a job; they do bestwith structured jobs that involve a degree of repetition.
Until the cause of autism is discovered, prevention is
not possible.
Resources
BOOKS
Barron, Sean, and Judy Barron. There’s a Boy in Here. New
York: Simon & Schuster, 1992.
Bratt, Berneen. No Time for Jello. Cambridge, MA: Brookline
Books, 1989.
Cohen, Donald J., and Fred R. V olkmar. Handbook of Autism

and Pervasive Developmental Disorders. John Wiley &
Sons, 1997.
Cohen, Shirley. Targeting Autism: What We Know, Don’t Know,
and Can Do to Help Young Children with Autism andRelated Disorders. Berkeley: University of California
Press, 1998.Grandin, Temple. Emergence: Labeled Autistic. Novato, Ca:
Arena Press, 1986.
Greenfield, Josh. A Child Called Noah. New York: Holt, Rine-
hart and Winston, 1971.
Hart, Charles. A Parent’s Guide to Autism: Answers to the Most

Common Questions. New York: Pocket Books, 1993.
Kaufman, Barry Neil. Son-Rise. New York: Harper & Row, 1976.
Williams, Donna. Nobody Nowhere. New York: Times
Books/Random House, 1992.
Cook, E. H., et. al. “Fluoxetine Treatment in Children and
Adults with Autistic Disorder and Mental Retardation.”Journal of the American Academy of Child and Adoles-cent Psychiatry 31 (1992): 739-45.
“How to Tell Asperger’s from Autism.” Brown University Child

and Adolescent Behavior Letter 12/1 (Jan. 1996): 1-2.
Rimland, Bernard. “DMG, A Nontoxic Metabolite, and
Autism.” Autism Research Review International 4/2
(1996).
Roeder, Jason. “Can Medication Change Behavior in Autism?”
The Exceptional Parent 25/11 (Nov. 1995): 50-54.
Shapiro, Joseph. “Beyond the Rain Main: A Singular Woman
Changes the Cattle Industry and Our Image of Autism.”U.S. News & World Report 120/21 (27 May 1996): 78-79.
Wing, Lorna. “Autism spectrum.” The Lancet 350/9093 (13

Dec. 1997): 1761-1767.
Autism Society of America. 7910 Woodmont Avenue, Suite
300, Bethesda, Maryland 20814-3067. (800) 328-8476.<http://www.autism-society.org>.
Autism Network International. PO Box 448, Syracuse, NY
13210.
Autism Research Institute. 4182 Adams Ave., San Diego, CA
92116. (619) 281-7165.
National Autism Hotline. c/o Autism Services Center, PO Box
507, 605 Ninth St., Huntington, WV 25710. (304) 525-8014.
National Fragile X Foundation. PO Box 190488, San Francis-

co, CA 94119. (800) 688-8765. <http://www.nfxf.org>.
National Institute of Neurological Disorders and Stroke. PO
Box 5801, Bethesda, MD 20824. (800) 352-9424.<http://www.ninds.nih.gov/index.htm>.
National Alliance for Autism Research. <naar@naar.org>.
OTHER
Autism Society of America. 7910 Woodmont Avenue. <http://
www.autism-society.org>.
National Alliance for Autism Research (NAAR). <http://www.
naar.org>.
National Information Center for Children and Youth with Dis-

abilities. <http://www.nichcy.org/transitn.htm>.
Autograft seeSkin grafting
GALE ENCYCLOPEDIA OF MEDICINE 2 421AutismGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 421

Autoimmune disorders
Autoimmune disorders are conditions in which a
person’s immune system attacks the body’s own cells,causing tissue destruction.
Autoimmunity is accepted as the cause of a wide

range of disorders, and it is suspected to be responsible formany more. Autoimmune diseases are classified as eithergeneral, in which the autoimmune reaction takes placesimultaneously in a number of tissues, or organ specific, inwhich the autoimmune reaction targets a single organ.
Autoimmune disorders include the following:
•Systemic lupus erythematosus . A general autoim-

mune disease in which antibodies attack a number ofdifferent tissues. The disease recurs periodically and isseen mainly in young and middle-aged women.
•Rheumatoid arthritis . Occurs when the immune sys-
tem attacks and destroys the tissues that line bone jointsand cartilage. The disease occurs throughout the body,although some joints may be more affected than others.
• Goodpasture’s syndrome. Occurs when antibodies are

deposited in the membranes of both the lung and kid-neys, causing both inflammation of kidney glomerulus(glomerulonephritis ) and lung bleeding. It is typically
a disease of young males.
• Grave’s disease. Caused by an antibody that binds to
specific cells in the thyroid gland, causing them tomake excessive amounts of thyroid hormone.
• Hashimoto’s thyroiditis . Caused by an antibody that

binds to cells in the thyroid gland. Unlike in Grave’sdisease, however, this antibody’s action results in lessthyroid hormone being made.
• Pemphigus vulgaris. A group of autoimmune disorders
that affect the skin.
•Myasthenia gravis . A condition in which the immune
system attacks a receptor on the surface of muscle cells,preventing the muscle from receiving nerve impulsesand resulting in severe muscle weakness.
•Scleroderma . Also called CREST syndrome or pro-

gressive systemic sclerosis, scleroderma affects theconnective tissue.
• Autoimmune hemolytic anemia . Occurs when the
body produces antibodies that coat red blood cells.• Autoimmune thrombocytopenic purpura. Disorder in
which the immune system targets and destroys bloodplatelets.
•Polymyositis and Dermatomyositis. Immune disorders
that affect the neuromuscular system.
•Pernicious anemia . Disorder in which the immune

system attacks the lining of the stomach in such a waythat the body cannot metabolize vitamin B
12.
• Sjögren’s syndrome. Occurs when the exocrine glands
are attacked by the immune system, resulting in exces-sive dryness.
•Ankylosing spondylitis . Immune system induced
degeneration of the joints and soft tissue of the spine.
•Vasculitis . A group of autoimmune disorders in which
the immune system attacks and destroys blood vessels.

• Type I diabetes mellitus . May be caused by an anti-
body that attacks and destroys the islet cells of the pan-creas, which produce insulin.
• Amyotrophic lateral schlerosis. Also called Lou
Gehrig’s disease. An immune disorder that causes thedeath of neurons which leads to progressive loss of
muscular control.
• Guillain-Barre syndrome. Also called infectious

polyneuritis. Often occurring after an infection or animmunization (specifically Swine flu), the diseaseaffects the myelin sheath, which coats nerve cells. Itcauses progressive muscle weakness and paralysis .
•Multiple sclerosis . An autoimmune disorder that may
involve a virus affects the central nervous system, caus-ing loss of coordination and muscle control.
To further understand autoimmune disorders, it is

helpful to understand the workings of the immune sys-tem. The purpose of the immune system is to defend thebody against attack by infectious microbes (germs) andforeign objects . When the immune system attacks an

invader, it is very specific—a particular immune systemcell will only recognize and target one type of invader.To function properly, the immune system must not onlydevelop this specialized knowledge of individualinvaders, but it must also learn how to recognize andnot destroy cells that belong to the body itself. Everycell carries protein markers on its surface that identifiesit in one of two ways: what kind of cell it is (e.g. nervecell, muscle cell, blood cell, etc.) and to whom that

muscle cell, blood cell, etc.) and to whom that cellbelongs. These markers are called major histocompata-bility complexes (MHCs). When functioning properly,cells of the immune system will not attack any othercell with markers identifying it as belonging to the

GALE ENCYCLOPEDIA OF MEDICINE 2 422Autoimmune disordersGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 422

recognize the cell as “self,” they attach themselves to itand put out a signal that the body has been invaded,which in turn stimulates the production of substancessuch as antibodies that engulf and destroy the foreignparticles. In case of autoimmune disorders, the immunesystem cannot distinguish between “self” cells andinvader cells. As a result, the same destructive operationis carried out on the body’s own cells that would nor-mally be carried out on bacteria, viruses, and other suchharmful

functional in this way is not well understood. However,most researchers agree that a combination of genetic,environmental, and hormonal factors play into autoim-munity. Researchers also speculate that certain mecha-nisms may trigger autoimmunity. First, a substance thatis normally restricted to one part of the body, and there-fore not usually exposed to the immune system, isreleased into other areas where it is attacked. Second,the immune system may mistake a component of thebody for a similar

may mistake a component of thebody for a similar foreign component. Third, cells ofthe body may be altered in some way, either by drugs,infection, or some other environmental factor, so thatthey are no longer recognizable as “self” to the immunesystem. Fourth, the immune system itself may be dam-aged, such as by a genetic mutation, and therefore can-not function properly.

Symptoms
The symptoms of the above disorders include:
• Systemic lupus erythematosus. Symptoms include
fever , chills, fatigue , weight loss, skin rashes (particu-

larly the classic “butterfly” rash on the face), vasculitis,polyarthralgia, patchy hair loss, sores in the mouth ornose, lymph-node enlargement, gastric problems, and,in women, irregular periods. About half of those whosuffer from lupus develop cardiopulmonary problems,and some may also develop urinary problems. Lupuscan also effect the central nervous system, causingseizures, depression, and psychosis.
• Rheumatoid arthritis. Initially may be characterized by a

low-grade fever, loss of appetite, weight loss, and a gener-alized pain in the joints. The joint pain then becomes
more specific, usually beginning in the fingers, thenspreading to other areas, such as the wrists, elbows,knees, and ankles. As the disease progresses, joint func-tion diminishes sharply and deformities occur, particular-ly the characteristic “swan’s neck” curling of the fingers.
• Goodpasture’s syndrome. Symptoms are similar to that

of iron deficiency anemia , including fatigue and pal-lor. Symptoms involving the lungs may range from a
cough that produces bloody sputum to outright hemor-
rhaging. Symptoms involving the urinary systeminclude blood in the urine and/or swelling.
• Grave’s disease. This disease is characterized by an
enlarged thyroid gland, weight loss without loss ofappetite, sweating, heart palpitations , nervousness,
and an inability to tolerate heat.
• Hashimoto’s thyroiditis. This disorder generally dis-

plays no symptoms.
• Pemphigus vulgaris. This disease is characterized by
blisters and deep lesions on the skin.
• Myasthenia gravis. Characterized by fatigue and mus-
cle weakness that at first may be confined to certainmuscle groups, but then may progress to the point ofparalysis. Myasthenia gravis patients often have expres-sionless faces as well as difficulty chewing and swal-lowing. If the disease progresses to the respiratory sys-tem, artificial respiration may be required.

• Scleroderma. Disorder is usually preceded by Ray-
naud’s phenomenon. Symptoms that follow includepain, swelling, and stiffness of the joints, and the skintakes on a tight, shiny appearance. The digestive systemalso becomes involved, resulting in weight loss, appetiteloss, diarrhea ,constipation , and distention of the
abdomen. As the disease progresses, the heart, lungs,and kidneys become involved, and malignant hyperten-
sion causes death in approximately 30% of cases.

• Autoimmune hemolytic anemia. May be acute or
chronic. Symptoms include fatigue and abdominal ten-derness due to an enlarged spleen.
• Autoimmune thrombocytopenic purpura. Characterized
by pinhead-size red dots on the skin, unexplainedbruises , bleeding from the nose and gums, and blood in
the stool.
• Polymyositis and Dermatomyositis. In polymyositis,

symptoms include muscle weakness, particularly in theshoulders or pelvis, that prevents the patient from per-forming everyday activities. In dermatomyositis, thesame muscle weakness is accompanied by a rash thatappears on the upper body, arms, and fingertips. A rashmay also appear on the eyelids, and the area around theeyes may become swollen.
• Pernicious anemia. Signs of pernicious anemia

include weakness, sore tongue, bleeding gums, andtingling in the extremities. Because the disease caus-es a decrease in stomach acid, nausea, vomiting, lossof appetite, weight loss, diarrhea, and constipationare possible. Also, because Vitamin B
12is essential
for the nervous system function, the deficiency of itbrought on by the disease can result in a host of neu-

GALE ENCYCLOPEDIA OF MEDICINE 2 423Autoimmune disordersGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 423

rological problems, including weakness, lack of coor-
dination, blurred vision, loss of fine motor skills, lossof the sense of taste, ringing in the ears, and loss ofbladder control.
• Sjögren’s syndrome. Characterized by excessive dry-
ness of the mouth and eyes.
• Ankylosing spondylitis. Generally begins with lower
back pain that progresses up the spine. The pain mayeventually become crippling.
• Vasculitis. Symptoms depend upon the group of veins
affected and can range greatly.

• Type I diabetes mellitus. Characterized by fatigue and
an abnormally high level of glucose in the blood(hyperglycemia).
• Amyotrophic lateral schlerosis. First signs are stum-

bling and difficulty climbing stairs. Later, musclecramps and twitching may be observed as well asweakness in the hands making fastening buttons orturning a key difficult. Speech may become slowed orslurred. There may also be difficluty swallowing. Asrespiratory muscles atrophy, there is increased dangerof aspiration or lung infection.
• Guillain-Barre syndrome. Muscle weakness in the legs

occurs first, then the arms and face. Paresthesias (aprickly, tingling sensation) is also felt. This disorderaffects both sides of the body and may involve paralysisand the muscles that control breathing.
• Multiple sclerosis. Like Lou Gehrig’s disease, the first
symptom may be clumsiness. Weakness or exhaustionis often reported, as well as blurry or double vision.There may be dizziness , depression, loss of bladder

control, and muscle weakness so severe that the patientis confined to a wheelchair.
Diagnosis
A number of tests are involved in the diagnosis of
autoimmune diseases, depending on the particular dis-ease; e.g. blood tests, cerebrospinal fluid analysis, elec-tromylogram (measures muscle function), and magnetic
resonance imaging of the brain. Usually, these tests

determine the location and extent of damage or involve-ment. They are useful in charting progress of the diseaseand as baselines for treatment.
The principle tool, however, for authenticating

autoimmune disease is antibody testing. Such testsinvolve measuring the level of antibodies found in theblood and determining if they react with specific anti-gens that would give rise to an autoimmune reaction. Anelevated amount of antibodies indicates that a humoralimmune reaction is occurring. Since elevated antibodylevels are also seen in common infections, they must be
ruled out as the cause for the increased antibody levels.

Antibodies can also be typed by class. There are five
classes of antibodies, and they can be separated in thelaboratory. The class IgG is usually associated withautoimmune diseases. Unfortunately, IgG class antibod-ies are also the main class of antibody seen in normalimmune responses.
The most useful antibody tests involve introducing

the patient’s antibodies to samples of his or her own tis-sue, usually thyroid, stomach, liver, and kidney tissue. Ifantibodies bind to the “self” tissue, it is diagnostic for anautoimmune disorder. Antibodies from a person withoutan autoimmune disorder would not react to “self” tissue.
Treatment
Treatment of autoimmune diseases is specific to

the disease, and usually concentrates on alleviating orpreventing symptoms rather than correcting the under-lying cause. For example, if a gland involved in anautoimmune reaction is not producing a hormone suchas insulin, administration of that hormone is required.Administration of a hormone, however, will restorethe function of the gland damaged by the autoimmunedisease.
The other aspect of treatment is controlling the

inflammatory and proliferative nature of the immuneresponse. This is generally accomplished with two typesof drugs. Steroid compounds are used to control inflam-mation. There are many different steroids, each havingside effects. The proliferative nature of the immuneresponse is controlled with immunosuppressive drugs.These drugs work by inhibiting the replication of cellsand, therefore, also suppress non-immune cells leadingto side effects such as anemia.

Systemic enzyme therapy is a new treatment that is
showing results for rheumatoid arthritis, multiple sclero-sis, ankylosing spondylitis, and other inflammatory dis-eases. Enzymes combinations of pancreatin, trypsin,chymotrypsin, bromelain, and papain help stimulate thebody’s own defenses, accelerate inflammation in order toreduce swelling and improve circulation, and break upthe immune complexes within the bloodstream. Symp-toms have been reduced using this treatment.

Other treatments that hold some promise are irradia-
tion of the spleen and gene therapy . Splenic irradiation
is touted to be a safe, alternative for patients with autoim-mune blood diseases, especially autoimmune hemolyticanemia, or others with compromised immune systems,such as HIV patients and the elderly. It is reported tohave few side effects and seems to be working. Cytokine
GALE ENCYCLOPEDIA OF MEDICINE 2 424Autoimmune disordersGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 424

and cytokine inhibitor genes injected directly into muscle
tissue also appear to be effective in treating Type I dia-betes mellitus, systemic lupus erythematosus, thyroditis,and arthritis.
Prognosis
Prognosis depends upon the pathology of each
autoimmune disease.
Most autoimmune diseases cannot be prevented.

Though the mechanisms involved in how these diseasesaffect the body are known, it is still unclear why the bodyturns on itself. Since more women than men seem to beaffected by some of these disorders (e.g. lupus), someresearchers are looking into hormones as a factor. This,and gene therapy, may be the preventatives of the future.
Resources
BOOKS
Abbas, A.K., A.H. Lichtman, and J.S. Pober. Cellular and Mol-

ecular Immunology. Philadelphia: W.B. Saunders Compa-
ny, 1997.
Roit, I. M. Roitt’s Essential Immunolgy. Oxford: Blackwell
Science Ltd., 1997.
Cichoke, Anthony J. “Natural Relief for Autoimmune Disor-
ders.” Better Nutrition. (June 2000)62(6): 24.
Henderson, Charles W. “Gene Therapy Uses Vectors Encoding

Cytokines or Cytokine Inhibitors (for treatment of autoim-mune disorders).” Immunotherapy Weekly. (September 27,
2000): pNA.
Riccio, Nina M. “Autoimmune Disorder: When the Body
Attacks Itself.” Current Health 2. (January 2000)26(5): 13.
“Splenic Irradiation Is an Option for Patients with Autoimmune
Disorders and Those with HIV .” AIDS Weekly. (April 9,
2001): pNA.
Janie F. FranzKEY TERMS
Autoantibody —An antibody made by a person
that reacts with their own tissues.

Paresthesias —A prickly, tingling sensation.Autoimmune hepatitis seeHepatitis,
autoimmune
Autologous transfusion seeTransfusion
Autologous transplant seeBone marrow
Automatic implantable cardioverter-
defibrillator seeImplantable
cardioverter-defibrillator
Autopsy
An autopsy is a postmortem assessment or examina-
tion of a body to determine the cause of death . An autop-
sy is performed by a physician trained in pathology.
Purpose

provide evidence for legal action. Medically, autopsiesdetermine the exact cause and circumstances of death,discover the pathway of a disease, and provide valuableinformation to be used in the care of the living. Whenfoul play is suspected, a government coroner or medicalexaminer performs autopsies for legal use. This branchof medical study is called forensic medicine. Forensicspecialists investigate deaths resulting from violence oroccurring under suspicious circumstances.

Benefits of research from autopsies include the pro-
duction of new medical information on diseases such astoxic shock syndrome , acquired immunodeficiency
syndrome ( AIDS ). Organ donation, which can potential-
ly save the lives of other patients, is also another benefitof autopsies.
When performed for medical reasons, autopsies

require formal permission from family members or thelegal guardian. (Autopsies required for legal reasonswhen foul play is suspected do not need the consent ofnext of kin.) During the autopsy, very concise notes anddocumentation must be made for both medical and legalreasons. Some religious groups prohibit autopsies.
GALE ENCYCLOPEDIA OF MEDICINE 2 425AutopsyGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 425

deceased human body with a detailed exam of the per-son’s remains. This procedure dates back to the Romanera when few human dissections were performed; autop-sies were utilized, however, to determine the cause ofdeath in criminal cases. At the beginning of the proce-dure the exterior body is examined and then the internalorgans are removed and studied. Some pathologistsargue that more autopsies are performed than necessary.However, recent studies show that autopsies can detectmajor findings

show that autopsies can detectmajor findings about a person’s condition that were notsuspected when the person was alive. And the growingawareness of the influence of genetic factors in diseasehas also emphasized the importance of autopsies.

Despite the usefulness of autopsies, fewer autopsies
have been performed in the United States during the pastKEY TERMS
Acquired immunodeficiency syndrome (AIDS)—A group of diseases resulting from infection withthe human immunodeficiency virus (HIV). A per-son infected with HIV gradually loses immunefunction, becoming less able to resist aliments andcancers, resulting in eventual death.
Computed tomography scan (CT scan)— The tech-

nique used in diagnostic studies of internal bodilystructures in the detection of tumors or brainaneurysms. This diagnostic test consists of a com-puter analysis of a series of cross-sectional scansmade along a single axis of a bodily structure ortissue that is used to construct a three-dimensionalimage of that structure
Creutzfeld-Jakob disease —A rare, often fatal dis-

ease of the brain, characterized by gradual demen-tia and loss of muscle control that occurs mostoften in middle age and is caused by a slow virus.
Hepatitis —Inflammation of the liver, caused by
infectious or toxic agents and characterized byjaundice, fever, liver enlargement, and abdominalpain.
Magnetic resonance imaging (MRI) —A diagnostic

tool that utilizes nuclear magnetic energy in theproduction of images of specific atoms and molec-ular structures in solids, especially human cells,tissues, and organs.
Postmortem —After death.10-20 years. A possible reason for this decline is concern

about malpractice suits on the part of the treating physi-cian. Other possible reasons are that hospitals are per-forming fewer autopsies because of the expense orbecause modern technology, such as CT scans and mag-
netic resonance imaging , can often provide sufficient
diagnostic information. Nonetheless, federal regulatorsand pathology groups have begun to establish new guide-lines designed to increase the number and quality ofautopsies being performed.

autopsies increases, hospitals may be forced to chargefamilies a fee for the procedure as autopies are not nor-mally covered by insurance companies or Medicare. Yet,according to several pathologists, the benefit of the pro-cedure for families and doctors does justify the cost. Inmedical autopsies, physicians remain cautious to exam-ine only as much of the body as permitted according tothe wishes of the family. It is important to note thatautopsies can also provide peace of mind for thebereaved

can also provide peace of mind for thebereaved family in certain situations.

If a medical autopsy is being performed, written per-
mission is secured from the family of the deceased
Aftercare
Once the autopsy has been completed, the body is
prepared for final arrangements according to the family’swishes
Risks
There are some risks of disease transmission from
the deceased. In fact, some physicans may refuse to doautopsies on specific patients because of a fear of con-tracting diseases such as AIDS, hepatitis, or Creutzfeld-Jakob disease.

In most situations the cause of death is determined
from the procedure of an autopsy without any transmis-sion of disease.
Abnormal results would include inconclusive results
from the autopsy and transmission of infectious diseaseduring the autopsy.
GALE ENCYCLOPEDIA OF MEDICINE 2 426AutopsyGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 426

Resources
BOOKS
Van de Graff, Kent M., and Stuart I. Fox. Concepts of Human
Anatomy and Physiology. Dubuque, IA: Wm. C. Brown
Publishers 1986.
American Medical Association. 515 N. State St., Chicago, IL
60612. (312) 464-5000. <http://www.ama-assn.org>.
OTHER
“When and Why an Autopsy is Ordered After Death.” Universi-
ty of Texas Lifetime Health Letter 9, no.5 (May 1997): 4-5.
Aviation medicine
Also known as aerospace medicine, flight medicine,

or space medicine, aviation medicine is a medical spe-cialty that focuses on the physical and psychologicalconditions associated with flying and space travel.
Purpose
Since flying airplanes and spacecraft involves great
risk and physical demands, such as changes in gravityand oxygen, pilots and astronauts need medical expertsto protect their safety and the public’s safety.
Pressure changes
In the United States, the Federal Aviation Adminis-

tration (FAA) requires all pilots who fly above 14,500 ft(4,420 m) to be prepared for pressure changes caused bylower oxygen levels at high altitude. Pilots must eitherhave a pressurized cabin or access to an oxygen mask.Without these protections, they could experience hypox-ia, or altitude sickness . Hypoxia reduces the amount of
oxygen in the brain, causing such symptoms asdizziness ,shortness of breath , and mental confusion.

These symptoms could cause the pilot to lose control ofthe plane. Hypoxia can be treated with oxygen therapy.
Rapid altitude increases and decreases can cause
pain because there is an air pocket in the middle portion

of the ear. To equalize pressure in the ear, physicians typ-ically advise pilots and passengers to clear their sinusesby plugging their nose and blowing until the eardrums“pop.” Other options include yawning, swallowing orchewing gum. For people with a cold or a severelyblocked middle ear, the use of decongestants ,antihista-
mines , or nasal sprays may help. Without taking steps to
equalize pressure, the tympanic membrane could rupture,causing hearing loss , vertigo, dizziness, and nausea.

Gravity’s impact
Fighter pilots who fly high-performance jets can

experience health problems during rapid acceleration andwhen executing tight turns at high speed. During thesemoves, a pilot experiences extreme gravity conditionsthat can pull blood away from the brain and heart andinto the lower body. This can cause the pilot to have tun-nel vision or pass out. To prevent these potentially deadlysituations, the military requires fighter pilots to wear spe-cial flight suits, or G suits, which have compartmentsthat fill with air or fluid to keep blood from

fill with air or fluid to keep blood from pooling inthe lower body.

Some pilots, like the Blue Angels, use a technique
called the Valsalva Maneuver instead of G suits to pre-
vent black outs during high-performance flying. The Val-salva Maneuver involves grunting and tightening theabdominal muscles to stop blood from collecting in thewrong parts of the body.
PREVENTIVE CARE. Since any routine health problem

that affects a pilot could mean the loss of hundreds oflives, aviation medicine specialists who work for com-mercial airlines and the military take special care to edu-cate pilots about proper diet, exercise and preventive
health tools. For example, physicians may frequentlyscreen pilots for vision changes caused by glaucoma or
cataracts . They also will check for hearing loss and

encourage the pilot to wear earplugs or headphones tobuffer engine noise. To monitor for heart disease, physi-cians will check blood pressure and may order diagnostictests such as an ECG or stress test .
Motion sickness
Many people experience nausea, vertigo, and disori-

entation when they first arrive in space. This is caused bychanges in the fluid in the inner ear, which is sensitive togravity and affects our sense of spatial orientation. Thesymptoms typically ease after several days, but oftenrecur when the astronaut returns to Earth. To treat thiscondition, physicians give astronauts motion sickness
medication, such as lorazepam.
Bone and muscle loss
In zero-gravity conditions, astronauts lose bone and

muscle mass. On earth, the natural resistance of gravityhelps build stronger muscles and bones during normal
GALE ENCYCLOPEDIA OF MEDICINE 2 427Aviation medicineGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 427

weight-bearing activities like walking or even sitting at a
desk. In space, however, astronauts must work harder toprevent bone and muscle loss. Exercise is an importanttreatment. Crew members may use an exercise cycle orresistive rubber bands to stay in shape. Physicians also maygive them medication to prevent bone loss and prescribenutritional supplements, such as a mixture of essentialamino acids and carbohydrates, to limit muscle atrophy.
Radiation

Radiation
Another health threat to space travelers is radiation.
Harmful rays can alter the DNA in human cells andcause cancer . Excess radiation also can weaken the
immune system. To prevent these problems, physiciansmay give astronauts nutritional supplements. For exam-ple, research has show that n-3 fatty acids found in fishoil reduce DNA damage.
Cardiovascular issues
When astronauts return to earth after a long mission,

they tend to feel dizzy and black out. Scientists are con-cerned about this dilemma because it could be dangerousif the crew members need to make an emergency exit.One way to prevent this problem, which is caused by adrop in blood pressure, is to have the astronauts drinkextra fluids and increase salt intake to increase blood vol-ume. Physicians also may prescribe medication thatcauses blood vessels to contract. As another precaution,astronauts also put on protective flight suits, or G

also put on protective flight suits, or G suits,before they re-enter the earth’s atmosphere.KEY TERMS

G suits —Special flight suits, worn by fighter pilots,
which have compartments that fill with air or fluidto keep blood from pooling in the lower body dur-ing rapid acceleration and tight turns.
Hypoxia —Hypoxia, or altitude sickness, reduces
the amount of oxygen in the brain causing suchsymptoms as dizziness, shortness of breath, andmental confusion.
Tympanic membrane —A structure in the middle
ear that can rupture if pressure in the ear is notequalized during airplane ascents and descents.

Valsalva Maneuver —Pilots grunt and tighten their
abdominal muscles to prevent black outs duringhigh-performance flying.Resources
BOOKS
Dehart, Roy L. Fundamentals of Aerospace Medicine.
Philadelphia: Lippincott, Williams & Wilkins, 1996.
Aviation, Space and Environmental Medicine. Monthly peer-
reviewed journal published by the Aerospace MedicalAssociation. Contact the editor: 3212 Swandale Dr., SanAntonio, TX 78230-4404. (210) 342-5670. ASEMJour-nal@worldnet.att.net.

Aerospace Medical Association. 320 S. Henry St., Alexandria,
V A 22314-3579. (703) 739-2240. <http://www.asma.org>.(
National Space Biomedical Research Institute. One Baylor
Plaza, NA-425, Houston, TX 77030. (713) 798-7412.info@www.nsbri.org. <http://www.nsbri.org>.
Wright State University Aerospace Medicine Program. P.O.
Box 92, Dayton, Ohio 45401-0927. (937) 276-8338.<http://www.med.wright.edu>.
OTHER
Society of USAF Flight Surgeons Online Catalog. <http://

www.sam.brooks.af.mil/ram/rammain.htm>.
Federal Aviation Administration Office of Aviation Medicine.
<http://www.faa.gov/avr/aamhome.htm>.
National Aeronautics and Space Administration Aerospace
Medicine. <http://spacelink.msfc.nasa.gov>.
AVM seeArteriovenous malformations
Avoidant personality disorder see
Personality disorders
Avulsions seeWounds
Ayurvedic medicine
Ayurvedic medicine is a system of healing that
originated in ancient India. In Sanskrit, ayur means

life or living, and veda means knowledge, so Ayurveda
has been defined as the “knowledge of living” or the“science of longevity.” Ayurvedic medicine utilizesdiet, detoxification and purification techniques,
herbal and mineral remedies, yoga , breathing exercis-
es,meditation , and massage therapy as holistic heal-
ing methods. Ayurvedic medicine is widely practicedin modern India and has been steadily gaining follow-ers in the West.

GALE ENCYCLOPEDIA OF MEDICINE 2 428Aviation medicineGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 428

Purpose
According to the original texts, the goal of Ayurveda
is prevention as well as promotion of the body’s owncapacity for maintenance and balance. Ayurvedic treat-ment is non-invasive and non-toxic, so it can be usedsafely as an alternative therapy or alongside conventionaltherapies. Ayurvedic physicians claim that their methodscan also help stress-related, metabolic, and chronic con-ditions. Ayurveda has been used to treat acne ,allergies ,

asthma ,anxiety , arthritis, chronic fatigue syndrome ,
colds, colitis, constipation , depression, diabetes, flu,
heart disease, hypertension , immune problems, inflam-
mation, insomnia , nervous disorders, obesity , skin prob-
lems, and ulcers.
Ayurvedic physicians seek to discover the roots of a

disease before it gets so advanced that more radical treat-ments are necessary. Thus, Ayurveda seems to be limitedin treating severely advanced conditions, traumaticinjuries, acute pain , and conditions and injuries requiringinvasive surgery. Ayurvedic techniques have also been
used alongside chemotherapy and surgery to assist
patients in recovery and healing.
Origins
Ayurvedic medicine originated in the early civiliza-

tions of India some 3,000-5,000 years ago. It is men-tioned in the Vedas , the ancient religious and philosophi-

cal texts that are the oldest surviving literature in theworld, which makes Ayurvedic medicine the oldest sur-viving healing system. According to the texts, Ayurvedawas conceived by enlightened wise men as a system ofliving harmoniously and maintaining the body so thatmental and spiritual awareness could be possible. Med-ical historians believe that Ayurvedic ideas were trans-ported from ancient India to China and were instrumentalin the development of Chinese medicine.

GALE ENCYCLOPEDIA OF MEDICINE 2 429Ayurvedic medicine
DEEPAK CHOPRA (1946– )
Deepak Chopra was born in India and studied medi-
cine at the All India Institute of Medical Science. He lefthis home for the United States in 1970 and completedresidencies in internal medicine and endocrinology. Hewent on to teaching posts at major medical institutions—Tufts University and Boston University schools of medi-

cine—while establishing a very successful private prac-tice. By the time he was thirty-five, Chopra had becomechief of staff at New England Memorial Hospital.
Disturbed by Western medicine’s reliance on med-

ication, he began a search for alternatives and discoveredone in the teachings of the Maharishi Mahesh Yogi, anIndian spiritualist who had gained a cult following in thelate sixties teaching Transcendental Meditation (TM).Chopra began practicing TM fervently and eventually metthe Maharishi. In 1985 Chopra established the AyurvedicHealth Center for Stress Management and BehavioralMedicine in Lancaster, Massachusetts, where he beganhis practice of integrating the best aspects of Eastern

In 1993, he published Creating Affluence: Wealth
Consciousness in the Field of All Possibilities , and the
enormously successful best seller, Ageless Body, Timeless
Mind . In the latter he presents his most radical thesis: that

aging is not the inevitable deterioration of organs andmind that we have been traditionally taught to think of itas. It is a process that can be influenced, slowed down,and even reversed with the correct kinds of therapies,almost all of which are self-administered or self-taught.He teaches that applying a regimen of nutritional bal-ance, meditation, and emotional clarity characterized bysuch factors as learning to easily and quickly expressanger, for instance, can lead to increased lifespans of

for instance, can lead to increased lifespans of upto 120 years.

(AP/Wide World Photos. Reproduced by permission.)GEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 429

population in India. Aided by the efforts of DeepakChopra and the Maharishi, it has become an increasinglyaccepted alternative medical treatment in America duringthe last two decades. Chopra is an M.D. who has writtenseveral bestsellers based on Ayurvedic ideas. He alsohelped develop the Center for Mind/Body Medicine inLa Jolla, California, a major Ayurvedic center that trainsphysicians in Ayurvedic principles, produces herbalremedies, and conducts research and documentation ofits healing

Key ideas
To understand Ayurvedic treatment, it is necessary to
have an idea how the Ayurvedic system views the body.The basic life force in the body is prana , which is also
found in the elements and is similar to the Chinesenotion of chi. As Swami Vishnudevananda, a yogi and

expert, put it, “Prana is in the air, but is not the oxygen,nor any of its chemical constituents. It is in food, water,and in the sunlight, yet it is not vitamin, heat, or light-rays. Food, water, air, etc., are only the media throughwhich the prana is carried.”
In Ayurveda, there are five basic elements that con-

tain prana: earth, water, fire, air, and ether. These ele-ments interact and are further organized in the humanbody as three main categories or basic physiologicalprinciples in the body that govern all bodily functionsknown as the doshas . The three doshas are vata, pitta,
and kapha . Each person has a unique blend of the three
doshas, known as the person’s prakriti , which is why

Ayurvedic treatment is always individualized. InAyurveda, disease is viewed as a state of imbalance inone or more of a person’s doshas, and an Ayurvedicphysician strives to adjust and balance them, using avariety of techniques.The vata dosha is associated with air and ether, and

in the body promotes movement and lightness. Vata peo-ple are generally thin and light physically, dry-skinned,and very energetic and mentally restless. When vata isout of balance, there are often nervous problems, hyper-activity, sleeplessness, lower back pains, and headaches.
Pitta is associated with fire and water. In the body, it

is responsible for metabolism and digestion. Pitta char-acteristics are medium-built bodies, fair skin, strongdigestion, and good mental concentration. Pitta imbal-ances show up as anger and aggression and stress-relat-ed conditions like gastritis , ulcers, liver problems, and
hypertension.
The kapha dosha is associated with water and earth.

People characterized as kapha are generally large orheavy with more oily complexions. They tend to be slow,calm, and peaceful. Kapha disorders manifest emotional-ly as greed and possessiveness, and physically as obesity,fatigue ,bronchitis , and sinus problems.
Diagnosis
In Ayurvedic medicine, disease is always seen as an

imbalance in the dosha system, so the diagnostic processstrives to determine which doshas are underactive oroveractive in a body. Diagnosis is often taken over acourse of days in order for the Ayurvedic physician tomost accurately determine what parts of the body arebeing affected. To diagnose problems, Ayurvedic physi-cians often use long questionnaires and interviews todetermine a person’s dosha patterns and physical andpsychological histories. Ayurvedic physicians also intri-cately observe

Ayurvedic physicians also intri-cately observe the pulse, tongue, face, lips, eyes, and fin-gernails for abnormalities or patterns that they believecan indicate deeper problems in the internal systems.Some Ayurvedic physicians also use laboratory tests toassist in diagnosis.

GALE ENCYCLOPEDIA OF MEDICINE 2 430Ayurvedic medicineAyurvedic Body Types
Vata Pitta Kapha
Physical characteristics Thin Average build Large build
Prominent features Fair, thin hair Wavy, thick hairCool, dry skin Warm, moist skin Pale, cool, oily skinConstipation Ulcers, heartburn, and hemorrhoids Obesity, allergies, and sinus problemsCramps Acne High cholesterol
Emotional characteristics Moody Intense Relaxed

Vivacious Quick tempered Not easily angeredImaginative Intelligent AffectionateEnthusiastic Loving TolerantIntuitive Articulate Compassionate
Behavioral characteristics Unscheduled sleep and meal times Orderly Slow, graceful
Nervous disorders Structured sleep and meal times Long sleeper and slow eaterAnxiety Perfectionist ProcrastinationGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 430

Treatment
Ayurvedic treatment seeks to re-establish balance
and harmony in the body’s systems. Usually the firstmethod of treatment involves some sort of detoxificationand cleansing of the body, in the belief that accumulatedtoxins must be removed before any other methods oftreatment will be effective. Methods of detoxificationinclude therapeutic vomiting, laxatives , medicated ene-
mas,fasting , and cleansing of the sinuses. Many Ayur-

vedic clinics combine all of these cleansing methods intointensive sessions known as panchakarma . Panchakarma
can take several days or even weeks and they are morethan elimination therapies. They also include herbalizedoil massage and herbalized heat treatments . After purifi-
cation, Ayurvedic physicians use herbal and mineralremedies to balance the body as well. Ayurvedic medicinecontains a vast knowledge of the use of herbs for specifichealth problems.

Ayurvedic medicine also emphasizes how people live
their lives from day to day, believing that proper lifestylesand routines accentuate balance, rest, diet, and preven-tion. Ayurveda recommends yoga as a form of exercise to
build strength and health, and also advises massage thera-py and self-massage as ways of increasing circulation andreducing stress . Yogic breathing techniques and medita-
tion are also part of a healthy Ayurvedic regimen, toreduce stress and improve mental energy.

basic and widely used therapy in the Ayurvedic system.An Ayurvedic diet can be a very well planned and indi-vidualized regimen. According to Ayurveda, there are sixbasic tastes: sweet, sour, salty, pungent, bitter, and astrin-gent. Certain tastes and foods can either calm or aggra-vate a particular dosha. For instance, sweet, sour, andsalty decrease vata problems and increase kapha. Sour,salty, and pungent can increase pitta. After an Ayurvedicphysician determines a person’s dosha profile, they

determines a person’s dosha profile, they willrecommend a specific diet to correct imbalances andincrease health. The Ayurvedic diet emphasizes primarilyvegetarian foods of high quality and freshness, tailored tothe season and time of day. Cooling foods are eaten inthe summer and heating ones in the winter, always withina person’s dosha requirements. In daily routine, the heav-iest meal of the day should be lunch, and dinner shouldeaten well before bedtime, to allow for complete diges-tion.

before bedtime, to allow for complete diges-tion. Also, eating meals in a calm manner with properchewing and state of mind is important, as is combiningfoods properly and avoiding overeating.

Cost
Costs of Ayurvedic treatments can vary, with initial
consultations running anywhere from $40 to over $100,KEY TERMS
Dosha —One of three constitutional types, either
vata, pitta, or kapha, found in Ayurvedic medicine.
Meditation —Technique of calming the mind.
Panchakarma —Intensive Ayurvedic cleansing and
detoxification program.
Prakriti —An individual’s unique dosha pattern.
Prana —Basic life energy found in the elements.
Yoga—System of body and breathing exercises.

with follow-up visits costing less. Herbal treatments may

cost from $10 to $50 per month, and are often availablefrom health food or bulk herb stores. Some clinics offerpanchakarma, the intensive Ayurvedic detoxificationtreatment, which can include overnight stays for up toseveral weeks. The prices for these programs can varysignificantly, depending on the services and length ofstay. Insurance reimbursement may depend on whetherthe primary physician is a licensed M.D.
Ayurveda is a mind/body system of health that con-

tains some ideas foreign to the Western scientificmodel. Those people considering Ayurveda shouldapproach it with an open mind and willingness toexperiment. Also, because Ayurveda is a whole-bodysystem of healing and health, patience and disciplineare helpful, as some conditions and diseases arebelieved to be brought on by years of bad health habitsand require time and effort to correct. Finally, theAyurvedic philosophy believes that each person has theability to heal themselves, so those

has theability to heal themselves, so those considering Ayurve-da should be prepared to bring responsibility and partic-ipation into the treatment.

An Ayurvedic practitioner should always be consulted.
During Ayurvedic detoxification programs, some
people report fatigue, muscle soreness, and general sick-ness. Also, as Ayurveda seeks to release mental stressesand psychological problems from the patient, some peo-ple can experience mental disturbances and depressionduring treatment, and psychological counseling may bepart of a sound program.

GALE ENCYCLOPEDIA OF MEDICINE 2 431Ayurvedic medicineGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 431

Because Ayurveda had been outside the Western sci-

entific system for years, research in the United States isnew. Another difficulty in documentation arises becauseAyurvedic treatment is very individualized; two peoplewith the same disease but different dosha patterns mightbe treated differently. Much more scientific research hasbeen conducted over the past several decades in India.Much research in the United States is being supported bythe Maharishi Ayur-Ved organization, which studies theAyurvedic products it sells and its clinical practices.

Some Ayurvedic herbal mixtures have been proven to
have high antioxidant properties, much stronger than vita-
mins A, C, and E, and some have also been shown in labo-
ratory tests to reduce or eliminate tumors in mice and toinhibit cancer growth in human lung tumor cells. In a
1987 study at MIT, an Ayurvedic herbal remedy wasshown to significantly reduce colon cancer in rats. Anoth-

er study was performed in the Netherlands with MaharishiAyur-Ved products. A group of patients with chronic ill-nesses, including asthma, chronic bronchitis, hyperten-sion, eczema, psoriasis , constipation, rheumatoid arthri-
tis, headaches, and non-insulin dependent diabetes melli-
tus, were given Ayurvedic treatment. Strong results were
observed, with nearly 80% of the patients improving andsome chronic conditions being completely cured.
Other studies have shown that Ayurvedic therapies

can significantly lower cholesterol and blood pressure instress-related problems. Diabetes, acne, and allergieshave also been successfully treated with Ayurvedic reme-dies. Ayurvedic products have been shown to increaseshort-term memory and reduce headaches. Also,Ayurvedic remedies have been used successfully to sup-port the healing process of patients undergoingchemotherapy, as these remedies have been demonstratedto increase immune system activity.
Resources
BOOKS

Resources
BOOKS
Gerson, Scott M.D. Ayurveda: The Ancient Indian Healing Art.
Boston: Element Books, 1993.Lad, Dr. Vasant. Ayurveda: The Science of Self-Healing. Wis-
consin: Lotus Press, 1984.
Lad, Dr. Vasant. The Complete Book of Ayurvedic Home Reme-
dies. Minneapolis: Three Rivers Press, 1999.
Tiwari, Maya. Ayurveda: A Life of Balance. Vermont: Healing
Arts Press, 1995.
American Institute of Vedic Studiess. P.O. Box 8357, Santa Fe,
NM 87504. (505) 983-9385

Ayurveda Holistic Center. Bayville, Long Island, NY .
(516)759-7731 mail@Ayurvedahc.com <http://www.Ayurvedahc.com>.
The Ayurvedic Institute. 11311 Menaul, NE Albuquerque, New
Mexico 87112. (505)291-9698. info@Ayurveda.com<http://www.Ayurveda.com>.
Ayurvedic and Naturopathic Medical Clinic. 10025 NE 4th
Street, Bellevue, WA 98004. (206)453-8022.
Bastyr University of Natural Health Sciences. 144 N.E. 54th
Street, Seattle, WA 98105. (206)523-9585.

Center for Mind/Body Medicine. P.O. Box 1048, La Jolla, CA
92038. (619)794-2425.
The College of Maharishi Ayur-Ved, Maharishi International
University. 1000 4th Street, Fairfield, IA 52557.(515)472-7000.
National Institute of Ayurvedic Medicine. (914)278-8700. 
drgerson@erols.com <http://www.niam.com>.
The Rocky Mountain Institute of Yoga and Ayurveda. P.O. Box
1091, Boulder, CO 80306. (303)443-6923.
OTHER

OTHER
“Inside Ayurveda: An Independent Journal of Ayurvedic Health
Care.” P.O. Box 3021, Quincy, CA 95971. <http://www.insideayurveda.com>.
Azithromycin seeErythromycins
AZT seeAntiretroviral drugs
GALE ENCYCLOPEDIA OF MEDICINE 2 432Ayurvedic medicineGEM - 0001 to 0432 - A  10/22/03 1:43 PM  Page 432

B-cell count seeLymphocyte typing
Babesiosis
Babesiosis is an infection of red blood cells caused
by the single-celled parasite, Babesia microti , which is
spread to humans by a tick bite.
Babesiosis is a rare, tick-transmitted disease that is
caused most often by the single-celled parasite Babesia
microti . By 1995, fewer than 500 cases of babesiosis had

been reported in the United States. The disease occursprimarily in New England and New York, especially onthe coastal islands. However, cases have occurred inother parts of the United States. Because of tick activity,the risk for babesiosis is highest during June and July.
Ticks are small, blood-sucking arachnids. Although
some ticks carry disease-causing organisms, most do not.Babesia microti is spread to humans through the bite of
the tick Ixodes scapularis (also called Ixodes dammini ).

Ixodes scapularis , called the “blacklegged deer tick,” usu-
ally feeds on deer and mice. A tick picks up the parasitesby feeding on an infected mouse and then passes them onby biting a new host, possibly a human. To pass on theparasites, the tick must be attached to the skin for 36-48hours. Once in the bloodstream, Babesia microti enters a
red blood cell, reproduces by cell division, and destroysthe cell. Humans infected with Babesia microti produce

antibodies that can be helpful in diagnosing the infection.
Babesia microti live and divide within red blood

cells, destroying the cells and causing anemia. Themajority of people who are infected have no visiblesymptoms. In those who become ill, symptoms appearone to six weeks following the tick bite. Because theticks are small, many patients have no recollection of atick bite. The symptoms are flu-like and include tired-ness, loss of appetite, fever , drenching sweats, and mus-
cle pain . Nausea, vomiting, headache , shaking chills,

blood in the urine, and depression can occur.
Persons who are over 40 years old, have had their
spleen removed (splenectomized), and/or have a seriousdisease ( cancer ,AIDS , etc.) are at a greater risk for
severe babesiosis. In severe cases of babesiosis, up to85% of the blood cells can be infected. This causes aserious, possibly fatal, blood deficiency.
Diagnosis
Babesiosis can be diagnosed by examining a blood

sample microscopically and detecting the presence ofBabesia microti within the blood cells. The blood can also
be checked for the presence of antibodies to the parasite.
Treatment
In serious cases, babesiosis is treated with a combi-

nation of clindamycin (Cleocin) and quinine. Clin-damycin is given by injection and quinine is given orallythree to four times a day for four to seven days. Toreduce the number of parasites in the blood, severely illpatients have been treated with blood transfusions.
Prognosis
Otherwise healthy patients will recover completely.
Babesiosis may last several months without treatmentand is a severe, potentially fatal disease in splenec-tomized patients.

The only prevention for babesiosis is to minimize
exposure to ticks by staying on trails when walkingB
GALE ENCYCLOPEDIA OF MEDICINE 2 433GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 433

through the woods, avoiding tall grasses, wearing long
sleeves and tucking pant legs into socks, wearing insectrepellent, and checking for ticks after an outing. Removea tick as soon as possible by grasping the tick with tweez-ers and gently pulling. Splenectomized people shouldavoid northeastern coastal regions during the tick season.
Resources
BOOKS
Blood: Textbook of Hematology. 2nd ed. Ed. James H. Jandl.
Boston: Little, Brown and Co., 1996.

Chiodini, Peter L. “Babesiosis.” In Manson’s Tropical Dis-
eases. 20th ed. Philadelphia: W. B. Saunders Co., 1996.
Infections and Diseases. 2nd ed. Ed. Sherood L. Gorbach, John
G. Bartlett, and Neil R. Blacklow. Philadelphia: W. B.Saunders Co., 1997.
OTHER
Bach flower remedies seeFlower remedies
Bacillary angiomatosis

A life-threatening but curable infection that causes
an eruption of purple lesions on or under the skin thatresemble Kaposi’s sarcoma . The infection, which
occurs almost exclusively in patients with AIDS , can be
a complication of cat-scratch disease .
Bacillary angiomatosis is a re-emerging bacterial

infection that is identical or closely related to one whichcommonly afflicted thousands of soldiers during WorldWar I. Today, the disease, caused by two versions of theKEY TERMS
Anemia —A below normal number of red blood
cells in the bloodstream.
Parasite —An organism that lives upon or within
another organism.same bacteria, is linked to homeless AIDS patients and to
those afflicted with cat-scratch disease.

The infection is rarely seen today in patients who
don’t have HIV . According to the U.S. Centers for Dis-ease Control and Prevention (CDC), an HIV patient diag-nosed with bacillary angiomatosis is considered to haveprogressed to full-blown AIDS.
Scientists have recently isolated two varieties of the
Bartonella bacteria as the cause of bacillary angiomato-sis:Bartonella (formerly Rochalimaeaquintana ) and B.

henselae (cause of cat-scratch disease).
B. quintana infection is known popularly as trench
fever , and is the infection associated with body lice that
sickened European troops during World War I. Lice carrythe bacteria, and can transmit the infection to humans.The incidence of trench fever was believed to have faded
away with the end of World War I. It was not diagnosedin the United States until 1992, when 10 cases werereported among homeless Seattle men.

The related bacteria B. henselae was first identified
several years ago as the cause of cat-scratch fever. It alsocan lead to bacillary angiomatosis in AIDS patients.Bacillary angiomatosis caused by this bacteria is trans-mitted to AIDS patients from cat fleas.
These two different types of bacteria both cause

bacillary angiomatosis, a disease which is characterizedby wildly proliferating blood vessels that form tumor-likemasses in the skin and organs. The nodules that appear inbacillary angiomatosis are firm and don’t turn white whenpressed. The lesions can occur anywhere on the body, innumbers ranging from one to 100. They are rarely foundon palms of the hands, soles of the feet, or in the mouth.As the number of lesions increase, the patient may devel-op a high fever, sweats, chills, poor appetite,

a high fever, sweats, chills, poor appetite, vomiting,and weight loss. If untreated, infection may be fatal.

In addition to the basic disease process, the two dif-
ferent types of bacteria cause some slightly differentsymptoms. Patients infected with B. henselae also expe-
rience blood-filled cysts within the liver and abnormalliver function, whereas B. quintana patients may have
tumor growths in the bone.
Diagnosis
This life-threatening but curable infection is often

misdiagnosed, because it may be mistaken for other con-ditions (such as Kaposi’s sarcoma). A blood test devel-oped in 1992 by the CDC detects antibodies to the bacte-ria. It can be confirmed by reviewing symptoms, history
GALE ENCYCLOPEDIA OF MEDICINE 2 434Bacillary angiomatosisGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 434

and negative tests for other diseases that cause swollen
lymph glands. It isn’t necessary to biopsy a small sampleof the lymph node unless there is a question of cancer of
the lymph node or some other disease.
Treatment
Recent research indicates that antibiotics used to

treat other HIV opportunistic infections can both preventand treat bacillary angiomatosis. Treatment is usuallygiven until the lesions disappear, which typically takesthree or four weeks. A severely affected lymph node orblister may have to be drained, and a heating pad mayhelp swollen, tender lymph glands. Acetaminophen
(Tylenol) may relieve pain , aches, and fever over 101°F
(38.3°C).
Prognosis
In most cases, prompt antibiotic treatment in

patients with AIDS cured the infection caused by eithervariety of the bacteria, and patients may resume normallife. Early diagnosis is crucial to a cure.
Studies suggest that antibiotics may prevent the dis-
ease. Patients also should be sure to treat cats for fleas.
Resources
Koehler, J. E. “Zoonoses: Cats, Fleas and Bacteria.” Journal of
the American Medical Association 271 (1994): 531-535.

Tsang, W. Y ., and J. K. Chan. “Bacillary Angiomatosis: A “New”
Disease With a Broadening Clinicopathologic Spectrum.”Histology and Histopathology 7 (Jan. 1992): 143-52.
Bacillary dysentery seeShigellosis
Bacitracin seeAntibiotics, topicalKEY TERMS
Cat-scratch disease —An infectious disease caused
by bacteria transmitted by the common cat fleathat causes a self-limiting, mild infection inhealthy people.
Kaposi’s sarcoma —A malignant condition that

begins as soft brown or purple lesions on the skinthat occurs most often in men with AIDS.Bacteremia
Bacteremia is an invasion of the bloodstream by
bacteria.
Bacteremia occurs when bacteria enter the blood-
stream. This may occur through a wound or infection, orthrough a surgical procedure or injection. Bacteremiamay cause no symptoms and resolve without treatment,or it may produce fever and other symptoms of infection.

In some cases, bacteremia leads to septic shock , a poten-
tially life-threatening condition.
Causes
Several types of bacteria live on the surface of the

skin or colonize the moist linings of the urinary tract,lower digestive tract, and other internal surfaces. Thesebacteria are normally harmless as long as they are kept incheck by the body’s natural barriers and the immune sys-tem. People in good health with strong immune systemsrarely develop bacteremia. However, when bacteria areintroduced directly into the circulatory system, especial-ly in a person who is ill or undergoing aggressive med-ical treatment, the immune system may not be able

treatment, the immune system may not be able tocope with the invasion, and symptoms of bacteremia maydevelop. For this reason, bacteremia is most common inpeople who are already affected by or being treated forsome other medical problem. In addition, medical treat-ment may bring a person in contact with new types ofbacteria that are more invasive than those already resid-ing in that person’s body, further increasing the likeli-hood of bacterial infection.

Conditions which increase the chances of develop-
ing bacteremia include:
• immune suppression, either due to HIV infection or
drug therapy
• antibiotic therapy which changes the balance of bacteri-
al types in the body
• prolonged or severe illness
• alcoholism or other drug abuse• malnutrition• diseases or drug therapy that cause ulcers in the
intestines, e.g. chemotherapy for cancer
Common immediate causes of bacteremia include:

GALE ENCYCLOPEDIA OF MEDICINE 2 435BacteremiaGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 435

• drainage of an abscess , including an abscessed tooth.
• urinary tract infection, especially in the presence of a
bladder catheter.
• decubitus ulcers (pressure sores).
• intravenous procedures using unsterilized needles,
including IV drug use.
• prolonged IV needle placement.
• use of ostomy tubes, including gastrostomy (surgically
making a new opening into the stomach), jejunostomy(surgically making an opening from the abdominal wallinto the jejunum), and colostomy (surgically creating

an articifical opening into the colon).
The bacteria most likely to cause bacteremia include
members of the Staphylococcus, Streptococcus, Pseudo-
monas, Haemophilus, and Esherichia coli (E. coli ) genera.
Symptoms
Symptoms of bacteremia may include:
• fever over 101°F (38.3°C)
• chills
• malaise
• nausea
• vomiting
• diarrhea
• anxiety
• shortness of breath• confusion
Not all of these symptoms are usually present. In the

elderly, confusion may be the only prominent symptom.Bacteremia may lead to septic shock , whose symptoms
include decreased consciousness, rapid heart and breath-ing rates and multiple organ failures.
Diagnosis
Bacteremia is diagnosed by culturing the blood for

bacteria. Samples may need to be tested several timesover several hours. Blood analysis may also reveal anelevated number of white blood cells. Blood pressure ismonitored closely; a decline in blood pressure may indi-cate the onset of septic shock.
Treatment
Antibiotics are the mainstay of treatment, and are
often begun before positive identification of the bacteriais made. Close observation is required to guard againstKEY TERMS
Colostomy —Surgical creation of an artificial anus

on the abdominal wall by cutting into the colonand bringing it up to the surface.
Gastrostomy —Surgical creation of an artificial
opening into the stomach through the abdominalwall to allow tube feeding.
Jejunostomy —Surgical creation of an opening to
the middle portion of the small intestine(jejunum), through the abdominal wall.
Septic shock —A life-threatening drop in blood
pressure caused by bacterial infection.
septic shock. Since bacteremia is usually associated with

an existing infection elsewhere in the body, finding andtreating this infection is an important part of treatment.
Bacteremia may cause no symptoms, but may be dis-
covered through a blood test for another condition. In thissituation, it may not need to be treated, except in patientsespecially at risk for infection, such as those with heartvalve defects or whose immune systems are suppressed.
Prognosis
Prompt antibiotic therapy usually succeeds in clear-

ing bacteria from the bloodstream. Recurrence may indi-cate an undiscovered site of infection. Untreated bacteriain the blood may spread, causing infection of the heart(endocarditis or pericarditis ) or infection of the cover-
ing of the central nervous system ( meningitis ).
Bacteremia can be prevented by preventing the

infections which often precede it. Good personalhygiene, especially during viral illness, may reduce therisk of developing bacterial infection. Treating bacterialinfections quickly and thoroughly can minimize the riskof spreading infection. During medical procedures, theburden falls on medical professionals to minimize thenumber and duration of invasive procedures, to reducepatients’ exposure to sources of bacteria when beingtreated, and to use scrupulous technique.
Resources
BOOKS

Resources
BOOKS
GALE ENCYCLOPEDIA OF MEDICINE 2 436BacteremiaGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 436

OTHER
The Meck Page. 13 Apr. 1998 <http://www.merck.com>.
Bacterial meningitis seeMeningitis
Bacterial vaginosis seeVulvovaginitis
Bacteroides infection seeAnaerobic
Bad breath
Bad breath, sometimes called halitosis, is an
unpleasant odor of the breath.
Bad breath is likely to be experienced by most adults
at least occasionally. Bad breath, either real or imagined,can have a significant impact on a person’s social andprofessional life.

Bad breath can be caused by a number of problems.

Oral diseases, fermentation of food particles in themouth, sinus infections, and unclean dentures can allcontribute to mouth odor. Many non-oral diseases, suchas lung infections, kidney failure, or severe liver disease,can also cause bad breath, though rarely. Many peoplethink that bad breath can originate in the stomach orintestines; this is extremely rare. The esophagus is usual-ly collapsed and closed, and, although a belch may carryodor up from the stomach, the chance of bad breathbeing

from the stomach, the chance of bad breathbeing caused from air continually escaping from thestomach is remote. Cigarette smoke can cause badbreath, not only in the cigarette smoker, but also in onewho is constantly exposed to second-hand smoke.

Diagnosis
The easiest way to determine if one has bad breath is
to ask someone who is trustworthy and discrete. This isusually not too difficult. Another, more private, method ofdetermining if one has bad breath is to lick one’s wrist,wait until it dries, then smell the area. Scraping the reararea of the tongue with a plastic spoon, then smelling thespoon, is another method one can use to assess bad breath.KEY TERMS
Halitosis —The medical term for bad breath.
Treatment

Treatment
The most effective treatment of bad breath is to treat
the cause. Poor oral hygiene can be improved by regular
brushing and flossing, as well as regular dental checkups.Gentle brushing of the tongue should be part of daily oralhygiene. In addition to good oral hygiene, the judicioususe of mouthwashes is helpful. Mouth dryness, experi-enced at night or during fasting , or due to certain med-

ications and medical conditions, can contribute to badbreath. Dryness can be avoided by drinking adequateamounts of water. Chewing gum may be beneficial.
As mentioned, some medications, such as some high
blood pressure medications, can cause dry mouth . If this
problem is significant, a medication change, under thesupervision of one’s health care provider, may improvethe dry-mouth condition. Oral or sinus infections, oncediagnosed, can be treated medically, usually with antibi-

otics . Lung infections and kidney or liver problems will,
of course, need medical treatment
Depending on the cause, a multitude of alternative
therapeutic remedies can be used. For example, sinusitis
can be treated with steam inhalation of essential oilsand/or herbs.
Prognosis
Most bad breath can be treated successfully with

good oral hygiene and/or medical care. Occasionally, forpatients who feel that these therapies are unsuccessful,some delusional or obsessive behavior pattern might per-tain, and mental health counseling may be appropriate.
Resources
BOOKS
Berkow, Robert, ed. The Merck Manual. 16th ed. Rahway, NJ:
Merck Sharp & Dohme Research Laboratories, 1992.
Rosenberg, M. “Clinical Assessment of Bad Breath.” Journal

of the American Dental Association (Apr. 1996): 475-481.
American Dental Association. 211 E. Chicago Ave., Chicago,
IL 60611. (312) 440-2500. <http://www.ada.org>.
GALE ENCYCLOPEDIA OF MEDICINE 2 437Bad breathGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 437

Joseph Knight, PA
Balance and coordination tests
Balance is the ability to maintain a position. Coordi-

nation is the capacity to move through a complex set ofmovements. Balance and coordination depend on theinteraction of multiple body organs and systems includ-ing the eyes, ears, brain and nervous system, cardiovas-cular system, and muscles. Tests or examination of anyor all of these organs or systems may be necessary todetermine the causes of loss of balance, dizziness , or the
inability to coordinate movement or activities.
Purpose
Tests of balance and coordination, and the examina-

tion of the organs and systems that influence balance andcoordination, can help to identify causes of dizziness,fainting , falling, or incoordination.
Tests for balance and coordination should be con-
ducted in a safe and controlled area where patients willnot experience injury if they become dizzy or fall.
Assessment of balance and coordination can include
discussion of the patient’s medical history and a com-plete physical examination including evaluation of the

heart, head, eyes, and ears. A slow pulse or heart rate, orvery low blood pressure may indicate a circulatory sys-tem problem, which can cause dizziness or fainting. Dur-ing the examination, the patient may be asked to rotatethe head from side to side while sitting up or while lyingdown with the head and neck extended over the edge ofthe examination table. If these tests produce dizziness ora rapid twitching of the eyeballs ( nystagmus ), the

patient may have a disorder of the inner ear, which isresponsible for maintaining balance.
An examination of the eyes and ears may also give

clues to episodes of dizziness or incoordination. Thepatient may be asked to focus on a light or on a distantpoint or object, and to look up, down, left, and right mov-ing only the eyes while the eyes are examined. Problemswith vision may, in themselves, contribute to balance andcoordination disturbances, or may indicate more seriousproblems of the nervous system or brain function. Hear-
ing loss , fluid in the inner ear, or ear infection might

indicate the cause of balance and coordination problems.
Various physical tests may also be used. A patient

may be asked to walk a straight line, stand on one foot,or touch a finger to the nose to help assess balance. Thepatient may be asked to squeeze or push against thedoctor’s hands, to squat down, to bend over, stand ontiptoes or stand on their heels. Important aspects ofthese tests include holding positions for a certain num-ber of seconds, successfully repeating movements acertain number of times, and repeating the test accu-rately with eyes closed. The patient’s reflexes may alsobe tested. For

The patient’s reflexes may alsobe tested. For example, the doctor may tap on the knees,ankles, and elbows with a small rubber mallet to testnervous system functioning. These tests may reveal

GALE ENCYCLOPEDIA OF MEDICINE 2 438Balance and coordination tests
A patient sits on a ball, working on his balance. He wears a
belt so that the physical therapist can catch him if he losesbalance. (Custom Medical Stock Photo. Reproduced by permis-
sion.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 438

muscle weakness or nervous system problems that
could contribute to incoordination.
No special preparation is required prior to adminis-
tration of balance and coordination tests. The patientmay be asked to disrobe and put on an examination gownto make it easier for the doctor to observe muscles andreflex responses.
Aftercare
No special aftercare is generally required, however,

some of the tests may cause episodes of dizziness orincoordination. Patients may need to use caution inreturning to normal activities if they are experiencing anysymptoms of dizziness, lightheadedness, or weakness.
Risks
These simple tests of balance and coordination are
generally harmless.
Under normal conditions, these test will not cause
dizziness, loss of balance, or incoordination.
The presence of dizziness, lightheadedness, loss of

coordination, unusual eye movements, muscle weakness,or impaired reflexes are abnormal results and may indi-cate the problem causing the loss of balance or incoordi-nation. In some cases, additional testing may be needed todiagnose the cause of balance or coordination problems.
Resources
BOOKS
Blakley, B. W., and M. E. Siegel. “Finding the Cause of Dizzi-
ness and Vertigo.” In Feeling Dizzy: Understanding and

Treating Dizziness, Vertigo, and Other Balancing Disor-ders. New York: Macmillan Publishing, 1995.
The Merck Manual. 16th ed. Ed. Robert Berkow. Rahway,
NJ: Merck & Co., Inc., 1992.KEY TERMS
Meniere’s disease —An abnormality of the inner
ear that causes dizziness, ringing in the ears, andhearing loss.Shaw, Michael, ed. Everything You Need to Know About Dis-
eases. Springhouse, PA: Springhouse Corporation, 1996.

Bowen, J. “Dizziness: A Diagnostic Puzzle.” Hospital Medi-
cine 34, no. 1 (1998): 39-44.
American Academy of Otolaryngology-Head and Neck
Surgery, Inc. One Prince St., Alexandria V A 22314-3357.(703) 836-4444. <http://www.entnet.org>.
Ear Foundation. 1817 Patterson St., Nashville, TN 37203.
(800) 545-4327. <http://www.earfoundation.org>.
Vestibular Disorders Association (VEDA). P.O. Box 4467,

Portland, OR 97208-4467. (800) 837-8428 or (503) 229-7705 (phone); (503) 229-8064 (FAX).
Balanitis
Balanitis is an inflammation of the head and fore-
skin of the penis.
Balanitis generally affects uncircumcised males. These

are men who have a foreskin, which is the “hood” of softskin that partially covers the head of the penis. In balanitis,the head and foreskin become red and inflamed. (In circum-cised men, who lack a foreskin, these symptoms only affectthe tip of the penis.) The condition often occurs due to thefungus Candida albicans , the same organism that causes

vaginal yeast infections in women. Balanitis (which is alsoreferred to as balanoposthitis) can be caused by a variety ofother fungal or bacterial infections, or may occur due to asensitivity reaction to common chemical agents.
Uncircumcised men are more at risk for balanitis

due to the presence of the foreskin. The snug fit of theforeskin around the top of the penis tends to create adamp, warm environment that encourages the growth ofmicroorganisms. Most of the organisms associated withbalanitis are already present on the penis, but in verysmall numbers. However, if the area between the headand foreskin is not cleansed thoroughly on a regularbasis, these organisms can multiply and lead to infection.

Diabetes can increase the risk of developing the con-
dition.
Balanitis is usually a result of poor hygiene—for
example, neglecting to bathe for several days. A failure
GALE ENCYCLOPEDIA OF MEDICINE 2 439BalanitisGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 439

to properly wash (or rinse) the area between the head and
foreskin can lead to the development of fungal or bacteri-al infections that cause the condition. In other cases, bal-anitis may occur due to an allergic reaction: Some menmay be sensitive to chemicals found in harsh soaps, laun-dry detergents, or contraceptive creams. Men who con-tract a sexually transmitted disease (STD) such as
trichimoniasis may also develop symptoms.
The symptoms of balanitis are limited to the fore-

skin and head of the penis (in circumcised men, only thehead is affected). These include redness, inflammation,pain , discharge, sore or itchy skin, and difficulty retract-
ing the foreskin.
Diagnosis
Balanitis is usually diagnosed based on a brief physi-
cal examination . This may be conducted by your regular

health care provider or by a urologist, the type of doctorwho specializes in such disorders. The doctor may take asample of the discharge (if any) to determine the nature ofthe possible infection. A urine test may be recommendedto evaluate glucose (sugar) levels in the urine. Balanitistreatment is typically covered by medical insurance.
Treatment
The treatment of balanitis depends on the specific
cause, which can vary from case to case. Antibiotics are

used to treat bacterial infections, while topical antifun-gals such as clotrimazole can combat balanitis caused byCandida . If an allergic reaction is causing symptoms, the
goal is to identify the chemical agent responsible. Oint-ments or creams may be used to ease skin irritation.
No matter what the cause, it is important to thor-

oughly clean the penis on a daily basis in order to allevi-ate symptoms. If the condition keeps occurring, or if theinflammation is interfering with urination, circumcision
may be advised.
According to practitioners of alternative medicine,

certain herbs may be effective in controlling or prevent-ing yeast infections—a common cause of balanitis.These remedies include garlic, calendula, and gold-enseal. Eating yogurt that contains acidophilus may alsohelp to clear up a Candida infection.
Prognosis
Most cases go away quickly once the cause is identi-
fied and treated. However, regular bouts of balanitis canresult in urethral stricture.KEY TERMS
Acidophilus —A bacteria believed to combat yeast

Circumcision —The surgical removal of the fore-
skin.
Urethral stricture —A narrowing of the urethra
(urine tube).
Proper hygiene is the best way to avoid balanitis.
Circumcision is sometimes performed to prevent repeat-ed cases.
Resources
BOOKS
Smith, Donald R. Smith’s General Urology. 14th ed. Norwalk,
CT: Appleton & Lange, 1995.
Tierney, Lawrence M., et al. Current Medical Diagnosis and
Treatment McGraw-Hill, 2000.

Edwards S. “Balanitis and balanoposthitis: a review.” Geni-
tourinary Medicine 72 (June 1996): 155-9.
Mayser, P. “Mycotic infections of the penis.” Andrologia 31
Suppl 1 (1999): 13-6.
U.S. National Library of Medicine. 8600 Rockville Pike, Bethes-
da, MD 20894. (888) 346-3656. <http://www.nlm.nih.gov>.
Balantidiasis
Balantidiasis is an infectious disease produced by a

single-celled microorganism (protozoan) called Balan-
tidium coli that infects the digestive tract. It is primarily a
disease of the tropics, although it is also found in cooler,temperate climates. Most persons with balantidiasis donot exhibit any noticeable symptoms (asymptomatic),but a few individuals will develop diarrhea with blood
and mucus and an inflamed colon (colitis).
Balantidiasis is caused by Balantidium coli , a para-

sitic protozoan that infects the large intestine. B. coli is
GALE ENCYCLOPEDIA OF MEDICINE 2 440BalantidiasisGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 440

the largest and only protozoan, having cilia or hair-like
structures, that is capable of causing disease in humans.Balantidiasis occurs most commonly in areas with poorsanitation and in settings where humans live in closecontact with pigs, sheep, or goats.
Balantidiasis is transmitted primarily by eating food
or drinking water that has been contaminated by humanor animal feces containing B. coli cysts. During its life

cycle, this organism exists in two very different forms: theinfective cyst or capsuled form, which cannot move butcan survive outside the human body because of its thick,protective covering; and the disease-producing form, thetrophozoite, which although capable of moving, cannotsurvive once excreted in the feces and, therefore, cannotinfect others. In the digestive tract, the cysts are transport-ed to the intestine where the walls of the cysts are brokenopen by digestive secretions, releasing

are brokenopen by digestive secretions, releasing the mobile tropho-zoites. Once released within the intestine, the tropho-zoites multiply by feeding on intestinal bacteria or byinvading the lining of the large intestine. Within the liningof the large intestine, the trophozoites secrete a substancethat destroys intestinal tissue and creates sores (ulcers) orabscesses. Trophozoites eventually form new cysts thatare carried through the digestive tract and excreted in thefeces. Under favorable

tract and excreted in thefeces. Under favorable temperature and humidity condi-tions, the cysts can survive in soil or water for weeks tomonths, ready to begin the cycle again.

Most individuals with balantidiasis have no notice-
able symptoms. Even though these individuals may notfeel ill, they are still capable of infecting others by per-son-to-person contact or by contaminating food or waterwith cysts that others may ingest, for example, by prepar-ing food with unwashed hands.
The most common symptoms of balantidiasis are
chronic diarrhea or severe colitis with abdominal cramps,pain , and bloody stools. Complications may include

intestinal perforation in which the intestinal wallbecomes torn, but the organisms do not spread to otherparts of the body in the blood stream.
Diagnosis
Diagnosis of balantidiasis, as with other similar dis-
eases, can be complicated, partly because symptoms mayor may not be present. A diagnosis of balantidiasis may beconsidered when a patient has diarrhea combined with apossible history of recent exposure to amebiasis through
travel, contact with infected persons, or anal intercourse.

Specifically, a diagnosis of balantidiasis is made by
finding B. coli cysts or trophozoites in the patient’s stoolsor by finding trophozoites in tissue samples (biopsy)
taken from the large bowel. A diagnostic blood test hasnot yet been developed.
sample for the presence of cysts and/or trophozoites of B.
coli.
To take a tissue sample from the large intestine, a

procedure called a sigmoidoscopy is performed. During
a sigmoidoscopy, a thin, flexible instrument is used tovisually examine the intestinal lining and obtain smalltissue specimens.
Treatment
Patients with balantidiasis are treated with prescrip-
tion medication, typically consisting of a ten day courseof either tetracycline or metronidazole. Alternative drugsthat have proven effective in treating balantidiasisinclude iodoquinol or paromomycin.
Prognosis

Prognosis
Although somewhat dependent on the patient’s over-
all health, in general, the prognosis for most patients withbalantidiasis is good. Severely infected patients occa-sionally die as a result of a tear in the intestinal wall(intestinal perforation) and consequent loss of blood.

tions that can be taken prior to potential exposure to pre-vent balantidiasis. Moreover, people who have had thedisease can become reinfected. Prevention requires effec-tive personal and community hygiene. Specific safe-guards include the following:

food from contamination by flies, cooking food proper-ly, washing one’s hands after using the bathroom andbefore cooking or eating, and avoiding foods that can-not be cooked or peeled when traveling in countrieswith high rates of balantidiasis.
• Careful disposal of human feces.• Monitoring the contacts of balantidiasis patients. The

GALE ENCYCLOPEDIA OF MEDICINE 2 441BalantidiasisGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 441

Resources
BOOKS
Gumprecht, Jeffrey P., and Murray Wittner. “Other Intestinal
Parasites.” In Current Diagnosis. V ol. 9. Ed. Rex B. Conn,
et al. Philadelphia: W. B. Saunders Co., 1997.
Weinberg, Adriana, and Myron J. Levin. “Infections: Parasitic &
Mycotic.” In Current Pediatric Diagnosis & Treatment ,e d .

William W. Hay Jr., et al. Stamford: Appleton & Lange, 1997.
Baldness seeAlopecia
Balloon angioplasty seeAngioplasty
Balloon valvuloplasty
Balloon valvuloplasty is a procedure in which a nar-
rowed heart valve is stretched open using a procedurethat does not require open heart surgery.KEY TERMS

Biopsy —The removal of a tissue sample for diag-
nostic purposes.
Ciliated —Covered with short, hair-like protru-
sions, like B. coli and certain other protozoa. The
cilia or hairs help the organism to move.Colitis —An inflammation of the large intestine
that occurs in some cases of balantidiasis. It ismarked by cramping pain and the passing ofbloody mucus.
organism, such as B. coli , that is eukaryotic and,

therefore, different from bacteria (prokaryotic).
Sigmoidoscopy —A procedure in which a thin,
flexible, lighted instrument, called a sigmoido-scope, is used to visually examine the lower partof the large intestine.Purpose
There are four valves in the heart, which are located

at the exit of each of the four chambers of the heart. Theyare called aortic valve, pulmonary valve, mitral valve,and tricuspid valve. The valves open and close to regu-late the blood flow from one chamber to the next. Theyare vital to the efficient functioning of the heart.
In some people the valves are too narrow (a condi-

tion called stenosis). Balloon valvuloplasty is performedon children and adults to improve valve function andblood flow by enlarging the valve opening. It is a treat-ment for aortic, mitral, and pulmonary stenosis. Balloonvalvuloplasty has the best results as a treatment for nar-rowed pulmonary valves. Results in treating narrowingof the mitral valve are generally good. It is more difficultto perform and less successful in treating narrowing ofthe aortic valve.

Balloon valvuloplasty is a procedure in which a thin
tube (catheter) that has a small deflated balloon at the tipis inserted through the skin in the groin area into a bloodvessel, and then is threaded up to the opening of the nar-rowed heart valve. The balloon is inflated, which stretch-es the valve open. This procedure cures many valveobstructions. It is also called balloon enlargement of anarrowed heart valve.
The procedure is performed in a cardiac catheteriza-

usually awake, but is given local anesthesia to make the areawhere the catheter is inserted numb. After the site where thecatheter will be inserted is prepared and anesthetized, thecardiologist inserts a catheter into the appropriate blood ves-sel, then passes a balloon-tipped catheter through the firstcatheter. Guided by a video monitor and an x ray, the physi-cian slowly threads the catheter into the heart. The deflatedballoon is positioned in the valve opening, then is inflatedrepeatedly.

in the valve opening, then is inflatedrepeatedly. The inflated balloon widens the valve’s openingby splitting the valve leaflets apart. Once the valve iswidened, the balloon-tipped catheter is removed. The othercatheter remains in place for 6 to 12 hours because in somecases the procedure must be repeated.

For at least six hours before balloon valvuloplasty,
the patient will have to avoid eating or drinking anything.An intravenous line is inserted so that medications can beadministered. The patient’s groin area is shaved andcleaned with an antiseptic. About an hour before the pro-cedure, the patient is given an oral sedative such asdiazepam (Valium).
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Aftercare
After balloon valvuloplasty, the patient is sent to the

recovery room for several hours, where he or she is moni-tored for vital signs (such as pulse and breathing) and heartsounds. An electrocardiogram, which is a record of theelectrical impulses in the heart, is done. The leg in whichthe catheter was inserted is temporarily prevented frommoving. The skin condition is monitored. The insertionsite, which will be covered by a sandbag, is observed forbleeding until the catheter is removed. Intravenous fluidswill be given to help eliminate the x-ray

fluidswill be given to help eliminate the x-ray dye; intravenousblood thinners or other medications to dilate the coronaryarteries may be given. Pain medication is available.

For at least 30 minutes after removal of the catheter,
direct pressure is applied to the site of insertion; after thisa pressure dressing will be applied. Following dischargefrom the hospital, the patient can usually resume normalactivities. After balloon valvuloplasty lifelong follow-upis necessary because valves sometimes degenerate ornarrowing recurs, making surgery necessary.
Risks
Balloon valvuloplasty can have serious complica-

tions. For example, the valve can become misshapen sothat it doesn’t close completely, which makes the condi-tion worse. Embolism , where pieces of the valve break

off and travel to the brain or the lungs, is another possiblerisk. If the procedure causes severe damage to the valveleaflets, immediate surgery is required. Less frequentcomplications are bleeding and hematoma (a local col-lection of clotted blood) at the puncture site, abnormalheart rhythms, reduced blood flow, heart attack , heart
puncture, infection, and circulatory problems.
Resources
BOOKS
“Balloon Valvuloplasty.” In Mayo Clinic Practice of Cardiolo-

gy.3rd ed. Ed. Emilio R. Giuliani, et al. St. Louis: Mosby,
1996.
Texas Heart Institute. “Congenital Heart Disease” and “Dis-
eases of the Heart Valves.” In Texas Heart Institute’s Heart
Owner’s Handbook. New York: John Wiley & Sons, 1996.
“Valvular Heart Disease” and “Pulmonary Stenosis.” In Current
Latson, Larry A. “Interventional Catheterization for Congenital

Heart Disease-Limited ‘Surgery’ Without the Chest Scar.”Clinical Pediatrics 36 (Mar. 1997): 125.
75231. (214) 373-6300. <http://www.americanheart.org>.KEY TERMS
Cardiac catheterization —A technique used to eval-
uate the heart and fix certain problems. Catheteri-zation is far less invasive than traditional surgery.
Stenosis —The narrowing of any valve, especially

one of the heart valves or the opening into the pul-monary artery from the right ventricle.
Valve —Tissue in the passageways between the
heart’s upper and lower chambers that controlspassage of blood and prevents regurgitation.
OTHER
“Congenital Heart Disease Treatments.” American Heart Associ-
ation. 1997. 9 Apr. 1998 <http://www.americanheart.org>.
Bancroftian filariasis seeElephantiasis
Bang’s disease seeBrucellosis

Barbiturate-induced coma
A barbiturate-induced coma , or barb coma, is a tem-
porary state of unconsciousness brought on by a con-trolled dose of a barbiturate drug, usually pentobarbitalor thiopental.
Purpose
Barbiturate comas are used to protect the brain dur-
ing major brain surgery, such as the removal of arteri-
ovenous malformations or aneurysms. Coma may also
be induced to control intracranial hypertension caused
by brain injury.

Barbiturate-induced comas are used when conven-
tional therapy to reduce intracranial hypertension hasfailed. Barbiturate dosing is geared toward burst suppres-sion—that is, reducing brain activity as measured byelectroencephalography . This reduction in brain activi-
ty has to be balanced against the potential side effects ofbarbiturates , which include allergic reactions and
effects on the cardiovascular system.

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One of the greatest hazards associated with brain
injury is intracranial hypertension. Brain injury may becaused by an accidental head injury or a medical condi-
tion, such as stroke , tumor, or infection. When the brain
is injured, fluids accumulate in the brain, causing it toswell. The skull does not allow for the expansion of thebrain; in effect, the brain becomes compressed.
If the pressure does not abate, oxygenated blood

may not reach all areas of the brain. Also, the brain tissuemay be forced against hard, bony edges on the interior ofthe skull. In either case, the brain tissue may die, causingpermanent brain damage or death .
Barbiturates reduce the metabolic rate of brain tis-

sue, as well as the cerebral blood flow. With these reduc-tions, the blood vessels in the brain narrow, decreasingthe amount of swelling in the brain. With the swellingrelieved, the pressure decreases and some or all braindamage may be averted.
Controversy exists, however, over the benefits of
using barbiturates to control intracranial hypertension.Some studies have shown that barbiturate-induced comacan reduce intracranial hypertension but does not neces-KEY TERMS

Aneurysm —A bulge or sack-like projection from a
blood vessel.
Arteriovenous malformation —An abnormal tan-
gle of arteries and veins in which the arteries feeddirectly into the veins without a normal interven-ing capillary bed.
Diuretic agent —A drug which increases urine out-
put.
Electroencephalography —The recording of elec-
trical potentials produced by the brain. Thesepotentials indicate brain activity.
Hyperventilation —A respiratory therapy involving

deeper and/or faster breathing to keep the carbondioxide pressure in the blood below normal.
Intracranial hypertension —Abnormally high blood
pressure within the skull.
Osmotherapy —Intravenous injection or oral
administration of an agent that induces dehydra-tion. The goal of dehydration is to reduce theamount of accumulated fluid in the brain.

Steroid —A type of drug used to reduce swelling.sarily prevent brain damage. Furthermore, the reduction
in intracranial hypertension may not be sustained.
Inducing a barbiturate coma is usually kept in

reserve for cases in which conventional treatments forcontrolling intracranial hypertension have failed.Before coma is induced, intracranial hypertension maybe treated by hyperventilation; by facilitation of bloodflow from the brain; by decompressive surgical proce-dures, such as draining excess fluids from under theskull or from the chambers within the brain (ventricles);or by drug therapy, including osmotherapy, diureticagents, or steroids.
Risks

accompanied by severe side effects. The side effects ofbarbiturates, especially the depressive effect on the car-diovascular system, can be too risky for some patients.Other side effects include impaired gastrointestinalmotility and impaired immune response and infection.Since barbiturates depress activity in the brain, measure-ments of brain activity may be unreliable. Careful moni-toring of the patient is required to ensure nutritionalneeds are being met and to guard against

are being met and to guard against complications,such as lung infection, fevers, or deep vein blood clots.

In many patients who do not respond to convention-
al therapy, barbiturate-induced coma can achieve thenecessary control of intracranial hypertension.
Resources
Lee, Michael W., et al. “The Efficacy of Barbiturate Coma in
the Management of Uncontrolled Intracranial Hyperten-sion Following Neurosurgical Trauma.” Journal of Neuro-
trauma 11, no. 3 (1994): 325.
Myles, Geraldine L., et al. “Quantifying Nursing Care in Bar-

biturate-Induced Coma with the Therapeutic InterventionScoring System.” Journal of Neuroscience Nursing 27, no.
1 (1995): 35.
Schwab, Stefan, et al. “Barbiturate Coma in Severe Hemispher-
ic Stroke: Useful or Obsolete?” Neurology 48 (1997):
1608.
Barbiturate withdrawal seeWithdrawal
syndromes
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Barbiturates
Barbiturates are medicines that act on the central ner-
vous system and cause drowsiness and can control seizures.
Purpose
Barbiturates are in the group of medicines known as
central nervous system depressants (CNS). Also known

as sedative-hypnotic drugs, barbiturates make people veryrelaxed, calm, and sleepy. These drugs are sometimesused to help patients relax before surgery. Some may alsobe used to control seizures (convulsions). Although barbi-turates have been used to treat nervousness and sleepproblems, they have generally been replaced by othermedicines for these purposes.
These medicines may become habit forming and
should not be used to relieve everyday anxiety and ten-

sion or to treat sleeplessness over long periods.
Barbiturates are available only with a physician’s
prescription and are sold in capsule, tablet, liquid, andinjectable forms. Some commonly used barbiturates arephenobarbital (Barbita) and secobarbital (Seconal).
Recommended dosage depends on the type of barbi-

turate and other factors such as the patient’s age and thecondition for which the medicine is being taken. Checkwith the physician who prescribed the drug or the phar-macist who filled the prescription for the correct dosage.
Always take barbiturates exactly as directed. Never

take larger or more frequent doses, and do not take thedrug for longer than directed. If the medicine does notseem to be working, even after taking it for severalweeks, do not increase the dosage. Instead, check withthe physician who prescribed the medicine.
Do not stop taking this medicine suddenly without

first checking with the physician who prescribed it. Itmay be necessary to taper down gradually to reduce thechance of withdrawal symptoms. If it is necessary to stoptaking the drug, check with the physician for instructionson how to stop.
See a physician regularly while taking barbiturates.

The physician will check to make sure the medicine isworking as it should and will note unwanted side effects.Because barbiturates work on the central nervous
system, they may add to the effects of alcohol and otherdrugs that slow the central nervous system, such as anti-
histamines , cold medicine, allergy medicine, sleep aids,
medicine for seizures, tranquilizers, some pain relievers,
and muscle relaxants . They may also add to the effects

of anesthetics, including those used for dental proce-dures. The combined effects of barbiturates and alcoholor other CNS depressants (drugs that slow the centralnervous system) can be very dangerous, leading tounconsciousness or even death . Anyone taking barbitu-
rates should not drink alcohol and should check with hisor her physician before taking any medicines classifiedas CNS depressants.
Taking an overdose of barbiturates or combining

barbiturates with alcohol or other central nervous systemdepressants can cause unconsciousness and even death.Anyone who shows signs of an overdose or a reaction tocombining barbiturates with alcohol or other drugsshould get emergency medical help immediately. Signsinclude:
• breathing problems• slurred speech• staggering
• severe confusion• severe weakness
Barbiturates may change the results of certain med-

ical tests. Before having medical tests, anyone taking thismedicine should alert the health care professional incharge.
People may feel drowsy, dizzy, lightheaded, or less
alert when using these drugs. These effects may evenoccur the morning after taking a barbiturate at bedtime.Because of these possible effects, anyone who takesthese drugs should not drive, use machines or do any-thing else that might be dangerous until they have foundout how the drugs affect them.

Barbiturates may cause physical or mental depen-
dence when taken over long periods. Anyone who showsthese signs of dependence should check with his or herphysician right away:
• the need to take larger and larger doses of the medicine
to get the same effect
• a strong desire to keep taking the medicine
• withdrawal symptoms, such as anxiety, nausea or vom-
iting, convulsions, trembling, or sleep problems, whenthe medicine is stopped

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Children may be especially sensitive to barbiturates.
This may increase the chance of side effects such asunusual excitement.
Older people may also be more sensitive that others
to the effects of this medicine. In older people, barbitu-rates may be more likely to cause confusion, depression,and unusual excitement. These effects are also more like-ly in people who are very ill.

taking certain other medicines can have problems if theytake barbiturates. Before taking these drugs, be sure to letthe physician know about any of these conditions:
to barbiturates in the past should let his or her physicianknow before taking the drugs again. The physicianshould also be told about any allergies to foods, dyes,

PREGNANCY. Taking barbiturates during pregnancy
increases the chance of birth defects and may cause
other problems such as prolonged labor and withdrawaleffects in the baby after birth. Pregnant women who musttake barbiturates for serious or life-threatening condi-tions should thoroughly discuss with their physicians thebenefits and risks of taking this medicine.
BREASTFEEDING. Barbiturates pass into breast milk

and may cause problems such as drowsiness, breathingproblems, or slow heartbeat in nursing babies whosemothers take the medicine. Women who are breastfeed-ing should check with their physicians before using bar-biturates.
OTHER MEDICAL CONDITIONS. Before using barbi-
turates, people with any of these medical problems shouldmake sure their physicians are aware of their conditions:
• alcohol or drug abuse

• hyperactivity (in children)• pain
• diabetes
• underactive adrenal gland
• chronic lung diseases such as asthma or emphysema
• severe anemia
• porphyriaUSE OF CERTAIN MEDICINES. Taking barbiturates
The most common side effects are dizziness , light-

headedness, drowsiness, and clumsiness or unsteadiness.These problems usually go away as the body adjusts tothe drug and do not require medical treatment unless theypersist or interfere with normal activities.
•fever
• muscle or joint pain• sore throat• chest pain or tightness in the chest
• wheezing

• wheezing
• skin problems, such as rash, hives , or red, thickened, or
scaly skin
• bleeding sores on the lips• sores or painful white spots in the mouth• swollen eyelids, face, or lips
In addition, check with a physician as soon as possi-
ble if confusion, depression, or unusual excitement occurafter taking barbiturates.
Patients who take barbiturates for a long time or at

high doses may notice side effects for some time afterthey stop taking the drug. These effects usually appearwithin 8-16 hours after the patient stops taking the medi-cine. Check with a physician if these or other trouble-some symptoms occur after stopping treatment with bar-biturates:
• dizziness, lightheadedness or faintness
• anxiety or restlessness•hallucinations
• vision problems• nausea and vomiting• seizures (convulsions)• muscle twitches or trembling hands
• weakness

• weakness
• sleep problems, nightmares, or increased dreaming
unusual symptoms during or after treatment with barbitu-rates should get in touch with his or her physician.
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Birth control pills may not work properly when
taken while barbiturates are being taken. To preventpregnancy, use additional or additional methods of birthcontrol while taking barbiturates.
Barbiturates may also interact with other medicines.

When this happens, the effects of one or both of thedrugs may change or the risk of side effects may begreater. Anyone who takes barbiturates should let thephysician know all other medicines he or she is taking.Among the drugs that may interact with barbiturates are:
• Other central nervous system (CNS) depressants such

as medicine for allergies, colds, hay fever, and asthma;sedatives; tranquilizers; prescription pain medicine;muscle relaxants; medicine for seizures; sleep aids; bar-biturates; and anesthetics.KEY TERMS
Adrenal glands —Two glands located next to the
kidneys. The adrenal glands produce the hor-mones epinephrine and norepinephrine and thecorticosteroid (cortisone-like) hormones.
Anemia —A lack of hemoglobin—the compound

in blood that carries oxygen from the lungsthroughout the body and brings waste carbon diox-ide from the cells to the lungs, where it is released.
Central nervous system —The brain, spinal cord,
objects, sounds, or events that seems real. Hallu-cinations usually result from drugs or mental dis-orders.
Hypnotic —A medicine that causes sleep.

things, such as chlorophyll which makes plantsgreen and hemoglobin which makes blood red.
Sedative —Medicine that has a calming effect and
may be used to treat nervousness or restlessness.

mental symptoms that may occur when a personsuddenly stops using a drug to which he or she hasbecome dependent.• Blood thinners.
• Adrenocorticoids (cortisone-like medicines).
• Antiseizure medicines such as valproic acid (Depakote
and Depakene), and carbamazepine (Tegretol).

interact with barbiturates. Be sure to check with a physi-cian or pharmacist before combining barbiturates withany other prescription or nonprescription (over-the-counter) medicine.
Resources
Miller, Norman S. “Sedative-Hypnotics: Pharmacology and
Use.” Journal of Family Practice 29 (Dec. 1989): 665.
Barium enema
A barium enema, also known as a lower GI (gastroin-

testinal) exam, is a test that uses x-ray examination toview the large intestine. There are two types of this test:the single-contrast technique where barium sulfate isinjected into the rectum in order to gain a profile view ofthe large intestine; and the double-contrast (or “air con-trast”) technique where air is inserted into the rectum.
Purpose
A barium enema may be performed for a variety of

reasons, including to aid in the diagnosis of colon andrectal cancer (or colorectal cancer ), and inflammatory

disease. Detection of polyps (a benign growth in the tis-sue lining of the colon and rectum), diverticula (a pouchpushing out from the colon), and structural changes inthe large intestine can also be established with this test.The double-contrast barium enema is the best method fordetecting small tumors (such as polyps), early inflamma-tory disease, and bleeding caused by ulcers.
The decision to perform a barium enema is based on a

person’s history of altered bowel habits. These can includediarrhea ,constipation , any lower abdominal pain they
are currently exhibiting, blood, mucus, or pus in theirstools. It is also recommended that this exam be used everyfive to 10 years to screen healthy people for colorectal can-cer, the second most deadly type of tumor in the UnitedStates. Those who have a close relative with colorectal can-cer or have had a precancerous polyp are considered to be

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at an increased risk for the disease and should be screened
more frequently to look for abnormalities.
While barium enema is an effective screening
method in the detection of symptoms and may lead to atimely diagnosis of several diseases, it is not the onlymethod to do this. As of 1997, some studies have shownthat the colonoscopy procedure performed by experi-

enced gastroenterologists is a more accurate initial diag-nostic tool for detecting early signs of colorectal cancer.A colonoscopy is the most accurate way for the physi-cian to examine the entire colon and rectum for polyps. Ifabnormalities are seen at this time the procedure isaccompanied by a biopsy. Some physicians use sigmoi-
doscopy plus a barium enema instead of colonoscopy.
To begin a barium enema, the patient will lie with

their back down on a tilting radiographic table in order tohave x rays of the abdomen taken. After being assisted toa different position, a well-lubricated rectal tube is insert-ed through the anus. This tube allows the physician orassistant to slowly administer the barium into the intes-tine. While this filling process is closely monitored, it isimportant for the patient to keep the anus tightly con-tracted against the rectal tube to help maintain its posi-tion and prevent the barium from

its posi-tion and prevent the barium from leaking. This step isemphasized to the patient due to the inaccuracy that maybe caused if the barium leaks. A rectal balloon may alsobe inflated to help retain the barium. The table may betilted or the patient moved to a different position to aid inthe filling process.

As the barium fills the intestine, x rays of the abdomen
are taken to distinguish significant findings.There are manyways to perform a barium enema. One way is that shortlyafter filling, the rectal tube is removed and the patientexpels as much of the barium as possible. Upon completingthis, an additional x ray is taken, and a double-contrast

enema may follow. If this is done immediately, a thinfilm of barium will remain in the intestine, and air isthen slowly injected to expand the bowel lumen.Sometimes no x rays will be taken until after the air isinjected.
In order to conduct the most accurate barium enema

test, the patient must follow a prescribed diet and bowelpreparation instructions prior to the test. This preparationcommonly includes restricted intake of diary productsand a liquid diet for 24 hours prior to the test, in additionto drinking large amounts of water or clear liquids 12–24
hours before the test. Patients may also be given laxa-
tives , and asked to give themselves a cleansing enema.
In addition to the prescribed diet and bowel prepara-

tion prior to the test, the patient can expect the followingduring a barium enema:
• They will be well draped with a gown as they are
secured to a tilting x-ray table.
• As the barium or air is injected into the intestine, they
may experience cramping pains or the urge to defecate.
• The patient will be instructed to take slow, deep breaths
through the mouth to ease any discomfort.
Aftercare
Patients should follow several steps immediately
after undergoing a barium enema, including:

• Drink plenty of fluids to help counteract the dehydrat-
ing effects of bowel preparation and the test.
• Take time to rest. A barium enema and the bowel prepa-
ration taken before it can be exhausting.
• A cleansing enema may be given to eliminate any
remaining barium. Lightly colored stools will be preva-lent for the next 24-72 hours following the test.
Risks
While a barium enema is considered a safe screen-

ing test used on a routine basis, it can cause complica-tions in certain people. The following indications shouldbe kept in mind before a barium enema is performed:
• Those who have a rapid heart rate, severe ulcerative
colitis , toxic megacolon, or a presumed perforation in
the intestine should not undergo a barium enema.
• The test can be cautiously performed if the patient has a

blocked intestine, ulcerative colitis, diverticulitis, orsevere bloody diarrhea.
• Complications that may be caused by the test include
perforation of the colon, water intoxication, bariumgranulomas (inflamed nodules), and allergic reaction.These are all very rare.
When the patient undergoes a single-contrast enema,

their intestine is steadily filled with barium to differenti-ate the colon’s markings. A normal result displays uni-form filling of the colon. As the barium is expelled, theintestinal walls collapse. A normal result on the x rayafter defecation will show the intestinal lining as havinga standard, feathery appearance.
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Accordingly, the double-contrast enema expands the
intestine which is already lined with a thin layer of bari-um, but with air to display a detailed image of themucosal pattern. Varying positions taken by the patientallow the barium to collect on the dependent walls of theintestine by way of gravity.
A barium enema allows abnormalities to appear on an

x ray that may aid in the diagnosis of several different con-ditions. Although most colon cancers occur in the rectosig-moid region, or upper part of the rectum and adjoiningportion of the sigmoid colon, and are better detected with adifferent test called a proctosigmoidoscopy, an enema canidentify other early signs of cancer.
Identification of polyps, diverticulosis, inflammato-

ry disease, such as diverticulitis and ulcerative colitis isattainable through a barium x ray. Structural changes inthe intestine, gastroenteritis , and some cases of acute
appendicitis may also be apparent by viewing this x ray.
Resources
BOOKS
Boston: Houghton Mifflin, 1997.KEY TERMS
Barium sulfate —A barium compound used during
a barium enema to block the passage of x raysduring the exam.

Bowel lumen —The space within the intestine.
Colonoscopy —An examination of the upper por-
tion of the rectum performed with a colonoscopeor elongated speculum.
Diverticula —A diverticulum of the colon is a sac
or pouch in the colon walls which is usuallyasymptomatic (without symptoms) but may causedifficulty if it becomes inflamed.
Diverticulitis —A condition of the diverticulum of

the intestinal tract, especially in the colon, whereinflammation may cause distended sacs extendingfrom the colon and pain.
Ulcerative colitis —An ulceration or erosion of the
mucosa of the colon.
Proctosigmoidoscopy —A visual examination of
the rectum and sigmoid colon using a sigmoido-scope.PERIODICALS
“Detecting Colon Cancer: Colonoscopy Superior To Barium
Enema.” Geriatrics (Apr. 1997): 101.
“Screening Tests.” US News & World Report 10 (Feb. 1997): 64.

American Cancer Society. 1599 Clifton Rd., NE, Atlanta, GA
30329-4251. (800) 227-2345. <http://www.cancer.org>.
Barium swallow seeUpper GI exam
Barlow’s syndrome seeMitral valve prolapse
Bartholin’s gland cyst
A Bartholin’s gland cyst is a swollen fluid-filled lump

that develops from a blockage of one of the Bartholin’sglands, which are small glands located on each side of theopening to the vagina. Bartholin’s gland cysts and abscess-es are commonly found in women of reproductive age,developing in approximately 2% of all women.
The Bartholin’s glands are located in the lips of the

labia that cover the vaginal opening. The glands (normal-ly the size of a pea) provide moisture for the vulva area.A Bartholin’s gland cyst may form in the gland itself orin the duct draining the gland. A cyst normally does notcause pain , grows slowly, and may go away without
treatment. It usually ranges in size from 0.4-1.2 in (1–3cm), although some may grow much larger.
If infected, a Bartholin’s gland cyst can form an
abscess that will increase in size over several days and is

very painful. In order to heal, a Bartholin’s gland cystusually must be drained.
A Bartholin’s gland cyst occurs if the duct becomes
blocked for any reason, such as infection, injury, orchronic inflammation. Very rarely a cyst is caused bycancer , which usually occurs only in women over the
age of 40. In many cases, the cause of a Bartholin’s glandcyst is unknown.
Symptoms of an uninfected Bartholin’s gland cyst

include a painless lump on one side of the vulva area(most common symptom) and redness or swelling in thevulva area.
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Symptoms of an abscessed Bartholin’s gland include:
• pain that occurs with walking, sitting, physical activity,
or sexual intercourse
• increased swelling in the vulva area over a two- to four-
day period
• drainage from the cyst, normally occurring four to five
days after the swelling starts
Abscesses may be caused by sexually transmitted

bacteria, such as those causing chlamydial or gonococcalinfections, while others are caused by bacteria normallyoccurring in the vagina. Over 60 types of bacteria havebeen found in Bartholin’s gland abscesses.
Diagnosis
A Bartholin’s gland cyst or abscess is diagnosed by
a gynecological pelvic exam . If the cyst appears to be
infected, a culture is often performed to identify the typeof bacteria causing the abscess.
Treatment

Treatment
Treatment for this condition depends on the size of
the cyst, whether it is painful, and whether the cyst isinfected.
If the cyst is not infected, treatment options include:
• watchful waiting by the woman and her health care pro-
fessional
• soaking of the genital area with warm towel compresses
• soaking of the genital area in a sitz bathKEY TERMS
Marsupialization —Cutting out a wedge of the cyst
wall and putting in stitches so the cyst cannotreoccur.

Sitz bath —A warm bath in which just the buttocks
and genital area soak in water; used to reducepain and aid healing in the genital area.
Window operation —Cutting out a large oval-
shaped piece of the cyst wall and putting in stitch-es to create a window so the cyst cannot reoccur.
Word catheter —A small rubber catheter with an

inflatable balloon tip that is inserted into a stabincision in the cyst, after the contents of the cysthave been drained.• use of non-prescription pain medication to relieve mild
discomfort
If the Bartholin’s gland is infected, there are several
treatments available to treat the abscess, including:
• soaking of the genital area in a sitz bath
• treatment with antibiotics

• use of prescription or non-prescription pain medication• incision and drainage, i.e., cutting into the cyst and
draining the fluid (not usually successful, as the cystoften reoccurs)
• placement of a drain (Word catheter) in the cyst for two
to four weeks so fluid can drain and prevent reoccur-rence of the cyst
• marsupialization• window operation
• use of a carbon dioxide laser to open the cyst and heat

the cyst wall tissue so that the cyst cannot form a sacand reoccur
• incision and drainage, followed by treatment with silver
nitrate to burn the cyst wall so the cyst cannot form asac and reoccur
• removal of the entire Bartholin’s gland cyst, if the cyst
has reoccurred several times after use of other treatmentmethods
During surgical treatment, the area will be numbed

with a local anesthetic to reduce pain. General anesthesiamay be used for treatment of an abscess, as the procedurecan be painful.
In a pregnant woman, surgical treatment of cysts
that are asymptomatic should be delayed until afterdelivery to avoid the possibility of excessive bleeding.However, if the Bartholin’s gland is infected and mustbe drained, antibiotics and local anesthesia are generallyconsidered safe.
If the cyst is caused by cancer, the gland must be

excised, and the woman should be under the care of agynecologist familiar with the treatment of this type ofcancer.
If a Bartholin’s gland cyst has no or mild symptoms,
or has opened on its own to drain, a woman may decideto use watchful waiting, warm sitz baths, and non-pre-scription pain medication. If symptoms become worse ordo not improve, a health care professional should then beconsulted.
Infected Bartholin’s glands should be evaluated and

treated by a health care professional.
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Prognosis
A Bartholin’s gland cyst should respond to treatment
in a few days. If an abscess requires surgery, healing maytake days to weeks, depending on the size of the abscessand the type of surgical procedure used. Most of the sur-gical procedures, except for incision and drainage,should be effective in preventing recurring infections.
There are few ways to prevent the formation of

Bartholin’s gland cysts or abscesses. However, as aBartholin’s gland abscess may be caused by a sexuallytransmitted disease, the practice of safe sex is recommend-ed. Using good hygiene, i.e., wiping front to back after abowel movement, is also recommended to prevent bacteriafrom the bowels from contaminating the vaginal area.
Resources
BOOKS
Toth, P. P. “Management of Bartholin’s Gland Duct Cysts and

Abscesses.” In Saunders Manual of Medical Practice.
Philadelphia: W.B. Saunders, 2000.
Hill, D. A., and J. J. Lense. “Office Management of Bartholin
Gland Cysts and Abscesses.” American Family Physician
57, no. 7 (1998): 1611-1616.
Bartonella bacilliformis infection see
Bartonellosis
Bartonellosis is an infectious bacterial disease with

an acute form (which has a sudden onset and shortcourse) and a chronic form (which has more gradualonset and longer duration). The disease is transmitted bysandflies and occurs in western South America. Charac-terized by a form of red blood cell deficiency ( hemolytic
anemia ) and fever , the potentially fatal acute form is
called Oroya fever or Carrion’s disease. The chronicform is identified by painful skin lesions .
The acute form of the disease gets its name from an

outbreak that occurred in 1871 near La Oroya, Peru.KEY TERMS
Acute —Referring to the course of a disease, or a
phase of a disease, the short-term experience ofprominent symptoms.
Chronic —Referring to the course of a disease, or a
phase of a disease, the long-term experience ofprominent symptoms.
Erythrocytes —Red blood cells.
Hemolytic anemia —A form of erythrocyte deficien-
cy caused by the destruction of the red blood cells.
Host —The organism that harbors or nourishes

another organism (parasite). In bartonellosis, theperson infected with Bartonella basilliformis .
Vector —An organism, such as insects or rodents,
that can transmit disease to humans.
More than 7,000 people perished. Some survivors later
developed a skin disease, called verruga peruana (Peru-vian warts ). These skin lesions were observed prior to

the 1871 outbreak—perhaps as far back as the pre-Columbian era—but a connection to Oroya fever wasunknown. In 1885, a young medical researcher, DanielCarrion, inoculated himself with blood from a lesion tostudy the course of the skin disease. When he became illwith Oroya fever, the connection became apparent.Oroya fever is often called Carrion’s disease in honor ofhis fatal experiment.
The bacteria, Bartonella bacilliformis , was isolated

by Alberto Barton in 1909, but wasn’t identified as thecause of the fever until 1940. The Bartonella genus
includes at least 11 bacteria species, four of which causehuman diseases, including cat-scratch disease and
bacillary angiomatosis . However, bartonellosis refers
exclusively to the disease caused by B. bacilliformis . The

disease is limited to a small area of the Andes Mountainsin western South America; nearly all cases have been inPeru, Colombia, and Ecuador. A large outbreak involvingthousands of people occurred in 1940–41, but bartonel-losis has since occurred sporadically. Control of sand-flies, the only known disease carrier (vector), has beencredited with managing the disease.
Bartonellosis is transmitted by the nocturnal sandfly

and arises from infection with B. bacilliformis . The sand-
fly,Lutzomyia verrucarum , dines on human blood and,
in so doing, can inject bacteria into the bloodstream. The
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sandfly is found only in certain areas of the Peruvian
Andes; other, as-yet-unidentified vectors are suspected inEcuador and Colombia.
Once in the bloodstream, the bacteria latch onto red
blood cells (erythrocytes), burrow into the cells, andreproduce. In the process, up to 90% of the host’s ery-throcytes are destroyed, causing severe hemolytic ane-mia. The anemia is accompanied by high fever, muscleand joint pain ,delirium , and possibly coma .

Two to eight weeks after the acute phase, an infected
individual develops verruga peruana. However, individu-als may exhibit the characteristic lesions without everexperiencing the acute phase. Left untreated, the lesionsmay last months or years. These lesions resemble blood-filled blisters, up to 1.6 in (4 cm) in diameter, and appearprimarily on the head and limbs. They can be painful tothe touch and may bleed or ulcerate.
Diagnosis
Bartonellosis is identified by symptoms and the

patient’s history, such as recent travel in areas where bar-tonellosis occurs. Isolation of B. bacilliformis from the
bloodstream or lesions can confirm the diagnosis.
Treatment
Antibiotics are the mainstay of bartonellosis treat-
ment. The bacteria are susceptible to several antibiotics,including chloramphenicol, penicillins , and aminogly-
cosides . Blood transfusions may be necessary to treat the
anemia caused by bartonellosis.
Prognosis

Prognosis
Antibiotics have dramatically decreased the fatality
associated with bartonellosis. Prior to the development ofantibiotics, the fever was fatal in 40% of cases. Withantibiotic treatment, that rate has dropped to 8%. Fatali-ties can result from complications associated with severeanemia and secondary infections. Once the infection ishalted, an individual can recover fully.
Avoiding sandfly bites is the primary means of pre-

vention. Sandfly eradication programs have been helpfulin decreasing the sandfly population, and insect repellantcan be effective in preventing sandfly bites.
Resources
BOOKS
Daly, Jennifer S. “Bartonella Species.” In Infectious Diseases.
2nd ed. Ed. Sherwood F. Gorbach, John S. Bartlett, andNeil R. Blacklow. Philadelphia: W. B. Saunders Co., 1998.PERIODICALS
Alexander, Bruce. “A Review of Bartonellosis in Ecuador and
Colombia.” American Journal of Tropical Medicine and

Hygiene 52, no. 4 (1995): 354.
Maurin, M., R. Birtles, and D. Raoult. “Current Knowledge of
Bartonella Species.” European Journal of Clinical Micro-
biology and Infectious Disease 16, no. 7 (1997): 487.
Nosal, Jane M. “Bacillary Angiomatosis, Cat-Scratch Disease,
and Bartonellosis: What’s the Connection?” International
Journal of Dermatology 36 (1997): 405.
Basal cell cancer seeSkin cancer, non-
melanoma
Basal gastric secretion test seeGastric acid
determination

Battered child syndrome
Battered child syndrome refers to injuries sustained
by a child as a result of physical abuse , usually inflicted
by an adult caregiver. Alternative terms include: shakenbaby; shaken baby syndrome ; child abuse ; and non-
accidental trauma (NAT).
Internal injuries, cuts, burns ,bruises and broken or

fractured bones are all possible signs of battered childsyndrome. Emotional damage to a child is also often theby-product of child abuse, which can result in seriousbehavioral problems such as substance abuse or thephysical abuse of others. Approximately 14% of childrenin the United States are physically abused each year, andan estimated 2,000 of those children die as a result of theabuse. Between 1994–1995, 1.1 million cases of childabuse were recorded in the United States; of that number,55%

recorded in the United States; of that number,55% of the victims were less than a year old.

Battered child syndrome (BCS) is found at every
level of society, although the incidence may be higher inlow-income households where adult caregivers suffergreater stress and social difficulties, without having had
the benefit of higher education. The child abuser mostoften injures a child in the heat of anger, and was oftenabused as a child himself. The incessant crying of an

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infant or child may trigger abuse. Symptoms may include
a delayed visit to the emergency room with an injuredchild; an implausible explanation of the cause of a child’sinjury; bruises that match the shape of a hand, fist or belt;cigarette burns; scald marks; bite marks; black eyes;unconsciousness; bruises around the neck; and a bulgingfontanel in infants.
Diagnosis
Battered child syndrome is most often diagnosed by

an emergency room physician or pediatrician, or byteachers or social workers. Physical examination will
detect bruises, burns, swelling, retinal hemorrhages. Xrays, and other imaging techniques, such as MRI or scansmay confirm fractures or other internal injuries. The

presence of injuries at different stages of healing (i.e.having occurred at different times)is nearly alwaysindicative of BCS. Establishing the diagnosis is oftenhindered by the excessive cautiousness of caregivers orby actual concealment of the true origin of the child˛sinjuries, as a result of fear, shame and avoidance ordenial mechanisms.
Treatment
Medical treatment for battered child syndrome will

vary according to the type of injury incurred. Counselingand the implementation of an intervention plan for thechild’s parents or guardians is necessary. The child abusermay be incarcerated, and/or the abused child removedfrom the home to prevent further harm. Reporting childabuse to authorities is mandatory for doctors, teachers,and childcare workers in most states as a way to preventcontinued abuse. Both physical and psychological therapyare often recommended as treatment for the abused

Prognosis
The prognosis for battered child syndrome will
depend on the severity of injury, actions taken by theauthorities to ensure the future safety of the injured child,and the willingness of parents or guardians to seek coun-seling for themselves as well as for the child.
Recognizing the potential for child abuse in a situa-

tion, and the seeking or offering of intervention andcounseling before battered child syndrome occurs is thebest way to prevent it. Signs that physical abuse may beforthcoming include parental alcohol or substance abuse;previous abuse of the child or the child’s siblings; historyof mental or emotional problems in parents; parentsKEY TERMS
Fontanel —Soft spot on top of an infant’s skull.
Subdural hematoma —Bleeding over the brain.
Multiple retinal hemorrhages —Bleeding in the
back of the eye.

abused as children; absence of visible parental love or
concern for the child; child’s hygiene neglected.
Resources
BOOKS
Lukefahr, James L. ”Treatment of Child Abuse. ” Baltimore,
MD: Johns Hopkins University Press, 2000.
Helfer, Mary Edna, Kempe, Ruth S., and Krugman, Richard D.
The Battered Child, 5th ed. ” Chicago, IL, and London,
England: University of Chicago Press, 1997.
Mulryan, Kathleen, “Protecting the Child.” Nursing (July, 2000)

Childhelp National Abuse Hotline. (800)422-4453.
Mary Jane Tenerelli
Becker muscular dystrophy seeMuscular
dystrophy
Bed-wetting
Bed-wetting is the unintentional (involuntary) dis-

charge of urine during the night. Although most childrenbetween the ages of three and five begin to stay dry atnight, the age at which children are physically and emo-tionally ready to maintain complete bladder controlvaries. Enuresis is a technical term that refers to the con-tinued, usually involuntary, passage of urine during thenight or the day after the age at which control is expected.
Most children wet the bed occasionally, and defini-

tions of the age and frequency at which bed-wettingbecomes a medical problem vary somewhat. Manyresearchers consider bed-wetting normal until age 6.
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once a month. More boys than girls have this problem.The American Psychiatric Association, however, definesenuresis as repeated voiding of urine into the bed orclothes at age five or older. The wetting is usually invol-untary but in some cases it is intentional. For a diagnosisof enuresis, wetting must occur twice a week for at leastthree months with no underlying physiological cause.Enuresis, both nighttime (nocturnal) and daytime (diur-nal), at age five affects 7% of boys and 3% of girls.

at age five affects 7% of boys and 3% of girls. Byage 10, it affects 3% of boys and 2% of girls; only 1% ofadolescents experience enuresis.

Enuresis is divided into two classes. A child with
primary enuresis has never established bladder control. Achild with secondary enuresis begins to wet after a pro-longed dry period. Some children have both nocturnaland diurnal enuresis.
The causes of bed-wetting are not entirely known. It

tends to run in families. Most children with primary enure-sis have a close relative—a parent, aunt, or uncle—whoalso had the disorder. About 70% of children with two par-ents who wet the bed will also wet the bed. Twin studieshave shown that both of a pair of identical twins experienceenuresis more often than both of a pair of fraternal twins.
Sometimes bed-wetting can be caused by a serious

medical problem like diabetes, sickle-cell anemia, orepilepsy. Snoring and episodes of interrupted breathing
during sleep ( sleep apnea ) occasionally contribute to
bed-wetting problems. Enlarged adenoids can causethese conditions. Other physiological problems, such asurinary tract infection, severe constipation , or spinal
cord injury , can cause bed-wetting.
Children who wet the bed frequently may have a

smaller than normal functional bladder capacity. Func-tional bladder capacity is the amount of urine a personcan hold in the bladder before feeling a strong urge tourinate. When functional capacity is small, the bladderwill not hold all the urine produced during the night.Tests have shown that bladder size in these children isnormal. Nevertheless, they experience frequent strongurges to urinate. Such children urinate often during thedaytime and may wet several times at night. Although asmall

may wet several times at night. Although asmall functional bladder capacity may be caused by adevelopmental delay, it may also be that the child’s habitof voiding frequently slows bladder development.

Parents often report that their bed-wetting child is an
extremely sound sleeper and difficult to wake. However,several research studies found that bed-wetting childrenhave normal sleep patterns and that bed-wetting canoccur in any stage of sleep.Recent medical research has found that many chil-

dren who wet the bed may have a deficiency of an impor-tant hormone known as antidiuretic hormone (ADH).ADH helps to concentrate urine during sleep hours,meaning that the urine contains less water and thereforetakes up less space. This decreased volume of water usu-ally prevents the child’s bladder from overfilling duringthe night, unless the child drank a lot just before going tobed. Testing of many bed-wetting children has shownthat these children do not have the usual increase in ADHduring

do not have the usual increase in ADHduring sleep. Children who wet the bed, therefore, oftenproduce more urine during the hours of sleep than theirbladders can hold. If they do not wake up, the bladderreleases the excess urine and the child wets the bed.

Research demonstrates that in most cases bed-wet-
ting does not indicate that the child has a physical or psy-chological problem. Children who wet the bed usuallyhave normal-sized bladders and have sleep patterns thatare no different from those of non-bed-wetting children.Sometimes emotional stress , such as the birth of a sib-
ling, a death in the family, or separation from the family,

may be associated with the onset of bed-wetting in a pre-viously toilet-trained child. Daytime wetting, however,may indicate that the problem has a physical cause.
While most children have no long-term problems as

a result of bed-wetting, some children may develop psy-chological problems. Low self-esteem may occur whenthese children, who already feel embarrassed, are furtherhumiliated by angry or frustrated parents who punishthem or who are overly aggressive about toilet training.The problem can by aggravated when playmates tease orwhen social activities such as sleep-away camp areavoided for fear of teasing.
Diagnosis

Diagnosis
If a child continues to wet the bed after the age of
six, parents may feel the need to seek evaluation anddiagnosis by the family doctor or a children’s specialist(pediatrician). Typically, before the doctor can make adiagnosis, a thorough medical history is obtained. Thenthe child receives a physical examination , appropriate
laboratory tests, including a urine test ( urinalysis ), and,
if necessary, radiologic studies (such as x rays).

If the child is healthy and no physical problem is found,
which is the case 90% of the time, the doctor may not rec-ommend treatment but rather may provide the parents andthe child with reassurance, information, and advice.
Treatment
Occasionally a doctor will determine that the prob-
lem is serious enough to require treatment. Standard
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treatments for bed-wetting include bladder training
exercises, motivational therapy, drug therapy, psy-chotherapy, and diet therapy.
Bladder training exercises are based on the theory
that those who wet the bed have small functional bladdercapacity. Children are told to drink a large quantity ofwater and to try to prolong the periods between urina-tions. These exercises are designed to increase bladdercapacity but are only successful in resolving bed-wettingin a small number of patients.

In motivational therapy, parents attempt to encour-
age the child to combat bed-wetting, but the child mustwant to achieve success. Positive reinforcement, such aspraise or rewards for staying dry, can help improve self-image and resolve the condition. Punishment for “wet”nights will hamper the child’s self-esteem and compoundthe problem.
The following motivational techniques are common-
ly used:
• Behavior modification. This method of therapy is

aimed at helping children take responsibility for theirnighttime bladder control by teaching new behaviors.For example, children are taught to use the bathroombefore bedtime and to avoid drinking fluids after din-ner. While behavior modification generally producesgood results, it is long-term treatment.
• Alarms. This form of therapy uses a sensor placed in

the child’s pajamas or in a bed pad. This sensor triggersan alarm that wakes the child at the first sign of wet-ness. If the child is awakened, he or she can then go tothe bathroom and finish urinating. The intention is tocondition a response to awaken when the bladder isfull. Bed-wetting alarms require the motivation of bothparents and children. They are considered the mosteffective form of treatment now available.
A number of drugs are also used to treat bed-wetting.

These medications are usually fast acting; children oftenrespond to them within the first week of treatment. Amongthe drugs commonly used are a nasal spray of desmo-pressin acetate (DDA VP), a substance similar to the hor-mone that helps regulate urine production; and imipraminehydrochloride, a drug that helps to increase bladder capac-ity. Studies show that imipramine is effective for as manyas 50% of patients. However, children often wet the bedagain after the drug is discontinued, and it has

after the drug is discontinued, and it has some sideeffects. Some bed-wetting with an underlying physicalcause can be treated by surgical procedures. These causesinclude enlarged adenoids that cause sleep apnea, physicaldefects in the urinary system, or a spinal tumor.

Psychotherapy is indicated when the child exhibits
signs of severe emotional distress in response to eventssuch as a death in the family, the birth of a new child, a
change in schools, or divorce. Psychotherapy is also indi-cated if a child shows signs of persistently low self-esteem or depression.
In rare cases, allergies or intolerances to certain

foods—such as dairy products, citrus products, or choco-late—can cause bed-wetting. When children have foodsensitivities, bed-wetting may be helped by discoveringthe substances that trigger the allergic response and elim-inating these substances from the child’s diet.
A number of alternative treatments are available for
bed-wetting.
Massage
According to practitioners of this technique, pres-

sure applied to various points on the body may help alle-viate the condition. Acupressure or massage, when done
by a trained therapist, may also be helpful in bed-wettingcaused by a neurologic problem.
Herbal and homeopathic remedies
Some herbal remedies, such as horsetail ( Equisetum
arvense ) have also been used to treat bed-wetting. A

trained homeopathic practitioner, working at the consti-tutional level, will seek to rebalance the child’s vitalforce, eliminating the imbalanced behavior of bed-wet-ting. Common homeopathic remedies used in this treat-ment include Causticum, Lycopodium, and Pulsatilla.
Hypnosis
Hypnosis is another approach that is being used suc-

cessfully by practitioners trained in this therapy. It trainsthe child to awaken and go to the bathroom when his orher bladder feels full. Hypnosis is less expensive, lesstime-consuming, and less dangerous than mostapproaches; it has virtually no side effects. Recent med-ical studies show that hypnotherapy can work quickly—
within four to six sessions.
Prognosis
Occasional bed-wetting is not a disease and it does

not have a “cure.” If the child has no underlying physicalor psychological problem that is causing the bed-wetting,in most cases he or she will outgrow the condition with-out treatment. About 15% of bedwetters become dry eachyear after age 6. If bed-wetting is frequent, accompaniedby daytime wetting, or falls into the American PsychiatricAssociation’s diagnostic definition of enuresis, a doctor
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should be consulted. If treatment is indicated, it usually
successfully resolves the problem. Marked improvementis seen in about 75% of cases treated with wetness alarms.
Although preventing a child from wetting the bed is
not always possible, parents can take steps to help thechild keep the bed dry at night. These steps include:
• Encouraging and praising the child for staying dry
instead of punishing when the child wets.
• Reminding the child to urinate before going to bed, if

he or she feels the need.
• Limiting liquid intake at least two hours before bed-
time.KEY TERMS
Acupressure —A technique using pressure to vari-
ous points on the body to alleviate health prob-lems.
ADH —Antidiuretic hormone, or the hormone that
helps to concentrate urine during the night.
Behavior modification —Techniques used to change
harmful behavior patterns.
Bladder —The muscular sac or container that

stores urine until it is released from the bodythrough the tube that carries urine from the blad-der to the outside of the body (urethra).
DDAVP —Desmopressin acetate, a drug used to
regulate urine production.
Hypnosis —The technique by which a trained pro-
fessional relaxes the subject and then asks ques-tions or gives suggestions.
Imipramine hydrochloride —A drug used to
increase bladder capacity.
Kidneys —A pair of organs located on each side of

the spine in the lower back area. They excrete, orget rid of, urine.
Nocturnal enuresis —Involuntary discharge of
urine during the night.
Urinalysis —A urine test.
Urine —The fluid excreted by the kidneys, stored
in the bladder, then discharged from the bodythrough the tube that carries urine from the blad-der to the outside of the body (urethra).
Void—To empty the bladder.Resources
BOOKS

BOOKS
American Psychiatric Association Diagnostic and Statistical
Manual of Mental Disorders. DSM-IV . 4th ed. Washing-
ton, DC: American Psychiatric Association, 1994.
Arnold, Samuel J. No More Bedwetting: How to Help Your
Child Stay Dry. New York: John Wiley & Sons, Inc., 1997.
Kagan, Jerome, ed. The Gale Encyclopedia of Childhood and
Adolescence. Detroit: Gale Research, 1998.
Gosnell, John. “Enuresis—The Cause That Dares Not Speak

Its Name.” British Medical Journal 315 (16 Aug. 1997):
435.
Schmitt, Barton D. “Nocturnal Enuresis.” Pediatrics in Review
18 (June 1997): 6.
Ullom-Minnich, Marla R. “Diagnosis and Management of
Nocturnal Enuresis.” American Family Physician 54 (15
Nov. 1996): 2259-2267.
White, Kevin, and Ray D. Wallace. “The Challenge of Inconti-
nence.” Exceptional Parent 27 (Aug. 1997): 361-363.
Association for the Care of Children’s Health (ACCH). 7910

Woodmont Ave., Suite 300, Bethesda, MD 20814. 800-808-2224.
National Association of Continence. P.O. Box 8310, Sparten-
burg, SC 29305. (800) 252-3337. <http://www.nafc.org>.
National Enuresis Society. 7777 Forest Lane, Suite C-737, Dal-
las, TX 75230-2518. (800) 697-8080. <http://www.peds.umn.edu/Centers/NES>.
Genevieve Slomski, PhD
Beclomethasone seeCorticosteroids
Bedsores
Bedsores are also called decubitus ulcers, pressure

ulcers, or pressure sores. These tender or inflamed patch-es develop when skin covering a weight-bearing part ofthe body is squeezed between bone and another bodypart, or a bed, chair, splint, or other hard object.
Each year, about one million people in the United
States develop bedsores ranging from mild inflammationto deep wounds that involve muscle and bone. This often

painful condition usually starts with shiny red skin thatquickly blisters and deteriorates into open sores that canharbor life-threatening infection.
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Bedsores are not cancerous or contagious. They are
most likely to occur in people who must use wheelchairsor who are confined to bed. In 1992, the federal Agencyfor Health Care Policy and Research reported that bed-sores afflict:
• 10% of hospital patients
• 25% of nursing home residents
• 60% of quadriplegics
The Agency also noted that 65% of elderly people
hospitalized with broken hips develop bedsores and thatdoctors fees for treatment of bedsores amounted to$2,900 per person.

Bedsores are most apt to develop on the:
• ankles
• back of the head
• heels
• hips
• knees
• lower back
• shoulder blades
• spine
People over the age of 60 are more likely than younger
people to develop bedsores. Risk is also increased by:
• atherosclerosis (hardening of arteries)
• diabetes or other conditions that make skin more sus-
ceptible to infection
• diminished sensation or lack of feeling
• heart problems
• incontinence (inability to control bladder or bowel
movements)
• malnutrition

• obesity
• paralysis or immobility
• poor circulation
• prolonged bed rest, especially in unsanitary conditions
or with wet or wrinkled sheets
• spinal cord injury
Bedsores most often develop when constant pressure

pinches tiny blood vessels that deliver oxygen and nutri-ents to the skin. When skin is deprived of oxygen andnutrients for as little as an hour, areas of tissue can dieand bedsores can form.Slight rubbing or friction against the skin can cause
minor pressure ulcers. They can also develop when apatient stretches or bends blood vessels by slipping into adifferent position in a bed or chair.
Urine, feces, or other moisture increases the risk of

skin infection, and people who are unable to move or rec-ognize internal cues to shift position have a greater thanaverage risk of developing bedsores.
Other risk factors include:
• malnutrition• anemia (lack of red blood cells)
• diuse atrophy (muscle loss or weakness from lack of
use)
• infection
Diagnosis
Physical examination , medical history, and patient

and caregiver observations are the basis of diagnosis.Special attention must be paid to physical or mentalproblems, like incontinence or confusion, that couldcomplicate a patient’s recovery.
Bedsores usually follow six stages:
• redness of skin• redness, swelling, and possible peeling of outer layer of
skin
• dead skin, draining wound, and exposed layer of fat
• tissue death through skin and fat, to muscle
• inner fat and muscle death• destruction of bone, bone, infection, fracture, and blood

infection
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Bedsore. (Photograph by Michael English, M.D., Custom Med-
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Treatment
Prompt medical attention can prevent surface pres-
sure sores from deepening into more serious infections.For mild bedsores, treatment involves relieving pressure,keeping the wound clean and moist, and keeping the areaaround the ulcer clean and dry. Antiseptics , harsh soaps,
and other skin cleansers can damage new tissue, so asaline solution should be used to cleanse the woundwhenever a fresh non-stick dressing is applied.
The patient’s doctor may prescribe infection-fight-

ing antibiotics , special dressings or drying agents, or
lotions or ointments to be applied to the wound in a thinfilm three or four times a day. Warm whirlpool treat-ments are sometimes recommended for sores on the arm,hand, foot, or leg.
In a procedure called debriding, a scalpel may be
used to remove dead tissue or other debris from thewound. Deep, ulcerated sores that don’t respond to othertherapy may require skin grafts or plastic surgery.
A doctor should be notified whenever a person:

• will be bedridden or immobilized for an extended time
• is very weak or unable to move
• develops bedsores
Immediate medical attention is required whenever:
• skin turns black or becomes inflamed, tender, swollen,
or warm to the touch.
• the patient develops a fever during treatment.
• the sore contains pus or has a foul-smelling discharge.
With proper treatment, bedsores should begin to heal
two to four weeks after treatment begins.

Zinc and vitamins A, C, E, and B complex help skin
repair injuries and stay healthy, but large doses of vita-mins or minerals should never be used without a doc-
tor’s approval.
A poultice made of equal parts of powdered slippery
elm ( Ulmus fulva ), marsh mallow ( Althaea officinalis ),
and echinacea (Echinacea spp.) blended with a small

amount of hot water can relieve minor inflammation. Aninfection-fighting rinse can be made by diluting twodrops of essential tea tree oil ( Melaleuca spp.) in eight
ounces of water. An herbal tea made from the calendula(Calendula officinalis ) can act as an antiseptic and
wound healing agent. Calendula cream can also be used.
Contrasting hot and cold local applications can

increase circulation to the area and help flush out wasteproducts, speeding the healing process. The temperaturesshould be extreme (hot hot and ice cold), yet tolerable to
the skin. Hot compresses should be applied for threeminutes, followed by 30 seconds of cold compress appli-cation, repeating the cycle three times. The cycle shouldalways end with the cold compress.
It is usually possible to prevent bedsores from devel-

oping or worsening. The patient should be inspected reg-ularly; should bathe or shower every day, using warmwater and mild soap; and should avoid cold or dry air. Abedridden patient should be repositioned at least onceevery two hours while awake. A person who uses awheelchair should shift his weight every 10 or 15 min-utes, or be helped to reposition himself at least once anhour. It is important to lift, rather than drag, a personbeing repositioned. Bony parts of the body should not bemassaged.

Bony parts of the body should not bemassaged. Even slight friction can remove the top layerof skin and damage blood vessels beneath it.

If the patient is bedridden, sensitive body parts can
be protected by:
• sheepskin pads
• special cushions placed on top of a mattress
• a water-filled mattress• a variable-pressure mattress whose sections can be
individually inflated or deflated to redistribute pressure
Pillows or foam wedges can prevent a bedridden

patient’s ankles from irritating each other, and pillowsplaced under the legs from mid-calf to ankle can raise theheels off the bed. Raising the head of the bed slightly andbriefly can provide relief, but raising the head of the bedmore than 30 degrees can cause the patient to slide,thereby causing damage to skin and tiny blood vessels.
A person who uses a wheelchair should be encour-

aged to sit up as straight as possible. Pillows behind thehead and between the legs can help prevent bedsores, ascan a special cushion placed on the chair seat. Donut-shaped cushions should not be used because they restrictblood flow and cause tissues to swell.
Prognosis
Bedsores can usually be cured, but about 60,000

deaths a year are attributed to complications caused bybedsores. Bedsores can be slow to heal. Without propertreatment, they can lead to:
• gangrene (tissue death)• osteomyelitis (infection of the bone beneath the bed-
sore)
• sepsis (tissue-destroying bacterial infection)
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• other localized or systemic infections that slow the
healing process, increase the cost of treatment, lengthenhospital or nursing home stays, or cause death
Resources
BOOKS
International Association of Enterstomal Therapy. 27241 La
Paz Road, Suite 121, Laguna Niguel, CA 92656. (714)476-0268.

National Pressure Ulcer Advisory Panel. SUNY at Buffalo,
Beck Hall, 3435 Main St., Buffalo, NY 14214. (716) 881-3558. <http://www.npuap.org>.
OTHER
“Bed Sores.” American Health and Herbs Ministry. 15 Mar.
1998 <http://www.healthherbs.com>.
“Break the Connection Between the O.R. and Pressure Ulcers.”
SpringNet Page .16 Mar. 1998 <http://www.springnet.
com/top.shtml>.
“Pressure Sores.” ThriveOnline .14 Mar. 1998 <http://thrive

“Preventing Pressure Ulcers.” Health Pages.org .15 Mar. 1998
<http://www.healthpages.org/AHP/LIBRARY/HLTHTOP/MISC/bedsore.htm>.
“Treatment of Bed Sores.” U. S. Department of Health and
Human Services .15 Mar. 1998 <http://www.os.dhhs.gov>.
Beef tapeworm infection seeTapeworm
diseases
Behavior therapy seeCognitive-behavioral
therapy
Behcet’s syndrome
A group of symptoms that affect a variety of body sys-

tems, including musculoskeletal, gastrointestinal, and thecentral nervous system. These symptoms include ulcerationof the mouth or the genital area, skin lesions , and inflam-
mation of the uvea (an area around the pupil of the eye).
Behcet’s syndrome is a chronic disease that involves

multiple body systems. The disease is named for a Turk-ish dermatologist, Hulusi Behcet, who first reported apatient with recurrent mouth and genital ulcers alongwith uveitis in 1937. The disease occurs worldwide, but
is most prevalent in Japan, the Middle East, and in theMediterranean region. There is a wider prevalenceamong males than females in a ratio of two to one.
The cause of Behcet’s syndrome is unknown. Symp-

toms include recurring ulcers in the mouth or the genitalarea, skin lesions, arthritis that affects mainly the kneesand ankles, pain and irritation in the eyes, and fever . The

mouth and genital ulcers tend to occur in multiples andcan be quite painful. In the mouth, these ulcers are gener-ally found on the tongue, gums, and the inside of the lipsor jaws. In the genital area, the ulcers usually occur onthe penis and scrotum in males and on the vulva ofwomen. The eye inflammation can lead to blindness.
Diagnosis
Because Behcet’s syndrome is a multisystem disease,

it is difficult to diagnose. International criteria have beenproposed to assist in classifying this disease. There is noone diagnostic feature of this disease, so diagnosis dependson grouping together enough symptoms in order to identifythe disease. Symptoms of Behcet’s syndrome also occur inother diseases, so it is often necessary to rule out the otherdiseases before a definitive diagnosis can be reached.
Treatment
Some of the current drugs used to treat Behcet’s syn-
drome include:

• corticosteroids
• cyclosporin
• azathioprine
• chlorambucil• interferon alpha• thalidomide• levamisole• pulse cyclophosphamide• cyclosporine
Prognosis
The prognosis for Behcet’s syndrome is generally
poor. There has been a documented case of Behcet’s last-ing for 17 years. Although the disease is consideredpainful but not fatal, when the central nervous system isinvolved there is usually severe disability and death

often occurs. The condition is usually chronic, althoughthere can be remissions during the course of the disease.
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There is no predictable method to determine which
patients will progress into the more serious symptoms,and which might move into remission.
There is no known prevention for Behcet’s syndrome.
Resources
BOOKS
Berkow, Robert. The Merck Manual of Medical Information.
Whitehouse Station: Merck Research Laboratories, 1997.
Ruddy, Shaun. Kelley’s Textbook of Rheumatology. Philadel-
phia: W.B. Saunders Company, 2001.
Tierney, Lawrence, et. al. Current Medical Diagnosis and

Treatment. Los Altos: Lange Medical Publications, 2001.
Okada, A. A. “Drug Therapy in Behcet’s Disease.” Ocular
Immunology and Inflammation (June 2000): 85-91.
Shed, L. P. “Thalomide Responsiveness in an Infant with
Behcet’s Syndrome.” Pediatrics (June 1999): 1295-1297.
American Behcet’s Disease Association. P.O. Box 280240,
Memphis, TN 38168-0240. <http://www.behcets.com>.
Behcet’s Organization Worldwide, Head Office. P.O. Box 27,

Watchet, Somerset TA23 OYJ, United Kingdom. <http://www.behcets.org>.
National Eye Institute. National Institute of Health. Bldg. 31,
Rm. 6A32, Bethesda, MD 30892-2510. (800) 869-2020.<http://www.nei.nih.gov>.
Fairfield, CT 06812-8923. (800) 999-6673. <http://www.rarediseaes.org>.
Kim Sharp, M.Ln.
Bejel
Bejel, also known as endemic syphilis , is a chronic
but curable disease, seen mostly in children in aridKEY TERMS

Remission —When active symptoms of a chronic
disease are absent.
Uveitis —Inflammation of the area of the eye
around the pupil.regions. Unlike the better-known venereal syphilis,
endemic syphilis is not a sexually transmitted disease .
Bejel has many other names depending on the locali-

ty: siti, dichuchwa, njovera, belesh, and skerljevo aresome of the names. It is most commonly found in theMiddle East (Syria, Saudi Arabia, Iraq), Africa, centralAsia, and Australia. Bejel is related to yaws and pinta ,
but has different symptoms.
Treponema pallidum , the bacteria that causes bejel,

is very closely related to the one that causes the sexuallytransmitted form of syphilis, but transmission is very dif-ferent. In bejel, transmission is by direct contact, withbroken skin or contaminated hands, or indirectly by shar-ing drinking vessels and eating utensils. T. pallidum is
passed on mostly between children living in poverty invery unsanitary environments and with poor hygiene.
The skin, bones, and mucous membranes are affect-

ed by bejel. Patches and ulcerated sores are common inthe mouth, throat, and nasal passages. Gummy lesionsmay form, even breaking through the palate. Other find-ings may include a region of swollen lymph nodes anddeep bone pain in the legs. Eventually, bones may
become deformed.
Diagnosis
T. pallidum can be detected by microscopic study of

samples taken from the sores or lymph fluid. However,since antibody tests don’t distinguish between the types ofsyphilis, specific diagnosis of the type of syphilis dependson the patient’s history, symptoms, and environment.
Treatment
Large doses of benzathine penicillin G given by injec-

tion into the muscle can cure this disease in any stage,although it may take longer and require additional doses inlater stages. If penicillin cannot be given, the alternative istetracycline. Since tetracycline can permanently discolornew teeth still forming, it is usually not prescribed for chil-dren unless no viable alternative is available.
Prognosis
Bejel is completely curable with antibiotic treatment.
The World Health Organization (WHO) has worked

with many countries to prevent this and other diseases, and
GALE ENCYCLOPEDIA OF MEDICINE 2 460BejelGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 460

the number of cases has been reduced somewhat. Wide-
spread use of penicillin has been responsible for reducingthe number of existing cases, but the only way to eliminatebejel is by improving living and sanitation conditions.
Resources
BOOKS
Jill S Lasker
Bell’s palsy
Bell’s palsy describes an unexplained weakness or
paralysis of the muscles on one side of the face. Afflict-

ed individuals may be unable to close the eye on theaffected side of the face, and may also experience tear-ing, drooling, and hypersensitive hearing. The onset canbe quite sudden, sometimes occurring overnight.Although Bell’s palsy is unsettling and inconvenient, it istypically not indicative of a serious health problem. Theweakness and paralysis resolve completely in the majori-ty of cases.
Bell’s palsy has been described as a diagnosis of

exclusion because several other disorders present similarKEY TERMS
Endemic disease —An infectious disease that
occurs frequently in a specific geographicallocale. The disease often occurs in cycles. Influen-za is an example of an endemic disease.
Lymph— This is a clear, colorless fluid found in
lymph vessels and nodes. The lymph nodes con-tain organisms that destroy bacteria and other dis-ease causing organisms (also called pathogens).

Syphilis— This disease occurs in two forms. One is
a sexually transmitted disease caused by a bacte-ria. The second form is not sexually transmitted,but passed on by direct contact with the patient orthrough use of shared food dishes and utensils.symptoms. Facial palsies have been linked to conditions
such as Lyme disease , ear infection, meningitis ,
syphilis , German measles (rubella ),mumps ,chicken-
pox (varicella), and infection with Epstein-Barr virus

(e.g., infectious mononucleosis ). True Bell’s palsy is an
idiopathic facial palsy, meaning the root cause cannot beidentified. Although Bell’s palsy is not life-threatening, itcan present symptoms similar to truly serious conditions,such as a stroke , ruptured aneurysm, or tumors.
Every year, approximately 40,000-65,000 Americans

are stricken with Bell’s palsy. Worldwide, there is anannual incidence of 20-30 cases per 100,000 individuals.An individual can be affected at any age, but young andmiddle-aged adults are the most likely to be affected. It isunusual to see Bell’s palsy in people less than 10 yearsold. Bell’s palsy can affect either side of the face, and nei-ther gender seems to be at a greater risk. Pregnant womenand individuals with diabetes, influenza , a cold, or an

upper respiratory infection seem to be at a greater risk.Although it cannot be considered a serious condition froma health standpoint, it can cause extreme stress , embar-
rassment, and inconvenience for those affected.
In the large majority of cases (80-85%), the facial

weakness or paralysis is temporary. However, individualswho experience complete paralysis seem to have a poorerrecovery rate with only 60% returning to normal. Approx-imately 4-6% of all Bell’s palsy cases result in permanentfacial deformity, and another 10-15% experience perma-nent problems with spasms, twitching, or contracted mus-cles. Between 2% and 7.3% of individuals who haveexperienced Bell’s palsy will have a recurrence. On aver-age, the first recurrence happens 9.8 years after the

the first recurrence happens 9.8 years after the firstepisode; the second, 6.7 years later. One recurrence isvery infrequent, and a second is extremely rare.

The symptoms of Bell’s palsy arise from an inflam-

mation or swelling of the seventh cranial nerve, other-wise called the facial nerve. Both sides of the face have afacial nerve which controls the muscles on that side ofthe face. The course of the facial nerve passes through abony canal in the skull. When the nerve becomesswollen, it is compressed since the canal does not allowfor any expansion. As further swelling increases the com-pression, nerve signal conduction is impeded or evenprevented. The interference with the nerve signals is seenin

The interference with the nerve signals is seenin the loss of muscle control and tone.

Why the facial nerve becomes inflamed in Bell’s
palsy is a matter of some debate, and medical researchersand doctors are not in complete agreement. The best-sup-ported evidence implicates the herpes simplex virus(HSV), which is responsible for cold sores and fever
GALE ENCYCLOPEDIA OF MEDICINE 2 461Bell’s palsyGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 461

blisters. HSV infection has been discovered in up to 70%
of Bell’s palsy cases. Most people harbor this virus,although they may not exhibit symptoms.
The major symptom of Bell’s palsy is one-sided

facial weakness or paralysis. Muscle control is eitherinadequate or completely missing. There may also beinvoluntary facial movements, such as twitches, thataccompany certain facial expressions. Afflicted individu-als frequently have difficulty shutting the affected eyeand may not be able to close it at all.
Diagnosis
Although Bell’s palsy is not life-threatening, it

shares symptoms in common with serious conditions,such as stroke. Therefore, emergency medical attention isa wise and necessary precaution. Bell’s palsy affects thefacial nerve, unlike most strokes associated with facialweakness which affect higher nerve centers ultimatelysupplying the facial nerve. These two disorders can bedistinquished clinically because most strokes do notcause weakness of the forehead or eyelid muscles.

The fact that Bell’s palsy is a diagnosis of exclusion
becomes apparent in the course of the medical examina-tion—the usual mode of examination is to rule out other
disorders until only Bell’s palsy is left. Disorders thatneed to be excluded include demyelinating disease (e.g.,multiple sclerosis ), stroke, tumors, bacterial or viral
infection, and bone fracture.
During the physical examination , the afflicted indi-

vidual is asked about recent illnesses, accidents, infec-tions, and any other symptoms. A visual exam of theears, throat, and sinus is done, and hearing is tested. Theextent of the symptoms is assessed by grading the sym-metry of the face at rest and during voluntary move-ments, such as wrinkling the forehead, puckering thelips, and closing the affected eye. Involuntary move-ments are assessed in combination with the voluntarymovements. Neurologic exam is done to rule out

involvement of other parts of the nervous system exceptfor the facial muscles, which would exclude the diagno-sis of Bell’s palsy.
In response to the individual’s medical history,
blood tests and possibly a cerebrospinal fluid (CSF)
analysis are ordered. The results of these tests help

determine the presence of a bacterial or viral infection oran inflammatory disease. Electrophysiological tests, inwhich a muscle or nerve is artificially stimulated, may beused to assess the condition of facial muscles and thefacial nerve. Common tests include electromyography ,

which measures voluntary muscle movement, and nerveconduction velocity, which determines the extent ofnerve degeneration. Radiological tests may also beincluded, such as an x ray, as well as imaging tests, suchas magnetic resonance imaging (MRI) and computed
tomography. These tests—especially MRI—allow anexcellent view of the nerve itself.
Once all other possibilities are exhausted, a diagno-

sis of Bell’s palsy is made. The following weeks are aperiod of watchful waiting. Further examinations aredone to track recovery. Results from nerve conductiontests may be used to predict an outcome. However, thisuse is questioned by some doctors and medicalresearchers since evidence for their predictive value isinconclusive.
If facial movement, even a small amount, has not
returned within 3-4 months, the diagnosis of Bell’s palsymay need to be reevaluated.
Treatment

Treatment
Many doctors prescribe an antiviral and/or a steroid
for Bell’s palsy, but there is some controversy aboutwhether these drugs actually help. The consensus opin-ion seems to be that, although drugs might not be neces-sary, they are not dangerous, and they may help in some
GALE ENCYCLOPEDIA OF MEDICINE 2 462Bell’s palsy
This boy’s facial paralysis was caused by a tick-borne
meningopadiculitis. (Photo Researchers, Inc. Reproduced by

cases, especially if there is complete paralysis. If drugs
are used, they need to be taken as soon as possible fol-lowing the onset of symptoms. Antiviral drugs , such as
acyclovir, famciclovir, or valacyclovir, are prescribed todestroy actively replicating viruses and prevent furtherdamage to the facial nerve. Steroids, such as prednisone,are thought to be useful in reducing swelling and, there-fore, compression on the nerve.
In the past, surgery was performed to relieve the

compression on the nerve. However, this treatmentoption is now used very infrequently because it does notguarantee recovery, and it carries the risk of permanentnerve damage.
The need to protect the affected eye is universally

promoted. Since the individual may not be able to lowerthe affected eyelid, the eye may become dry, particularlyat night. Excessive dryness can damage the cornea. Day-time treatment includes artificial tears and may includean eye patch or other protective measures. Nighttimetreatment involves a more intense effort at keeping theeye protected. Eye lubricants or viscous ointments, alongwith taping the eye shut, are frequently recommended.
In cases of permanent nerve damage, cosmetic treat-

ment options, such as therapeutic injections of botulism
toxin or surgery, may be sought or suggested.
Practitioners of traditional Chinese medicine have
historically used acupuncture to treat Bell’s palsy. There
are also some indications that facial massage and chiro-
practic manipulation may help treat the symptoms and
improve the outcome. There are also claims of therapeu-tic value for local injections or ingestion of vitamin B
12
supplements.
Prognosis

12
Prognosis
Most individuals with Bell’s palsy begin to notice

improvement in their condition within 2-3 weeks of thesymptoms’ onset. At least 80% of them will be fully recov-ered within three months. Among the other 20% of afflict-ed individuals, symptoms may take longer to resolve orthey may be permanent. Individuals suffering permanentnerve damage may not regain control of the muscles onthe affected side of the face. These muscles may remainweak or paralyzed. If the nerve recovers imperfectly, theymay experience involuntary facial twitches or spasms

experience involuntary facial twitches or spasms thataccompany normal facial expressions.

Bell’s palsy is not preventable.KEY TERMS
Antiviral —A drug that prevents viruses from repli-
cating and therefore spreading infection.
Computed tomography —Cross-sectional x rays of
the body are compiled to create a three-dimen-sional image of the body’s internal structures.
Electromyography —A recording of the electrical
activity generated in the muscle.Facial nerve —A cranial nerve that controls the
muscles in the face.
Magnetic resonance imaging (MRI) —This imag-

ing technique uses a large circular magnet andradio waves to generate signals from atoms in thebody. These signals are used to construct images ofinternal structures.
Nerve conduction velocity —A recording of how
well a nerve conducts electrical impulses.Steroid —A drug used to reduce swelling and fluid
accumulation.
Resources
Billue, Joyce S. “Bell’s Palsy: An Update on Idiopathic Facial

Palsy.” The Nurse Practitioner 22, no. 8 (1997): 88.
Kakaiya, Ram. “Bell’s Palsy: Update on Causes, Recognition,
and Management.” Consultant 37, no. 8 (1997): 2217.
Bell’s Palsy Research Foundation. 9121 E. Tanque Verde, Suite
105-286, Tucson, AZ 85749. (520) 749-4614.
Benazepril seeAngiotensin-converting
Bence Jones protein test
Bence Jones proteins are small proteins (light chains

of immunoblobulin) found in the urine. Testing for theseproteins is done to diagnose and monitor multiple
myeloma and other similar diseases.
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Purpose
Bence Jones proteins are considered the first tumor
marker. A tumor marker is a substance, made by thebody, that is linked to a certain cancer , or malignancy.
Bence Jones proteins are made by plasma cells, a typeof white blood cell. The presence of these proteins in aperson’s urine is associated with a malignancy of plas-ma cells.
Multiple myeloma, a tumor of plasma cells, is the

disease most often linked with Bence Jones proteins. Theamount of Bence Jones proteins in the urine indicateshow much tumor is present. Physicians use Bence Jonesproteins testing to diagnose the disease as well as tocheck how well the disease is responding to treatment.
Other diseases involving cancerous or excessive

growth of plasma cells or cells similar to plasma cellscan cause Bence Jones proteins in the urine. Thesediseases include: Waldenström’s macroglobulinemia,some lymphomas and leukemias, osteogenic sarcoma,cryoglobulinemia, malignant B-cell disease, amyloi-
dosis , light chain disease, and cancer that has spread
to bone.
Urine is the best specimen in which to look for

Bence Jones proteins. Proteins are usually too large tomove through a healthy kidney, from the blood into theurine. Bence Jones proteins are an exception. They aresmall enough to move quickly and easily through thekidney into the urine.
A routine urinalysis will not detect Bence Jones

proteins. There are several methods used by laboratoriesto detect and measure these proteins. The classic BenceJones reaction involves heating urine to 140°F (60°C). Atthis temperature, the Bence Jones proteins will clump.The clumping disappears if the urine is further heated toboiling and reappears when the urine is cooled. Otherclumping procedures using salts, acids, and other chemi-cals are also used to detect these proteins. These types ofKEY TERMS

Bence Jones protein —Small protein, composed of
a light chain of immunoglobulin, made by plasmacells.
Multiple myeloma —A tumor of the plasma cells.
Plasma cells —A type of white blood cell.test will reveal whether or not Bence Jones proteins are
present, but not how much is present.
A more complex procedure is done to measure the
exact amount of Bence Jones proteins. This procedure—immunoelectrophoresis—is usually done on urine thathas been collected for 24-hours.

The test is covered by insurance when medically nec-
essary. Results are usually available within several days.
Urine is usually collected throughout a 24-hour time
period. A person is given a large container in which tocollect the urine. The urine should be refrigerated until itis brought to the laboratory or physician’s office.
Bence Jones proteins normally are not present in the
urine.
Bence Jones proteins are present in 50–80% of peo-

ple with multiple myeloma. People with other malignan-cies also can have a positive Bence Jones proteins test,but less frequently.
Certain nonmalignant diseases, such as rheumatoid
arthritis ,systemic lupus erythematosus , and chronic
renal insufficiency, can have Bence Jones proteins in theurine. High doses of penicillin or aspirin before collect-
ing the urine can give a false positive result.
Resources
BOOKS

Bender-Gestalt test
The Bender Visual Motor Gestalt test (or Bender-
Gestalt test) is a psychological assessment used to evalu-

GALE ENCYCLOPEDIA OF MEDICINE 2 464Bender-Gestalt testGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 464

ate visual-motor functioning, visual-perceptual skills,
neurological impairment, and emotional disturbances inchildren and adults ages three and older.
Purpose
The Bender-Gestalt is used to evaluate visual-
motor maturity and to screen children for developmen-tal delays. The test is also used to assess brain damageand neurological deficits. Individuals who have suf-fered a traumatic brain injury may be given the Bender-Gestalt as part of a battery of neuropsychological mea-sures, or tests.

The Bender-Gestalt is sometimes used in conjunc-
tion with other personality tests to determine the pres-ence of emotional and psychiatric disturbances such asschizophrenia .
Psychometric testing requires a clinically trained

examiner. The Bender Visual Motor Gestalt Test shouldbe administered and interpreted by a trained psychologistor psychiatrist. The Bender-Gestalt should always beemployed as only one element of a complete battery ofpsychological or developmental tests, and should neverbe used alone as the sole basis for a diagnosis.
The original Bender Visual Motor Gestalt test was

developed in 1938 by psychiatrist Lauretta Bender. Thereare several different versions of the Bender-Gestalt avail-able today (i.e., the Bender-Gestalt test; Modified Ver-sion of the Bender-Gestalt test for Preschool and PrimarySchool Children; the Hutt Adaptation of the Bender-Gestalt test; the Bender Visual Motor Gestalt test forChildren; the Bender-Gestalt test for Young Children; theWatkins Bender-Gestalt Scoring System; the CanterBackground Interference Procedure for the Bender-Gestalt

Interference Procedure for the Bender-Gestalt test). All use the same basic test materials, butvary in their scoring and interpretation methods.

The standard Bender Visual Motor Gestalt test con-
sists of nine figures, each on its own 3 /H110035 card. An

examiner presents each figure to the test subject one at atime and asks the subject to copy it onto a single piece ofblank paper. The only instruction given to the subject isthat he or she should make the best reproduction of thefigure possible. The test is not timed, although standardadministration time is typically 10-20 minutes. Aftertesting is complete, the results are scored based on accu-racy and organization. Interpretation depends on theform of the test in use. Common features

on theform of the test in use. Common features considered inevaluating the drawings are rotation, distortion, symme-KEY TERMS

Neuropsychological test —A test or assessment
given to diagnose a brain disorder or disease.
Perserveration —The persistence of a repetitive
response after the cause of the response has beenremoved, or the response continues to differentstimuli.
Visual-motor skills —Hand-eye coordination; in
the Bender-Gestalt test, visual-motor skills aremeasured by the subject’s ability to accurately per-ceive and then reproduce figures.
Visual-perceptual skills —The capacity of the mind

and the eye to “see” something as it objectivelyexists.
try, and perseveration. As an example, a patient with
frontal lobe injury may reproduce the same pattern overand over (perserveration)
The Bender-Gestalt can also be administered in a

group setting. In group testing, the figures are shown totest subjects with a slide projector, in a test booklet, or onlarger versions of the individual test cards. Both the indi-vidual and group- administered Bender-Gestalt evaluationmay take place in either an outpatient or hospital setting.Patients should check with their insurance plans to deter-mine if these or other mental health services are covered.

Children normally improve in this test as they age,
but, because of the complexity of the scoring process,results for the Bender-Gestalt should only be interpretedby a clinically trained psychologist or psychiatrist.
Resources
BOOKS
Maddox, Taddy. Tests: A Comprehensive Reference for Assess-
ments in Psychology, Education, and Busines. 4th ed.
Austin, TX: Pro-ed, 1997.
Shore, Milton F, et al. When Your Child Needs Testing. New
York: Crossroad Publishing, 1992.

Wodrich, David L. Children’s Psychological Testing: A Guide
for Nonpsychologists. Baltimore: Paul H. Brookes Pub-
lishing, 1997.
Piotrowski, C. “A Review of the Clinical and Research Use of
the Bender-Gestalt Test.” Perceptual Motor Skills 81, no.
3, pt. 2 (Dec. 1995): 1271-74.
GALE ENCYCLOPEDIA OF MEDICINE 2 465Bender-Gestalt testGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 465

American Psychological Association (APA). 750 First St. NE,
Washington, DC 20002-4242. (202) 336-5700. <http://www.apa.org>.
Bends seeDecompression sickness
Benign seeUterine fibroids
Benign prostatic hyperplasia seeEnlarged
prostate
Benign prostatic hypertrophy seeEnlarged
prostate
Benzocaine seeAntiseptics
Benzodiazepines
Benzodiazepines are medicines that help relieve ner-

vousness, tension, and other symptoms by slowing thecentral nervous system.
Purpose
Benzodiazepines are a type of antianxiety drugs .
While anxiety is a normal response to stressful situa-

tions, some people have unusually high levels of anxietythat can interfere with everyday life. For these people,benzodiazepines can help bring their feelings under con-trol. The medicine can also relieve troubling symptomsof anxiety, such as pounding heartbeat, breathing prob-lems, irritability, nausea, and faintness.
Physicians may sometimes prescribe these drugs for
other conditions, such as muscle spasms, epilepsy andother seizure disorders, phobias ,panic disorder , with-

drawal from alcohol, and sleeping problems. However,this medicine should not be used every day for sleepproblems that last more than a few days. If used this way,the drug loses its effectiveness within a few weeks.
Benzodiazepines should not be used to relieve the
nervousness and tension of normal everyday life.
The family of antianxiety drugs known as benzodi-

azepines includes alprazolam (Xanax), chlordiazepoxide(Librium), diazepam (Valium), and lorazepam (Ativan).These medicines take effect fairly quickly, starting to workwithin an hour after they are taken. Benzodiazepines areavailable only with a physician’s prescription and areavailable in tablet, capsule, liquid, or injectable forms.

benzodiazepine, its strength, and the condition for whichit is being taken. Doses may be different for differentpeople. Check with the physician who prescribed thedrug or the pharmacist who filled the prescription for thecorrect dosage.
Always take benzodiazepines exactly as directed.

Never take larger or more frequent doses, and do not takethe drug for longer than directed. If the medicine does notseem to be working, check with the physician who pre-scribed it. Do not increase the dose or stop taking the
medicine unless the physician says to do so. Stopping the

drug suddenly may cause withdrawal symptoms, espe-cially if it has been taken in large doses or over a longperiod. People who are taking the medicine for seizuredisorders may have seizures if they stop taking it sudden-ly. If it is necessary to stop taking the medicine, checkwith a physician for directions on how to stop. The physi-cian may recommend tapering down gradually to reducethe chance of withdrawal symptoms or other problems.

Seeing a physician regularly while taking benzodi-
azepines is important, especially during the first fewmonths of treatment. The physician will check to makesure the medicine is working as it should and will noteunwanted side effects.
People who take benzodiazepines to relieve nervous-
ness, tension, or symptoms of panic disorder shouldcheck with their physicians every two to three months tomake sure they still need to keep taking the medicine.

Patients who are taking benzodiazepines for sleep
problems should check with their physicians if they arenot sleeping better within 7-10 days. Sleep problems thatlast longer than this may be a sign of another medicalproblem.
People who take this medicine to help them sleep
may have trouble sleeping when they stop taking themedicine. This effect should last only a few nights.
Some people, especially older people, feel drowsy,

dizzy, lightheaded, or less alert when using benzodi-azepines. The drugs may also cause clumsiness orunsteadiness. When the medicine is taken at bedtime,these effects may even occur the next morning. Anyonewho takes these drugs should not drive, use machines ordo anything else that might be dangerous until they havefound out how the drugs affect them.
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Benzodiazepines may also cause behavior changes
in some people, similar to those seen in people who actdifferently when they drink alcohol. More extremechanges, such as confusion, agitation, and hallucina-
tions , also are possible. Anyone who starts having
strange or unusual thoughts or behavior while taking thismedicine should get in touch with his or her physician.
Because benzodiazepines work on the central ner-

vous system, they may add to the effects of alcohol andother drugs that slow down the central nervous system,such as antihistamines , cold medicine, allergy medicine,
sleep aids, medicine for seizures, tranquilizers, some pain
relievers, and muscle relaxants . They may also add to the

effects of anesthetics, including those used for dental pro-cedures. These effects may last several days after treat-ment with benzodiazepines ends. The combined effects of
benzodiazepines and alcohol or other CNS depressants(drugs that slow the central nervous system) can be verydangerous, leading to unconsciousness or, rarely, evendeath. Anyone taking benzodiazepines should not drink

alcohol and should check with his or her physician beforeusing any CNS depressants. Taking an overdose of benzo-
diazepines can also cause unconsciousness and possiblydeath. Anyone who shows signs of an overdose or of theeffects of combining benzodiazepines with alcohol orother drugs should get immediate emergency help. Warn-
ing signs include slurred speech or confusion, severedrowsiness, staggering, and profound weakness.
Some benzodiazepines may change the results of

certain medical tests. Before having medical tests, any-one taking this medicine should alert the health care pro-fessional in charge.
Children are generally more sensitive than adults to
the effects of benzodiazepines. This sensitivity mayincrease the chance of side effects.
Older people are more sensitive than younger adults

to the effects of this medicine and may be at greater riskfor side effects. Older people who take these drugs tohelp them sleep may be drowsy during the day. Olderpeople also increase their risk of falling and injuringthemselves when they take these drugs.
taking certain other medicines can have problems if theytake benzodiazepines. Before taking these drugs, be sureto let the physician know about any of these conditions:

benzodiazepines or other mood-altering drugs in the pastshould let his or her physician know before taking thedrugs again. The physician should also be told about anyallergies to foods, dyes, preservatives, or other substances.PREGNANCY. Some benzodiazepines increase the
likelihood of birth defects . Using these medicines during
pregnancy may also cause the baby to become dependent

on them and to have withdrawal symptoms after birth.When taken late in pregnancy or around the time of laborand delivery, these drugs can cause other problems in thenewborn baby, such as weakness, breathing problems,slow heartbeat, and body temperature problems.
Women who are pregnant or who may become preg-
nant should not use benzodiazepines unless their anxietyis so severe that it threatens their pregnancy. Any woman

who must take this medicine while pregnant should besure to thoroughly discuss its risks and benefits with herphysician.
BREASTFEEDING. Benzodiazepines may pass into
breast milk and cause problems in babies whose motherstaken the medicine. These problems include drowsiness,breathing problems, and slow heartbeat. Women who arebreastfeeding their babies should not use this medicinewithout checking with their physicians.
OTHER MEDICAL CONDITIONS. Before using ben-

zodiazepines, people with any of these medical problemsshould make sure their physicians are aware of their con-ditions:
• current or past drug or alcohol abuse• depression• severe mental illness
• epilepsy or other seizure disorders
• swallowing problems• chronic lung disease such as emphysema ,asthma ,o r
chronic bronchitis
• kidney disease• liver disease
• brain disease
•glaucoma
• hyperactivity• myasthenia gravis• porphyria
• sleep apnea

USE OF CERTAIN MEDICINES. Taking benzodiaze-
pines with certain other drugs may affect the way thedrugs work or may increase the chance of side effects.
headedness, drowsiness, clumsiness, unsteadiness, and
GALE ENCYCLOPEDIA OF MEDICINE 2 467BenzodiazepinesGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 467

slurred speech. These problems usually go away as the
body adjusts to the drug and do not require medical treat-ment unless they persist or they interfere with normalactivities.
• behavior changes• memory problems• difficulty concentrating
• depression• seizures (convulsions)• hallucinations
• sleep problems

• increased nervousness, excitability, or irritability• involuntary movements of the body, including the eyes•lLow blood pressureKEY TERMS
Bronchitis —Inflammation of the air passages of the

lungs.
Emphysema —An irreversible lung disease in which
breathing becomes increasingly difficult.

eye is abnormally high. If not treated, glaucomamay lead to blindness.Myasthenia gravis —A chronic disease with symp-
Panic disorder —A disorder in which people have

things.

• unusual bleeding or bruising• yellow skin or eyes• sore throat• sores in the mouth or throat•fever and chills
Patients who take benzodiazepines for a long time or
at high doses may notice side effects for several weeks afterthey stop taking the drug. They should check with theirphysicians if these or other troublesome symptoms occur:
• irritability• nervousness• sleep problems

unusual symptoms during or after treatment with benzo-diazepines should get in touch with his or her physician.
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Benzodiazepines may interact with a variety of other
medicines. When this happens, the effects of one or bothof the drugs may change or the risk of side effects maybe greater. Anyone who takes benzodiazepines should letthe physician know all other medicines he or she is tak-ing. Among the drugs that may interact with benzodi-azepines are:

medicine for allergies, colds, hay fever, and asthma;sedatives; tranquilizers; prescription pain medicine;muscle relaxants; medicine for seizures; sleep aids;barbiturates ; and anesthetics.
Medicines other than those listed above may interact
with benzodiazepines. Be sure to check with a physicianor pharmacist before combining benzodiazepines withany other prescription or nonprescription (over-the-counter) medicine.
Resources
OTHER
“Medications.” National Institute of Mental Health Page .1995

<http://www.nimh.nih.gov>.
Benzoyl peroxide seeAntiacne drugs
Benztropine seeAntiparkinson drugs
Berger’s disease seeIdiopathic primary
renal hematuric/proteinuric syndrome
Beriberi
Beriberi is a disease caused by a deficiency of thi-
amine (vitamin B1) that affects many systems of the

body, including the muscles, heart, nerves, and digestivesystem. Beriberi literally means “I can’t, I can’t” in Sing-halese, which reflects the crippling effect it has on itsvictims. It is common in parts of southeast Asia, wherewhite rice is the main food. In the United States, beriberiis primarily seen in people with chronic alcoholism .
Beriberi puzzled medical experts for years as it rav-

aged people of all ages in Asia. Doctors thought it wascaused by something in food. Not until the early 1900sdid scientists discover that rice bran, the outer coveringthat was removed to create the polished white rice pre-ferred by Asians, actually contained something that pre-vented the disease. Thiamine was the first vitamin identi-fied. In the 1920s, extracts of rice polishings were usedto treat the disease.
In adults, there are different forms of beriberi, classi-

fied according to the body systems most affected. Dryberiberi involves the nervous system; wet beriberi affectsthe heart and circulation. Both types usually occur in thesame patient, with one set of symptoms predominating.
A less common form of cardiovascular, or wet
beriberi, is known as “shoshin.” This condition involves arapid appearance of symptoms and acute heart failure . It
is highly fatal and is known to cause sudden death in

young migrant laborers in Asia whose diet consists ofwhite rice.
Cerebral beriberi, also known as Wernicke-Korsakoff
syndrome, usually occurs in chronic alcoholics and affectsthe central nervous system (brain and spinal cord). It canbe caused by a situation that aggravates a chronic thiaminedeficiency, like an alcoholic binge or severe vomiting.
Infantile beriberi is seen in breastfed infants of thi-
amine-deficient mothers, who live in developing nations.

Although severe beriberi is uncommon in the United
States, less severe thiamine deficiencies do occur. About25% of all alcoholics admitted to a hospital in the UnitedStates show some evidence of thiamine deficiency.
Thiamine is one of the B vitamins and plays an
important role in energy metabolism and tissue building.It combines with phosphate to form the coenzyme thi-
amine pyrophosphate (TPP), which is essential in reac-

tions that produce energy from glucose or that convertglucose to fat for storage in the tissues. When there is notenough thiamine in the diet, these basic energy functionsare disturbed, leading to problems throughout the body.
Special situations, such as an over-active metabo-
lism, prolonged fever ,pregnancy , and breastfeeding,
can increase the body’s thiamine requirements and leadto symptoms of deficiency. Extended periods of diar-
rhea or chronic liver disease can result in the body’s

inability to maintain normal levels of many nutrients,including thiamine. Other persons at risk are patientswith kidney failure on dialysis and those with severedigestive problems who are unable to absorb nutrients.Alcoholics are susceptible because they may substitutealcohol for food and their frequent intake of alcoholdecreases the body’s ability to absorb thiamine.
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The following systems are most affected by beriberi:
• Gastrointestinal system. When the cells of the smooth
muscles in the digestive system and glands do not getenough energy from glucose, they are unable to pro-duce more glucose from the normal digestion of food.There is a loss of appetite, indigestion , severe consti-
pation , and a lack of hydrochloric acid in the stomach.
• Nervous System. Glucose is essential for the central

nervous system to function normally. Early deficiencysymptoms are fatigue , irritability, and poor memory. If
the deficiency continues, there is damage to the periph-eral nerves that causes loss of sensation and muscleweakness, which is called peripheral neuropathy . The

legs are most affected. The toes feel numb and the feethave a burning sensation; the leg muscles become soreand the calf muscles cramp. The individual walksunsteadily and has difficulty getting up from a squattingposition. Eventually, the muscles shrink (atrophy) andthere is a loss of reflexes in the knees and feet; the feetmay hang limp (footdrop).
• Cardiovascular system. There is a rapid heartbeat and

sweating. Eventually the heart muscle weakens.Because the smooth muscle in the blood vessels isaffected, the arteries and veins relax, causing swelling,known as edema , in the legs.
• Musculoskeletal system. There is widespread muscle
pain caused by the lack of TPP in the muscle tissue.
Infants who are breastfed by a thiamine-deficient mother

usually develop symptoms of deficiency between thesecond and fourth month of life. They are pale, restless,unable to sleep, prone to diarrhea, and have musclewasting and edema in their arms and legs. They have acharacteristic, sometimes silent, cry and develop heartfailure and nerve damage.
Diagnosis
A physical examination will reveal many of the

early symptoms of beriberi, such as fatigue, irritation,nausea, constipation, and poor memory, but the deficien-cy may be difficult to identify. Information about theindividual’s diet and general health is also needed.
There are many biochemical tests based on thiamine

metabolism or the functions of TPP that can detect a thi-amine deficiency. Levels of thiamine can be measured inthe blood and urine and will be reduced if there is a defi-ciency. The urine can be collected for 24 hours to mea-sure the level of thiamine excreted. Another reliable testmeasures the effect of TPP on red blood cell activitysince all forms of beriberi affect the metabolism of redblood cells.An electroencephalogram (EEG), which measures

electrical activity in the brain, may be done to rule outother causes of neurologic changes. Observing improve-ments in the patient after giving thiamine supplementswill also confirm the diagnosis.
Treatment
Treatment with thiamine reverses the deficiency in

the body and relieves most of the symptoms. Severe thi-amine deficiency is treated with high doses of thiaminegiven by injection into a muscle (intramuscular) or in asolution that goes into a vein (intravenously) for severaldays. Then smaller doses can be given either by injectionor in pill form until the patient recovers. Usually thereare other deficiencies in the B vitamins that will alsoneed treatment.
The cardiovascular symptoms of wet beriberi can

respond to treatment within a few hours if they are nottoo severe. Heart failure may require additional treatmentwith diuretics that help eliminate excess fluid and with
heart-strengthening drugs like digitalis.
Recovery from peripheral neuropathy and other
symptoms of dry beriberi may take longer and patientsfrequently become discouraged. They should stay active;physical therapy will also help in recovery.

Infantile beriberi is treated by giving thiamine to
both the infant and the breast feeding mother until levelsare normal.
In Wernicke-Korsakoff syndrome, thiamine should
be given intravenously or by injection at first because theintestinal absorption of thiamine is probably impairedand the patient is very ill. Most of the symptoms will berelieved by treatment, though there may be residualmemory loss.
Excess thiamine is excreted by the body in the urine,

and negative reactions to too much thiamine are rare.Thiamine is unstable in alkali solutions, so it should notbe taken with antacids or barbiturates .
Alternative treatments for beriberi deal first with
correcting the thiamine deficiency. As in conventionaltreatments, alternative treatments for beriberi stress a

diet rich in foods that provide thiamine and other B vita-mins, such as brown rice, whole grains, raw fruits andvegetables, legumes, seeds, nuts, and yogurt. Drinkingmore than one glass of liquid with a meal should beavoided, since this may wash out the vitamins beforethey can be absorbed by the body. Thiamine should betaken daily, with the dose depending on the severity of
GALE ENCYCLOPEDIA OF MEDICINE 2 470BeriberiGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 470

the disease. Additional supplements of B vitamins, a
multivitamin and mineral complex, and Vitamin C arealso recommended. Other alternative therapies may helprelieve the person’s symptoms after the thiamine defi-ciency is corrected.
Prognosis
Beriberi is fatal if not treated and the longer the defi-

ciency exists, the sicker the person becomes. Most of thesymptoms can be reversed and full recovery is possiblewhen thiamine levels are returned to normal and main-tained with a balanced diet and vitamin supplements asneeded.
A balanced diet containing all essential nutrients

will prevent a thiamine deficiency and the developmentof beriberi. People who consume large quantities of junkfood like soda, pretzels, chips, candy, and high carbohy-drate foods made with unenriched flours may be defi-cient in thiamine and other vital nutrients. They mayneed to take vitamin supplements and should improvetheir diets .
Dietary Requirements
The body’s requirements for thiamine are tied to car-

bohydrate metabolism and expressed in terms of totalintake of calories. The current recommended dietaryallowances (RDA) are 0.5 mg for every 1,000 calories,with a minimum daily intake of 1 mg even for those whoeat fewer than 2,000 calories in a day. The RDA for chil-dren and teenagers is the same as for adults: 1.4 mg dailyfor males over age eleven, and 1.1 mg for females. Dur-ing pregnancy, an increase to 1.5 mg daily is needed.Because of increased energy needs and the secretion ofthiamine in

energy needs and the secretion ofthiamine in breast milk, breast feeding mothers need 1.5mg every day. In infants, 0.4 mg is advised.

Food Sources
The best food sources of thiamine are lean pork,
beef, liver, brewer’s yeast, peas and beans, whole orenriched grains, and breads. The more refined the food,as in white rice, white breads, and some cereals, thelower the thiamine. Many food products are enrichedwith thiamine, along with riboflavin, niacin, and iron, toprevent dietary deficiency.
During the milling process, rice is polished and all the

vitamins in the exterior coating of bran are lost. Boiling therice before husking preserves the vitamins by distributingthem throughout the kernel. Food enrichment programshave eliminated beriberi in Japan and the PhillipinesKEY TERMS
B vitamins —This family of vitamins consists of thi-
amine (B1), riboflavin (B2), niacin (B3), pantothenic
acid (B5), pyridoxine (B6), biotin, folic acid (B9),
and cobalamin (B12). They are interdependent and
involved in converting glucose to energy.

Coenzyme —A substance needed by enzymes to
produce many of the reactions in energy and pro-tein metabolism in the body.
Edema —An excess accumulation of fluid in the
cells and tissues.
Enzyme —A protein that acts as a catalyst to pro-
duce chemical changes in other substances with-out being changed themselves.Metabolism —All the physical and chemical
changes that take place within an organism.
Peripheral neuropathy —A disease affecting the

portion of the nervous system outside the brainand spinal chord. One or more nerves can beinvolved, causing sensory loss, muscle weaknessand shrinkage, and decreased reflexes.
Thiamine pyrophosphate (TPP) —The coenzyme
containing thiamine that is essential in convertingglucose to energy.
Like all B vitamins, thiamine is water soluble, which

means it is easily dissolved in water. It will leach out dur-ing cooking in water and is destroyed by high heat andovercooking.
Resources
BOOKS
Anderson, Jean, and Barbara Deskins. The Nutrition Bible.
New York: William Morrow, 1997.
The Burton Goldberg Group. Alternative Medicine: The Defin-
itive Guide. Fife, WA: Future Medicine Publishing, 1995.
Rivlin, Richard. “Vitamin Deficiency.” In Conn’s Current
Therapy, 1996 , ed. Robert E. Rakel. Philadelphia: W. B.
Saunders Co., 1996.

Williams, Sue Rodwell. Essentials of Nutrition and Diet Thera-
py.Philadelphia: Mosby, 1997.
Ryan, Ruth, et al. “Beriberi Unexpected.” Psychosomatics
(May/June 1997):191-294.
Karen Ericson, RN
Berry aneurysm seeCerebral aneurysm
GALE ENCYCLOPEDIA OF MEDICINE 2 471BeriberiGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 471

Berylliosis
Berylliosis is lung inflammation caused by inhaling
dust or fumes that contain the metallic element beryllium.Found in rocks, coal, soil, and volcanic dust, beryllium isused in the aerospace industry and in many types of man-ufacturing. Berylliosis occurs in both acute and chronicforms. In some cases, appearance of the disease may bedelayed as much as 20 years after exposure to beryllium.
In the 1930s, scientists discovered that beryllium

could make fluorescent light bulbs last longer. During thefollowing decade, the hard, grayish metal was identifiedas the cause of a potentially debilitating, sometimesdeadly disease characterized by shortness of breath and
inflammation, swelling, and scarring of the lungs.
The manufacture of fluorescent light bulbs is no

longer a source of beryllium exposure, but serious healthhazards are associated with any work environment orprocess in which beryllium fumes or particles becomeairborne. Working with pure beryllium, beryllium com-pounds (e.g. beryllium oxide), or beryllium alloys causesoccupational exposure. So do jobs involving:
• electronics
• fiber optics
• manufacturing ceramics, bicycle frames, golf clubs,
mirrors, and microwave ovens

• mining• nuclear weapons and reactors• reclaiming scrap metal
• space and atomic engineering.
• dental and laboratory technology
Beryllium dust and fumes are classified as toxic air
pollutants by the Environmental Protection Agency(EPA). It is estimated that 2–6% of workers exposed tothese contaminants eventually develop berylliosis.
Coughing, shortness of breath, and weight loss that

begin abruptly can be a symptom of acute berylliosis. Thiscondition is caused by beryllium air pollution that inflamesthe lungs making them rigid; it can affect the eyes and skinas well. People who have acute berylliosis are usually veryill. Most recover, but some die of the disease.
Chronic berylliosis is an allergic reaction to long-

term exposure to even low levels of beryllium dust orfumes. A systemic disease that causes formation ofabnormal lung tissue and enlargement of the lymphnodes, chronic berylliosis also may affect other parts ofthe body. The symptoms of chronic berylliosis are large-ly the same as those seen in acute berylliosis, but theydevelop more slowly.
Diagnosis
Berylliosis is initially suspected if a patient with symp-

toms of the disease has a history of beryllium exposure. Achest x ray shows characteristic changes in the lungs.
However, since these changes can resemble those causedby other lung diseases, further testing may be necessary.
The beryllium lymphocyte proliferation test (BeLPT),

a blood test that can detect beryllium sensitivity (i.e. anallergic reaction to beryllium), is used to screen individualsat risk of developing berylliosis. When screening resultsreveal a high level of sensitivity, BeLPT is performed oncells washed from the lungs. This test is now consideredthe most definitive diagnostic test for berylliosis.
Treatment
Individuals with beryllium sensitivity or early-stage

berylliosis should be transferred from tasks that involveberyllium exposure and regularly examined to determinewhether the disease has progressed.
Acute berylliosis is a serious disease that occasion-
ally may be fatal. Ventilators can help patients with acuteberylliosis breathe. Prompt corticosteroid therapy isrequired to lessen lung inflammation.
Chronic beryllium disease is incurable. Corticos-

teroid therapy is often prescribed, but it is not certain thatsteroids can alter the progression of the disease, and theyhave no effect on scarring of lung tissue. Cleansing thelungs of beryllium is a slow process, so long-term thera-py may be required. Chelation therapy is currently
under investigation as a treatment for the disease.
Prognosis
Most patients with acute berylliosis recover fully

7–10 days after treatment begins, and the disease usuallycauses no after effects.
Patients whose lungs are severely damaged by
chronic berylliosis may experience fatal heart failure
because of the strain placed on the heart.
Eliminating exposure to beryllium is the surest way
to prevent berylliosis. Screening workers who areexposed to beryllium fumes or dust or who develop anallergic reaction to these substances is an effective wayto control symptoms and prevent disease progression.

GALE ENCYCLOPEDIA OF MEDICINE 2 472BerylliosisGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 472

Resources
BOOKS
Thoene, Jess G., ed. Physicians’ Guide to Rare Diseases. 2nd
ed. Montvale, NJ: Dowden Publishing Co., 1995.
Beryllium Support Group. P.O. Box 2021, Broomfield, CO
80038-2021. (303) 412-7065. <http://www.dimensional.com/~mhj>.
Environmental Health Center. 1025 Connecticut Ave., NW,
Washington, DC 20036 (202) 293-2270.
OTHER

OTHER
“Beryllium Chemical Backgrounder.” Environmental Health
Center Page. 28 May 1998 <http://www.nsc.org/ehc/ew/
chems/berylliu.htm>.
“Beryllium Disease: Reducing the Risks.” National Jewish
Medical Research Center Page. 28 May 1998 <http://
www.nationaljewish.org/main.html>.
Epler, Gary R. Home Page. 29 May 1998. “Environmental and
Occupational Lung Diseases.” <http://www.epler.com/occu2.html>.
Beryllium pneumonosis seeBerylliosis

Beryllium poisoning seeBerylliosis
Beta-adrenergic blockers seeBeta blockers
Beta-thalassemia seeThalassemia
Beta2-microglobulin test
Beta2-microglobulin is a protein found on the sur-
face of many cells. Testing is done primarily when evalu-KEY TERMS
Beryllium —A steel-grey, metallic mineral used in
the aerospace and nuclear industries and in a vari-ety of manufacturing processes.
Chelation therapy —A treatment using chelating

agents, compounds that surround and bind to tar-get substances allowing them to be excreted fromthe body.
Corticosteroids —A group of anti-inflammatory
drugs.ating a person for certain kinds of cancer affecting white
blood cells including chronic lymphocytic leukemia,non-Hodgkin’s lymphoma, and multiple myeloma or
kidney disease.
Purpose
Beta2-microglobulin is plentiful on the surface of

white blood cells. Increased production or destruction ofthese cells causes Beta
2-microglobulin levels in the blood
to increase. This increase is seen in people with cancersinvolving white blood cells, but it is particularly mean-ingful in people newly diagnosed with multiple myelo-ma. Multiple myeloma is a malignancy (cancer) of a cer-tain kind of white blood cell, called a plasma cell. At thetime of diagnosis, the Beta
2-microglobulin levels reflect

how advanced the disease is and the likely prognosis forthat person.
When kidney disease is suspected, comparing blood
and urine levels helps identify where the kidney is dam-aged. Beta
2-microglobulin normally is filtered out of the

blood by the kidney’s glomeruli (a round mass of capil-lary loops leading to each kidney tubule), only to be par-tially reabsorbed back into the blood when it reaches thekidney’s tubules. In glomerular kidney disease, theglomeruli can’t filter it out of the blood, so levelsincrease in the blood and decrease in the urine. In tubularkidney disease, the tubules can’t reabsorb it back into theblood, so urine levels rise and blood levels fall. After akidney transplant, increased blood levels may be

akidney transplant, increased blood levels may be an earlysign of rejection.

Increased urinary levels are found in people with
kidney damage caused by high exposure to the heavymetals cadmium and mercury. Periodic testing of work-ers exposed to these metals helps to detect beginning kid-ney damage.
Beta
2-microglobulin levels also rise during infec-
tion with some viruses, including cytomegalovirus andhuman immunodeficiency virus (HIV). Studies show
that as HIV disease advances, beta
2-microglobulin lev-
els rise.

els rise.
Testing methods vary, but most involve adding the
person’s serum—the yellow, liquid part of blood—orurine to one or more substances that bind to beta
2-
microglobulin in the serum or urine. The amount of thesubstance(s) bound to beta
2-microglobulin is measured
and the original amount of beta2-microglobulin is
determined.

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The blood test requires 5 mL of blood. A healthcare
worker ties a tourniquet on the person’s upper arm,locates a vein in the inner elbow region, and inserts aneedle into that vein. Vacuum action draws the bloodthrough the needle into an attached tube. Collection ofthe sample takes only a few minutes.
Urine may be a single collection or collected
throughout a 24-hour time period. The urine should berefrigerated until it is brought to the laboratory and mustnot become acidic.
Aftercare

Aftercare
site or the person may feel dizzy or faint. Pressure to thepuncture site until the bleeding stops reduces bruising.Warm packs on the puncture site relieve discomfort.
• Serum: less than or equal to 2.7 g/mL
• Urine: less than 1 mg/24 hours or 0-160 g/L
The meaning of an abnormal result varies with the
clinical condition of the person tested. In a person withKEY TERMS

Beta2-microglobulin —A protein found on the sur-
face of many cells, particularly white blood cells.
Chronic lymphocytic leukemia —A cancer of the
blood cells characterized by large numbers of can-cerous, mature white blood cells and enlargedlymph nodes.
Glomerular kidney disease —Disease of the kid-
ney that affects the glomeruli, the part of the kid-ney that filters certain substances out of the blood.
Muliple myeloma —A malignancy (cancer) of a

certain kind of white blood cell, called a plasmacell.
Non-Hodgkin’s lymphoma —Cancer that origi-
nates in the lymphatic system and typicallyspreads throughout the body.
Tubular kidney disease —Disease of the kidney
that affect the tubules, the part of the kidney thatallows certain substances to be reabsorbed backinto the blood.multiple myeloma, a higher level means a poorer prognosis

than a lower level. In a person with kidney disease, anincreased blood level means the problem is tubular, notglomerular. In a kidney transplant patient, an increase maybe a sign of rejection, toxic amounts of antirejection med-ication, or a viral infection. An increased level in a workerexposed to cadmium or mercury may signal beginning kid-ney damage and in a person with HIV , advancing disease.
Resources
BOOKS

Lehmann, Craig A. Saunders Manual of Clinical Laboratory
Bethea, Marc, and Donald R. Forman. “Beta2-Microglobulin:
Its Significance and Clinical Usefulness.” Annals of Clini-
cal and Laboratory Science (May/June 1990): 163–168.

Henne, V ., P. Frei, and P. L. Burgisser. “Beta2-microglobulin-A
Rapid and Automated Determination for a Broad Rangeof Clinical Applications.” Anticancer Research (July/Aug.
1997): 2915–2918.
Beta blockers
Beta blockers are medicines that affect the body’s
response to certain nerve impulses. This, in turn, decreasesthe force and rate of the heart’s contractions, which lowersblood pressure and reduces the heart’s demand for oxygen.
Purpose

Purpose
The main use of beta blockers is to treat high blood
pressure. Some also are used to relieve the type of chestpain called angina or to prevent heart attacks in people
who already have had one heart attack . These drugs
may also be prescribed for other conditions, such asmigraine, tremors , and irregular heartbeat. In eye drop
form, they are used to treat certain kinds of glaucoma .
Beta blockers, also known as beta-adrenergic block-

ers, are available only with a physician’s prescription.
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The come in capsule, tablet, liquid, and injectable forms.
Some common beta blockers are atenolol (Tenormin),metoprolol (Lopressor), nadolol (Corgard), propranolol(Inderal), and timolol (Blocadren). Timolol and certainother beta blockers are also sold in eye drop form fortreating glaucoma. Eye drops that contain beta blockersinclude betaxolol (Betoptic), cartelol (Ocupress), andtimolol (Timoptic).
The recommended dosage depends on the type,

strength, and form of beta blocker and the condition forwhich it is prescribed. Check with the physician whoprescribed the drug or the pharmacist who filled the pre-scription for the correct dosage.
This medicine may take several weeks to noticeably
lower blood pressure. Taking it exactly as directed isimportant.

with the physician who prescribed it. Some conditionsmay get worse when patients stop taking beta blockersabruptly. This may also increase the risk of heart attackin some people. Because of these possible effects, it isimportant to keep enough medicine on hand to getthrough weekends, holidays, and vacations.
Physicians may recommend that patients check their

pulse before and after taking this medicine. If the pulsebecomes too slow, circulation problems may result.
Seeing a physician regularly while taking beta

blockers is important. The physician will check to makesure the medicine is working as it should and will watchfor unwanted side effects. People who have high bloodpressure often feel perfectly fine. However, they shouldcontinue to see their physicians even when they feel wellso that the physician can keep a close watch on their con-dition. Patients also need to keep taking their medicineeven when they feel fine.

will help control the condition. To avoid the serioushealth problems that high blood pressure can cause,patients may have to take medicine for the rest of theirlives. Furthermore, medicine alone may not be enough.Patients with high blood pressure may also need to avoidcertain foods and keep their weight under control. Thehealth care professional who is treating the condition canoffer advice on what measures may be necessary.Patients being treated for high blood pressure should notchange their

for high blood pressure should notchange their diets without consulting their physicians.Anyone taking beta blockers for high blood pressure

should not take any other prescription or over-the-counter medicine without first checking with his or herphysician. Some medicines may increase blood pressure.
Anyone who is taking beta blockers should be sure
Some beta blockers may change the results of cer-

tain medical tests. Before having medical tests, anyonetaking this medicine should alert the health care profes-sional in charge.
Some people feel drowsy, dizzy, or lightheaded
when taking beta blockers. Anyone who takes thesedrugs should not drive, use machines or do anything elsethat might be dangerous until they have found out howthe drugs affect them.
Beta blockers may increase sensitivity to cold, espe-

cially in older people or people who have poor circula-tion. Anyone who takes this medicine should dresswarmly in cold weather and should be careful not to beexposed to the cold for too long.
People who usually have chest pain when they exer-
ciseor exert themselves may not have the pain when they
are taking beta blockers. This could lead them to be moreactive than they should be. Anyone taking this medicineshould ask his or her physician how much exercise andactivity is safe.

Older people may be unusually sensitive to the
effects of beta blockers. This may increase the chance ofside effects.
Physicians may advise people taking beta blockers
to wear or carry medical identification indicating thatthey are taking this medicine.
People who have certain medical conditions or who
are taking certain other medicines may have problems ifthey take beta blockers. Before taking these drugs, be sureto let the physician know about any of these conditions:

to beta blockers in the past should let his or her physicianknow before taking the drugs again. The physicianshould also be told about any allergies to insect stings,

medicines, foods, dyes, preservatives, or other sub-stances. In people with allergies to medicines, foods, orinsect stings, beta blockers may make the allergic reac-tions more severe and harder to treat. Anyone who has anallergic reaction while taking beta blockers should getmedical attention right away and should make sure the
GALE ENCYCLOPEDIA OF MEDICINE 2 475Beta blockersGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 475

physician in charge knows that he or she is taking this
medicine.
Beta blockers may also cause serious reactions in
people who take allergy shots. Anyone taking this medi-cine should be sure to alert the physician before havingany allergy shots.
DIABETES. Beta blockers may make blood sugar lev-
els rise and may hide some symptoms of low bloodsugar. Diabetic patients should discuss these possibleproblems with their physicians.
PREGNANCY. Some studies of beta blockers show

that these drugs cause problems in newborns whosemothers use them during pregnancy . Other studies do
not show such effects. Women who are pregnant or whomay become pregnant should check with their physiciansabout the use of beta blockers.
BREASTFEEDING. Some beta blockers pass into

breast milk and may cause breathing problems, slowheartbeat, and low blood pressure in nursing babieswhose mothers take the drugs. Women who need to takebeta blockers and who want to breastfeed their babiesshould check with their physicians.
OTHER MEDICAL CONDITIONS. Beta blockers may
increase breathing problems or make allergic reactionsmore severe in people who have allergies, bronchitis ,o r
emphysema .

In people with an overactive thyroid, stopping beta
blockers suddenly may cause an increase in symptoms.Also, taking this medicine may hide a fast heartbeat,
which is one of the symptoms of overactive thyroid.
Effects of these drugs may be greater in people with
kidney or liver disease because the medicine is clearedfrom the body more slowly.
Beta blockers may also make the following medical
conditions worse:
• Heart or blood vessel disease

• Unusually slow heartbeat (bradycardia)• Myasthenia gravis (chronic disease causing muscle
weakness and possibly paralysis )
• Psoriasis (itchy, scaly, red patches of skin)
• Depression (now, or in the past).
Before using beta blockers, people with any of the
medical problems listed in this section should make suretheir physicians are aware of their conditions.
USE OF CERTAIN MEDICINES. Taking beta blockers

drowsiness, lightheadedness, sleep problems, unusualtiredness or weakness, and decreased sexual ability. Inmen, this can occur as impotence or delayed ejaculation.

These problems usually go away as the body adjusts tothe drug and do not require medical treatment unless theypersist or they interfere with normal activities.
More serious side effects are possible. If any of the
following side effects occur, check with the physicianwho prescribed the medicine as soon as possible:
• Breathing problems
• Slow heartbeat• Cold hands and feet• Swollen ankles, feet, or lower legs.• Mental depression.

unusual symptoms after taking beta blockers should getin touch with his or her physician.
Beta blockers may interact with a number of other
medicines. When this happens, the effects of one or bothof the drugs may change or the risk of side effects may begreater. Anyone who takes beta blockers should let thephysician know all other medicines he or she is taking.Among the drugs that may interact with beta blockers are:

GALE ENCYCLOPEDIA OF MEDICINE 2 476Beta blockers
Blister packs of Tenormin LS (atenolol), a type of beta-
receptor blocking drug or beta blocker.This type of drug iswidely used to treat angina, to lower blood pressure, or tocorrect abnormal heart rhythms. (Photograph by Adam Hart-
Davis, Photo Researchers, Inc. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 476

• Calcium channel blockers and other blood pressure
drugs. Using these drugs with beta blockers may causeunwanted effects on the heart.
• Insulin and diabetes medicines taken by mouth. Beta
blockers cause high blood sugar or hide the symptomsof low blood sugar.
• Monoamine oxidase inhibitors (MAO) such as phenel-
zine (Nardil) or tranylcypromine (Parnate), used to treatconditions including depression and Parkinson’s dis-
ease. Taking beta blockers at the same time or within

two weeks of taking MAO inhibitors may cause severehigh blood pressure.
• Airway-opening drugs ( bronchodilators ) such as
aminophylline (Somophyllin), dyphylline (Lufyllin)oxtriphylline (Choledyl), or theophylline (Somo-phyllin-T). When combined with beta blockers, theeffects of both the beta blockers and the airway-open-ing drugs may be lessened.
•Cocaine . High blood pressure, fast heartbeat, and heart

problems are possible when cocaine and beta blockersare combined. Also, cocaine may interfere with theeffects of beta blockers.
• Allergy shots or allergy skin tests. Beta blockers may
increase the chance of serious reactions to these medi-cines.
acts with beta blockers. Be sure to check with a physi-cian or pharmacist before combining beta blockers withany other prescription or nonprescription (over-the-counter) medicine.

Betamethasone seeCorticosteroids
Bile duct atresia seeBiliary atresiaKEY TERMS
ness, or pain in the chest, caused by a lack of oxy-gen in the muscular wall of the heart.
eye is abnormally high. If not treated, glaucomamay lead to blindness.Migraine —A throbbing headache that usually

affects only one side of the head. Nausea, vomit-ing, increased sensitivity to light, and other symp-toms often accompany migraine.Bile duct cancer
Bile duct cancer , or cholangiocarcinoma, is a malig-
nant tumor of the bile ducts within the liver (intrahepatic),or leading from the liver to the small intestine (extrahepat-ic). It is a rare tumor with poor outcome for most patients.
Bile is a substance manufactured by the liver that

aids in the digestion of food. Bile ducts are channels thatcarry the bile from the liver to the small intestine. Likethe tributaries of a river, the small bile ducts in the liverconverge into two large bile ducts called the left and righthepatic ducts. These exit the liver and join to form thecommon hepatic duct. The gallbladder, which concen-trates and stores the bile, empties into the commonhepatic duct to form the common bile duct. Finally, thislarge duct connects to the small intestine

thislarge duct connects to the small intestine where the bilecan help digest food. Collectively, this network of bileducts is called the biliary tract.

Bile duct cancer originates from the cells that line
the inner surface of the bile ducts. A tumor may ariseanywhere along the biliary tract, either within or outsideof the liver. Bile duct tumors are typically slow-growingtumors that spread by local invasion of neighboringstructures and by way of lymphatic channels.
Bile duct cancer is an uncommon malignancy. In the

United States, approximately one case arises per 100,000people per year, but it is more common in SoutheastAsia. It occurs in men only slightly more often than inwomen, and it is most commonly diagnosed in people intheir 50s and 60s.
A number of risk factors are associated with the
development of bile duct cancer:
• Primary sclerosing cholangitis . This disease is charac-

terized by extensive scarring of the biliary tract, some-times associated with inflammatory bowel disease.
• Choledochal cysts. These are abnormal dilatations of
the biliary tract that usually form during fetal develop-ment. There is evidence that these cysts may rarelyarise during adulthood.
• Hepatolithiasis. This is the condition of stone formation
within the liver (not including gallbladder stones).
• Liver flukes. Parasitic infection with certain worms is

thought to be at least partially responsible for the higherprevalence of bile duct cancer in Southeast Asia.
GALE ENCYCLOPEDIA OF MEDICINE 2 477Bile duct cancerGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 477

• Thorotrast. This is a chemical that was previously
injected intravenously during certain types of x rays. Itis not in use anymore. Exposure to Thorotrast has beenimplicated in the development of cancer of the liver aswell as the bile ducts.
Symptoms
Jaundice is the first symptom in 90% of patients.

This occurs when the bile duct tumor causes an obstruc-tion in the normal flow of bile from the liver to the smallintestine. Bilirubin, a component of bile, builds up withinthe liver and is absorbed into the bloodstream in excessamounts. This can be detected in a blood test, but it canalso manifest as yellowish discoloring of the skin andeyes. The bilirubin in the bloodstream also makes theurine appear dark. Additionally, the patient may experi-ence generalized itching due to the deposition of

components in the skin. Normally, a portion of the bile isexcreted in stool; bile actually gives stool its browncolor. But when the biliary tract is obstructed by tumor,the stools may appear pale.
Abdominal pain ,fatigue , weight loss, and poor
appetite are less common symptoms. Occasionally, ifobstruction of the biliary tract causes the gallbladder toKEY TERMS
Angiography —Radiographic examination of
blood vessels after injection with a special dye
Cholangiography —Radiographic examination of

the bile ducts after injection with a special dye
Computed tomography —Radiographic examina-
tion by which images of cross-sectional planes ofthe body are obtained
Jaundice —Yellowish staining of the skin and eyes
due to excess bilirubin in the bloodstream
Lymphatic —Pertaining to lymph, the clear fluid
that is collected from tissues, flows through spe-cial vessels, and joins the venous circulationMetastasis —The spread of tumor cells from one

part of the body to another
Resection —To surgically remove a part of the
body
Stent —Slender hollow catheter or rod placed
within a vessels for duct to provide support ormaintain patency
Ultrasound —Radiographic imaging technique uti-
lizing high frequency sound wavesswell enormously yet without causing pain, the physician
may be able to feel the gallbladder during a physical
examination . Sometimes the biliary tract can become

infected, but this is normally a rare consequence of inva-sive tests. Infection causes fever , chills, and pain in the
right upper portion of the abdomen.
Diagnosis
Certain laboratory tests of the blood may aid in the
diagnosis. The most important one is the test for elevatedbilirubin levels in the bloodstream. Levels of alkalinephosphatase and CA 19-9 may also be elevated.
When symptoms, physical signs, and blood tests

poinmt toward an abnormality of the biliary tract, thenthe next step involves radiographic tests. Ultrasound andcomputed tomography (CT scan) are noninvasive andrapid. These tests can often detect the actual tumor aswell as dilatation of the obstructed biliary tract. If thesetests indicate the presence of a tumor, then cholangiogra-phy is required. This procedure involves injecting dyeinto the biliary tract to obtain anatomic images of the bileducts and the tumor. The specialist that performs

and the tumor. The specialist that performs this testcan also insert small tubes, or stents, into a partiallyobstructed portion of the bile duct to prevent furtherobstruction by growth of the tumor. This is vitally impor-tant since it may be the only intervention that is possiblein certain patients. Cholangiography is an invasive testthat carries a small risk of infection of the biliary tract.The objective of these radiological tests is to determinethe size and location of the tumor, as well as

size and location of the tumor, as well as the extent ofspread to nearby structures.

The treatment of bile duct tumors is usually not
affected by the specific type of cancer cells that comprisethe tumor. For this reason, some physicians forego biop-sy of the tumor.
Treatment
The treatment is with surgical resection (removal) of

the tumor and all involved structures. Unfortunately,sometimes the cancer has already spread too far when thediagnosis is made. Thus, in the treatment of bile duct can-cer, the first question to answer is if the tumor may besafely resected by surgery with reasonable benefit to thepatient. If the cancer involves certain blood vessels or hasspread widely throughout the liver, then resection may notbe possible. Sometimes further invasive testing is required.

Angiography can determine if the blood vessels are
involved. Laparoscopy is a surgical procedure that allows
the surgeon to directly assess the tumor and nearby lymphnodes without making a large incision in the abdomen. Onlyabout 45% of bile duct cancers are ultimately resectable.
GALE ENCYCLOPEDIA OF MEDICINE 2 478Bile duct cancerGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 478

enough to tolerate the operation, then the specific type ofsurgery performed depends on the location of the tumor.For tumors within the liver or high up in the biliary tract,resection of part of the liver may be required. Tumors inthe middle portion of the biliary tract can be removedalone. Tumors of the lower end of the biliary tract mayrequire extensive resection of part of the pancreas, smallintestine, and stomach to ensure complete resection.
Unfortunately, sometimes the cancer appears

resectable by all the radiological and invasive tests, but isfound to be unresectable during surgery. In this scenario, abypass operation can relieve the biliary tract obstruction,but does not remove the tumor itself. This does not producea cure but it can offer a better quality of life for the patient.
Chemotherapy and radiation therapy have not
been proven effective in the treatment of bile duct cancer.
Prognosis

Prognosis
Prognosis depends on the stage and resectability of
the tumor. If the patient cannot undergo surgical resec-tion, then the survival rate is commonly less than oneyear. If the tumor is resected, the survival rate improves,with 20% of these patients surviving past five years.
Clinical trials
Studies of new treatments in patients are known as

clinical trials. These trials seek to compare the standardmethod of care with a new method, or the trials may be try-ing to establish whether one treatment is more beneficialfor certain patients than others. Sometimes, a new treat-ment that is not being offered on a wide scale may be avail-able to patients participating in clinical trials, but participat-ing in the trials may involve some risk. To learn more aboutclinical trials, patients can call the National Cancer Institute(NCI) at

can call the National Cancer Institute(NCI) at 1-800-4-CANCER or visit the NCI web site forpatients at <http://www.cancertrials.nci.nih.gov>.

Other than the avoidance of infections caused by liver
flukes, there are no known preventions for this cancer.
Resources
BOOKS
Ahrendt, Steven A. and Henry A. Pitt. “Biliary Tract.” In Sabis-
ton Textbook of Surgery , Edited by Courtney Townsend
Jr., 16th ed. Philadelphia: W.B. Saunders Company, 2001,pp. 1076-1111.
Callery, Mark P. and William C. Meyers. “Bile Duct Cancer.”
In Current Surgical Therapy , Edited by John L. Cameron,

sixth ed. St Louis: Mosby, 1998, pp.455-161.“Cholangiocarcinoma.” In Clinical Oncology , Edited by
Abeloff, Martin D., second ed. New York: Churchill Liv-ingstone, 2000, pp.1722-1723.
The American Cancer Society. 1-800-ACS 2345. <http://www.
National Cancer Institute Cancer Information Service. 1-800-4-
CANCER. <http://www.nci.nih.gov>.
American Liver Foundation. 1-800-GO-LIVER (1-800-465-
4837). <http://www.liverfoundation.org>.
Kevin O. Hwang, M.D.

Bile duct infection seeCholangitis
Bile flow obstruction seeCholestasis
Bilharziasis seeSchistosomiasis
Biliary atresia
Biliary atresia is the failure of a fetus to develop an
adequate pathway for bile to drain from the liver to theintestine.
Biliary atresia is the most common lethal liver disease
in children, occurring once every 10,000–15,000 livebirths. Half of all liver transplants are done for this reason.

in the liver, where thousands of tiny bile ducts collectbile from liver cells. These ducts merge into larger andlarger channels, like streams flowing into rivers, untilthey all pour into a single duct that empties into the duo-denum (first part of the small intestine). Between theliver and the duodenum this duct has a side channel con-nected to the gall bladder. The gall bladder stores bileand concentrates it, removing much of its water content.Then, when a meal hits the stomach, the gall

when a meal hits the stomach, the gall bladdercontracts and empties its contents.

removes from the circulation and excretes through thebiliary system into the intestine. On its way out, bileassists in the digestion of certain nutrients. If bile cannotget out because the channels are absent or blocked, itbacks up into the liver and eventually into the rest of thebody. The major pigment in bile is a chemical calledbilirubin, which is yellow. Bilirubin is a breakdown prod-uct of hemoglobin (the red chemical in blood that carriesoxygen). If the body accumulates an excess of

GALE ENCYCLOPEDIA OF MEDICINE 2 479Biliary atresiaGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 479

KEY TERMS
Duodenum —The first part of the small intestine,
beginning at the outlet of the stomach.
Hemoglobin —The red, iron-containing chemical
in the blood that carries oxygen to the tissues.
Jaundice —The yellow color taken on by a patient
whose liver is unable to excrete bilirubin. A normalcondition in the first week of life due to the infant’sdelayed ability to process certain waste products.
Kernicterus —A potentially lethal disease of new-

borns caused by excessive accumulation of thebile pigment bilirubin.
it turns yellow (jaundiced). Bile also turns the stool
brown. Without it, stools are the color of clay.
It is possible that a viral infection is responsible for
this disease, but evidence is not yet convincing. Thecause remains unknown.
The affected infant will appear normal at birth and

during the newborn period. After two weeks the normaljaundice of the newborn will not disappear, and the
stools will probably be clay-colored. At this point, thecondition will come to the attention of a physician. If not,the child’s abdomen will begin to swell, and the infantwill get progressively more ill. Nearly all untreated chil-dren will die of liver failure within two years.
Diagnosis
The persistence of jaundice beyond the second week

in a newborn with clay-colored stools is a sure sign ofobstruction to the flow of bile. An immediate evaluationthat includes blood tests and imaging of the biliary sys-tem will confirm the diagnosis.
Treatment
Surgery is the only treatment. Somehow the surgeon
must create an adequate pathway for bile to escape theliver into the intestine. The altered anatomy of the biliarysystem is different in every case, calling upon the sur-geon’s skill and experience to select and execute the most

effective among several options. If the obstruction is onlybetween the gall bladder and the intestine, it is possible toattach a piece of intestine directly to the gall bladder. Morelikely, the upper biliary system will also be inadequate,and the surgeon will attach a piece of intestine directly tothe liver—the Kasai procedure. In its wisdom, the bodywill discover that the tiny bile ducts in that part of the liverare discharging their bile directly into the intestine. Bilewill begin to flow in

into the intestine. Bilewill begin to flow in that direction, and the channels willgradually enlarge. Survival rates for the Kasai procedureare commonly 50% at five years and 15% at 10 years. Per-sistent disease in the liver gradually destroys the organ.

Liver transplantation must be anticipated in all but
the few patients who continue to do well after a Kasaiprocedure. Accumulating experience and newer tech-niques of liver transplantation are producing very gratify-ing early results.
Prognosis
Before liver transplants became available, even

prompt and effective surgery did not cure the wholeproblem. Biliary drainage can usually be established, butthe patients still have a defective biliary system thatdevelops progressive disease and commonly leads to anearly death . Transplantation now achieves up to 90%
one-year survival rates and promises to prevent thechronic disease that used to accompany earlier proce-dures.
The specific cause of this birth defect is unknown, so

all that women can do is to practice the many generalpreventive measures, even before they conceive.
GALE ENCYCLOPEDIA OF MEDICINE 2 480Biliary atresiaLiver Cystic duct
Pyloric sphincter
PancreasDuodenumGallbladder
Common bile duct
Biliary atresia is a congenital condition in which the path-

way for bile to drain from the liver to the intestine is unde-veloped. It is the most common lethal liver disease in chil-dren. (Illustration by Electronic Illustrators Group).GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 480

Resources
BOOKS
Balistreri, William F. “Cholestasis.” In Nelson Textbook of
Pediatrics , ed. Richard E. Behrman. Philadelphia: W. B.
Feldman, Mark, et al. “Diseases of the Bile Ducts.” Sleisenger
& Fordtran’s Gastrointestinal and Liver Disease.Philadelphia: W. B. Saunders Co., 1998.
Ryckman, F., R. Fisher, and S. Pedersen, et al. “Improved Sur-
vival in Biliary Atresia Patients in the Present Era of LiverTransplantation.” Journal of Pediatric Surgery 28 (1993):

382.
Biliary duct cancer seeGallbladder cancer
Biliary tract cancer seeBile duct cancer
Bilirubin test seeLiver function tests
Binge-eating disorder
Binge eating disorder (BED) is characterized by a

loss of control over eating behaviors. The binge eaterconsumes unnaturally large amounts of food in a shorttime period, but unlike a bulimic, does not regularlyengage in any inappropriate weight-reducing behaviors(for example, excessive exercise , vomiting, taking laxa-
tives ) following the binge episodes.
BED typically strikes individuals sometime between

adolescence and the early twenties. Because of the natureof the disorder, most BED patients are overweight orobese. Studies of weight loss programs have shown thatan average of 30% of individuals enrolling in these pro-grams report binge eating behavior.
Binge eating episodes may act as a psychological
release for excessive emotional stress . Other circum-

stances that may predispose an individual to BED includeheredity and affective disorders, such as major depression.BED patients are also more likely to have a comorbid, orco-existing, diagnosis of impulsive behaviors (for exam-ple, compulsive buying), post-traumatic stress disorder
(PTSD), panic disorder , or personality disorders .Individuals who develop BED often come from fam-

ilies who put an unnatural emphasis on the importance offood, for example, as a source of comfort in times ofemotional distress. As children, BED patients may havebeen taught to clean their plate regardless of theirappetite, or that finishing a meal made them a “good”girl or boy. Cultural attitudes towards beauty and thin-ness may also be a factor in the BED equation.
During binge episodes, BED patients experience a

definite sense of lost control over their eating. They eatquickly and to the point of discomfort even if they aren’thungry. They typically binge alone two or more times aweek, and often feel depressed and guilty once theepisode has concluded.
Diagnosis
Binge eating disorder is usually diagnosed and treated

by a psychiatrist and/or a psychologist. In addition to aninterview with the patient, personality and behavioralinventories, such as the Minnesota Multiphasic Person-
ality Inventory (MMPI), may be administered as part of
the assessment process. One of several clinical inventories,or scales, may also be used to assess depressive symptoms,including the Hamilton Depression Scale (HAM-D) orBeck Depression Inventory (BDI). These tests may beadministered in an outpatient or hospital setting.

Treatment
Many BED individuals binge after long intervals of
excessive dietary restraint; therapy helps normalize thispattern. The initial goal of BED treatment is to teach thepatient to gain control over his eating behavior by focus-ing on eating regular meals and avoiding snacking. Cog-
nitive-behavioral therapy ,group therapy , or interper-
sonal psychotherapy may be employed to uncover theemotional motives, distorted thinking, and behavioralpatterns behind the binge eating.

Because the prevalence of depression in BED
patients is high, psychopharmacological treatment withantidepressants may also be prescribed. Once the bingeeating behavior is curbed and depressive symptoms arecontrolled, the physical symptoms of BED can beaddressed. The overweight BED patient may be placedon a moderate exercise program and a nutritionist may beconsulted to educate the patient on healthy food choicesand strategies for weight loss.
Prognosis

Prognosis
The poor dietary habits and obesity that are sympto-
matic of BED can lead to serious health problems, such ashigh blood pressure, heart attacks, and diabetes, if left
GALE ENCYCLOPEDIA OF MEDICINE 2 481Binge-eating disorderGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 481

unchecked. BED is a chronic condition that requires ongo-
ing medical and psychological management. To bringlong-term relief to the BED patient, it is critical to addressthe underlying psychological causes behind binge eatingbehaviors. It appears that up to 50% of BED patients willstop bingeing with cognitive behavioral therapy (CBT).
Resources
BOOKS
Abraham, Suzanne, and Derek Llewellyn-Jones. Eating Disor-
ders: The Facts. 4th ed. Oxford, England: Oxford Univer-
sity Press, 1997.

Siegel, Michele, Judith Brisman, and Margot Weinshel. Surviv-
ing an Eating Disorder: Strategies for Family andFriends. 2nd ed. New York: Harper Perennial, 1997.
Brewerton, Timothy D. “Binge Eating Disorder: Recognition,
Diagnosis, and Treatment.” Medscape Mental Health 2,
no. 5 (1997).

“Binge Eating Disorder Comes Out of the Closet: Experts Say
Leading Obesity Factor Has Long Been Overlooked.”Tufts University Diet & Nutrition Letter , 14, no. 11 (Jan.
1997): 4-5.

Eating Disorders Awareness and Prevention. 603 Stewart St.,
Suite 803, Seattle, WA 98101. (206) 382-3587.
National Eating Disorders Organization (NEDO). 6655 South
Yale Ave., Tulsa, OK 74136. (918) 481-4044.
Overeaters Anonymous World Service Office. 6075 Zenith Ct.
NE, Rio Rancho, NM 87124. (505) 891-2664. <http://www.overeatersanonymous.org>.
Paula Anne Ford-MartinKEY TERMS
Bulimia —An eating disorder characterized by

binge eating and inappropriate compensatorybehavior, such as vomiting, misusing laxatives, orexcessive exercise.
Cognitive behavioral therapy —A therapy that
pays particular attention to a patient’s behaviorand thinking processes rather than underlying psy-chological causes of an activity.Biofeedback
Biofeedback, or applied psychophysiological feed-

back, is a patient-guided treatment that teaches an indi-vidual to control muscle tension, pain , body temperature,
brain waves, and other bodily functions and processesthrough relaxation, visualization, and other cognitive con-trol techniques. The name biofeedback refers to the bio-logical signals that are fed back, or returned, to the patientin order for the patient to develop techniques of manipu-lating them.
Purpose

Purpose
Biofeedback has been used to successfully treat a
number of disorders and their symptoms, including tem-
poromandibular joint disorder (TMJ), chronic pain,
irritable bowel syndrome (IBS), Raynaud’s syndrome,
epilepsy, attention-deficit hyperactivity disorder(ADHD ), migraine headaches, anxiety , depression, trau-
matic brain injury, and sleep disorders .
Illnesses that may be triggered at least in part by
stress are also targeted by biofeedback therapy. Certain

types of headaches, high blood pressure, bruxism (teeth
grinding), post-traumatic stress disorder , eating disor-
ders, substance abuse, and some anxiety disorders may
be treated successfully by teaching patients the ability torelax and release both muscle and mental tension.Biofeedback is often just one part of a comprehensivetreatment program for some of these disorders.
NASA has used biofeedback techniques to treat

astronauts who suffer from severe space sickness, duringwhich the autonomic nervous system is disrupted. Scien-tists at the University of Tennessee have adapted thesetechniques to treat individuals suffering from severenausea and vomiting that is also rooted in autonomic
nervous system dysfunction.
Recent research also indicates that biofeedback may
be a useful tool in helping patients with urinary inconti-

nence regain bladder control. Individuals learning pelvic-
floor muscle strengthening exercises can gain better con-trol over these muscles by using biofeedback. Sensors areplaced on the muscles to train the patient where they areand when proper contractions are taking place.
Origins
In 1961, Neal Miller, an experimental psychologist,
suggested that autonomic nervous system responses (for
GALE ENCYCLOPEDIA OF MEDICINE 2 482BiofeedbackGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 482

activity, regional blood flow) could be under voluntarycontrol. As a result of his experiments, he showed thatsuch autonomic processes were controllable. This workled to the creation of biofeedback therapy. Willer’s workwas expanded by other researchers. Thereafter, researchperformed in the 1970s by UCLA researcher Dr. BarrySterman established that both cats and monkeys could betrained to control their brain wave patterns. Sterman thenused his research techniques on human patients withepilepsy,

techniques on human patients withepilepsy, where he was able to reduce seizures by 60%with the use of biofeedback techniques. Throughout the1970s, other researchers published reports of their use ofbiofeedback in the treatment of cardiac arrhythmias ,

headaches, Raynaud’s syndrome, and excess stomachacid, and as a tool for teaching deep relaxation. Since theearly work of Miller and Sterman, biofeedback hasdeveloped into a front-line behavioral treatment for aneven wider range of disorders and symptoms.
During biofeedback, special sensors are placed on

the body. These sensors measure the bodily function thatis causing the patient problem symptoms, such as heartrate, blood pressure, muscle tension (EMG or elec-tromyographic feedback), brain waves (EEC or elec-troencophalographic feedback), respiration, and bodytemperature (thermal feedback), and translates the infor-mation into a visual and/or audible readout, such as apaper tracing, a light display, or a series of beeps.

from the biofeedback monitors, he or she begins to recog-nize what thoughts, fears, and mental images influence hisor her physical reactions. By monitoring this relationshipbetween mind and body, the patient can then use thesesame thoughts and mental images as subtle cues, as theseact as reminders to become deeply relaxed, instead of anx-ious. These reminders also work to manipulate heart beat,brain wave patterns, body temperature, and other bodilyfunctions. This is achieved through relaxation

This is achieved through relaxation exercises,mental imagery, and other cognitive therapy techniques.

As the biofeedback response takes place, patients
can actually see or hear the results of their efforts instant-ly through the sensor readout on the biofeedback equip-ment. Once these techniques are learned and the patientis able to recognize the state of relaxation or visualiza-tion necessary to alleviate symptoms, the biofeedbackequipment itself is no longer needed. The patient thenhas a powerful, portable, and self-administered treatmenttool to deal with problem symptoms.

Biofeedback that specializes in reading and altering
brain waves is sometimes called neurofeedback . The
brain produces four distinct types of brain waves—delta,theta, alpha, and beta—that all operate at a different fre-quency. Delta, the slowest frequency wave, is the brain

wave pattern associated with sleep. Beta waves, whichoccur in a normal, waking state, can range from 12-35Hz. Problems begin to develop when beta wave averagesfall in the low end (underarousal) or the high end (over-arousal) of that spectrum. Underarousal might be presentin conditions such as depression or attention-deficit dis-order, and overarousal may be indicative of an anxietydisorder, obsessive compulsive disorder, or excessivestress. Beta wave neurofeedback focuses on normalizingthat

wave neurofeedback focuses on normalizingthat beta wave pattern to an optimum value of around 14Hz. A second type of neurofeedback, alpha-theta, focus-es on developing the more relaxing alpha (8-13 Hz) andtheta waves (4-9 Hz) that are usually associated withdeep, meditative states, and has been used with somesuccess in substance abuse treatment.

can be useful in treating a variety of disorders that aresuspected or proven to impact brain wave patterns, suchas epilepsy, attention-deficit disorder, migraineheadaches, anxiety, depression, traumatic brain injury,and sleep disorders. The equipment used for neurofeed-back usually uses a monitor as an output device. Themonitor displays specific patterns that the patientattempts to change by producing the appropriate type ofbrain wave. Or, the monitor may reward the patient forproducing the

monitor may reward the patient forproducing the appropriate brain wave by producing apositive reinforcer, or reward. For example, children maybe rewarded with a series of successful moves in a dis-played video game.

GALE ENCYCLOPEDIA OF MEDICINE 2 483Biofeedback
A patient undergoing biofeedback therapy. (Photo
Researchers, Inc. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 483

Depending on the type of biofeedback, individuals
may need up to 30 sessions with a trained professional tolearn the techniques required to control their symptomson a long-term basis. Therapists usually recommend thattheir patients practice both biofeedback and relaxationtechniques on their own at home.
Before initiating biofeedback treatment, the thera-

pist and patient will have an initial consultation to recordthe patients medical history and treatment backgroundand discuss goals for therapy.
Before a neurofeedback session, an EEG is taken
from the patient to determine his or her baseline brain-wave pattern.
Biofeedback typically is performed in a quiet and

relaxed atmosphere with comfortable seating for thepatient. Depending on the type and goals of biofeedbackbeing performed, one or more sensors will be attached tothe patient’s body with conductive gel and/or adhesives.These may include:
• Electromyographic (EMG) sensors. EMG sen-

sors measure electrical activity in the muscles, specifical-ly muscle tension. In treating TMJ or bruxism, these sen-sors would be placed along the muscles of the jaw.Chronic pain might be treated by monitoring electricalenergy in other muscle groups.
• Galvanic skin response (GSR) sensors. These are elec-
trodes placed on the fingers that monitor perspiration,or sweat gland, activity. These may also be called skinconductance level (SCL).

• Temperature sensors. Temperature, or thermal, sensors
measure body temperature and changes in blood flow.
• Electroencephalography (EEG) sensors. These elec-
trodes are applied to the scalp to measure the electricalactivity of the brain, or brain waves.
• Heart rate sensors. A pulse monitor placed on the finger
tip can monitor pulse rate.
• Respiratory sensors. Respiratory sensors monitor oxy-
gen intake and carbon dioxide output.
Individuals who use a pacemaker or other

implantable electrical devices should inform theirbiofeedback therapist before starting treatments, as cer-tain types of biofeedback sensors have the potential tointerfere with these devices.
Biofeedback may not be suitable for some patients.
Patients must be willing to take a very active role in thetreatment process. And because biofeedback focuses

strictly on behavioral change, those patients who wish togain insight into their symptoms by examining their pastmight be better served by psychodynamic therapy.
Biofeedback may also be inappropriate for cogni-
tively impaired individuals, such as those patients withorganic brain disease or a traumatic brain injury, depend-ing on their levels of functioning.
Patients with specific pain symptoms of unknown

origin should undergo a thorough medical examinationbefore starting biofeedback treatments to rule out anyserious underlying disease. Once a diagnosis has beenmade, biofeedback can be used concurrently with con-ventional treatment.
Biofeedback may only be one component of a com-
prehensive treatment plan. For illnesses and symptomsthat are manifested from an organic disease process, suchas cancer or diabetes, biofeedback should be an adjunct

to (complementary to), and not a replacement for, con-ventional medical treatment.
There are no known side effects to properly adminis-
tered biofeedback or neurofeedback sessions.
Preliminary research published in late 1999 indicat-
ed that neurofeedback may be a promising new tool inthe treatment of schizophrenia . Researchers reported

that schizophrenic patients had used neurofeedback tosimulate brain wave patterns that antipsychotic medica-tions produce in the brain. Further research is needed todetermine what impact this may have on treatment forschizophrenia.
The use of biofeedback techniques to treat an array of

disorders has been extensively described in the medical lit-erature. Controlled studies for some applications are limit-ed, such as for the treatment of menopausal symptoms andpremenstrual disorder (PMS). There is also some debateover the effectiveness of biofeedback in ADHD treatment,and the lack of controlled studies on that application. Whilemany therapists, counselors, and mental health profession-als have reported great success with treating their ADHDpatients with neurofeedback

treating their ADHDpatients with neurofeedback techniques, some criticsattribute this positive therapeutic impact to a placebo effect.

There may also be some debate among mental
health professionals as to whether biofeedback should beconsidered a first line treatment for some mental illness-es, and to what degree other treatments, such as medica-tion, should be employed as an adjunct therapy.
GALE ENCYCLOPEDIA OF MEDICINE 2 484BiofeedbackGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 484

Resources
BOOKS
Robbins, Jim. A Symphony in the Brain: The Evolution of the
New Brain Wave Biofeedback. Boston, MA: Atlantic
Monthly Press, 2000.
Burgio, K.L. et al. “Behavioral vs. Drug Treatment for Urge
Urinary Incontinence in Older Women: A randomizedcontrolled trial.” Journal of the American Medical Associ-
ation 280 (Dec. 1998): 1995-2000.
Robbins, Jim. “On the Track with Neurofeedback.” Newsweek
135, no. 25 (June 2000): 76.KEY TERMS

Autonomic nervous system —The part of the ner-
vous system that controls so-called involuntaryfunctions, such as heart rate, salivary gland secre-tion, respiratory function, and pupil dilation.
Bruxism —Habitual, often unconscious, grinding
of the teeth.
Epilepsy —A neurological disorder characterized
by the sudden onset of seizures.
Placebo effect —Placebo effect occurs when a treat-

ment or medication with no known therapeuticvalue (a placebo) is administered to a patient, andthe patient’s symptoms improve. The patientbelieves and expects that the treatment is going towork, so it does. The placebo effect is also a factorto some degree in clinically-effective therapies, andexplains why patients respond better than others totreatment despite similar symptoms and illnesses.
Raynaud’s syndrome —A vascular, or circulatory

system, disorder which is characterized by abnor-mally cold hands and feet. This chilling effect iscaused by constriction of the blood vessels in theextremities, and occurs when the hands and feetare exposed to cold weather. Emotional stress canalso trigger the cold symptoms.
Schizophrenia —Schizophrenia is a psychotic dis-

order that causes distortions in perception (delu-sions and hallucinations), inappropriate moodsand behaviors, and disorganized or incoherentspeech and behavior.
Temporomandibular joint disorder —Inflamma-
tion, irritation, and pain of the jaw caused byimproper opening and closing of the temporo-mandibular joint. Other symptoms include click-ing of the jaw and a limited range of motion.ORGANIZATIONS

The Association for Applied Psychotherapy and Biofeedback.
10200 W. 44th Avenue, Suite 304, Wheat Ridge, CO80033-2840. (303) 422-8436. <http://www.aapb.org
Biofeedback Certification Institute of America.10200 W. 44th
Avenue, Suite 310, Wheat Ridge, CO 80033. (303) 420-2902.
Biopsy seeBone biopsy; Bone marrow

aspiration and biopsy; Brain biopsy;Breast biopsy; Cervical conization; CT-guided biopsy; Endometrial biopsy; Jointbiopsy; Kidney biopsy; Liver biopsy; Lungbiopsy; Lymph node biopsy; Myocardialbiopsy; Pleural biopsy; Prostate biopsy;Skin biopsy; Small intestine biopsy;Thyroid biopsy
Bipolar disorder
Bipolar, or manic-depressive disorder, is a mood dis-

order that causes radical emotional changes and moodswings, from manic highs to depressive lows. The major-ity of bipolar individuals experience alternating episodesof mania and depression.
In the United States alone, bipolar disorder afflicts

almost two million people at an annual cost of over $45billion, according to a report by the National Institutes ofMental Health. The average age of onset of bipolar disor-der is from adolescence through the early twenties. How-ever, because of the complexity of the disorder, a correctdiagnosis can be delayed for several years or more. In asurvey of bipolar patients conducted by the NationalDepressive and Manic Depressive Association(MDMDA), one-half of respondents reported visitingthree or

one-half of respondents reported visitingthree or more professionals before receiving a correctdiagnosis, and over one-third reported a wait of ten yearsor more before they were correctly diagnosed.

The Diagnostic and Statistical Manual of Mental
Disorders, Fourth Edition ( DSM-IV ), the diagnostic stan-
dard for mental health professionals in the United States,defines four separate categories of bipolar disorder: bipo-lar I, bipolar II, cyclothymia, and bipolar not-otherwise-specified (NOS).
GALE ENCYCLOPEDIA OF MEDICINE 2 485Bipolar disorderGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 485

episodes, the “high” of the manic-depressive cycle. Abipolar patient experiencing mania often has feelings ofself-importance, elation, talkativeness, increased socia-bility, and a desire to embark on goal-oriented activities,coupled with the characteristics of irritability, impa-tience, impulsiveness, hyperactivity, and a decreasedneed for sleep. Usually this manic period is followed bya period of depression, although a few bipolar I individu-als may not experience a major depressive

may not experience a major depressive episode.Mixed states, where both manic or hypomanic symptomsand depressive symptoms occur at the same time, alsooccur frequently with bipolar I patients (for example,depression with the racing thoughts of mania). Also, dys-phoric mania is common (mania characterized by angerand irritability).

Bipolar II disorder is characterized by major depres-
sive episodes alternating with episodes of hypomania, amilder form of mania. Bipolar depression may be diffi-cult to distinguish from a unipolar major depressiveepisode. Patients with bipolar depression tend to haveextremely low energy, retarded mental and physicalprocesses, and more profound fatigue (for example,
hypersomnia; a sleep disorder marked by a need forexcessive sleep or sleepiness when awake) than unipolardepressives.

Cyclothymia refers to the cycling of hypomanic
episodes with depression that does not reach major depres-sive proportions. A third of patients with cyclothymia willdevelop bipolar I or II disorder later in life.
A phenomenon known as rapid cycling occurs in up

to 20% of bipolar I and II patients. In rapid cycling,manic and depressive episodes must alternate frequently;at least 4 times in 12 months; to meet the diagnostic defi-nition. In some cases of “ultra-rapid cycling,” the patientmay bounce between manic and depressive states severaltimes within a 24-hour period. This condition is veryhard to distinguish from mixed states.
Bipolar NOS is a category for bipolar states that do

not clearly fit into the bipolar I, II, or cyclothymia diag-noses.
The source of bipolar disorder has not been clearly

defined. Because two-thirds of bipolar patients have afamily history of affective or emotional disorders,researchers have searched for a genetic link to the disor-der. Several studies have uncovered a number of possiblegenetic connections to the predisposition for bipolar dis-order. Another possible biological cause under investiga-tion is the presence of an excessive calcium build-up inthe cells of bipolar patients. Also, dopamine and other

neurochemical transmitters appear to be implicated inbipolar disorder and these are under intense investigation.
Over half of patients diagnosed with bipolar disorder
have a history of substance abuse. There is a high rate ofassociation between cocaine abuse and bipolar disorder.

Some studies have shown up to 30% of abusers meetingthe criteria for bipolar disorder. The emotional and physi-cal highs and lows of cocaine use correspond to themanic depression of the bipolar patient, making the dis-order difficult to diagnosis.
For some bipolar patients, manic and depressive
episodes coincide with seasonal changes. Depressiveepisodes are typical during winter and fall, and manicepisodes are more probable in the spring and summermonths.

Symptoms of bipolar depressive episodes include
low energy levels, feelings of despair, difficulty concen-trating, extreme fatigue, and psychomotor retardation(slowed mental and physical capabilities). Manicepisodes are characterized by feelings of euphoria, lackof inhibitions, racing thoughts, diminished need forsleep, talkativeness, risk taking, and irritability. Inextreme cases, mania can induce hallucinations and
other psychotic symptoms such as grandiose illusions.
Diagnosis

Diagnosis
Bipolar disorder is usually diagnosed and treated by
a psychiatrist and/or a psychologist with medical assis-tance. In addition to an interview, several clinical inven-tories or scales may be used to assess the patient’s mentalstatus and determine the presence of bipolar symptoms.These include the Millon Clinical Multiaxial InventoryIII (MCMI-III), Minnesota Multiphasic Personality
Inventory II (MMPI-2 ), the Internal State Scale (ISS),

the Self-Report Manic Inventory (SRMI), and the YoungMania Rating Scale (YMRS). The tests are verbal and/orwritten and are administered in both hospital and outpa-tient settings.
Psychologists and psychiatrists typically use the cri-
teria listed in the Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV ) as a guide-
line for diagnosis of bipolar disorder and other mentalillnesses. DSM-IV describes a manic episode as an

abnormally elevated or irritable mood lasting a period ofat least one week that is distinguished by at least three ofthe mania symptoms: inflated self-esteem, decreasedneed for sleep, talkativeness, racing thoughts, dis-tractibility, increase in goal-directed activity, or exces-sive involvement in pleasurable activities that have ahigh potential for painful consequences. If the mood of
GALE ENCYCLOPEDIA OF MEDICINE 2 486Bipolar disorderGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 486

the patient is irritable and not elevated, four of the symp-
toms are required.
Although many clinicians find the criteria too rigid,
a hypomanic diagnosis requires a duration of at least fourdays with at least three of the symptoms indicated formanic episodes (four if mood is irritable and not elevat-ed). DSM-IV notes that unlike manic episodes, hypoman-

ic episodes do not cause a marked impairment in socialor occupational functioning, do not require hospitaliza-tion, and do not have psychotic features. In addition,because hypomanic episodes are characterized by highenergy and goal directed activities and often result in apositive outcome, or are perceived in a positive mannerby the patient, bipolar II disorder can go undiagnosed.
Bipolar symptoms often present differently in chil-

dren and adolescents. Manic episodes in these age groupsare typically characterized by more psychotic featuresthan in adults, which may lead to a misdiagnosis of schiz-
ophrenia . Children and adolescents also tend toward irri-

tability and aggressiveness instead of elation. Further,symptoms tend to be chronic, or ongoing, rather thanacute, or episodic. Bipolar children are easily distracted,impulsive, and hyperactive, which can lead to a misdiag-nosis of attention deficit hyperactivity disorder ( ADHD ).
Furthermore, their aggression often leads to violence,which may be misdiagnosed as a conduct disorder .
Substance abuse, thyroid disease, and use of pre-

scription or over-the-counter medication can mask ormimic the presence of bipolar disorder. In cases of sub-stance abuse, the patient must ordinarily undergo a peri-od of detoxification and abstinence before a mood disor-
der is diagnosed and treatment begins.
Treatment
Treatment of bipolar disorder is usually by means of

medication. A combination of mood stabilizing agentswith antidepressants, antipsychotics, and anticonvulsantsis used to regulate manic and depressive episodes.
Mood stabilizing agents such as lithium, carba-
mazepine, and valproate are prescribed to regulate themanic highs and lows of bipolar disorder:
• Lithium (Cibalith-S, Eskalith, Lithane, Lithobid,

Lithonate, Lithotabs) is one of the oldest and most fre-quently prescribed drugs available for the treatment ofbipolar mania and depression. Because the drug takesfour to ten days to reach a therapeutic level in the blood-stream, it is sometimes prescribed in conjunction withneuroleptics and/or benzodiazepines to provide more

immediate relief of a manic episode. Lithium has alsobeen shown to be effective in regulating bipolar depres-sion, but is not recommended for mixed mania. Lithiummay not be an effective long-term treatment option for
rapid cyclers, who typically develop a tolerance for it, ormay not respond to it. Possible side effects of the druginclude weight gain, thirst, nausea, and hand tremors .
Prolonged lithium use may also cause hyperthyroidism
(a disease of the thryoid that is marked by heart palpita-

tions , nervousness, the presence of goiter , sweating,
and a wide array of other symptoms.)
• Carbamazepine (Tegretol, Atretol) is an anticonvulsant
drug usually prescribed in conjunction with other moodstabilizing agents. The drug is often used to treat bipo-lar patients who have not responded well to lithiumtherapy. Blurred vision and abnormal eye movementare two possible side effects of carbamazepine therapy.As of early 1998, carbamazepine did not have an FDA-cleared indication for mania.

• Valproate (divalproex sodium, or Depakote; valproic
acid, or Depakene) is one of the few drugs available thathas been proven effective in treating rapid cycling bipo-lar and mixed states patients. Valproate is prescribedalone or in combination with carbamazepine and/or lithi-um. Stomach cramps, indigestion ,diarrhea , hair loss,
appetite loss, nausea, and unusual weight loss or gain aresome of the common side effects of valproate. Note: val-proate is also approved for the treatment of mania.

Because antidepressants may stimulate manic
episodes in some bipolar patients, their use is typicallyshort-term. Selective serotonin reuptake inhibitors
(SSRIs) or, less often, monoamine oxidase inhibitors
(MAO inhibitors) are prescribed for episodes of bipolardepression. Tricyclic antidepressants used to treat unipo-lar depression may trigger rapid cycling in bipolarpatients and are, therefore, not a preferred treatmentoption for bipolar depression.

• SSRIs, such as fluoxetine (Prozac), sertraline (Zoloft),
and paroxetine (Paxil), regulate depression by regulatinglevels of serotonin, a neurotransmitter. Anxiety , diarrhea,
drowsiness, headache , sweating, nausea, sexual prob-
lems, and insomnia are all possible side effects of SSRIs.
• MAOIs such as tranylcypromine (Parnate) and phenel-

zine (Nardil) block the action of monoamine oxidase(MAO), an enzyme in the central nervous system.Patients taking MAOIs must cut foods high in tyramine(found in aged cheeses and meats) out of their diet toavoid hypotensive side effects.
• Bupropion (Wellbutrin) is a heterocyclic antidepres-

sant. The exact neurochemical mechanism of the drugis not known, but it has been effective in regulatingbipolar depression in some patients. Side effects ofbupropion include agitation, anxiety, confusion, tremor,dry mouth , fast or irregular heartbeat, headache, and
insomnia.
GALE ENCYCLOPEDIA OF MEDICINE 2 487Bipolar disorderGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 487

rate for treating both unipolar and bipolar depression,and mania. However, because of the convenience ofdrug treatment and the stigma sometimes attached toECT therapy, ECT is usually employed after all phar-maceutical treatment options have been explored. ECTis given under anesthesia and patients are given a mus-cle relaxant medication to prevent convulsions. Thetreatment consists of a series of electrical pulses thatmove into the brain through electrodes on the patient’shead. Although the

electrodes on the patient’shead. Although the exact mechanisms behind the suc-cess of ECT therapy are not known, it is believed thatthis electrical current alters the electrochemicalprocesses of the brain, consequently relieving depres-sion. Headaches, muscle soreness, nausea, and confu-sion are possible side effects immediately following anECT procedure. Temporary memory loss has also beenreported in ECT patients. In bipolar patients, ECT isoften used in conjunction with drug therapy.

Adjunct treatments are used in conjunction with a
long-term pharmaceutical treatment plan:
• Long-acting benzodiazepines such as clonazepam (Klon-
apin) and alprazolam (Xanax) are used for rapid treat-ment of manic symptoms to calm and sedate patients untilmania or hypomania have waned and mood stabilizingagents can take effect. Sedation is a common effect, and
clumsiness, lightheadedness, and slurred speech are otherpossible side effects of benzodiazepines.

• Neuroleptics such as chlorpromazine (Thorazine) and
haloperidol (Haldol) are also used to control maniawhile a mood stabilizer such as lithium or valproatetakes effect. Because neuroleptic side effects can besevere (difficulty in speaking or swallowing, paralysis

of the eyes, loss of balance control, muscle spasms,severe restlessness, stiffness of arms and legs, tremorsin fingers and hands, twisting movements of body, andweakness of arms and legs), benzodiazepines are gener-ally preferred over neuroleptics.
• Psychotherapy and counseling. Because bipolar disorder

is thought to be biological in nature, therapy is recom-mended as a companion to, but not a substitute for, phar-maceutical treatment of the disease. Psychotherapy, suchas cognitive-behavioral therapy , can be a useful tool in
helping patients and their families adjust to the disorder,in encouraging compliance to a medication regimen, andin reducing the risk of suicide. Also, educative counsel-ing is recommended for the patient and family.
Calcium channel blockers (nimodipine, or Nimo-

top), typically used to treat angina and hypotension ,h a v e
been found effective, in a few small studies, for treatingrapid cyclers. Calcium channel blockers stop the excesscalcium build up in cells that is thought to be a cause ofbipolar disorder. They are usually used in conjunction with
other drug therapies such as carbamazepine or lithium.
Clozapine (Clozaril) is an atypical antipsychotic

medication used to control manic episodes in patientswho have not responded to typical mood stabilizingagents. The drug has also been a useful prophylactic, orpreventative treatment, in some bipolar patients. Commonside effects of clozapine include tachycardia (rapid heartrate), hypotension, constipation , and weight gain. Agran-

ulocytosis, a potentially serious but reversible conditionin which the white blood cells that typically fight infec-tion in the body are destroyed, is a possible side effect ofclozapine. Patients treated with the drug should undergoweekly blood tests to monitor white blood cell counts.
Risperidone (Risperdal) is an atypical antipsychotic

medication that has been successful in controlling maniain several clinical trials when low doses were adminis-tered. The side effects of risperidone are mild comparedto many other antipsychotics (constipation, coughing,diarrhea, dry mouth, headache, heartburn , increased
length of sleep and dream activity, nausea, runny nose,sore throat , fatigue, and weight gain).
Lamotrigine (Lamictal, or LTG), an anticonvulsant

medication, was found to alleviate manic symptoms in a1997 trial of 75 bipolar patients. The drug was used inconjunction with divalproex (divalproate) and/or lithium.Possible side effects of lamotrigine include skin rash,dizziness , drowsiness, headache, nausea and vomiting .
rTMS, or repeated transcranial magnetic stimulation

is a new and still experimental treatment for the depres-sive phase of bipolar disorder. In rTMS, a large magnet isplaced on the patient’s head and magnetic fields of dif-ferent frequency are generated to stimulate the left frontcortex of the brain. Unlike ECT, rTMS requires no anes-thesia and does not induce seizures.
General recommendations include maintaining a

calm environment, avoiding over stimulation, gettingplenty of rest, regular exercise , and proper diet. Chinese
herbs may soften mood swings. Biofeedback is effective
in helping some patients control symptoms such as irri-tability, poor self control, racing thoughts, and sleepproblems. A diet low in vanadium (a mineral found inmeats and other foods) and high in vitamin C may behelpful in reducing depression.
Prognosis

Prognosis
While most patients will show some positive response
to treatment, response varies widely, from full recovery to acomplete lack of response to all drug and/or ECT therapy.
GALE ENCYCLOPEDIA OF MEDICINE 2 488Bipolar disorderGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 488

maximum benefit for the patient. Bipolar disorder is achronic recurrent illness in over 90% of those afflicted, andone that requires lifelong observation and treatment afterdiagnosis. Patients with untreated or inadequately treatedbipolar disorder have a suicide rate of 15-25% and a nine-year decrease in life expectancy. With proper treatment, thelife expectancy of the bipolar patient will increase by nearlyseven years and work productivity increases by ten years.

The ongoing medical management of bipolar disor-
der is critical to preventing relapse, or recurrence, ofmanic episodes. Even in carefully controlled treatmentprograms, bipolar patients may experience recurringepisodes of the disorder. Patient education in the form ofpsychotherapy or self-help groups is crucial for trainingbipolar patients to recognize signs of mania and depres-sion and to take an active part in their treatment program.
Resources
BOOKS

Resources
BOOKS
American Psychiatric Press, Inc., 1994.KEY TERMS
Affective disorder —An emotional disorder involv-
ing abnormal highs and/or lows in mood. Nowtermed mood disorder.
Anticonvulsant medication —A drug used to pre-

vent convulsions or seizures; often prescribed in thetreatment of epilepsy. Several anticonvulsant med-ications have been found effective in the treatmentof bipolar disorder.
Antipsychotic medication —A drug used to treat
psychotic symptoms, such as delusions or halluci-nations, in which patients are unable to distinguishfantasy from reality.Benzodiazpines —A group of tranquilizers having

sedative, hypnotic, antianxiety, amnestic, anticon-vulsant, and muscle relaxant effects.
DSM-IV —Diagnostic and Statistical Manual of
Mental Disorders, Fourth Edition (DSM-IV). This ref-erence book, published by the American Psychi-atric Association, is the diagnostic standard for mostmental health professionals in the United States.ECT— Electroconvulsive therapy is sometimes used
to treat depression or mania when pharmaceuticaltreatment fails.
Hypomania —A milder form of mania which is

characteristic of bipolar II disorder.
Mixed mania/mixed state —A mental state in which
symptoms of both depression and mania occursimultaneously.
Mania —An elevated or euphoric mood or irritable
state that is characteristic of bipolar I disorder.
Neurotransmitter —A chemical in the brain that

transmits messages between neurons, or nerve cells.Changes in the levels of certain neurotransmitters,such as serotonin, norepinephrine, and dopamine,are thought to be related to bipolar disorder.
Psychomotor retardation —Slowed mental and
physical processes characteristic of a bipolardepressive episode.
Maxmen, Jerrold S. and Nicholas G. Ward. “Mood Disorders.”
In Essential Psychopathology and Its Treatment. 2nd ed.

Whybrow, Peter C. A Mood Apart. New York: Harper Collins,
1997.
Biederman, Joseph A. “Is There a Childhood form of Bipolar
Disorder?” Harvard Mental Health Letter , 13, no. 9 (Mar.
1997): 8.
Bowden, Charles L. “Choosing the Appropriate Therapy for
Bipolar Disorder.” Medscape Mental Health , 2, no. 8
(1997).
Bowden, Charles L. “Update on Bipolar Disorder: Epidemiolo-
gy, Etiology, Diagnosis, and Prognosis.” Medscape Men-
tal Health , 2, no. 6 (1997).

Francis, A., J. P. Docherty, and D. A. Kahn. “The Expert Con-
sensus Guideline Series: Treatment of Bipolar Disorder.”Journal of Clinical Psychiatry , 57, supplement 12A (Nov.
1996): 1-89.
Hirschfeld, Robert “Recent Developments in Clinical Aspects
of Bipolar Disorder.” The Decade of the Brain: A Publica-
tion of the National Alliance for the Mentally Ill 6, no. 2
(Winter 1995).

GALE ENCYCLOPEDIA OF MEDICINE 2 489Bipolar disorderGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 489

National Alliance for the Mentally Ill (NAMI). Colonial Place
Three, 2107 Wilson Blvd., Ste. 300, Arlington, V A 22201-3042. (800) 950-6264. <http://www.nami.org>.
National Depressive and Manic-Depressive Association
(NDMDA). 730 N. Franklin St., Suite 501, Chicago, IL60610. (800) 826-3632. <http://www.ndmda.org>.

Birth control seeCondom; Contraception;
Diaphragm (birth control)
Birth control pills seeOral contraceptives
Birth defects
Birth defects are physical abnormalities that are pre-
sent at birth; they are also called congenital abnormali-ties. More than 3,000 have been identified.
Birth defects are found in 2-3% of all newborn

infants. This rate doubles in the first year, and reaches10% by age five, as more defects become evident and canbe diagnosed. Almost 20% of deaths in newborns arecaused by birth defects.
Abnormalities can occur in any major organ or part

of the body. Major defects are structural abnormalitiesthat affect the way a person looks and require medicaland/or surgical treatment. Minor defects are abnormali-ties that do not cause serious health or social problems.When multiple birth defects occur together and have asimilar cause, they are called syndromes. If two or moredefects tend to appear together but do not share the samecause, they are called associations.
The specific cause of many congenital abnormalities

is unknown, but several factors associated with pregnan-
cyand delivery can increase the risk of birth defects.
Teratogens
Any substance that can cause abnormal develop-

ment of the egg in the mother’s womb is called a terato-gen. In the first two months after conception, the devel-oping organism is called an embryo; developmentalstages from two months to birth are called fetal. Growthis rapid, and each body organ has a critical period inwhich it is especially sensitive to outside influences.About 7% of all congenital defects are caused by expo-sure to teratogens.
DRUGS. Only a few drugs are known to cause birth

defects, but all have the potential to cause harm. Thalido-mide is known to cause defects of the arms and legs; sev-eral other types also cause problems.
• Alcohol. Drinking large amounts of alcohol while preg-
nant causes a cluster of defects called fetal alcohol
syndrome , which include mental retardation , heart
problems, and growth deficiency.
•Antibiotics . Certain antibiotics are known tetratogens.

Tetracycline affects bone growth and discolors theteeth. Drugs used to treat tuberculosis can lead to hear-
ing problems and damage to a nerve in the head (cra-nial). Sulfa drugs are associated with abnormally highlevels of bilirubin in the newborn, which can causedeath .
• Anticonvulsants. Drugs given to prevent seizures can
cause serious problems in the developing fetus, includ-ing mental retardation and slow growth.
• Antipsychotic and antianxiety agents. Several drugs

given for anxiety and mental illness are known to cause
specific defects.
• Antineoplastic agents. Drugs given to treat cancer can
cause major congenital malformations, especially centralnervous system defects. They may also be harmful to thehealth care worker who is giving them while pregnant.
• Hormones. Male hormones may cause masculinization

of a female fetus. A synthetic estrogen (DES) given inthe 1940s and 1950s causes an increased risk of cancerin the adult female children of the mothers whoreceived the drug.
• Recreational drugs. Drugs such as LSD have been asso-
ciated with arm and leg abnormalities and central ner-vous system problems in infants. Crack cocaine has
also been associated with birth defects. Since drugabusers tend to use many drugs and have poor nutri-
tion and prenatal care, it is hard to determine the effects

of individual drugs.
CHEMICALS. Environmental chemicals such as
fungicides, food additives, and pollutants are suspectedof causing birth defects, though this is difficult to prove.
RADIATION. Exposure of the mother to high levels of
radiation can cause small skull size (microcephaly), blind-ness, spina bifida , and cleft palate. How severe the defect
is depends on the duration and timing of the exposure.

GALE ENCYCLOPEDIA OF MEDICINE 2 490Birth defectsGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 490

INFECTIONS. Three viruses are known to harm a
developing baby: rubella , cytomegalovirus (CMV), and
herpes simplex. Toxoplasma gondii, a parasite that can be
contracted from undercooked meat, from dirt, or fromhandling the feces of infected cats, causes serious prob-lems. Untreated syphilis in the mother is also harmful.
Genetic factors
A gene is a tiny, invisible unit containing informa-

tion (DNA) that guides how the body forms and func-tions. Each individual inherits tens of thousands of genesfrom each parent, arranged on 46 chromosomes. Genescontrol all aspects of the body, how it works, and all itsunique characteristics, including eye color and body size.Genes are influenced by chemicals and radiation, butsometimes changes in the genes are unexplained acci-dents. Each child gets half of its genes from each parent.In each pair of genes one will take precedence (domi-nant)

of genes one will take precedence (domi-nant) over the other (recessive) in determining each trait,or characteristic. Birth defects caused by dominant inher-itance include a form of dwarfism called achondropla-

sia; high cholesterol ; Huntington’s disease, a progres-sive nervous system disorder; Marfan syndrome , which
affects connective tissue; some forms of glaucoma , and
polydactyly (extra fingers or toes).
If both parents carry the same recessive gene, they
have a one-in-four chance that the child will inherit thedisease. Recessive diseases are severe and may lead to anearly death. They include sickle cell anemia, a blood disor-der that affects blacks, and Tay-Sachs disease , which

causes mental retardation in people of eastern EuropeanJewish heritage. Two recessive disorders that affect mostlywhites are: cystic fibrosis , a lung and digestive disorder,
and phenylketonuria (PKU), a metabolic disorder. If only

one parent passes along the genes for the disorder, the nor-mal gene received from the other parent will prevent thedisease, but the child will be a carrier. Having the gene isnot harmful to the carrier, but there is the 25% chance ofthe genetic disease showing up in the child of two carriers.
Some disorders are linked to the sex-determining
chromosomes passed along by parents. Hemophilia ,a
condition that prevents blood from clotting, andDuchenne muscular dystrophy , which causes muscle

weakness, are carried on the X chromosome. Genetic
GALE ENCYCLOPEDIA OF MEDICINE 2 491Birth defects
Unknown causes–70%Cytogenetic diseases–4%Drugs, chemicals, radiation–2%Maternal infection–2%Maternal metabolic factors–1%Birth trauma and uterine factors–1%
Hereditary diseases–20%
The specific cause of many birth defects is unknown, but several factors associated with pregnancy and delivery can

increase the risk of birth defects.These factors include exposure to teratogens, drugs and other chemicals, exposure to radi-ation, and infections present in the womb. (Illustration by Electronic Illustrators Group.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 491

defects can also take place when the egg or sperm are
forming if the mother or father passes along some faultygene material. This is more common in older mothers.The most common defect of this kind is Down syn-
drome , a pattern of mental retardation and physical
abnormalities, often including heart defects, caused byinheriting three copies of a chromosome rather than thenormal pair.
A less understood cause of birth defects results from

the interaction of genes from one or both parents plusenvironmental influences. These defects are thought toinclude:
• Cleft lip and palate, which are malformations of the
mouth
• Clubfoot, ankle or foot deformities.• Spina bifida, an open spine caused when the tube that
forms the brain and spinal chord does not close properly.
• Water on the brain ( hydrocephalus ), which causes
brain damage.
•Diabetes mellitus , an abnormality in sugar metabolism
that appears later in life.

• Heart defects.• Some forms of cancer.
A serious illness in the mother, such as an underac-
tive thyroid, or diabetes mellitus, in which her body can-not process sugar, can also cause birth defects in the child.

An abnormal amount of amniotic fluid may indicate orcause birth defects. Amniotic fluid is the liquid that sur-rounds and protects the unborn child in the uterus. Too lit-tle of this fluid can interfere with lung or limb develop-ment. Too much amniotic fluid can accumulate if thefetus has a disorder that interferes with swallowing.
Diagnosis
If there is a family history of birth defects or if the

mother is over 35 years old, then screening tests can bedone during pregnancy to gain information about thehealth of the baby.
• Alpha-fetoprotein test. This is a simple blood test that
measure the level of a substance called alpha-fetopro-tein that is associated with some major birth defects. Anabnormally high or low level may indicate the need forfurther testing.
• Ultrasound. The use of sound waves to examine the

shape, function, and age of the fetus is a common proce-dure. It can also detect many malformations, such asspina bifida, limb defects, and heart and kidney problems.
• Amniocentesis. This test is usually done between the
13th and 15th weeks of pregnancy. A small sample ofamniotic fluid is withdrawn through a thin needleinserted into the mother’s abdomen. Chromosomalanalysis can rule out Down syndrome and other geneticconditions.
• Chorionic villus sampling (CVS). This test can be done

as early as the ninth week of pregnancy to identifychromosome disorders and some genetic conditions. Athin needle is inserted through the abdomen or a slimtube is inserted through the vagina that takes a tiny tis-sue sample for testing.
If a birth defect is suspected after a baby is born,
then confirmation of the diagnosis is very important. Thepatient’s medical records and medical history may holdessential information. A careful physical examination

and laboratory tests should be done. Special diagnostictests can also provide genetic information in some cases.
Treatment
Treatment depends on the type of birth defect and

how serious it is. When an abnormality has been identi-fied before birth, then delivery can be planned at a healthcare facility that is prepared to offer any special careneeded. Some abnormalities can be corrected withsurgery. Experimental procedures have been used suc-cessfully in correcting some defects, like excessive fluidin the brain (hydrocephalus), even before the baby is
GALE ENCYCLOPEDIA OF MEDICINE 2 492Birth defects

Congenital absence of three fingers. Deformities such as
this are usually caused by damage to the developing fetus
in utero. (Photograph by Dr. P . Marazzi, Photo Researchers, Inc.
Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 492

born. Patients with complicated conditions usually need
the help of experienced medical and educational special-ists with an understanding of the disorder.
Prognosis
The prognosis for a disorder varies with the specific
condition.
Pregnant women should eat a nutritious diet. Taking
folic acid supplements before and during pregnancy

reduces the risk of having a baby with serious problemsof the brain or spinal chord (neural tube defects). It isimportant to avoid any teratogen that can harm the devel-oping baby, including alcohol and drugs. When there is afamily history of congenital defects in either parent, thengenetic counseling and testing can help parents plan forKEY TERMS
Chromosome —One of the bodies in the cell
nucleus that carries genes. There are normally 46chromosomes in humans.

Cleft lip and palate —An opening in the lip, the
roof of the mouth (hard palate), or the soft tissue inthe back of the mouth (soft palate).
Embryo —The developing baby from conception
to the end of the second month.Gene —The The functional unit of heredity that
direct all growth and development of an organism.Each human being has over 100,000 genes thatdetermine hair color, body build, and all other traits.
Fetus —In humans, the developing organism from

the end of the eighth week to the moment of birth.
Neural tube defects —A group of birth defects that
affect the backbone and sometimes the spinalchord.
Rubella —A mild, highly contagious childhood ill-
ness caused by a virus; it is also called Germanmeasles. It causes severe birth defects if a preg-nant woman is not immune and gets the illness inthe first three months of pregnancy.
Spina bifida —One of the more common birth

defects in which the backbone never closes.
Trait—A distinguishing feature of an individual.
Virus —A very small organism that causes infec-
tion and needs a living cell to reproduce.future children. Often, counselors can determine the risk

of a genetic condition occurring and the availability oftests for it. Talking to a genetic counselor after a child isborn with a defect can provide parents with informationabout medical management and community resourcesthat are available.
Resources
BOOKS
Jones, Kenneth Lyons. “Dysmorphology.” In Textbook of Pedi-
atrics , ed. Waldo E. Nelson, et al. Philadelphia: W. B.
Lott, Judy Wright. “Fetal Development: Environmental Influ-

ences and Critical Periods.” In Comprehensive Neonatal
Nursing , ed. Carol Kenner, et al. Philadelphia: W. B.
Saunders Co., 1998.
Van Allen, Margot I., and Judith G. Hall. “Congenital Anom-
alies.” In Cecil Textbook of Medicine , ed. J. Claude Bennett
and Fred Plum. Philadelphia: W. B. Saunders Co., 1996.
“Down Syndrome: New Trends in Testing.” Mayo Clinic
Health Newsletter , 15 Apr. 1997.

OTHER
March of Dimes. Public Health Education Information Sheets.
Birthmarks
Birthmarks, including angiomas and vascular mal-

formations, are benign (noncancerous) skin growthscomposed of rapidly growing or poorly formed bloodvessels or lymph vessels. Found at birth (congenital) ordeveloping later in life (acquired) anywhere on the body,they range from faint spots to dark swellings coveringwide areas.
Skin angiomas, also called vascular (pertaining to

vessel) nevi (marks), are composed of blood vessels(hemangiomas) or lymph vessels (lymphangiomas), thatlie beneath the skin’s surface. Hemangiomas, composedof clusters of cells that line the capillaries, the body’ssmallest blood vessels, are found on the face and neck
GALE ENCYCLOPEDIA OF MEDICINE 2 493BirthmarksGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 493

genital hemangiomas, 90% of which appear at birth orwithin the first month of life, grow quickly, and disap-pear over time. They are found in 1-10% of full-terminfants, and 25% of premature infants. About 65% arecapillary hemangiomas (strawberry marks), 15% are cav-ernous (deep) hemangiomas, and the rest are mixtures.Hemangiomas are three times more common in girls.Usually, only one hemangioma is found, in 20% two arefound, while fewer than 5% have three or more. Lym-phangiomas are skin bumps

have three or more. Lym-phangiomas are skin bumps caused by enlarged lymphvessels anywhere on the body.

Vascular malformations are poorly formed blood or
lymph vessels that appear at birth or later in life. Onetype, the salmon patch (nevus simplex), a pink markcomposed of dilated capillaries, is found on the back ofthe neck (also called a stork bite) in 40% of newborns,and on the forehead and eyelids (also called an angel’skiss) in 20%. Stork bites are found in 70% of white and60% of black newborns.
Found in fewer than 1% of newborns, port-wine

stains (nevus flammeus), are vascular malformationscomposed of dilated capillaries in the upper and lowerlayers of the skin of the face, neck, arms, and legs. Oftenpermanent, these flat pink to red marks develop into darkpurple bumpy areas in later life; 85% appear on only oneside of the body.
Acquired hemangiomas include spider angiomas

(nevus araneus), commonly known as spider veins, andcherry angiomas (senile angiomas or Campbell de Mor-gan spots). Found around the eyes, cheekbones, arms,and legs, spider angiomas are red marks formed fromdilated blood vessels. They occur during pregnancy in

70% of white women and 10% of black women, in alco-holics and liver disease patients, and in 50% of children.Cherry angiomas, dilated capillaries found mainly on thetrunk, appear in the 30s, and multiply with aging .
There are no known causes for congenital skin
angiomas; they may be related to an inherited weakness ofvessel walls. Exposure to estrogen causes spider angiomasin pregnant women or those taking oral contraceptives .

Spider angiomas tend to run in families, and may be asso-ciated with liver disease, sun exposure, and trauma.
Hemangiomas
Hemangiomas first appear as single or multiple,
white or pale pink marks, ranging from 2-20 cm (average2-5 cm) in size. Some are symptomless while otherscause pain or bleeding, or interfere with normal function-ing when they are numerous, enlarged, infected, or ulcer-

ated. Vision is affected by large marks on the eyelids. Spi-der and cherry angiomas are unsightly but symptomless.
Each type of hemangioma has a characteristic
appearance:
• Capillary hemangiomas (strawberry marks). These
round, raised marks are bright red and bumpy like astrawberry, and become white or gray when fading.
• Cavernous hemangiomas. These slightly raised, dome-

shaped, blue or purple swellings are sometimes associ-ated with lymphangiomas or involve the soft tissues,bone, or digestive tract.
• Spider angiomas. These are symptomless, reddish blue
marks formed from blood-filled capillaries radiatingaround a central arteriole (small artery) in the shape ofa spider web.
• Cherry angiomas. These harmless, dilated capillaries
appear as tiny, bright red-to-violet colored bumps.
• Lymphangiomas. These dilated lymph vessels form light

pink or yellow cysts (fluid- filled sacs) or swellings.
V ascular malformations
These are faint, flat, pink stains that grow as the

child grows into larger dark red or purple marks. Someare symptomless but others bleed if enlarged or injured.Disfiguring port-wine stains can cause emotional andsocial problems. About 5% of port-wine stains on theforehead and eyelids increase eye pressure due toinvolvement of the eye and surrounding nerves. Abnor-malities of the spinal cord, soft tissues, or bone may beassociated with severe port-wine stains.
Each type has a characteristic appearance:

• Salmon patches. These symptomless, light red-to-pink
marks usually fade with time.
• Port-wine stains. These flat, pink marks progress to
raised, dark red-to-purple grape-like lumps distortingthe facial features, arms, or legs.
Diagnosis
Patients are treated by pediatricians (doctors who

specialize in the care of children), dermatologists (skindisease specialists), plastic surgeons (doctors who spe-cialize in correcting abnormalities of the appearance),and ophthalmologists (eye disease specialists).
Angiomas and vascular malformations are not diffi-
cult to diagnose. The doctor takes a complete medicalhistory and performs a physical examination including
inspection and palpation of the marks. The skin is exam-ined for discoloration, scarring, bleeding, infection, or

GALE ENCYCLOPEDIA OF MEDICINE 2 494BirthmarksGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 494

ulceration. The type, location, size, number, and severity
of the marks are recorded. The doctor may empty themark of blood by gentle pressure. Biopsies or specializedx rays or scans of the abnormal vessels and their sur-rounding areas may be performed. Patients with port-wine stains near the eye may require skull x rays ,com-
puted tomography scans , and vision and central ner-
vous system tests. Most insurance plans pay for diagno-sis and treatment of these conditions.
Treatment

Treatment
Treatment choices for skin angiomas and vascular
malformations depend on their type, location, and severity,and whether they cause symptoms, pain, or disfigurement.
Watchful waiting
No treatment is given, but the mark is regularly exam-
ined. This continues until the mark disappears, or requirestreatment. This approach is particularly appropriate for thetreatment of hemangiomas, which often do not requiretreatment, since they eventually shrink by themselves.
Drugs

Drugs
CORTICOSTEROIDS. Daily doses of the anti-inflam-
matory drugs prednisone or prednisolone are given for upto 2 months with gradual reduction of the dose. The marksbegin to subside within 7-10 days, but may take up to 2months to fully disappear. If no response is seen in 2weeks, the drug is discontinued. Treatment may be repeat-ed. Side effects include growth retardation, increased bloodpressure and blood sugar, cataracts , glandular disorders,

and infection. The corticosteroids triamcinolone acetate
and betamethasone sodium phosphate or acetate are inject-ed directly into the marks with a response usually achievedwithin a week; additional injections are given in 4-6 weeks.Side effects include tissue damage at the injection site.
INTERFERON ALPHA-2A. This drug reduces cell

growth, and is used for vascular marks that affect vision,and that are unresponsive to corticosteroids. Given in dailyinjections under the skin, a response rate of 50% isachieved after about 7 months. Side effects include fever ,
chills, muscle and joint pain, vision disorders, low whiteand red blood cell counts, fatigue , elevated liver enzymes,
nausea, blood clotting problems, and nerve damage.
ANTIBIOTICS. Oral or topical (applied to the skin)

antibiotics are prescribed for infected marks.
Surgery
LASER SURGERY. Lasers create intense heat that
destroys abnormal blood vessels beneath the skin, with-out damaging normal skin. Two types of lasers are used:

the flashlamp-pulsed dye laser (FPDL) and the neodymi-um:YAG (Nd:YAG) laser. The FPDL, used mainly forstrawberry marks and port-wine stains, penetrates to adepth of 1.8 mm and causes little scarring, while theNd:YAG laser penetrates to a depth of 6 mm, and is usedto treat deep hemangiomas. Laser surgery is not usually

painful, but can be uncomfortable. Anesthetic cream isused for FPDL treatment. Treatment with the Nd:YAGlaser requires local or general anesthesia. Children areusually sedated or anesthetized. Healing occurs within 2weeks. Side effects include bruising, skin discoloration,swelling, crusting, and minor bleeding.
SURGICAL EXCISION. Under local or general anes-

thesia, the skin is cut with a surgical instrument, and vas-cular marks or their scars are removed. The cut isrepaired with stitches or skin clips.
CRYOSURGERY. Vascular marks are frozen with an
extremely cold substance sprayed onto the skin. Wounds
heal with minimal scarring.
ELECTRODESICCATION. Affected vessels are des-
troyed with the current from an electric needle.
These include:

• Sclerotherapy. Injection of a special solution causes
blood clotting and shrinkage with little scarring. Sideeffects include stinging, swelling, bruising, scarring,muscle cramping, and allergic reactions. This treatmentis used most commonly for spider angiomas.
• Embolization. Material injected into the vessel blocks
blood flow which helps control blood loss during orreduces the size of inoperable growths. A serious side

GALE ENCYCLOPEDIA OF MEDICINE 2 495Birthmarks
A fading capillary hemangioma on the nose of a child. (Pho-
tograph by Dr. P . Marazzi, Custom Medical Stock Photo. Repro-duced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 495

effect, stroke , can occur if a major blood vessel
becomes blocked.
• Make-up. Special brands are designed to cover birth-
marks (Covermark or Dermablend).
• Cleaning and compression. Bleeding marks are cleaned
with soap and water or hydrogen peroxide, and com-pressed with a sterile bandage for 5-10 minutes.
Alternative treatments for strengthening weak blood

vessels include eating high-fiber foods and those con-taining bioflavonoids, including citrus fruit, blueberries,and cherries, supplementing the diet with vitamin C, andtaking the herbs, ginkgo ( Ginkgo biloba ) and bilberry
(Vaccinium myrtillus .)
Prognosis
The various types of birthmarks have different prog-
noses:
• Capillary hemangiomas. Fewer than 10% require treat-

ment. Without treatment, 50% disappear by age 5, 70%by age 7, and 90% by age 9. No skin changes are foundin half while others have some discoloration, scarring,or wrinkling. From 30-90% respond to oral corticos-KEY TERMS
Angioma —A benign skin tumor composed of
rapidly growing, small blood or lymph vessels.
Capillaries —The smallest blood vessels, they con-
nect the arteries and veins.
Corticosteroids —Drugs that fight inflammation.
Hemangioma —A benign skin tumor composed of

abnormal blood vessels.
Lymph vessels —Part of the lymphatic system,
these vessels connect lymph capillaries with thelymph nodes; they carry lymph, a thin, wateryfluid resembling blood plasma and containingwhite blood cells.
Lymphangioma —A benign skin tumor composed
of abnormal lymph vessels.
Nevus —A mark on the skin.
Ulcer —A red, shallow sore on the skin.
Vascular malformation —A poorly formed blood

or lymph vessels.teroids, and 45% respond to injected corticosteroids;
50% respond to interferon Alpha-2a. About 60%improve after laser surgery.
• Cavernous hemangiomas. Some do not disappear and
some are complicated by ulceration or infection. About75% respond to Nd:YAG laser surgery but have scar-ring. Severe marks respond to oral corticosteroids, butsome require excision.
• Spider angiomas. These fade following childbirth and

in children, but may recur. About 90% respond to scle-rotherapy, electrodesiccation, or laser therapy.
• Cherry angiomas. These are easily removed by elec-
trodesiccation.
• Lymphangiomas. These require surgery.
• Salmon patches. Eyelid marks disappear by 6-12 months
of age, and forehead marks fade by age 6; however, 50%of stork bites on the neck persist into adulthood.
• Port-wine stains. Some flat birthmarks are easily cov-

ered with make-up. Treatment during infancy or child-hood improves results. About 95% of the stains respondto FPDL surgery with minimal scarring; 25% will com-pletely and 70% will partially disappear. For unknownreasons, 5% show no improvement.
Congenital hemangiomas or vascular malformations
cannot be prevented, but spider angiomas may be pre-vented by exercise , weight control, and a high-fiber diet,
as well as avoidance of sun exposure, alcohol drinking,or wearing tight hosiery.

Resources
BOOKS
Fitzpatrick, Thomas B., et al. “Benign Neoplasms and Hyper-
plasias. Disorders of the Blood Vessels.” In Color Atlas
and Synopsis of Clinical Dermatology. Common and Seri-ous Diseases , ed. Martin J. Wonsiewicz, et al. New York:
Lookingbill, Donald P., and James G. Marks. “Dermal and
Subcutaneous Growths.” In Principles of Dermatology.

Philadelphia: W. B. Saunders Co., 1993.
Errickson, Carla V ., and Nancy R. Matus. “Skin Disorders of
Pregnancy.” American Family Physician 15 (Feb. 1994):
605-610.
Morelli, Joseph G., et al. “Initial Lesion Size as a Predictive
Factor in Determining the Response of Port-Wine Stainsin Children Treated with the Pulse Dye Laser.” Archives of
Pediatrics and Adolescent Medicine (Oct. 1995): 1142-
1145.

1145.
GALE ENCYCLOPEDIA OF MEDICINE 2 496BirthmarksGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 496

Nanda, Vandana, S. “Management of Capillary Heman-
giomas.” The Western Journal of Medicine (Apr. 1994):
364.
Tanner, J. Lane, Martha P. Dechert, and Ilona J. Frieden.
“Growing Up With a Facial Hemangioma: Parent andChild Coping and Adaptation.” Pediatrics (Mar. 1998):
446-452.
Vander Schaff, Rachelle. “Lasers Zap Strawberry Birthmarks.”
Parents , Oct. 1997, 37.
Wirth Fern A., and Mark H. Lowitt. “Diagnosis and Treatment
of Cutaneous Vascular Lesions.” American Family Physi-

cian 15 (Feb. 1998): 765-773.
American Academy of Pediatrics. 141 Northwest Point Boule-
vard, Elk Grove Village, IL 60007-1098. (847) 434-4000.<http://www.aap.org>.
Congenital Nevus Support Group. 1400 South Joyce St., Num-
ber C-1201, Arlington, V A 22202. (703) 920-3249.
National Congenital Port Wine Stain Foundation. 123 East

63rd St., New York, NY 10021. (516) 867-5137.
Bismuth subsalicylate seeAntidiarrheal drugs
Bites and stings
Humans can be injured by the bites or stings of
many kinds of animals, including mammals such asdogs, cats, and fellow humans; arthropods such as spi-ders, bees, and wasps; snakes; and marine animals suchas jellyfish and stingrays.
Mammals
DOGS. In the United States, where the dog popula-

tion exceeds 50 million, dogs surpass all other mammalsin the number of bites inflicted on humans. However,most dog-bite injuries are minor. A telephone survey ofU.S. households conducted in 1994 led researchers toestimate that 3,737,000 dog bites not requiring medicalattention occurred in the United States that year, versus757,000 that did require medical treatment. Studies alsoshow that most dog bites are from pets or other dogsknown to the bitten person, that males are more likelythan

the bitten person, that males are more likelythan females to be bitten, and that children face a greaterrisk than adults. Each year, about 10-20 Americans,mostly children under 10 years of age, are killed by dogs.

room visits annually throughout the United States. Morethan half of the bites seen by emergency departmentsoccur at home. Children under 10 years old, especiallyboys between 5 and 9 years of age, are more likely thanolder people to visit an emergency room for bite treat-ment. Children under 10 years old were also much moreliable to be bitten on the face, neck, and head. Nearly allof the injuries suffered by people seeking treatment inemergency rooms were of “low severity,” and most weretreated

were of “low severity,” and most weretreated and released without being admitted to hospital orsent to another facility. Many of the bites resulted frompeople attempting to break up fights between animals.

CATS. Although cats are found in nearly a third of
U.S. households, cat bites are far less common than dogbites. According to one study, cats inflict perhaps400,000 harmful bites in the United States each year. Thetissue damage caused by cat bites is usually limited, butthey carry a high risk of infection. Whereas the infectionrate for dog bite injuries is 15-20%, the infection rate forcat bites is 30-40%. A typical person who has been bittenis a young girl playing with a pet.

HUMANS. Bites from mammals other than dogs and
cats are uncommon, with one exception—human bites.There are approximately 70,000 human bites each yearin the United States. Because the human mouth containsa multitude of potentially harmful microorganisms,human bites are more infectious than those of most otheranimals.
Arthropods
Arthropods are invertebrates belonging to the phy-

lum Arthropoda, which includes insects, arachnids, crus-taceans, and other subgroups. There are more than700,000 species in all. The list of arthropods that bite orsting humans is extensive and includes lice, bedbugs,fleas, mosquitoes, black flies, ants, chiggers, ticks, cen-tipedes, scorpions, and other species. Spiders, bees, andwasps are the three kinds of arthropod that most oftenbite people.
SPIDERS. In the United States, only two kinds of ven-

omous spider are truly dangerous: widow spiders andbrown (violin or fiddle) spiders. The black widow, whichis found in every state but Alaska, is probably the mostnotorious widow spider. It prefers dark, dry places such asbarns, garages, and outhouses, and also lives under rocksand logs. Disturbing a female black widow or its webmay provoke a bite. Brown spiders also prefer shelteredplaces, including clothing, and may bite if disturbed.

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defend their nests or if they are disturbed. Species com-mon to the United States include honeybees, bumble-bees, yellow jackets, bald-faced hornets, brown hornets,and paper wasps. Of note are also Africanized beespecies, also called “killer bees” that are now found inthe United States since 1990. More than fifty Americansdie each year after being stung by a bee, wasp, or ant.Almost all of those deaths are the result of allergic reac-tions, and not of exposure to the venom itself.
Snakes

Snakes
There are 20 species of venomous snakes in the
United States. These snakes are found in every stateexcept Maine, Alaska, and Hawaii. Each year about8,000 Americans receive a venomous snakebite, but nomore than about 15 die, mostly from rattlesnake bites.
The venomous snakes of the United States are divid-

ed into two families, the Crotalidae (pit vipers) and theElapidae. Pit vipers, named after the small heat-sensingpit that lies between each eye and nostril, are responsiblefor about 99% of the venomous snakebites suffered byAmericans. Rattlesnakes, copperheads, and cottonmouths(also called water moccasins) are pit vipers. This familyof snakes delivers its venom through two long, hingedfangs in the upper jaw. Some pit vipers carry a potentvenom that can threaten the brain and spinal cord.

that can threaten the brain and spinal cord. Thevenom of others, such as the copperheads, is less harmful.

The Elapidae family includes two kinds of ven-
omous coral snakes indigenous to the southern and west-ern states. Because coral snakes are bashful creaturesthat come out only at night, they almost never bitehumans, and are responsible for approximately 25 bites ayear in the United States. Coral snakes also have shortfangs and a small mouth, which lowers the risk of a biteactually forcing venom into a person’s body. However,their venom is quite poisonous.
Marine animals

Several varieties of marine animal may bite or sting.
Jellyfish and stingrays are two kinds that pose a threat topeople who live or vacation in coastal communities.
Mammals
DOGS. A typical dog bite results in a laceration, tear,
puncture, or crush injury. Bites from large, powerful dogsmay even cause fractures and dangerous internal
injuries. Also, dogs trained to attack may bite repeatedlyduring a single episode. Infected bites usually cause pain,

cellulitis (inflammation of the connective tissues), and apus-filled discharge at the wound site within 8-24 hours.
Most infections are confined to the wound site, but manyof the microorganisms in the mouths of dogs can causesystemic and possibly life-threatening infections. Exam-ples are bacteremia and meningitis , especially severe in
people diagnosed with acquired immunodeficiency syn-
drome ( AIDS ) or other health condition that increases

their susceptibility to infection. Rabies is rare among pet
dogs in the United States, most of which have been vacci-nated against the disease. Tetanus is also rare but can be
transmitted by a dog bite if the victim is not immunized.
CATS. The mouths of cats and dogs contain many of
the same microorganisms. Cat scratches and bites arealso capable of transmitting the Bartonella henselae bac-
terium, which can lead to cat-scratch disease ,a n
unpleasant but usually not life-threatening illness.

Sharp cat teeth typically leave behind a deep puncturewound that can reach muscles, tendons, and bones, whichare vulnerable to infection because of their comparativelypoor blood supply. This is why cat bites are much morelikely to become infected than dog bites. Also, people areless inclined to view cat bites as dangerous requiringimmediate attention; the risk that infection has set in bythe time a medical professional is consulted is thus greater.

HUMANS. Humans bites result from fights, sexual
activity, medical and dental treatment, and seizures. Bitesalso raise the possibility of spousal or child abuse . Chil-
dren often bite other children, but those bites are hardlyever severe. Human bites are capable of transmitting awide range of dangerous diseases, including hepatitis B ,
syphilis , and tuberculosis .
Human bites fall into two categories: occlusional

(true) bites and clenched-fist injuries. The former presenta lower risk of infection. The latter, which are very infec-tious and can permanently damage the hand, usuallyresult from a fist hitting teeth during a fight. People oftenwait before seeking treatment for a clenched-fist injury,with the result that about half of such injuries are infect-ed by the time they are seen by a medical professional.

bite, nor do they feel the bite as it occurs. The first (andpossibly only) evidence that a person has been bitten maybe a mild swelling of the injured area and two red punc-ture marks. Within a short time, however, some victimsbegin to experience severe muscle cramps and rigidity ofthe abdominal muscles. Other possible symptoms includeexcessive sweating, nausea, vomiting, headaches, andvertigo as well as breathing, vision, and speech problems.

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A brown spider’s bite can lead to necrotic arachni-
dism, in which the tissue in an area of up to several inch-es around the bite becomes necrotic (dies), producing anopen sore that can take months or years to disappear. Inmost cases, however, the bite simply produces a hard,painful, itchy, and discolored area that heals withouttreatment in 2-3 days. The bite may also be accompaniedby a fever , chills, edema (an accumulation of excess tis-
sue fluid), nausea and vomiting ,dizziness , muscle and

joint pain, and a rash.
BEES AND WASPS. The familiar symptoms of bee
and wasp stings include pain, redness, swelling, and itch-iness in the area of the sting. Multiple stings can havemuch more severe consequences, such as anaphylaxis ,a
life-threatening allergic reaction that occurs in hypersen-sitive persons.
Snakes
Venomous pit viper bites usually begin to swell

within 10 minutes and sometimes are painful. Othersymptoms include skin blisters and discoloration, weak-ness, sweating, nausea, faintness, dizziness, bruising, andtender lymph nodes. Severe poisoning can also lead to
tingling in the scalp, fingers, and toes, muscle contrac-tions, an elevated heart rate, rapid breathing, large dropsin body temperature and blood pressure, vomiting ofblood, and coma .

Many pit viper and coral snake bites (20-60%) fail to
poison (envenomate) their victim, or introduce only asmall amount of venom into the victim’s body. Thewounds , however, can still become infected by the harm-
ful microorganisms that snakes carry in their mouths.
Coral snake bites are painful but may be hard to see.

One to seven hours after the bite, a bitten person begins toexperience the effects of the venom, which include tinglingat the wound site, weakness, nausea, vomiting, excessivesalivation, and irrational behavior. Major nerves of thebody can become paralyzed for 6-14 days, causing doublevision, difficulty swallowing and speaking, respiratory
failure , and other problems. Six to eight weeks may be
needed before normal muscular strength is regained.

JELLYFISH. Jellyfish venom is delivered by barbs
called nematocysts, which are located on the creature’stentacles and penetrate the skin of people who brush upagainst them. Instantly painful and itchy red lesions usu-ally result. The pain can continue up to 48 hours. Severecases may lead to skin necrosis, muscle spasms and
cramps , vomiting, nausea, diarrhea , headaches, exces-sive sweating, and other symptoms. In rare instances,
cardiorespiratory failure may also occur.

STINGRAYS. Tail spines are the delivery mechanism

for stingray venom. Deep puncture wounds result that cancause an infection if pieces of spine become embedded inthe wound. A typical stingray injury scenario involves aperson who inadvertently steps on a resting stingray and islashed in the ankle by its tail. Stingray venom producesimmediate, excruciating pain that lasts several hours.Sometimes the victim suffers a severe reaction, includingvomiting, diarrhea, hemorrhage (bleeding), a drop in bloodpressure, and cardiac arrhythmia (disordered

Diagnosis
Mammals
DOGS. Gathering information on the circumstances

of a dog attack is a crucial part of treatment. Medicalprofessionals need to know when the attack occurred (thechances of infection increase dramatically if the woundhas been left untreated for more than eight hours) andwhat led to the attack (unprovoked attacks are more like-ly to be associated with rabies). A person’s general healthmust also be assessed, including the tetanus immuniza-tion history if any, as well as information concerningpossible allergies to medication and pre-existing

problems that may increase the risk of infection.
A physical examination requires careful scrutiny of

the wound, with special attention to possible bone, joint,ligament, muscle, tendon, nerve, or blood-vessel damagecaused by deep punctures or severe crush injuries. Seri-ous hand injuries should be evaluated by a specializedsurgeon. Most of the time, laboratory tests for identifyingthe microorganisms in bite wounds are performed ifinfection is present. X rays and other diagnostic proce-dures may also be necessary.
GALE ENCYCLOPEDIA OF MEDICINE 2 499Bites and stings

An insect bite caused this person’s lower lip to swell. (Cus-
tom Medical Stock Photo. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 499

CATS. The diagnostic procedures used for dog bites
also apply to cat bites.
HUMANS. Testing the blood of a person who has

been bitten for immunity to hepatitis B and other dis-eases is always necessary after a human bite. Ideally, thebiter should be tested as well for the presence of trans-missible disease. Clenched-fist injuries often requireevaluation by a hand surgeon or orthopedist. Becausemany people will deny having been in a fight, medicalprofessionals usually consider lacerations over the fourthand fifth knuckles—the typical result of a clenched-fistinjury—to be evidence of a bite wound. Medical

be evidence of a bite wound. Medical profes-sionals also look for indications of spousal or childabuse when evaluating human bites.

SPIDERS. Because bites from widow spiders and
brown spiders require different treatments, capturing andidentifying the spider helps to establish diagnosis.
Snakes
Diagnosis relies on a physical examination of the
victim, information about the circumstances of the bite,and a look at the snake itself (if it can safely be killed andbrought in for identification). Blood tests and urinalysis

supply important data on the victim’s condition. Chest x-rays and electrocardiography (a procedure for measur-
ing heart activity) may also be necessary.
Treatment
Mammals
DOGS. Minor dog bites can be treated at home. The
American Academy of Family Physicians recommendsgently washing the wound with soap and water and thenapplying pressure to the injured area with a clean towel

to stop the bleeding. The next step is to apply antibioticointment and a sterile bandage to the wound. To reduceswelling and fend off infection, ice should be applied andthe injured area kept elevated above the level of the heart.The wound should be cleaned and covered with ointmenttwice a day until it heals.
Any dog bite that does not stop bleeding after 15

minutes of pressure must be seen by a medical profes-sional. The same is true for bites that are deep or gaping;for bites to the head, hands, or feet; and for bites thatmay have broken a bone, damaged nerves, or caused amajor injury of another kind. Bite victims must alsowatch for infection. A fever is one sign of infection, asare redness, swelling, warmth, increased tenderness, andpus at the wound site. Diabetics, people with AIDS orcancer , individuals who have not had a tetanus shot in

five years, and anyone else who has a medical problemthat can increase susceptibility to infection should seekmedical treatment no matter how minor the bite appears.
Medical treatment of dog bites involves washing the

wound with an anti-infective solution. Removal of deadand damaged tissue (under local, regional, or generalanesthetic) may be required after the wound has beenwashed, and any person whose tetanus shots are not up todate should receive a booster injection. Some wounds areleft open and allowed to heal on their own, while othersrequire stitches (stitching may be delayed a few days ifinfection is a concern). Many emergency departmentsprescribe antibiotics for all people with dog bites, but

some researchers suggest that antibiotics are usuallyunnecessary and should be limited to those whoseinjuries or other health problems make them likely candi-dates for infection. A follow-up visit after one or twodays is generally required for anyone who has receivedbite treatment.
CATS. Because of the high risk of infection, people

who are bitten by a cat should always see a doctor. Catscratches do not require professional medical treatmentunless the wound appears infected or the scratched per-son has a weakened immune system.
Medical treatment for cat bites generally follows the
procedures used for dog bites. Experts advise, however,that cat-bite wounds should always be left open to pre-vent infection. Persons who have been bitten by cats gen-erally receive antibiotics as a preventive measure.

HUMANS. Human bites should always be examined
by a doctor. Such bites are usually treated with antibi-otics and left open because of the high risk of infection.A person who has been bitten may also require immu-nization against hepatitis B and other diseases. Persons
GALE ENCYCLOPEDIA OF MEDICINE 2 500Bites and stings
A close-up view of lacerations on the shin of an adult
woman inflicted by a Rottweiler dog. (Custom Medical Stock

Photo. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 500

who are being treated for a clenched-fist injury will
require a daily follow-up examination for 3-5 days.
SPIDERS. No spider bite should be ignored. The anti-
dote for severe widow spider bites is a substance calledantivenin, which contains antibodies taken from theblood serum of horses injected with spider venom. Doc-tors exercise caution in using antivenin, however,
because it can trigger anaphylactic shock , a potentially
deadly (though treatable) allergic reaction, and serum

sickness , an inflammatory response that can give rise to
joint pain, a fever, rashes , and other unpleasant, though
rarely serious, consequences.
An antivenin for brown spider bites exists as well,
but it is not yet available in the United States. The drugdapsone, used to treat leprosy , can sometimes stop the
tissue death associated with a brown spider bite. Necrot-
ic areas may need debridement (removal of dead and
damaged tissue) and skin grafts. Pain medications, anti-

histamines , antibiotics, and tetanus shots are a few of the
other treatments that are sometimes necessary after a bitefrom a brown spider or widow spider.
BEES AND WASPS. Most stings can be treated at
home. A stinger that is stuck in the skin can be scrapedoff with a blade, fingernail, credit card, or piece of paper(using tweezers may push more venom out of the venomsac and into the wound). The area should be cleaned andcovered with an ice pack. Aspirin and other pain med-

ications, oral antihistamines, and calamine lotion aregood for treating minor symptoms. Putting meat tender-izer on the wound has no effect.
Persons who have been stung and experience an

allergic reaction, or who are at risk due to their medicalhistory, require immediate medical attention. The dangersigns, which usually begin 10 minutes after an individualis stung (though possibly not for several hours), includenausea, faintness, chest pain, abdominal cramps, diar-rhea, and difficulty swallowing or breathing.
Snakes
Although most snakes are not venomous, any

snakebite should immediately be examined at a hospital.While waiting for emergency help to arrive, the victimshould wash the wound site with soap and water, andthen keep the injured area still and at a level lower thanthe heart. Ice should never be used on the wound site norshould attempts be made to suck out the venom. Makinga cut at the wound site is also dangerous. It is importantto stay calm and wait for emergency medical aid if it canarrive quickly. Otherwise, the victim should

canarrive quickly. Otherwise, the victim should proceeddirectly to a hospital.

When the victim arrives at a hospital, the medical
staff must determine whether the bite was inflicted by avenomous snake and, if so, whether envenomationoccurred and how much venom the person has received.
GALE ENCYCLOPEDIA OF MEDICINE 2 501Bites and stings
Triangular headPit
Profile and top views of typically nonpoisonous and poisonous snakes. Characteristic triangular head and pits on the side of

the head are indicative of poisonous pit vipers found in the United States. (Illustration by Argosy Inc.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 501

Patients may develop low blood pressure, abnormal
blood clotting, or severe pain, all of which requireaggressive treatment. Fortunately, the effects of somesnakebites can be counteracted with antivenin. Minor rat-tlesnake envenomations can be successfully treated with-out antivenin, as can copperhead and water-moccasinbites. However, coral snake envenomations and the moredangerous rattlesnake envenomations require antivenin,sometimes in large amounts. Other treatment measures

include antibiotics to prevent infection and a tetanusbooster injection.
JELLYFISH. Vinegar and other acidic substances are
used to neutralize jellyfish nematocysts still clinging to
GALE ENCYCLOPEDIA OF MEDICINE 2 502Bites and stings
Yellow jacket
Paper waspBlack
widow
spider
(underside)Brown
recluse
spiderLouse
Hornet
Fire antHoney bee
Types of spiders and insects that bite and sting. (Illustration by Argosy Inc.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 502

the skin, which are then scraped off. Anesthetic oint-
ments, antihistamine creams, and steroid lotions appliedto the skin are sometimes beneficial. Other measuresmay be necessary to counter the many harmful effects ofjellyfish stings, which, if severe, require emergency med-ical care.
STINGRAYS. Stingray wounds should be washed

with saltwater and then soaked in very hot water for 30-90 minutes to neutralize the venom. Afterwards, thewound should be examined by a doctor to ensure that nopieces of spine remain.
Several alternative self-care approaches are used to
treat minor bee, wasp, and other arthropod stings, includ-ing aromatherapy ,ayurvedic medicine ,flower reme-
dies, herbs, homeopathy , and nutritional therapy.
Prognosis
Mammals

Prognosis
Mammals
Prompt treatment and recognizing that even appar-
ently minor bites can have serious consequences are thekeys to a good outcome after a mammal bite. Infectedbites can be fatal if neglected. Surgery and hospitaliza-tion may be needed for severe bites.
SPIDERS. Even without treatment, adults usually

recover from black widow bites after 2-3 days. Thosemost at risk of dying are very young children, the elderly,and people with high blood pressure. In the case ofbrown spider bites, the risk of death is greatest for chil-dren, though rare.
BEES AND WASPS. The pain and other symptoms of a
bee or wasp sting normally fade away after a few hours.People who are allergic to such stings, however, canexperience severe and occasionally fatal anaphylaxis.

Snakes
A snakebite victim’s chances of survival are excel-
lent if medical aid is obtained in time. Some bites, how-ever, result in amputation , permanent deformity, or loss
of function in the injured area.
STINGRAYS. Stingray venom kills its human victims
on rare occasions.Prevention
Mammals
DOGS. The risk of a dog bite injury can be reduced

by avoiding sick or stray dogs, staying away from dog-fights (people often get bitten when they try to separate theanimals), and not behaving in ways that might provoke orupset dogs, such as wrestling with them or bothering themwhile they are sleeping, eating, or looking after their pup-pies. Special precautions need to be taken around infantsand young children, who must never be left alone with adog. Pit bulls, rottweilers, and German shepherds (respon-sible for nearly half of all fatal dog

(respon-sible for nearly half of all fatal dog attacks in the UnitedStates in 1997-2000) are potentially dangerous pets inhouseholds where children live or visit. For all breeds ofdog, obedience training as well as spaying or neuteringlessen the chances of aggressive behavior.

CATS. Prevention involves warning children to stay
away from strange cats and to avoid rough play and otherbehavior that can anger cats and cause them to bite.
SPIDERS. Common-sense precautions include clear-
ing webs out of garages, outhouses, and other placesfavored by venomous spiders; keeping one’s hands awayfrom places where spiders may be lurking; and, whencamping or vacationing, checking clothing, shoes, andsleeping areas.
BEES AND WASPS. When possible, avoid the nests of

bees and wasps and do not eat sweet food or wear brightclothing, perfumes, or cosmetics that attract bees andwasps.
Emergency medical kits containing self-administra-
ble epinephrine to counter anaphylactic shock are avail-able for allergic people and should be carried by them atall times. People who suspect they are allergic shouldconsult an allergist about shots that can reduce reactionsto bee and wasp venom.
Snakes

mowing the lawn, keeping hedges trimmed, and remov-ing brush from the yard also discourages snakes from liv-ing close to human dwellings. Tongs should be used tomove brush, lumber, and firewood, to avoid exposingone’s hands to snakes that might be lying underneath.Similarly, golfers should never use their hands to retrievegolf balls from a water hole, since snakes can be hidingin the rocks and weeds. Caution is also necessary whenwalking through weedy or grassy areas, and childrenshould be

weedy or grassy areas, and childrenshould be prevented from playing in weedy, vacant lots

GALE ENCYCLOPEDIA OF MEDICINE 2 503Bites and stingsGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 503

and other places where snakes may live. Leather boots
and long pants offer hikers and campers some protectionfrom bites. Approaching a snake, even a dead one, can bedangerous, for the venom of recently killed snakes maystill be active.
JELLYFISH. Prevention of jellyfish stings includes

obeying posted warning signs at the beach. Also, jelly-fish tentacles may be transparent and up to 120 ft (36.5m) long, therefore great caution must be exercised when-ever a jellyfish is sighted nearby.
STINGRAYS. Shuffling while walking through shal-
low areas that may be inhabited by stingrays will disturbthe water, causing the animal to move before it can bestepped on.
Resources
BOOKS
Holve, Steve. “Envenomations.” In Cecil Textbook of Medicine,

21st ed., edited by Goldman, Lee and Bennett, J. Claude.
Philadelphia: W.B. Saunders, 2000, 2174-2178.
Linden, Christopher H and Lovejoy, Frederick H. “ Disorders
caused by reptile bites and marine animal evenomations.”In Harrison’s Principles of Internal Medicine, 14th ed.
edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, 2544-2548.
Norris, Robert L, Oslund, Scott and Auerbach, Paul S.
“Ectoparasite infestations and arthropod bites and stings.”KEY TERMS

Anaphylaxis —A life-threatening allergic reaction
occurring in persons hypersensitive to bites andstings.
Antibiotics —Substances used against bacteria that
cause infection.
Antibodies —Substances created by the body to
combat infection.
Antihistamines —Drugs used to treat allergic reac-
tions by acting against a substance called histamine.
Arachnid —Large class of arthropods that include

spiders, scorpions, mites, and ticks. Arachnids havea segmented body divided into two parts, one ofwhich has four pairs of legs but no antennae.
Arachnidism —Poisoning resulting from the bite or
sting of an arachnid.
Bacteremia —Bacteria in the blood.Blood serum —A component of blood.
Immune system —The body system that fights infec-
tion and protects the body against foreign invadersand disease.
Killer bees —Hybrids of African bees accidentally

introduced into the wild in South and North Ameri-ca in 1956 and first reported in Texas in 1990. Theywere first imported by Brazilian scientists attempt-ing to create a new hybrid bee to improve honeyproduction.
Lymph nodes —Small, kidney-shaped organs that fil-
ter a fluid called lymph and that are part of thebody’s immune system.
Pus—A thick yellowish or greenish fluid composed

of the remains of dead white blood cells, pathogensand decomposed cellular debris.
In Harrison’s Principles of Internal Medicine, 14th ed.,
edited by Anthony S. Fauci, et al. New York: McGraw-Hill, 1998, 2548-2554.
Sutherland, Struan and Tibballs, James. Australian Animal Tox-
ins, 2nd ed. New York, Oxford Univ Press, 2001.
Graudins A, Padula M, Broady K, Nicholson GM. “Red-back

spider (Latrodectus hasselti) antivenom prevents the toxi-city of widow spider venoms.” Annals of Emergency Med-
icine 37(2): 154-160, 2001.
Jarvis RM, Neufeld MV , Westfall CT. “Brown recluse spider bite
to the eyelid.” Ophthalmology 107(8): 1492-1496, 2000.
Kasdan ML, Kasdan AS, Hamilton DL. “Lionfish envenoma-
tion.” Plastic and Reconstructive Surgery 80(4): 613-614,
1987.
Metry DW, Hebert AA. “Insect and arachnid stings, bites, infesta-

tions, and repellents.” Pediatric Annals 29(1): 39-48, 2000.
Sams HH, Dunnick CA, Smith ML, King LE. “Necrotic arach-
nidism.” Journal of the American Academy of Dermatol-
ogy44(4): 561-573, 2001.
Sams HH. “Nineteen documented cases of Loxosceles reclusa
envenomation.” Journal of the American Academy of Der-
matology 44(4): 603-608, 2001.
American Academy of Clinical Toxicology. 777 East Park

Drive, PO Box 8820, Harrisburg, PA 17105-8820. (717)558-7750, Fax: (717) 558-7845. <http://www.clintox.org/index.html>. hmiller@pamedsoc.org.
American Academy of Emergency Medicine. 611 East Wells
Street, Milwaukee, WI 53202. (800) 884-2236, Fax: (414)276-3349. <http://www.aaem.org/>.
GALE ENCYCLOPEDIA OF MEDICINE 2 504Bites and stingsGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 504

American Academy of Family Physicians, 11400 Tomahawk
Creek Parkway, Leawood, KS 66211-2672. (913) 906-6000. <http://www.aafp.org/>. fp@aafp.org.
American Academy of Pediatrics, 141 Northwest Point Boule-
vard, Elk Grove Village, IL 60007-1098. (847) 434-4000,Fax: (847) 434-8000. <http://www. aap.org/default.htm>.kidsdoc@aap.org.
American Association of Poison Control Centers, 3201 New
Mexico Avenue NW, Washington, DC 20016. (202) 362-7217. Fax: (202) 362-8377. <http://www. aapcc.org/>.

American College of Occupational and Environmental Medi-
cine. 55 West Seegers Road, Arlington Heights, IL 60005.(708) 228-6850. Fax: (708) 228-1856. <http://www.acoem.org/>.
American Medical Association, 515 N. State Street, Chicago,
IL 60610. (312) 464-5000. <http://www.ama-assn.org/>.
OTHER
City of Phoenix, Arizona. <http://www.ci.phoenix.az.us/FIRE/
bitessna.html>.
Southwestern University School of Medicine. <http://www.
swmed.edu/toxicology/toxlinks.htm>

Toxicology Professional Groups. <http://www.pitt.edu/~mar-
tint/pages/motoxorg.htm#AAPCC>.
University of Sydney, Australia. <http://www.usyd.edu.au/su/
anaes/spiders.html>.
Vanderbilt University. <http://www.mc.vanderbilt.edu/clintox/>.
L. Fleming Fallon, Jr., MD, PhD
Black death seePlague
Black lung disease
Black lung disease is the common name for coal

workers’ pneumoconiosis (CWP) or anthracosis, alung disease of older workers in the coal industry,caused by inhalation, over many years, of smallamounts of coal dust.
The risk of having black lung disease is directly

related to the amount of dust inhaled over the years; thedisease typically affects workers over age 50. Its com-mon name comes from the fact that the inhalation ofheavy deposits of coal dust makes miners lungs lookblack instead of a healthy pink. Although people wholive in cities often have some black deposits in theirlungs from polluted air, coal miners have much moreextensive deposits.In the years since the federal government has regu-

lated dust levels in coal mines, the number of cases ofblack lung disease has fallen sharply. Since the FederalCoal Mine Health and Safety Act of 1969, average dustlevels have fallen from 8.0 mg. per cubic meter to thecurrent standard of 2.0 mg. per cubic meter. The 1969law also set up a black lung disability benefits programto compensate coal miners who have been disabled byon-the-job dust exposure.
Despite the technology available to control the

hazard, however, miners still run the risk of develop-ing this lung disease. The risk is much lower today,however; fewer than 10% of coal miners have any xray evidence of coal dust deposits. When there is suchevidence, it often shows up as only small black spotsless than 0.4 in (1 cm). in diameter, and may havebeen caused by smoking rather than coal dust. This
condition is called “simple CWP” and does not lead tosymptoms or disability.

Since the particles of fine coal dust, which a miner
breathes when he is in the mines, cannot be destroyedwithin the lungs or removed from them, builds up. Even-tually, this build-up causes thickening and scarring,making the lungs less efficient in supplying oxygen tothe blood.
The primary symptom of the disease is shortness of
breath , which gradually gets worse as the disease pro-
gresses. In severe cases, the patient may develop cor pul-

monale , an enlargement and strain of the right side of the
heart caused by chronic lung disease. This may eventual-ly cause right-sided heart failure .
GALE ENCYCLOPEDIA OF MEDICINE 2 505Black lung disease
A light micrograph of a human lung containing particles of
inspired coal dust (anthracosis).The black masses shownare groups of coal dust particles. (Photograph by Astrid &

Hanns-Frieder Michler, Photo Researchers, Inc. Reproduced bypermission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 505

which the tiny air sacs in the lungs become damaged,leading to shortness of breath, and respiratory and heartfailure) as a complication of black lung disease. Othersdevelop a severe type of black lung disease called pro-gressive massive fibrosis, in which damage continues inthe upper parts of the lungs even after exposure to thedust has ended. Scientists aren’t sure what causes thisserious complication. Some think that it may be due tothe breathing of a mixture of coal and silica dust that

of a mixture of coal and silica dust that isfound in certain mines. Silica is far more likely to lead toscarring than coal dust alone.

Diagnosis
Black lung disease can be diagnosed by checking a
patient’s history for exposure to coal dust, followed by achest x-ray to discover if the characteristic spots in thelungs caused by coal dust are present. A pulmonary
function test may aid in diagnosis.
X rays can detect black lung disease before it causes
any symptoms. If exposure to the dust is stopped at thatpoint, progression of the disease may be prevented.
Treatment
There is no treatment or cure for this condition,

although it is possible to treat complications such as lunginfections and cor pulmonale. Further exposure to coaldust must be stopped.KEY TERMS
Emphysema —A disease in which the tiny air sacs
in the lungs become damaged, leading to short-ness of breath, and respiratory and heart failure.
Fibrosis —The growth of scar tissue, often as a
response to injury, infection, or inflammation.
Pulmonary function test —A group of procedures

used to evaluate the function of the lungs and con-firm the presence of certain lung disorders.
Silica dust —A type of dust from silica (crystalline

quartz) which causes breathing problems in work-ers in the fields of mining, stone cutting, quarrying(especially granite), blasting, road and buildingconstruction industries that manufacture abra-sives, and farming. Breathing the dust causes sili-cosis, a severe disease that can scar the lungs.Prognosis
Those miners with simple CWP can lead a normal

life. However, patients who develop black lung disease atan early age, or who have progressive massive fibrosis,have a higher risk of premature death .
The only way to prevent black lung disease is to
avoid long-term exposure to coal dust. Coal mines mayhelp prevent the condition by lowering coal dust levelsand providing protective clothes to coal miners.
Resources
BOOKS
The Merck Manual. 6th ed. Ed. Robert Berkow, et. al. Rahway,

NJ: Merck and Co., Inc., 1992.
Mine Safety and Health Administration. 4015 Wilson Blvd.
Arlington, V A 22203. (703) 235-1910. <http://www.msha.gov>.
Bladder calculi seeBladder stones
Bladder cancer
Bladder cancer is a disease in which the cells lining
the urinary bladder lose the ability to regulate theirgrowth and start dividing uncontrollably. This abnormalgrowth results in a mass of cells that form a tumor.

Bladder cancer is the fifth most common cancer in
the United States. The American Cancer Society (ACS)estimates that in 1998, approximately 55,000 new casesof bladder cancer will be diagnosed, and it will cause atleast 12,500 deaths. The disease is three times more com-mon among men than women, and the incidence is alsohigher in caucasians.
The urinary bladder is a hollow muscular organ that

stores urine from the kidneys until it is excreted out ofthe body. Two tubes called the ureters bring the urinefrom the kidneys to the bladder. The urethra carries theurine from the bladder to the outside of the body.
Bladder cancer has a very high rate of recurrence.
Even after superficial tumors are completely removed,
GALE ENCYCLOPEDIA OF MEDICINE 2 506Bladder cancerGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 506

there is a 75% chance that new tumors will develop in
other areas of the bladder. Hence, patients need very fre-quent and thorough follow-up care.
Although the exact cause of bladder cancer is not
known, smokers are twice as likely as nonsmokers to getthe disease. Hence, smoking is considered the greatest

risk factor for bladder cancer. Workers who are exposedto certain chemicals that are used in the dye industry andin the rubber, leather, textile, and paint industries arebelieved to be at a higher risk for bladder cancer. The dis-ease is also three times more common in men than inwomen; caucasians also are at an increased risk. The riskof bladder cancer increases with age. Most cases arefound in people who are 50–70 years old.
Frequent urinary infections, kidney and bladder

stones , and other conditions that cause long-term irrita-
tion to the bladder may increase the risk of getting blad-der cancer. A past history of tumors in the bladder couldalso increase one’s risk of getting other tumors.
One of the first warning signals of bladder cancer is

blood in the urine. Sometimes, there is enough blood in theurine to change the color of the urine to a yellow-red or adark red. At other times, the color of the urine appears nor-mal but chemical testing of the urine reveals the presenceof blood cells. A change in bladder habits such as painfulurination, increased frequency of urination and a feeling of

needing to urinate but not being able to do so are some ofthe signs of possible bladder cancer. All of these symptomsmay also be caused by conditions other than cancer, but itis important to see a doctor and have the symptoms evaluat-ed. When detected early and treated appropriately, patientshave a very good chance of being cured completely.
Diagnosis
If a doctor has any reason to suspect bladder cancer, he

may use several tests to find out if the disease is present. Asa first step, a complete medical history will be taken tocheck for any risk factors. A thorough physical examina-
tion will be conducted to assess all the signs and symp-

toms. Laboratory testing of a urine sample will help to ruleout the presence of a bacterial infection. In a urine cytologytest, the urine is examined under a microscope to look forany abnormal or cancerous cells. A catheter (tube) can beadvanced into the bladder through the urethra, and a saltsolution is passed through it to wash the bladder. The solu-tion can then be collected and examined under a micro-scope to check for the presence of any cancerous cells.

A test known as the intravenous pyelogram (IVP) is
an x-ray examination that is done after a dye is injectedinto the blood stream through a vein in the arm. The dyetravels through the blood stream and then reaches thekidneys to be excreted. It clearly outlines the kidneys,
GALE ENCYCLOPEDIA OF MEDICINE 2 507Bladder cancer
UrethraEpithalial Lining
MuscleUreterBladder
Cancer

Cancer
Bladder cancer on the inner lining of the bladder. (Illustration by Argosy Inc.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 507

ureters, bladder, and urethra. Multiple x rays are taken to
detect any abnormality in the lining of these organs.
The physician may use a procedure known as a cys-
toscopy to view the inside of the bladder. A thin hollow

lighted tube is introduced into the bladder through theurethra. If any suspicious looking masses are seen, asmall piece of the tissue can be removed from it using apair of biopsy forceps. The tissue is then examinedmicroscopically to verify if cancer is present, and if so, toidentify the type of cancer.
If cancer is detected and there is evidence to indicate
that it has metastasized (spread) to distant sites in the body,imaging tests such as chest x rays, computed tomography

scans (CT), and magnetic resonance imaging (MRI) may
be done to determine which organs are affected. Bladdercancer generally tends to spread to the lungs, liver, and bone.
Treatment
Treatment for bladder cancer depends on the stage

of the tumor. The patient’s medical history, overall healthstatus, and personal preferences are also taken intoaccount when deciding on an appropriate treatment plan.The three standard modes of treatment that are availablefor bladder cancer are surgery, radiation therapy , and
chemotherapy . In addition, newer treatment methods
such as photodynamic therapy and immunotherapy arealso being investigated in clinical trials.

is in its early stages. If the tumor is localized to a small areaand has not spread to the inner layers of the bladder, thenthe surgery is done without cutting open the abdomen. Acytoscope is introduced into the bladder through the ure-thra, and the tumor is removed through it. This procedure iscalled a transurethral resection (TUR). Passing a high-ener-gy laser beam through the cytoscope and burning the can-cer may treat any remaining cancer. This procedure isknown as electrofulguration. If

This procedure isknown as electrofulguration. If the cancer has invaded thewalls of the bladder, surgery will be done through an inci-sion in the abdomen. Cancer that is not very large can beremoved by partial cystectomy , a procedure where a part

of the bladder is removed. If the cancer is large or is presentin more than one area of the bladder, a radical cystectomyis done. In this operation, besides the entire bladder, theadjoining organs may also be removed. In men, the prostateis removed, while in women, the uterus, ovaries, and fal-lopian tubes are removed.
If the entire urinary bladder is removed, then an alter-

nate storage place must be created for the urine to bestored before it is excreted out of the body. To do this, apiece of intestine is converted into a small bag andattached to the ureters. This is then connected to an open-ing (stoma) that is made in the abdominal wall. The proce-

dure is called a urostomy. In some urostomy procedures,the urine from the intestinal sac is routed into a bag that isplaced over the stoma in the abdominal wall. The bag ishidden by the clothing and has to be emptied occasionallyby the patient. In a different procedure, the urine is collect-ed in the intestinal sac, but there is no bag on the outside ofthe abdomen. The intestinal sac has to be emptied by thepatient, by placing a drainage tube through the stoma.

Radiation therapy that uses high-energy rays to kill
cancer cells is generally used after surgery to destroy anyremaining cancer cells that may not have been removedduring surgery. If the tumor is in a location that makessurgery difficult, or if it is large, radiation may be usedbefore surgery to shrink the tumor. In cases of advancedbladder cancer, radiation therapy is used to ease thesymptoms such as pain , bleeding, or blockage. Radiation

can be delivered by external beam radiation where asource of radiation that is outside the body focuses theradiation on the area of the tumor. Occasionally, a smallpellet of radioactive material may be placed directly intothe cancer. This is known as interstitial radiation therapy.
Chemotherapy uses anticancer drugs to destroy the

cancer cells that may have migrated to distant sites. Thedrugs are introduced into the bloodstream by injecting theminto a vein in the arm or taking them orally in pill form.Generally a combination of drugs is more effective than anysingle drug in treating bladder cancer. Chemotherapy maybe given following surgery to kill any remaining cancercells. It may also be given even when no remaining cancercells can be seen. This is called adjuvant chemotherapy.Anticancer drugs, including thiotepa,

drugs, including thiotepa, doxorubicin, and mit-omycin, may also be instilled directly into the bladder(intravesicular chemotherapy) to treat superficial tumors.

Immunotherapy or biological therapy, uses the
body’s own immune cells to fight the disease. To treatsuperficial bladder cancer, bacille Calmette-Guerin(BCG) may be instilled directly into the bladder. BCG isa weakened (attenuated) strain of the tuberculosis bacil-
lus that stimulates the body’s immune system to fight thecancer. This therapy has been shown to be effective incontrolling superficial bladder cancer.
Photodynamic treatment is a novel mode of treat-

ment that uses special chemicals and light to kill the can-cerous cells. First, a drug is introduced into the bladderthat makes the cancer cells more susceptible to light. Fol-lowing that, a special light is shone on the bladder in anattempt to destroy the cancerous cells.
Prognosis
When detected at the early stages, the prognosis for
bladder cancer is excellent. At least 94% of the people

GALE ENCYCLOPEDIA OF MEDICINE 2 508Bladder cancerGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 508

survive five years or more after initial diagnosis. Howev-
er, if the disease has spread to the nearby tissues, the sur-vival rates drop to 49%. If it has metastasized to distantorgans such as the lung, and the liver, commonly only6% of the patients will survive five years or more.
Since we do not know what exactly causes bladder
cancer, there is no certain way to prevent it. Avoiding riskfactors whenever possible is the best alternative.

Since smoking doubles one’s risk of getting bladder
cancer, avoiding tobacco may prevent at least half thedeaths that result from bladder cancer. Taking appropriatesafety precautions when working with organic cancer-caus-ing chemicals is another way of preventing the disease.KEY TERMS
Biopsy —The surgical removal and microscopic
examination of living tissue for diagnostic purposes.
Chemotherapy —Treatment with drugs that are anti
cancer.
Computed tomography (CT) scan —A medical pro-

cedure where a series of X-rays are taken and puttogether by a computer in order to form detailedpictures of areas inside the body.
Cystoscopy —A diagnostic procedure where a hol-
low lighted tube, (cystoscope) is used to look insidethe bladder and the urethra.
Electrofulguration —A procedure where a high-ener-
gy laser beam is used to burn the cancerous tissue.Immunotherapy —Treatment of cancer by stimulat-
ing the body’s immune defense system.

Intravenous pyelogram (IVP) —A procedure where
a dye is injected into a vein in the arm. The dye trav-els through the body and then concentrates in theurine to be excreted. It outlines the kidneys, ureters,and the urinary bladder. An x-ray of the pelvicregion is then taken and any abnormalities of theurinary tract are revealed.
Magnetic Resonance Imaging (MRI) —A medical

procedure used for diagnostic purposes where pic-tures of areas inside the body can be created usinga magnet linked to a computer.
Partial cystectomy —A surgical procedure where
the cancerous tissue is removed by cutting out asmall piece of the bladder.Photodynamic therapy —A novel mode of treatment

where a combination of special light rays and drugsare used to destroy the cancerous cells. First, thedrugs, which make the cancerous cells more sus-ceptible to the light rays, are introduced into thebladder. Then the light is shone on the bladder tokill the cells.
Radiation therapy —Treatment using high- energy
radiation from X-ray machines, cobalt, radium, orother sources.
Radical cystectomy —A surgical procedure that is

used when the cancer is in more than one area ofthe bladder. Along with the bladder, the adjoiningorgans are also removed. In men, the prostate isremoved, while in women, the ovaries, fallopiantubes and uterus may be removed.
Stoma —An artificial opening between two cavities
or between a cavity and the surface of the body.
Transurethral resection —A surgical procedure to

remove abnormal tissue from the bladder. The tech-nique involves the insertion of an instrument calleda cytoscope into the bladder through the urethra,and the tumor is removed through it.Urostomy —A surgical procedure consisting of cut-
ting the ureters from the bladder and connectingthem to an opening (see Stoma) on the abdomen,allowing urine to flow into a collection bag.
If a person has had a history of bladder cancer, or

has been exposed to cancer-causing chemicals, then he orshe is considered to be at an increased risk of gettingbladder cancer. Similarly, kidney stones , frequent uri-

nary infections, and other conditions that cause long-term irritation to the bladder also increases the chance ofgetting the disease. In such cases, it is advisable to under-go regularscreening tests such as urine cytology, cys-toscopy and x rays of the urinary tract, so that bladdercancer can be detected at its early stages and treatedappropriately.
Resources
BOOKS
Berkow, Robert, ed. Merck Manual of Diagnosis and Therapy.
16th ed. Rahway, NJ: Merck Research Laboratories, 1992.

GALE ENCYCLOPEDIA OF MEDICINE 2 509Bladder cancerGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 509

Dollinger, Malin, et al. Everyone’s Guide to Cancer Therapy:
How Cancer is Diagnosed, Treated, and Managed Day toDay. 3rd ed. Kansas City: Andres & McMeel, 1998.
Morra, Marion E., and Eve Potts. Choices: The New, Most Up-
To-Date Sourcebook for Cancer Information. New York:
Avon Books, 1994.
Murphy, Gerald P., Lois B. Morris, and Dianne Lange.
Informed Decisions: The Complete Book of Cancer Diag-nosis, Treatment and Recovery. New York: Viking, 1997.

American Foundation for Urologic Disease. 300 W. Pratt St.,
Suite 401. Baltimore, MD 21201. Phone: (800)-828-7866.
Cancer Research Institute. 681 Fifth Ave., New York, N.Y .
10022. (800) 992-2623. <http://www.cancerresearch.org>.

National Kidney and Urologic Diseases Information Clearing-
house (NKUDIC). 3 Information Way, Bethesda, MD20892-3580. (800) 891-5388. <http://www.niddk.nih.gov/health/urolog/pubs/kuorg/kuorg.htm>.
Oncolink. University of Pennsylvania Cancer Center. <http://
cancer.med.upenn.edu>.
OTHER
“Bladder Cancer.” National Cancer Institute Page. <http://
www.nci.nih.gov>.

“1998 Cancer Facts and Figures.” American Cancer Society
Page. <http://www.cancer.orgl>.
Lata Cherath, PhD
Bladder removal seeCystectomy
Bladder resection seeTransurethral bladder
resection
Bladder stones
Bladder stones are crystalline masses that form from
the minerals and proteins, which naturally occur in
urine. These types of stones are much less common thankidney stones .
Bladder stones can form anywhere in the urinary

tract before depositing in the bladder. They begin as tinygranules about the size of a grain of sand, but they cangrow to more than an inch in diameter. These stones canblock the flow of urine causing pain and difficulty with
urination. They can also scratch the bladder wall, whichmay lead to bleeding or infection.
While the exact causes of the formation of bladder

stones are not completely understood, bladder stonesusually occur because of urinary tract infection (UTI),obstruction of the urinary tract, enlargement of theprostate gland in men, or the presence of foreign bodiesin the urinary tract. Diet and the amount of fluid intakealso appear to be important factors in the development ofbladder stones.
Ninety-five percent of all bladder stones occur in
men, most of who have an enlarged prostate gland or a

UTI. These stones are rarely seen in children or inAfrican Americans. People with gout may develop blad-
der stones composed almost entirely of uric acid.
The symptoms of bladder stones may become evi-
dent when the wall of the bladder is scratched or whenthe urinary tract becomes obstructed by the stone. Thesesymptoms include:
• abnormally dark colored urine
• blood in the urine• difficulty urinating
• frequent urge to urinate
• lower abdominal pain• pain or discomfort in the penis

Some people with bladder stones also may experi-
ence an inability to control urination ( urinary inconti-
nence ).
Diagnosis
The diagnosis of bladder stones is usually made after a
physical examination , which may include a rectal exami-
nation to check for enlargement of the prostate gland.

Urine tests are then used to determine if there is blood orindications of an UTI in the urine. If bladder stones are sus-pected, bladder or pelvic x rays may be ordered. Stones thatare large enough to cause problems with urinary functionare almost always detectable by x ray.
Treatment
Many bladder stones can be passed out of the body

in the urine. People with small bladder stones will beasked to increase their fluid intakes to at least six to eighteight-ounce glasses of water per day to increase urinaryoutput. If the stones do not pass after two weeks, or if the
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patient’s symptoms become worse, further medical treat-
ment may be required.
A large bladder stone, or small stone that the patient
cannot pass in the urine, may be broken up into smallerstones using ultrasound (shock waves). These smallerstones may then pass in the urine. Stones that cannot bebroken into pieces by these methods, or that the patientcannot pass, may have to be surgically removed.
Traditional herbal remedies for bladder stones include

celery seed and horsetail. Also, because incomplete blad-der emptying may cause bladder stones, many patientsmay benefit from methods and remedies aimed at improv-ing overall bladder function. These include Kegel exercis-es, which are used to strengthen the muscles involved inurination; herbal supplements (cornsilk, hydrangea,juniper berries, parsley, and uva ursi) used to increaseurine flow and flush out sediment from the bladder; and,the consumption of cranberry juice and/or fresh,

consumption of cranberry juice and/or fresh, unsweet-ened, lemon juice. Cranberry juice helps to control urinarytract infection and contains a chemical that coats the wallsof the bladder, making them more resistant to infection.Lemon juice helps to flush out the urinary system.

Prognosis
Most bladder stones can be, and are, passed out of
the body in the urine without any permanent damage tothe bladder or the rest of the urinary tract. However, mostbladder stones arise from an underlying medical condi-tion. Therefore, if this medical condition is not correctedapproximately half of all patients will experience a recur-rence of bladder stones within five years.
Bladder stones may, in some cases, be prevented by

the patient receiving prompt medical treatment for anenlarged prostate gland or UTI. The consumption of atleast six to eight eight-ounce glasses of water per dayand/or the regular consumption of cranberry juice mayhelp to prevent recurrences of bladder stones.
Resources
BOOKS
Ross, Linda M. and Peter Dresser, eds. Kidney and Urinary
Tract Diseases and Disorders Sourcebook. Detroit, MI:
Omnigraphics, Inc., 1997.
Schwartz, B.F. and M.L. Stoller. “The vesical calculus.” Uro-

logic Clinics of North America 27 (May 2000): 333-46.KEY TERMS
Bladder —A small organ that serves as the reser-
voir for urine prior to its passing from the bodyduring urination.
Prostate gland —A small gland in the male genitals
that contributes to the production of seminal fluid.
Urinary tract —The system of organs that produces

and expels urine from the body. This system beginsat the kidneys, where the urine is formed; passesthrough the bladder; and, ends at the urethra,where urine is expelled.
American Foundation for Urologic Disease. 1128 North
Charles Street, Baltimore, Maryland 21201. (410) 468-1800. Fax: (410) 468-1808. <http://www.afud.org/>.
OTHER
“Bladder Stones.” MEDLINEplus Health Information. <http://

medlineplus.adam.com/ency/article/001275.htm>. (12May 2001).
Paul A. Johnson
Bladder training
Bladder training is a behavioral modification treat-
ment technique for urinary incontinence that involves
placing a patient on a toileting schedule. The time inter-val between urination is gradually increased in order totrain the patient to remain continent.
Purpose
Bladder training is used to treat urinary urge inconti-

nence. Urge incontinence occurs when an individualfeels a sudden need to urinate and cannot control the urgeto do so and, as a consequence, involuntarily loses urinebefore making it to the toilet.
Incontinence may be controlled through a number of
invasive and non-invasive treatment options, includingKegel exercises, biofeedback , bladder training, medica-
tion, insertable incontinence devices, and surgery. Eachpatient should undergo a full diagnostic work-up to

GALE ENCYCLOPEDIA OF MEDICINE 2 511Bladder trainingGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 511

determine the type and cause of the incontinence in order
to determine the best course of treatment.
Bladder training may be prescribed and implement-

ed by a general physician, urologist, or urogynecologist.A urination schedule is created for the patient. Theschedule typically starts out with fairly short intervalsbetween bathroom breaks (e.g., an hour). As soon as thepatient is able to consistently remain continent for sever-al days at a certain toileting time interval, the time spanis increased. Bladder training continues until the patientregularly achieves continence at a time interval he/shefeels comfortable with.

A complete evaluation to determine the cause of uri-
nary incontinence is critical to proper treatment. A thor-ough medical history and physical examination should

be performed on patients considering bladder training.Diagnostic testing may include x rays, ultrasound, urinetests, and a physical examination of the pelvis. It mayinclude a series of exams called urodynamic testing thatmeasure bladder pressure and capacity and the urinaryflow. The patient may also be asked to keep a diary oftheir urination output and frequency and episodes ofincontinence over a period of several days or a week.
Risks
Bladder training may not be successful in all

patients with urge incontinence. Patients who demon-strate a strong desire to control their continence and arecommitted to sticking with a training program tend tohave the most success with bladder training.
Patients who undergo successful bladder training gain
complete or improved control over their urination. In someKEY TERMS
Biofeedback —Biofeedback training monitors

temperature and muscle contractions in the vagi-na to help incontinent patients control theirpelvic muscles.
Pelvic muscle exercises —Exercises that tighten
and tone the pelvic floor, or perineal, muscles.Also known as Kegel and PC muscle exercises.cases, additional alternate treatment such as biofeedback
or pelvic muscle exercises may be recommended to sup-plement the progress made with bladder training.
Resources
BOOKS

Resources
BOOKS
Blaivas, Jerry. Conquering Bladder and Prostate Problems:
The Authoritative Guide for Men and Women. New York:
Plenum, 1998.
King, Barbara, and Judy Harke. Coping With Bowel and Bladder
Problems. San Diego: Singular Publishing Group, 1994.
Strange, Carolyn J. “Incontinence Can Be Controlled.” FDA
Consumer 31 (July/Aug. 1997): 28-31.
American Foundation for Urologic Disease. 1128 North Charles

St., Baltimore, MD 21201. (800) 242-2383. <http://www.afud.org>.
National Association for Continence. P.O. Box 8310, Spartan-
burg, SC 29305-8310. (800) 252-3337. <http://www.nafc.org>.
Blastomyces dermatitidis see Blastomycosis
Blastomycosis

Blastomycosis is an infection caused by inhaling
microscopic particles (spores) produced by the fungusBlastomyces dermatitidis . Blastomycosis may be limited
to the lungs or also involve the skin and bones. In itsmost severe form, the infection can spread throughoutthe body and involve many organ systems (systemic).
Blastomycosis is a fungal infection caused by Blas-
tomyces dermatitidis . Although primarily an airborne

disease, farmers and gardeners may become infectedfrom contact with spores in the soil through cuts andscrapes. The fungus that causes the disease is found inmoist soil and wood in the southeastern United States,the Mississippi River valley, southern Canada, and Cen-tral America. Blastomycosis is also called Gilchrist’s dis-
GALE ENCYCLOPEDIA OF MEDICINE 2 512BlastomycosisGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 512

ease, Chicago disease, or North American blastomycosis.
Another South and Central American disease, paracoc-cidioidomycosis, is sometimes called South American
blastomycosis , but despite the similar name, this disease
is substantially different from North American blastomy-cosis. Canine blastomycosis, a common dog disease, iscaused by the same fungus that infects humans. Howev-er, people do not get this disease from their dogs exceptonly very rarely through dog bites.

Blastomycosis is a rare disease infecting only about
4 in every 100,000 people. It is at least six times morecommon in men than in women and tends to more ofteninfect children and individuals in the 30–50 year old agegroup. People who have diabetes mellitus or who are
taking drugs that suppress the immune system (immuno-compromised) are more likely to develop blastomycosis.Although people with AIDS can get blastomycosis

because of their weakened immune system, blastomyco-sis has not been one of the more common fungal infec-tions associated with AIDS.
Once inhaled, the spores of B. dermatitidis can lodge
in the lungs and cause a localized inflammation. This isknown as primary pulmonary blastomycosis. The diseasedoes not spread from one person to another. In the earlystages, symptoms may include a dry cough ,fever , heavy
sweating, fatigue , and a general feeling of ill health. In

approximately 25% of blastomycosis cases, only thelungs are affected. As the disease progresses, smalllesions form in the lungs causing the air sacs deep withinthe lungs (alveoli) to break down and form small cavities.
In another 35%, the disease involves both the lungs

and the skin. Bumps develop on the skin, graduallybecoming small, white, crusted blisters filled with pus.The blisters break open, creating abscesses that do notheal. Approximately 19% of infected people have skinsores without infection in the lungs.
The remaining approximately 20% of the infected
population has blastomycosis that has spread or dissemi-nated to other systems of the body. Symptoms mayinclude pain and lesions on one or more bones, the male

genitalia, and/or parts of the central nervous system. Theliver, spleen, lymph nodes, heart, adrenal glands, anddigestive system may also be infected.
Diagnosis
A positive diagnosis of blastomycosis is made when
the fungus B. dermatitidis is identified by direct micro-
scopic examination of body fluids such as sputum andprostate fluid or in tissue samples (biopsies) from thelung or skin. Another way to diagnose blastomycosis is

to culture and isolate the fungus from a sample of spu-tum. Chest x rays are used to assess lung damage, butalone cannot lead to a definitive diagnosis of blastomy-cosis because any damage caused by other diseases, suchas by pneumonia or tuberculosis , may appear look on
the x ray. Because its symptoms vary widely, blastomy-cosis is often misdiagnosed.
Treatment
Blastomycosis must be treated or it will gradually
lead to death . Treatment with the fungicidal drug keto-

conazole (Nizoral) taken orally is effective in about 75%of patients. Amphotericin B (Fungizone) given intra-venously is also very effective, but it has more toxic sideeffects than ketoconazole. Treatment with amphotericinB usually requires hospitalization, and the patient mayalso receive other drugs to minimize the its side effects.
Alternative treatment for fungal infections focuses

on creating an internal environment where the funguscannot survive. This is accomplished by eating a diet lowin dairy products, sugars, including honey and fruit juice,and foods like beer that contain yeast. This is comple-mented by a diet consisting, in large part, of uncookedand unprocessed foods. Supplements of vitamins C, E,
A-plus, and B complex may also be useful. Lactobacillus
acidophilus and Bifidobacterium will replenish the good

bacteria in the intestines. Some antifungal herbs, likegarlic ( Allium sativum ), can be consumed in relatively
large doses and for an extended period of time in order toincrease effectiveness. A variety of antifungal herbs,such as myrrh ( Commiphora molmol ), tea tree oil
(Melaleuca spp.), citrus seed extract, pau d’arco tea
GALE ENCYCLOPEDIA OF MEDICINE 2 513Blastomycosis
Blastomycosis is usually attributed to contact with yeast-like

fungi. (Custom Medical Stock Photo. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 513

(Tabebuia impetiginosa ), and garlic may also be applied
directly to the infected skin.
Prognosis
Left untreated, blastomycosis gradually leads to
death. When treated, however, patients begin to improvewithin one week and, with intensive treatment, may becured within several weeks. The highest rate of recoveryis among patients who only have skin lesions . People
with the disseminated form of the disease are least likelyto be cured and and most likely to suffer a relapse.

Because the fungus that causes blastomycosis is air-
borne and microscopic, the only form of prevention is toavoid visiting areas where it is found in the soil. Formany people this is impractical. Since the disease is rare,people who maintain general good health do not need toworry much about infection.
Resources

Abscess —An area of inflamed and injured body
tissue that fills with pus.
Acidophilus —The bacteria called Lactobacillus
acidophilus that is usually found in yogurt.
Alveoli —Small air pockets in the lungs that
increase the surface area for oxygen absorption.
Bifidobacteria —A group of bacteria normally pre-
sent in the intestine. Commercial supplementscontaining these bacteria are available.

nostic purposes.Immunocompromised —A state in which the
immune system is suppressed or not functioningproperly.Spores —The small, thick-walled reproductive
from airways.
Systemic —Not localized to a single area of the body
but, instead, involving one or more body systems.OTHER
McGinnis, Michael R. “Blastomycosis.” Medical Mycology

Research Center Page. University of Texas MedicalBranch. Apr. 1997 <http://www.fungus.utmb.edu/f-atlas/blastom.htm.>.
“Blastomycosis.” Vanderbilt University Medical Center. <http://
www.mc.vanterbilt.edu/peds/pid/infect/blastomy.html>.
Bleeding disorders seeCoagulation disorders
Bleeding time
Bleeding time is a crude test of hemostasis (the arrest
or stopping of bleeding). It indicates how well plateletsinteract with blood vessel walls to form blood clots.
Purpose

defects of platelets, such as V on Willebrand’s disease. Thetest helps identify people who have defects in theirplatelet function. This is the ability of blood to clot fol-lowing a wound or trauma. Normally, platelets interactwith the walls of blood vessels to cause a blood clot.There are many factors in the clotting mechanism, andthey are initiated by platelets. The bleeding time test isusually used on patients who have a history of prolongedbleeding after cuts, or who have a family history of

after cuts, or who have a family history of bleed-ing disorders. Also, the bleeding time test is sometimesperformed as a preoperative test to determine a patient’slikely bleeding response during and after surgery. Howev-er, in patients with no history of bleeding problems, orwho are not taking anti-inflammatory drugs, the bleedingtime test is not usually necessary.

Before administering the test, patients should be
questioned about what medications they may be taking.Some medications will adversely affect the results of thebleeding time test. These medications include anticoagu-lants, diuretics ,anticancer drugs ,sulfonamides , thi-
azide, aspirin and aspirin-containing preparations, and
nonsteroidal anti-inflammatory drugs . The test may

also be affected by anemia (a deficiency in red bloodcells). Since the taking of aspirin or related drugs are themost common cause of prolonged bleeding time, noaspirin should be taken two weeks prior to the test.
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test. The Ivy method is the traditional format for thistest. In the Ivy method, a blood pressure cuff is placedon the upper arm and inflated to 40 mM Hg. A lancet orscalpel blade is used to make a stab wound on theunderside of the forearm. An automatic, spring-loadedblade device is most commonly used to make a stan-dard-sized cut. The area stabbed is selected so that nosuperficial or visible veins are cut. These veins, becauseof their size, may have longer bleeding times, especial-ly in people

have longer bleeding times, especial-ly in people with bleeding defects. The time from whenthe stab wound is made until all bleeding has stopped ismeasured and is called the bleeding time. Every 30 sec-onds, filter paper or a paper towel is used to draw offthe blood. The test is finished when bleeding hasstopped completely.

The three other methods of performing the bleeding
test are the template, modified template, and Dukemethods. The template and modified template methodsare variations of the Ivy method. A blood pressure cuffis used and the skin on the forearm prepared as in theIvy method. A template is placed over the area to bestabbed and two incisions are made in the forearm usingthe template as a location guide. The main differencebetween the template and the modified method is thelength of the cut made.

or a fingertip is pricked to cause bleeding. As in the Ivymethod, the test is timed from the start of bleeding untilbleeding is completely stopped. The disadvantage to theDuke method is that the pressure on the blood veins inthe stab area is not constant and the results achieved areless reliable. The advantage to the Duke method is thatno scar remains after the test. The other methods mayresult in a tiny, hairline scar where the wound was made.However, this is largely a cosmetic concern.

There is no special preparation required of the
patient for this test. The area to be stabbed should bewiped clean with an alcohol pad. The alcohol should beleft on the skin long enough for it to kill bacteria at thewound site. The alcohol must be removed before stab-bing the arm because alcohol will adversely affect thetests results by inhibiting clotting.
Aftercare
If a prolonged bleeding time is caused by unknown

factors or diseases, further testing is required to identifythe exact cause of the bleeding problem.KEY TERMS
Hemostasis —The stopping of bleeding or blood
flow through a blood vessel or organ.
A normal bleeding time for the Ivy method is less

than five minutes from the time of the stab until allbleeding from the wound stops. Some texts extend thenormal range to eight minutes. Normal values for thetemplate method range up to eight minutes, while forthe modified template methods, up to 10 minutes isconsidered normal. Normal for the Duke method isthree minutes.
A bleeding time that is longer than normal is an

abnormal result. The test should be stopped if the patienthasn’t stopped bleeding by 20-30 minutes. Bleeding timeis longer when the normal function of platelets isimpaired, or there are a lower-than-normal number ofplatelets in the blood.
A longer-than-normal bleeding time can indicate
that one of several defects in hemostasis is present,including severe thrombocytopenia , platelet dysfunc-

tion, vascular defects, V on Willebrand’s disease, or otherabnormalities.
Resources
BOOKS
Henry, J. B. Clinical Diagnosis and Management by Laborato-
ry Methods. Philadelphia: W. B. Saunders Co., 1996.
Jandl, J. H. Blood, Textbook of Hematology. New York: Little,
Brown and Co., 1996.
Bleeding varices
Bleeding varices are bleeding, dilated (swollen)

veins in the esophagus (gullet), or the upper part of thestomach, caused by liver disease.
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Engorged veins are called varices (plural of varix).
Varices may occur in the lining of the esophagus, thetube that connects the mouth to the stomach, or in theupper part of the stomach. Such varices are calledesophageal varices. These varices are fragile and canbleed easily because veins are not designed to handlehigh internal pressures.
Liver disease often causes an increase in the blood

pressure in the main veins that carry blood from thestomach and intestines to the liver (portal veins). As thepressure in the portal veins increases, the veins of thestomach and esophagus swell, until they eventuallybecome varices. Bleeding varices are a life-threateningcomplication of this increase in blood pressure (portalhypertension ). The most common cause of bleeding
varices is cirrhosis of the liver caused by chronic alcohol

abuse or hepatitis. Bleeding varices occur in approxi-mately one in every 10,000 people.
Symptoms of bleeding varices include
• vomiting blood, sometimes in massive amounts
• black, tarry stools
• decreased urine outputKEY TERMS
Cirrhosis of the liver —A type of liver disease, most
often caused by chronic alcohol abuse. It is charac-terized by scarring of the liver, which leads to anincrease in the blood pressure in the portal veins.
Endoscopy —Medical imaging technique for visual-

izing the interior of a hollow organ.
Esophagus —The tube in the body which takes food
from the mouth to the stomach.
Esophagogastroduodenoscopy (EGD) —An imaging
test that involves visually examining the lining ofthe esophagus, stomach, and upper duodenum witha flexible fiberoptic endoscope.
Portal hypertension —Portal hypertension forces the

blood flow backward, causing the portal veins toenlarge and the emergence of bleeding varicesacross the esophagus and stomach from the pressurein the portal vein. Portal hypertension is most com-monly caused by cirrhosis, but can also be seen inportal vein obstruction from unknown causes.Portal veins —The main veins that carry blood from
the stomach and intestines to the liver.
Shock —A state of depression of the vital processes

of the body characterized by pallor, a rapid andweak pulse, rapid and shallow respiration, and low-ered blood pressure. Shock results from severe trau-ma, such as crushing injuries, hemorrhage, burns,or major surgery.
Transjugular intrahepatic portosystemic shunt
(TIPS) —A transjugular intrahepatic portosystemic
shunt (TIPS) is a radiology procedure in which atubular device is inserted in the middle of the liverto redirect the blood flow.
Varices —A type of varicose vein that develops in

veins in the linings of the esophagus and upper stom-ach when these veins fill with blood and swell due toan increase in blood pressure in the portal veins.
• excessive thirst
• nausea• vomiting• and blood in the vomit
If bleeding from the varices is severe, a patient may
go into shock from the loss of blood, characterized by
pallor, a rapid and weak pulse, rapid and shallow respira-tion, and lowered systemic blood pressure.
Diagnosis

Diagnosis
Bleeding varices may be suspected in a patient who
has any of the above-mentioned symptoms, and who haseither been diagnosed with cirrhosis of the liver or whohas a history of prolonged alcohol abuse. The definitivediagnosis is established via a specialized type of endo-scopy, namely, esophagogastroduodenoscopy (EGD), a
procedure that involves the visual examination of the lin-ing of the esophagus, stomach, and upper duodenumwith a flexible fiberoptic endoscope.
Treatment

Treatment
The objective during treatment of bleeding varices is
to stop and/or prevent bleeding and to restore/maintainnormal blood circulation throughout the body. Patientswith severe bleeding should be treated in intensive caresince uncontrolled bleeding can lead to death .
GALE ENCYCLOPEDIA OF MEDICINE 2 516Bleeding varicesGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 516

Initial treatment of bleeding varices begins with stan-
dard resuscitation, including intravenous fluids and bloodtransfusions as needed. Definitive treatment is usuallyendoscopic, with the endoscope used to locate the sites ofthe bleeding. An instrument, inserted along with the endo-scope, is used either to inject these sites with a clottingagent or to tie off the bleeding sites with tiny rubber bands.
Repeated endoscopic treatments (usually four to six)

are generally required to eliminate the varices and to pre-vent the recurrence of bleeding. These endoscopic tech-niques are successful in about 90 percent of cases.
Patients who cannot be treated endoscopically may

be considered for an alternative procedure called TIPS(transjugular intrahepatic portosystemic shunt). This pro-cedure involves placing a hollow metal tube (shunt) inthe liver connecting the portal veins with the hepaticveins (veins that leave the liver and drain to the heart).This shunt lowers the pressure in the portal veins andprevents bleeding and portal hypertension. The TIPS pro-cedure is performed by a radiologist and has become anaccepted method for reducing portal vein pressure

method for reducing portal vein pressure since1992. Although the procedure continues to evolve, TIPScan routinely be created in more than 93% of patients.

Medications aimed at controlling bleeding may also
be prescribed. These include propanolol, vasopressin,octreotide acetate, and isosorbide mononitrate.
Some alternative treatments are aimed at preventing
the cirrhosis of the liver that often causes bleeding varicesand most are effective. However, once a patient hasreached the bleeding varice stage, standard intervention tostop the bleeding is required or the patient may die.
Prognosis

complications of portal hypertension. They contribute tothe estimated 32,000 deaths per year attributed to cirrho-sis. Half or more of patients who survive episodes ofbleeding varices are at risk of renewed esophageal bleed-ing during the first one to two years. The risk of recur-rence can be lowered by endoscopic and drug treatment.Prognosis is usually more related to the underlying liverdisease. Approximately 30 to 50 percent of people withbleeding varices will die from this condition within

varices will die from this condition within thesix weeks of the first bleeding episode.

The best way to possibly prevent the development or
recurrence of bleeding varices is to eliminate the risk fac-tors for cirrhosis of the liver. The most common cause ofcirrhosis is prolonged alcohol abuse, and alcohol con-sumption must be completely eliminated. People with
hepatitis B or hepatitis C also have an increased risk of
developing cirrhosis of the liver. Vaccination against
hepatitis B and avoidance of intravenous drug usagereduce the risk of contracting hepatitis.

Resources
BOOKS
Shannon, Joyce Brennfleck, ed. Liver Disorders Sourcebook.
Detroit, MI: Omnigraphics, Inc., 2000.
Burroughs, Andrew K. and David Patch. “Primary prevention
of bleeding from esophageal varices.” New England Jour-
nal of Medicine 340 (April 1, 1999): 1033-5.
Hegab, Ahmed M. and Velimir A. Luketic. “Bleeding
esophageal varices: How to treat this dreaded complica-tion of portal hypertension.” Postgraduate Medicine 109
(February 2001): 75-89.

American Liver Foundation. 75 Maiden Lane, Suite 603, New
York, NY 10038. (800) 465-4837. <http://www.liverfoundation.org/>.
OTHER
Goff, John. “Portal hypertensive bleeding.” <http://www.nysge.
org/PostGrad1999/Goff_VaricealBleeding.htm> (12 May2001).
Blepharitis seeEyelid disorders
Blepharoplasty
Blepharoplasty is a cosmetic surgical procedure that

removes fat deposits, excess tissue, or muscle from theeyelids to improve the appearance of the eyes.
Purpose
The primary use of blepharoplasty is for improving
the cosmetic appearance of the eyes. In some olderpatients, however, sagging and excess skin surroundingthe eyes can be so extensive that it limits the range ofvision. In those cases, blepharoplasty serves a more func-tional purpose.
Before performing blepharoplasty, the surgeon will

assess whether the patient is a good candidate for the
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treatment. A good medical history is important. The sur-
geon will want to know about any history of thyroid dis-ease, hypertension , or eye problems, which may
increase the risk of complications.
Blepharoplasty can be performed on the upper or
lower eyelid; it can involve the removal of excess skinand fat deposits and the tightening of selected musclessurrounding the eyelids. The goal is to provide a moreyouthful appearance.
The surgeon will begin by deciding whether excess

skin, fat deposits, or muscle looseness are at fault. Whilethe patient is sitting upright, the surgeon will mark on theskin where incisions will be made. Care will be taken tohide the incision lines in the natural skin folds above andbelow the eye. The patient then receives injections of alocal anesthetic to numb the pain. Many surgeons also give
the patient a sedative intravenously during the procedure.

After a small, crescent-shaped section of eyelid skin
is removed, the surgeon will work to tease out smallpockets of fat that have collected in the lids. If musclelooseness is also a problem, the surgeon may trim tissueor add a stitch to pull it tighter. Then the incision isclosed with stitches.
In some patients, fat deposits in the lower eyelid may

be the only or primary problem. Such patients may begood candidates for transconjunctival blepharoplasty. Inthis procedure the surgeon makes no incision on the sur-face of the eyelid, but instead enters from behind to teaseout the fat deposits from a small incision. The advantageof this procedure is that there is no visible scar.
Prior to surgery, patients meet with their surgeon to

discuss the procedure, clarify the results that can beachieved, and discuss the potential problems that mightoccur. Having realistic expectations is important in anycosmetic procedure. Patients will learn, for example, thatalthough blepharoplasty can improve the appearance ofthe eyelid, other procedures, such as a chemical peel,will be necessary to reduce the appearance of wrinklesaround the eye. Some surgeons prescribe vitamin C andvitamin K for 10 days prior to surgery in the belief thatthis

10 days prior to surgery in the belief thatthis helps the healing process. Patients are also told tostop smoking in the weeks before and after the proce-

dure, and to refrain from alcohol and aspirin .
Aftercare
An antibiotic ointment is applied to the line of stitch-
es for several days after surgery. Patients also take an
GALE ENCYCLOPEDIA OF MEDICINE 2 518Blepharoplasty
Cutting the skin off
Closing the incisionsPinching the 
redundant skin
The illustration above depicts a procedure to eliminate der-
mochalasia, or baggy skin around the eyes. (Illustration by
Electronic Illustrators Group.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 518

cold compresses are applied to the eyes continuously forthe first day following surgery, and several times a day forthe next week or so, to reduce swelling. Some swellingand discoloration around the eyes is expected with theprocedure. Patients should avoid aspirin or alcoholic bev-erages for one week and should limit their activities,including bending, straining, and lifting. The stitches areremoved a few days after surgery. Patients can generallyreturn to their usual activities within a week

Risks
As with any surgical procedure, blepharoplasty can
lead to infection and scarring. Good care of the wound fol-lowing surgery can minimize these risks. In cases wheretoo much skin is removed from the eyelids, the patientmay have difficulty closing his eyes. Dry eye syndromemay develop, requiring the use of artificial tears to lubri-cate the eye. In a rare complication, called retrobulbarhematoma, a pocket of blood forms behind the eyeball.

Most patients can expect good results from blepharo-
plasty, with the removal of excess eyelid skin and fat pro-ducing a more youthful appearance. Some swelling anddiscoloration is expected immediately following the pro-cedure, but this clears in time. Small scars will be leftwhere the surgeon has made incisions; but these generallylighten in appearance over several months, and, if placedcorrectly, will not be readily noticeable.

As noted, if too much excess skin is removed from

the upper eyelid, the patient may be unable to close hiseyes completely; another surgery to correct the defectmay be required. Similarly, too much skin can beremoved from the lower eyelid, allowing too much of thewhite of the eye (the sclera) to show. In extreme cases,the lower lid may be pulled down too far, revealing theunderlying tissue. Called an ectropion, this, too, mayrequire a second, corrective surgery. The eye’s ability tomake tears may also be compromised, leading to dry eyesyndrome.

also be compromised, leading to dry eyesyndrome. Dry eye syndrome is potentially dangerous; inrare cases it leads to damage to the cornea of the eye andvision loss.

Resources
BOOKS
Asken, Saul. “Blepharoplasty.” In Cosmetic Surgery of the
Skin: Principles and Techniques , ed. William P. Coleman.
St. Louis: Mosby, 1997.KEY TERMS
Ectropion —A complication of blepharoplasty, in
which the lower lid is pulled downward, exposingthe surface below.
Intravenous sedation —A method of injecting a
fluid sedative into the blood through the vein
Retrobulbar hematoma —A rare complication of
blepharoplasty, in which a pocket of blood formsbehind the eyeball.

Transconjuctival blepharoplasty —A type of ble-
pharoplasty in which the surgeon makes no inci-sion on the surface of the eyelid, but, instead,enters from behind to tease out the fat deposits.
Flowers, Robert S. “Blepharoplasty and Brow Lifting.” In
Roenigk and Roenigk’s Dermatologic Surgery: Principlesand Practice , ed. Randall K. Roenigk and Henry H.
Roenigk. New York: Marcel Dekker, 1996.
Baylis, Henry I., et al. “Blepharoplasty and Periorbital

Surgery.” Dermatologic Clinics 15 (Oct. 1997): 635-647.
American Society for Dermatologic Surgery. 930 N. Meacham
Road, P.O. Box 4014, Schaumburg, IL 60168-4014. (847)330-9830. <http://www.asds-net.org>.
American Society of Plastic and Reconstructive Surgeons. 44
E. Algonquin Rd., Arlington Heights, IL 60005. (847)228-9900. <http://www.plasticsurgery.org>.
Blindness seeVisual impairment
Blood-viscosity reducing drugs

Blood-viscosity reducing drugs are medicines that
improve blood flow by making the blood less viscous(sticky).
Purpose
The main use of blood-viscosity reducing drugs is to
relieve painful leg cramps caused by poor circulation, acondition called intermittent claudication. Physicians
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also may prescribe this medicine for other conditions,
including stroke ,impotence , male infertility ,Ray-
naud’s disease , and nerve and circulation problems
caused by diabetes.
Blood-viscosity reducing drugs are available only
with a physician’s prescription and come in extended-release tablet form. Examples of blood-viscosity reducingdrugs are pentoxifylline (Trental) and oxypentifylline.
The usual dosage for adults is 400 mg, two to three

times a day, with meals. However, the dose may be dif-ferent for different patients. Check with the physicianwho prescribed the drug or the pharmacist who filled theprescription for the correct dosage. Dosages for childrenmust be determined by a physician.
Taking an antacid with this medicine may help pre-
vent upset stomach.
This medicine may relieve leg pain that results from

poor circulation, but it should not be considered a substi-tute for other treatments the physician recommends, suchas physical therapy or surgery.
This medicine may take several weeks to produce
noticeable results. Be sure to keep taking it as directed,even if it doesn’t seem to be helping.
Patients being treated with this medicine should not
smoke, as smoking may worsen the conditions for which
the medicine is prescribed.
Anyone who has had unusual reactions to pentoxi-

fylline, aminophylline, caffeine , dyphylline, ethylenedi-
amine (contained in aminophylline), oxtriphylline, theo-bromine, or theophylline in the past should let his or herphysician know before taking a blood-viscosity reducingdrug. The physician should also be told about any aller-
giesto foods, dyes, preservatives, or other substances.KEY TERMS
Raynaud’s disease —A blood vessel disorder in

which the fingers and toes become numb and turnwhite when exposed to cold.Women who are pregnant or breastfeeding or who
may become pregnant should check with their physiciansbefore using a blood-viscosity reducing drug.
effects of this medicine, which may increase the chanceof side effects.
Before using blood-viscosity reducing drugs, people

with any of these medical problems should make suretheir physicians are aware of their conditions:
• recent stroke• any condition in which there is an increased chance of
bleeding
Minor discomforts, such as dizziness ,headache ,
upset stomach, nausea, or vomiting usually go away asthe body adjusts to the drug and do not require medicaltreatment unless they persist or they interfere with nor-mal activities.

More serious side effects are rare. However, if these
or any other unusual or troublesome symptoms occur,check with the physician who prescribed the medicine assoon as possible:
Blood-viscosity reducing drugs may interact with a

other medicines, changing the effects of one or both ofthe drugs or increasing the risk of side effects. Anyonewho takes blood-viscosity reducing drugs should let thephysician know all other prescription or nonprescription(over-the-counter) medicines he or she is taking. Amongthe drugs that may interact with blood-viscosity reducingdrugs are:
• anticoagulants such as warfarin (Coumadin)(also called
blood thinners or clot inhibitors)

used to treat high blood pressure
• angiotensin-converting enzyme (ACE) inhibitors such
as enalapril (Vasotec), used to treat high blood pressure
• theophylline (Theo-Dur)
• medicines such as cimetidine (Tagamet), taken for
ulcers or heartburn
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Blood count
One of the most commonly ordered clinical labora-
tory tests, a blood count, also called a complete bloodcount (CBC), is a basic evaluation of the cells (red bloodcells, white blood cells, and platelets) suspended in theliquid part of the blood (plasma). It involves determiningthe numbers, concentrations, and conditions of the differ-ent types of blood cells.
Purpose
The CBC is a useful screening and diagnostic test
that is often done as part of a routine physical examina-

tion. It can provide valuable information about the blood
and blood-forming tissues (especially the bone marrow),as well as other body systems. Abnormal results can indi-cate the presence of a variety of conditions—includinganemias , leukemias, and infections—sometimes before
the patient experiences symptoms of the disease.
A complete blood count is actually a series of tests

in which the numbers of red blood cells, white bloodcells, and platelets in a given volume of blood are count-ed. The CBC also measures the hemoglobin content andthe packed cell volume ( hematocrit ) of the red blood

cells, assesses the size and shape of the red blood cells,and determines the types and percentages of white bloodcells. Components of the complete blood count (hemo-globin, hematocrit, white blood cells, platelets, etc.) canalso be tested separately, and are sometimes done thatway when a doctor wants to monitor a specific condition,such as the white cell count of a patient diagnosed withleukemia, or the hemoglobin of a patient who has recent-ly received a blood transfusion . Because of its

though, as an indicator of a person’s overall health, theCBC package is most frequently ordered.
The blood count is performed relatively inexpen-

sively and quickly. Most laboratories routinely use sometype of automated equipment to dilute the blood, samplea measured volume of the diluted suspension, and countthe cells in that volume. In addition to counting actualnumbers of red cells, white cells, and platelets, the auto-mated cell counters also measure the hemoglobin andcalculate the hematocrit and the red blood cell indices

(measures of the size and hemoglobin content of the redblood cells). Technologists then examine a stained bloodsmear under the microscope to identify any abnormali-ties in the appearance of the red blood cells and to reportthe types and percentages of white blood cells observed.The red blood cell (RBC) count determines the total

number of red cells (erythrocytes) in a sample of blood.The red cells, the most numerous of the cellular ele-ments, carry oxygen from the lungs to the body’s tissues.Hemoglobin (Hgb) is the protein-iron compound in thered blood cells that enables them to transport oxygen. Itsconcentration corresponds closely to the RBC count.Also closely tied to the RBC and hemoglobin values isthe hematocrit (Hct), which measures the percentage ofred blood cells in the total blood volume. The

ofred blood cells in the total blood volume. The hematocrit(expressed as percentage points) is normally about threetimes the hemoglobin concentration (reported as gramsper deciliter).

size and hemoglobin content of the red cells. They areuseful in differentiating types of anemias. The indicesinclude four measurements that are calculated using theRBC count, hemoglobin, and hematocrit results. Meancorpuscular volume (MCV) is a measurement of the aver-age size of the red blood cells and indicates whether thatis small, large or normal. The red blood cell distributionwidth (RDW) is an indication of the variation in RBCsize. Mean corpuscular hemoglobin (MCH) measures theaverage

corpuscular hemoglobin (MCH) measures theaverage amount (weight) of hemoglobin within a redblood cell. A similar measurement, mean corpuscularhemoglobin concentration (MCHC), expresses the aver-age concentration of hemoglobin in the red blood cells.

The white blood cell (WBC) count determines the
total number of white cells (leukocytes) in the blood
GALE ENCYCLOPEDIA OF MEDICINE 2 521Blood count
A white blood cell. (Photograph by Institut Pasteur, Phototake
NYC. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 521

the body’s primary means of fighting infection. There arefive main types of white cells (neutrophils, lymphocytes,monocytes, eosinophils, and basophils), each of whichplays a different role in responding to the presence offoreign organisms in the body. A differential white cellcount is done by staining a smear of the patient’s bloodwith a Wright’s stain, allowing the different types ofwhite cells to be clearly seen under the microscope. Atechnologist then counts a minimum of 100 WBCs andreports

then counts a minimum of 100 WBCs andreports each type of white cell as a percentage of the totalwhite blood cells counted.

The platelet count is an actual count of the number
of platelets (thrombocytes) in a given volume of blood.Platelets, the smallest of the cellular elements of blood,are involved in blood clotting. Because platelets canclump together, the automated counting method is sub-ject to a certain level of error and may not be accurateenough for low platelet counts. For this reason, very lowplatelet levels are often counted manually.
Blood count values can vary by age and sex. The

normal red blood cell count ranges from 4.2–5.4 millionRBCs per microliter of blood for men and 3.6–5.0 mil-lion for women. Hemoglobin values range from 14–18grams per deciliter of blood for men and 12–16 grams forwomen. The normal hematocrit is 42–54% for men and36–48% for women. The normal number of white bloodcells for both men and women is approximately4,000–10,000 WBCs per microliter of blood.

Abnormal blood count results are seen in a variety of
conditions. One of the most common is anemias, whichare characterized by low RBC counts, hemoglobins, andhematocrits. Infections and leukemias are associatedwith increased numbers of WBCs.
Resources
BOOKS
ry Methods. New York: W. B. Saunders Co., 1996.

Karen A. Boyden
Blood crossmatching seeBlood typing and
crossmatchingBlood culture
A blood culture is done when a person has symp-
toms of a blood infection, also called bacteremia . Blood
is drawn from the person one or more times and is testedin a laboratory to find and identify any microorganismpresent and growing in the blood. If a microorganism isfound, more testing is done to determine the antibiotics

that will be effective in treating the infection.
Purpose
Bacteremia is a serious clinical condition and can
lead to death . To give the best chance for effective treat-
ment and survival, a blood culture is done as soon as aninfection is suspected.
Symptoms of bacteremia are fever , chills, mental
confusion, anxiety , rapid heart beat, hyperventilation,
blood clotting problems, and shock . These symptoms are

especially significant in a person who already has anoth-er illness or infection, is hospitalized, or has troublefighting infections because of a weak immune system.Often, the blood infection results from an infectionsomewhere else in the body that has now spread.
Additionally, blood cultures are done to find the
causes of other infections. These include bacterial pneu-
monia (an infection of the lung), and infectious endo-
carditis (an infection of the inner layer of the heart).

Both of these infections leak bacteria into the blood.
After a blood infection has been diagnosed, con-
firmed by culture, and treated, an additional blood cul-ture may be done to make sure the infection is gone.
Culture strategies
There are many variables involved in performing a
blood culture. Before the person’s blood is drawn, thephysician must make several decisions based on a knowl-edge of infections and the person’s clinical condition andmedical history.

Several groups of microorganisms, including bacte-
ria, viruses, mold, and yeast, can cause blood infections.The bacteria group can be further broken down into aer-obes and anaerobes. Most aerobes do not need oxygen tolive. They can grow with oxygen (aerobic microbes) orwithout oxygen (anaerobic microbes).
Based on the clinical condition of the patient, the
physician determines what group of microorganisms islikely to be causing the infection and then orders one or

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more specific types of blood culture, including aerobic,
anaerobic, viral, or fungal (for yeasts and molds). Eachspecific type of culture is handled differently by the labo-ratory. Most blood cultures test for both aerobic andanaerobic microbes. Fungal, viral, and mycobacterialblood cultures can also be done, but are less common.
The physician must also decide how many blood

cultures should be done. One culture is rarely enough,but two to three are usually adequate. Four cultures areoccasionally required. Some factors influencing thisdecision are the specific microorganisms the physicianexpects to find based on the person’s symptoms or previ-ous culture results, and whether or not the person has hadrecent antibiotic therapy.
The time at which the cultures are to be drawn is

another decision made by the physician. During mostblood infections (called intermittent bacteremia) microor-ganisms enter the blood at various time intervals. Blooddrawn randomly may miss the microorganisms. Sincemicroorganisms enter the blood 30–90 minutes before theperson’s fever spikes, collecting the culture just after thefever spike offers the best likelihood of finding themicroorganism. The second and third cultures may becollected at the same time, but from different places onthe

at the same time, but from different places onthe person, or spaced at 30-minute or one-hour intervals,as the physician chooses. During continuous bacteremia,such as infective endocarditis, microorganisms are alwaysin the blood and the timing of culture collection is lessimportant. Blood cultures should always be collectedbefore antibiotic treatment has begun.

Laboratory analysis
Bacteria are the most common microorganisms
found in blood infections. Laboratory analysis of a bacte-rial blood culture differs slightly from that of a fungalculture and significantly from that of a viral culture.
Blood is drawn from a person and put directly into a
blood culture bottle containing a nutritional broth. Afterthe laboratory receives the blood culture bottle, severalprocesses must be completed:

• provide an environment for the bacteria to grow• detect the growth when it occurs• identify the bacteria that grow• test the bacteria against certain antibiotics to determine
which antibiotic will be effective
There are several types of systems, both manual and
automated, available to laboratories to carry out theseprocesses.
The broth in the blood culture bottle is the first step

in creating an environment in which bacteria will grow. Itcontains all the nutrients that bacteria need to grow. If the
physician expects anaerobic bacteria to grow, oxygenwill be kept out of the blood culture bottle; if aerobes areexpected, oxygen will be allowed in the bottle.
The bottles are placed in an incubator and kept at

body temperature. They are watched daily for signs ofgrowth, including cloudiness or a color change in thebroth, gas bubbles, or clumps of bacteria. When there isevidence of growth, the laboratory does a gram stain anda subculture. To do the gram stain, a drop of blood isremoved from the bottle and placed on a microscopeslide. The blood is allowed to dry and then is stained withpurple and red stains and examined under the micro-scope. If bacteria are seen, the color of stain they pickedup

are seen, the color of stain they pickedup (purple or red), their shape (such as round or rectan-gular), and their size provide valuable clues as to whattype of microorganism they are and what antibioticsmight work best. To do the subculture, a drop of blood isplaced on a culture plate, spread over the surface, andplaced in an incubator.

If there is no immediate visible evidence of growth
in the bottles, the laboratory looks for bacteria by doinggram stains and subcultures. These steps are repeateddaily for the first several days and periodically after that.
When bacteria grows, the laboratory identifies it

using biochemical tests and the gram stain. Sensitivitytesting, also called antibiotic susceptibility testing, is alsodone. The bacteria are tested against many differentantibiotics to see which antibiotics can effectively kill it.
All information is passed on to the physician as soon

as it is known. An early report, known as a preliminaryreport, is usually available after one day. This report willtell if any bacteria have been found yet, and if so, theresults of the gram stain. The next preliminary report mayinclude a description of the bacteria growing on the sub-culture. The laboratory notifies the physician immediatelywhen an organism is found and as soon as sensitivity testsare complete. Sensitivity tests may be complete before thebacteria is completely identified. The

before thebacteria is completely identified. The final report may notbe available for five to seven days. If bacteria was found,the report will include its complete identification and alist of the antibiotics to which the bacteria is sensitive.

important recent technical advances in blood cultures. Itis called continuous-monitoring blood culture systems(CMCCS). The instruments automatically monitor thebottles containing the patient blood for evidence ofmicroorganisms, usually every 10 minutes. Many datapoints are collected daily for each bottle, and fed into acomputer for analysis. Sophisticated mathematical calcu-lations can determine when microorganisms have grown.This, combined with more frequent blood tests, make it

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possible to detect microbial growth earlier. In addition,
all CMBCS instruments have the detection system, incu-bator, and agitation unit in one unit.
Ten ml (milliliter) of blood is usually needed for

each blood culture bottle. First a healthcare workerlocates a vein in the inner elbow region. The area of skinwhere the blood will be drawn must be disinfected toprevent any microorganisms on a person’s skin fromentering the blood culture bottle and contaminating it.The area is disinfected by wiping the area with alcohol ina circular fashion, starting with tiny circles at the spotwhere the needle will puncture the skin and enlarging thesize of the circles while wiping away from the

thesize of the circles while wiping away from the puncturesite. The same pattern of wiping is repeated using aniodine or iodophor solution. The top of the bottle is disin-fected using alcohol. After the person’s skin has beendisinfected, the healthcare worker draws the blood andabout 10 ml of blood is injected into each blood culturebottle. The type of bottles used will vary based onwhether the physician is looking for bacteria (aerobes oranaerobes), yeast, mold, or viruses.

Aftercare
Normal results will be negative. A single negative
culture does not rule out a blood infection. False nega-tives can occur if the person was started on antibioticsbefore the blood was drawn, if the environment forKEY TERMS
Aerobe —Bacteria that require oxygen to live.

Anaerobe —Bacteria that live where there is no
oxygen.
Bacteremia —Bacteria in the blood.
Continuous bacteremia —A kind of bacteremia
where bacteria is always in the blood.
Intermittent bacteremia —A kind of bacteremia
where the bacteria enter the blood at various timeintervals.growth was not right, the timing was off, or for some

unknown reason the microorganism just didn’t grow.Three negative cultures may be enough to rule out bac-teremia in the case of endocarditis.
The physician’s skill in interpreting the culture

results and assessing the person’s clinical condition isessential in distinguishing a blood culture that is positivebecause of a true infection from a culture that is positivebecause it became contaminated. In true bacteremia, thepatient’s clinical condition should be consistent with ablood infection caused by the microorganism that wasfound. The microorganism is usually found in more thanone culture, it usually grows soon after the bottles areincubated, and it is often the cause of an

areincubated, and it is often the cause of an infection some-where else in the person’s body.

When the culture is positive because of contamina-
tion, the patient’s clinical condition usually is not consis-tent with an infection from the identified microorganism.In addition, the microorganism is often one commonlyfound on skin, it rarely causes infection, it is found inonly one bottle, and it may appear after several days ofincubation. More than one microorganism often grow incontaminated cultures.
Resources
BOOKS
Warren, John R. “Sepsis.” In The Biologic and Clinical Basis

of Infectious Diseases Ed. Standford T. Shulman, et.al.
Philadelphia: W. B. Saunders Co., 1997.
Reimer, L. G., M. L. Wilson, and M. P. Weinstein. “Update on
Detection of Bacteremia and Fungemia.” Clinical Micro-
biology Review (July 1997): 444-465.
American Society of Microbiology. 1752 N Street N.W., Wash-
ington, D.C. 20036. (202) 737-3600. <http://www.asmusa.org>.
Blood donation and registry

Blood donation refers to the process of collecting,
testing, preparing, and storing blood and blood compo-nents. Donors are most commonly unpaid volunteers, butthey may also be paid by commercial enterprises. Blood
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registry refers to the collection and sharing of data about
donated blood and ineligible donors.
Purpose
The purpose of the blood collection and distribution
system is to help ensure an adequate supply of blood foraccident victims, people needing surgery, and people suffer-ing from certain diseases, as well as for medical research.
Sometimes, donors give blood specifically to benefit

a particular person. People preparing for elective surgerymay donate their own blood to be held and then returnedto them during surgery. This is known as autologousblood donation. Directed donor blood has been donatedby someone known to the intended recipient, such as afamily member or friend.
Each year, more than four million Americans receive

blood transfusions involving more than 26 million unitsof blood (one unit equals 450 milliliters, or about onepint), or an average of about 32,000 units per day. All ofthat blood must be collected, tested, prepared, stored, anddelivered to the appropriate sites. Roughly eight millionpeople in the United States donate blood each year; abouthalf of the total amount needed is provided by the 36regional blood centers of the American Red Cross.
Whole blood and the various blood components have

many uses. Red blood cells, which carry oxygen, are usedto treat anemia. Platelets, which play a role in controllingbleeding, are commonly used in the treatment ofleukemia and other cancers. Fresh frozen plasma is alsoused to control bleeding in people deficient in certainclotting factors. Cryoprecipitated AHF, made from freshfrozen plasma, contains a few specific clotting factors.
To ensure the safety of the blood supply, a multi-

tiered process of donor screening and deferral isemployed. This involves donor education, taking adetailed health history of each prospective donor, andgiving potential donors a simple physical examination

(which includes taking a few drops of blood to test foranemia). At any point in the process, a potential donormay be “deferred,” or judged ineligible to donate blood.This deferral may be temporary or permanent, dependingon the reason. Potential donors are also encouraged to“self-defer,” or voluntarily decline to donate, rather thanput future blood recipients at risk.
All donated blood is extensively tested before being

used. The first step is determining the blood type, whichindicates who can receive the blood. Receiving the wrongtype of blood can cause death . Blood is also screened for
any antibodies that could cause complications for recipi-ents. In addition, blood is tested to screen out donors
infected with the following diseases: Hepatitis B surface
antigen ADD, hepatitis B core antibody, hepatitis C virus

antibody, HIV-1 and HIV-2 antibody, HIV p24 antigen,HTLV-I and HTLV-II antibodies, and syphilis . Nucleic
Acid Amplification testing is also performed, and othertests may be done if a doctor requests them.
In order to detect the greatest possible number of

infections, these screening tests are extremely sensitive.For this reason, however, donors sometimes receive falsepositive test results. In these cases, more specific confir-matory tests are performed, to help rule out false positiveresults. Blood found to be abnormal is discarded, and allitems coming into direct contact with donors are usedonly once and then discarded. Donors of infected bloodare entered into the Donor Deferral Register, a confiden-tial national data base used to prevent

confiden-tial national data base used to prevent deferred peoplefrom donating blood.

In general, blood donors must be at least 17 years
old (some states allow younger people to donate bloodwith their parents’ consent), must weigh at least 110pounds (50 kg), and must be in good health.
Many factors can temporarily or permanently dis-

qualify potential donors. Most of them have to do withhaving engaged in behaviors that put them at risk ofinfection or having spent time in certain specified areas.Among these factors are having had a tattoo, having hadsex with people in high-risk groups, having had certaindiseases, and having been raped.
There are eight different blood types in all—four

ABO groups, each of which may be either Rh positive orRh negative. These types, and their approximate distribu-tion in the U.S. population, are as follows: O+ (38%), O-(7%), A+ (34%), A- (6%), B+ (9%), B- (2%), AB+ (3%),AB- (1%). In an emergency, anyone can safely receivetype O red blood cells, and people with this blood type areknown as “universal donors. “ People with type AB blood,known as “universal recipients,” can receive any type ofred blood cells and can give plasma to all blood types.

centers, at hospitals or in bloodmobiles, which visitschools, churches and workplaces. The actual process ofdonating whole blood takes about 20 minutes. A sterileneedle is inserted into a vein in the donor’s arm. Theblood flows through plastic tubing into a blood bag.Donors may be asked to clench their fist to encourageblood to flow. Usually, one unit of blood is collected.Afterward, donors are escorted to an observation area,given light refreshments, and allowed to rest.

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blood cells, platelets and other elements are suspended, isalso collected, often by commercial enterprises that sell itto companies manufacturing clotting factors and otherblood products. This is done using a process known asapheresis, in which whole blood is collected, the desiredblood component is removed, and the remainder is returnedto the donor. Collecting plasma generally takes one to twohours. Apheresis may also be used to collect other bloodcomponents, such as platelets and

Once whole blood has been collected, it is sent to a lab
for testing and processing. Most donated blood is separatedinto its constituent components, such as red blood cells,platelets, and cryoprecipitate. This enables more than oneperson to benefit from the same unit of donated blood.
Different blood components vary in how long they

can be stored. Red blood cells can be refrigerated for upto 42 days or frozen for as much as 10 years. Platelets,stored at room temperature, may be kept for up to fivedays. Fresh frozen plasma and cryoprecipitated AHF canbe kept for as much as one year.
Aftercare
It generally takes about 24 hours for the donor’s

body to replenish the lost fluid. Replacing the lost redblood cells, however, may take as much as two months.Whole blood donors must wait a minimum of eightweeks before donating again. Some states place furtherlimits on the frequency and/or total number of times anindividual may donate blood within a 12-month period.
Risks
Thanks to the use of a multi-tiered screening sys-
tem and advances in the effectiveness of screening tests,KEY TERMS

Apheresis —Extraction of a specific component
from donated blood, with the remainder returnedto the donor.
Autologous donation —Blood donated for the
donor’s own use.
Granulocytes —White blood cells.
Plasma —The liquid part of blood.
Platelets —Tiny, disklike elements of plasma that
promote clotting.the transmission of infectious diseases via transfusion

has been significantly diminished. Nonetheless, there isstill a minuscule risk that blood recipients could con-tract HIV , Hepatitis C, or other infections via transfu-sion. Other diseases that could conceivably be contract-ed in this way, or that are of particular concern toblood-collection agencies, include babesiosis , Chagas
disease, HTLV-I and -II, Creutzfeldt-Jakob disease ,
cytomegalovirus, Lyme disease ,malaria , and new
variant Creutzfeldt-Jakob disease.

Autologous blood donors run a tiny risk of having
the wrong blood returned to them due to clerical error.There is also a faint possibility of bacterial contamina-tion of the autologous blood.
For most donors, the process is quick and painless
and they leave feeling fine. They may also find satisfac-tion in knowing that they have contributed to the nation’sblood supply and may even have helped save lives.

Most blood donors suffer no significant aftereffects.
Occasionally, however, donors feel faint or dizzy, nau-seous, and/or have pain , redness, or a bruise where the
blood was taken. More serious complications, whichrarely occur, include fainting , muscle spasms, and nerve
damage.
Resources
BOOKS
Starr, Douglass. Blood: An Epic History of Medicine and Com-
merce. New York: Alfred A Knopf, 1998.
McKenna, C. “Blood Minded” Nursing Times (6 April 2000) :
27-28.

27-28.
Wagner, H. “Umbilical Cord Blood Banking: Insurance
Against Future Diseases?” USA Today Magazine (March
2000) : 59-61.
American Association of Blood Banks. 8101 Glenbrook Road,
Bethesda, MD 20814-2749. (301) 907-6977. <http://www.aabb.org>.
American Red Cross. 430 17th Street NW, Washington, D.C.
20006. <http://www.redcross.org>.
National Blood Data Resource Center. (301) 215-6506. <http://
www.nbdrc.org>.
Blood fluke infection seeSchistosomiasis

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Blood gas analysis
Blood gas analysis, also called arterial blood gas
(ABG) analysis, is a test which measures the amounts ofoxygen and carbon dioxide in the blood, as well as theacidity (pH) of the blood.
Purpose
An ABG analysis evaluates how effectively the

lungs are delivering oxygen to the blood and how effi-ciently they are eliminating carbon dioxide from it. Thetest also indicates how well the lungs and kidneys areinteracting to maintain normal blood pH (acid-base bal-ance). Blood gas studies are usually done to assess respi-ratory disease and other conditions that may affect thelungs, and to manage patients receiving oxygen therapy(respiratory therapy). In addition, the acid-base compo-nent of the test provides information on kidney function.

Blood gas analysis is performed on blood from an
artery. It measures the partial pressures of oxygen andcarbon dioxide in the blood, as well as oxygen content,oxygen saturation, bicarbonate content, and blood pH.
Oxygen in the lungs is carried to the tissues through

the bloodstream, but only a small amount of this oxygencan actually dissolve in arterial blood. How much dis-solves depends on the partial pressure of the oxygen (thepressure that the gas exerts on the walls of the arteries).Therefore, testing the partial pressure of oxygen is actu-ally measuring how much oxygen the lungs are deliver-ing to the blood. Carbon dioxide is released into theblood as a by-product of cell metabolism. The partialcarbon dioxide pressure indicates how well the lungs

dioxide pressure indicates how well the lungs areeliminating this carbon dioxide.

The remainder of oxygen that is not dissolved in the
blood combines with hemoglobin, a protein—iron com-pound found in the red blood cells. The oxygen contentmeasurement in an ABG analysis indicates how muchoxygen is combined with the hemoglobin. A relatedvalue is the oxygen saturation, which compares theamount of oxygen actually combined with hemoglobin tothe total amount of oxygen that the hemoglobin is capa-ble of combining with.
Carbon dioxide dissolves more readily in the blood

than oxygen does, primarily forming bicarbonate andsmaller amounts of carbonic acid. When present in nor-mal amounts, the ratio of carbonic acid to bicarbonatecreates an acid-base balance in the blood, helping to keepthe pH at a level where the body’s cellular functions aremost efficient. The lungs and kidneys both participate inmaintaining the carbonic acid-bicarbonate balance. Thelungs control the carbonic acid level and the kidneys reg-ulate the bicarbonate. If either organ is not

reg-ulate the bicarbonate. If either organ is not functioningproperly, an acid-base imbalance can result. Determina-tion of bicarbonate and pH levels, then, aids in diagnos-ing the cause of abnormal blood gas values.

The procedure
The blood sample is obtained by arterial puncture (usu-

ally in the wrist, although it could be in the groin or arm) orfrom an arterial line already in place. If a puncture is need-ed, the skin over the artery is cleaned with an antiseptic. Atechnician then collects the blood with a small sterile needleattached to a disposable syringe. The patient may feel abrief throbbing or cramping at the site of the puncture. Afterthe blood is drawn, the sample must be transported to thelaboratory as soon as possible for analysis.

GALE ENCYCLOPEDIA OF MEDICINE 2 527Blood gas analysis
A blood gas analyzer from Corning Corporation. (Photo-
graph by Hank Morgan, Photo Researchers, Inc. Reproduced bypermission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 527

There are no special preparations. Patients have no
restrictions on drinking or eating before the test. If thepatient is receiving oxygen, the oxygen concentrationmust remain the same for 20 minutes before the test; ifthe test is to be taken without oxygen, the gas must beturned off for 20 minutes before the test is taken. Thepatient should breathe normally during the test.
Aftercare
After the blood has been taken, the technician or the

patient applies pressure to the puncture site for 10–15minutes to stop the bleeding, and then places a dressingover the puncture.The patient should rest quietly whileapplying the pressure to the puncture site. Health careworkers will observe the patient for signs of bleeding orcirculation problems
Risks
Risks are very low when the test is done correctly.

Risks include bleeding or bruising at the site, or delayedbleeding from the site. Very rarely, there may be a prob-lem with circulation in the puncture area.
Normal blood gas values are as follows:
• partial pressure of oxygen (PaO 2): 75–100 mm Hg
• partial pressure of carbon dioxide (PaCO2): 35–45 mm
Hg
• oxygen content (O2CT): 15–23%
• oxygen saturation (SaO2): 94–100%
• bicarbonate (HCO3): 22–26 mEq/liter
• pH: 7.35–7.45KEY TERMS
Acid-base balance —The condition that exists

when the body’s carbonic acid-bicarbonate buffersystem is in equilibrium, helping to maintain theblood pH at a normal level of 7.35–7.45.
Hemoglobin —A protein-iron compound in red
blood cells that functions primarily in carryingoxygen from the lungs to the tissues of the body.
pH—A measure of the acidity of a solution. Nor-
mal blood pH ranges from 7.35–7.45.Abnormal results
Values that differ from those listed above may indi-

cate respiratory, metabolic, or kidney disease. Theseresults also may be abnormal if the patient has experi-enced trauma that may affect breathing (especially headand neck injuries). Disorders, such as anemia, that affectthe oxygen-carrying capacity of blood, can produce anabnormally low oxygen content value.
Resources
BOOKS
Thompson, June, et al. Mosby’s Clinical Nursing. 4th ed. St.

Louis: Mosby, 1997.
Blood poisoning seeAcute lymphangitis
Blood registry seeBlood donation and
registry
Blood removal seePhlebotomy
Blood sugar tests
Blood sugar tests include several different tests that
measure the amount of sugar (glucose) in a person’sblood. These tests are done either on an empty stomach,or after consuming a meal or premeasured glucose drink.Blood sugar tests are done primarily to diagnose andevaluate a person with diabetes mellitus .
Purpose

Purpose
The body uses sugar, also called glucose, to supply
the energy it needs to function. People get sugar fromtheir diet and from their body tissues. Insulin is made bythe pancreas and affects the outer membrane of cells,making it easy for glucose to move from the blood intothe cells. When insulin is active, blood glucose levels fall.Sugar from body tissues is stored in the form of glycogen.When glycogen is active, blood glucose levels rise.

After a meal, blood glucose levels rise sharply. The
pancreas responds by releasing enough insulin to takecare of all the newly added sugar found in the body. Theinsulin moves the sugar out of the blood and into thecells. Only then does the blood sugar start to level off and
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begin to fall. A person with diabetes mellitus either does
not make enough insulin, or makes insulin that does notwork properly. The result is blood sugar that remainshigh, a condition called hyperglycemia.
Diabetes must be diagnosed as early as possible. If
left untreated, it can damage or cause failure of the eyes,kidneys, nerves, heart, blood vessels, and other bodyorgans. Hypoglycemia , or low blood sugar, may also be

discovered through blood sugar testing. Hypoglycemia iscaused by various hormone disorders and liver disease,as well as by too much insulin.
There are a variety of ways to measure a person’s
blood sugar.
Whole blood glucose test
Whole blood glucose testing can be performed by a

person in his or her home, and kits are available for thispurpose. The person pricks his or her finger (a fingerstick) with a sterile sharp blade from the kit. A singledrop of blood is placed on a strip in a portable instrumentcalled a glucometer. The glucometer quickly determinesthe blood sugar and shows the results on a small screenin usually a few seconds.
Fasting plasma glucose test
The fasting plasma glucose test is done on an empty

stomach. For the eight hours before the test, the personmust fast (nothing to eat or drink, except water). The per-son’s blood is drawn from a vein by a healthcare worker.The blood sample is collected into a tube containing ananticoagulant. Anticoagulants stop the blood from clot-ting. In the laboratory, the tube of blood spins at highspeed within a machine called a centrifuge. The bloodcells sink to the bottom and the liquid stays on the top.This straw-colored liquid on the top is the plasma.

straw-colored liquid on the top is the plasma. Tomeasure the glucose, a person’s plasma is combined withother substances. From the resulting reaction, the amountof glucose in the plasma is determined.

Oral glucose tolerance test
The oral glucose tolerance test is done to see how

well the body handles a standard amount of glucose. Thistest measures the amount of glucose in a person’s plasmabefore and two hours after drinking a large premeasuredbeverage containing glucose. The person must eat a con-sistent diet, containing at least 5.25oz (150 g) of carbohy-drates each day, for three days before this test. For eighthours before the test, the person must fast. A healthcareprovider draws the first sample of blood at the end of thefast to determine the glucose level at the

of thefast to determine the glucose level at the start of the test.

The healthcare provider then gives the person a beveragecontaining 2.6 oz (75 g) of glucose. Two hours later, theperson’s blood is drawn again. These blood samples arecentrifuged and processed in the laboratory. A doctor canthen compare the before and after glucose levels to seehow well the body processed the sugar.
Two-hour postprandial blood glucose test
The two-hour postprandial blood glucose test mea-

sures the amount of glucose in plasma after a person eatsa specific meal containing a certain amount of sugar.Although the meal follows a predetermined menu, it isdifficult to control many factors associated with this test-ing method.
Blood sugar tests can be used in a variety of situa-
tions including:
• Testing people suspected for diabetes. The American

Diabetic Association (ADA) recommends that either afasting plasma glucose test or an oral glucose tolerancetest be used to diagnose diabetes. If the person alreadyhas symptoms of diabetes, a blood glucose test withoutfasting (called a casual plasma glucose test) may bedone. If the test result is abnormal, it must be confirmedwith another test performed on another day. The twotests can be different or they can be the same, but theymust be done on different days. If the second test is

be done on different days. If the second test is alsoabnormal, the person has diabetes. A two-hour post-prandial test is not recommended by the ADA as a testto use for the diagnosis of diabetes. A doctor may orderthis test, and follow it with the oral glucose tolerancetest or the fasting plasma glucose test if the results areabnormal.

• Testing pregnant women. Diabetes that occurs during
pregnancy (gestational diabetes ) is dangerous for

both the mother and the baby. Women who may be atrisk are screened when they are 24-28 weeks pregnant.A woman is considered at risk if she is older than 25years, is not at her normal body weight, has a parent orsibling with diabetes, or if she is in an ethnic group thathas a high rate of diabetes (Hispanics, Native Ameri-cans, Asians, African Americans). The blood sugar testto screen for gestational diabetes is a variation of theoral glucose tolerance test. Fasting is not required. Ifthe result

test. Fasting is not required. Ifthe result is abnormal, a more complete test is done onanother day.

• Testing healthy people. Healthy people without symp-
toms of diabetes should be screened for diabetes whenthey are 45 years old and again every three years. Eitherthe fasting plasma glucose or oral glucose tolerance testis used for screening. People in high risk groups shouldbe tested before the age of 45 and tested more frequently.
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• Testing of people already diagnosed with diabetes. The
ADA recommends that a person with diabetes keep theamount of glucose in the blood at a normal level as muchas possible. This can be done by the diabetic person test-ing his or her own blood at home one or more times a day.
Each blood sugar test that uses plasma requires a 5

mL blood sample. A healthcare worker ties a tight band(tourniquet) on the person’s upper arm, locates a vein inthe inner elbow region, and inserts a needle into thatvein. Vacuum action draws the blood through the needleinto an attached tube. Collection of the sample takes onlya few minutes.
When fasting is required, the person should have

nothing to eat or drink (except water) for eight hoursbefore the test and until the test or series of tests is com-pleted. The person should not smoke before or during thetesting period because this can temporarily increase theamount of glucose in the blood. Other factors that cancause inaccurate results are a change in diet before thetest, illness or surgery two weeks before the test, certaindrugs, and extended bed rest. The doctor may tell a per-son on insulin or taking pills for diabetes to

on insulin or taking pills for diabetes to stop themedication until after the test.

Aftercare
After the test or series of tests is completed (and
with the approval of his or her doctor), the person shouldeat, drink, and take any medications that were stoppedfor the test.
The patient may feel discomfort when blood is drawn
from a vein. Bruising may occur at the puncture site orthe person may feel dizzy or faint. Pressure to the punc-ture site until the bleeding stops will reduce bruising.Warm packs to the puncture site will relieve discomfort.
Risks

Risks
If the person experiences any weakness, fainting ,
sweating, or any other unusual reaction while fasting orduring the test, he or she should immediately tell the per-son giving the test.
Normal results are:
• fasting plasma glucose test less than 120 mg/dL
• oral glucose tolerance test, 2 hours less than 140 mg/dL
For the diabetic person, the ADA recommends an ongo-
ing blood sugar goal of less than or equal to 120 mg/dL.Abnormal results

These abnormal results indicate diabetes and must
be confirmed with repeat testing:
• fasting plasma glucose test less than or equal to 126
mg/dL
• oral glucose tolerance test, 2 hours less than or equal to
200 mg/dL
• casual plasma glucose test (nonfasting, with symptoms)
less than or equal to 200 mg/dL
• gestational oral glucose tolerance test, 1 hour less than
or equal to 140 mg/dL
Brain damage can occur from glucose levels below
40 mg/dL and coma from levels above 470 mg/dL.

Other hormone disorders can cause both hyper-
glycemia and hypoglycemia. Abnormal results must beinterpreted by a doctor who is aware of the person’s med-ical condition and medical history.
Resources
BOOKS

American Diabetes Association. “Report of the Expert Com-
mittee on the Diagnosis and Classification of DiabetesMellitus.” Diabetes Care 20, no, 7(July 997): 1183-1197.

Way, Bethesda, MD 20892-3560. (800) 860-8747. <http://www.niddk.nih.gov/health/diabetes/ndic.htm>.
Blood thinners seeAnticoagulant and
Blood transfusion seeTransfusion

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Blood typing and
Blood typing is a laboratory test done to determine a
person’s blood type. If the person needs a blood transfu-
sion, another test called crossmatching is done after the
blood is typed to find blood from a donor that the per-son’s body will accept.
Purpose
Blood typing and crossmatching are most common-

ly done to make certain that a person who needs a trans-fusion will receive blood that matches (is compatiblewith) his own. People must receive blood of the sameblood type, otherwise, a serious, even fatal, transfusionreaction can occur.
Parents who are expecting a baby have their blood
typed to diagnose and prevent hemolytic disease of thenewborn (HDN), a type of anemia also known as ery-
throblastosis fetalis . Babies who have a blood type dif-

ferent from their mothers are at risk for developing thisdisease. The disease is serious with certain blood typedifferences, but is milder with others.
A child inherits factors or genes from each parent
that determine his blood type. This fact makes blood typ-ing useful in paternity testing. To determine whether ornot the alleged father could be the true father, the bloodtypes of the child, mother, and alleged father are com-pared.
Legal investigations may require typing of blood or

other body fluids, such as semen or saliva, to identifypersons involved in crimes or other legal matters.
Blood typing and crossmatching tests are performed
in a blood bank laboratory by technologists trained inblood bank and transfusion services. The tests are doneon blood, after it has separated into cells and serum(serum is the yellow liquid left after the blood clots.)Costs for both tests are covered by insurance when thetests are determined to be medically necessary.

Blood bank laboratories are usually located in facili-
ties, such as those operated by the American Red Cross,that collect, process, and supply blood that is donated, aswell as in facilities, such as most hospitals, that prepareblood for transfusion. These laboratories are regulated bythe United States Food and Drug Administration (FDA)and are often inspected and accredited by a professionalassociation such as the American Association of BloodBanks (AABB).

the reaction between antigens and antibodies. An antigencan be anything that causes the body to launch an attack,known as an immune response, against it. The attackbegins when the body builds a special protein, called anantibody, that is uniquely designed to attack and makeineffective (neutralize) the specific antigen that causedthe attack. A person’s body normally doesn’t make anti-bodies against its own antigens, only against antigensthat are foreign to it.

A person’s body contains many antigens. The anti-
gens found on the surface of red blood cells are impor-tant because they determine a person’s blood type. Whenred blood cells having a certain blood type antigen aremixed with serum containing antibodies against that anti-gen, the antibodies attack and stick to the antigen. In atest tube, this reaction is observed as the formation ofclumps of cells (clumping).
When blood is typed, a person’s cells and serum are

mixed in a test tube with commercially-prepared serumand cells. Clumping tells which antigens or antibodiesare present and reveals the person’s blood type. Whenblood is crossmatched, patient serum is mixed with cellsfrom donated blood that might be used for transfusion.Clumping or lack of clumping in the test tube tellswhether or not the blood is compatible.
Although there are over 600 known red blood cell

antigens, organized into 22 blood group systems, routineblood typing and crossmatching is usually concernedwith only two systems: the ABO and Rh blood groupsystems.
Blood typing
ABO BLOOD GROUP SYSTEM. In 1901, Karl Land-

steiner, an Austrian pathologist, randomly combined theserum and red blood cells of his colleagues. From thereactions he observed in test tubes, he discovered theABO blood group system. This discovery earned him the1930 Nobel Prize in Medicine.
A person’s ABO blood type—A, B, AB, or O—is

based on the presence or absence of the A and B antigenson his red blood cells. The A blood type has only the Aantigen and the B blood type has only the B antigen. TheAB blood type has both A and B antigens, and the Oblood type has neither A nor B antigen.
By the time a person is six months old, he naturally

will have developed antibodies against the antigens hisred blood cells lack. That is, a person with A blood typewill have anti-B antibodies, and a person with B blood
GALE ENCYCLOPEDIA OF MEDICINE 2 531Blood typing and crossmatchingGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 531

type will have anti-A antibodies. A person with AB blood
type will have neither antibody, but a person with Oblood type will have both anti-A and anti-B antibodies.Although the distribution of each of the four ABO bloodtypes varies between racial groups, O is the most com-mon and AB is the least common.
ABO typing is the first test done on blood when it is

tested for transfusion. A person must receive ABO-matched blood. ABO incompatibilities are the majorcause of fatal transfusion reactions. ABO antigens arealso found on most body organs, so ABO compatibility isalso important for organ transplants.
An ABO incompatibility between a pregnant woman
and her baby is a minor cause of HDN and usually causesno problem for the baby. The structure of ABO antibod-ies makes it unlikely they will cross the placenta to attackthe baby’s red blood cells.

Paternity testing compares the ABO blood types of
the child, mother, and alleged father. The alleged fathercan’t be the true father if the child’s blood type requires agene that neither he nor the mother have. For example, achild with blood type B whose mother has blood type O,requires a father with either AB or B blood type; a man
with blood type O cannot be the true father.
In some people, ABO antigens can be found in body

fluids other than blood, such as saliva and semen. ABOtyping of these fluids provides clues in legal investigations.
RH BLOOD GROUP SYSTEM. The Rh, or Rhesus,
system was first detected in 1940 by Landsteiner andWiener when they injected blood from rhesus monkeysinto guinea pigs and rabbits. More than 50 antigens havesince been discovered belonging to this system, makingit the most complex red blood cell antigen system.

In routine blood typing and crossmatching tests,
only one of these 50 antigens, the D antigen, also knownas the Rh factor or Rh
o[D], is tested for. If the D antigen
is present, that person is Rh-positive; if the D antigen isabsent, that person is Rh-negative.
Other important antigens in the Rh system are C, c,

E, and e. These antigens are not usually tested for in rou-tine blood typing tests. However, testing for the presenceof these antigens is useful in paternity testing, and whena technologist tries to identify unexpected Rh antibodies
GALE ENCYCLOPEDIA OF MEDICINE 2 532Blood typing and crossmatchingRecipient's blood
ABO
antigensABO
antibodiesDonor type
O cellsDonor type
A cellsDonor type
B cellsDonor type
AB cellsABO blood
type
O
AB
ABNoneAnti-A
Anti-B
A Anti-B
B Anti-A
A & B None

Anti-B
A Anti-B
B Anti-A
A & B None
Compatible Not compatibleReactions with donor's red blood cells
Blood typing is a laboratory test done to discover a person’s blood type. If the person needs a blood transfusion, cross-
matching is done following blood typing to locate donor blood that the person’s body will accept. (Illustration by Electronic
Illustrators Group.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 532

or find matching blood for a person with antibodies to
one or more of these antigens.
Unlike the ABO system, antibodies to Rh antigens
don’t develop naturally. They develop only as an immuneresponse after a transfusion or during pregnancy .
The incidence of the Rh blood types varies between
racial groups, but not as widely as the ABO blood types:85% of whites and 90% of blacks are Rh-positive; 15%of whites and 10% of blacks are Rh-negative.
In transfusions, the Rh system is next in importance

after the ABO system. Most Rh-negative people whoreceive Rh-positive blood will develop anti-D antibodies.A later transfusion of Rh-positive blood could result in asevere or fatal transfusion reaction.
Rh incompatibility is the most common and severe

cause of HDN. This incompatibility can happen when anRh-negative woman and an Rh-positive man produce anRh-positive baby. Cells from the baby can cross the pla-centa and enter the mother’s bloodstream, causing themother to make anti-D antibodies. Unlike ABO antibod-ies, the structure of anti-D antibodies makes it likely thatthey will cross the placenta and enter the baby’s blood-stream. There, they can destroy the baby’s red bloodcells, causing severe or fatal anemia.

The first step in preventing HDN is to find out the Rh
types of the expectant parents. If the mother is Rh-negativeand the father is Rh-positive, the baby is at risk for devel-oping HDN. The next step is to test the mother’s serum tomake sure she doesn’t already have anti-D antibodies fromKEY TERMS
ABO blood type —Blood type based on the pres-
ence or absence of the A and B antigens on the redblood cells.
Antibody —A special protein made by the body as a

defense against foreign material that enters the body.It is uniquely designed to attack and neutralize thespecific antigen that triggered the immune response.
Antigen —Anything that causes the body to launch
an immune response against that antigen throughthe production of antibodies.Blood bank —A laboratory that specializes in blood
typing, antibody identification, and transfusion ser-vices.
Blood type —Blood categories based on the pres-

ence or absence of certain antigens on the redblood cells.Crossmatch —A laboratory test done to confirm that
blood from a donor and blood from the recipientare compatible.
Gene —A piece of DNA, located on a chromosome,
that determines how traits such as blood type areinherited and expressed.
Immune response —The body’s attack against an

antigen that it considers foreign to itself. The attackbegins with the production of antibodies against theantigen.
Rh blood type —Blood type based on the presence
or absence of the D antigen on the red blood cells.
Transfusion —The therapeutic introduction of blood
or a blood component into a patient’s bloodstream.
a previous pregnancy or transfusion. This procedure is

similar to blood typing. Finally, the Rh-negative mother isgiven an injection of Rh Immunoglobulin (RhIg) at 28weeks of gestation and again after delivery, if the baby isRh positive. The RhIg attaches to any Rh-positive cellsfrom the baby in the mother’s bloodstream, preventingthem from triggering anti-D antibody production in themother. An Rh-negative woman should also receive RhIgfollowing a miscarriage , abortion, or ectopic pregnancy .
OTHER BLOOD GROUP SYSTEMS. Several other

blood group systems may be involved in HDN and trans-fusion reactions, although they are much less frequentthan ABO and Rh. They are the Duffy, Kell, Kidd, MNS,and P systems. Tests for antigens from these systems arenot included in routine blood typing, but they are com-monly used in paternity testing.
Like Rh antibodies, antibodies in these systems do

not develop naturally, but as an immune response aftertransfusion or during pregnancy. An antibody screeningtest is done before a crossmatch to check for unexpectedantibodies to antigens in these systems. A person’s serumis mixed in a test tube with commercially-prepared cellscontaining antigens from these systems. If clumpingoccurs, the antibody is identified.
Crossmatching
Crossmatching is the final step in pretransfusion

testing. It is commonly referred to as compatibility test-ing, or “Type and Cross.”
GALE ENCYCLOPEDIA OF MEDICINE 2 533Blood typing and crossmatchingGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 533

Before blood from a donor and the recipient are
crossmatched, both are ABO and Rh typed. In addition,antibody screening is done to look for antibodies to cer-tain Rh, Duffy, MNS, Kell, Kidd, and P system antigens.If an antibody to one of these antigens is found, onlyblood without that antigen will be compatible in a cross-match. This sequence must be repeated before eachtransfusion a person receives.
To begin the crossmatch, blood from a donor with

the same ABO and Rh type as the rcipient is selected. Ina test tube, serum from the patient is mixed with redblood cells from the donor. If clumping occurs, the bloodis not compatible; if clumping does not occur, the bloodis compatible. If an unexpected antibody is found ineither the patient or the donor, the blood bank does fur-ther testing to make sure the blood is compatible.
In an emergency, when there is not enough time for

blood typing and crossmatching, O red blood cells maybe given, preferably Rh-negative. O blood type is calledthe universal donor because it has no ABO antigens for apatient’s antibodies to attack. In contrast, AB blood typeis called the universal recipient because it has no ABOantibodies to attack the antigens on transfused red bloodcells. If there is time for blood typing, red blood cells ofthe recipient type (type specific cells) are given. In eithercase, the crossmatch is continued, even

In eithercase, the crossmatch is continued, even though the trans-fusion has begun.

To collect the 10 mL blood needed for these tests, a
healthcare worker ties a tourniquet above the patient’selbow, locates a vein in the inner elbow region, andinserts a needle into that vein. Vacuum action draws theblood through the needle into an attached tube. Collec-tion of the sample takes only a few minutes.
Blood typing and crossmatching must be done three

days or less before a transfusion. A person doesn’t need tochange diet, medications, or activities before these tests.He should tell his healthcare provider if, during the lastthree months, he has received a blood transfusion or aplasma substitute, or has had a radiology procedure usingintravenous contrast media. These can give false clump-ing reactions in both typing and crossmatching tests.
Aftercare

Aftercare
The possible side effects of any blood collection are
discomfort or bruising at the site where the needle punc-tured the skin, as well as dizziness or fainting . Bruising
is reduced if pressure is applied with a finger to the punc-ture site until the bleeding stops. Discomfort is treatedwith warm packs to the puncture site.Risks
There are no risks from the blood collection or test

procedures. Blood transfusions always have the risk of anunexpected transfusion reaction. A nurse watches a patientfor signs of a reaction during the entire transfusion.
There is no normal blood type. The desired result of a

crossmatch is that compatible donor blood is found. Com-patibility testing procedures are designed to provide thesafest blood product possible for the recipient, but a com-patible crossmatch is no guarantee that an unexpectedadverse reaction will not appear during the transfusion.
Except in an emergency, a person cannot receive a
transfusion without a compatible crossmatch result.
Resources
BOOKS
American Association of Blood Banks. Technical Manual. 12th

ed. Bethesda: American Association of Blood Banks, 1996.
Boral, Leonard I., and John B. Henry. “Transfusion Medicine.”
In Clinical Diagnosis and Management by Laboratory
Methods. 19th ed. Ed. John B. Henry. Philadelphia: W. B.
Daniels, Geoff. Human Blood Groups. Oxford: Blackwell,
1995.
Harmening, Denise M. Modern Blood Banking and Transfu-
sion Practices. 3rd ed. Philadelphia: F. A. Davis, 1994.
Henry, John B., and Wendy V . Beadling. “Immunohematol-

ogy.” In Clinical Diagnosis and Management by Labora-
tory Methods. 19th ed. Ed. John B. Henry. Philadelphia:
Silberstein, Leslie E., ed. Molecular and Functional Aspects of
Blood Group Antigens. Bethesda: American Association
of Blood Banks, 1995.
Beck, Malcolm L., and Lowell L. Tilzer. “Red Cell Compati-
bility Testing: A Perspective for the Future.” Transfusion
Medical Reviews (Apr. 1996): 118-130.
Widman, Frances. “Early Observations about the ABO Blood

Groups.” Transfusion (June 1997): 665-667.
Bethesda, MD 20814. (301) 907-6977. <http://www.aabb.org>.
American Red Cross Blood Services. 430 17th Street NW,
Washington, DC 20006. (202) 737-8300. <http://www.redcross.org>.

GALE ENCYCLOPEDIA OF MEDICINE 2 534Blood typing and crossmatchingGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 534

Blood urea nitrogen test
The blood urea nitrogen (BUN) test measures the

level of urea nitrogen in a sample of the patient’s blood.Urea is a substance that is formed in the liver when thebody breaks down protein. Urea then circulates in theblood in the form of urea nitrogen. In healthy people,most urea nitrogen is filtered out by the kidneys andleaves the body in the urine. If the patient’s kidneys arenot functioning properly or if the body is using largeamounts of protein, the BUN level will rise. If the patienthas severe liver disease, the BUN will drop.
Purpose

Purpose
The BUN level may be checked in order to assess or
monitor:
• the presence or progression of kidney or liver disease.
• blockage of urine flow.
• mental confusion. Patients with kidney failure are
sometimes disoriented and confused.
• abnormal loss of water from the body ( dehydration ).
• recovery from severe burns . The body uses larger than
normal amounts of protein following serious burns.
The BUN test is performed on a sample of the

patient’s blood, withdrawn from a vein into a vacuumtube. The procedure, which is called a venipuncture,takes about five minutes.
The doctor should check to make sure that the
patient is not taking any medications that can affect BUNresults. These drugs include the antibiotics chloram-
phenicol, streptomycin, amphotericin B, methicillin,gentamicin, tobramycin, and kanamycin, as well asdiuretics and corticosteroids .

The patient should be advised not to eat large
amounts of meat the day before the test.
Aftercare
Aftercare consists of routine care of the area around
the venipuncture.
Risks
The primary risk is the possibility of a bruise or
swelling in the area of the venipuncture. The patient canapply moist warm compresses.KEY TERMS
Urea —A compound containing nitrogen that
occurs in the urine and other body fluids as aresult of protein metabolism.

Normal BUN levels are 5-18 mg/dL for children; 7-
18 mg/dL for adults; and 8-20 mg/dL in the elderly.
BUN levels can be too low as well as too high.
Abnormally low BUN
Low levels of BUN may indicate overhydration ,
malnutrition ,celiac disease [a disease characterized by
the inability ot tolerate foods containing wheat protein(gluten)], liver damage or disease, or use of corticos-teroids. Low BUN may also occur in early pregnancy .
Abnormally high BUN

High levels of BUN may indicate kidney disease or
failure; blockage of the urinary tract by a kidney stone ortumor; a heart attack or congestive heart failure ; dehy-
dration; fever ; shock ; or bleeding in the digestive tract.
High BUN levels can sometimes occur during late preg-nancy or result from eating large amounts of protein-richfoods. A BUN level higher than 100 mg/dL points tosevere kidney damage.
Resources
BOOKS

Sobel, David S., and Tom Ferguson. The People’s Book of
Medical Tests. New York: Summit Books, 1985.
Blood vessel scan seeDoppler
ultrasonography
Body lice seeLice infestation

GALE ENCYCLOPEDIA OF MEDICINE 2 535Blood urea nitrogen testGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 535

Boils often occur from a bacterial infection in a hair follicle
or skin gland. (Custom Medical Stock Photo. Reproduced by
permission.)Boils
Boils and carbuncles are bacterial infections of hair
follicles and surrounding skin that form pustules (smallblister-like swellings containing pus) around the follicle.Boils are sometimes called furuncles. A carbuncle isformed when several furuncles merge to form a singledeep abscess with several heads or drainage points.

Boils and carbuncles are firm reddish swellings about

0.2-0.4 in (5-10 mm) across that are slightly raised abovethe skin surface. They are sore to the touch. A boil usuallyhas a visible central core of pus; a carbuncle is larger andhas several visible heads. Boils occur most commonly onthe face, back of the neck, buttocks, upper legs and groinarea, armpits, and upper torso. Carbuncles are less commonthan single boils; they are most likely to form at the back ofthe neck. Males are more likely to develop carbuncles.

Boils and carbuncles are common problems in the
general population, particularly among adolescents andadults. People who are more likely to develop these skininfections include those with:
• diabetes, especially when treated by injected insulin• alcoholism or drug abuse• poor personal hygiene• crowded living arrangements• jobs or hobbies that expose them to greasy or oily sub-
stances, especially petroleum products
• allergies or immune system disorders, including HIV

• family members with recurrent skin infections
Boils and carbuncles are caused by Staphylococcus
aureus , a bacterium that causes an infection in an oil
gland or hair follicle. Although the surface of human skinis usually resistant to bacterial infection, S. aureus can

enter through a break in the skin surface—includingbreaks caused by needle punctures for insulin or druginjections. Hair follicles that are blocked by greasycreams, petroleum jelly, or similar products are morevulnerable to infection. Bacterial skin infections can bespread by shared cosmetics or washcloths, close humancontact, or by contact with pus from a boil or carbuncle.
As the infection develops, an area of inflamed tissue

gradually forms a pus-filled swelling or pimple that ispainful to touch. As the boil matures, it forms a yellowishhead or point. It may either continue to swell until thepoint bursts open and allows the pus to drain, or it maybe gradually reabsorbed into the skin. It takes betweenone and two weeks for a boil to heal completely after itcomes to a head and discharges pus. The bacteria thatcause the boil can spread into other areas of the skin oreven into the bloodstream if the skin around the

into the bloodstream if the skin around the boil isinjured by squeezing. If the infection spreads, the patientwill usually develop chills and fever , swollen lymph

nodes ( lymphadenitis ), and red lines in the skin running
outward from the boil.
Furunculosis is a word that is sometimes used to
refer to recurrent boils. Many patients have repeatedepisodes of furunculosis that are difficult to treat becausetheir nasal passages carry colonies of S. aureus . These
bacterial colonies make it easy for the patient’s skin to bereinfected. They are most likely to develop in patientswith diabetes, HIV infection, or other immune systemdisorders.

Carbuncles are formed when the bacteria infect sev-
eral hair follicles that are close together. Carbunculosis isa word that is sometimes used to refer to the develop-ment of carbuncles. The abscesses spread until theymerge with each other to form a single large area ofinfected skin with several pus-filled heads. Patients withcarbuncles may also have a low-grade fever or feel gen-erally unwell.
Diagnosis
The diagnosis of boils and carbuncles is usually

made by the patient’s primary care doctor on the basis ofvisual examination of the skin. In some cases involvingrecurrent boils on the face, the doctor may need to con-sider acne as a possible diagnosis, but for the most part
GALE ENCYCLOPEDIA OF MEDICINE 2 536BoilsGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 536

boils and carbuncles are not difficult to distinguish from
other skin disorders.
S. aureus can easily be cultured in the laboratory if
the doctor needs to rule out inclusion cysts or deep fun-gal infections that gardeners sometimes get. The doctorcan make a culture from pus taken from the boil or car-buncle to confirm the diagnosis of a staphylococcalinfection. He or she can also culture the patient’s nasaldischarge to test for the presence of a S. aureus colony.
Treatment

Treatment
Patient and family education
Patient education is an important part of the treatment

of boils and carbuncles. Patients need to be warned againstpicking at or squeezing boils because of the danger ofspreading the infection into other parts of the skin orbloodstream. It is especially important to avoid squeezingboils around the mouth or nose because infections in theseareas can be carried to the brain. Patients should also beadvised about keeping the skin clean, washing their handscarefully before and after touching the boil or carbuncle,avoiding the use of greasy cosmetics or

carbuncle,avoiding the use of greasy cosmetics or creams, and keep-ing their towels and washcloths separate from those ofother family members. Some doctors may recommend anantiseptic soap or gel for washing the infected areas.

If the patient has had several episodes of furunculo-
sis, the doctor may examine family members or closecontacts to see if they are carriers of S. aureus . In many
cases they also need treatment for boils or carbuncles.Skin infections and reinfections involving small groupsor clusters of people are being reported more frequentlyin the United States.
Boils are usually treated with application of antibiot-

ic creams—usually clindamycin or polymyxin—follow-ing the application of hot compresses. The compresseshelp the infection to come to a head and drain.
Carbuncles and furunculosis are usually treated with
oral antibiotics as well as antibiotic creams or oint-

ments. The specific medications that are given are usual-ly dicloxacillin (Dynapen) or cephalexin (Keflex). Ery-thromycin may be given to patients who are allergic topenicillin. The usual course of oral antibiotics is 5-10days; however, patients with recurrent furunculosis maybe given oral antibiotics for longer periods. Furunculosisis treated with a combination of dicloxacillin andrifampin (Rifadin).
Patients with bacterial colonies in their nasal pas-

sages are often given mupirocin (Bactroban) to applydirectly to the lining of the nose.Surgical treatment
Boils and carbuncles that are very large, or that are
not draining, may be opened with a sterile needle or sur-gical knife to allow the pus to drain. The doctor will usu-ally give the patient a local anesthetic if a knife is used;surgical treatment of boils is painful and usually leavesnoticeable scars.
Naturopathic therapy
Naturopathic practitioners usually recommend

changes in the patient’s diet as well as applying herbalpoultices to the infected area. The addition of zinc sup-plements and vitamin A to the diet is reported to beeffective in treating boils. The application of a paste orpoultice containing goldenseal ( Hydrastis canadensis )
root is recommended by naturopaths on the groundsthat goldenseal helps to kill bacteria and reduceinflammation.
Homeopathy
Homeopaths maintain that taking the proper homeo-

pathic medication in the first stages of a boil or carbunclewill bring about early resolution of the infection and pre-vent pus formation. The most likely choices are Bel-
ladonna or Hepar sulphuris . If the boil has already
formed, Mercurius vivus or Silica may be recommended
to bring the pus to a head.
Western herbal therapies
A variety of herbal remedies can be applied topi-

cally to boils to fight infection. These include essentialoils of bergamot ( Citrus bergamia ), chamomile ( Matri-
GALE ENCYCLOPEDIA OF MEDICINE 2 537Boils
A close-up view of a carbuncle on person’s back. (Photo-
graph by John Watney, Photo Researchers, Inc. Reproduced bypermission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 537

KEY TERMS
Abscess —A localized collection of pus in the skin
or other body tissue.
Carbuncle —A large, deep skin abscess formed by
a group or cluster of boils.
Follicle —The small sac at the base of a hair shaft.
The follicle lies below the skin surface.
Furunculosis —A condition in which the patient
suffers from recurrent episodes of boils.
Pustule —A small raised pimple or blister-like
swelling of the skin that contains pus.
caria recutita ), lavender ( Lavandula officinalis ), and

sage ( Salvia officinalis ), as well as tea tree oil
(Melaleuca spp.). Herbalists also recommend washing
the skin with a mixture of goldenseal and witch hazel.To fight the inflammation associated with boils,herbalists suggest marsh mallow ( Althaea officinalis )
ointment, tinctures (herbal solutions made with alco-hol) of blue flag ( Iris versicolor ) or myrrh ( Com-
miphora molmol ), and slippery elm ( Ulmus fulva )
made into a poultice.
Prognosis

Prognosis
The prognosis for most boils is excellent. Some
patients, however, suffer from recurrent carbuncles orfurunculosis. In addition, although the spread of infec-tion from boils is relatively unusual, there have beendeaths reported from brain infections caused by squeez-ing boils on the upper lip or in the tissue folds at thebase of the nose.
There are some precautions that people can take to
minimize the risk of developing bacterial skin infections:

• cleanse skin properly with soap and water, and take
showers rather than tub baths
• do not share washcloths, towels, or facial cosmetics
with others
• cut down on greasy or fatty foods and snacks
• always wash hands before touching the face• consider using antiseptic soaps and shower gels• consult a doctor if furunculosis is a persistent prob-
lem—it may indicate an underlying disease such asdiabetesResources
BOOKS
Berger, Timothy G. “Skin and Appendages.” In Current Med-

ical Diagnosis and Treatment, 1996. 35th ed. Ed. Stephen
“Folliculitis, Furunculosis, and Carbunculosis.” In Professional
Guide to Diseases. 5th ed. Springhouse, PA: Springhouse
Corporation, 1995.
Hacker, Steven M. “Common Bacterial and Fungal Infections
of the Integument.” In Current Diagnosis. V ol. 9. Ed. Rex
B. Conn, et al. Philadelphia: W. B. Saunders Co., 1997.
Rasmussen, James E. “Bacterial Infections of the Skin.” In

Conn’s Current Therapy, 1996 , Ed. Robert E. Rakel.
Turkington, Carol A., and Jeffrey S. Dover. Skin Deep: An A-Z
of Skin Disorders, Treatments, and Health. New York:
Facts On File, 1996.
Bone biopsy
Bone biopsy is the removal of a piece of bone for
laboratory examination and analysis.
Purpose
Bone biopsy is used to distinguish between malig-
nant tumors and benign bone disease such as osteoporo-

sisand osteomyelitis . This test may be ordered to deter-
mine why a patient’s bones ache or feel sore, or when amass or deformity is found on an x ray, CT scan, bonescan, or other diagnostic imaging procedure.
The patient’s doctor and the surgeon who performs
the bone biopsy must be told about any prescription andover-the-counter medications the patient is taking, andabout allergies or reactions the patient has had to anes-
thetics or pain relievers. Special care must be taken with

patients who have experienced bleeding problems.
A bone biopsy involves using a special drill or other
surgical instruments to remove bone from the patient’sbody. The procedure usually lasts about 30 minutes andmay be performed in the hospital, a doctor’s office, or asurgical center.
GALE ENCYCLOPEDIA OF MEDICINE 2 538Bone biopsyGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 538

specimen. After the skin covering the bone has beencleansed with an antiseptic and shaved, the patient isgiven a local anesthetic. The doctor will not begin theprocedure until the anesthetic has numbed the area fromwhich the bone is to be removed, but the patient may feelpressure or mild pain when the needle pierces the bone.The surgeon turns the needle in a half-circle to extract asample from the core, or innermost part, of the bone. Thesample is drawn into the hollow stem of the biopsy

is drawn into the hollow stem of the biopsy nee-dle. The sample is then sent to a laboratory, where it isexamined under a microscope.

An open biopsy is used when a larger specimen is
needed. After the area covering the bone has beencleansed with an antiseptic and shaved, the patient isgiven a general anesthetic. After the anesthetic takeseffect and the patient is unconscious, the surgeon makesan incision and removes a bone specimen. The specimenis sent to the laboratory for immediate analysis. Resultsof that analysis may indicate that additional surgeryshould be performed right away.

No special preparation is needed for a drill biopsy,
but a patient must fast for at least 12 hours before anopen biopsy.
Aftercare
Pain medication will be prescribed after a biopsy,

and vital signs will be monitored until they return to nor-mal. Most patients can go home in about an hour. If bonewas removed from the spine, the patient may stay in thehospital overnight. The surgical site must be kept cleanand dry for 48 hours, and the patient’s doctor should benotified if any of these symptoms appear:
•f e v e r• headache• pain on movement• inflammation or pus near the biopsy site
• bleeding through the bandage at the biopsy site
Risks

Risks
Risks include bone fracture, injury to nearby tissue,
and infection. Bleeding is a rare complication. Factorsthat increase risk include:
• stress
• obesity
• poor nutritionKEY TERMS
Biopsy —Removal and examination of tissue to
determine if cancer is present.
Osteomyelitis —An infection of the bone that is
usually treated with antibiotics but sometimesrequires surgery.
Osteoporosis —Thinning and loss of bone tissue.
• some medications
• mind-altering drugs

Normal bone is made up of collagen fibers and bone
tissue.
Bone biopsy can reveal the presence of benign dis-
ease, infection, or malignant tumors that have spread tothe bone from other parts of the body.
Results of this test are considered reliable, but may
be affected by:
• failure to fast before open biopsy
• failure to obtain an adequate specimen
• delayed microscopic examination or laboratory analysis
Resources
BOOKS

Resources
BOOKS
Cancer Group Institute. 1814 N.E. Miami Gardens Drive,
North Miami Beach, FL 33179. (305) 651-5070. <http://www.cancergroup.com/em19.html>.

Diseases Information Clearinghouse. National Institutesof Health. 1 AMS Circle, Bethesda, MD 20892-3695.(301) 495-3675.
OTHER
ThriveOnline. 17 Feb. 1998 <http://thriveonline.oxygen.com>.
GALE ENCYCLOPEDIA OF MEDICINE 2 539Bone biopsyGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 539

Bone break fever seeDengue fever
Bone cancer seeSarcomas
Bone densitometry seeBone density test
Bone density test
A bone density test, or scan, is designed to check for
osteoporosis , a disease that occurs when the bones
become thin and weak. Osteoporosis happens when thebones lose calcium and other minerals that keep them
strong. Osteoporosis begins after menopause in many
women, and worsens after age 65, often resulting in seri-ous fractures . These fractures may not only bring dis-

ability, but may affect longevity. As many as one-fourthof women who fracture their hip after age 50 die withinone year.
Most people today will get a bone density scan from

a machine using a technology called Dual Energy X-rayAbsorptiometry or DEXA for short. This machine takes apicture of the bones in the spine, hip, total body andwrist, and calculates their density. If a DEXA machine isnot available, bone density scans can also be done withdual photon absorptiometry (measuring the spine, hipand total body) and quantitative computed tomography
scans (measuring the spine). Bone density scanners that

use DEXA technology to just measure bone density inthe wrist (called pDEXA scans) provide scans at somedrugstores. Yet these tests are not as accurate as thosethat measure density in the total body, spine or hip—where most fractures occur.Purpose
A bone density scan measures the strength of an
individual’s bones and determines the risk of fracture. Anobservation of any osteoporosis present can be made.
To take a DEXA bone density scan, the patient lies on

a bed underneath the scanner, a curving plastic arm thatemits x rays. These low-dose x rays form a fan beam thatrotates around the patient. During the test, the scannermoves to capture images of the patient’s spine, hip or entirebody. A computer then compares the patient’s bonestrength and risk of fracture to that of other people in theUnited States at the same age and to young people at peakbone density. Bones reach peak density at age 30 and thenstart to lose mass. The test takes about 20

thenstart to lose mass. The test takes about 20 minutes to do andis painless. The DEXA bone scan costs about $250. Someinsurance companies and Medicare cover the cost. pDEXAwrist bone scans in drugstores are available for about $30.

The patient puts on a hospital gown and lies on the
bed underneath the scanner. Not all doctors routinelyschedule this test. If the following factors apply to apatient, they may need a bone density scan and can dis-cuss this with their doctor. The patient:
• is at risk for osteoporosis
• is near menopause
• has broken a bone after a modest trauma• has a family history of osteoporosis
• uses steroid or antiseizure medications
GALE ENCYCLOPEDIA OF MEDICINE 2 540Bone density test

Computer read-out of a bone density scan. (Photo
Researchers. Reproduced by permission.)
Patient undergoing a bone density scan. (Photo Researchers.
Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 540

• has had a period of restricted mobility for more than six
months
Risks
The DEXA bone scan exposes the patient to only a
small amount of radiation—about one-fiftieth that of achest x ray , or about the amount you get from taking a
cross-country airplane flight.
The patient, when compared with people at “young

normal bone density” (called the T-score) has the same ordenser bones than a healthy 30-year-old. T scores above1 mean that a patient has a healthy bone mass. Scoresfrom 0 to /H110021 mean that the patient has borderline bone
mass and should repeat the test in two to five years.
The patient has two to four times the risk of a broken

bone as other people in the United States at the same ageand those at peak bone density. If a patient’s T scoreKEY TERMS
Calcium —A mineral that helps build bone. After
menopause, when women start making less of thebone-protecting hormone estrogen, they mayneed to increase their intake of calcium.
DEXA bone density scan —A bone density scan
that uses a rotating x-ray beam to measure thestrength of an individual’s bones and his or herfracture risk.
Osteoporosis —A disease that occurs when the

bones lose the calcium and structure that keepthem strong. It often occurs after menopause(around age 50) in women and in old age in men.
ranges from /H110021 to /H110022.5 they have low bone mass and
are at risk for osteoporosis. A T score below /H110022.5 means
osteoporosis is already evident. These patients shouldhave a repeat bone density scan every year or two.
Resources
BOOKS
Bonnick, Sydney Lou. The Osteoporosis Handbook. Taylor

Publishing, 1994.
Brown, Susan E. Better Bones, Better Body: A Comprehensive
Self-Help Program for Preventing, Halting and OvercomingOsteoporosis. New Canaan, CT: Keats Publishing, 1996.
Bilger, Burkhard. “Bone Medicine.” Health , May/June 1996,
125-128.
“Bone Density Testing: Should You Be Checked?” Mayo Clinic
Health Newsletter 15 (June 1997): 6
Hanlon, Toby, et al. “Size Up Your Bones Now.” Prevention ,
Feb. 1996, 75.

National Osteoporosis Foundation. 1150 17th St., NW, Suite
500, Washington, DC 20036-4603. (800) 223-9994. <http://www.nof.org>.
Bone disorder drugs
Bone disorder drugs are medicines used to treat dis-
eases that weaken the bones.
GALE ENCYCLOPEDIA OF MEDICINE 2 541Bone disorder drugs
A bone densitometry scan of identical twins.Their bone
density is normal and identical to one another. (Photo

Researchers. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 541

Purpose
The drugs described here are used to treat or prevent
osteoporosis (brittle bone disease) in women past
menopause as well as older men. They also are used pre-
scribed for Paget’s disease, a painful condition that weak-ens and deforms bones, and they are used to control calci-um levels in the blood.
Bone is living tissue. Like other tissue, bone is con-

stantly being broken down and replaced with new materi-al. Normally, there is a balance between the breakdownof old bone and its replacement with new bone. Butwhen something goes wrong with the process, bone dis-orders may result.
Osteoporosis is a particular concern for women

after menopause, as well as for older men. In osteo-porosis, the inside of the bones become porous and thin.Over time, this condition weakens the bones and makesthem more likely to break. Osteoporosis is four timesmore common in women than in men. This is becausewomen have less bone mass than men, tend to livelonger and take in less calcium, and need the femalehormone estrogen to keep their bones strong. If menlive long enough, they are also at risk of getting osteo-porosis later in life. Once

risk of getting osteo-porosis later in life. Once total bone mass has peaked—around age 35—all adults start to lose it. In women, therate of bone loss speeds up during menopause, when

estrogen levels fall. Bone loss may also occur if bothovaries are removed by surgery. Ovaries make estrogen.Hormone replacement therapy is one approach to
preventing osteoporosis. However, not all people canuse hormone replacement therapy. Bone disorder drugsare a good alternative for people who already haveosteoporosis or who are at risk of developing it. Riskfactors include lack of regular exercise , early
menopause, being underweight, and a strong familyhistory of osteoporosis.

physician’s prescription and come in tablet, nasalspray, and injectable forms. Commonly used bone dis-order drugs are alendronate (Fosamax), calcitonin(Miacalcin, Calcimar), and raloxifene (Evista). Ralox-ifene belongs to a group of drugs known as selectiveestrogen receptor modulators (SERMs), which act likeestrogen in some parts of the body but not in others.This makes the drugs less likely to cause some of theharmful effects that estrogen may cause. Unlike estro-gen, raloxifene does not

may cause. Unlike estro-gen, raloxifene does not increase the risk of breast

cancer . In fact, research suggests that raloxifene may
even reduce that risk.Recommended dosage
Alendronate
FOR OSTEOPOROSIS. The usual dose is 10 mg once
a day. Treatment usually continues over many years.
FOR PAGET’S DISEASE. The usual dose is 40 mg once
a day for six months.
This medicine works only when it is taken with a full

glass of water first thing in the morning, at least 30 min-utes before eating or drinking anything or taking anyother medicine. Do not lie down for at least 30 minutesafter taking it because the drug can irritate the esophagus,the tube that delivers food form the mouth to the stomach.
Calcitonin
NASAL SPRAY. The usual dose is one spray into the
nose once a day. Alternate nostrils, spraying the rightnostril one day, the left nostril the next day, and so on.

INJECTABLE. The recommended dosage depends on
the condition for which the medicine is prescribed andmay be different for different people. Check with thephysician who prescribed the medicine or the pharmacistwho filled the prescription for the proper dosage.
Raloxifene
The usual dose is one 60-mg tablet daily.
Aldendronate
People with low levels of calcium in their blood

should not take this medicine. It also is not recommendedfor women on hormone replacement therapy or for anyonewith kidney problems. Before using alendronate, anyonewho has digestive or swallowing problems should makesure that his or her physician knows about the condition.
Calcitonin nasal spray may cause irritation or small

sores in the nose. Check with a physician if this becomesvery uncomfortable or if there is bleeding from the nose.
The injectable form of calcitonin has caused serious
allergic reactions in a few people. The nasal spray is notknown to cause such reactions, but the possibility exists.Before starting treatment with calcitonin, the physicianwho prescribes the drug may order an allergy test tomake sure there will not be a problem.
A rare, but serious side effect of raloxifene is an

increased risk of blood clots that form in the veins and
GALE ENCYCLOPEDIA OF MEDICINE 2 542Bone disorder drugsGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 542

may break away and travel to the lungs. This is about as
likely in women who take raloxifene as it is in womenwho take estrogen. Because of this possible problem,women with a history of blood clots in their veins shouldnot take raloxifene.
Women who have had breast cancer or cancer of the
uterus should check with their physicians about whetherthey can safely use raloxifene.
General precautions for bone disorder drugs
To keep bones strong, the body needs calcium and

vitamin D. Dairy products and fish such as salmon, sar-dines and tuna are good sources of both calcium and vita-min D. People who are taking bone disorder drugs forosteoporosis and who do not get enough of these nutri-ents in their diets should check with their physicians
about taking supplements. Other important bone-savingsteps are avoiding smoking and alcohol and getting

enough of the kind of exercise that puts weight on thebones (such as walking or lifting weights).
People who are taking these drugs because they have
too much calcium in their blood may need to limit the
amount of calcium in their diets. Too much calcium may pre-vent the medicine from working properly. Discuss the properdiet with the physician who prescribed the drug, and do notmake any diet changes without the physician’s approval.
Anyone who has had unusual reactions to bone dis-

order drugs in the past should let his or her physicianknow before taking the drugs again. The physician alsoshould be told about any allergies to foods, dyes, preser-
vatives, or other substances.

nant and women who are breastfeeding should checkwith their physicians before using this alendronate or cal-citonin. Raloxifene should not be used by women whoare pregnant or who may become pregnant. In laboratorystudies of rats, raloxifene caused birth defects .
Common side effects include constipation ,diar-
rhea ,indigestion , nausea, pain in the abdomen, and

pain in the muscles and bones. These problems usuallygo away as the body adjusts to the medicine and do notneed medical attention unless they continue or they inter-fere with normal activities.
The most common side effects of calcitonin nasal
spray are nose problems, such as dryness, redness, itch-KEY TERMS
Estrogen —The main sex hormone that controls
normal sexual development in females. Duringthe menstrual cycle, estrogen helps prepare thebody for possible pregnancy.

Fracture —A break or crack in a bone.
Menopause —The stage in a woman’s life when
the ovaries stop producing egg cells at regulartimes and menstruation stops.
Osteoporosis —A disease in which bones become

very porous and weak. The bones are then morelikely to fracture and take longer to heal. The con-dition is most common in women after menopausebut can also occur in older men.
ing, sores, bleeding and general discomfort. These prob-
lems should go away as the body adjusts to the medicine,but if they do not or if they are very uncomfortable,check with a physician. Other side effects that should bebrought to a physician’s attention include headache ,

back pain and joint pain.
Injectable calcitonin may cause minor side effects
such as nausea or vomiting; diarrhea; stomach pain; lossof appetite; flushing of the face, ears, hands or feet; anddiscomfort or redness at the place on the body where it isinjected. Medical attention is not necessary unless theseproblems persist or cause unusual discomfort.
Anyone who has a skin rash or hives after taking
injectable calcitonin should check with a physician assoon as possible.

Common side effects include hot flashes, leg
cramps, nausea and vomiting . Women who have these
problems while taking raloxifene should check with theirphysicians.
Taking aspirin with alendronate may increase the
chance of upset stomach, especially if the dose of alen-dronate is more than 10 mg per day. If an analgesic is
GALE ENCYCLOPEDIA OF MEDICINE 2 543Bone disorder drugsGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 543

necessary, switch to another drug, such as aceta-
minophen (Tylenol) or use buffered aspirin. Ask a physi-
cian or pharmacist for the correct medication to use.
Some calcium supplements, antacids and other
medicines keep the body from absorbing alendronate. Toprevent this problem, do not take any other medicinewithin 30 minutes of taking alendronate.
Calcitonin may keep certain other drugs for Paget’s
disease, such as etidronate (Didronel), from working asthey should.

Raloxifene may affect blood clotting. Patients who
are taking other drugs that affect blood clotting, such aswarfarin (Coumadin), should check with their physiciansbefore using raloxifene.
Resources
Foundation For Osteoporosis Research & Education. (888)
266-3015. <http://www.fore.org>.
National Association for the Relief of Paget’s Disease. <http://
www.demon.co.uk/narpd>.
National Osteoporosis Foundation 1150 17th Street NW Suite

500 Washington, D.C. 20036-4603. <http://www.nof.org>.
Bone grafting
Bone grafting is a surgical procedure by which new
bone or a replacement material is placed into spacesbetween or around broken bone ( fractures ) or holes in
bone (defects) to aid in healing.
Purpose
Bone grafting is used to repair bone fractures that

are extremely complex, pose a significant risk to thepatient, or fail to heal properly. Bone graft is also used tohelp fusion between vertebrae, correct deformities, orprovide structural support for fractures of the spine. Inaddition to fracture repair , bone graft is used to repair
defects in bone caused by birth defects , traumatic injury,
or surgery for bone cancer .Description
Bone is composed of a matrix, mainly made up of a

protein called collagen. It is strengthened by deposits ofcalcium and phosphate salts, called hydroxyapatite.Within and around this matrix are located the cells of thebones, which are of four types. Osteoblasts produce thebone matrix. Osteocytes are mature osteoblasts and serveto maintain the bone. Osteoclasts break down andremove bone tissue. Bone lining cells cover bone sur-faces. Together, these four types of cells are responsiblefor building the bone matrix, maintaining it, and remod-eling

the bone matrix, maintaining it, and remod-eling the bone as needed.

repair a defect. The first is called osteogenesis, the for-mation of new bone by the cells contained within thegraft. The second is osteoinduction, a chemical processin which molecules contained within the graft (bonemorphogenetic proteins) convert the patient’s cells intocells that are capable of forming bone. The third is osteo-conduction, a physical effect by which the matrix of thegraft forms a scaffold on which cells in the recipient areable to form new bone.

bones in the patient’s own body (e.g., hip bones or ribs),called autograft, or from bone taken from other peoplethat is frozen and stored in tissue banks, called allograft.A variety of natural and synthetic replacement materialsare also used instead of bone, including collagen (theprotein substance of the white fibers of the skin, bone,and connective tissues); polymers, such as silicone andsome acrylics; hydroxyapatite; calcium sulfate; andceramics. A new material, called resorbable

andceramics. A new material, called resorbable polymericgrafts, is also being studied. These resorbable grafts pro-vide a structure for new bone to grow on; the grafts thenslowly dissolve, leaving only the new bone behind.

To place the graft, the surgeon makes an incision in
the skin over the bone defect and shapes the bone graft orreplacement material to fit into the defect. After the graftis placed into the defect, it is held in place with pins,plates, or screws. The incision is closed with stitches anda splint or cast is used to prevent movement of the boneswhile healing.
The costs associated with a bone graft vary. These

costs include: the surgeon’s fee (variable); anesthesiolo-gist’s fees (averaging $350 to $400 per hour); hospitalcharges (averaging $1,500 to $1,800 per day, more forintensive care or private rooms); medication charges($200 to $400); and additional charges, including anassisting surgeon, treatment of complications, diagnosticprocedures (e.g., blood work or x rays), medical sup-plies, and equipment use. The cost for the graft itself canrange from $250 to $900.

GALE ENCYCLOPEDIA OF MEDICINE 2 544Bone graftingGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 544

This procedure is covered by many third-party insur-
ers; insurance coverage should be explored for each indi-vidual case.
Aftercare
The time required for convalescence for fractures or
spinal fusion may vary from one to 10 days, and vigor-ous exercise may be limited for up to three months.
Most bone grafts are successful in helping the bone

defect to heal. The extent of recovery will depend on thesize of the defect and the condition of the bone sur-rounding the graft at the time of surgery. Severe defectsmay take some time to heal and may require furtherattention after the initial graft. In one study of over1,000 patients who received very large allografts aftersurgery for bone cancer, researchers found that approxi-mately 85% of the patients were able to return to workor normal physical activities without using crutches.However,

activities without using crutches.However, about 25% of these patients required a secondoperation, because the first did not heal properly. Lesssevere bone defects, though, should heal completelywithout serious complications.

Risks
The risks for any surgical procedure requiring anes-
thesia include reactions to the medications and breathingproblems. The risks for any surgical procedure includebleeding and infection.
The drawbacks of autografts include: the additional
surgical and anesthesia time (typically 30 minutes perprocedure) to obtain, or harvest, the bone for grafting;added costs of the additional surgery; pain and infection

that might occur at the site from which the graft is taken;and the relatively small amount of bone that is availablefor grafting.
The drawbacks of allografts include: variability

between lots, since the bone is harvested from a varietyof donors; the bone may take longer to incorporate withthe host bone than an autograft would; the graft may beless effective than an autograft; and the possibility oftransferring diseases to the patient. Other complicationsmay result from the immune response mounted by thepatient’s immune system against the grafted bone tissue.With the use anti-rejection agents (drugs to combatrejection of grafted bone tissue) immune rejection is lessof a

Resources
Brown, Edwin H. “New Bones from the Sea: Tropical Coral.”
Medical Update 20 (Jan. 1997): 2.KEY TERMS
Allograft —Tissue for transplantation that is taken
from another person.
Autograft —Tissue for transplantation that is taken
from the patient.
Hydroxyapatite —A calcium phosphate complex
that is the primary mineral component of bone.
Osteoblasts —Bone cells that build new bone tissue.
Osteoclasts —Bone cells that break down and
remove bone tissue.

Osteoconduction —Provision of a scaffold for the
growth of new bone.
Osteocytes —Bone cells that maintain bone tissue.
Osteogenesis —Growth of new bone.
Osteoinduction —Acceleration of new bone for-
mation by chemical means.
Cowley, Geoffrey. “Replacement Parts.” Newsweek 129 (27
Jan. 1997): 66.
DeLacure, Mark D. “Physiology and Healing of Bone Grafts.”
Otolaryngologic Clinics of North America 27, no. 5
(1994): 859.
Farley, Dixie. “New Ways to Heal Broken Bones.” FDA Con-

sumer 30 (Apr. 1996): 14.
Hayes, Ketra Marie, and Nancy L. Combs. “Perioperative
Nursing Care of Patients with Craniofacial Injuries.”ADRN Journal 64 (Sept. 1996): 383.
Hotter, David S. “Band-Aids for Broken Bones.” Machine
Design 68 (4 Apr. 1996): 39.
Kopp, Marleen. “Caring for the Adult Patient Undergoing
Anterior/Posterior Spinal Fusion.” Orthopedic Nursing
16, no. 2 (1997): 55.
Larkin, Brenda G. “Understanding Bone Banking.” Orthopedic
Nursing 16, NO. 4, 1997: 49.

Morgan, Peggy, and Toby Hanlon. “Power Medicine in 2000:
Breakthrough Treatments for a New Millennium.” Med-
ical Update 20 (Jan. 1997): 2.
“New Ways to Fix Bone Fractures.” USA Today Magazine 124
(Feb. 1996): 4.
Oseph, Lou. “The New World of Dental Care.” Consumers
Digest 35 (May 1996): 59.
“Restoring Severely Disfigured Faces.” USA Today Magazine ,
125 (Oct. 1996): 8.
Scaggs, David L., and George S. Bassett. “Adolescent Idio-

pathic Scoliosis: An Update.” American Family Physician
53 (15 May 1996): 2327.
Vangsness, C. Thomas, et al. “Soft Tissue for Allograft Recon-
struction of the Human Knee: A Survey of the AmericanAssociation of Tissue Banks.” American Journal of Sports
Medicine 24 (Mar. 1996): 230.
GALE ENCYCLOPEDIA OF MEDICINE 2 545Bone graftingGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 545

American Association of Tissue Banks. 1350 Beverly Road,
Suite 220-A, McLean, V A 22101. (703) 827-9582.
Lisa Christenson, PhD
Bone growth stimulation
Bone growth stimulation is the technique of promot-
ing bone growth in difficult to heal fractures by apply-
ing a low electrical current or ultrasound to the fracture.
Purpose
Bone growth stimulation is done when satisfactory

healing is not occurring naturally or when the pace ofhealing is too slow. This condition is called fracturenonunion, and it occurs more frequently among adultsthan children, in people with severe or complex fractures,and in people who smoke.
The theory behind applying an electric current to

fractures to stimulate healing is based on the fact thatthe concave side of the bone becomes negativelycharged and the convex side is positively charged. It isbelieved that artificially encouraging this charging withan electric current will speed healing. In 1996, the Foodand Drug Administration (FDA) also approved theapplication of low intensity ultrasound pulses as a treat-ment for fracture nonunion.

Ultrasound and electromagnetic stimulation are
expensive and are used only when healing problems existfor a substantial length of time. Each method must beused for at least three to six months to be effective.
Bone growth stimulation cannot be used if the gap
between the ends of the fracture is too large.
Electric stimulation can be applied either from the

inside of the body (invasively) or from the outside thebody (noninvasively). Ultrasound is a noninvasive pro-cedure. The type of stimulation selected depends on thedoctor’s preference, the type and location of the fracture,and the patient’s motivation to comply with the treat-ment schedule. Treatment can take anywhere from threeto six months.Invasive stimulators
Invasive electric stimulators are either fully or partial-

ly implantable. The advantage of these devices is that theyapply a direct electric current to the fracture 24 hours aday. The fully implantable stimulator requires little dailyattention from the patient. Patients using a semi-implantedstimulator must regulate their own treatment schedule andhave to care for the external power pack. The disadvantageof implantable and semi-implantable stimulators is thattheir implantation is a surgical procedure.
Fully implantable direct current stimulators are

installed in a hospital under general or regional anesthesia.Both the stimulator and the power source are implanted.The surgeon makes an incision and places a spiral shapedcathode inside the bone. A wire leads to the power sourceand a small anode. The power source is a battery pack thatis implanted in the nearby muscle. The body transmitselectrical current to close the circuit. The incision is thenclosed. Once in place, the device provides continuousdirect electric current for bone growth

Partially implanted stimulators use cathode pins that
are implanted at the edge of each bone that is fractured.Wires lead to the surface of the skin where a powersource and the anode are located. Wires complete the cir-cuit. The external portion of the device is held in place bya cast. This source of stimulation also runs continuously.
Noninvasive stimulators
In the noninvasive stimulator, external electromag-

netic coils are placed on either side of the fracture andare held in place by a strap or cuff. Locating the coilscorrectly is important, and their location relative to thefracture is usually confirmed by x rays.
The coils produce a pulsating electromagnetic field.
It is up to the patient to maintain the prescribed treatmentschedule. Effective treatment requires stimulation any-where from three to ten hours each day in periods of noless than one hour.

Ultrasound stimulation is the most recent treatment
for stimulating bone growth. A device that generates lowintensity pulses of sound is applied to the skin over thefracture. The advantage of this technique is that it is non-invasive and the period of application of the sound pulsescan be as short as 20-30 minutes each day. The results ofthis treatment have been studied less than the effect ofelectromagnetic stimulation.
Bone growth stimulation is done only when healing

has failed to occur for many months. Before it is started,
GALE ENCYCLOPEDIA OF MEDICINE 2 546Bone growth stimulationGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 546

x rays are done of the fracture area. If the device is to be
implanted, standard preoperative blood and urine testsare done. The patient may meet with an anesthesiologistto discuss any conditions that might affect the adminis-tration of anesthesia.
Aftercare
If a noninvasive, pulsating, electromagnetic field
device is used, the patient must not put any stress or

weight on the fracture until it is healed, which is a matterof months in most cases. In all lower limb fractures,regardless of the stimulation method used, the patient cannot bear weight on the limb with the fracture until heal-ing is complete. This limits the patient’s mobility formany months. Patients have the responsibility for regu-larly making sure that the unit works and caring forexternal devices and the casts that hold them in place.
Risks

Risks
Noninvasive devices have few risks associated with
them. The main risk associated with implantable devicesis the development of infection at the site of implantation.
Success in healing a fracture nonunion using bone
growth stimulation depends on the type, location, andseverity of the fracture and the age and general health ofthe patient.
Resources
Mayo Clinic. “Fractures - Treatment Methods are Tailored to
the Break.” Mayo Clinic Health Letter 14, no. 4

(Apr.1996):1-3.
Bone infection seeOsteomyelitis
Bone marrow aspiration 
and biopsy
Bone marrow aspiration, also called bone marrow
sampling, is the removal by suction of fluid from thesoft, spongy material that lines the inside of most bones.Bone marrow biopsy, or needle biopsy, is the removal ofa small piece of bone marrow.KEY TERMS
Anode —The positive electrode to which an elec-
tromagnetic current flows.

Cathode —The negative electrode from which an
electromagnetic current flows.
Purpose
Bone marrow aspiration is used to:
• pinpoint the cause of abnormal blood test results
• confirm a diagnosis or check the status of severe ane-
mia (abnormally low numbers of red blood cells in thebloodstream) of unknown cause, or other irregularitiesin the way blood cells are produced or become mature
• evaluate abnormalities in the blood’s ability to store
iron
• diagnose infection

iron
Bone marrow biopsy is used to:
• obtain intact bone marrow for laboratory analysis
• diagnose and stage some types of cancer or anemia and
other blood disorders
• identify the source of an unexplained fever
• diagnose fibrosis of bone marrow or myeloma (a tumor
composed of cells normally found in the bone marrow)when bone marrow aspiration has failed to provide anappropriate specimen
Bone marrow aspiration and bone marrow biopsy

are also used to gauge the effectiveness of chemothera-
pyand other medical treatments. These procedures are
often used together to ensure the availability of the bestpossible bone marrow specimen.
Allergies or previous adverse reactions to medica-

tions should be discussed with the doctor. Any currentmedications, including herbal or nutritional supplements,should be evaluated for the potential to interfere withproper coagulation (clot formation). These would includecoumadin, aspirin , and other agents used as blood thin-
ners. Caution should be used when the herbs gingko, gin-ger, garlic, or ginseng have been utilized as supplements,due to a risk of bleeding.
Pregnancy ,lactation (production and secretion of

milk), and preexisting platelet or bleeding disordersshould be evaluated before either procedure is undertaken.
GALE ENCYCLOPEDIA OF MEDICINE 2 547Bone marrow aspiration GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 547

Bone marrow aspiration and biopsy should be per-
formed by a physician or nurse clinician. Each proce-dure takes about 20 to 30 minutes and is usually per-formed on an outpatient basis, but can be done in a hos-pital if necessary.
The skin covering the biopsy site is cleansed with an

antiseptic, and the patient may be given a mild sedative.A local anesthetic is administered. The hematologist ornurse clinician performing the procedure will not beginuntil the anesthetic has numbed the area from which thespecimen is to be extracted. In both adults and children,aspiration and biopsy are most commonly performed onthe rear bone of the hip (posterior iliac crest). In adults,sampling from the sternum (breastbone) is sometimesdone. The latter location is technically easier, but

The latter location is technically easier, but issomewhat more painful for the patient and presents therisk of heart injury. On rare occasions, a long bone of theleg (tibia) may be used as a sample site for an infant.

In a bone marrow aspiration, a special needle is
inserted beneath the skin and rotated until it penetratesthe cortex, or outer covering of the bone. At least half ateaspoon of marrow is withdrawn from the bone by a

syringe attached to the needle. The patient may experi-ence discomfort when the needle is inserted or when themarrow is aspirated. If more marrow is needed, the nee-dle is repositioned slightly, a new syringe is attached, anda second sample is taken. The samples are transferredfrom the syringes to slides and vials, then sent to a labo-ratory for analysis.
Bone marrow biopsy may be performed immediately

before or after bone marrow aspiration. The procedure uti-lizes a special large-bore needle that is used to drill out acore of marrow. In bone marrow biopsy, the needle isinserted, rotated from side to side, withdrawn, and reinsert-ed at a different angle. This procedure is repeated if neededuntil a small core, about 0.4 inches (1 cm) long, is separat-ed from the bone marrow. The needle is again removed,and a piece of fine wire threaded through its tip transfersthe specimen onto sterile gauze.

its tip transfersthe specimen onto sterile gauze. The patient may feel dis-comfort or pressure when the needle is inserted and experi-ence a brief, pulling sensation when the marrow is with-drawn. Unlike aspiration specimens, which are smeared,these samples contain structurally intact bone marrow.Microscopic examination can show what material its cells

GALE ENCYCLOPEDIA OF MEDICINE 2 548Bone marrow aspiration 
CortexAspiration needle
Inner spongy layer
Bone marrow
In a bone marrow aspiration, a needle is inserted beneath the skin and rotated until it penetrates the cortex, or outer covering
of the bone. A small amount of marrow is suctioned out of the bone by a syringe attached to the needle. (Illustration by Elec-
tronic Illustrators Group.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 548

contain and how they are alike or different from one anoth-
er. The bone may either be embedded intact in paraffin (atype of wax), or be decalcified (a process which takes placeovernight) for a different type of staining and examination.Each type of preparation has certain advantages.
A current history and physical are obtained from the

patient, along with proper consent. The patient is gener-ally placed in a prone position (lying face down) forpreparation, and local anesthetic, with or without seda-
tion, is administered.
Aftercare
After the needle is removed, the biopsy site will be

covered with a clean, dry bandage. Pressure is applied tocontrol bleeding. The patient’s pulse, breathing, bloodpressure, and temperature are monitored until they returnto normal, and the patient may be instructed to remain ina supine position (lying face up) for half an hour beforegetting dressed.
The patient should be able to leave the clinic and

resume normal activities immediately. Patients who havereceived a sedative often feel sleepy for the rest of the day;driving, cooking, and other activities that require clearthinking and quick reactions should therefore be avoided.
The biopsy site should be kept covered and dry for
several hours. Walking or taking prescribed pain medica-
tions usually ease any discomfort felt at the biopsy site,and ice can be used to reduce swelling.
A doctor should be notified if the patient:

• feels severe pain more than 24 hours after the procedure.• experiences persistent bleeding or notices more than a
few drops of blood on the wound dressing.
• has a temperature above 101°F (38.3°C). Inflammation
and pus at the biopsy site and other signs of infectionshould also be reported to a doctor without delay
Risks
Bleeding and discomfort often occur at the biopsy

site. Infection and hematoma may also develop. In rareinstances, the heart or a major blood vessel is piercedwhen marrow is extracted from the sternum during bonemarrow biopsy. This can lead to severe hemorrhage.
Healthy adult bone marrow contains yellow fat cells,
connective tissue, and red marrow that produces blood.KEY TERMS
Aspiration —A procedure to withdraw fluid from
the body.

the body.
Connective tissue —Material that links one part of
the body with another.
Fibrosis —A condition characterized by the pres-
ence of scar tissue or fiber-containing tissues thatreplace normal tissues.
Hematologist —A medical specialist who treats
diseases and disorders of the blood and blood-forming organs.
Hematoma —Blood that collects under the skin
and causes swelling.
Hemorrhage —Heavy bleeding.
Myeloma —A tumor that originates in bone mar-

row and usually spreads to more than one bone.
Nurse practitioner —A registered nurse who is
qualified to perform some specialized duties.
The bone marrow of a healthy infant is primarily red due
to active production of red cells necessary for growth.
Culture of bone marrow aspirate may yield informa-
tion about an infectious agent. Microscopic examinationof bone marrow can reveal granulomas, myelofibrosis ,

lymphomas, leukemias, or other cancers. Analyzing spec-imens can help doctors diagnose iron deficiency, vitaminB
12deficiency, and folate deficiency, as well as anemia.
Obesity can affect the ease with which a bone mar-
row biopsy can be done, and the results of either proce-dure can be affected if the patient has had radiation
therapy at the biopsy site.
Resources
BOOKS
Bain, Barbara, et al. Bone Marrow Pathology. Oxford, UK:
Blackwell Science, Ltd., 1996.

Gatter, Kevin, and David Brown. An Illustrated Guide to Bone
Marrow Diagnosis. Oxford, UK: Blackwell Science, Ltd.,
1997.
Zaret, Barry L., et al. The Yale University Patient’s Guide to
Medical Tests. Boston: Houghton Mifflin Company, 1997.
Leukemia Society of America. 600 Third Ave., New York, NY
10016. (800) 955-4572. <http://www.leukemia.org>.
GALE ENCYCLOPEDIA OF MEDICINE 2 549Bone marrow aspiration GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 549

National Cancer Institute Cancer Information Service. 9000
Rockville Pike, Bethesda, MD 20892. (800) 422-6237.<http://cis.nci.nih.gov>.
National Marrow Donor Program. 3433 Broadway St. NE,
#400, Minneapolis, MN 55413. (800) 627-7692. <http://www.marrow.org>.
The Wellness Community. 35 E. Seventh St., Suite 412,
Cincinnati, OH 45202. (888) 793-WELL. <http://www.wellness-community.org>.
OTHER
“Bone Marrow Biopsy.” CanCareSA Website. 2 July 1998. 25

June 2001 <http://www.health.sa.gov.au/cancare/Treatment/PROCEDURES-TESTS/BMBiopsy.htm>.
Bone marrow transplantation
The bone marrow—the sponge-like tissue found in

the center of certain bones—contains stem cells that arethe precursors of white blood cells, red blood cells, andplatelets. These blood cells are vital for normal bodyfunctions, such as oxygen transport, defense againstinfection and disease, and clotting. Blood cells have alimited lifespan and are constantly being replaced; there-fore, healthy stem cells are vital.
In association with certain diseases, stem cells may

produce too many, too few, or otherwise abnormal bloodcells. Also, medical treatments may destroy stem cells oralter blood cell production. The resultant blood cellabnormalities can be life threatening.
Bone marrow transplantation involves extracting

bone marrow containing normal stem cells from ahealthy donor, and transferring it to a recipient whosebody cannot manufacture proper quantities of normalblood cells. The goal of the transplant is to rebuild therecipient’s blood cells and immune system and hopefullycure the underlying ailment.
Purpose
A person’s red blood cells, white blood cells, and

platelets may be destroyed or may be abnormal due todisease. Also, certain medical therapies, particularlychemotherapy or radiation treatment, may destroy a

person’s stem cells. The consequence to a person’s healthis severe. Under normal circumstances, red blood cellscarry oxygen throughout the body and remove carbondioxide from the body’s tissues. White blood cells formthe cornerstone of the body’s immune system and defendit against infection. Platelets limit bleeding by enablingthe blood to clot if a blood vessel is damaged.
A bone marrow transplant is used to rebuild the

body’s capacity to produce these blood cells and bringtheir numbers to normal levels. Illnesses that may betreated with a bone marrow transplant include both can-cerous and noncancerous diseases.
Cancerous diseases may or may not specifically
involve blood cells; but, cancer treatment can destroy the

body’s ability to manufacture new blood cells. Bone mar-row transplantation may be used in conjunction withadditional treatments, such as chemotherapy, for varioustypes of leukemia, Hodgkin’s disease , lymphoma, breast
and ovarian cancer , and other cancers. Noncancerous
diseases for which bone marrow transplantation can be atreatment option include aplastic anemia ,sickle cell
disease ,thalassemia , and severe immunodeficiency .
Bone marrow transplants are not for everyone.

Transplants are accompanied by a risk of infection, trans-plant rejection by the recipient’s immune system, andother complications. The procedure has a lower successrate the greater the recipient’s age. Complications areexacerbated for people whose health is already seriouslyimpaired as in late-stage cancers. Therefore, a person’sage or state of health may prohibit use of a bone marrowtransplant. The typical cut-off age for a transplant rangesfrom 40 to 55 years; however, a person’s general

40 to 55 years; however, a person’s general health isusually the more important factor.

Even in the absence of complications, the transplant
and associated treatments are hard on the recipient. Bonemarrow transplants are debilitating. A person’s ability towithstand the rigors of the transplant is a key considera-tion in deciding to use this treatment.
Autologous and allogeneic transplants
Two important requirements for a bone marrow

transplant are the donor and the recipient. Sometimes,the donor and the recipient may be the same person. Thistype of transplant is called an autologous transplant. It istypically used in cases in which a person’s bone marrowis generally healthy but will be destroyed due to medicaltreatment for diseases such as breast cancer and

Hodgkin’s disease. Most bone marrow transplants areautologous. If a person’s bone marrow is unsuitable foran autologous transplant, the bone marrow must bederived from another person in an allogeneic transplant.
Allogeneic transplants are more complicated
because of proteins called human lymphocyte antigens
GALE ENCYCLOPEDIA OF MEDICINE 2 550Bone marrow transplantationGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 550

(HLA) that are on the surface of bone marrow cells. If
the donor and the recipient have very dissimilar antigens,the recipient’s immune system regards the donor’s bonemarrow cells as invaders and launches a destructiveattack against them. Such an attack negates any benefitsoffered by the transplant.
HLA matching
There are only five major HLA classes or types—

designated HLA–A,–B, –C,–D, and class III—but muchvariation within the groupings. For example, HLA–Afrom one individual may be similar to, but not the sameas, HLA–A in another individual; such a situation canrender a transplant from one to the other impossible.
HLA matching is more likely if the donor and recip-

ient are related, particularly if they are siblings; however,an unrelated donor may be a potential match. Only inrare cases is matching HLA types between two peoplenot an issue: if the recipient has an identical twin. Identi-cal twins carry the same genes; therefore, the same anti-gens. A bone marrow transplant between identical twinsis called a syngeneic transplant.
Peripheral blood stem cell transplants
A relatively recent development in stem cell trans-

plantation is the use of peripheral blood cells instead ofstem cells from bone marrow. Peripheral blood stem cells(PBSCs) are obtained from circulating blood rather thanfrom bone marrow, but the amount of stem cells found inthe peripheral blood is much smaller than the amount ofstem cells found in the bone marrow. Peripheral bloodstem cells can be used in either autologous or allogeneictransplants. The majority of PBSC transplants are autolo-gous. However, recent clinical studies indicate

However, recent clinical studies indicate thatPBSCs are being used more frequently than bone mar-row for allogeneic bone marrow transplantation.

The advantages of PBSC transplants when compared
to bone marrow transplants are: in allogeneic transplanta-tion, haematopoietic and immune recovery are faster withPBSCs which reduces the potential for disease recur-rence, primarily graft-versus-host-disease. In autologoustransplantation, the use of PBSCs can result in fasterblood count recoveries. Also, some medical conditions

exist in which the recipient cannot accept bone marrowstem cell transplants, but can accept PBSC transplants.Some possible disadvantages to PBSC transplant versusbone marrow transplantation are: so much more fluid vol-ume is necessary to collect enough PBSCs that, at thetime of infusing the new stem cells into the recipient, thefluid can collect in the lungs or cause temporary kidneyproblems. Also, the time commitment for the donor for aPBSC transplant is considerable. When the PBSCs arebeing

is considerable. When the PBSCs arebeing collected, several outpatient sessions are needed

and each session lasts approximately two–four hours.
The transplant procedure
BONE MARROW TRANSPLANTATION. The bone mar-

row extraction, or harvest, is the same whether for an autol-ogous or allogeneic transplant. Harvesting is done undergeneral anesthesia (i.e., the donor sleeps through the proce-dure), and discomfort is usually minimal afterwards. Bonemarrow is drawn from the iliac crest (the part of the hipbone to either side of the lower back) with a special needleand a syringe. Several punctures are usually necessary tocollect the needed amount of bone marrow, approximately1–2 quarts (0.9-1.91). (This amount

approximately1–2 quarts (0.9-1.91). (This amount is only a small percent-age of the total bone marrow and is typically replaced with-in four weeks.) The donor remains at the hospital for 24–48hours and can resume normal activities within a few days.

If the bone marrow is meant for an autologous trans-
plant, it is stored at –112 to –320°F (–80 to –196°C) untilit is needed. Bone marrow for an allogeneic transplant issometimes treated to remove the donor’s T cells (a typeof white blood cell) or to remove ABO (blood type) anti-gens; otherwise, it is transplanted without modification.
GALE ENCYCLOPEDIA OF MEDICINE 2 551Bone marrow transplantation
In autologous bone marrow transplantation, stem cells are

collected from the patient. Once the patient has undergonechemotherapy, the cells are replaced in the blood via an intra-venous catheter.The cells return to the bone marrow andbegin producing healthy new cells. (Illustration by Argosy Inc.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 551

The bone marrow is administered to the recipient via
a catheter (a narrow, flexible tube) inserted into a largevein in the chest. From the bloodstream, it migrates tothe cavities within the bones where bone marrow is nor-mally stored. If the transplant is successful, the bonemarrow begins to produce normal blood cells once it is inplace, or engrafted.
PERIPHERAL BLOOD STEM CELL TRANSPLANTATION.

Before collection for a PBSC transplant, donors receivedaily four injections of the drug G-CSF, or filgrastim.(Patients can give it to themselves at home if need be.)These pretreatments stimulate the body to release stemcells into the blood. After these pretreatments, theKEY TERMS
ABO antigen —Protein molecules located on the
surfaces of red blood cells that determine a person’sblood type: A, B, or O.
AML —Acute myelogenous leukemia, also called

acute myelocytic leukemia. Malignant disorderwhere myeloid blast cells accumulate in the mar-row and bloodstream.
Allogeneic —Referring to bone marrow transplants
between two different, genetically dissimilar peo-ple.
Anemia —Decreased red cell production which
results in deficiency in oxygen-carrying capacity ofthe blood.
Antigen —A molecule that is capable of provoking
an immune response.
Aplastic anemia —A disorder in which the body

produces inadequate amounts of red blood cellsand hemoglobin due to underdeveloped or missingbone marrow.
Autologous —Referring to bone marrow transplants
in which recipients serve as their own donors.
Blank —If an individual has inherited same HLA
antigen from both parents, the HLA typing is desig-nated by the shared HLA antigen followed by a“blank”(–).
Blast cells —Blood cells in early stage of cellular
development.

Blast crisis —Stage of chronic myelogenous
leukemia where large quantities of immature cellsare produced by the marrow and is not responsiveto treatment.Bone marrow —A spongy tissue located within flat
bones, including the hip and breast bones and theskull. This tissue contains stem cells, the precursorsof platelets, red blood cells, and white blood cells.
Bone marrow transplant —Healthy marrow is

infused into people who have had high-dosechemotherapy for one of the many forms ofleukemias, immunodeficiencies, lymphomas, ane-mias, metabolic disorders, and sometimes solidtumors.
Chemotherapy —Medical treatment of a disease,
particularly cancer, with drugs or other chemicals.
Chronic myelogenous leukemia (CML) —Also

called chronic myelocytic leukemia, malignant dis-order that involves abnormal accumulation of whitecells in the marrow and bloodstream.
Cytomegalovirus (CMV) —Virus that can cause
pneumonia in post bone marrow transplant patients.
Conditioning —Process of preparing patient to
receive marrow donation, often through the use ofchemotherapy and radiation therapy.
Confirmatory typing —Repeat tissue typing to con-

firm the compatibility of the donor and patientbefore transplant.
Donor —A healthy person who contributes bone
marrow for transplantation.
Graft versus host disease —A life-threatening com-
plication of bone marrow transplants in which thedonated marrow causes an immune reactionagainst the recipient’s body.Histocompatibility —The major histocompatibility
determinants are the human leukocyte antigens

donors’ experience is similar to that of a whole blood

donor’s experience—PBSC donors’ blood is collected ata clinic or hospital as an outpatient procedure. The differ-ences are that several sessions will be needed over daysor weeks and the blood is collected in a process calledapheresis. The blood travels from one arm into a bloodcell separator that removes only the stem cells, and therest of the blood is returned back to the donor, in theother arm. The cells are then frozen for later use.
The PBSCs are administered to the recipient using

the same methods as those used in bone marrow trans-plantation. As stated, the amount of fluid with PBSCsinfused into the recipient’s body can be an issue.
GALE ENCYCLOPEDIA OF MEDICINE 2 552Bone marrow transplantationGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 552

Costs
Bone marrow transplantation is an expensive proce-
dure. (Bone marrow donors are volunteers and do notpay for any part of the procedure.) Insurance companiesand health maintenance organizations (HMOs) may notcover the costs.
A bone marrow transplant recipient can expect to spend
four to eight weeks in the hospital. In preparation for receiv-ing the transplant, the recipient undergoes “conditioning”—apreparative regimen in which the bone marrow and abnor-KEY TERMS

(HLA) and characterize how well the patient anddonor are matched.
HLA (human leuckocyte antigen) —A group of pro-
tein molecules located on bone marrow cells thatcan provoke an immune response. A donor’s and arecipient’s HLA types should match as closely aspossible to prevent the recipient’s immune systemfrom attacking the donor’s marrow as a foreignmaterial that does not belong in the body.
Hodgkin’s disease —A type of cancer involving the

lymph nodes and potentially affecting nonlymphat-ic organs in the later stage.
Immunodeficiency —A disorder in which the
immune system is ineffective or disabled either dueto acquired or inherited disease.
Leukemia —A type of cancer that affects leukocytes,
a particular type of white blood cell. A characteris-tic symptom is excessive production of immature orotherwise abnormal leukocytes.
Lymphoma —A type of cancer that affects lymph

cells and tissues, including certain white blood cells(T cells and B cells), lymph nodes, bone marrow,and the spleen. Abnormal cells (lymphocyte/leuko-cyte) multiply uncontrollably.
Match —How similar the HLA typing, out of a pos-
sible six antigens, is between the donor and therecipient.
Mixed lymphocyte culture (MLC) —Test that mea-
sures level of reactivity between donor and recipi-ent lymphocytes.
Neuroblastoma —Solid tumor in children, may be

treated by BMT.Platelets —Fragments of a large precursor cell, a
megakaryocyte found in the bone marrow. Thesefragments adhere to areas of blood vessel damageand release chemical signals that direct the forma-tion of a blood clot.
Recipient —The person who receives the donated
blood marrow.
Red blood cells —Cells that carry hemoglobin (the
molecule that transports oxygen) and help removewastes from tissues throughout the body.

Sickle cell disease —An inherited disorder charac-
terized by a genetic flaw in hemoglobin produc-tion. (Hemoglobin is the substance within redblood cells that enables them to transport oxygen.)The hemoglobin that is produced has a kink in itsstructure that forces the red blood cells to take on asickle shape, inhibiting their circulation and caus-ing pain. This disorder primarily affects people ofAfrican descent.
Syngeneic —Referring to a bone marrow transplant

from one identical twin to the other.
Thalassemia —A group of inherited disorders that
affects hemoglobin production. (Hemoglobin is thesubstance within red blood cells that enables themto transport oxygen.) Because hemoglobin produc-tion is impaired, a person with this disorder maysuffer mild to severe anemia. Certain types of tha-lassemia can be fatal.
White blood cells —A group of several cell types

that occur in the bloodstream and are essential for aproperly functioning immune system.
mal cells are destroyed. Conditioning rids the body of dis-

eased cells and makes room for the marrow to be transplant-ed. It typically involves chemotherapy and/or radiation treat-ment, depending on the disease being treated. Unfortunately,this treatment also destroys healthy cells and has many sideeffects such as extreme weakness, nausea, vomiting, anddiarrhea . These side effects may continue for several weeks.
Aftercare
A two– to four–week waiting period follows the mar-

row transplant before its success can begin to be judged.The marrow recipient is kept in isolation during this time
to minimize potential infections. The recipient also
GALE ENCYCLOPEDIA OF MEDICINE 2 553Bone marrow transplantationGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 553

receives antibiotic medications and blood and platelet
transfusions to help fight off infection and prevent exces-sive bleeding. Further side effects, such as nausea and
vomiting , can be treated with other medications. Once
blood counts are normal and the side effects of the trans-plant abate, the recipient is taken off antibiotics and usu-
ally no longer needs blood and platelet transfusions.
Following discharge from the hospital, the recipient is

monitored through home visits by nurses or out-patient vis-its for up to a year. For the first several months out of thehospital, the recipient needs to be careful in avoidingpotential infections. For example, contact with other peoplewho may be ill should be avoided or kept to a minimum.Further blood transfusions and medications may be neces-sary, but barring complications, the recipient can return tonormal activities about 6–8 months after the transplant.
Risks

ous and life-threatening risks. Furthermore, they are notalways an absolute assurance of a cure for the underlyingailment; a disease may recur in the future. Approximate-ly 30% of people receiving allogeneic transplants do notsurvive. Autologous transplants have a much better sur-vival rate—nearly 90%—but are not appropriate for alltypes of ailments requiring a bone marrow transplant.Furthermore, they have a higher failure rate with certaindiseases, specifically leukemia.

or other infectious disease, excessive bleeding, or liverdisorder caused by blocked blood vessels. The transplantmay be rejected by the recipient’s immune system, or thedonor bone marrow may launch an immune-mediatedattack against the recipient’s tissues. This complication iscalled acute graft versus host disease, and it can be a life-threatening condition. Characteristic signs of the diseaseinclude fever , rash, diarrhea, liver problems, and a com-
promised immune system.

Approximately 25–50% of bone marrow transplant
recipients develop long-term complications. Chronic graftversus host disease symptoms include skin changes such asdryness, altered pigmentation, and thickening; abnormalliver function tests ; dry mouth and eyes; infections; and
weight loss. Other long-term complications includecataracts (due to radiation treatment), abnormal lung func-

tion, hormonal abnormalities resulting in reduced growthor hypothyroidism , secondary cancers, and infertility .
In a successful bone marrow transplant, the donor’s
marrow migrates to the cavities in the recipient’s bonesand produces normal numbers of healthy blood cells.
Bone marrow transplants can extend a person’s life,improve quality of life, and may aid in curing the under-lying ailment.
Resources
BOOKS
Armitage, J. O. “Bone Marrow Transplantation.” Harrison’s

Principles of Internal Medicine 14th Ed. New York, NY:
McGraw Hill, Inc., 1998: 724-730.
Lonergan, Jean Nelson, et al. Homecare Management of the
Bone Marrow Transplant Patient. 2nd ed. Boston: Jones
and Bartlett Publishers, 1996.
Treleaven, Jennifer, and Peter Wiernik, ed. Color Atlas and
Text of Bone Marrow Transplantation. St. Louis: Mosby-
Wolfe, 1995.
Dreger, P. and N. Schmitz. “Allogeneic transplantation of blood
stem cells: coming of age?” Annals of Hematology

(March, 2001) 80(3):127-36.
Nuzhat, Iqbal, Donna Salzman, Audrey J. Lazenby, et al.
“Diagnosis of Gastrointestinal Graft-Versus-Host Dis-ease.” The American Journal of Gastroenterology
(November, 2000) 95:3034- 3038.
American Society for Blood and Marrow Transplantation
(ASBMT) 85 W. Algonquin Road, Suite 550 Arlington

Heights, IL 60005. (847) 427-0224. mail@asbmt.org.Founded in 1990, a national professional association thatpromotes advancement of the field of blood and bonemarrow transplantation in clinical practice and research.
Blood & Marrow Transplant Newsletter (Formerly BMT

Newsletter). 2900 Skokie Valley Road, Suite B, HighlandPark, IL 60035 (847) 433-3313. 1-888-597-7674. help@bmtinfonet.org. <http://www2.bmtnews.org>. Blood &Marrow Transplant Newsletter is a not-for-profit organiza-tion that provides publications and support services tobone marrow, peripheral blood stem cell, and cord bloodtransplant patients and survivors.
International Bone Marrow Transplant Registry/Autologous
Blood and Marrow Transplant Registry N. America ,

Health Policy Institute, Medical College of Wisconsin,8701 Watertown Plank Road, P.O. Box 26509, Milwau-kee, WI 53226 USA, 414-456-8325, ibmtr@mcw.edu.V oluntary organizations of more than 400 institutions in47 countries that submit data on their allogeneic andautologous blood and marrow transplant recipients to theIBMTR/ABMTR Statistical Center at the Medical Col-lege of Wisconsin in Milwaukee.

Health Resources and Services Administration. 5600 Fishers
Lane, Rm. 14-45, Rockville, MD 20857, 301-443-3376,comments@hrsa.gov. <http://www.hrsa.gov>. HRSAmanages contracts for the Organ Procurement and Trans-plantation Network, Scientific Registry of TransplantRecipients and National Marrow Donor Program and pro-vides public education and technical assistance to increase
GALE ENCYCLOPEDIA OF MEDICINE 2 554Bone marrow transplantationGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 554

donation. HRSA also monitors the performance of the
nation’s transplant centers and provides potential trans-plant recipients with survival rates and other vital infor-mation.
Leukemia & Lymphoma Society, Inc. 1311 Mamaroneck
Avenue White Plains, NY 10605, 914-949-5213<http://www.leukemia-lymphoma.org/>. National volun-tary health agency dedicated to curing leukemia, lym-phoma, Hodgkin’s disease and myeloma, and to improv-ing the quality of life of patients and their families.

National Marrow Donor Program . Suite 500, 3001 Broadway
Street Northeast, Minneapolis, MN 55413-1753. (800)MARROW-2. <http://www.marrow.org>. Founded in1986, The National Marrow Donor Program (NMDP) is anon-profit international leader in the facilitation of unre-lated marrow and blood stem cell transplantation.
BMT Information <http://www.bmtinfo.org/>. Web site, spon-

sored by a variety of other bone marrow transplant organi-zations, lists basic information and resources about bonemarrow transplants.
National Organ and Tissue Donation Initiative <http://www.
organdonor.gov/>. Created by Health Resources and Ser-vices Administration (HRSA) Department of Health andHuman Services (DHHS) <http://www.os.dhhs.gov/>.Provides information and resources on organ donation andtransplantation issues.
Bone nuclear medicine scan

A bone scan is a diagnostic procedure used to evalu-
ate abnormalities involving bones and joints. A radioac-tive substance is injected intravenously, and the image ofits distribution in the skeletal system is analyzed to detectcertain diseases or conditions.
Purpose
Bone scans are most frequently ordered to check
whether a cancer that originated elsewhere has spread to

the bones. Cancers which begin in the breasts, kidneys,lungs, prostate, thyroid, or urinary bladder are most like-ly to spread, or metastasize, to the bones. If metastasesare found, periodic bone scans may be ordered to see iftherapy is effective against a cancer.
Some cancers arise in bone. These are called primary

bone cancers. When an abnormality is found on an x ray ofa bone, a bone scan may be helpful in deciding if it is a pri-mary bone cancer, or a non-cancerous (benign) condition.Infection in the bone ( osteomyelitis ) can be detected

or confirmed by a bone scan, often days or weeks beforean x ray would reveal it. Bone scans are useful in diag-nosing early arthritic changes, and monitoring both theprogression of the disease and the effectiveness of treat-ment. Unexplained pain may be evaluated with a bone
scan, because it can demonstrate fractures which are dif-

ficult to detect on x ray. Bone scans can be used to see ifartificial joints have loosened or become infected. Sus-pected child abuse may be evaluated with a bone scan,
due to its ability to see an overall pattern of repeatedtrauma. Abnormalities caused by altered circulation tothe bone may be diagnosed with a bone scan.
Women who are pregnant or breastfeeding should
not have this test. A patient who is unable to remain stillfor an extended period of time may require sedation for

a bone scan.
This test is performed in a radiology facility, either

in a hospital department or an outpatient x-ray center.The patient usually sits or lies down while a radioactivesubstance is injected through a vein in the arm. For abone scan, the radionuclide used is specifically chosen toaccumulate in the bone. The patient then waits from threeto four hours, for the substance to collect within theskeletal system. During this time, he or she will beinstructed to drink several glasses of water. Patients arefree to get up and move around as they desire during

to get up and move around as they desire during thiswaiting time, and should urinate frequently. Just beforethe scanning begins, the patient should empty his or herbladder again. This ensures that a lot of radioactive mate-rial is not concentrated in the urinary bladder, whichcould obscure part of the pelvic bones.

During the scan, the patient lies on his or her back
on a table, but may be repositioned to the stomach or sideduring the study. It is important for the patient not tomove, except when directed to by the technologist.
The radionuclide scanner, sometimes called a

gamma camera, or scintillation camera, is positionedagainst the body part to be examined. Either the camera,the table, or both, may change position during the study.For a total body bone scan, the patient is scanned fromhead to foot, over a period of 30-60 minutes. Patientsshould experience no discomfort from this examination.
A special kind of bone scan, called a SPECT (Single

Photon Emission Computed Tomography) scan may beadded, to study a particular part of the body in moredetail. Suspected diseases of the hips, lower back, or jaw
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are often evaluated using this study. It usually takes an
additional 30-45 minutes. The camera circles completelyaround the area in question or multiple cameras are usedto create a cross-sectional image. This helps pinpoint thelocation of the abnormality being evaluated.
Another variation is called a three-phase, or three-

stage, bone scan. The procedure is the same, except thescanning takes place immediately after the radioactivesubstance is injected, approximately 20 minutes after theinjection, then two to four hours later.
Some specialized blood studies should be drawn
before this study is begun. Jewelry or metallic objectsneed to be removed. No other special physical prepara-tion is required.
The patient should understand that there is no dan-

ger of radioactive exposure to themselves or others, asonly small amounts of the radioisotope are used. Thetotal dose of radiation absorbed is minimal, often lessthan the amount received from ordinary x rays. Theradionuclide scanner does not emit any radiation at all,but detects and records it from the patient.
Aftercare
Fluids are encouraged after the scan to aid in the
excretion of the radioisotope. It is almost completelyeliminated from the body within 24 hours.

The normal appearance of the scan will vary accord-
ing to the patient’s age. In general, a uniform concentra-tion of radionuclide uptake is present in all bones in anormal scan.
A high concentration of radionuclide occurs in areas
of increased bone activity. These regions appear brighterand may be referred to as “hot spots”. They may indicateKEY TERMS
Radioisotope —A radioactive, or radiation-emit-
ting form, of an element.

Radionuclide —A substance which emits radiation
as it disintegrates.healing fractures, tumors, infections, or other processes
which trigger new bone formation. Lower concentrationsof radionuclide may be called “cold spots”. Poor bloodflow to an area of bone, or bone destruction from tumormay produce a cold spot.
The bone scan is a very sensitive test and can detect

subtle conditions more readily than other studies. How-ever, it is not a very specific examination, and often can-not distinguish exactly what disease process is causingan abnormality. Results need to be correlated with thepatient’s medical history, and other radiologic and labo-ratory studies to make a definite diagnosis.
Resources
BOOKS
Christian, Paul E., and R. Edward Coleman. “Skeletal System.”
In Nuclear Medicine , Ed. Donald R. Bernier, et al. St.

Sutter, Charles W., and David K. Shelton “Three-Phase Bone
Scan in Osteomyelitis and Other Musculoskeletal Disor-ders.” American Family Physician 54 (Oct. 1996): 1639-
1648.
Ellen S. Weber, MSN
Bone tumor seeSarcomas
Bone x rays
Bone x rays are a diagnostic test in which ionizing
radiation passing through the bones being examinedenables an image to be produced on film.
Purpose
Bone x rays are ordered to detect disease or injury to

the bone such as broken bones, tumors, and other prob-lems. They can determine bone density, texture, erosion,and changes in bone relationships. Bone x rays also eval-uate the joints for diseases such as osteoarthritis .
Precautions should be taken to protect patients from

unnecessary exposure to radiation. Patients should beshielded with lead aprons as much as possible. Women ofchildbearing age who could be pregnant should not havex rays of their trunk or pelvic regions. The fetus is espe-
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cially at risk during the first trimester of pregnancy .
Women who are pregnant should not have x rays of theirpelvic region, lumbar spine, and abdomen unlessabsolutely necessary. If other types of x rays are neces-sary, a lead apron should be used to shield the abdominaland pelvic regions.
X rays are a common diagnostic test in which a form

of energy called x-ray radiation penetrates the patient’sbody. In bone x rays, electrical current passes through anx-ray tube and produces a beam of ionizing radiation thatpasses through the bone(s) being examined. This producesa picture of the inside of the body on film. The physicianreads the developed x ray on a wall-mounted light box.
Digital x rays are a new type of x ray in which con-

ventional equipment is used to take the x ray but theimage is produced via computer. In a digital x ray, theimage is created on a reusable plate. After being read bya laser reader, the information is sent in digital form to astorage unit connected to a computer network fromwhich the radiologist reads the x ray. An electronic reportcan then be sent to the patient’s physician.
Problems with bones that x rays can detect result

from injury or from disease caused by a malfunction inthe patient’s bone chemistry. Bone injuries, especiallybroken bones ( fractures ), are common and can be
accurately diagnosed by bone x rays. X rays are espe-cially helpful in diagnosing simple and incomplete frac-tures which can’t be detected during a physical exami-
nation . X rays can also be used to check for bone posi-

tion in a fracture. Some bone diseases can be definitive-ly diagnosed with bone x rays while others requireadditional tests.
Osteoporosis , a common bone disease, can be detect-
ed in bone x rays but other tests are then ordered to deter-mine the extent of the disease. For osteomalacia and rick-ets, a blood test and x rays of the affected bone are usuallydefinitive; in some cases a bone biopsy (microscopic

analysis of a small ammount of tissue) is also done. In arare bone disease called Paget’s disease, x rays may beused in conjunction with bone, blood, and urine tests tomake a diagnosis. In another rare bone disease, fibrousdysplasia, bone x rays or a bone biopsy (microscopicanalysis of a small amount of tissue) are used to confirmthe diagnosis. Bone x rays are definitive in diagnosingosteogenesis imperfecta . For osteomyelitis , bone x rays

are used in conjunction with a blood test, bone scan, orneedle biopsy to make the diagnosis. For arthritis, x raysof the bone are occasionally used in conjunction withblood tests. In bone tumors, bone x rays are helpful butthey may not be definitive.Bone x rays are performed by a technician or radiol-

ogist, and interpreted by a radiologist. They are taken ina physician’s office, radiology unit, outpatient clinic, ordiagnostic clinic. Bone x rays generally take less than 10minutes. There is no pain or discomfort associated with
the test, but some people find it difficult to remain still.The results are often available in minutes.
During the test, the patient lies on a table. The tech-

nician taking the x ray will check the patient’s position-ing and place the x-ray machine over the part of the bodybeing examined. After asking the patient to remainmotionless, he or she steps out of the area and presses abutton to take the picture.
The patient is asked to remove clothing, jewelry, and
any other metal objects from the area being x rayed. Ifappropriate, a lead shield will be placed over other bodyparts to minimize exposure to radiation.
Aftercare

Aftercare
The patient can immediately resume normal activities.
Risks
The human body contains some natural radiation

and is also exposed to radiation in the environment.There is a slight risk from exposure to radiation duringbone x rays, however, the amount of radiation is smalland the risk of harm is very low. If reproductive organsare exposed to radiation, genetic alterations may occur.Excessive or repeated doses of radiation can causechanges in other types of body tissue. No radiationremains in the body after the x ray.

Normal bones show no fractures, dislocations, or
other abnormalities.
Results that indicate the presence of bone injury or
disease differ in appearance according to the nature of theinjury/disease. For example, fractures show up as clearbreaks in the bones, while osteoporotic bone has the sameshape as a normal bone on an x ray but is less dense.
Resources
BOOKS

GALE ENCYCLOPEDIA OF MEDICINE 2 557Bone x raysGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 557

“Tumors and Tumor-Like Lesions of the Bone.” In Current Med-
“FDA Approves Bone Density Measurement Device.” Women’s
Health Weekly 23 (Mar. 1998), 13.
Tanner, Lisa. “New Radiology Saving Money-And Maybe
Lives.” Dallas Business Journal , 20 (25 July 1997): 23.
Wu, C. “Nylon May Take X Rays into Digital Age.” Science
News , 150 (3 Aug. 1996): 70.
OTHER

OTHER
“Bone Fracture,” and “Osteporosis: Improved Detection and
Treatment.” ThriveOnline. 15 Apr. 1998 <http://thriveonline.oxygen.com>.
Borderline personality disorder see
Bordetella pertussis infection seeWhooping
cough
Borrelia burgdorferi infection seeLyme
disease
Botanical medicine seeHerbalism, western
Botox injections seeBotulinum toxin
injectionsKEY TERMS
Arthritis —A disease of the joints that arises from

wear and tear, age and less often from inflammation.
Osteogenesis imperfecta —Also called brittle bones,
this is a condition present at birth in which bonesare abnormally fragile, brittle and break easily.
Osteomalacia —A disease in which bones gradual-
ly soften and bend.Osteomyelitis —An infection of the bone marrow
and the bone.
Osteoporosis —A disease which occurs primarily
in post-menopausal women in which the amountof bone is reduced or skeletal tissue wastes away.

Paget’s disease —A disease, whose cause is
unknown, which is generally found in older peo-ple. Symptoms include bone pain, bowed legs,curves spine, and broken bones. Another name forthis disease is osteitis deformans.Botulinum toxin injections
Botulinum is a bacterium ( Clostridium botulinum ) that
produces seven different toxins that can cause botulism
and is also medically used to block muscle contractions.
Purpose
Botulinum toxin (Botox) injection is used in condi-

tions of excessive and inappropriate muscle contraction,hyperhidiosis (excess sweating) in armpits and palms,spasticity (persistent states of muscle contraction), sphinc-ter contraction, eye-movement disorders, tics and tremors ,
and cosmetically to treat facial lines and wrinkles.
Botox has also been explored in the treatment of

chronic muscle tension and migraine headaches. Therelief is likely due to the decrease in localized musclespasms, as no direct effect of Botox on the sensorynerves has been established.
Botulinum toxin is produced from the bacterium that
causes food poisoning in humans. High doses of the
toxin can be fatal; however, doses administered therapeu-tically are so small that harmful effects are uncommon.

The number of potential applications for botulinum
toxin extends to every muscle group. The first therapeu-tic use of Botox was in the treatment of strabismus (eyes

are unable to direct towards the same object) and sincethen it has been used to treat a variety of involuntarymuscle contractions or disorders. Its cosmetic use is theresult of treatment for facial spasms where smoothing offacial lines was reported by patients. In general, 90% ofinjections for facial spasms are resolved satisfactorily.
Toxin type A has a duration of effect that lasts
approximately three months and is the therapeutic agentof choice for most conditions.

The dosage of Botox must be monitored and adjust-
ed, with multiple injections showing a lower incidence ofcomplications versus administration by one larger dose.
Risks
In over 30 years of therapeutic use in humans, botu-
linum toxin has proven to be remarkably safe. Difficul-
GALE ENCYCLOPEDIA OF MEDICINE 2 558Botulinum toxin injectionsGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 558

ties associated with administration of toxin are: different
patients may experience different effects at the samedose, patients new to the treatment may experience exag-gerated effects at subsequent visits and/or neighboringmuscles may become activated at subsequent treatments.
Additional side effects may include excessive mus-

cle weakness at the injection site or adjacent muscles.These effects typically resolve quickly. Occasionally,patients report flu-like symptoms but they are usuallyself-limited.
A certain percentage of patients may also experience

resistance to the toxin. The presence of circulating anti-bodies to the toxin is presumed to be the primary reasonfor resistance to Botox injections. Patients who have lit-tle reaction to Botox ‘A’ may benefit from injectionsusing one of the other six serotypes. Using the smallesteffective dose limits the likelihood of immunoresistancein unresponsive patients.
The anticipated outcome of Botox injections is

relaxation of the target muscle tissue. The pharmacologi-cal effects of botulinum toxin are typically isolated tolocal areas and do not result in tissue destruction or pro-longed paralysis . Varying the dose can deliver a precise
amount of toxin to achieve graded degrees of paralysisfor the desired level of response.
Resources
BOOKS
Brin M.F. Botulinum Toxin Therapy: Basic Science and
Overview of Other Therapeutic Applications Department

of Neurology, Movement Disorders Program, The MountSinai Medical Center, New York, New York 10029.KEY TERMS
Antibodies —A protein developed in response to
the presence of a foreign substance.
Immunoresistance —The presence of circulating
antibodies.
Neuromuscular junction —Interface between
motor nerve ending and muscle tissue.
Serotype —Microorganisms differing in the type of
surface antigens.
Antigen —A foreign substance inducing an anti-

body response within the body.Blitzer, A., W. J. Binder, J. Brian Boyd, and Alastair Car-
ruthers. Management of Facial Lines and Wrinkles.
Philadelphia: Lippincott Williams & Wilkins, 1999.
OTHER
Blitzer A and L. Sulica. “Botulinum toxin: basic science and
clinical uses in otolaryngology.” New York Center forV oice and Swallowing Disorders, St. Luke’s RooseveltHospital Center.
Bonny McClain, DC
Botulism

Botulism
Botulism is caused by botulinum toxin, a natural
poison produced by certain bacteria in the Clostridium
genus. Exposure to the botulinum toxin occurs mostlyfrom eating contaminated food, or in infants, from cer-tain clostridia growing in the intestine. Botulinum toxinblocks motor nerves’ ability to release acetylcholine, theneurotransmitter that relays nerve signals to muscles, andflaccid paralysis occurs. As botulism progresses, the

muscles that control the airway and breathing fail.
Botulism occurs rarely, but it incites concern
because of its high fatality rate. Clinical descriptions ofbotulism possibly reach as far back in history as ancientRome and Greece. However, the relationship betweencontaminated food and botulism wasn’t defined until thelate 1700s. In 1793 the German physician, JustiniusKerner, deduced that a substance in spoiled sausages,which he called wurstgift (German for sausage poison),

caused botulism. The toxin’s origin and identityremained elusive until Emile von Ermengem, a Belgianprofessor, isolated Clostridium botulinum in 1895 and
identified it as the poison source.
Three types of botulism have been identified: food-

borne, wound, and infant botulism. The main differencebetween types hinges on the route of exposure to thetoxin. In the United States, there are approximately 110cases of botulism reported annually. Food-borne botu-lism accounts for 25% of all botulism cases and can betraced to eating contaminated home-preserved food.Infant botulism accounts for 72% of all cases, but therecovery rate is good (about 98%) with proper treatment.
Though domestic food poisoning is a problem

world-wide, there has been a growing concern regardingthe use of botulism toxin in biological warfare and terror-
GALE ENCYCLOPEDIA OF MEDICINE 2 559BotulismGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 559

ist acts. The Iraqi government admitted in 1995 that it
had loaded 11,200 liters of botulinum toxin into SCUDmissiles during the Gulf War. Luckily, these special mis-siles were never used. As of 1999, there were 17 coun-tries known to be developing biological weapons, includ-ing the culture of botulism toxins.
Causes
Toxin produced by the bacterium Clostridium botu-
linum is the main culprit in botulism. Other members of
the clostridium genus can produce botulinum toxin,

they are minor sources. To grow, these bacteria require alow-acid, oxygen-free environment that is warm (40-120°F or 4.4-48.8°C) and moist. Lacking these condi-tions, the bacteria transform themselves into spores that,like plant seeds, can remain dormant for years. Clostridiaand their spores exist all over the world, especially in soiland aquatic sediments. They do not threaten human oranimal health until the spores encounter an environmentthat favors growth. The spores then germinate, and

favors growth. The spores then germinate, and thegrowing bacteria produce the deadly botulism toxin.

at least seven types of botulism toxin, identified as A, B,C, D, E, F, and G. Humans are usually affected by A, B, E,and very rarely F. Domesticated animals such as dogs, cat-tle, and mink are affected by botulism C toxin, which alsoaffects birds and has caused massive die-offs in domesticbird flocks and wild waterfowl. Botulism D toxin cancause illness in cattle, and horses succumb to botulism A,B, and C toxin. There have been no confirmed human oranimal botulism cases linked to the G toxin.

proteins in nerve endings and irreversibly destroysthem. These proteins control the release of acetyl-choline, a neurotransmitter that stimulates musclecells. With acetylcholine release blocked, nerves arenot able to stimulate muscles. Ironically, botulinumtoxin has found a beneficial niche in the world of med-icine due to this action. Certain medical disorders arecharacterized by involuntary and uncontrollable mus-cle contractions. Medical researchers have discoveredthat injecting a strictly

have discoveredthat injecting a strictly controlled dose of botulinumtoxin into affected muscles inhibits excessive musclecontractions. The muscle is partially paralyzed andnormal movement is retained.

Symptoms
The three types of human botulism include the fol-
lowing symptoms:• Food-borne. Food that has been improperly preserved or
stored can harbor botulinum toxin-producing clostridia.Botulism symptoms typically appear within 18-36 hoursof eating contaminated food, with extremes of fourhours to eight days. Initial symptoms include blurred ordouble vision and difficulty swallowing and speaking.Possible gastrointestinal problems include constipation ,

nausea, and vomiting. As botulism progresses, the vic-tim experiences weakness or paralysis, starting with thehead muscles and progressing down the body. Breathingbecomes increasingly difficult. Without medical care,respiratory failure and death are very likely.
• Infant. Infant botulism was first described in 1976.
Unlike adults, infants younger than 12 months are vul-nerable to C. botulinum colonizing the intestine. Infants

ingest spores in honey or simply by swallowing spore-containing dust. The spores germinate in the largeintestine and, as the bacteria grow, they produce botu-linum toxin that is absorbed into the infant’s body. Thefirst symptoms include constipation, lethargy, and poorfeeding. As infant botulism progresses, sucking andswallowing (thus eating) become difficult. A nursingmother will often notice breast engorgement as the firstsign of her infant’s illness. The baby suffers overallweakness and

illness. The baby suffers overallweakness and cannot control head movements. Becauseof the flaccid paralysis of the muscles, the baby appears“floppy.” Breathing is impaired, and death from respira-tory failure is a very real danger.

• Wound. Confirmed cases of wound botulism have been
linked to trauma such as severe crush injuries to theextremities, surgery, and illegal drug use. Wound botu-lism occurs when clostridia colonize an infected woundand produce botulinum toxin. The symptoms usuallyappear four to 18 days after an injury occurs and aresimilar to food-borne botulism, although gastrointesti-nal symptoms may be absent.
Diagnosis
Diagnosis of botulism can be tricky because symp-

toms mimic those presented by other diseases. Botulismmay be confused with Guillain-Barre syndrome, myas-
thenia gravis , drug reactions, stroke , or nervous system
infection, intoxications (e.g. carbon monoxide oratropine), or shellfish poisoning . Sepsis is the most com-
mon initial diagnosis for infant botulism. Failure to
thrive may also be suspected. Some reports have linked
infant botulism to 5-15% of sudden infant death syn-

drome (SIDS, crib death) cases. Laboratory tests are
used for definitive diagnosis, but if botulism seems like-ly, treatment starts immediately.
While waiting for laboratory results, doctors ask
about recently consumed food and work to dismiss other
GALE ENCYCLOPEDIA OF MEDICINE 2 560BotulismGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 560

disease possibilities. A physical examination is done
with an emphasis on the nervous system. As part of thisexamination, CT scans, MRIs, electromyographic tests,or lumbar punctures may be ordered. Laboratory testsinvolve testing a suspected food and/or the patient’sserum, feces, or other specimens for traces of botulinumtoxin or clostridia.
Treatment
Drugs
Adults with botulism are treated with an antitoxin

derived from horse serum that is distributed by the Cen-ters for Disease Control and Prevention. The antitoxin(effective against toxin types A, B, and E) inactivatesonly the botulinum toxin that is unattached to nerve end-ings. Early injection of antitoxin (usually within 24 hoursof onset of symptoms) can preserve nerve endings, pre-vent progression of the disease, and reduce mortality.
Infants, however, cannot receive the antitoxin used

for adults. For them, human botulism immune globulin(BIG) is available in the United States through the InfantBotulism Treatment and Prevention Program in Berkeley,California. BIG neutralizes toxin types A, B, C, D, and EKEY TERMS
Acetylcholine —A chemical released by nerve cells
to signal other cells.
Antitoxin —A substance that inactivates a poison
(e.g., toxin) and protects the body from beinginjured by it.
CT scan —The abbreviated term for computed or

computerized axial tomography. The test involvesinjecting a radioactive substance into the body.Computers are used to scan for radiation and createthree-dimensional images of internal organs.
Electromyographic test —A medical test which
determines if a muscle’s response to electrical stim-uli. The test results allow medical personnel toassess how nerves to the muscle are functioning.
Flaccid paralysis —Paralysis characterized by limp,

unresponsive muscles.
Lumbar puncture —A procedure in which a small
amount of cerebrospinal fluid is removed from thelower spine. Examination of this fluid helps diag-nose certain illnesses.MRI—The abbreviated term for magnetic resonance
imaging. MRI uses a large circular magnet and radiowaves to generate signals from atoms in the body.These signals are used to construct images of inter-nal structures.
Neurotransmitter —A chemical found in nerves

which relays nerve signals to other cells. Acetyl-choline is a neurotransmitter.
Sepsis —The presence of infection-causing organ-
isms or associated toxins in the blood or withinbody tissues.
Spores —A state of “suspended animation” that
some bacteria can adopt when conditions are notideal for growth. Spores are analogous to plantseeds and can germinate into growing bacteriawhen conditions are right.
Toxin —A poisonous substance produced by a

microorganism, plant, or animal.
Tracheostomy —The procedure used to open a hole
in the neck to the trachea, or windpipe. It is some-times used in conjunction with a respirator.
before they can bind to nerves. This antitoxin can pro-
vide protection against A and B toxins for approximatelyfour months. Though many infants recover with support-ive care, BIG cuts hospital stay in half, and thereforereduces hospital costs by 50% as well.

Aside from antitoxin, no drugs are used to treat botu-
lism. Antibiotics are not effective for preventing or treating
botulism. In fact, antibiotic use is discouraged for infantsbecause dying bacteria could potentially release more toxininto a baby’s system. Antibiotics can be used, however, totreat secondary respiratory tract and other infections.
Respiratory support
Treatment for infants usually involves intensive respi-

ratory support and tube feeding for weeks or even months.Once an infant can breathe unaided, physical therapy isinitiated to help the child relearn how to suck and swallow.A respirator is often required to help adult patientsbreathe, and a tracheostomy may also be necessary.
Surgery
Surgery may be necessary to clean an infected wound
and remove the source of the bacteria that is producing thetoxin. Antimicrobial therapy may be necessary.

GALE ENCYCLOPEDIA OF MEDICINE 2 561BotulismGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 561

Gastric lavage
When botulism is caused by food, it often is neces-
sary to flush the gastrointestinal tract (gastric lavage).Often cathartic agents or enemas are used. It is important
to avoid products that contain magnesium, since magne-sium enhances the effect of the toxin.
Prognosis
With medical intervention, botulism victims can

recover completely, albeit slowly. It takes weeks tomonths to recover from botulism, and severe cases cantake years before a total recovery is attained. Recoverydepends on the nerve endings building new proteins toreplace those destroyed by botulinum toxin.
Vaccines against botulism do not exist to prevent

infant botulism or other forms of the disease. Foodsafety is the surest prevention for botulism. Botulinumtoxin cannot be seen, smelled, or tasted, so the wisestcourse is to discard any food that seems spoiled without
tasting it . Home canners must be diligent about using

sterile equipment and following U.S. Department ofAgriculture canning guidelines. If any part of a cannedfood container is rusty or bulging, the food should notbe eaten. Infant botulism is difficult to prevent, becausecontrolling what goes into an infant’s mouth is oftenbeyond control, especially in regard to spores in the air.One concrete preventative is to never feed honey toinfants younger than 12 months since it is one knownsource of botulism spores. As infants begin eating solidfoods, the

spores. As infants begin eating solidfoods, the same food precautions should be followed asfor adults.

Resources
BOOKS
Arnon, Stephen S. “Infant Botulism.” In Textbook of Pediatric
Infectious Diseases, 4th edition, edited by R.D. Feigen
and J.D. Cherry, Philidelphia: W.B. Saunders, 1998.
Arnon, Stephen S. “Botulism as an Intestinal Toxemia.” In
Infections of the Gastrointestinal Tract, edited by M.J.
Blaser et al., New York: Raven Press, 1995.
Cadou, Stephanie G. “Diagnosing Infant Botulism.” The Nurse
Practitioner. (March 2001) 26(3): 76.

Kessler, Kirn R., and Reiner Benecke. “Botulinum Toxin: From
Poison to Remedy.” NeuroToxicology 18(1997): 761.
Shapiro, Roger L. and David L. Swerdlow. “Botulism: Keys to
Prompt Recognition and Therapy.” Consultant. (April
1999): 1021- 1024.
Janie FranzBovine spongiform encephalopathy see
Creutzfeldt-Jakob disease
Bowel incontinence seeFecal incontinence
Bowel preparation
Bowel preparation is a procedure usually undertaken

before a diagnosis and /or treatment can be initiated for cer-tain colon and rectum diseases. Bowel preparation is acleansing of the intestines from fecal matter and secretions.
Purpose
The ultimate goal of bowel preparation is priming the
bowel for a diagnosis procedure (using x rays to detect adisease process in the intestines) or for surgical interven-tion (such as removal of polyps, cancer , or narrowing of
the intestinal diameter). Colonoscopy is an effective

treatment procedure for polyps (a growing mass of tis-sue). This procedure enables visualization of the entirelarge bowel. During a colonoscopy, polyps can be cauter-ized (applying an electric current which incinerates thepolyp). The procedure can be both diagnostic and thera-peutic. A sigmoidoscopy scope is a flexible tube that

allows clinicians to view the sigmoid colon (the part ofthe large intestine before the rectum). This procedure isimportant for detection of colon/rectal cancer. It is safe,quick to perform (usually 30–45 minutes in about 90% ofcases), and an effective diagnostic tool for evaluation of:
• rectal bleeding
• other studies that showed an abnormality
• removal of polyps
• biopsy
• evaluation of chronic diarrhea or inflammatory bowel
disease
• to detect recurrences for colon/rectal cancer or polyps

• relieving a twisted bowel
• foreign body removal• treating bleeding lesions
• preventive surveillance of cancer in patients with a pos-
itive family history of colon cancer
Antibiotic prophylaxis is not routinely recommend-
ed. In some cases of prosthetic heart valves, antibiotics
can be prescribed. Evidence exists that evacuation ofintestinal waste products in conjunction with antibiotics

GALE ENCYCLOPEDIA OF MEDICINE 2 562Bowel preparationGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 562

before (prophylactic) the procedure reduces the possibili-
ty of sepsis (infection which spreads from the primary
site to blood).
The bowel is emptied of any contents for procedures
such as barium enema (introducing a barium containing

chemical to promote better visualization of intestinesduring x rays) or colonoscopy. Preparation of the boweldistally—from the rectum—is necessary for diagnosticprocedures such as sigmoidoscopy. Prior to surgical pro-cedures bowel preparation is recommended to decreasethe possibility of developing more medical problems.Patients may also be given a course of antibiotics to pre-vent the possibility of infection.
Bowel preparation for visualization of the colon is per-

formed to ensure the procedure will be accurate and com-plete. There are several effective cleansing preparationsthat include: Polyethylene glycol solution, Magnesium cit-rate with bisacodyl tablets, and Castor oil with bisacodyltablets. One of these preparations should be administeredstarting at 4:00 
P.M. the day before the procedure.
Aftercare
After the preparation has been ingested the patient is
advised to only ingest clear liquids until midnight.
Risks

Risks
The current standard of care dictates that patients
receive antibiotic prophylaxis if they are high risk fordeveloping an infection. High-risk patients include thosewith cardiac diseases or patients who have a prostheses.
Absence of anatomical changes or abnormalities in
the intestines would result in normal diagnosis.
Polyps can be treated with electrocautery. A biopsy

is taken of any suspicious polyps and further analyzed.Sigmoidoscopy can detect masses, bleeding, and ulcera-tive disease.
Resources
BOOKS
Pfenninger, John L., et al. Procedures for Primary Care Physi-
cians. 1994.
Tierney, Lawrence M., et al, eds. Current Medical Diagnosis
and Treatment 2001. 40th ed. MCGraw-Hill, 2001.KEY TERMS
Lesion —An abnormal change in tissues.
Polyp —A growing mass of tissue.
Sturmann, K. “Neurologic Emergencies: The Neurologic

Examination.” Emergency Medicine Clinics of North
America 15 (Aug. 1997).
American College of Gastroenterology. 4900 B South 31st
Street, Arlington, V A 22206. (703) 820-7400. <http://www.acg.gi.org/ct_html>.
Bowel resection
A bowel resection is a surgical procedure in which a
part of the large or small intestine is removed.
Purpose
Bowel resection may be performed to treat various

disorders of the intestine, including cancer , obstruction,
inflammatory bowel disease, ruptured diverticulum,ischemia (compromised blood supply), or traumatic injury.
The preferred type of bowel resection involves

removal of the diseased portion of intestine, and surgical-ly re-joining the remaining ends. In this procedure, thecontinuity of the bowel is maintained and normal passageof stool is preserved. When deemed necessary by the sur-geon, the diseased portion of the bowel may be removed,and the functioning end of the intestine may be broughtout onto the surface of the abdomen, forming an tempo-rary or permanent ostomy . Use of the large intestine to

form the ostomy results in a colostomy ; use of small
intestine to form the ostomy results in an ileostomy.
As with any surgical procedure, the patient will be
required to sign a consent form after the procedure is
GALE ENCYCLOPEDIA OF MEDICINE 2 563Bowel resectionGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 563

explained thoroughly. Blood and urine studies, along
with various x rays and an electrocardiogram (EKG) maybe ordered as the doctor deems necessary. In order toempty and cleanse the bowel, the patient may be placedon a low residue diet for several days prior to surgery. Aliquid diet may be ordered for at least the day beforesurgery, with nothing taken by mouth after midnight. Aseries of enemas and/or oral preparations (GoLytely or

Colyte), may be ordered to empty the bowel of stool.Oral anti-infectives (neomycin, erythromycin, orkanamycin sulfate) may be ordered to decrease bacteriain the intestine and help prevent post-operative infection.A nasogastric tube is inserted through the nose into thestomach on the day of surgery or during surgery. Thisremoves the gastric secretions and prevents nausea and
vomiting . A urinary catheter (thin tube inserted into the

bladder) may also be inserted to keep the bladder emptyduring surgery, giving more space in the surgical fieldand decreasing chances of accidental injury.
Aftercare
Post-operative care for the patient who has had a
bowel resection, as with those who have had any majorsurgery, involves monitoring of blood pressure, pulse,respirations, and temperature. Breathing tends to be shal-low because of the effect of anesthesia and the patient’sreluctance to breathe deeply and experience pain that is

caused by the abdominal incision. The patient is instruct-ed how to support the operative site during deep breath-ing and coughing, and is given pain medication as neces-sary. Fluid intake and output is measured, and the opera-tive site is observed for color and amount of wounddrainage. The nasogastric tube will remain in place,KEY TERMS
Diverticulum —Small tubes or pouches that pro-

ject off the wall of the intestine, visible as opaqueon an x ray after the patient has swallowed a con-trast (dye) substance.
Embolism —Blockage of a blood vessel by any
small piece of material traveling in the blood. Theemboli may be caused by germs, air, blood clots,or fat.
Ischemia —A compromise in blood supply to body
tissues that causes tissue damage or death.
Ostomy —A surgically-created opening in the

abdomen for elimination of waste products (urineor stool).attached to low intermittent suction until bowel activity

resumes. Fluids and electrolytes are infused intravenous-ly until the patient’s diet can gradually be resumed,beginning with liquids and advancing to a regular diet astolerated. The patient is generally out of bed approxi-mately eight to 24 hours after surgery. Postoperativeweight loss follows almost all bowel resections. Weightand strength are slowly regained over a period of months.
Risks
Potential complications of this abdominal surgery
include:
• excessive bleeding• surgical wound infection

• incisional hernia (An organ projects through the mus-
cle wall that surrounds it. The hernia occurs through thesurgical scar.)
• thrombophlebitis (inflammation and blood clot to veins
in the legs)
• pneumonia• pulmonary embolism (blood clot or air bubble in the
lungs’ blood supply)
Complete healing is expected without complications

after bowel resection. The period of time required forrecovery from the surgery may vary depending of thepatient’s overall health status prior to surgery.
The doctor should be made aware of any of the fol-
lowing problems after surgery:
• increased pain, swelling, redness, drainage, or bleeding
in the surgical area
• headache, muscle aches, dizziness ,f e v e r
• increased abdominal pain or swelling, constipation , nau-
sea or vomiting, rectal bleeding, or black, tarry stools

Resources
BOOKS
Doughty, Dorothy. Urinary and Fecal Incontinence. St. Louis:
Mosby-Year Book, Inc., 1991.
Hampton, Beverly, and Ruth Bryant. Ostomies and Continent
Diversions. St. Louis: Mosby-Year Book, Inc., 1992.
Monahan, Frances. Medical-Surgical Nursing. Philadelphia: W.
B. Saunders Co., 1998.
Suddarth, Doris. The Lippincott Manual of Nursing. Philadel-
phia: J. B. Lippincott, 1991.
GALE ENCYCLOPEDIA OF MEDICINE 2 564Bowel resectionGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 564

United Ostomy Association, Inc. (UOA). 19772 MacArthur
Blvd., Suite 200, Irvine, CA 92612-2405. (800) 826-0826.<http://www.uoa.org>.
Wound Ostomy and Continence Nurses Society. 1550 South
Coast Highway, Suite #201, Laguna Beach, CA 92651.(888) 224-WOCN. Fax: (949) 376-3456.<http://www.wocn.org>.
Kathleen D. Wright, RN
Bowel surgery with ostomy seeColostomy
Bowel training
Bowel training helps to reestablish normal bowel
movements in persons who suffer from constipation ,

diarrhea , incontinence, or irregularity. Healthy bowel
activity is considered one or two movements of moderatesize every day.
Purpose
Many people for many reasons have irregular bowel

function. In some cases, the irregularity lasts beyond thecondition that caused it. The bowels by themselves developbad habits that can be retrained with suitable exercises andeducation. Normal bowel habits not only improve the qual-ity of life, they help prevent several common diseases—forexample, diverticulitis and fecal impaction. Gall stones,appendicitis ,colon cancer , hiatal hernia , diabetes, and

heart disease have also been related to the quality of bowelmovements and the foods that affect them.
• One of the most common causes of constipation is the
laxative habit. Repeated artificial stimulation of thebowels destroys their natural emptying reflex, so thatthey will no longer move without artificial stimulants.The laxative habit begins innocently enough with thecorrect belief that bowels should move every day, how-ever, laxatives will cause the evacuation of several days

worth of stool in a single movement. Impatient for stoolto reaccumulate for the necessary few days, the patienttakes another laxative, and the cycle begins.
• The other major cause of constipation is a diet with
insufficient bulk or roughage. The bowel works moresmoothly the more contents it has. Western diets of
highly refined foods have eliminated most of the residuefrom food. The result is that most food is absorbed, leav-ing little to pass through and be excreted as feces.

• Constipation occurs acutely with impaction—the pres-
ence in the rectum of a mass of feces too large to pass.Fecal impaction is usually the result of poor bowelhabits, a diet with too little liquid and roughage, andinadequate physical activity.
• Diarrhea, whether acute or chronic, can disrupt the
bowel’s normal rhythm and lead to irregularity.
• Several diseases of the nervous system affect bowel
reflexes.
Bowel training reestablishes the bowel’s normal

reflexes by repeating a routine until it becomes a habit.Naturally the patient must be able and willing to cooper-ate. Some patients are so convinced they need daily laxa-tives that they are afraid to do without them. It takes timefor a changed diet to effect the bowels and for the bowel toregain its normal rhythm. Trust and patience are necessary.
After gaining the patient’s cooperation, the next step

is to optimize the diet. Healthy bowel movements requireingestion of a large amount of liquids and bulk foods.The patient should drink two to three quarts of liquidsevery day, with liberal inclusion of prune juice and per-haps coffee for their natural laxative effect. Bulk comesfrom unrefined foods. Oat bran, wheat bran, brown rice,green vegetables, apples, and pears are a few examples ofhigh residue foods. Many patients will benefit fromadding bulk preparations of psyllium. Constipating

bulk preparations of psyllium. Constipating foodslike bananas and cheese should be avoided until a naturalrhythm is well established.

To assure that stools are soft enough to pass easily, it
is a good idea to add a pure stool softener like DOSS(dioctyl sodium sulfosuccinate), two to four per day asneeded. DOSS also helps prevent impaction.
There is usually a time of day when bowel move-

ments are more likely to occur. In anticipation of thistime, the patient should participate in activities that stim-ulate a normal bowel movement. Walking, eating unre-fined foods, and drinking prune juice or coffee, encour-age natural evacuation. It is acceptable to use lubricantssuch as glycerine suppositories or oil enemas at this
time. For severe constipation, water enemas may beneeded to initiate a movement.

It is also important for the patient to recognize the
urge to defecate and to respond right away to that urge.The longer stool sits in the rectum, the more water therectum will absorb from it, making it harder and moredifficult to pass.
With patience and diligence, normal bowel habits
and the health that comes with them will return in mostpatients.
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Resources
BOOKS
“Bowel Training.” Mosby’s Medical, Nursing, and Allied
Health Dictionary. Mosby-Year Book, Inc., 1994.
Burkitt, D. P., and H. C. Trowell, ed. Refined Carbohydrate
Foods and Disease: Some Implications of Dietary Fibre.New York: Academic Press, 1975.
Barker, L. Randol, et al., eds. Principles of Ambulatory Medi-
cine. Baltimore: William & Wilkins, 1994.
Braces seeImmobilization
Brachytherapy seeRadioactive implants
Brain abscess

Brain abscess is a bacterial infection within the brain.
The brain is usually well insulated from infection by

bacteria, protected by the skull, the meninges (tissue lay-ers surrounding the brain), the immune system, and thehighly regulated barrier between the bloodstream and thebrain. Under certain circumstances, however, bacteriacan invade the brain and cause a localized infectioncalled an abscess. Brain abscess is relatively rare,accounting for 1 in 10,000 hospital admissions. Singleabscess occurs in 75% of cases, and the remainder ofcases involve multiple abscesses. If not treated, brainabscess is

abscesses. If not treated, brainabscess is almost always fatal.KEY TERMS

Defecate —To pass feces (stool) out of the rectum
Diverticulitis —Infection of outpouchings in the
large bowel.
Fecal impaction —Obstruction of the rectum by a
large mass of feces (stool).
Hiatal hernia —Part of the stomach displaced
through the diaphragm into the chest.Causes and symptoms
One-half of all brain abscesses are caused by the
spread of bacteria from a nearby infection. Sources ofbacteria include:
• middle ear infections ( otitis media ) or infections in the

bony spaces in front of the middle ear ( mastoiditis )
• sinus infections
• an abscessed tooth.
Other sources of bacteria include:• lung infections
• abdominal infection
• infection of the heart’s lining ( endocarditis )
• penetrating head wounds
• neurosurgery
Acquired Immune Deficiency Syndrome ( AIDS ) or
the presence of another immune deficiency greatlyincreases the risk of brain abscess. Approximately 25%of cases have no detectable cause of infection.

Brain abscess can be caused by a variety of organ-
isms, many of them related to ear and sinus infections.Many times brain abscess cases are caused by two ormore bacteria. In 30–60% of cases, the bacteria combina-tion includes streptococci, microorganisms that can livewithout oxygen (anaerobes), and enterobacteria. A smallnumber of cases are caused by yeast, fungi, and single-cell organisms (protozoa).
The symptoms of brain abscess often develop slow-

ly, usually within a period of about two weeks. The mostcommon symptoms are:
• headache• neurologic symptoms related to the specific part of the
brain that is infected
• altered mental status
• seizures
Fever and stiff neck occur in less than one-third of
cases. Additional symptoms may include vomiting, eyetremor ( nystagmus ), poor balance, and uncoordinated
movements.
Diagnosis
Diagnosis of brain abscess is performed by using a

computed tomography scan (CT) or a magnetic reso-
nance imaging (MRI) scan to determine the site of
infection. Tissue removal (biopsy) is usually performedas well. A biopsy is performed to determine the type ofbacterium involved. Biopsies can also be used to rule out
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tumor or other noninfectious localized lesions, which
may look the same on the scans.
Other tests are performed to determine the source of
the infection. These tests include blood cultures, x raysof the chest, and a physical exam of the ears, sinuses, andteeth. A test for human immunodeficiency virus (HIV)
is usually also performed.
Treatment
Treatment for brain abscess begins with intravenous
antibiotics , chosen to match the infecting bacterium if

known, or to cover a wide spectrum of possibilities if not.Treatment usually continues for six to eight weeks.
Aspiration surgery is almost always done to drain the

abscess. In this procedure, a needle is guided to the infect-ed site by CT scan, and fluid is removed (aspirated) fromthe abscess. Aspiration may be repeated several timesuntil the bacteria are completely killed or removed. Surgi-cal removal of infected or dead tissue may be needed insome cases. For patients with many sites of infection,aspiration or surgical removal is not done because of theincreased difficulty and risk of the procedure. For thesepatients, antibiotic therapy alone is used.

thesepatients, antibiotic therapy alone is used. Steroid treat-ment is controversial, but may be indicated in some cases.

Prognosis
Even with prompt treatment, brain abscess is fatal in
about 20% of cases. About half of those who survivehave some residual neurological problems, includingseizures in many patients.
There are several reasons why patients with brain

abscess can have a poor prognosis. The illness may notbe diagnosed correctly or an accurate diagnosis may takeadditional time. The patient may receive an antibioticthat does not match the infecting organism. Sometimesthe infection may not be limited to a definite area in thebrain, making diagnosis and treatment difficult. Thesmall number of cases caused by fungal infection maytake additional time to diagnose. A patient may also havea poor prognosis because there is more than one abscess,the

because there is more than one abscess,the location of the abscess may be deep within the brain,or the infection may have moved into many locationswithin the brain. Severe complications can result frombrain abscess, including comma and brain rupture. In 80-100% of cases involving brain rupture, the patient dies.

Brain abscess may be preventable by prompt and
aggressive treatment of the infections which give rise toit, especially sinus and ear infections.KEY TERMS
Biopsy —The removal of a tissue sample for exami-
nation.
Aspiration —Removal of fluid from a closed space
through a needle.
Resources
BOOKS
Rolak, Loren A. “Brain and Spinal Abscesses.” In Office Prac-

tice of Neurology , Ed. Martin Samuels and Steven Feske.
New York: Churchill Livingstone, 1996.
Wispelwey, Brian, and Carole A. Sable. “Intracranial Suppura-
tion.” In Current Therapy of Infectious Disease , Ed. David
Schlossberg. St. Louis: Mosby-Year Book, 1996.
Brain aneurysm seeCerebral aneurysm
Brain biopsy
A brain biopsy is the removal of a small piece of

brain tissue for the diagnosis of abnormalities of thebrain, such as Alzheimer’s disease , tumors, infection, or
inflammation.
Purpose
By examining the tissue sample under a microscope,
the biopsy sample provides doctors with the informationnecessary to guide diagnosis and treatment.
Imaging of the brain is performed to determine the
precise positioning of the needle to enter the brain.

When an abnormality of the brain is suspected,
Stereotactic (probing in three dimensions) brain needlebiopsy is performed and guided precisely by a computersystem to avoid serious complications. A small hole is
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brain tissue guided by computer-assisted imaging tech-niques (CT or MRI scans). Historically, the patient’shead was held in a rigid frame to direct the probe into thebrain; however since the early nineties, it has been possi-ble to perform these biopsies without the frame. Sincethe frame was attached to the skull with screws, thisadvancement is less invasive and better tolerated by thepatient. The doctor (pathologist) prepares the sample foranalysis and studies it further under a microscope.

A CT or MRI brain scan is done to find the position
where the biopsy will be performed. Prior to the biopsy,the patient is placed under general anesthesia.
Aftercare
The patient is monitored in the recovery room for
several hours and is usually required to spend a few daysin the hospital since general anesthesia is required.
Risks
The procedure is invasive and includes risks associ-
ated with anesthesia and surgery. Brain injury may occurKEY TERMS

Alzheimer’s disease —A progressive, neurodegen-
erative disease characterized by loss of functionand death of nerve cells in several areas of thebrain, leading to loss of mental functions such asmemory and learning.
Computed axial tomography (CT) —Computed
axial tomography (CT) is a x-ray technique that hasthe ability to image soft tissue, bone, and bloodvessels.
Cortex —The thin convoluted surface of the brain
comprised primarilyof cell bodies of neurons.

MRI—Magnetic resonance imaging is an imaging
technique that uses radiowaves, magnetic fields,and computer analysis to visualize body tissueand structures.
Stereotactic brain needle biopsy —In this proce-
dure a computer uses information from a CT orMRI to create a three-dimensional map of theoperation site to better guide the needle to per-form the biopsy.due to removal of brain tissue. The resulting scar, left on

the brain has the potential to trigger seizures.
After examining the brain tissue directly, no abnor-
malities are detected.
Various brain abnormalities can be diagnosed by

microscopic analysis of the tissue sample. The pathologist(a physician trained in how disease affects the body’s tis-sues) looks for abnormal growth, changes in cell mem-branes, and/or abnormal collections of cells. In Alzheimer’sdisease, the cortex of the brain contains abnormal collec-tions of plaques. If infection is suspected, the infectiousorganism can be cultured from the tissue and identified.Classification of tumors is also possible after biopsy.
Resources
BOOKS

Resources
BOOKS
Zaret, B. L. The Yale University School of Medicine Patient’s
Guide to Medical Tests. Yale University School of Medi-
cine and G.S. Sharpe Communications Inc., 1997.
Alzheimer’s Association. 919 North Michigan Avenue, Suite
1100 Chicago, IL 60611-1676.(800) 272-3900 <http://www.alz.org/chapter/>.
American Brain Tumor Association. 2720 River Road, Suite
146, Des Plaines, IL 60018-4110. (800) 886-2282. <http://www.abta.org>.

National Institute of Neurological Disorders and Stroke, NIH
Neurological Institute. P.O. Box 5801 Bethesda, MD20824. (800) 352-9424. <http://www.ninds.nih.gov/index.htm>.
Bonny McClain, MS
Brain circulation scan seeTranscranial
Doppler ultrasonography
Brain infection seeEncephalitis
Brain injury seeHead injury
Brain surgery seeCraniotomy
Brain tumor
A brain tumor is an abnormal growth of tissue in the
brain. Unlike other tumors, brain tumors spread by local

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extension and rarely metastasize (spread) outside the
brain. A benign brain tumor is composed of non-cancer-ous cells and does not metastasize beyond the part of thebrain where it originates. A brain tumor is consideredmalignant if it contains cancer cells, or if it is composed
of harmless cells located in an area where it suppressesone or more vital functions.
Each year, more than 17,000 brain tumors are diag-

nosed in the United States. About half of all primarybrain tumors are benign, but in life-threatening locations.The rest are malignant and invasive.
Benign brain tumors
Benign brain tumors, composed of harmless cells,
have clearly defined borders, can usually be completelyremoved, and are unlikely to recur. Benign brain tumorsdo not infiltrate nearby tissues but can cause severe pain ,
permanent brain damage, and death . Benign brain
tumors sometimes become malignant.
Malignant brain tumors

Malignant brain tumors do not have distinct borders.
They tend to grow rapidly, increasing pressure within thebrain (IICP) and can spread in the brain or spinal cordbeyond the point where they originate. It is highly unusu-al for malignant brain tumors to spread beyond the cen-tral nervous system (CNS).
Primary brain tumors
Primary brain tumors originate in the brain. They
represent about 1% of all cancers and 2.5% of all cancerdeaths.
Metastatic or secondary brain tumors

Approximately 25% of all cancer patients develop
secondary or metastatic brain tumors when cancer cellsspread from another part of the body to the brain. Sec-ondary brain tumors are most apt to occur in patientswho have:
• breast cancer.• colon cancer.• kidney cancer.• lung cancer.• melanoma (cancer) of the skin. These metastatic brain
tumors can develop on any part of the brain or spinalcord.• cancer within the nasal passages and/or throat that fol-

low the nerve pathways into the skull, and metastasizeto the brain.
Who gets brain tumors
Brain tumors can develop at any age, but are most

common in children between the ages of 3-12, and inadults aged 55-65. Primary brain cancer is the secondmost common cause of cancer death between birth andthe age of 34, and the fourth most common cause of can-cer death in men aged 35-54. Primary tumors of the brainand central nervous system are often associated with HIVinfection. Men and caucasians have a higher risk of devel-oping brain tumors. Other risk factors being studiedinclude children with a history of previous radiation treat-ment to

a history of previous radiation treat-ment to the head for cancer; parents with certain cancers(nervous system, salivary gland, colon); having an olderfather; having well-educated parents; occupational expo-sure to vinyl chloride, lead, and pesticides; history ofepilepsy; history of certain genetic conditions (tuberoussclerosis, neurofibromatosis , von Hippel Lindau, famil-

ial polyposis , Osler-Weber-Rendu, Li-Fraumeni).
Naming and grading brain tumors
The name of a brain tumor describes where it origi-
nates, how it grows, and what kind of cells it contains. Atumor in an adult is also graded or staged according to:
• how malignant it is
• how rapidly it is growing and how likely it is to invade
other tissues
• how closely its cells resemble normal cells. (The more
abnormal a tumor cell looks, the faster it is likely togrow)

Low-grade brain tumors usually have well-defined
borders. Some low-grade brain tumors form or areenclosed (encapsulated) in cysts. Low-grade braintumors grow slowly, if at all. They may spread through-out the brain, but rarely metastasize to other parts of thebody.
Mid-grade and high-grade tumors grow more rapid-

ly than low-grade tumors. Described as “truly malig-nant,” these tumors usually infiltrate healthy tissue. Thegrowth pattern makes it difficult to remove the entiretumor, and these tumors recur more often than low-gradetumors.
A single brain tumor can contain several different

types of cells. The tumor’s grade is determined by thehighest-grade (most malignant) cell detected under amicroscope, even if most of the cells in the tumor are lessmalignant. An infiltrating tumor is a tumor of any gradethat grows into surrounding tissue.
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Types of brain tumors
Glioma is the term used to refer to the most preva-
lent primary brain tumors. Gliomas arise from glial tis-sue, which supports and nourishes cells that send mes-sages from the brain to other parts of the body. Thesetumors may be either malignant or benign. Astrocy-tomas, ependymomas, and mixed gliomas are three ofthe most common gliomas.
ASTROCYTOMAS. Named for the star-like shape of

their cells, astrocytomas can develop on any part of thebrain or spinal cord. Non-infiltrating astrocytomas growslowly, and rarely spread to nearby tissue. Mild-to-mod-erately anaplastic astrocytomas with well-differentiatedborders do not grow as slowly as non-infiltrating astrocy-tomas, and they do spread to surrounding tissues.
Anaplastic astrocytomas, which are also called

Grade III astrocytomas, look more abnormal and growmore rapidly than non-infiltrating or mild-to-moderatelyanaplastic tumors.
Grade IV astrocytomas are also called glioblastoma

multiforme (GBM) tumors. Accounting for 30% of allprimary brain tumors, GBMs are the most common braintumors in middle-aged adults. GBMs are the most malig-nant of all brain tumors. Because they contain a greatermixture of cells than any other brain tumor, they are themost difficult to treat.
EPENDYMOMAS. Also called ependymal tumors,

ependymomas account for 9% of all gliomas, and 5% ofall intracranial tumors. These tumors, which are mostcommon in children and adolescents, begin in the verythin membranes that help form cerebrospinal fluid (CSF)and line the brain cavities (ventricles) that contain it.
Ependymomas are usually benign, have well-differ-

entiated borders, resemble normal cells, and grow veryslowly. The cells of anaplastic (malignant) ependymo-mas look abnormal and grow more rapidly than the cellsof benign tumors.
MIXED GLIOMAS. These heterogeneous tumors con-

tain elements of astrocytomas and ependymomas and/oroligodendrogliomas. These are rare tumors that usuallyoccur in middle-aged adults, grow slowly, and do notusually spread beyond the part of the brain where theyoriginate. Mixed gliomas behave like tumors composedof the highest-grade cells they contain.
Non-glial brain tumors
The most common brain tumors that do not develop

from glial cells are medulloblastomas, meningiomas, andSchwannomas.MEDULLOBLASTOMAS. Scientists once thought
medulloblastomas (MDLs) developed from glial cells.These fast-growing, malignant tumors are now believedto originate in developing cells not normally present inthe body after birth. They are sometimes called primitiveneurodectal tumors (PNET).
MDL tumors are most common in children and are

more common in boys than in girls. Only 30% of MDLtumors occur in adults. MDL tumors usually originatein the cerebellum (the part of the brain that controlscoordination and some muscle activity), and are oftencarried to other parts of the brain by cerebrospinal fluid.MDL tumors rarely metastasize beyond the brain andspinal cord.
MENINGIOMAS. Meningiomas, which represent

more than 20% of all primary brain tumors, originate inthe membranes that enclose the brain and spinal cord(meninges). These tumors are usually benign and mostoften occur in women aged 30-50 years old. Menin-giomas grow so slowly that the brain can sometimesbecome accustomed to their presence. Meningiomascompress, rather than invade, brain tissue and may growto be quite large before any symptoms appear.
SCHWANNOMAS. Schwannomas originate in the

Schwann cells. These cells produce myelin, material thatprotects the acoustic nerve, which controls hearing.These benign tumors are twice as common in women asin men, and are most often diagnosed in patients betweenthe ages 30-60.
Schwannomas grow very slowly, and many people
adapt to the slight hearing loss and balance problems

that are the tumors’ earliest symptoms. A pear-shapedSchwannoma can cause sudden or gradual loss of hear-ing in an ear. As the tumor progresses, it can press on thenerves that control movement and feeling in the face, andcause headaches and facial numbness or tingling. Thepatient may have trouble walking, swallowing, or con-trolling eye movements, and the sense of taste can beaffected. A Schwannoma that grows large enough topress on the brainstem can be deadly.

CHILDHOOD BRAIN TUMORS. Brain tumors that
occur in children are described as supratentorial (in theupper part of the brain) or infratentorial (in the lowestpart of the brain). Astrocytomas and ependymomas arecommon supratentorial tumors. Infratentorial tumorsinclude medulloblastomas, astrocytomas, and ependy-momas.
The cause of primary brain tumors is unknown, but
people who work with rubber and certain chemicals havea greater-than-average risk of developing them. There is

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no evidence that head injury causes brain tumors, but
researchers are trying to determine the relationship, ifany, between brain tumors and viruses, family history,and long-term exposure to electromagnetic fields.
Symptoms do not usually appear until the tumor
grows large enough to displace, damage, or destroy deli-cate brain tissue. When that happens, the patient mayexperience:
• headaches that become increasingly painful and are
most painful when lying down

• nausea and vomiting or sudden attacks of vomiting not
accompanied by nausea
• seizures• dizziness, loss of coordination or balance• personality changes• sudden loss of vision• memory loss• speech problems• sensory changes• mental impairment• weakness or paralysis on one side of the body
A doctor should be notified whenever a patient expe-
riences one or more of the symptoms.
Diagnosis
Although brain tumor symptoms resemble those of

many other illnesses, the presence of a brain tumor maybe indicated by:
• persistent headaches with vomiting or convulsions• progressive deterioration of sight, speech, hearing,
touch; or deterioration in the ability to use an arm,hand, foot, or leg
When a patient experiences one or more of the
above symptoms, a primary care physician will performa complete physical examination , take a detailed med-

ical history, and conduct a basic neurologic examinationto evaluate:
• balance and coordination• abstract thinking and memory• eye movements• hearing, touch, and sense of smell• reflexes• control of facial muscles and movements of the head
and tongue
• awarenessIf the results of these examinations suggest a patient
may have a brain tumor, a neurologist recommends someor all of these additional diagnostic tests:
• computed tomography scan (CT scan) to reveal brain
abnormalities

• magnetic resonance imaging (MRI) to detect tumors
beneath the bones of the skull
• complex imaging techniques such as Positron emis-
sion tomography (PET scan), Single photon emission
tomography (SPECT scan)
• electroencephalography (EEG) to measure electrical
activity in the brain
• magnetoencephalography (MEG scan) to measure the
magnetic fields produced by nerve cells and their elec-tric currents
• x rays to reveal any distortion in the bones of the skull

• angiography to outline a tumor and the blood vessels
that lead to it
• a brain scan to identify and record the location of
abnormal cells in the brain
• radionuclide brain scintigraphy to view the capillaries
feeding the tumor after highlighting them with aradioactive substance
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A scan of a brain with a tumor located in the central right
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• myelography (x ray of the spine) to detect a spinal cord
tumor
• a lumbar puncture (spinal tap) to obtain spinal fluid,
which may contain tumor cells.
• digital holography to view a complete three-dimension-
al map of the tumor and surrounding brain structures
Interpreting these images and results of laboratory
analysis allows neurologists to determine whether atumor is present, but microscopic examination of tumortissue (biopsy) is the only way to identify the kind ofcells it contains.

Treatment
Brain tumors are treated by multidisciplinary teams
of highly skilled specialists whose decisions are based on:
• results of diagnostic tests
• tumor size, position, and growth pattern
• the patient’s health history and current medical status• the wishes of the patient and his family
Surgery
Surgery is the treatment of choice for accessible

brain tumors, which can be removed without causingserious neurologic damage. The procedure most oftenperformed is a craniotomy , but the goals of any type of
brain tumor surgery include:
• removing as much of the tumor as possible (called
debulking the tumor)
• removing tumor tissue for microscopic analysis• allowing neurosurgeons to see exactly how the tumor is
situated and how it is growing

• creating an entry channel for chemotherapy drugs and
forms of radiation that are implanted in the brain
Depending on the type of brain tumor, its location,
and its size, a number of different techniques may beused to surgically remove it. Surgical techniques include:
• classic operation
• laser microsurgery (uses high temperatures to vaporize
tumor cells
• ultrasonic aspiration (uses ultrasound waves to break up

the tumor into smaller bits which can be “vacuumed”out
Before undergoing brain surgery, patients are often
given:
• steroids to reduce swelling of brain tissue• snticonvulsant medications to prevent or control seizures• radiation treatments to reduce tumor size
Patients whose benign brain tumors can be com-

pletely removed may not require any additional treat-ment, but periodic physical and neurologic examinationsand CT or MRI scans are sometimes recommended todetermine whether the tumor has returned. Because sur-geons cannot be sure that every bit of an infiltrating ormetastasizing tumor has been removed, radiation andchemotherapy are used to eradicate cells that may haveescaped the scalpel.
If a tumor cannot be completely removed, removing

a portion of it (debulking) can alleviate the patient’ssymptoms, enhance the sense of well-being, and increasethe effectiveness of other treatments.
Radiation therapy
External radiotherapy, generally delivered on an out-
patient basis, directs radiation to the tumor and the areaaround it. Implant radiation therapy involves placing tiny

pieces of radioactive material in the brain. Left in placepermanently, or for a short time, these radioactive pelletsrelease measured doses of radiation each day. This tech-nique is called brachytherapy. Patients are usually hospi-talized during the several days the pellets are most active.
Stereoactic radiosurgery involves fitting the patient

with a frame to stabilize the head, using imaging tech-niques to determine the exact location of tumor cells, andusing a sophisticated instrument to administer radiationprecisely to that point. Instruments used for delivery ofradiation include the gamma knife, adapted linear accel-erator (LINAC), and cyclotron.
A variety of drugs may also be given during radia-

tion therapy, to protect brain cells from the effects ofradiation (radioprotective drugs), to increase the sensitiv-ity of tumor cells to radiation (radiosensitizers), or toboost radiation’s effects (radioenhancers).
Chemotherapy
One or more cancer-killing drugs may be taken by

mouth or injected into a blood vessel, muscle, or the cere-brospinal fluid. Chemotherapy may be used with radia-tion and surgery as part of a patient’s initial treatment, orused alone to treat tumors that recur in the same place orin another part of the body. The usual chemotherapy regi-men for a brain tumor is a combination approach, mostcommonly using procarbazine, CCNU, and vincristine.
New methods of delivering chemotherapy are being

used as well. These include:
• interstitial chemotherapy is performed at the time of
surgery. A chemotherapy-soaked wafer is placed in thecavity left after tumor removal.
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• Intrathecal chemotherapy instills the medications right
into the spinal fluid.
• Intraarterial chemotherapy uses tiny catheter tubes to
delivery high-dose chemotherapy directly into the arter-ies of the brain.
• Potentially toxic chemotherapy drugs can be wrapped
in special biologic envelopes called liposomes, to allowthe drugs to be delivered to the tumor without adverselyaffecting other healthy tissues along the way.
• Electrochemotherapy uses electric voltage to transport

chemotherapy agents into the brain.
When a young child has a brain tumor, chemotherapy
is often used to eliminate or delay the need for radiation.
If a brain tumor cannot be cured, treatment is
designed to make the patient as comfortable as possibleand preserve as much of his neurologic functioning aspossible. The patient’s doctor may prescribe:
• analgesics to relieve pain
• anticancer drugs to limit tumor growth

• anticonvulsants to control seizures• steroids to reduce swelling of brain tissue
Potential therapies
Scientists are studying ways to empower chemother-

apy drugs to penetrate the blood-brain barrier (whichprotects the CNS by separating the brain from blood cir-culating throughout the body), and attack cancer cellsthat have infiltrated tissue inside it. Agents under investi-gation include both mannitol and substances calledreceptor-mediated permeabilizers
Brain tumor researchers are also investigating:
• Less invasive surgical procedures.
• Monoclonal antibodies, which pair antibodies with

radioactive substances. The antibodies are directed tofind and attach to tumor cells, at which time theradioactive substance kills the tumor cell.
• Interleukin and interferon, which are substances pro-
duced naturally by the human immune system whichseem to kill tumor cells. Scientists seek to producethese substances in the laboratory and incorporate theiruse in brain tumor treatment.
• T-lymphocytes, which are also produced normally by

the human immune system, and are being used to injectdirectly into the tumor location during surgery and toinfuse into the bloodstream after surgery, in the hopesthat they will boost the immune system’s ability to fighttumor cells.• Tumor vaccines, which use elements of tumor cells to
stimulate the patient’s immune system.
• Methods of incorporating chemotherapy drugs into
tumor cells to reduce the need for radiation.
• Laboratory techniques that enable physicians to select

the chemotherapy drugs most likely to kill particulartypes of tumors.
• Gene therapy in which genetically engineered material
is transported to tumor cells by viruses that infect tumorcells and convert them to normal cells, stop theirgrowth, or kill them.
Alternative treatments have not been shown to cure

brain tumors and should never be substituted for conven-tional therapy. However, complementary therapies (usedwith, not instead of, standard treatments) can help somepatients cope with the stress of their illness and side
effects of their treatment.
Biofeedback can teach patients to influence and
control heart rate, muscle tension, and other stress-relat-ed body functions. Some patients claim that guided
imagery (visualization) helps them feel healthier and
more in control of their disease.

Massage, meditation , and reflexology help some
patients relax; while yoga is said to soothe the body, spir-
it, and mind. Hydrotherapy uses ice, liquid, and steam
to improve circulation and relieve pain. Therapeutic
touch practitioners say they can relieve pain and other
symptoms by moving their hands in slow, rhythmicmotions several inches above the patient’s body.
Botanical therapies, homeopathic treatment, tradi-

tional Chinese medicine treatments, nutritional focuses
on diet and supplements, and detoxification can also be
incorporated as complementary therapies.
Prognosis
The patient’s prognosis depends on where the tumor

is located, what type of cells it contains, the size of thetumor, and the effect its already had on adjacent brainstructures. A patient whose tumor is discovered early andremoved completely may make a full recovery, but thesurgery itself can harm or destroy normal brain tissueand cause:
• problems with thought, speech, and coordination
• seizures• weakness• personality changes
GALE ENCYCLOPEDIA OF MEDICINE 2 573Brain tumorGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 573

Although these post-operative problems may initial-
ly be more severe than the symptoms produced by thetumor, they will probably diminish or disappear in time.
Occupational therapy can teach patients and their

families new ways to approach daily tasks. Physical ther-apy can benefit patients who have difficulty keeping theirbalance, expressing their thoughts, speaking, or swallow-ing. Children may need special tutors before and afterreturning to school. For patients who have incurablebrain tumors, hospice care may be available. Hospicesprovide a supportive environment and help patients man-age pain and remain comfortable.

Consequences of radiation therapy
Cells killed by radiation can cluster in the brain,
resembling tumors. They can cause headaches, seizures,and memory loss. Children treated with radiation maylose some of their eyesight and develop learning prob-lems. Radiation damage to the pituitary gland can hindernormal growth and development.
Consequences of chemotherapy
Some drugs used to treat brain tumors can cause kid-

ney damage and temporary or permanent tingling in thefingers and ringing in the ears.
Inoperable tumors
Brain tumors that cannot be removed may cause
irreversible brain damage and death.
The cause of primary brain tumors has not been
determined, so there is no known way to prevent them.KEY TERMS
Central nervous system (CNS) —The division of
the nervous system that consists of the brain andspinal cord.
Cerebrospinal fluid (CSF) —Clear liquid that fills

brain cavities and protects the brain and spinalcord.
Gamma knife —High-dose radiation treatment for
intracranial tumors.
Intracranial —Located within or on the surface of
the brain.The best way to prevent secondary or metastatic
brain tumors is to eliminate such risk factors as:
• poor nutrition and a low-fiber diet; since these con-
tribute to development of intestinal cancers
• smoking, which causes lung cancer
• excessive use of alcohol, which is associated with liver
cancer

cancer
• excessive exposure to the sun, which can cause
melanoma (a deadly form of skin cancer).
Monthly self-examinations of the breasts and testi-
cles can detect breast and testicular cancer at their earli-
est, most curable stages.
Resources
BOOKS
The Editors of Time-Life Books, Inc. The Medical Advisor:
The Complete Guide to Alternative and ConventionalTreatment. Alexandria, V A: Time-Life, Inc., 1996.
Moulignier, Antoine, et al., “Cerebral Glial Tumors and Human

Immunodeficiency Virus-1 Infection: More Than a Coin-cidental Association.” Cancer 74, no. 2 (July 15, 1994):
686-87.
American Brain Tumor Association. 2770 River Road, Des
Plaines, IL 60018. (847) 827-9918, (800) 886-2289.<http:/www.abta.org>.
Brain Tumor Foundation for Children, Inc. 2231 Perimeter
Park Drive, Suite 9, Atlanta, GA 30341. (404) 454-5554.
Brain Tumor Information Services. Box 405, Room J341, Uni-

versity of Chicago Hospitals, 5841 S. Maryland Avenue,Chicago, IL 60637. (312) 684-1400.
MedHelp International. 6300 N. Wickham, Suite 130, Box 188,
Melbourne, FL 32940. (407) 253-9048. <http://www.medhlp.netusa.net/
National Brain Tumor Foundation. 785 Market Street, #1600,
San Francisco, CA 94103. <http://www.oncolink.penn.edu/psychosocial.
OTHER
Adult Brain Tumor. <http://cancernet.nci.nih.gov/clinpdq/pif/
Adult_brain_tumor_Patient.html (May 2001).

Brain Tumor, Primary. Nidus Information Services,Well Con-
nected,2001.
“Brain Tumors,” Goldman: Cecil Textbook of Medicine, 21st
Ed., Copyright (c) 2000 W. B. Saunders Company
“Brain Tumors,” Abeloff: Clinical Oncology, 2nd Ed., Copy-
right (c) 2000 Churchill Livingstone, Inc.
Childhood Brain Tumor. <http://cancernet.nci.nih.gov/clinpdq/
pif/Childhood_brain_tumor_Patient.html (May 2001).
A Primer on Brain Tumors. <http://neurosurgery.mgh.harvard.

edu/abta/primer.htm (12 March 1998).
Question: What is a Gamma Knife? <http://oncolink.upenn.
edu/specialty/med_phys/gamma.html (13 April 2001).
GALE ENCYCLOPEDIA OF MEDICINE 2 574Brain tumorGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 574

What You Need to Know About Brain Tumors. <http://rex.
nci.nih.gov/WTNK_PUBS/brain/index.htm (28 Septem-ber 1998).
Breast biopsy
A breast biopsy is removal of breast tissue for exam-
ination by a pathologist. This can be accomplished surgi-cally, or by withdrawing tissue through a needle.
Purpose
A biopsy is recommended when a significant
abnormality is found, either on physical examination

and/or by an imaging test. Examples of abnormality caninclude a breast lump felt during physical self examina-tion or tissue changes noticed from a mammogram test.Before a biopsy is performed, it is important to makesure that the threat of cancer cannot be disproved or

ruled out by a simpler, less invasive examination. Alump may be obviously harmless when examined byultrasound. If this is not decisive, the presence of canceror a variety of benign breast conditions can be deter-mined using a biopsy.
The type of biopsy recommended should be consid-

ered. This will depend on whether the area can be felt,how well it can be seen on mammogram or ultrasound,and how suspicious it feels or appears. Specializedequipment is needed for different types of biopsy andavailability may vary. Generally, needle biopsy is lessinvasive than surgical biopsy. It is appropriate for most,but not all situations. However, some surgeons feel it isfar less accurate.
Surgical biopsy

If an abnormality is not felt during a self examina-
tion, there are signs that indicate the need for medicalattention. These include:
• severe breast pain
• changes in the size of a breast or the nipple
• changes in the shape of both breast or nipple• pitting, dumpling or redness of the breast skin
• nipple redness, irritation, or inversion
• changes in the pattern of veins visible on the surface of
the breast
• some types of nipple discharge

the breast
If the abnormality is not felt, a needle localization
must be done before the actual surgery. After local anes-thetic is administered, a fine wire is placed in the area ofconcern. Either x ray or ultrasound guidance is used. Thepatient is awake and usually sitting up.
There are two types of breast biopsy considered

here, excisional and incisional. An excisional biopsy is asurgical procedure, where the entire area of concern andsome surrounding tissue is removed. It is usually done asan outpatient procedure, in a hospital or free standingsurgery center. The patient may be awake, and is some-times given medication to make her drowsy. The area tobe operated on is numbed with local anesthetic. Infre-quently, general anesthesia is used.

An excisional biopsy itself usually takes under one
hour. The total amount of time spent at the facilitydepends on the type of anesthesia used, whether a needlelocalization was done, and the extent of the surgery.
If a mass is very large, an incisional biopsy may be
performed. In this case only a portion of the area isremoved and sent for analysis. The procedure is the sameas an excisional biopsy in other respects.
Needle biopsy
A needle biopsy removes part of the suspicious area

for examination. There are two types, aspiration biopsy(using a fine needle), and large core needle biopsy. Eitherof these may be called a percutaneous needle biopsy. Per-cutaneous refers to a procedure done through the skin.
A fine needle aspiration biopsy uses a very thin nee-

dle to withdraw fluid and cells that can be studied. It canbe done in a doctor’s office, clinic, or hospital. Localanesthetic may be used, but is sometimes withheld, as itmay be more painful than the biopsy needle. The area toplace the needle may be located by touch. No specializedequipment is needed. However, using ultrasound guid-ance enables the physician to feel and see the lesion atthe same time. The actual withdrawing of fluid and cellscan be visualized as it occurs. This helps ensure

be visualized as it occurs. This helps ensure that thespecimen is taken from the right place.

A large core needle biopsy uses a larger diameter
needle to remove small pieces of tissue, about the size ofa grain of rice. It can be done in a clinic or hospital thathas the appropriate facilities. Local anesthetic is routine-
GALE ENCYCLOPEDIA OF MEDICINE 2 575Breast biopsyGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 575

ly used. Ultrasound or x ray is used for guidance of a
large core needle biopsy.
If the suspicious area is seen best with x ray, a stereo-

tactic device is used. This means that x rays are taken fromseveral angles. This information is fed into a computer,which analyzes the data and guides the needle to the correctplace. The patient may be sitting up, or she may be lying onher stomach, with her breast positioned through an openingin the table. The breast is held firmly, but comfortablybetween a plastic paddle and a metal plate, similar to thoseused for mammograms (a set of x rays taken of the frontand side of the breast). X rays

taken of the frontand side of the breast). X rays may be taken before, during,and after the tissue is drawn into the needle, to confirm thatthe correct spot is biopsied. This procedure may also bereferred to as a stereotactic core biopsy, or a mammotomy.

Ultrasound is used to guide needle placement for
some lesions. The patient lies on her back or side. After thearea is numbed, sterile gel is applied. The physician placesa transducer, an instrument about the size of an electricshaver, over the skin. This produces an image from thereflection of sound waves. A special needle, usually in aspring loaded device, is used to obtain the tissue. The pro-cedure is observed on a monitor as it is happening.

A surgical breast biopsy may require the patient to
have nothing to eat or drink for a period of time beforethe operation. This will typically be from midnight the
night before, if general anesthesia is planned. No foodrestrictions are necessary for needle biopsy. It is advis-able to eat lightly before the procedure. This is especiallyimportant if the patient will be lying on her stomach for astereotactic biopsy.
Aftercare
After a surgical biopsy, the incision will be closed

with stitches, and covered with a bandage. The bandagecan usually be removed in one or two days. Stitches aretaken out approximately one week afterward. Dependingon the extent of the operation, normal activities can beresumed in approximately one to three days. Vigorousexercise may be limited for one to three weeks.
The skin opening for a needle biopsy is minimal. It

may be closed with thin, clear tape, called a steri strip, orcovered with a bandaid and a small gauze bandage. Thepatient can return to her usual routine immediately afterthe biopsy. Strenuous activity or heavy lifting is not rec-ommended for 24 hours. Any bandages can be removedone or two days after the biopsy.
Risks
Infection is always a possibility when the skin is
broken, although this rarely occurs. Redness, swelling, orsevere pain at the biopsy site would indicate a possible

GALE ENCYCLOPEDIA OF MEDICINE 2 576Breast biopsy
TumorSubcutaneous 
fatty tissue
Lactiferous 
duct
Excisional biopsyLobule of gland TumorAreola
Fine needle aspiration biopsy
A fine needle aspiration biopsy uses a very thin needle to withdraw fluid and cells from the breast to be examined. An exci-

sional biopsy is a surgical procedure in which the entire area of concern and some surrounding tissue is removed for analy-sis.(Illustration by Electronic Illustrators Group.)GEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 576

infection. Another possible consequence of a breast biop-
sy is a hematoma. This is a collection of blood at thebiopsy site. It is usually absorbed naturally by the body.If it is very large and uncomfortable, it may need to bedrained. A surgical breast biopsy may produce a visiblescar on the breast. Sometimes this may make futuremammograms harder to interpret accurately.
A false negative pathology report is another risk.

This means that no cancer was found when a cancer waspresent. The incidence of this varies with the biopsytechnique. In general, fine needle aspiration biopsieshave the highest rate of false negative results, but theremay be variation in results between facilities.
A normal pathology report indicates no malignancy
is present. The tissue sample may be further classified asa benign breast condition, such as tumor of the breast(fibroadenoma ) or connective tissue that resembles

fiber (fibrosis). Studies have demonstrated that approxi-mately 80% of all breast biopsies result in a benignpathology report.
An abnormal pathology report indicates a cancer is

present. If a fine needle aspiration biopsy was performed,the pathologist has viewed individual cells under amicroscope to see if they appear cancerous. Large coreneedle biopsy and surgical biopsy will be able to givemore information. This includes the type of cancer,whether it has invaded surrounding tissue, and how likelyit is to spread quickly. There are some conditions whichare not malignant but indicate high risk for future devel-opment of breast cancer . If these are identified, more

frequent monitoring of the area may be recommended.
Resources
BOOKS
Baron-Faust, Rita. Breast Cancer: What Every Woman Should
Know. New York: Hearst Books, 1995.
Love, Susan and Karen Lindsey. Dr. Susan Love’s Breast Book.
2nd ed. Reading, MA: Addison-Wesley, 1995.
Bassett, Lawrence, et al. “Stereotactic Core-Needle Biopsy of
the Breast.” CA: A Journal for Clinicians 47 (May/June
1997): 171-190.
Cady, Blake, et al. “Evaluation of Common Breast Problems:

Guidance for Primary Care Providers.” CA:A Journal for
Clinicians 48 (Jan./Feb. 1998): 49-63.
Castleman, Michael. “News About Breast Cancer That Could
Save Your Life.” Family Circle , 11 (13 May 1997): 60-65.KEY TERMS
Fine needle aspiration biopsy —A procedure using
a thin needle to remove fluid and cells from alump in the breast.
Large core needle biopsy —A procedure using a
thicker needle to remove a core of tissue, aboutthe size of a grain of rice, from the breast.

Weber, Ellen. “Questions and Answers About Breast Cancer
Diagnosis.” American Journal of Nursing 97 (Oct. 1997):
34-38.
Breast cancer
Breast cancer is caused by the development of

malignant cells in the breast. The malignant cells origi-nate in the lining of the milk glands or ducts of the breast(ductal epithelium), defining this malignancy as a cancer.Cancer cells are characterized by uncontrolled divisionleading to abnormal growth and the ability of these cellsto invade normal tissue locally or to spread throughoutthe body, in a process called metastasis.
Breast cancer arises in the milk-producing glands of

the breast tissue. Groups of glands in normal breast tis-sue are called lobules. The products of these glands aresecreted into a ductal system that leads to the nipple.Depending on where in the glandular or ductal unit of thebreast the cancer arises, it will develop certain character-istics that are used to sub-classify breast cancer intotypes. The pathologist will denote the subtype at the timeof evaluation with the microscope. Ductal carcinomabegins in the ducts, lobular carcinoma has a

in the ducts, lobular carcinoma has a patterninvolving the lobules or glands. The more important clas-sification is related to the evaluated tumor’s capability to

GALE ENCYCLOPEDIA OF MEDICINE 2 577Breast cancerGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 577

invade, as this characteristic defines the disease as a true
cancer. The stage before invasive cancer is called in situ ,
meaning that the early malignancy has not yet becomecapable of invasion. Thus, ductal carcinoma in situ isconsidered a minimal breast cancer.
How breast cancer spreads
The primary tumor begins in the breast itself but once

it becomes invasive, it may progress beyond the breast tothe regional lymph nodes or travel (metastasize) to otherorgan systems in the body and become systemic in nature.Lymph is the clear, protein-rich fluid that bathes the cellsthroughout the body. Lymph will work its way back to thebloodstream via small channels known as lymphatics.Along the way, the lymph is filtered through cellular sta-tions known as nodes, thus they are called lymph nodes.Nearly all organs in the body have a primary

all organs in the body have a primary lymph nodegroup filtering the tissue fluid, or lymph, that comes fromthat organ. In the breast, the primary lymph nodes areunder the armpit, or axilla. Classically, the primary tumorbegins in the breast and the first place to which it is likelyto spread is the regional lymph nodes. Cancer, as itinvades in its place of origin, may also work its way intoblood vessels. If cancer gets into the blood vessels, theblood vessels provide yet another route for the

vessels provide yet another route for the cancer tospread to other organs of the body.

Breast cancer follows this classic progression though
it often becomes systemic or widespread early in thecourse of the disease. By the time one can feel a lump inthe breast it is often 0.4 inches, or one centimeter, in sizeand contains roughly a million cells. It is estimated that atumor of this size may take one to five years to develop.During that time, the cancer may metastasize, or spreadby lymphatics or blood to areas elsewhere in the body.

to the regional lymph nodes under the armpit, the axil-lary nodes. If this occurs, regional metastasis exists. If itproceeds elsewhere either by lymphatic or blood-bornespread, the patient develops systemic metastasis that mayinvolve a number of other organs in the body. Favoritesites of systemic involvement for breast cancer are thelung, bones, liver, and the skin and soft tissue. As it turnsout, the presence of, and the actual number of, regionallymph nodes containing cancer remains the

regionallymph nodes containing cancer remains the single bestindicator of whether or not the cancer has become widelymetastatic. Because tests to discover metastasis in otherorgans may not be sensitive enough to reveal minutedeposits, the evaluation of the axilla for regional metasta-sis becomes very important in making treatment deci-sions for this disease.

If breast cancer spreads to other major organs of the
body, its presence will compromise the function of thoseorgans. Death is the result of extreme compromise of
vital organ function.
Demographics
Every woman is at risk for breast cancer. If she lives

to be 85, there is a one out of nine chance that she willdevelop the condition sometime during her life. As awoman ages, her risk of developing breast cancer risesdramatically regardless of her family history. The breastcancer risk of a 25-year-old woman is only one out of19,608; by age 45, it is one in 93. In fact, less than 5% ofcases are discovered before age 35 and the majority of allbreast cancers are found in women over age 50.
In 1999, there were 180,000 new cases of breast can-

cer diagnosed. About 45,000 women die of breast cancereach year, accounting for 16% of deaths caused by cancerin women. For the first time ever, mortality rates decreasedan average of 1.7% per year from 1995 through 1999, areflection of earlier diagnosis and improving therapies.
There are a number of risk factors for the develop-
ment of breast cancer, including:
• family history of breast cancer in mother or sister• early onset of menstruation and late menopause

• reproductive history: women who had no children or
have children after age 30 and women who have neverbreastfed have increased risk
• history of abnormal breast biopsies
Though these are recognized risk factors, it is impor-

tant to note that more than 70% of women who get breastcancer have no known risk factors. Having several riskfactors may boost a woman’s chances of developingbreast cancer, but the interplay of predisposing factors iscomplex. In addition to those accepted factors listedabove, some studies suggest that high-fat diets ,obesity ,
or the use of alcohol may contribute to the risk profile.Another factor that may contribute to a woman’s riskprofile is hormone replacement therapy (HRT).

HRT provides significant relief of menopausal
symptoms, prevention of osteoporosis , and possibly pro-
tection from cardiovascular disease and stroke . Howev-
er, studies show that there is a small increased risk ofdeveloping breast cancer with HRT use. Thus, the use ofhormone replacement therapy should be based on per-sonal risk factors.
Of all the risk factors listed above, family history is
the most important. In The Biological Basis of Cancer ,

the authors estimate that probably about half of all famil-
GALE ENCYCLOPEDIA OF MEDICINE 2 578Breast cancerGEM -0433 to 0624 - B  10/22/03 6:08 PM  Page 578

breast cancer frequency) have mutations affecting thetumor suppressor gene BRCA-1. Another gene (BRCA-2) also appears to confer inherited vulnerability to early-onset breast cancers. However, breast cancer due toheredity is only a small proportion of breast cancer cases;only 5%–10% of all breast cancer cases will be womenwho inherited a susceptibility through their genes. Nev-ertheless, when the family history is strong for develop-ment of breast cancer, a woman’s risk is increased.

Not all lumps detected in the breast are cancerous.
Fibrocystic changes in the breast are extremely common.Also known as fibrocystic condition of the breast , fibro-
cystic changes are a leading cause of non-cancerous lumpsin the breast. Fibrocystic changes also cause symptoms ofpain , swelling, or discharge and may become evident to

the patient or physician as a lump that is either solid orfilled with fluid. Complete diagnostic evaluation of anysignificant breast abnormality is mandatory becausethough women commonly develop fibrocystic changes,breast cancer is common also, and the signs and symptomsof fibrocystic changes overlap with those of breast cancer.
Diagnosis
The diagnosis of breast cancer is accomplished by the

biopsy of any suspicious lump or mammographic abnor-mality that has been identified. (A biopsy is the removal oftissue for examination by a pathologist. A mammogram isa low-dose, 2-view, x-ray examination of the breast.) Thepatient may be prompted to visit her doctor upon finding alump in a breast, or she may have noticed skin dimpling,nipple retraction, or discharge from the nipple. Or, thepatient may not have noticed anything abnormal, and alump is detected by the mammogram.

When a patient has no signs or symptoms
Screening involves the evaluation of women who
have no symptoms or signs of a breast problem, so whenthe screening mammogram leads to the evaluation, thepatient has no symptoms and may not have any abnor-mality on examination of the breast. Mammography has
been very helpful in detecting breast cancer that one can-not identify on physical examination . However,

10%–13% of breast cancer does not show up on mam-mography, and a similar number of patients with breastcancer have an abnormal mammogram and a normalphysical examination. These figures emphasize the needfor examination as part of the screening process.
Screening
It is recommended that women get into the habit of
doing monthly breast self examinations to detect anylump at an early stage. If an uncertainty or a lump is

found, evaluation by an experienced physician and mam-mography is recommended. The American Cancer Soci-ety (ACS) has made recommendations for the use ofmammography on a screening basis. There has been con-troversy about the timing and appropriate frequency ofmammography when used as a screening tool, but theACS recommendations are as follows: Women shouldget annual mammograms after age 40. Those with a sig-nificant family history (one or more first-degree relativeswho have been treated for

first-degree relativeswho have been treated for breast cancer), should startannual mammograms 10 years younger than theyoungest relative was when she was diagnosed, but notearlier than 35.

Because of the greater awareness of breast cancer in
recent years, screening evaluations by examinations andmammography are performed much more frequently thanin the past. The result is that the number of breast cancersdiagnosed increased, but the disease is being diagnosed atan earlier stage than previously. The earlier the stage of
GALE ENCYCLOPEDIA OF MEDICINE 2 579Breast cancer
Mammogram indicating a tumor in the center of the breast.

(Chris Bjornberg, Photo Researchers. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 579

disease at the time of presentation, the better the long-
term outcome after treatment, or prognosis, becomes.
When a patient has physical signs or symptoms
A very common finding that leads to diagnosis is the

presence of a lump within the breast. Skin dimpling, nip-ple retraction, or discharge from the nipple are less fre-quent initial findings prompting biopsy. Though bloodynipple discharge is distressing, it is most often caused bybenign disease. Skin dimpling or nipple retraction in thepresence of an underlying breast mass on examination isa more advanced finding. Actual skin involvement, withedema or ulceration of the skin, are late findings.
A very common presenting sign is the presence of a

breast lump. If the lump is suspicious and the patient hasnot had a mammogram by this point, a study should bedone on both breasts prior to anything else so that theoriginal characteristics of the lesion can be studied. Theopposite breast should also be evaluated mammographi-cally to determine if other problems exist that were unde-tected by physical examination.
Whether an abnormal screening mammogram or one

of the signs mentioned above followed by a mammogramprompted suspicion, the diagnosis is established byobtaining tissue by biopsy of the area. There are differenttypes of biopsy, each utilized with its own indicationdepending on the presentation of the patient. If signs ofwidespread metastasis are already present, biopsy of themetastasis itself may establish diagnosis.
Biopsy
Depending on the situation, different types of biopsy

may be performed. The types include incisional and exci-sional biopsies. In an incisional biopsy, the physiciantakes a sample of tissue, and in excisional biopsy, themass is removed. Fine needle aspiration biopsy and coreneedle biopsy are kinds of incisional biopsies.
FINE NEEDLE ASPIRATION BIOPSY. In a fine needle

aspiration biopsy, a fine-gauge needle may be passed intothe lesion and cells from the area suctioned into the nee-dle can be quickly prepared for microscopic evaluation(cytology). (The patient experiencing nipple dischargecan have a sample taken of the discharge for cytologicalevaluation, also.) Fine needle aspiration is a simple pro-cedure that can be done under local anesthesia, and willtell if the lesion is a fluid-filled cyst or whether it is solid.The sample obtained will yield much

it is solid.The sample obtained will yield much diagnostic informa-tion. Fine needle aspiration biopsy is an excellent tech-nique when the lump is palpable and the physician caneasily hit the target with the needle. If the lesion is a sim-ple cyst, the fluid will be evacuated and the mass willdisappear. If it is solid, the diagnosis may be obtained.

Care must be taken, however, because if the mass is solidand the specimen is non-malignant, a complete removalof the lesion may be appropriate to be sure.
CORE NEEDLE BIOPSY. Core needle biopsies are also

obtained simply under local anesthesia. The larger pieceof tissue obtained with its preserved architecture may behelpful in confirming the diagnosis short of open surgicalremoval. An open surgical incisional biopsy is rarelyneeded for diagnosis because of the needle techniques. Ifthere remains question as to diagnosis, a complete opensurgical biopsy may be required.
EXCISIONAL BIOPSY. When performed, the excision-

al, (complete removal) biopsy is a minimal outpatientprocedure often done under local anesthesia.
NON-PALPABLE LESIONS. As screening increases,

non-palpable lesions demonstrated only by mammogra-phy are becoming more common. The use of x rays andcomputers to guide the needle for biopsy or to placemarkers for the surgeon performing the excisional biopsyare commonly employed. Some benign lesions can befully removed by multiple directed core biopsies. Thesetechniques are very appealing because they are minimal-ly invasive; however, the physician needs to be careful toobtain a good sample.

Other tests
If a lesion is not palpable and has simple cystic char-
acteristics on mammography, ultrasound may be utilizedboth to determine that it is a cyst and to guide its evacua-tion. Ultrasound may also be used in some cases to guidefine needle or core biopsies of the breast.
Computed tomography (CT scan, CAT scans), and
magnetic resonance imaging , (MRI), have only a very
occasional use in the evaluation of breast lesions.
Treatment
Staging

Treatment
Staging
Once diagnosis is established, before treatment is
rendered, more tests are done to determine if the cancerhas spread beyond the breast. These tests include a chest
x ray and blood count with liver function tests . Along

with the liver function measured by the blood sample, thelevel of alkaline phosphatase, an enzyme from bone, isalso determined. A radionuclear bone scan may beordered. This test looks at the places in the body to whichbreast cancer usually metastasizes. A CT scan may alsobe ordered. The physician will do a careful examinationof the axilla to assess likelihood of regional metastasisbut unfortunately this exam is not very accurate. Since

GALE ENCYCLOPEDIA OF MEDICINE 2 580Breast cancerGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 580

the axillary node status is the best reflection of possible
widespread disease, these nodes in part or all will beremoved at the time of surgical treatment.
Using the results of these studies, clinical stage is

defined for the patient. This helps define treatment proto-col and prognosis. After surgical treatment, the final, orpathologic, stage is defined as the true axillary lymphnode status is known. Detailed staging criteria are avail-able from the American Joint Commission on CancerManual and are generalized here:
• Stage 1—The cancer is no larger than 2 cm (0.8 in) and
no cancer cells are found in the lymph nodes.
• Stage 2—The cancer is between 2 cm and 5 cm, and the

cancer has spread to the lymph nodes.
• Stage 3A—Tumor is larger than 5 cm (2 in) or is small-
er than 5 cm, but has spread to the lymph nodes, whichhave grown into each other.
• Stage 3B—Cancer has spread to tissues near the breast,
(local invasion), or to lymph nodes inside the chestwall, along the breastbone.
• Stage 4—Cancer has spread to skin and lymph nodes
beyond the axilla or to other organs of the body.
Treatment
Surgery, radiation, and chemotherapy are all uti-

lized in the treatment of breast cancer. Depending on thestage, they will be used in different combinations orsequences to effect an appropriate strategy for the typeand stage of the disease being treated.
SURGERY. Historically, surgical removal of the
entire breast and axillary contents along with the musclesdown to the chest wall was performed as the lone thera-py, (radical mastectomy ). In the last twenty-five years,

as it has been appreciated that breast cancer is often sys-temic early in its course, the role of surgery is still prima-ry but of less and less magnitude.
Today, surgical treatment is best thought of as a
combination of removal of the primary tumor and stag-ing of the axillary lymph nodes. If the whole breast isremoved along with the entire axillary contents, but themuscles of the chest wall are not, the modified radicalmastectomy has been performed.

If the tumor is less than 1.5 in (4 cm) in size and
located so that it can be removed without destroying areasonable cosmetic appearance of the residual breast,just the primary tumor and a rim of normal tissue will beremoved. The axillary nodes will still be removed forstaging purposes, usually through a separate incision.Because of the risk of recurrence in the remaining breasttissue, radiation is used to lessen the chance of localrecurrence. This type of primary therapy is known as

lumpectomy , (or segmental mastectomy), and axillary
dissection.
Currently the necessary extent of the axillary dissec-
tion is being questioned. Sentinel lymph node biopsy ,a
technique for identifying which nodes in the axilla drainthe tumor, has been developed to provide selective sam-pling and further lessen the degree of surgical trauma thepatient experiences.
When patients are selected appropriately based on

the preoperative clinical stage, all of these surgicalapproaches have been shown to produce similar results.In planning primary surgical therapy, it is imperative thatthe operation is tailored to fit the clinical circumstance ofthe patient.
The pathologic stage is determined after surgical

treatment absolutely defines the local parameters. Inaddition to stage, there are other tests that are very neces-sary to aid in decisions regarding treatment. Handling ofthe surgical specimen is thus very important. The tissueneeds to be analyzed for the presence or absence of hor-mone receptors and a receptor called HER-2. The pres-ence of these receptors will influence additional thera-
GALE ENCYCLOPEDIA OF MEDICINE 2 581Breast cancer
15% 50%

15% 50%
11% 18%6%
This illustration shows the frequency of breast cancer
developing in the four quadrants of the breast and the nip-ple.(Illustration by Electronic Illustrators Group.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 581

assessment of lymphatic or blood vessel invasion asthese predict a worse outcome. The DNA of the tumorcells is quantitatively analyzed to help decide the biolog-ic aggressiveness of the tumor. These parameters will beutilized collectively along with the axillary lymph nodestatus to define the anticipated aggressiveness of the can-cer. This assessment, along with the age and general con-dition of the patient, will be considered when planningthe adjuvant therapies. Adjuvant therapies are

adjuvant therapies. Adjuvant therapies are treatmentsutilized after the primary treatment to help ensure that nomicroscopic disease exists and to help prolong patients’survival time.

RADIATION. Like surgical therapy, radiation thera-
pyis a local modality—it treats the tissue exposed to it
and not the rest of the body. Radiation is usually givenpost-operatively after surgical wounds have healed. The

pathologic stage of the primary tumor is now known andthis aids in treatment planning. The extent of the localsurgery also influences the planning. Radiation may notbe needed at all after modified radical mastectomy forstage I disease, but is almost always utilized when breast-preserving surgery is performed. If the tumor was exten-sive or if multiple nodes were involved, the field of tissueexposed will vary accordingly. Radiation is utilized as anadjunct to surgical therapy and is considered

anadjunct to surgical therapy and is considered an importantmodality in gaining local control of the tumor. The use ofradiation therapy does not affect decisions for adjuvanttreatment. In the past, radiation was used as an alternativeto surgery on occasion. However, now that breast-pre-serving surgical protocols have been developed, primaryradiation treatment of the tumor is no longer performed.Radiation also has an important role in the treatment ofthe patient with disseminated disease,

ofthe patient with disseminated disease, particularly if itinvolves the skeleton. Radiation therapy can effect paincontrol and prevention of fracture in this circumstance.

those originating in post-menopausal women, areresponsive to hormones. These cancers have receptors ontheir cells for estrogen and progesterone. Part of primarytumor assessment after removal of the tumor is the evalu-ation for the presence of these estrogen and progesteronereceptors. If they are present on the cancer cells, alteringthe hormone status of the patient will inhibit tumorgrowth and have a positive impact on survival. The drugtamoxifen binds up these receptors on the cancer cells

binds up these receptors on the cancer cells sothat the hormones can’t have an effect and, in so doing,inhibits tumor growth. If the patient has these receptorspresent, tamoxifen is commonly prescribed for five yearsas an adjunct to primary treatment. Adjuvant hormonaltherapy with tamoxifen has few side effects but they haveto be kept in mind, particularly the need for yearly evalu-ation of the uterus. Other agents directed at altering hor-mone environment are under study. Because of these

agents, there is rarely any need for surgical removal ofhormone-producing glands, such as the ovary or adrenal,that was sometimes necessary in the past.
Shortly after the modified radical mastectomy

replaced the radical mastectomy as primary surgicaltreatment, it was appreciated that survival after localtreatment in stage II breast cancer was improved by theaddition of chemotherapy. Adjuvant chemotherapy for aninterval of four to six months is now standard treatmentfor patients with stage II disease. The addition of sys-temic therapy to local treatment in patients who have noevidence of disease is performed on the basis that somepatients have metastasis that are not currently demonstra-ble

metastasis that are not currently demonstra-ble because they are microscopic. By treating the wholepatient early, before widespread disease is diagnosed, theadjuvant treatment improves survival rates from roughly60% for stage II to about 75% at five years after treat-ment. The standard regimen of cytoxan, methotrexate,and 5-flourouracil, (CMF), is given for six months and iswell tolerated. The regimen of cytoxan, adriamycin (dox-orubicin), and 5-floururacil, (CAF), is a bit more toxicbut only

5-floururacil, (CAF), is a bit more toxicbut only requires four months. (Adriamycin and cytoxinmay also be used alone, without the fluorouracil.) Thetwo methods are about equivalent in results. Adjuvanthormonal therapy may be added to the adjuvant chemo-therapy as they work through different routes.

adjuvant therapy in stage II disease have led to the studyof similar therapy in stage I disease. The results are notas dramatic, but they are real. Currently, stage I disease isdivided into categories a, b, and c on the basis of tumorsize. Stage Ia is less than a centimeter in diameter. Adju-vant hormonal or chemotherapy is now commonly rec-ommended for stage Ib and Ic patients. The toxicity ofthe treatment must be weighed individually for thepatient as patients with stage I disease have a

as patients with stage I disease have a survivor-ship of over 80% without adjuvant chemotherapy.

If patients are diagnosed with stage IV disease or, in
spite of treatment, progress to a state of widespread dis-ease, systemic chemotherapy is utilized in a moreaggressive fashion. In addition to the adriamycin-con-taining regimens, the taxols (docetaxel and paclitaxel)have been found to be effective in inducing remission.
On the basis of prognostic factors such as total num-

ber of involved nodes over 10, aneuploid DNA with ahigh synthesis value, or aggressive findings on micro-scopic evaluation, some patients with stage II or III dis-ease can be predicted to do poorly. If their performancestatus allows, they can be considered for treatment withhighly aggressive chemotherapy. The toxicity is such thatbone marrow failure will result. To get around this antici-
GALE ENCYCLOPEDIA OF MEDICINE 2 582Breast cancerGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 582

pated side effect of the aggressive therapy, either the
patients will be transplanted with their own stem cells,(the cells that will give rise to new marrow), or a tradi-tional bone marrow transplantation will be required.

This therapy can be a high-risk procedure for patients. Itis given with known risk to patients predicted to do poor-ly and then only if it is felt they can tolerate it. Mostpatients who receive this therapy receive it as part of aclinical trial. At present, it is unclear that such aggressivetherapy can be justified and it is under study.
For patients who are diagnosed with advanced local

disease, surgery may be preceded with chemotherapyand radiation therapy. The disease locally regressesallowing traditional surgical treatment to those whocould not receive it otherwise. Chemotherapy and some-times radiation therapy will continue after the surgery.The regimens of this type are referred to as neo-adjuvanttherapy. This has been proven to be effective in stage IIIdisease. Neo-adjuvant therapy is now being studied inpatients with large tumors that are stage II in an effort tobe able

tumors that are stage II in an effort tobe able to offer breast preservation to these patients.

A drug known as Herceptin (trastuzumab), a mono-
clonal antibody, is now being used in the treatment ofthose with systemic disease. The product of the HumanKEY TERMS
Adjuvant therapy —Treatment involving radiation,
chemotherapy (drug treatment), or hormone thera-py, or a combination of all three given after the pri-mary treatment for the possibility of residual micro-scopic disease.
Aneuploid —An abnormal number of chromosomes
in a cell.
Aspiration biopsy —The removal of cells in fluid or

tissue from a mass or cyst using a needle for micro-scopic examination and diagnosis.Benign —Not malignant, noncancerous.
Biopsy —A procedure in which suspicious tissue is
removed and examined by a pathologist for canceror other disease. For breast biopsies, the tissue maybe obtained by open surgery, or through a needle.
Estrogen-receptor assay —A test to see if a breast
cancer needs estrogen to grow.
Hormones —Chemicals produced by glands in the

body which circulate in the blood and control theactions of cells and organs. Estrogens are hormoneswhich affect breast cancer growth.Hormone therapy —Treating cancers by changing
the hormone balance of the body, instead of byusing cell-killing drugs.
Lumpectomy —A surgical procedure in which only
the cancerous tumor in the breast is removed,together with a rim of normal tissue.
Lymph nodes —Small, bean-shaped masses of tissue

scattered along the lymphatic system that act as fil-ters and immune monitors, removing fluids, bacte-ria, or cancer cells that travel through the lymphsystem. Breast cancer cells in the lymph nodesunder the arm or in the chest are a sign that the can-cer has spread, and that it might recur.
Malignant —Cancerous.
Mammography —X-ray imaging of the breast that
can often detect lesions in the tissue too small ortoo deep to be felt.

Oncogene —A gene that has to do with regulation
of cancer growth. An abnormality can producecancer.
Epidermal Growth Factor 2 gene, (HER-2) is overex-
pressed in 25%–30% of breast cancers. Herceptin bindsto the HER-2 receptors on the cancer, resulting in thearrest of growth of these cells.
Prognosis
The prognosis for breast cancer depends on the type

and stage of cancer. Over 80% of stage I patients arecured by current therapies. Stage II patients survive over-all about 70% of the time, those with more extensivelymph nodal involvement doing worse than those withdisease confined to the breast. About 40% of stage IIIpatients survive five years, and about 20% of stage IVpatients do so.
Coping with cancer treatment
Surgery for breast cancer is physically well-tolerated

by the patient, especially those undergoing minimalsurgery in the axilla. Most patients can return to a normallifestyle within a month or so after surgery. Exercises canhelp the patient regain strength and flexibility. Arm,shoulder, and chest exercises help, and complete recov-ery of activity is to be expected.
GALE ENCYCLOPEDIA OF MEDICINE 2 583Breast cancerGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 583

About 5-7% of patients undergoing complete axil-
lary lymph node resection as part of their therapy maydevelop clinically significant lymphedema , or swelling

in the arm on the side of involvement. If present, eleva-tion and massage may be needed intermittently. Thoughusually not serious, on occasion this complication mayinterfere with complete physical recovery. The incidenceof lymphedema is less with less axillary surgery. This isthe reason for the enthusiasm for sentinel node biopsy asthe surgical staging procedure in the axilla.
It is common after breast cancer treatment to be

depressed or moody, to cry, lose appetite, or feel unwor-thy or less interested in sex. The breast is involved with awoman’s identity and loss of it may be disturbing. Forsome, counseling or a support group can help. Manywomen have found a support group of breast cancer sur-vivors to be an invaluable help during this stage. Involve-ment with volunteers from the local chapter of the Reachto Recovery program may be very helpful.

Nearly all patients undergo some form of adjuvant
therapy for breast cancer. The magnitude of the toxicity ofthese adjuvant therapies is usually small and many patientsreceiving chemotherapy on this basis are capable of normalactivity during this time. Certainly, those who progress toadvanced disease are treated with more toxic chemothera-peutic regimens in an attempt to induce remission.
The use of tamoxifen and other agents which alter

the hormone status of the patient are under study. TheNational Surgical Adjuvant Breast and Bowel Project(NSABP) with support from the National Cancer Insti-tute began a study in 1992 (called the Breast Cancer Pre-vention Trial, or BCPT) studying the use of tamoxifen asa breast cancer preventative for high-risk women. Theresults yielded from the study showed that tamoxifen sig-nificantly reduced breast cancer risk, and the U.S. Foodand Drug Administration approved the use of tamoxifento reduce

approved the use of tamoxifento reduce breast cancer risk for high-risk patients in1998. Another NSABP study, known as STAR, is seek-ing to understand if another drug, raloxifene, is as effec-tive as tamoxifen in reducing breast cancer risk in high-risk patients. That study was begun in 1999, and partici-pants are to be monitored for five years.

Neo-adjuvant therapies to allow the use of breast
preservation in those with more advanced local diseaseare under investigation.
Immune therapies have not been helpful to date
though there are vaccines being developed against pro-teins such as that produced by HER-2 that may be bene-ficial in the future.High-dose chemotherapy with bone marrow rescue

remains controversial. Factors can be identified that pre-dict certain patients will develop metastatic disease. Thistreatment has been offered to this select group of patientsbut the toxicity is such that defining a clear indication forthis treatment remains under study.
As mentioned above, because of the results yielded
from the BCPT clinical trial, tamoxifen can now be pre-scribed to high-risk women to help prevent breast cancer.

And, while most breast cancer can’t be prevented, it
can be diagnosed from a mammogram at an early stagewhen it is most treatable. The results of awareness androutine screening have allowed earlier diagnosis, whichresults in a better prognosis for those discovered.
Special Concerns
Though breast-preserving therapy is being done more

frequently than in years past, modified radical mastectomyremains an option when selecting therapy for the primarytumor. This option may allow treatment without radiationin earlier stage patients, or may be necessary if the presen-tation of the tumor does not allow breast preservation. Lossof the breast is disfiguring and many patients so treateddesire reconstruction of the breast. Breast reconstruction

is performed either at the time of initial surgery (immedi-ate) or it may be delayed. Alternatives include placement ofimplants or the rotation of muscle flaps from the abdomenor back. Most agree that breast preservation gives superiorresults to any form of reconstruction. When the breast isremoved as part of primary therapy, these reconstructionsare available and do produce very reasonable results.
Resources
BOOKS
Abelhoff, Armitage, Lichter, Niederhuber. Clinical Oncology

Library. Philadelphia: Churchill Livingstone 1999.
American Joint Committee on Cancer. AJCC Clinical Staging
Manual. Philadelphia: Lippincott-Raven, 1997.
Reading, MA: Addison-Wesley, 1995.
Mayers, Musa. Holding Tight, Letting Go: Living with Metastatic
Breast Cancer. Sebastopol, CA: O’Reilly & Associates, 1997.
McKinnell, Robert G., Ralph E. Parchment, Alan O. Perantoni,
and G. Barry Pierce. The Biological Basis of Cancer. New

York: Cambridge University Press, 1998.
Schwartz, Spencer, Galloway, Shires, Daly, Fischer. Principles
of Surgery. New York: McGraw Hill, 1999.
Esteva and Hortobagyi. “Adjuvant Systemic Therapy for Pri-
mary Breast Cancer.” Surgical Clinics of North America
V olume 79 No. 5 (October 1999) p 1075-1090.
GALE ENCYCLOPEDIA OF MEDICINE 2 584Breast cancerGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 584

Krag, et al, “The Sentinel Node in Breast Cancer.” New Eng-
land Journal of Medicine V olume 339 No. 14 (October 1,
1998), p 941-946.
Margolese, R. G., M.D. “Surgical Considerations For Invasive
Breast Cancer.” Surgical Clinics of North America V olume
79 No. 5 (October 1999), p 1031-1046.
Munster and Hudis. “Adjuvant Therapy for Resectable Breast
Cancer.” Hematology Oncology Clinics of North America
V olume 13 No. 2 (April 1999) p 391-413.

Shuster, et al. “Multidisciplinary Care For Patients With Breast
Cancer.” Surgical Clinics of North America V olume 80
No. 2 (April, 2000) p 505-533.
American Cancer Society’s Reach to Recovery Program:
<http://www2.cancer.org/bcn/reach.html>.
Cancer Care, Inc. (800) 813-HOPE. <http://www.cancercare
inc.org>.
Cancer Information Service of the NCI. 1-800-4-CANCER.

<http://wwwicic.nci.nih.gov>.
National Alliance of Breast Cancer Organizations. 9 East 37th
St., 10th floor, New York, NY 10016. (888) 80-NABCO.
National Coalition for Cancer Survivorship. 1010 Wayne Ave.,
5th Floor, Silver Spring, MD 20910. (301) 650-8868.
National Women’s Health Resource Center. 2425 L St. NW,
3rd floor, Washington, DC 20037. (202) 293-6045.
OTHER
Breast Cancer Online. <http://www.bco.org/>.National Alliance of Breast Cancer Organizations. <http://
www.nabco.org/>.

National Cancer Institute. <http://rex.nci.nih.gov/PATIENTS/
INFO_PEOPL_DOC.html>.
Richard A. McCartney, M.D.
Breast enlargement seeBreast implants
Breast-feeding seeLactation
Breast implants
Breast implantation is a surgical procedure for
enlarging the breast. Breast-shaped sacks made of a sili-cone outer shell and filled with silicone gel or saline (saltwater), called implants, are used.
Purpose
Breast implantation is usually performed to make

normal breasts larger for cosmetic purposes. Sometimesa woman having a breast reconstruction after a mastec-
tomy will need the opposite breast enlarged to make thebreasts more symmetric. Breasts that are very unequal in
size due to trauma or congenital deformity may also becorrected with an enlargement procedure.
A woman in poor health or with a severe chronic
disease is not a good candidate for this procedure.

tient procedure. It may be done under local or generalanesthesia, depending on patient and physician prefer-ence. The incision is made through the armpit, under thebreast, or around the areola (the darkened area aroundthe nipple). These techniques create the most inconspicu-ous scars. The implant is placed between the breast tissueand underlying chest muscle, or under the chest muscle.The operation takes approximately one to two hours. Thecost of a cosmetic procedure is rarely covered by insur-

GALE ENCYCLOPEDIA OF MEDICINE 2 585Breast implants
A silicone breast implant. (Photograph by Dale O’Dell, The
Stock Market. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 585

ance. However, if enlargement is part of breast recon-
struction after a mastectomy, health plans may pay forsome or all of it. The surgeon’s fee ranges from $2,700-$4,200 and up. The procedure may also be called breastaugmentation or augmentation mammaplasty.
Before the surgery is performed, the woman should

have a clear understanding of what her new breasts willlook like. She and her physician should agree about thedesired final result. Many surgeons find it helpful to havethe patient review before and after pictures, to clarifyexpectations.
Aftercare
Driving and normal activities may be restricted for

up to one week. Stitches are usually removed in seven to10 days. Typically, a woman can resume all routines,including vigorous exercise , in about three weeks. The
scars will be red for approximately one month, but willfade to their final appearance within one or two years.
Risks
Risks which are common to any surgical procedure

include bleeding, infection, anesthesia reaction, or unex-pected scarring. A breast enlargement may also result indecreased sensation in the breast, or interference withbreast-feeding. Implants can also make it more difficultto read and interpret mammograms, possibly delayingbreast cancer detection. Also, the implant itself can rup-

ture and leak, or become displaced. A thick scar that nor-mally forms around the implant, called a capsule, canbecome very hard. This is called capsular contracture,and may result in pain and/or an altered appearance of
the breast. The older the implant, the greater the chancesthat these problems will occur.
There has been intermittent publicity about possible

health risks from breast implants. Most concerns havefocused on silicone gel-filled implants. As of 1992, theFood and Drug Administration (FDA) restricted the use ofthis type of implant, and ordered further studies. Todayonly saline-filled implants are used for cosmetic breastsurgery. Recent studies have shown no evidence long-term health risks from silicone implants. However,research on the possible links between these implants andautoimmune or connective tissue diseases is continuing.

Breasts of expected size and appearance would be
the normal results of this surgery.
Ellen S. Weber, MSNResources
BOOKS
Love, Susan M., with Karen Lindsey. Dr. Susan Love’s Breast
Book. 2nd ed. Reading, MA: Addison-Wesley, 1995.
“Breast Implant Update.” Harvard Women’s Health Watch 5
(Sept. 1997): 7.

Breast infection seeMastitis
Breast radiography seeMammography
Breast reconstruction
Breast reconstruction is a series of surgical proce-
dures performed to recreate a breast. Reconstructions arecommonly done after one or both breasts are removed asa treatment for breast cancer . Also, a breast may need to
be refashioned for other reasons, such as trauma orabnormalities that occur during breast development.
Purpose
Many authorities consider reconstruction an integral

part of the therapy for breast cancer . A breast that
appears natural offers a sense of wholeness and normal-cy, which can aid in the psychological recovery frombreast cancer. It eliminates the need for an external pros-thesis (false breast), which many women find physicallyuncomfortable as well as inconvenient.
Not all women are good candidates for breast recon-
struction. Overall poor physical health, or specific prob-lems such as cigarette smoking ,obesity , high blood

pressure, or diabetes, will increase the chance of compli-cations. Also, a difficult and/or prolonged recovery peri-od or failure of the reconstruction may be a result. Awoman’s physical ability to cope with major surgery andrecuperation also need to be considered.
Breast reconstruction is done in two stages, with the
ultimate goal of creating a breast which looks and feelsas natural as possible. It is important to remember that

GALE ENCYCLOPEDIA OF MEDICINE 2 586Breast reconstructionGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 586

while a good result may mimic a normal breast closely,
there will inevitably be scars and loss of sensation. Thereconstructed breast cannot be exactly like the original.
The first step is to form a structure called a breast
mound. This can be accomplished using artificial materialscalled breast implants , or by using tissues from other parts

of the woman’s body. The second step involves creating abalance between the newly constructed breast and thebreast on the opposite side. The nipple and areolar complex(darker area around the nipple) are recreated. This is usual-ly done several months after the mound is created, to allowswelling to go down. Other procedures may be necessary,such as lifting the opposite breast (mastopexy), or makingit larger or smaller to match the reconstructed breast.
Timing, immediate or delayed reconstruction

While immediate reconstruction (IR) is not recom-
mended for women with breast cancer who need to under-go other, more important treatments, breast reconstructioncan be done almost anytime. It even can be done during thesame procedure as the mastectomy , or it can be delayed.

There are psychological benefits to IR. The ability to returnto normal activities and routines is often enhanced whenreconstruction follows immediately after mastectomy. Abetter appearance may result from IR. There is less skinremoval, often resulting in a shorter scar. The surgeon isbetter able to preserve the normal boundaries of the breast,so it is easier to match the opposite breast more closely.
The cost of IR is generally lower than the cost of

delayed reconstruction (DR). There is one fewer opera-tion and hospital stay. Surgeon’s fees may be lower for acombined procedure than for two separate surgeries.
There are disadvantages of IR as well. The surgery
itself is longer, causing more time under anesthesia.Post-operative pain and recovery time will be greater
than for mastectomy alone.
Other authorities contend that delayed reconstruc-

tion (DR) offers different physical and psychologicaladvantages. The initial mastectomy procedure alonetakes less time, and has a shorter recovery period and lesspain than mastectomy and IR. The patient has more timeto adjust to her diagnosis and recover from additionaltherapy. She is better able to research her options, and toformulate realistic goals for reconstruction. Some recon-structive surgery requires blood transfusions. With DR,the patient can donate her own blood ahead of

DR,the patient can donate her own blood ahead of time(autologous transfusion ), and/or arrange to have family

and friends donate blood for her use (directed donation).
The psychological stress of living without a breast is
a disadvantage of DR. The extra procedure DR entailsresults in higher costs. Although initial recovery is faster,an additional recuperation period is required after the
delayed operation.
Type of reconstruction
There are two basic choices for breast reconstruc-

tion. The breast tissue can be replaced with an implant orthe breast is created using some of the woman’s own tis-sues (autologous reconstruction).
ARTIFICIAL IMPLANTS. In general, implant proce-
dures take less time, and are less expensive than autolo-gous ones. Implants are breast shaped pouches. They aremade of silicone outer shells, which may be smooth ortextured. The inside may contain silicone gel, saline (saltwater), or a combination of both.

An implant may be a fixed volume type, which can-
not change its size. Implants that have the capacity to befilled after insertion are called tissue expanders. Thesemay be temporary or permanent.
The initial procedure for any implant insertion uses

the mastectomy incision to make a pocket of tissue, usu-ally underneath the chest wall muscle. In DR, the mas-tectomy scar may be re opened and used for this purpose,or a more cosmetic incision may be made. The implant isinserted into the pocket, the skin is stretched as neededand stitched closed.
If there is inadequate tissue to achieve the desired size,

or a naturally sagging breast is desired, a tissue expander isused. It resembles a partially deflated balloon, with anattached valve or port through which saline can be injected.After the initial surgical incision is healed, the womanreturns to the doctor’s office, on a weekly or bi-weeklybasis, to have small amounts of saline injected. Injectionscan continue for about six to eight weeks, until the preferredsize is obtained. In some cases it may be overfilled, and laterpartially deflated to

may be overfilled, and laterpartially deflated to allow for a more pliable, natural result.A temporary tissue expander will be removed after severalmonths and replaced with a permanent implant.

IR surgery using an implant takes approximately
two to three hours, and usually requires up to a three dayhospital stay. Implant insertion surgery, as part of DR,takes one to two hours and can sometimes be done as anoutpatient, or it or it may entail overnight hospitalization.
AUTOLOGUS RECONSTRUCTION. Attached flap and

free flap are two types of surgery where a woman’s tissueis used in reconstruction. An attached flap uses skin, mus-cle, and fat, leaving blood vessels attached to their origi-nal source of blood. The flap is maneuvered to the recon-struction site, keeping its original blood supply for nour-ishment. This may also be known as a pedicle flap. Thesecond kind of surgery is called a free flap. This also usesskin, muscle, and fat, but severs the blood vessels, and

GALE ENCYCLOPEDIA OF MEDICINE 2 587Breast reconstructionGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 587

attaches them to other vessels where the new breast is to
be created. The surgeon uses a microscope to accomplishthis delicate task of sewing blood vessels together. Some-times the term microsurgery is used to refer to free flapprocedures. Either type of surgery may also be called amyocutaneous flap, referring to the skin and muscle used.
The skin and muscle used in autologous reconstruc-

tion can come from one of several possible places on thebody, including the abdomen (TRAM flap or “tummytuck”), the back (latissimus dorsi flap), or the buttocks(gluteus maximus free flap).
Finishing the reconstruction
Other procedures may be necessary to achieve the goal
of symmetrical breasts. It may be necessary to make theopposite breast larger (augmentation), smaller (reduction),

or higher (mastopexy). These, or any other refinementsshould be completed before the creation of a nipple andareola. Tissue to form the new nipple may come from thereconstructed breast itself, the opposite breast, or a moredistant donor site, such as the inner thigh or behind the ear.The nipple and areolar construction is usually an outpatientprocedure. A final step, often done in the doctor’s office, istattooing the new nipple and areola, to match the color ofthe opposite nipple and areola as

the color ofthe opposite nipple and areola as closely as possible.

Insurance
Insurance coverage for breast reconstruction varies
widely. Some policies will allow procedures on the affect-ed breast, but refuse to pay for alterations to the opposite
GALE ENCYCLOPEDIA OF MEDICINE 2 588Breast reconstruction Breast implant
Latissimus dorsi procedure
TRAM flap procedure
Breast reconstruction surgery may be performed by inserting an artificial substance, or implant, to replace breast tissue.

Autologous reconstruction, in which a woman’s own tissues are used, includes the latissimus dorsi flap, where skin andmuscle taken from the back is rotated around to the breast area, and the TRAM flap, in which abdominal fat and muscle aretunneled under the skin to the breast area. (Illustration by Electronic Illustrators Group.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 588

breast. Other plans may cover the cost of an external pros-
thesis, or reconstructive surgery, but not both. As of Janu-ary 1998, 25 states had different laws regarding requiredinsurance coverage for post mastectomy reconstruction.
Implants may pose additional insurance concerns.

Some companies will withdraw coverage for womenwith implants, or add a disclaimer for future implant-related problems. Careful reading of insurance policies,including checking on the need for pre-approval and/or asecond opinion, is strongly recommended.
Routine preoperative preparations, such as taking

nothing to eat or drink the night before surgery are need-ed for reconstructive procedures. Blood transfusions areoften necessary for autologous reconstructive surgeries.The patient may donate her own blood, and/or have fami-ly and friends donate several weeks before the surgery.
Emotional preparation is also important. Breast

reconstruction will not resolve a psychological problemthe woman had before mastectomy, nor make an unstablerelationship strong. An expectation of physical perfectionis unrealistic. A woman who cites any of these reasonsfor reconstruction shows that she has not been adequate-ly informed or prepared. Complete understanding of thebenefits and limitations of this surgery is necessary for asatisfactory result.
Aftercare

frequency of visits to the doctor after surgery varies consid-erably with the different kinds of reconstruction. In general,autologous procedures require longer hospitalization andrecovery time than implant procedures. Bandages anddrainage tubes remain in place for at least a day for all surg-eries. Microsurgical or free flaps are most closely moni-tored in the first day or two after surgery. The circulation tothe breast may be checked as often as every hour. Completebreast reconstruction

as every hour. Completebreast reconstruction requires at least one additionalsurgery to create a nipple and areola. Scars may remain redand raised for a month or longer. The true, final appearanceof the breasts will not be visible for at least one year.

Risks
Some women have reported various types of autoim-
mune related connective-tissue disorders, which theyattribute to their implants usually involving silicone gelimplants. Lawsuits have been filed against the manufac-turers of implants. Food and Drug Administration guide-lines, issued in 1992, now limit their use to women whoneed to replace an existing silicone gel-filled implant,KEY TERMS
Autologous —From the same person. An autolo-

gous breast reconstruction uses the woman’s owntissues. An autologous blood transfusion is bloodremoved then transfused back to the same personat a later time.
Capsular contracture —Thick scar tissue around a
breast implant, which may tighten and cause dis-comfort and/or firmness.
Flap—A section of tissue moved from one area of
the body to another.
Free flap —A section of tissue detached from its

blood supply, moved to another part of the body,and reattached by microsurgery to a new bloodsupply.
Mastopexy —Surgical procedure to lift up a breast.
May be used on opposite breast to achieve sym-metrical appearance with a reconstructed breast.
Pedicle flap —Also called an attached flap. A sec-
tion of tissue, with its blood supply intact, which ismaneuvered to another part of the body.
have had surgery for breast cancer, or have a medical

condition which results in serious breast abnormality. Inaddition, patients must sign a consent form which detailsthe potential risks of silicone gel-filled implants, andbecome enrolled in a long range study. Saline filledimplants are permitted for all uses, although manufactur-ers must collect data on possible risks.
The FDA issued a status report on Breast Implant

Safety in 1995, and revised it in March 1997. It notedthat studies so far have not shown a serious increase inthe risk of recognized autoimmune diseases in womenwith silicone gel-filled breast implants. It also addressedconcerns about other complications and emphasized theneed for further study of this issue.
There are a number of risks common to any surgical

procedure such as bleeding, infection, anesthesia reac-tion, or unexpected scarring. Hematoma (accumulationof blood at the surgical site), or seroma (collection offluid at the surgical site) can delay healing if not drained.Any breast reconstruction also poses a risk of asymmetryand/or the need for unplanned surgical revision. Persis-tent pain is another potential complication possible withall types of breast reconstruction.
Implants have some unique problems that may

develop. A thick scar, also called a capsule, forms around
GALE ENCYCLOPEDIA OF MEDICINE 2 589Breast reconstructionGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 589

foreign substance. Capsular contracture occurs when thescar becomes firm or hardened. This may cause painand/or change the texture and appearance of the breast.Implants can rupture and leak, deflate, or become dis-placed. The chances of capsular contracture or ruptureincrease with the age of the implant. These complica-tions can usually be remedied with outpatient surgery toloosen the capsule or remove and/or replace the implantas needed. There is some evidence that using implantswith textured

is some evidence that using implantswith textured surfaces may decrease the incidence ofthese problems. An implant tends to remain firm indefi-nitely. It will not grow larger or smaller as the woman’sweight changes. Asymmetry can develop if a womangains or loses a large amount of weight.

The autologous procedures all carry a risk of flap
failure—loss of blood supply to the tissue forming thenew breast. If a large portion of the flap develops inade-quate blood supply, another reconstructive techniquemay be necessary. TRAM flap procedures can result indecreased muscle tone and weakness in the abdomenand/or abdominal hernia . Arm weakness may occur after
latissimus dorsi flap surgery.
A normal result of breast reconstruction depends on

the woman’s goals and expectations. It will not be thesame as the breast it replaces. In general, it should be sim-ilar in size and shape to the opposite breast, but will haveless sensation and be less mobile than a natural breast. Areconstruction using implants will usually be firmer androunder than the other breast. It may feel cooler to touch,depending on the amount of tissue over it. Scars areunavoidable, but should be as unobtrusive as possible.
Resources
BOOKS

Resources
BOOKS
Berger, Karen, and John Bostwick III. A Woman’s Decision:
Breast Care, Treatment and Reconstruction. St. Louis:
Quality Medical Publishing, Inc., 1994.
Bostwick III, John. “Breast Reconstruction Following Mastec-
tomy.” CA: A Cancer Journal for Clinicians 45
(Sept./Oct. 1995): 289-303.

30329-4251. (800) 227-2345. <http://www.cancer.org>.American Society of Plastic and Reconstructive Surgeons. 44
U.S. Department of Health and Human Services, U.S. Food
and Drug Administration, Office of Consumer Affairs.5600 Fishers Lane, Rockville, MD 20857. (800) 532-4440. <http://www.fda.gov/fdahomepage.html>.

Breast reduction
Breast reduction is a surgical procedure performed
in order to decrease the size of the breasts.
Purpose
Women with very large breasts (macromastia or
mammary hyperplasia) seek breast reduction for relief ofpain in the back, shoulder, and neck. They may also feel

uncomfortable about their breast size and have difficultyfinding clothing that will fit properly. Additionally, breastreduction may be needed after reconstructive surgery fol-lowing the surgical removal of cancerous breast tissue(mastectomy ), to make the breasts more symmetric.
Men who have enlarged breasts ( gynecomastia ) may
also be candidates for breast reduction. However, excessivealcohol intake, smoking marijuana , or using anabolic

steroids may cause gynecomastia, and surgery is not rec-ommended for men who continue to use these products.
Breast reduction is not recommended for women
whose breasts are not fully developed or who plan tobreast feed.
Breast reduction may also be called reduction

mammaplasty. It is most often done in the hospital, undergeneral anesthetic. However, studies have suggested thatan outpatient procedure, using local anesthetic and mildsedation may be appropriate for some patients. The

operation takes approximately two to four hours. Themost commonly made incision encircles the areola (dark-ened area around the nipple) and extends downward andaround the underside of the breast. This produces theleast conspicuous scar. The excess tissue, fat, and skinare removed, and the nipple and areola are repositioned.In certain cases, liposuction (fat suctioning) is used to
GALE ENCYCLOPEDIA OF MEDICINE 2 590Breast reductionGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 590

remove extra fat from the armpit area. A hospital stay of
up to three days may be needed for recovery.
If deemed medically necessary, breast reduction is
covered by some insurance plans. However, a specifiedamount of breast tissue may need to be removed in orderto qualify for coverage. Surgeon’s fees range from$4,800-$6,500 and up.
Consultation between surgeon and patient is impor-

tant to ensure that the woman understands and agreeswith the expected final results of the procedure. Mea-surements and photographs may be taken. Many doctorsalso recommend a mammogram before the operation, tomake sure there is no cancer .
Aftercare
After the surgery, an elastic bandage or special support-

ive bra is placed over gauze bandages and drainage tubes.The bandages and tubes are removed in a day or two. Thebra will need to be worn around the clock for several weeks.Stitches are removed one to three weeks after the operation.Normal activities, including sexual relations may be restrict-ed for several weeks. Scars will typically remain red, andperhaps lumpy for up to several months, but will graduallyfade and become less noticeable. It may take up to a yearbefore the breasts achieve their

take up to a yearbefore the breasts achieve their final position and size.

Risks
Risks common to any operation include bleeding,
infection, anesthesia reactions, or unexpected scarring.Breast reduction may result in decreased feeling in thebreasts or nipples and/or impaired ability to breastfeed.When healing is complete, the breasts may be slightlyuneven, or the nipples may be asymmetric.
Smaller breast size should be achieved, and with
that, the accompanying pain and discomfort should bealleviated.KEY TERMS
Gynecomastia —Overly developed or enlarged

breasts in a male.
Macromastia —Excessive size of the breasts.
Mammary hyperplasia —Increased size of the
breast.Resources
BOOKS
Book. Reading, MA: Addison-Wesley, 1995.
Breast self-examination

A breast self-examination (BSE) is an inspection by
a woman of her breasts to detect breast cancer .
Purpose
A BSE is one of three tests the American Cancer

Society recommends to help detect breast cancer in itsearliest stages. By regularly examining her own breasts, awoman is more likely to find any changes that may haveoccurred. The best time to perform a BSE is about a weekafter a woman’s period ends, when her breasts are not ten-der or swollen. If her periods are not regular, a BSEshould be completed on the same day every month. ABSE should also be regularly completed by women whoare pregnant, breastfeeding, or have breast implants . By

combining a BSE with a mammography and clinical
breast examination, a woman is offered the best opportu-nity for reducing chances of death from breast cancer

through early detection. Close to 90% of breast cancersare found through a BSE. The American Cancer Societyrecommends that beginning at the age of 20, women com-plete a BSE each month by feeling for lumps or anythingsuspicious, as well as looking at their breasts carefully ina mirror for any changes in contour, swelling, dimpling,puckering of the skin, or changes in the nipple.
To complete a monthly BSE:
• When lying down, place a pillow under the right shoul-

der and position the right arm behind the head. Usingthe finger pads of the three middle fingers on the lefthand, check the entire breast area. Use small circles andfollow an up-and-down pattern while pressing firmlyenough to know how the breast feels from month tomonth. This exam should then be repeated on the left
GALE ENCYCLOPEDIA OF MEDICINE 2 591Breast self-examinationGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 591

breast using the finger pads of the right hand with the
pillow under the left shoulder.
• When standing before a mirror, any changes in the
shape or look of the breasts should be checked. In orderto look for any skin or nipple changes such as dimplingor nipple discharge, the arms should first be placed atthe sides and then overhead. Hands are then placedfirmly on hips to flex chest muscles, and then the bodyshould be bent forward.
• When taking a shower, the right arm should be raised.

By using soapy hands and fingers flat the right breastand outer part of the breast can be examined. The samesmall circles and up-and-down pattern used when lyingdown should be used in an upright position. Repeat onthe left breast.
Before beginning a monthly BSE, a woman’s breasts
should be completely exposed.
Each woman’s breasts has their own normal look

and feel. By completing a BSE each month, a woman candetermine what is normal for her and check for changesthat may arise. A regular pattern of lumpiness in thebreasts is normal.
If any changes are noticed during a monthly BSE,
such as a new, hard lump in the breast or underarms, adoctor should examine the area immediately. Other trou-ble signs that should not be ignored include:
• change in breast size or shape

• dimpling or puckering of the skin• redness, swelling, or warmth that does not go away•a  pain in one area that does not vary with a woman’s
monthly cycle
• a nipple that pulls in
• discharge from the nipple that begins suddenly and
appears only in one breast
• one nipple that has an itchy, sore, or scaling area
Resources
BOOKS
Altman, Roberta and  Michael J. Sarg. “Breast Self-examina-

tion.” The Cancer Dictionary. Checkmark Books, 2000.ORGANIZATIONS
American Cancer Society. (800) 227-2345. <http://www.
The Komen Foundation. 5005 LBJ Freeway, Suite 250, Dallas,
Texas 75244. (972) 855-1600. <http://www.komen.org>.
OTHER
“How to do a Breast Self-Exam.” Women.com. 5 May 2001.
<http://www.women.com>.
Breast sonogram seeBreast ultrasound
Breast ultrasound
Breast ultrasound (or sonography) is an imaging

technique for diagnosing breast disease, such as cancer .
It uses harmless, high frequency sound waves to form animage (sonogram). The sound waves pass through thebreast and bounce back or echo from various tissues toform a picture of the internal structures. It is not invasiveand involves no radiation.
Purpose
Breast ultrasound may be used in several ways. The

most common application is to investigate a specific areaof the breast where a problem is suspected. A palpablelump and/or a lump or density discovered by x ray(mammogram) can be further evaluated by ultrasound. Itis especially helpful in distinguishing between a fluid-filled cyst and a solid mass. It can also identify smalllesions that are too tiny to be felt.
Breast ultrasound is often the first study performed to

evaluate masses in women under 35 whose mammogramscan be difficult to interpret due to the density of theirbreast tissue. The lack of radiation used with ultrasoundmakes it ideal for studying breast abnormalities in womenwho are pregnant. Assessing breast implants for leakage
or rupture is another way ultrasound is used. Breastinflammation, where pockets of infection or abscessesmay form, can be diagnosed and monitored by ultrasound.
Thickened and swollen breast skin may be a sign of

inflammatory breast cancer . Ultrasound can sometimes
identify a cancerous growth within the breast causing thethickened skin. These cases are usually followed by acore biopsy guided by ultrasound (described below).
Breast ultrasound is employed to observe and guide a
needle for several interventional procedures. These includecyst aspiration, fine needle aspiration, large core needle
GALE ENCYCLOPEDIA OF MEDICINE 2 592Breast ultrasoundGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 592

biopsy (as a first step in determining treatment for a lesion
that is likely to be cancerous), and needle localization insurgical breast biopsy . Biopsies guided by ultrasound have

distinct advantages. The ultrasound guides the needle sothat a lesion can be removed for the biopsy. Patients usuallyfind that the procedure is less traumatic and more comfort-able than surgical biopsies. Ultrasound is known for itsaccuracy in determining how far a cancerous growthextends into the surrounding tissue in lesions that cannot befelt. Biopsies guided by ultrasound are generally less costlythan surgical biopsies. Additionally, if the abnormality thatrequires biopsy can be seen on

abnormality thatrequires biopsy can be seen on both a mammogram andultrasound, an ultrasound-guided biopsy is often morecomfortable for the patient as no compression is necessary.

Ultrasound can be done in a doctor’s office or anoth-
er outpatient setting, such as a hospital or imaging center.
The patient removes her clothing from the waist up

and puts on a hospital gown, open in the front. She lieson her back or side on an examining table. A gel thatenhances sound transmission is spread over the area to beexamined. The technologist then places a transducer, aninstrument about the size of an electric shaver, againstthe skin. The images from reflected sound waves appearon a monitor screen.
A good ultrasound study is difficult to obtain if the
patient is unable to remain quietly in one position. Obe-

sitymay hinder clear viewing of internal structures, and
the accuracy of an ultrasound study is highly dependenton the skill of the person performing the examination.The images recorded vary with the angle and pressure ofthe transducer and the equipment settings. The examina-tion may take from 30 to 45 minutes. Most insuranceplans cover the cost of an ultrasound examination.Normal results
An ultrasound examination may reveal either normal

tissue or a benign condition such as a cyst. Ultrasoundcan confidently diagnose a benign structure that has cer-tain characteristics of a simple cyst. In the case of a sim-ple cyst with no symptoms, additional treatment beyondcontinued observation is usually not needed.
A potentially malignant mass can be identified by
breast ultrasound. Abnormal results fall into the following
GALE ENCYCLOPEDIA OF MEDICINE 2 593Breast ultrasound

A breast ultrasound image. (Custom Medical Stock Photo.
Reproduced by permission.)KEY TERMS
Cyst—A thin-walled, fluid-filled benign structure
in the breast.
Ductal carcinoma —A type of cancer that
accounts for as much as 80% of breast cancers.These tumors feel bigger than they look on ultra-sound or mammogram.
Fibroadenoma —A benign breast growth made up
of fibrous tissue. It is the most common mass inwomen under 35 years of age, and is found inboth breasts in 3% of cases.

Infiltrating lobular carcinoma —A type of cancer
that accounts for 8% to 10% of breast cancers. Inbreasts that are especially dense, ultrasound canbe useful in identifying these masses.Microcalcifications —Tiny flecks that are too small
to be felt. They are important markers of cancerthat show up on ultrasound and mammogram.
Mucinous (colloid) carcinoma —A type of cancer

that accounts for 1% to 2% of breast cancers.Resembles medullary carcinoma in ultrasound andmammogram, but usually affects older women.
Nonpalpable —Cannot be felt by hand. In cancer,
growths that are nonpalpable are too small to befelt, but may be seen on ultrasound or mammo-gram.
Papillary carcinoma —A type of breast cancer that

primarily occurs in older women. On ultrasound,this type of tumor may look like a solid or com-plex mass, or it may show up as solid tissue pro-truding into a cyst.
Tubular carcinoma —A type of cancer that accounts
for approximately 1% to 2% of breast cancers. Canappear small on ultrasound or mammogram.GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 593

categories: benign fibrous nodule, complex cyst, suspi-
cious lesion, and lesion highly suggestive of cancer. Incases where ultrasound shows the presence of a complexcyst or fibrous nodule, a biopsy is justified because 10% to15% of these growths are malignant. Lesions falling intothe last two categories (suspicious or highly suggestive ofcancer) have a higher chance of being cancerous, andshould be investigated further, either by biopsy or surgery.

on ultrasound: ductal carcinoma, infiltrating lobular carci-noma, medullary carcinoma, mucinous (colloid) carcino-ma, tubular carcinoma, and papillary carcinoma. On ultra-sound, the shape of a lesion and the type of edges it has cansometimes indicate if it is benign or cancerous, but thereare exceptions. For example, benign fibroadenomas areusually oval, and some cancers can be similarly shaped.Cancerous tumors usually have jagged edges, but somebenign growths can have these edges as well.

somebenign growths can have these edges as well. Ultrasound isnot a definitive test. Tissue diagnosis is often required.

Resources
BOOKS
Rumack, Carol M. et al., eds. Diagnostic Ultrasound St. Louis:
Mosby–Year–Book, Inc., 1998.
Jackson, Valerie. “The Current Role of Ultrasonography in
Breast Imaging.” Radiologic Clinics of North America 33
(November 1995): 1161-70.
Rubin, Eva, et al. “Reducing the Cost of Diagnosis of Breast

Carcinoma: Impact of Ultrasound and Imaging–GuidedBiopsies on a Clinical Breast Practice.” Cancer 91 (Janu-
ary 2001) 324-31.
Smith, LaNette F. et al. “Intraoperative Ultrasound–guided
Breast Biopsy.” The American Journal of Surgery 180
(December 2000): 419-23.
Velez, Nitzet et al. “Diagnostic and Interventional Ultrasound
for Breast Disease.” The American Journal of Surgery 180
(October 2000): 284-7.
Ellen S. Weber
Breast x ray seeMammography
Breech birth

Breech birth is the delivery of a fetus (unborn baby)
hind end first. Between 3-4% of fetuses will start labor in thebreech position, which is a potentially dangerous situation.Description
Throughout most of pregnancy , the developing

fetus is completely free to move around within theuterus. Between 32-36 weeks, it becomes so large thatmovement is restricted. It is much harder for the fetus toturn over, so whatever position it has assumed by thispoint is likely to be the same position that he or she willbe in when labor begins.
For reasons that are not fully understood, almost all

unborn babies settle into a head down position. The fetusis upside down in the uterus, and the head will lead theway during the birth process.
Unfortunately, some fetuses do not cooperate. Most
of these are in the breech position. The buttocks lead theway out of the uterus, and the legs are folded in front ofthe body (frank breech). Delivery from the breech posi-tion poses far more risks than delivery head first (vertexposition).
The biggest part of the fetus’s body is usually its

head. If the head fits through the mother’s pelvis, thenthe rest of the fetus’s body should slip out fairly easily. Ifthe fetus is born bottom first, it is possible that the bodywill fit through the mother’s pelvis, but the baby’s headwill get stuck at the level of the chin. This condition,known as a trapped head, is very dangerous.
When the baby’s head comes first, it has a chance to

“mold” during labor. The bones of the baby’s skull arenot yet fastened together the way they are in a child oradult’s skull, meaning that the bones of the baby’s skullcan move. During the long hours of labor the skull canchange shape to fit through the pelvis more easily, whichis why many babies are born with a “cone head”. If thebaby is born from the breech position, the skull does nothave a chance to change shape to fit the pelvis, and it iseven more likely to get stuck.

If the baby’s head gets trapped, the possibility of
injury is high. Once the baby’s body is born, the umbilicalcord usually stops pulsating (just as it would during a nor-mal delivery). This cuts off the oxygen supply from themother to the baby. If the baby’s head is still inside theuterus the baby cannot yet breathe on its own. Therefore,it is essential to deliver the baby as quickly as possible.
The life saving attempts to deliver the baby’s head

can cause injury to the baby’s neck or head resulting inpermanent handicaps. In extreme cases, if the baby can-not be delivered within a few minutes, the baby mightdie. Obviously, it is critical to avoid a breech deliverywith a trapped head.
Of course, many babies are safely delivered from the
breech position. There are certain factors that make abreech delivery more likely to be successful: if ultra-

GALE ENCYCLOPEDIA OF MEDICINE 2 594Breech birthGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 594

sound (a technique that uses sound waves to visualize the
fetus) shows that the fetus is in the frank breech position,the fetus’s head is tucked on its chest, and the fetus is notbig, it is less likely that its head will get stuck.
Among breech babies born after the full nine-month

term, smaller babies usually do better. This is not true forpremature babies. Premature babies are more likely to havea trapped head because the body of a premature baby isusually much smaller than his or her head. Prematurebabies are generally not delivered from the breech position.
The risks of vaginal breech delivery can be avoided by
delivering the baby through a surgical procedure ( cesarean
section , also known as c-section). For the past twenty

years, cesarean section has been recommended when thefetus is breech. More recently, many providers have offeredthe option of version, attempting to turn the fetus within theuterus to a head first position before labor begins.
Version is based on a very simple idea. If a fetus in
the breech position does a somersault, it will end up headdown. During a version, the obstetrician tries to make thefetus do a somersault.
A version should only be done in a hospital, with an

ultrasound machine used to guide the obstetrician inturning the fetus. The fetus should be monitored with afetal monitor before and after the version. Some obstetri-cians give the mother an injection of medication to relaxthe mother’s uterus and prevent any contractions.
During the procedure, the obstetrician places his or

her hands on the mother’s abdomen to feel the location ofthe unborn baby’s buttocks and head. The buttocks arelifted up slightly and the doctor pushes on the baby’shead to encourage him to perform a somersault. It maytake several tries before the fetus cooperates, but overhalf will eventually turn.
A version is not appropriate for every fetus who is in

the breech position at the end of pregnancy. It can only betried if there is one fetus in the uterus, if the placenta is notlying in front of the fetus, and if the umbilical cord doesnot appear to be wrapped around the fetus at any point.
The cause of breech birth is not known. There are

generally no identifiable symptoms. However, somewomen can tell the position of the fetus by where theyfeel the fetus kicking. Most women cannot tell whatposition the fetus is in at any given moment.
Diagnosis
A health care provider can often tell the position of
the fetus by feeling it through the wall of the mother’sabdomen. Another clue to the position is the location

where the heartbeat is heard best. If the fetus’s heartbeatis best heard below the level of the mother’s navel, it islikely to be positioned head first. On the other hand, ifthe heartbeat is best heard above the level of the navel, itis likely to be breech.
The only way to really be sure, however, is to do an
ultrasound exam. Using this technique it is very easy totell the position of the fetus.
Treatment
If a fetus is in the breech position in the last weeks of

pregnancy, there are three possible courses of action: Cesare-an section, attempted version, or vaginal breech delivery.
Cesarean section is the most common way to deliver
a breech baby. This surgical procedure carries more riskfor the mother, but many women prefer to take the risk ofsurgery on themselves rather than let the baby face therisks of breech delivery.
Version is gaining in popularity. Version is a medical

procedure in which the obstetrician tries to turn thebreech fetus to the head first position. Version is success-ful more than 50% of the time. However, some babieswho are successfully turned will turn back to the breechposition after the procedure is done.
GALE ENCYCLOPEDIA OF MEDICINE 2 595Breech birth
Placenta
Uterus
Umbilical cord
Breech Birth
Approximately 3-4% of babies will start labor in the breech

(buttocks first) position. While this is a potentially danger-ous situation, many full-term babies can be safely deliveredfrom the breech position. (Illustration by Electronic Illustrators
Group.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 595

Some women choose breech vaginal delivery. This
should only be attempted if ultrasound shows that thefetus is in a favorable breech position. Most babies willdo very well during a breech delivery, but it is alwayspossible that the fetus will be injured, perhaps seriously.
There is no way to prevent a fetus from settling into
the breech position at the end of pregnancy. A womanwho has had one breech fetus is more likely than averageto have another.
Amy B. Tuteur, MD
Resources
BOOKS

Resources
BOOKS
“Techniques for Breech Delivery.” In Williams Obstetrics. 20th
ed. Ed. F. Gary Cunningham, et al. Stamford: Appleton &Lange, 1997.
Breech presentation seeBreech birth
Brill-Zinsser disease seeTyphus
Brittle bone disease seeOsteogenesis
imperfecta
Broken nose seeNasal trauma
Bronchiectasis
Bronchiectasis is a condition in which an area of the
bronchial tubes is permanently and abnormally widened(dilated), with accompanying infection.

tubes which deliver air to the tiny sacs of the lungs (alve-oli). In bronchiectasis, the diameter of the bronchi isunusually large. Examination of the walls of the bronchialtubes reveals destruction of the normal structural elements,with replacement by scar tissue. Pus collects within thebronchi, and the normal flow of oxygen into the lungs, andcarbon dioxide out of the lungs (air exchange) is impaired.The bronchi show signs of inflammation, with swellingand invasion by a variety of immune

with swellingand invasion by a variety of immune cells. The inflamedareas show signs of increased growth of blood vessels. Thearea of the lung which should be served by a diseasedbronchial tube is also prone to inflammation and infection.Causes and symptoms

Prior to the widespread use of immunizations,
bronchiectasis was often the result of a serious infectionwith either measles or whooping cough . Currently,
viruses that cause influenza (flu) or influenza-like syn-
dromes, as well as a number of bacteria may precede thedevelopment of bronchiectasis. Patients who have beeninfected with tuberculosis or the virus which causes
AIDS (HIV or human immunodeficiency virus) also
have an increased chance of bronchiectasis.

A number of pre-existing conditions may cause an
individual to be more susceptible than normal to infec-tion, with increased risk of bronchiectasis developing.These conditions include disorders of cilia, and immunedisorders.
Cilia are the tiny hairs which usually line the

bronchial tubes. Cilia wave constantly, sweeping thebronchial tubes clean of bacterial or viral invaders, andcleaning away excess secretions (mucus, sputum) whichmay be produced by the bronchi. When these cilia areabnormal or absent at birth, various bacterial or viralinvaders may remain in the respiratory tract, multiply,and cause serious infections.
Immune disorders include decreased production of

certain immune chemicals (immunoglobulins) whichusually serve to fight off infection by bacterial or viralinvasion. When these immunoglobulins are not producedin large enough quantity, bacterial and viral invaders arenot effectively killed off, and infection occurs.
Other causes of bronchiectasis include an abnormal-

ly blocked (obstructed) airway. This can be due to tumorgrowth within the bronchial tube, or due to a child acci-dentally inhaling a small object which then blocks off thebronchial tube. People with the disease called cystic
fibrosis (CF) often have their bronchial tubes obstructed

by the thick, sticky mucus which is a hallmark of CF.Toxic exposures (breathing ammonia, for example) canharm the bronchi, and lead to bronchiectasis. An extremeallergic response of the immune system to the presenceof certain fungi (especially one called Aspergillus ) can
also damage the bronchial tubes enough to result inbronchiectasis.
Symptoms of bronchiectasis include constant cough

and the production of infected sputum (sputum is a mix-ture of mucus and pus), which may be bloody. In somecases, there may be wheezing and shortness of breath .
The constant, low-level of infection may flare, resultingin increased production of sputum, worsening of thecough, and fever . The area of the lung served by the
affected bronchial tube may become severely infected,resulting in pneumonia .

GALE ENCYCLOPEDIA OF MEDICINE 2 596BronchiectasisGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 596

Diagnosis
Chest x ray may reveal evidence of bronchiectasis,
and CT scans are particularly good at revealing the thick,dilated bronchial walls of bronchiectasis. Sputum willneed to be collected and cultured (grown in a laboratorydish), in order to examine it microscopically for the spe-cific type of organism responsible for infection. A carefulsearch for other underlying diseases is important, look-ing in particular for ciliary abnormalities, cystic fibrosis,or immunoglobulin deficiencies.

Treatment
Treatment should involve efforts to resolve any
underlying disorder. Infections will require antibiotics ,
obstruction may require the removal of a foreign object ortumor. Medications are available to help thin the sputum,so that it can be more effectively coughed up. Rhythmicclapping on the chest and back, while the patient assumesa number of positions (head down, primarily), may helpthe lungs to drain more effectively. This is called chest

physical therapy , or percussion and postural drainage.
When a particular area of the lung is constantly and
severely infected, surgery may be needed to remove it. Whenbleeding occurs from irritated bronchial tubes and over-grown bronchial blood vessels, surgery may be requiredeither to remove an area of the bronchial tube, or to inject thebleeding blood vessel with a material to stop the bleeding.
In some patients, bronchiectasis eventually leads to a

constantly low level of blood oxygen, despite other treat-ments. These patients usually have an associated increasein the size of the right side of their hearts, along with adecrease in the heart’s ability to pump blood through thelungs. Some patients with extremely severe symptoms anddisability have been treated with lung transplantation .Prognosis
Prognosis varies widely, depending on how wide-
spread or focal the bronchiectasis, and the presence ofother underlying disorders.
Resources
BOOKS

Resources
BOOKS
Sherris Medical Microbiology: An Introduction to Infectious
Diseases. 3rd ed. Ed. Kenneth J. Ryan. Norwalk, CT:
Appleton & Lange, 1994.
Weinberger, Steven. “Bronchiectasis.” In Harrison’s Principles
Marwah, Onkarjit S., and Om P. Sharma. “Bronchiectasis: How
to Identify, Treat, and Prevent.” Postgraduate Medicine 97
(Feb. 1995): 149+.

Nicotra, M. Brooke, et al. “Clinical, Pathophysiologic, and
Microbiologic Characterization of Bronchiectasis in anAging Cohort.” Chest 108 (Oct. 1995): 955+.
Weinberger, Steven E., and Ann Giudici Fettner. “Disease in
Disguise: Bronchiectasis.” Harvard Health Letter 21 (Feb.
1996): 6+.
Bronchiolitis seeRespiratory syncytial virus

infection
Bronchitis
Bronchitis is an inflammation of the air passages
between the nose and the lungs, including the windpipe or
GALE ENCYCLOPEDIA OF MEDICINE 2 597Bronchitis
Colorized bronchogram of lungs—right tree has almost no
structure caused by chronic inflammation. (Mehau Kulyk,
Photo Researchers. Reproduced by permission.)KEY TERMS
Bronchi —The network of tubular passages which

carry air to the lung and allow air to be expelledfrom the lungs.
Cilia —Hair-like projections which line the
bronchial tubes (also present in other areas of thebody). Normal cilia beat consistently, sweepingthe bronchi clean of bacteria, viruses, and mucus.GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 597

trachea and the larger air tubes of the lung that bring air in
from the trachea (bronchi). Bronchitis can either be ofbrief duration (acute) or have a long course (chronic).Acute bronchitis is usually caused by a viral infection, butcan also be caused by a bacterial infection and can healwithout complications. Chronic bronchitis is a sign of seri-ous lung disease that may be slowed but cannot be cured.
Although acute and chronic bronchitis are both

inflammations of the air passages, their causes and treat-ments are different. Acute bronchitis is most prevalent inwinter. It usually follows a viral infection, such as a coldor the flu, and can be accompanied by a secondary bacter-ial infection. Acute bronchitis resolves within two weeks,although the cough may persist longer. Acute bronchitis,
like any upper airway inflammatory process, can increasea person’s likelihood of developing pneumonia .

Anyone can get acute bronchitis, but infants, young
children, and the elderly are more likely to get the dis-ease because people in these age groups generally haveweaker immune systems. Smokers and people with heartor other lung diseases are also at higher risk of develop-ing acute bronchitis. Individuals exposed to chemicalfumes or high levels of air pollution also have a greaterchance of developing acute bronchitis.
Chronic bronchitis is a major cause of disability and

death in the United States. The American Lung Associa-
tion estimates that about 14 million Americans sufferfrom the disease. Like acute bronchitis, chronic bronchi-tis is an inflammation of airways accompanied by cough-ing and spitting up of phlegm. In chronic bronchitis,these symptoms are present for at least three months ineach of two consecutive years.
Chronic bronchitis is caused by inhaling bronchial

irritants, especially cigarette smoke. Until recently, moremen than women developed chronic bronchitis, but asthe number of women who smoke has increased, so hastheir rate of chronic bronchitis. Because this disease pro-gresses slowly, middle-aged and older people are morelikely to be diagnosed with chronic bronchitis.
Chronic bronchitis is one of a group of diseases that

fall under the name chronic obstructive pulmonary dis-ease (COPD). Other diseases in this category includeemphysema and chronic asthmatic bronchitis. Chronic
bronchitis may progress to emphysema, or both diseasesmay be present together.
Acute bronchitis
Acute bronchitis usually begins with the symptoms
of a cold, such as a runny nose, sneezing, and dry cough.However, the cough soon becomes deep and painful.

Coughing brings up a greenish yellow phlegm or sputum.These symptoms may be accompanied by a fever of up
to 102°F (38.8°C). Wheezing after coughing is common.
In uncomplicated acute bronchitis, the fever and

most other symptoms, except the cough, disappear afterthree to five days. Coughing may continue for severalweeks. Acute bronchitis is often complicated by a bacter-ial infection, in which case the fever and a general feel-ing of illness persist. To be cured, the bacterial infectionshould be treated with antibiotics .
Chronic bronchitis
Chronic bronchitis is caused by inhaling respiratory

tract irritants. The most common irritant is cigarettesmoke. The American Lung Association estimates that80-90% of COPD cases are caused by smoking . Other
irritants include chemical fumes, air pollution, and envi-ronmental irritants, such as mold or dust.
Chronic bronchitis develops slowly over time. The

cells that line the respiratory system contain fine, hair-like outgrowths from the cell called cilia. Normally, thecilia of many cells beat rhythmically to move mucusalong the airways. When smoke or other irritants areinhaled, the cilia become paralyzed or snap off. Whenthis occurs, the cilia are no longer able to move mucus,and the airways become inflamed, narrowed, andclogged. This leads to difficulty breathing and canprogress to the life-threatening disease emphysema.

A mild cough, sometimes called smokers’ cough, is
usually the first visible sign of chronic bronchitis.Coughing brings up phlegm, although the amount variesconsiderably from person to person. Wheezing andshortness of breath may accompany the cough. Diag-
nostic tests show a decrease in lung function. As the dis-ease advances, breathing becomes difficult and activitydecreases. The body does not get enough oxygen, lead-ing to changes in the composition of the blood.
Diagnosis

Diagnosis
Initial diagnosis of bronchitis is based on observing
the patient’s symptoms and health history. The physicianwill listen to the patient’s chest with a stethoscope forspecific sounds that indicate lung inflammation, such asmoist rales and crackling, and wheezing, that indicatesairway narrowing. Moist rales is a bubbling sound heardwith a stethoscope that is caused by fluid secretion in thebronchial tubes.
A sputum culture may be performed, particularly if

the sputum is green or has blood in it, to determine whethera bacterial infection is present and to identify the disease-
GALE ENCYCLOPEDIA OF MEDICINE 2 598BronchitisGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 598

causing organism so that an appropriate antibiotic can be
selected. Normally, the patient will be asked to coughdeeply, then spit the material that comes up from the lungs(sputum) into a cup. This sample is then grown in the labo-ratory to determine which organisms are present. Theresults are available in two to three days, except for tests fortuberculosis , which can take as long as two months.
Occasionally, in diagnosing a chronic lung disorder,

the sample of sputum is collected using a procedurecalled a bronchoscopy . In this procedure, the patient is
given a local anesthetic, and a tube is passed into the air-ways to collect a sputum sample.
A pulmonary function test is important in diagnos-

ing chronic bronchitis and other variations of COPD.This test uses an instrument called a spirometer to mea-sure the volume of air entering and leaving the lungs.The test is done in the doctor’s office and is painless. Itinvolves breathing into the spirometer mouthpiece eithernormally or forcefully. V olumes less than 80% of thenormal values indicate an obstructive lung disease.
To better determine what type of obstructive lung
disease a patient has, the doctor may do a chest x ray ,

electrocardiogram (ECG), and blood tests. An electrocar-diogram is an instrument that is used to measure the elec-trical activity of the heart and is useful in the diagnosis ofheart conditions. Other tests may be used to measure howeffectively oxygen and carbon dioxide are exchanged inthe lungs.
Treatment
When no secondary infection is present, acute bron-
chitis is treated in the same way as the common cold .

Home care includes drinking plenty of fluids, resting, notsmoking, increasing moisture in the air with a cool misthumidifier, and taking acetaminophen (Datril, Tylenol,
Panadol) for fever and pain . Aspirin should not be given
to children because of its association with the serious ill-ness, Reye’s syndrome .
Cough suppressants are used only when the cough

is dry and produces no sputum. If the patient is coughingup phlegm, the cough should be allowed to continue. Thepurpose of the cough it to bring up extra mucus and irri-tants from the lungs. When coughing is suppressed, themucus accumulates in the plugged airways and canbecome a breeding ground for pneumonia bacteria.
Expectorant cough medicines, unlike cough suppres-

sants, do not stop the cough. Instead they are used to thinthe mucus in the lungs, making it easier to cough up. Thistype of cough medicine may be helpful to individuals suf-fering from bronchitis. People who are unsure about whatKEY TERMS
Acute —Disease or condition characterized by the
rapid onset of severe symptoms.
Bronchi —The larger air tubes of the lung that
bring air in from the trachea.
Chronic —Disease or condition characterized by
slow onset over a long period of time.

Chronic obstructive pulmonary disease (COPD) —
A term used to describe chronic lung diseases, likechronic bronchitis, emphysema, and asthma.
Emphysema —One of the several diseases called

chronic obstructive pulmonary diseases, emphyse-ma involves the destruction of air sac walls to formabnormally large air sacs that have reduced gasexchange ability and that tend to retain air withinthe lungs. Symptoms include labored breathing,the inability to forcefully blow air out of the lungs,and an increased susceptibility to respiratory tractinfections.
type of medications are in over-the-counter cough syrups

should ask their pharmacist for an explanation.
If a secondary bacterial infection is present, the

infection is treated with an antibiotic. Patients need totake the entire amount of antibiotic prescribed. Stoppingthe antibiotic early can lead to a return of the infection.Tetracycline or ampicillin are often used to treat adults.Other possibilities include trimethoprim/sulfamethoxa-zole (Bactrim or Septra) and the newer erythromycin-like drugs, such as azithromycin (Zithromax) and clar-ithromycin (Biaxin). Children under age eight are usual-ly given amoxicillin (Amoxil, Pentamox, Sumox,

given amoxicillin (Amoxil, Pentamox, Sumox, Tri-mox), because tetracycline discolors permanent teeth thathave not yet come in.

The treatment of chronic bronchitis is complex and
depends on the stage of chronic bronchitis and whetherother health problems are present. Lifestyle changes, suchas quitting smoking and avoiding secondhand smoke orpolluted air, are an important first step. Controlled exer-cise performed on a regular basis is also important.
Drug therapy begins with bronchodilators . These

drugs relax the muscles of the bronchial tubes and allowincreased air flow. They can be taken by mouth orinhaled using a nebulizer. A nebulizer is a device thatdelivers a regulated flow of medication into the airways.
GALE ENCYCLOPEDIA OF MEDICINE 2 599BronchitisGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 599

Common bronchodilators include albuterol (Ventolin,
Proventil, Apo-Salvent) and metaproterenol (Alupent,Orciprenaline, Metaprel, Dey-Dose).
Anti-inflammatory medications are added to reduce
swelling of the airway tissue. Corticosteroids , such as
prednisone, can be taken orally or intravenously. Othersteroids are inhaled. Long-term steroid use can have seri-ous side effects. Other drugs, such as ipratropium (Atro-vent), are given to reduce the quantity of mucus produced.

As the disease progresses, the patient may need sup-
plemental oxygen. Complications of COPD are manyand often require hospitalization in the latter stages of thedisease.
Alternative practitioners focus on prevention by eat-
ing a healthy diet that strengthens the immune system andpracticing stress management. Bronchitis can become

serious if it progresses to pneumonia, therefore, antibi-otics may be required. In addition, however, there are amultitude of botanical and herbal medicines that can beformulated to treat bronchitis. Some examples includeinhaling eucalyptus or other essential oils in warm steam.Herbalists recommend a tea made of mullein ( Verbascum
thapsus ), coltsfoot ( Tussilago farfara ), and anise seed
(Pimpinella anisum ). Homeopathic medicine and tradi-
tional Chinese medicine may also be very useful for

bronchitis, and hydrotherapy can contribute to cleaning
the chest and stimulating immune response.
Prognosis
When treated, acute bronchitis normally resolves in

one to two weeks without complications, although acough may continue for several more weeks. The pro-gression of chronic bronchitis, on the other hand, may beslowed, and an initial improvement in symptoms may beachieved. Unfortunately, however, there is no cure forchronic bronchitis, and the disease can often lead to orcoexist with emphysema. Taken together, all forms ofCOPD are a leading cause of death.
The best way to prevent bronchitis is not to begin

smoking or to stop smoking. Smokers are ten times morelikely to die of COPD than non-smokers. Smokers whostop show improvement in lung function. Other preventa-tive steps include avoiding chemical and environmentalirritants, such as air pollution, and maintaining goodoverall health. Immunizations against certain types ofpneumonia (as well as influenza ) are an important pre-ventative measure for anyone with lung or immune sys-
tem diseases.
Resources
BOOKS

Resources
BOOKS
Shayevits, Myra, Berton Shayevits, and the editors of Consumer
Reports Books. Living Well with Chronic Asthma, Bronchi-
tis, and Emphysema. Consumer Report Books, 1991.
Tiep, Brian L. “Disease Management of COPD with Pul-
monary Rehabilitation.” Chest 112, no. 6 (Dec. 1997):
1630-1657.

National Jewish Center for Immunology and Respiratory Med-
icine. 1400 Jackson St., Denver, CO 80206. (800) 222-5864. <http://www.nationaljewish.org/main.html>.
Bronchodilators
Bronchodilators are medicines that help open the

bronchial tubes (airways) of the lungs, allowing more airto flow through them.
Purpose
People with asthma have trouble breathing, because

their airways are inflamed and become narrowed. Nor-mally, air moves smoothly from the mouth and nosethrough the airways and into the tiny air sacs of the lungsas a person breathes in. Breathing out (exhaling) happensautomatically when the person stops breathing in. In aperson with asthma, breathing in (inhaling) is not a prob-lem. Incoming air can slide around the blockage, becausethe act of breathing in makes the airways expand. Theproblem comes when the person with asthma tries tobreathe

comes when the person with asthma tries tobreathe out. The air can no longer get past the blockage,and it remains trapped in the lungs. The person can thenonly take shallow breaths. Bronchodilators work byrelaxing the smooth muscles that line the airways. Thismakes the airways open wider and allows air to leave thelungs. These drugs also are used to relieve breathingproblems associated with emphysema , chronic bronchi-

tis, and other lung diseases.
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Some bronchodilators are inhaled, using a nebulizer
or an inhalation aerosol. Others are taken as injections orby mouth. Most are available only by prescription, but afew, such as ephedrine, can be bought without a physi-cian’s prescription. Examples of bronchodilators arealbuterol (Proventil, Ventolin), epinephrine (Primatene),ipratropium (Atrovent), metaproterenol (Alupent,Metaprel), and terbutaline (Brethine).

bronchodilator and may be different for differentpatients. Check with the physician who prescribed thedrug or the pharmacist who filled the prescription for thecorrect dosage.
Bronchodilators come with patient instructions. Be

sure to carefully read them before using the medicine. Ifthere is any confusion about how to use the medicine,check with the physician or pharmacist. Always use thesemedicines exactly as directed. Taking larger than recom-mended doses or using the medicine too often can lead toserious side effects and even death .
If symptoms do not improve or if they get worse
after using a bronchodilator, call a physician right away.
Although some bronchodilators are available with-

out a physician’s prescription, these medicines shouldnot be used unless a physician has diagnosed thepatient’s condition as asthma.
Some asthma experts believe that the overuse of

bronchodilators can cause asthma to get worse. Theyadvise patients and their physicians to consider control-ling asthma with anti-inflammatory drugs includinginhaled steroids such as beclomethasone dipropionate(Beclovent, Vanceril), flunisolide (AeroBid) or triamci-nolone acetonide (Azmacort) Ideally, asthma should becontrolled with an inhaled steroid that is used along withthe bronchodilator. The more the inhaled steroid steroidcontrols the inflammation that causes the asthma, the

the inflammation that causes the asthma, the lessbronchodilator the patient needs to use because symp-toms are under control.

Persons with diabetes should be aware that the bron-
chodilator epinephrine may raise their blood sugar levels.
Patients who are using an aerosol bronchodilator and
an aerosol form of either ipratropium or a corticosteroidsuch as beclomethasone dipropionate (Beclovent,Vanceril) should use the bronchodilator first, then wait 5minutes before using the other medicine. Check with aphysician before using any other inhaled medications or

other asthma medicines. The physician must determinethe proper amount of time between doses.
Some bronchodilator products contain sulfites, that
trigger an allergic reaction in certain people. Anyonewho has a sulfite allergy should read the label carefullyor check with a physician or pharmacist before using abronchodilator. Call a physician immediately if any ofthese signs of an allergic reaction to sulfite occur:
• bluish coloration of the skin
• flushed or red face or skin

• faintness• severe dizziness
• increased wheezing or other breathing problems
• swelling of the face, lips, or eyelids
taking certain other medicines can have problems if theyuse bronchodilators. Before using these drugs, be sure tolet the physician know about any of these conditions:

to any bronchodilator or an inhaled form of any otherdrug in the past should let his or her physician knowbefore taking the drugs again. The physician should alsobe told about any allergies to foods, dyes, preservatives,
Patients who are allergic to soybeans, soy lecithin,
peanuts, or drugs based on atropine should not use thebronchodilator ipratropium (Atrovent).
PREGNANCY. In studies of laboratory animals, some

bronchodilators cause birth defects or miscarriage
when the animals are given doses many times the usualhuman dose. Whether these drugs cause such problemsin humans in unknown. Any woman who is pregnant orplans to become pregnant should check with her physi-cian before using a bronchodilator.
BREASTFEEDING. Some bronchodilators pass into
breast milk. Breastfeeding mothers should check withtheir physicians before using bronchodilators.

OTHER MEDICAL CONDITIONS. Before using bron-
chodilators, people with any of these medical problemsshould make sure their physicians are aware of their con-ditions:
• glaucoma• brain damage
GALE ENCYCLOPEDIA OF MEDICINE 2 601BronchodilatorsGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 601

• convulsions (seizures)—recently or anytime in the past
• mental illness
• parkinson’s disease• diabetes• heart or blood vessel diseases
• rapid or irregular heartbeat
• high blood pressure• overactive thyroid• enlarged prostate
• obstruction of the neck of the bladder
USE OF CERTAIN MEDICINES. Using bronchodilators
Some patients have a dry or irritated throat or a dry

mouth after using bronchodilators. To help prevent these
problems, gargle and rinse the mouth or take a sip ofwater after each dose.
The most common side effects are nervousness or
restlessness and trembling. These problems usually goaway as the body adjusts to the drug and do not requiremedical treatment. Less common side effects, such asbad taste in the mouth, coughing, dizziness or lighthead-KEY TERMS
Anti-inflammatory —Medicine used to relieve

swelling, pain, and other symptoms of inflamma-tion.
the lungs.

medicine into a fine spray that can be inhaled.
Sulfite —A type of preservative that causes allergic
reactions in some people.edness, drowsiness, headache , sweating, fast or pound-
ing heartbeat, muscle cramps or twitches, nausea, vomit-ing, diarrhea , sleep problems and weakness also may
occur and do not need medical attention unless they donot go away or they interfere with normal activities.

• chest pain or discomfort
• irregular or fluttery heartbeat
• unusual bruising
• hives or rash
• swelling
• wheezing or other breathing problems
• numbness in the hands or feet

unusual symptoms after using a bronchodilator shouldget in touch with his or her physician.
Bronchodilators may interact with a number of other
medicines. When this happens, the effects of one or both ofthe drugs may change or the risk of side effects may begreater. Anyone who takes these drugs should let the physi-cian know all other medicines he or she is taking. Amongthe drugs that may interact with bronchodilators are:

as phenelzine (Nardil) and tranylcypromine (Parnate),used to treat depression
• other bronchodilators
• beta blockers such as propranolol (Inderal) and atenolol
(Tenormin), used to control high blood pressure
• digitalis medicines, used to treat heart conditions, such
as digoxin (Lanoxin)
• drugs, such as certain diuretics (water pills), that lower

potassium levels
• ergoloid mesylates such as Hydergine, used to treat
symptoms of Alzheimer’s disease or multiple small
stokes
• ergotamine (Cafergot, Ergostat, and other brands), used
to treat migraine and cluster headaches
• the antidepressant maprotiline (Ludiomil)
GALE ENCYCLOPEDIA OF MEDICINE 2 602BronchodilatorsGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 602

interact with bronchodilators. Be sure to check with aphysician or pharmacist before combining bronchodila-tors with any other prescription or nonprescription (over-the-counter) medicine.
Resources
Fackelmann, Kathy A. “Anti-inflammatory Drugs May Quell
Asthma.” Science News (26 Sept. 1992): 197.

American Academy of Allergy, Asthma, and Immunology. 611
East Wells St., Milwaukee, WI 53202. (800) 822-2762.<http://www.aaaai.org>.
Bronchoscopy
Bronchoscopy is a procedure in which a cylindrical

fiberoptic scope is inserted into the airways. This scopecontains a viewing device that allows the visual examina-tion of the lower airways.
Purpose
During a bronchoscopy, a physician can visually

examine the lower airways, including the larynx, trachea,bronchi, and bronchioles. The procedure is used to exam-ine the mucosal surface of the airways for abnormalitiesthat might be associated with a variety of lung diseases.Its use includes the visualization of airway obstructionssuch as a tumor, or the collection of specimens for thediagnosis of cancer originating in the bronchi of the

lungs (bronchogenic cancer). It can also be used to collectspecimens for culture to diagnose infectious diseases suchas tuberculosis . The type of specimens collected can

include sputum (composed of saliva and discharges fromthe respiratory passages), tissue samples from the bronchior bronchioles, or cells collected from washing the liningof the bronchi or bronchioles. The instrument used inbronchoscopy, a bronchoscope, is a slender cylindricalinstrument containing a light and an eyepiece. There aretwo types of bronchoscopes, a rigid tube that is some-times referred to as an open-tube or ventilating broncho-scope, and a more flexible fiberoptic tube. This tube

and a more flexible fiberoptic tube. This tube con-tains four smaller passages—two for light to passthrough, one for seeing through and one that can accom-modate medical instruments that may be used for biopsyor suctioning, or that medication can be passed through.

Bronchoscopy may be used for the following pur-
poses:
• to diagnose cancer, tuberculosis, lung infection, or
other lung disease
• to examine an inherited deformity of the lungs
• to remove a foreign body in the lungs, such as a mucus
plug, tumor, or excessive secretions
• to remove tissue samples, also known as biopsy, to test
for cancer cells, help with staging the advancement ofthe lung cancer, or to treat a tumor with laser therapy
• to allow examination of a suspected tumor, obstruction,

secretion, bleeding, or foreign body in the airways
• to determine the cause of a persistent cough ,wheezing ,
or a cough that includes blood in the sputum
• to evaluate the effectiveness of lung cancer treatments
Patients not breathing adequately on their own due
to severe respiratory failure may require mechanical

ventilation prior to bronchoscopy. It may not be appro-priate to perform bronchoscopy on patients with anunstable heart condition. All patients must be constantlymonitored while undergoing a bronchoscopy so that anyabnormal reactions can be dealt with immediately.
There are two types of bronchoscopes, a rigid tube
and a fiberoptic tube. Because of its flexibility, the fiberop-
GALE ENCYCLOPEDIA OF MEDICINE 2 603Bronchoscopy
Instruments used in bronchoscopy procedures. (Custom

Medical Stock Photo. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 603

tic tube is usually preferred. However, if the purpose of the
procedure is to remove a foreign body caught in the wind-pipe or lungs of a child, the more rigid tube must be usedbecause of its larger size. The patient will either lie face-upon his/her back or sit upright in a chair. Medication todecrease secretions, lessen anxiety , and relax the patient

are often given prior to the procedure. While breathingthrough the nose, anesthesia is sprayed into the mouth ornose to numb it. It will take one to two minutes for theanesthesia to take effect. Once this happens, the broncho-scope will be put into the patient’s mouth or nose andmoved down into the throat. While the bronchoscope ismoving down the throat, additional anesthesia is put intothe bronchoscope to numb the lower parts of the airways.Using the eyepiece, the physician then observes the

the eyepiece, the physician then observes the tra-chea and bronchi, and the mucosal lining of these passage-ways, looking for any abnormalities that may be present.

If the purpose of the bronchoscopy is to take tissue
samples or biopsy, forceps or a bronchial brush are usedto obtain cells. If the purpose is to identify an infectiousagent, a bronchoalveolar lavage (BAL) can be used togather fluid for culture purposes. Also, if any foreignmatter is found in the airways, it can be removed.
Another procedure using bronchoscopy is called flu-
orescence bronchoscopy. This can be used to detect pre-cancerous cells present in the airways. By using a fluo-

rescent light in the bronchoscope, precancerous tissuewill appear dark red, while healthy tissue will appeargreen. This technique can help detect lung cancer at anearly stage, so that treatment can be started early.
Alternative procedures
Depending upon the purpose of the bronchoscopy,

alternatives might include a computed tomography scan(CT) or no procedure at all. Bronchoscopy is often per-formed to investigate an abnormality that shows up on achest x ray or CT scan. If the purpose is to obtain biopsy
specimens, one option is to perform surgery, which carriesgreater risks. Another option is percutaneous (through theskin) biopsy guided by computed tomography.
The doctor should be informed of any allergies and

all the medications that the patient is currently taking. Thedoctor may instruct the patient not to take medicationslike aspirin or anti-inflammatory drugs, which interfere

with clotting, for a period of time prior to the procedure.The patient needs to fast for 6 to 12 hours prior to the pro-cedure and refrain from drinking any liquids the day ofthe procedure. The bronchoscopy takes about 45 to 60minutes, with results usually available in one day. Prior tothe bronchoscopy, several tests may be done, including achest x ray and blood work. Sometimes a bronchoscopy isdone under general anesthesia. Patients usually have anintravenous (IV) line in the arm. Most likely,

anintravenous (IV) line in the arm. Most likely, the proce-dure will be done under local anesthesia, which is sprayedinto the nose or mouth. This is necessary to decrease thegag reflex. A sedative may also be used to help the patientrelax. It is important that the patient understands that at notime will the airway be blocked and that oxygen can besupplied through the bronchoscope. A signed consentform is necessary for this procedure.

for vital signs such as heart rate, blood pressure, andbreathing, while resting in bed. Sometimes patients havean abnormal reaction to anesthesia. All saliva should bespit into a basin so that it can be examined for the pres-ence of blood. If a biopsy was taken, the patient shouldnot cough or clear the throat as this might dislodge anyblood clot that has formed and cause bleeding. No food ordrink should be consumed for about two hours after theprocedure or until the anesthesia wears off. Diet

or until the anesthesia wears off. Diet is gradu-ally progressed from ice chips and clear liquids to thepatient’s regular diet. There will also be a temporary sore

throat and hoarseness that may last for a few days.
GALE ENCYCLOPEDIA OF MEDICINE 2 604BronchoscopyBronchoscope
Bronchoscopy is a procedure in which a hollow, flexible
tube is inserted into the airways, allowing the physician tovisually examine the lower airways, including the larynx, tra-chea, bronchi, and bronchioles. It can also be used to col-lect specimens for bacteriological culture to diagnose infec-tious diseases such as tuberculosis. (Illustration by Electronic

Illustrators Group.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 604

Risks
Minor side effects arise from the bronchoscope caus-
ing abrasion of the lining of the airways. This results insome swelling and inflammation, as well as hoarsenesscaused from abrading the vocal cords. If this abrasion ismore serious, it can lead to respiratory difficulty or bleed-ing of the airway lining. A more serious risk involved inhaving a bronchoscopy performed is the occurrence of apneumothorax , due to puncturing of the lungs, which

allows air to escape into the space between the lung andthe chest wall. These risks are greater with the use of arigid bronchoscope than with a fiberoptic bronchoscope.If a rigid tube is used, there is also a risk of chipped teeth.
Normal tracheal appearance consists of smooth
muscle with C-shaped rings of cartilage at regular inter-vals. The trachea and the bronchi are lined with a mucousmembrane.
Abnormal bronchoscopy findings may involve

abnormalities of the bronchial wall such as inflamma-tion, swelling, ulceration, or anatomical abnormalities.The bronchoscopy may also reveal the presence ofabnormal substances in the trachea and bronchi. If sam-ples are taken, the results could indicate cancer, disease-causing agents or other lung disease. Other abnormalitiesinclude constriction or narrowing (stenosis), compres-sion, dilation of vessels, or abnormal branching of thebronchi. Abnormal substances that might be found in theairways

substances that might be found in theairways include blood, secretions, or mucous plugs. Anyabnormalities are discussed with the patient.KEY TERMS

Anesthesia —A drug used to loss of sensation. It is
used to lessen the pain of surgery and medicalprocedures.
Bronchi —The network of tubular passages that
carry air to the lungs and allow air to be expelledfrom the lungs.
Bronchioles —Small airways extending from the
bronchi into the lobes of the lungs.
Bronchoalveolar lavage —Washing cells from the
air sacs at the end of the bronchioles.
Trachea —The windpipe.Resources
BOOKS
Bone, Roger C., ed. Pulmonary & Critical Care Medicine. St.

Louis, MO: Mosby-Year Book, Inc., 1998.
Loeb, S., ed. Illustrated Guide to Diagnostic Tests. Spring-
house, PA: Springhouse Corporation, 1994.
“Fluorescence Bronchoscopy Technology Used in Early
Detection.” Cancer Weekly Plus (Feb 3, 1997): 17.
American College of Chest Physicians. 3300 Dundee Rd., North-
brook, IL 60062. (800) 343-2227. <www.chestnet.org>.
Cindy L. Jones, Ph.D.
Brucellosis
Brucellosis is a bacterial disease caused by members

of the Brucella genus that can infect humans but primari-
ly infects livestock. Symptoms of the disease includeintermittent fever , sweating, chills, aches, and mental
depression. The disease can become chronic and recur,particularly if untreated.
Also known as undulant fever, Malta fever, Gibraltar

fever, Bang’s disease, or Mediterranean fever, brucellosisis most likely to occur among those individuals who reg-ularly work with livestock. The disease originated indomestic livestock but was passed on to wild animalspecies, including the elk and buffalo of the westernUnited States. In humans, brucellosis continues to bespread via unpasteurized milk obtained from infectedcows or through contact with the discharges of cattle andgoats during miscarriage . In areas of the world where

milk is not pasteurized, for example in Latin Americaand the Mediterranean, the disease is still contracted byingesting unpasteurized dairy products. However, in theUnited States, the widespread pasteurization of milk andnearly complete eradication of the infection from cattlehas reduced the number of human cases from 6,500 in1940 to about 70 in 1994.
The disease is caused by several different species of
parasitic bacteria of the genus Brucella. B. abortus is

found in cattle and can cause cows to abort their fetuses.
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B. suis is most often found in hogs and is more deadly
when contracted by humans than the organism found incattle. B. melitensis is found in goats and sheep and caus-
es the most severe illness in humans. B. rangiferi infects
reindeer and caribou, and B. canis is found in dogs.
A human contracts the disease by coming into con-

tact with an infected animal and either allowing the bac-teria to enter a cut, breathing in the bacteria, or by con-suming unpasteurized milk or fresh goat cheese obtainedfrom a contaminated animal. In the United States, thedisease is primarily confined to slaughterhouse workers.
Scientists do not agree about whether brucellosis

can be transmitted from one person to another, althoughsome people have been infected from a tainted bloodtransfusion or bone marrow transplant. Newborn babies
have also contracted the illness from their mothers dur-ing birth. Currently, it is believed that brucellosis canalso be transmitted sexually.
The disease is not usually fatal, but the intermittent

fevers (a source of its nickname, “undulant fever”) can beexhausting. Symptoms usually appear between five daysand a month after exposure and begin with a single boutof high fever accompanied by shivering, aching, anddrenching sweats that last for a few days. Other symp-toms may include headache , poor appetite, backache,
weakness, and depression. Mental depression can be sosevere that the patient may become suicidal.
In rare, untreated cases, the disease can become so

severe that it leads to fatal complications, such as pneu-
monia or bacterial meningitis . B. melitensis can cause
miscarriages, especially during the first three months ofpregnancy . The condition can also occur in a chronic
form, in which symptoms recur over a period of monthsor years.KEY TERMS

Parasite —An organism living in or on, and obtain-
ing nourishment from, another organism.
Pasteurization —The process of applying heat,
usually to milk or cheese, for the purpose ofkilling, or retarding the development of, pathogen-ic bacteria.Diagnosis
Brucellosis is usually diagnosed by detecting one or
more Brucella species in blood or urine samples. The

bacteria may be positively identified using biochemicalmethods or using a technique whereby, if present in thesample, the brucellosis bacteria are made to fluoresce.Brucellosis may also be diagnosed by culturing and iso-lating the bacteria from one of the above samples. Bloodsamples will also indicate elevated antibody levels orincreased amounts of a protein produced directly inresponse to infection with brucellosis bacteria.
Treatment
Prolonged treatment with antibiotics , including

tetracyclines (with streptomycin), co-trimoxazole, and
sulfonamides , is effective. Bed rest is also imperative. In
the chronic form of brucellosis, the symptoms may recur,requiring a second course of treatment.
Prognosis
Early diagnosis and prompt treatment is essential to
prevent chronic infection. Untreated, the disease may lingerfor years, but it is rarely fatal. Relapses may also occur.

There is no human vaccine for brucellosis, but
humans can be protected by controlling the disease inlivestock. After checking to make sure an animal is notalready infected, and destroying those that are, all live-stock should be immunized. Butchers and those whowork in slaughterhouses should wear protective glassesand clothing, and protect broken skin from infection.
Some experts suggest that a person with the disease

refrain from engaging in unprotected sex until free of thedisease. The sexual partners of an infected person shouldalso be closely monitored for signs of infection.
Resources
BOOKS
Adams, L. Garry, ed. Advances in Brucellosis Research. Texas
A & M University Press, 1990.
Madkour, M. Monir. Brucellosis. Butterworth-Heinemann,
1989.
Nielsen, Klaus, and Robert J. Duncan. Animal Brucellosis.

CRC Press, 1990.
Wilks, David, Mark Farrington, and David Rubenstein. The
Infectious Diseases Manual. Oxford, England: Blackwell
Scientific, Inc., 1995.
GALE ENCYCLOPEDIA OF MEDICINE 2 606BrucellosisGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 606

Ruben, Bruce, et al. “Person-to-Person Transmission of Bru-
cella melitensis.” The Lancet 337 (5 Jan. 1991): 8732.

OTHER
Brugian filariasis seeElephantiasis
Bruises
Bruises, or ecchymoses, are a discoloration and ten-

derness of the skin or mucous membranes due to theleakage of blood from an injured blood vessel into thetissues. Pupura refers to bruising as the result of a diseasecondition. A very small bruise is called a petechia. Theseoften appear as many tiny red dots clustered together,and could indicate a serious problem.
Bruises change colors over time in a predictable pat-

tern, so that it is possible to estimate when an injuryoccurred by the color of the bruise. Initially, a bruise willbe reddish, the color of the blood under the skin. Afterone to two days, the red blood cells begin to break down,and the bruise will darken to a blue or purplish color.This fades to green at about day six. Around the eighth orninth day, the skin over the bruised area will have abrown or yellowish appearance, and it will graduallydiminish back to its normal color.

Long periods of standing will cause the blood that
collects in a bruise to seep through the tissues. Bruisesare actually made of little pools of blood, so the blood inone place may flow downhill after awhile and appear inanother. For instance, bruising in the back of theabdomen may eventually appear in the groin; bruising inthe thigh or the knee will work its way down to the ankle.
Healthy people may develop bruises from any injury

that doesn’t break through the skin. Vigorous exercise
may also cause bruises due to bringing about small tearsin blood vessels walls. In a condition known as purpurasimplex, there is a tendency to bruise easily due to anincreased fragility of the blood vessels. Bruises alsodevelop easily in the elderly, because the skin and bloodvessels have a tendency to become thinner and morefragile with aging , and there is an increased use of med-

ications that interfere with the blood clotting system. Inthe condition known as purpura senilis, the elderly devel-op bruises from minimal contact that may take up to sev-eral months to completely heal.
The use of nonsteroidal anti-inflammatories such as
ibuprofen (Advil) and naproxen (Aleve) may lead toincreased bruising. Aspirin , antidepressants, asthma

medications, and cortisone medications also have thiseffect. The anti-clotting medications also known as bloodthinners, especially the drug Warfarin (Coumadin), maybe the cause of particularly severe bruising.
Sometimes bruises are connected with more serious

illnesses. There are a number of diseases that causeexcessive bleeding or bleeding from injuries too slight tohave consequences in healthy people. An abnormal ten-dency to bleed may be due to hereditary bleeding disor-ders, certain prescription medications, diseases of the
GALE ENCYCLOPEDIA OF MEDICINE 2 607Bruises
A close-up view of woman’s bruised left eye. (Custom Med-

ical Stock Photo. Reproduced by permission.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 607

blood such as leukemia, and diseases that increase the
fragility of blood vessels. If there are large areas of bruis-ing or bruises develop very easily, this may herald aproblem. Other causes that should be ruled out includeliver disease, alcoholism , drug addiction , and acquired
immune deficiency syndrome ( AIDS ). Bruising that

occurs around the navel may indicate dangerous internalbleeding; bruising behind the ear, called Battle’s sign,may be due to a skull fracture; and raised bruises maypoint to autoimmune disease.
Diagnosis
Bruising is usually a minor problem, which does not

require a medical diagnosis. However, faced with exten-sive bruising, bruising with no apparent cause, or bruis-ing in certain locations, a physician will pursue an evalu-ation that will include a number of blood tests. If the areaof the bruise becomes hard, an x ray may be required.
Treatment
A bruise by itself needs no medical treatment. It is

often recommended that ice packs be applied on and offduring the first 24 hours of injury to reduce the bruising.After that, heat, especially moist heat, is recommendedto increase the circulation and the healing of the injuredtissues. Rest, elevation of the effected part, and compres-sion with a bandage will also retard the accumulation ofblood. Rarely, if a bruise is so large that the body cannotcompletely absorb it or if the site becomes infected, itmay have to be surgically removed.

Several types of topical applications are usually rec-
ommend to speed healing and to reduce the pain associ-
ated with bruises. Vitamin K cream can be applied direct-ly to the site of injury. Astringent herbs such as witchhazel, Hamamelis virginiana , can be used. This will
tighten the tissues and therefore diminish the bruising.The homeopathic remedy, Arnica montana , can be
applied as a cream or gel to unbroken skin.
Oral homeopathic remedies may reduce bruising,

pain, and swelling as well. Arnica montana , at 30 ml (1
oz), taken one to two times per day is highly recom-mended. For ledum, 30 ml (1 oz) one to two times perday is also useful.
Prognosis
The blood under the skin which causes the discol-
oration of bruising should be totally reabsorbed by thebody in three weeks or less. At that time, the skin colorshould completely return to normal.Sometimes, a bruise may become solid and increase

in size instead of dissolving. This may indicate bloodtrapped in the tissues, which may be need to be drained.This is referred to as a hematoma. Less commonly, thebody may develop calcium deposits at the injury site in aprocess called heterotopic ossification.
Vitamin K promotes normal clotting in the blood,

and therefore may help reduce the tendency to bruiseeasily. Green leafy vegetables, alfalfa, broccoli, seaweed,and fish liver oils are dietary sources of vitamin K. Othergood foods to eat would be those containingbioflavonoids, such as reddish-blue berries. These canassist in strengthening the connective tissue, which willdecrease the spread of blood and bruising. Zinc and vita-min C supplements are also recommended for this.
Resources
BOOKS

Resources
BOOKS
Editors of Prevention Magazine Health Books, eds. The Doc-
tors Book of Home Remedies. Prevention Health Books,
2000.
Williams,William J. Williams’ Hematology. New York:
McGraw-Hill, 1995.
Feinstein, Alice, ed. Prevention’s Healing With Vitamins: The
Most Effective Vitamin and Mineral Treatments for Every-day Health Problems and Serious Disease. Prevention
Health Books, 1998.
Bruton’s agammaglobulinemia seeX-linked
agammaglobulinemia
Bruxism

Bruxism
Bruxism is the habit of clenching and grinding the
teeth. It most often occurs at night during sleep, but itmay also occur during the day. It is an unconsciousbehavior, perhaps performed to release anxiety , aggres-
sion, or anger.
Bruxism is one of the oldest disorders known, and
approximately one in four adults experiences it. Most peo-ple are not aware of it before their teeth have been damaged.

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While bruxism is typically associated with stress ,i t
may also be triggered by abnormal occlusion (the waythe upper and lower teeth fit together), or crooked ormissing teeth.
Symptoms of bruxism include: dull headaches; sore
and tired facial muscles; earaches; sensitive teeth; andlocking, popping, and clicking of the jaw.
During a dental examination, a dentist may recognize

damage resulting from bruxism, including: enamel lossfrom the chewing surfaces of teeth; flattened tooth surfaces;loosened teeth; and fractured teeth and fillings. Left untreat-ed, bruxism may lead to tooth loss and jaw dysfunction.
Diagnosis
Medical and dental histories and examinations are
necessary to differentiate bruxism from other conditionsthat may cause similar pain, such as ear infections, dental

infections, and temporomandibular joint (TMJ) dysfunc-tion. However, uncommonly worn-down teeth stronglysuggest a diagnosis of bruxism.
Treatment
To prevent further damage to the teeth, bruxism is
treated by placing a removable, custom-fitted plasticappliance called a night guard between the upper andlower teeth. Although the clenching and grinding behav-ior may continue, the teeth wear away the plastic insteadof each other.
In some cases, abnormal occlusion may be adjusted

and high spots removed so that the teeth fit together in amore comfortable position. Missing teeth may bereplaced and crooked teeth may be straightened withorthodontic treatment to eliminate possible underlyingcauses of bruxism. In cases where jaw muscles are verytight, a dentist may prescribe muscle relaxants .
Stress management and behavior modification tech-

niques may be useful to break the habit of clenching andteeth grinding. Tight jaw muscles may be relaxed byapplying warm compresses to the sides of the face.Herbal muscle relaxants also can be helpful. Massage
therapy and deep tissue realignment, including rolfing ,
can assist in releasing the clenching pattern. This is amore permanent alternative treatment for bruxism.
Prognosis
Bruxism may cause permanent damage to teeth and

chronic jaw pain unless properly diagnosed and promptlyKEY TERMS
Enamel —The hard outermost surface of a tooth.
High spot —An area of a tooth or restoration that
feels abnormal or uncomfortable because it hits itsopposing tooth before other teeth meet.
Night guard —A removable, custom-fitted plastic
appliance that fits between the upper and lowerteeth to prevent them from grinding against eachother.
Occlusion —The way upper and lower teeth fit

together during biting and chewing.
Rolfing —Based on the belief that proper align-
ment of various parts of the body is necessary forphysical and mental health, rolfing uses deep tis-sue massage and movement exercises in anattempt to bring the body into correct alignment.
Temporomandibular joint (TMJ) —The jaw joint
formed by the mandible (lower jaw bone) movingagainst the temporal bone of the skull.

treated. The behavior may be eliminated if its underlying
causes are found and addressed.
Increased awareness in patients prone to anxiety,
aggression, or anger may prevent the habit of bruxismfrom developing.
Resources
Academy of General Dentistry. Suite 1200, 211 East Chicago
Ave., Chicago, IL 60611.(312) 440-4300. <http://www.agd.org>.

Bubonic plague seePlague
Budd-Chiari syndrome
Budd-Chiari syndrome is a rare problem that results
from blood clotting in the veins flowing out of the liver
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(hepatic veins). The high pressure of blood in these veins
leads to an enlarged liver, and to an accumulation of fluidin the abdomen, called ascites .
The liver, the largest internal organ in the human

body, is responsible for many vital physiologic process-es. Blood flow through the liver nourishes the liver, car-ries in substances that the liver will process, and carriesaway substances that the liver has produced. When bloodcannot flow out freely from the liver, blood pressure risesin the veins of the liver, leading to blood clots within theliver. Also, some of the blood plasma can leak throughthe walls of the veins and accumulate within theabdomen (ascites).

The major symptoms include pain in the upper
right-hand portion of the abdomen and a build-up of fluidin the abdomen. In the United States, blood disorders arethe most common causes. Among these disorders arepolycythemia rubra vera (an increase in the number ofred blood cells), and sickle cell disease . In parts of the
world where liver cancer is common, a form of liver
cancer is the most frequent cause.
Other causes sometimes include:

• certain infections• use of oral contraceptives
• body changes in pregnancy and the postpartum period
• phlebitis (inflammation of a vein)• injury to the abdomen• membranous webs (especially in Asia)KEY TERMS
Ascites —Accumulation of fluid in the abdomen.
Biopsy —Surgical removal of a tiny bit of tissue for
examination under the microscope.
Catheter —A tubular surgical instrument.
Phlebitis —Inflammation of a vein.
Polycythemia rubra vera —An excess number of

red blood cells in the blood.
Sickle cell disease —An inherited disease in which
red blood cells take an unusual shape, leading tocirculation problems.Diagnosis
Diagnosis of Budd-Chiari syndrome can be made by
an internist (a specialist in diseases of the internalorgans), a gastroenterologist (a specialist in the diseasesof the digestive system), or a general surgeon. On physi-
cal examination , the doctor will note that the liver is

larger than normal. Often an ultrasound scan of the liverwill show abnormalities in the size of the liver, an abnor-mal pattern of the veins in the liver, and other abnormali-ties. A CT scan will often show similar abnormalities.
Once these abnormalities are confirmed, the key test

is called hepatic vein catheterization. In this test, a narrowtube is snaked through the body until it reaches the hepat-ic veins. An instrument at the tip of the catheter can mea-sure the pressure within each segment of the hepatic vein.
In some cases, a tiny amount of radioactive material is
injected into a patient, and then an abnormal pattern ofradioactivity in the liver can be revealed. In other cases, aliver biopsy enables a physician to examine cells from the

liver itself. Cells damaged by Budd-Chiari syndrome have acharacteristic appearance easily identifiable to a physician.
Treatment
Surgery
Most patients with Budd-Chiari syndrome must

have surgery. A surgeon will re-route blood flow aroundthe clotted hepatic vein into a large vein called the venacava. The exact technique will depend on the specificlocation of the clots and other factors. In certain patients,other surgical techniques may be used. For patients whootherwise would have less than six months to live, liver
transplantation is sometimes performed.
In a few patients, a “balloon catheter” can open the

blocked blood vessels, without the need for major surgery.
Drugs
Sometimes, anti-clotting drugs such as urokinase
can be used for patients with a sudden onset of clotting inthe veins of the liver. These drugs do not seem to workwhen the clots have become established.
Prognosis
If surgery is done before permanent liver damage sets

in, long-term survival is possible. In these cases, damagedliver cells can actually recover. If patients are already verysick with liver disease, the surgery may not be as helpful.
The best approach to prevention is to carefully control
the blood disorders that can lead to Budd-Chiari syndrome.
GALE ENCYCLOPEDIA OF MEDICINE 2 610Budd-Chiari syndromeGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 610

Resources
BOOKS
Gadacz, Thomas R., and John L. Cameron. “Budd-Chiari Syn-
drome and Surgery of the Hepatic Vasculature.” In Shack-
elford’s Surgery of the Alimentary Tract. 3rd ed. V ol. 3.
Ed. J.G. Turcotte. Philadelphia: W. B. Saunders Co., 1991.
Buerger’s disease
Buerger’s disease is an inflammation of the arteries,

veins, and nerves in the legs, principally, leading torestricted blood flow. Left untreated, Buerger’s diseasecan lead to gangrene of the affected areas. Buerger’s dis-
ease is also known as thromboangitis obliterans.
The exact cause of Buerger’s disease is not known. It

is seen most often in young to middle-aged men (ages20-40) who are heavy smokers of cigarettes. Cases ofthis disease in non-smokers are very rare, hence, ciga-rette smoking is considered a causative factor. Approxi-

mately 40% of the patients have a history of inflamma-tion of a vein (phlebitis), which may play a role in thedevelopment of Buerger’s disease. The disease is mainlyseen in the legs of affected persons, but may also appearin their arms. Early symptoms include decrease in theblood supply (arterial ischemia ) and superficial (near the
skin surface) phlebitis. The main symptom is pain in the

affected areas. Onset of the disease is gradual and firstoccurs in the feet or hands. Inflammation occurs in smalland medium-sized arteries and veins near the surface ofthe limb. In advanced cases, blood vessels in other partsof the body may be affected. There is a progressivedecrease in the blood flow to the affected areas. Thepulse in arteries of the feet is weak or undetectable. Thelack of blood flow can lead to gangrene, which is decayof tissue due to restricted blood supply. A cold

tissue due to restricted blood supply. A cold sensitivityin the hands, similar to that seen in Raynaud’s disease ,

can develop. In this case, the hands turn color—white,blue, and then red—when exposed to the cold.
Diagnosis
Diagnosis is usually made from the clinical symp-
toms. Patients frequently complain of numbness, tin-gling, or burning sensations in the affected area beforeevidence of vascular inflammation becomes apparent.KEY TERMS
Gangrene —A decay of the tissue in a part of the
body that experiences restricted blood flow.
Inflammation —A local reaction to irritation, injury,

or infection characterized by pain, swelling, red-ness, and occasional loss of function.
Ischemia —A decrease in the blood supply to an
area of the body caused by obstruction or con-striction of blood vessels.
Treatment
There is no effective medication or surgery for this
disease. Patients must stop smoking to halt further devel-opment of the symptoms. Vasodilators , drugs that

increase the diameter of the blood vessels, can be admin-istered, but may not be effective. Exposure of affectedareas to heat or cold should be avoided. Trauma to thefeet and other affected areas should be avoided and infec-tions must be treated promptly.
Prognosis
The disease is progressive in patients who do not
stop smoking. Areas with gangrene must be removed sur-gically.
Smoking is the only known causative agent for this
disease and should be avoided.
Resources
BOOKS

Resources
BOOKS
Berkow, R., ed. The Merck Manual. 17th ed. Rahway, NJ:
Merck and Co., 1997.
Bulging eyes seeExophthalmos
Bulimia nervosa
Bulimia nervosa is a serious and sometimes life-
threatening eating disorder affecting mainly young
GALE ENCYCLOPEDIA OF MEDICINE 2 611Bulimia nervosaGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 611

women. People with bulimia, known as bulimics, consume
large amounts of food (binge) and then try to rid them-selves of the food and calories (purge) by fasting , exces-
sive exercise , vomiting, or using laxatives . The behavior
often serves to reduce stress and relieve anxiety . Because
bulimia results from an excessive concern with weightcontrol and self-image, and is often accompanied bydepression, it is also considered a psychiatric illness.

Bulimia nervosa is a serious health problem for over
two million adolescent girls and young women in theUnited States. The bingeing and purging activity associ-ated with this disorder can cause severe damage, evendeath , although the risk of death is not as high as for
anorexia nervosa , an eating disorder that leads to exces-
sive weight loss.
Binge eating may in rare instances cause the stom-
ach to rupture. In the case of purging, heart failure can

result due to loss of vital minerals such as potassium.
V omiting causes other serious problems, including acid-related scarring of the fingers (if used to induce vomit-ing) and damage to tooth enamel. In addition, the tubethat brings food from the mouth to the stomach (theesophagus) often becomes inflamed and salivary glandscan become swollen. Irregular menstrual periods can alsoresult, and interest in sex may diminish.
Most bulimics find it difficult to stop their behavior

without professional help. Many typically recognize thatthe behavior is not normal, but feel out of control. Somebulimics struggle with other compulsive, risky behaviorssuch as drug and alcohol abuse. Many also suffer fromother psychiatric illnesses, including clinical depression,anxiety, and obsessive-compulsive disorder (OCD).
Most bulimics are females in their teens or early 20s.

Males account for only 5-10% of all cases. People of allraces develop the disorder, but most of those diagnosedare white.
Bulimic behavior is often carried out in secrecy,
accompanied by feelings of guilt or shame. Outwardly,many people with bulimia appear healthy and successful,while inside they have feelings of helplessness and lowself-esteem.
Causes
The cause of bulimia is unknown. Researchers

believe that it may be caused by a combination of geneticand environmental factors. Bulimia tends to run in fami-lies. Research shows that certain brain chemicals, knownas neurotransmitters, may function abnormally in acutelyill bulimia patients. Scientists also believe there may be a

link between bulimia and other psychiatric problems,such as depression and OCD. Environmental influencesinclude participation in work or sports that emphasizethinness, such as modeling, dancing, or gymnastics. Fam-ily pressures also may play a role. One study found thatmothers who are extremely concerned about their daugh-ters’ physical attractiveness and weight may help to causebulimia. In addition, girls with eating disorders tend tohave fathers and brothers who criticize their weight.

Symptoms
According to the American Anorexia/Bulimia Asso-
ciation, Inc., warning signs of bulimia include:
• eating large amounts of food uncontrollably (bingeing)
• vomiting, abusing laxatives or diuretics , or engaging in
fasting, dieting, or vigorous exercise (purging)
• preoccupation with body weight• using the bathroom frequently after meals• depression or mood swings• irregular menstrual periods
• onset of dental problems, swollen cheeks or glands,
heartburn or bloating
Diagnosis

Diagnosis
Bulimia is treated most successfully when diag-
nosed early. But because the bulimic may deny there is aproblem, getting medical help is often delayed. A com-plete physical examination in order to rule out other ill-
nesses is the first step to diagnosis.
According to the American Psychiatric Association,
a diagnosis of bulimia requires that a person have all ofthe following symptoms:
• recurrent episodes of binge eating (minimum average

of two binge-eating episodes a week for at least threemonths)
• a feeling of lack of control over eating during the
binges
• regular use of one or more of the following to prevent
weight gain: self-induced vomiting, use of laxatives ordiuretics, strict dieting or fasting, or vigorous exercise
• persistent over-concern with body shape and weight
Treatment
Early treatment is important otherwise bulimia may

become chronic, with serious health consequences. Acomprehensive treatment plan is called for in order toaddress the complex interaction of physical and psycho-
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logical problems in bulimia. A combination of drug and
behavioral therapies is commonly used.
Behavioral approaches include individual psychother-
apy, group therapy , and family therapy . Cognitive-
behavioral therapy , which teaches patients how to change
abnormal thoughts and behavior, is also used. Nutrition
counseling and self-help groups are often helpful.
Antidepressants commonly used to treat bulimia

include desipramine (Norpramin), imipramine (Tofranil),and fluoxetine (Prozac). These medications also maytreat any co-existing depression.
In addition to professional treatment, family support

plays an important role in helping the bulimic person.Encouragement and caring can provide the support neededto convince the sick person to get help, stay with treatment,or try again after a failure. Family members can help locateresources, such as eating disorder clinics in local hospitalsor treatment programs in colleges designed for students.
Light therapy—exposure to bright, artificial light—

may be useful in reducing bulimic episodes, especiallyduring the dark winter months. Some feel that massagemay prove helpful, putting people in touch with the reali-ty of their own bodies and correcting misconceptions ofbody image. Hypnotherapy may help resolve uncon-
scious issues that contribute to bulimic behavior.
Prognosis
Bulimia may become chronic and lead to serious
health problems, including seizures, irregular heartbeat,and thin bones. In rare cases, it may be fatal.

Timely therapy and medication can effectively man-
age the disorder and help the bulimic look forward to anormal, productive, and fulfilling life.
There is no known method to prevent bulimia.
Resources
BOOKS
Cassell, Dana K. The Encyclopedia of Obesity and Eating Dis-
orders. New York: Facts on File, Inc., 1994.
Jablow, Martha M. A Parent’s Guide to Eating Disorders and
Obesity. New York: Dell Publishing, 1992.
Kubersky, Rachel. Everything You Need to Know about Eating

Disorders. New York: The Rosen Publishing Group, Inc.,
1992.
Berg, Frances M. “Eating Disorders Affect Both the Mind and
Body.” Healthy Weight Journal 9, no. 2 (1995): 27-31.KEY TERMS
Binge —To consume large amounts of food uncon-
trollably within a short time period.
Diuretic —A drug that promotes the formation and
excretion of urine.
Neurotransmitters —Certain brain chemicals that
may function abnormally in acutely ill bulimicpatients.
Obsessive-compulsive disorder (OCD) —A disor-

der that may accompany bulimia, characterizedby the tendency to perform repetitive acts or ritu-als in order to relieve anxiety.
Purge —To rid the body of food and calories, com-
monly by vomiting or using laxatives.
Cismoski, Janet, et al. “Teen Nutrition.” Whose Kids? Our
Kids! no. 6 (1995).
Levine, Michael P. “10 Things Men Can Do and Be to Help
Prevent Eating Disorders.” Healthy Weight Journal 9, no.1
(1995): 15.

American Anorexia/Bulimia Association, Inc., 293 Central Park
West, Suite IR, New York, NY 10024. (212) 501-8351.
Anorexia Nervosa and Related Eating Disorders, Inc., P.O. Box
5102, Eugene, OR 97405. (541) 344-1144.
Center for the Study of Anorexia and Bulimia, 1 W. 91st St.,
New York, NY 10024. (212) 595-3449.
Eating Disorder Awareness & Prevention, Inc., 603 Stewart St.,

National Association of Anorexia Nervosa and Associated Dis-
orders, Box 7, Highland Park, IL 60035. (708) 831-3438.
National Eating Disorders Organization, 6655 South Yale Ave,
Tulsa, OK 74136. (918) 481-4044.
Bulla seeSkin lesions
Bumetanide seeDiuretics
BUN seeBlood urea nitrogen test
Bundle branch block
Bundle branch block (BBB) is a disruption in the
normal flow of electrical pulses that drive the heart beat.

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Bundle branch block belongs to a group of heart prob-

lems called intraventricular conduction defects (IVCD).There are two bundle branches, right and left. The rightbundle carries nerve impulses that cause contraction of theright ventricle (the lower chamber of the heart) and the leftbundle carries nerve impulses that cause contraction of theleft ventricle. The two bundles initially are together at ajunction called the bundle of His. Nerve impulses comethrough the sinus node of the heart to the bundle of Hisand then move into the right and left

of Hisand then move into the right and left bundle branches.Bundle branch block is a slowing or interruption of nerveimpulses. A problem may exist in any of the three bundles.

unless the disease is severe enough to cause a completeinfranodal A-V block and very slow heart rate. In patientswith right bundle branch block (RBBB), the nerve impulseis conducted slowly or not at all. The right ventricle finallyreceives the impulse through muscle-to-muscle spread,outside the regular nerve pathway. This mechanism ofimpulse transmission is slow and results in a delayed con-traction of the right ventricle. There are several types ofleft bundle branch block (LBBB), each

types ofleft bundle branch block (LBBB), each producing its owncharacteristic mechanism of failure. In each case, thenerve impulse is blocked or delayed. Patients with LBBBmay have left ventricular disease or cardiomyopathy.

Left bundle branch block usually happens as a con-
sequence of other diseases such as arteriosclerosis,rheumatic fever ,congenital heart disease ,myocardi-
tis, myocardial infarction, metastatic heart tumors, or
other invasions of the heart tissue. Right bundle branchblock happens less often from underlying heart disease.
Diagnosis
Detection of BBB usually takes place during a nor-
mal physical examination . The block shows up as aKEY TERMS

Electrocardiogram —The pattern of the heart’s
electrical impulses that indicate the order andcondition of the heart’s components.
QRS—A pattern seen in an electrocardiogram that
indicates the pulses in a heart beat and their dura-tion. Variations from a normal QRS pattern indi-cate heart disease.widening of the second heart sound. Confirmation of

BBB is obtained by electrocardiogram (ECG). The pat-tern seen in the electrocardiogram indicates pulses in aheart beat and their duration. A QRS duration of greaterthan 110 milliseconds is a diagnostic indication of BBB.There is a unique ECG pattern for blocks in each of thethree bundles.
Treatment
There is no specific therapy for BBB. Patients are
usually treated for associated heart diseases.
Prognosis
The prognosis of blockage in any of the three bundle

branches depends on the prognosis of the associated heartdisease. The associated diseases determine the outcomeof the patient’s health. Occasionally, disruptions in bundlebranches lead to complete infranodal A-V block, a moreserious blockage of nerve impulses. Approximately 2% ofpatients with BBB develop infranodal A-V blockage andthese patients often require artificial pacemakers .
Resources
BOOKS

Bunion
A bunion is an abnormal enlargement of the joint
(the first metatarsophalangeal joint, or MTPJ) at the baseof the great or big toe (hallux). It is caused by inflamma-tion and usually results from chronic irritation and pres-sure from poorly fitting footwear.

A displacement of two major bones of the foot (hal-
lux valgus) causes bunions, although not everyone withthis displacement will develop the joint swelling andbone overgrowth that characterize a bunion. One of thebones involved is called the first metatarsal bone. Thisbone is long and slender, with the big toe attached on one
GALE ENCYCLOPEDIA OF MEDICINE 2 614BunionGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 614

the ankle. This foot bone is displaced in the direction ofthe four other metatarsals connected with the toes. Theother bone involved is the big toe itself, which is dis-placed toward the smaller toes. As the big toe continuesto move toward the smaller toes, it may become dis-placed under or over the second toe. The displacement ofthese two foot bones causes a projection of bone on theinside portion of the forefoot. The skin over this projec-tion often becomes inflamed from rubbing against

often becomes inflamed from rubbing against theshoe, and a callus may form.

The joint contains a small sac (bursa) filled with
fluid that cushions the bones and helps the joint to movesmoothly. When a bunion forms, this sac becomesinflamed and thickened. The swelling in the joint causesadditional pain and pressure in the toe.
Bunions may form as a result of abnormal motion of
the foot during walking or running. One common exam-ple of an abnormal movement is an excessive amount ofstress placed upon the inside of the foot. This leads to

friction and irritation of the involved structures. Age hasalso been noted as a factor in developing bunions, in partbecause the underlying bone displacement worsens overtime unless corrective measures are taken.
Wearing improperly fitting shoes, especially those

with a narrow toe box and excessive heel height, oftencauses the formation of a bunion. This forefoot deformityis seen more often in women than men. The higher fre-quency in females may be related to the strong linkbetween footwear fashion and bunions. In fact, in arecent survey of more than 350 women, nearly 90% woreshoes that were at least one size too small or too narrow.
Because genetic factors can predispose people to the

hallux valgus bone displacement, a strong family historyof bunions can increase the likelihood of developing thisfoot disorder. Various arthritic conditions and severalgenetic and neuromuscular diseases, such as Down syn-
drome and Marfan syndrome , cause muscle imbal-

ances that can create bunions from displacement of thefirst metatarsal and big toe. Other possible causes ofbunions are leg-length discrepancies, with the bunionpresent on the longer leg, and trauma occurring to thejoint of the big toe.
Symptoms of bunions include the common signs of

inflammation such as redness, swelling, and pain. Thediscomfort is primarily located along the inside of thefoot just behind the big toe. Because of friction, a callusmay develop over the bunion. If an overlapping of thetoes is allowed, additional rubbing and pain occurs.Inflammation of this area causes a decrease in motion

with associated discomfort in the joint between the bigtoe and the first metatarsal. If allowed to worsen, the skinover the bunion may break down causing an ulcer, whichalso presents a problem of potential infection. (Footulcers can be particularly dangerous for people with dia-betes, who may have trouble feeling the ulcer formingand healing if it becomes infected.)
Diagnosis
A thorough medical history and physical exam by a

physician is always necessary for the proper diagnosis ofbunions and other foot conditions. X rays can help con-firm the diagnosis by showing the bone displacement,joint swelling, and, in some cases, the overgrowth ofbone that characterizes bunions. Doctors will also con-sider the possibility that the joint pain is caused by orcomplicated by arthritis (which causes destruction of thecartilage of the joint), gout (which causes the accumula-

tion of uric acid crystals in the joint), tiny fractures of a
bone in the foot (stress fractures), or infection and mayorder additional tests to rule out these possibilities.
Treatment
Conservative
The first step in treating a bunion is to remove as

much pressure from the area as possible. People withbunions should wear shoes that have enough room in thetoe box to accommodate the bunion and avoid high-heeledshoes and tight-fitting socks or stockings. Dressings andpads help protect the bunion from additional shoe pres-sure. The application of splints or customized shoe inserts(orthotics) to correct the alignment of the big toe joint iseffective for many bunions. Most patients are instructed to
GALE ENCYCLOPEDIA OF MEDICINE 2 615Bunion

Woman’s right foot with bunion on big toe. (Photograph by
Wedgworth, Custom Medical Stock Photo. Reproduced by per-mission.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 615

rest or choose exercises that put less stress on their feet, at
least until the misalignment is corrected. In some cases,physicians also use steroid injections with local anestheticaround the bunion to reduce inflammation.
Surgery
If conservative treatment is not successful, surgical

removal of the bunion may be necessary to correct thedeformity. This procedure is called a bunionectomy, andthere are many variations on the operation, which is usu-ally performed by a surgeon who specializes in treatingbone conditions (orthopedics) or by one who specializesin treating the foot (podiatry). Surgeons consider theangle of the bone misalignment, the condition of thebursa, and the strength of the bones when they choosewhich procedure to use. Most bunionectomies involvethe removal of

to use. Most bunionectomies involvethe removal of a section of bone and the insertion of pinsto rejoin the bone. Sometimes the surgeons may moveligaments (which connect bone to bone in the joint) ortendons (which connect bone to muscle) in order torealign the bones. After this procedure, the bones andother tissues are held in place while they heal by com-pression dressings or a short cast. The individual mustrefrain from vigorous exercise for six weeks.

Deep friction massage techniques by a physical or
massage therapist can be helpful to increase circulation,reduce inflammation, and prevent soft tissue build up.Physical therapy also provides useful approaches such asultrasound to help retard or reverse the formation of thebunion. Various taping techniques can be useful torealign the toe and decrease friction and rubbing thatmay be present. The homeopathic tissue salt Calcarea

phosphorica can be useful in balancing the bone forma-
tion/remodeling.KEY TERMS
Orthopedics —A medical specialty concerned
with treating diseases, injuries, and malformationsof the bones and supporting structures, such astendons, ligaments, and muscles.
Orthotic —A device or brace to control, correct,
or compensate for a bone deformity.
Podiatry —A medical specialty concerned with
treating diseases, injuries, and malformations ofthe feet.Prognosis

Often modifications in footwear allow a good prog-
nosis without surgery. If surgery is necessary, completehealing without complications requires approximatelyfour to six weeks. Even after surgery corrects the bonemisalignment, patients are usually instructed to continuewearing low-heeled, roomy shoes to prevent the bunionfrom reforming.
Prevention begins with proper foot wear. Shoes with a

wide and deep toe box are best. High-heeled shoes shouldnot be worn for long periods of time. If a bunion is presentand becomes inflamed, the foot should be elevated with theapplication of an ice pack over the painful area for not morethan 20 minutes every other hour. If pain and swelling con-tinue, a podiatrist or physician should be contacted.
Resources
BOOKS
Common Foot Problems in Primary Care. 2nd ed. Ed. Richard
B. Birrer, et al. Philadelphia: Hanley & Belfus, Inc., 1998.

Principles and Practice of Podiatric Medicine. Ed. Leonard A.
Levy and Vincent J. Hetherington. New York: ChurchillLivingstone, 1990.
American Orthopedic Foot and Ankle Society. 222 South
Prospect, Park Ridge, IL 60068.
American Podiatry Medical Association. 9312 Old George-
town Road, Bethesda, MD 20814.
OTHER
Griffith, H. Winter. “Complete Guide to Symptoms, Illness &
Surgery.” ThriveOnline .<http://thriveonline.oxygen.com>.
Burkitt’s lymphoma seeMalignant

lymphomas
Burns
Burns are injuries to tissues caused by heat, friction,
electricity, radiation, or chemicals.
Burns are characterized by degree, based on the
severity of the tissue damage. A first-degree burn causes
GALE ENCYCLOPEDIA OF MEDICINE 2 616BurnsGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 616

redness and swelling in the outermost layers of skin (epi-
dermis). A second-degree burn involves redness, swellingand blistering, and the damage may extend beneath theepidermis to deeper layers of skin (dermis). A third-degree burn, also called a full-thickness burn, destroys theentire depth of skin, causing significant scarring. Damagealso may extend to the underlying fat, muscle, or bone.
The severity of the burn is also judged by the

amount of body surface area (BSA) involved. Health careworkers use the “rule of nines” to determine the percent-age of BSA affected in patients more than 9 years old:each arm with its hand is 9% of BSA; each leg with itsfoot is 18%; the front of the torso is 18%; the back of thetorso, including the buttocks, is 18%; the head and neckare 9%; and the genital area (perineum) is 1%. This rulecannot be applied to a young child’s body proportions, soBSA is estimated using the palm of the patient’s

is estimated using the palm of the patient’s hand asa measure of 1% area.

The severity of the burn will determine not only the
type of treatment, but also where the burn patient shouldreceive treatment. Minor burns may be treated at home orin a doctor’s office. These are defined as first- or second-degree burns covering less than 15% of an adult’s bodyor less than 10% of a child’s body, or a third-degree burnon less than 2% BSA. Moderate burns should be treated

at a hospital. These are defined as first- or second-degreeburns covering 15%-25% of an adult’s body or 10%-20%of a child’s body, or a third-degree burn on 2%-10%BSA. Critical, or major, burns are the most serious andshould be treated in a specialized burn unit of a hospital.These are defined as first- or second-degree burns cover-ing more than 25% of an adult’s body or more than 20%of a child’s body, or a third-degree burn on more than10% BSA. In addition, burns involving the hands, feet,face,

addition, burns involving the hands, feet,face, eyes, ears, or genitals are considered critical. Otherfactors influence the level of treatment needed, includingassociated injuries such as bone fractures and smoke

inhalation , presence of a chronic disease, or a history of
being abused. Also, children and the elderly are morevulnerable to complications from burn injuries andrequire more intensive care.
Burns may be caused by even a brief encounter with
heat greater than 120°F (49°C). The source of this heat maybe the sun (causing a sunburn ), hot liquids, steam, fire,
electricity, friction (causing rug burns and rope burns), andchemicals (causing a caustic burn upon contact).

GALE ENCYCLOPEDIA OF MEDICINE 2 617Burns
Epidermis
DermisFirst-degree burn
Second-degree burn
Hair follicle NerveBlood vesselsThird-degree burnSubcutaneous
tissue
There are three classifications of burns: first-degree, second-degree, and third-degree burns. (Illustration by Electronic Illustra-
tors Group.)GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 617

Signs of a burn are localized redness, swelling, and
pain . A severe burn will also blister. The skin may also
peel, appear white or charred, and feel numb. A burn maytrigger a headache and fever . Extensive burns may
induce shock , the symptoms of which are faintness,
weakness, rapid pulse and breathing, pale and clammyskin, and bluish lips and fingernails.
Diagnosis
A physician will diagnose a burn based upon visual

examination, and will also ask the patient or family mem-bers questions to determine the best treatment. He or shemay also check for smoke inhalation, carbon monoxide
poisoning , cyanide poisoning , other event-related trau-
ma, or, if suspected, further evidence of child abuse .
Treatment
Burn treatment consists of relieving pain, preventing

infection, and maintaining body fluids, electrolytes, andcalorie intake while the body heals. Treatment of chemi-cal or electrical burns is slightly different from the treat-ment of thermal burns but the objectives are the same.
Thermal burn treatment
The first act of thermal burn treatment is to stop the

burning process. This may be accomplished by letting coolwater run over the burned area or by soaking it in cool (notcold) water. Ice should never be applied to the burn. Cool(not cold) wet compresses may provide some pain reliefwhen applied to small areas of first- and second-degreeburns. Butter, shortening, or similar salve should never beapplied to the burn since it prevents heat from escapingand drives the burning process deeper into the skin.

If the burn is minor, it may be cleaned gently with
soap and water. Blisters should not be broken. If the skinof the burned area is unbroken and it is not likely to befurther irritated by pressure or friction, the burn shouldbe left exposed to the air to promote healing. If the skinis broken or apt to be disturbed, the burned area shouldbe coated lightly with an antibacterial ointment and cov-ered with a sterile bandage. Aspirin ,acetaminophen

(Tylenol), or ibuprofen (Advil) may be taken to ease painand relieve inflammation. A doctor should be consulted
if these signs of infection appear: increased warmth, red-ness, pain, or swelling; pus or similar drainage from thewound; swollen lymph nodes; or red streaks spreadingaway from the burn.
In situations where a person has received moderate or

critical burns, lifesaving measures take precedence overburn treatment and emergency medical assistance must becalled. A person with serious burns may stop breathing,and artificial respiration (also called mouth-to-mouthresuscitation or rescue breathing) should be administeredimmediately. Also, a person with burns covering morethan 12% BSA is likely to go into shock; this conditionmay be prevented by laying the person flat and elevatingthe feet about 12 in (30 cm). Burned arms and handsshould

about 12 in (30 cm). Burned arms and handsshould also be raised higher than the person’s heart.

flames as the person is removed from danger. The personwhose clothing is on fire should “stop, drop, and roll” orbe assisted in lying flat on the ground and rolling to putout the fire. Afterwards, only burnt clothing that comesoff easily should be removed; any clothing embedded inthe burn should not be disturbed. Removing any smol-dering apparel and covering the person with a light, cool,wet cloth, such as a sheet but not a blanket or towel, willstop the burning process.

At the hospital, the staff will provide further med-
ical treatment. A tube to aid breathing may be inserted ifthe patient’s airways or lungs have been damaged, ascan happen during an explosion or a fire in a enclosedspace. Also, because burns dramatically deplete thebody of fluids, replacement fluids are administeredintravenously. The patient is also given antibiotics intra-
venously to prevent infection, and he or she may alsoreceive a tetanus shot, depending on his or her immu-

nization history. Once the burned area is cleaned andtreated with antibiotic cream or ointment, it is coveredin sterile bandages, which are changed two to threetimes a day. Surgical removal of dead tissue ( debride-
ment ) also takes place. As the burns heal, thick, taut
scabs (eschar) form, which the doctor may have to cut toimprove blood flow to the more elastic healthy tissuebeneath. The patient will also undergo physical and
GALE ENCYCLOPEDIA OF MEDICINE 2 618BurnsClassification Of Burns

First-Degree (Minor) The burned area is painful. The outer skin is reddened. Slight swelling is present.
Second-Degree (Moderate) The burned area is painful. The underskin is affected. Blisters may form. The area may have a wet, shin y appearance because of
exposed tissue.
Third-Degree (Critical) The burned area is insensitive due to the destruction of nerve endings. Skin is destroyed.Muscle tissues  and bone underneath

may be damaged. The area may be charred, white, or grayish in color.GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 618

occupational therapy to keep the burned areas from
becoming inflexible and to minimize scarring.
In cases where the skin has been so damaged that it

cannot properly heal, a skin graft is usually performed. Askin graft involves taking a piece of skin from anunburned portion of the patient’s body (autograft) andtransplanting it to the burned area. When doctors cannotimmediately use the patient’s own skin, a temporary graftis performed using the skin of a human donor (allograft),either alive or dead, or the skin of an animal (xenograft),usually that of a pig.
The burn victim also may be placed in a hyperbaric

chamber, if one is available. In a hyperbaric chamber(which can be a specialized room or enclosed space), thepatient is exposed to pure oxygen under high pressure,which can aid in healing. However, for this therapy to beeffective, the patient must be placed in a chamber within24 hours of being burned.
Chemical burn treatment
Burns from liquid chemicals must be rinsed with

cool water for at least 15 minutes to stop the burningprocess. Any burn to the eye must be similarly flushedwith water. In cases of burns from dry chemicals such aslime, the powder should be completely brushed awaybefore the area is washed. Any clothing which may haveabsorbed the chemical should be removed. The burnshould then be loosely covered with a sterile gauze padand the person taken to the hospital for further treatment.A physician may be able to neutralize the offendingchemical with

be able to neutralize the offendingchemical with another before treating the burn like athermal burn of similar severity.

Electrical burn treatment
Before electrical burns are treated at the site of the
accident, the power source must be disconnected if possi-ble and the victim moved away from it to keep the persongiving aid from being electrocuted. Lifesaving measuresagain take priority over burn treatment, so breathingmust be checked and assisted if necessary. Electricalburns should be loosely covered with sterile gauze padsand the person taken to the hospital for further treatment.

In addition to the excellent treatment of burns pro-
vided by traditional medicine, some alternativeapproaches may be helpful as well. (Major burns shouldalways be treated by a medical practitioner.) The homeo-pathic remedies Cantharis and Causticum can assist in
burn healing. A number of botanical remedies, appliedtopically, can also help burns heal. These include aloeKEY TERMS
Debridement —The surgical removal of dead tis-
sue.

sue.
Dermis —The basal layer of skin; it contains blood
and lymphatic vessels, nerves, glands, and hairfollicles.
Epidermis —The outer portion of skin, made up of
four or five superficial layers.
Shock —An abnormal condition resulting from low
blood volume due to hemorrhage or dehydration.Signs of shock include rapid pulse and breathing,and cool, moist, pale skin.
(Aloe barbadensis ), oil of St.-John’s-wort ( Hypericum
perforatum ), calendula ( Calendula officinalis ), comfrey

(Symphytum officinale ), and tea tree oil ( Melaleuca spp.).
Supplementing the diet with vitamin C, vitamin E, andzinc also is beneficial for wound healing.
Prognosis
The prognosis is dependent upon the degree of the

burn, the amount of body surface covered, whether criti-cal body parts were affected, any additional injuries orcomplications like infection, and the promptness of med-ical treatment. Minor burns may heal in five to 10 dayswith no scarring. Moderate burns may heal in 10-14 daysand may leave scarring. Critical or major burns takemore than 14 days to heal and will leave significant scar-ring. Scar tissue may limit mobility and functionality, butphysical therapy may overcome these limitations.

therapy may overcome these limitations. Insome cases, additional surgery may be advisable toremove scar tissue and restore appearance.

Burns are commonly received in residential fires.
Properly placed and working smoke detectors in combi-nation with rapid evacuation plans will minimize a per-son’s exposure to smoke and flames in the event of a fire.Children must be taught never to play with matches,lighters, fireworks, gasoline, and cleaning fluids.
Burns by scalding with hot water or other liquids

may be prevented by setting the water heater thermostatno higher than 120°F (49°C), checking the temperatureof bath water before getting into the tub, and turning pothandles on the stove out of the reach of children. Careshould be used when removing covers from pans of
GALE ENCYCLOPEDIA OF MEDICINE 2 619BurnsGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 619

steaming foods and when uncovering or opening foods
heated in a microwave oven.
Thermal burns are often received from electrical
appliances. Care should be exercised around stoves,space heaters, irons, and curling irons.
Sunburns may be avoided by the liberal use of a sun-

screen containing either an opaque active ingredient suchas zinc oxide or titanium dioxide or a nonopaque activeingredient such as PABA (para-aminobenzoic acid) orbenzophenone. Hats, loose clothing, and umbrellas alsoprovide protection, especially between 10 
A.M. and 3 P.M.
when the most damaging ultraviolet rays are present indirect sunlight.
Electrical burns may be prevented by covering unused

electrical outlets with safety plugs and keeping electricalcords away from infants and toddlers who might chew onthem. Persons should also seek shelter indoors during athunderstorm to avoid being struck by lightning.
Chemical burns may be prevented by wearing protec-
tive clothing, including gloves and eyeshields. Chemicalagents should always be used according to the manufac-turer’s instructions and properly stored when not in use.
Resources
BOOKS

Resources
BOOKS
The Merck Manual of Diagnosis and Therapy. 17th ed. Ed.
Robert Berkow. Rahway, NJ: Merck Research Laborato-ries, 1997.
Shriners Hospitals for Children. 2900 Rocky Point Drive,
Tampa, FL 33607-1435. (813) 281-0300. <http://www.shrinershq.org>.
OTHER
HealthAnswers.com .<http://www.healthanswers.com>.
Bursitis
Bursitis is the painful inflammation of the bursa, a

padlike sac found in areas subject to friction. Bursaecushion the movement between the bones, tendons andmuscles near the joints. Bursitis is most often caused byrepetitive movement and is known by several commonnames including weaver’s bottom, clergyman’s knee, andminer’s elbow, depending on the affected individual’soccupation and area of injury.Description
There are over 150 bursae in the human body. Usual-

ly bursae are present from birth, but they may form inresponse to repeated pressure. Each sac contains a smallamount of synovial fluid, a clear liquid that acts as a
lubricant. Inflammation causes pain on movement. The

most common site for bursitis to occur is the shoulder(subdeltoid), but it also is seen in the elbows (olecranon),hips (trochanteric), knees, heels (Achilles), and toes. Theaffected area may be referred to as “frozen,” becausemovement is so limited. In the knee there are four bursae,and all can become inflamed with overuse.
The most common cause of bursitis is repeated

physical activity, but it can flare up for no known reason.It can also be caused by trauma, rheumatoid arthritis ,
gout , and acute or chronic infection.
Pain and tenderness are common symptoms. If the

affected joint is close to the skin, as with the shoulder,knee, elbow, or Achilles tendon, swelling and redness areseen and the area may feel warm to the touch. The bursaearound the hip joint are deeper, and swelling is not obvi-ous. Movement may be limited and is painful. In theshoulder, it may be difficult to raise the arm out from theside of the body. Putting on a jacket or combing the hairbecomes a troublesome activity.

In acute bursitis symptoms appear suddenly; with
chronic bursitis, pain, tenderness, and limited movementreappear after exercise or strain.
Diagnosis
When a patient has pain in a joint, a careful physical
examination is needed to determine what type of move-

ment is affected and if there is any swelling present. Bur-sitis will not show up on x-rays, although sometimesthere are also calcium deposits in the joint that can beseen. Inserting a thin needle into the affected bursa andremoving (aspirating) some of the synovial fluid forexamination can confirm the diagnosis. In most cases,the fluid will not be clear. It can be tested for the pres-ence of microorganisms, which would indicate an infec-tion, and crystals, which could indicate gout. In

and crystals, which could indicate gout. In instanceswhere the diagnosis is difficult, a local anesthetic (a drugthat numbs the area) is injected into the painful spot. Ifthe discomfort stops temporarily, then bursitis is proba-bly the correct diagnosis.

Treatment
Conservative treatment of bursitis is usually effec-
tive. The application of heat, rest, and immobilization of
GALE ENCYCLOPEDIA OF MEDICINE 2 620BursitisGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 620

the affected joint area is the first step. A sling can be used
for a shoulder injury; a cane is helpful for hip problems.The patient can take nonsteroidal anti-inflammatory
drugs (NSAIDs) like aspirin , ibuprofin, and naproxen.

They can be obtained without a prescription and relievethe pain and inflammation. Once the pain decreases,exercises of the affected area can begin. If the nearbymuscles have become weak because of the disease orprolonged immobility, then exercises to build strengthand improve movement are best. A doctor or physicaltherapist can prescribe an effective regimen.
If the bursitis is related to an inflammatory condition

like arthritis or gout, then management of that disease isneeded to control the bursitis.
When bursitis does not respond to conservative

treatment, an injection into the joint of a long-acting cor-ticosteroid preparation, like prednisone, can bring imme-diate and lasting relief. A corticosteroid is a hormonalsubstance that is the most effective drug for reducinginflammation. The drug is mixed with a local anestheticand works on the joint within five minutes. Usually oneinjection is all that is needed.
Surgery to remove the damaged bursa may be per-
formed in extreme cases.

If the bursitis is caused by an infection, then addi-
tional treatment is needed. Septic bursitis is caused by the
presence of a pus-forming organism, usually staphylococ-
cus aureus. This is confirmed by examining a sample of
the fluid in the bursa and requires treatment with antibi-
otics taken by mouth, injected into a muscle or into a vein

(intravenously). The bursa will also need to be drained byneedle two or three times over the first week of treatment.When a patient has such a serious infection, there may beunderlying causes. There could be undiscovered diabetes,or an inefficient immune system caused by humanimmunodeficiency virus infection (HIV).
Alternative treatments take into consideration the

role of diet in causing bursitis. The faulty use of calciumby the body, magnesium deficiency, and food allergies
may have a role. Diet changes and vitamin supplementsmay be helpful. The use of herbs, homeopathy ,aro-
matherapy , and hydrotherapy can help relieve symp-
toms. Ginger is useful in reducing inflammation.Acupuncture has been proven effective in treating hip

and shoulder pain caused by bursitis and other condi-tions. Other therapies that deal effectively with muscu-loskeletal problems (relating to the muscles and skele-ton), may also be helpful, such as body work, magnetic
field therapy ,naturopathic medicine ,chiropractic ,
and applied kinesiology .KEY TERMS
Arthritis —Inflammation of a joint that may lead to
changes in the joint’s structure. It causes pain andswelling. Rheumatoid arthritis is a chronic diseasethat leads to crippling deformities.

Diabetes mellitus —A metabolic disease caused
by a deficiency of insulin, which is essential toprocess carbohydrates in the body.
Gout —A hereditary metabolic disease that is a
form of arthritis and causes inflammation of thejoints. It is more common in men.
Inflammation —The reaction of tissue to injury.
Kinesiology —The science or study of movement.
Prognosis
Bursitis usually responds well to treatment, but it
may develop into a chronic condition if the underlyingcause is not corrected.

bursitis. Overexercising or the repetition of a movementthat triggers the condition should be avoided. Doing exer-cises to strengthen the muscles around the joint will alsohelp. When doing repetitive tasks, frequent breaks shouldbe taken and the activity should be alternated with othersusing different parts of the body. To cushion the joints, itis a good idea to use cushioned chairs when sitting andfoam kneeling pads for the knees. Leaning on the elbows,kneeling or sitting on a hard surface for

elbows,kneeling or sitting on a hard surface for a long period oftime should be avoided. Not wearing high heels can helpprevent bursitis in the heel, as can changing to new run-ning shoes as soon as the old ones are worn out.

Resources
BOOKS
Bennett, Robert M. “Bursitis, Tendinitis, Myofascial Pain, and
Fibromyalgia.” In Conn’s Current Therapy. ed. Robert E.
Rakel. Philadelphia: W. B. Saunders Co., 1996.
“Bursitis.” Mayo Clinic Health Newsletter (June 1995.)

“Bursitis of the Hip.” Mayo Clinic Health Newsletter (Sept. 1997):
Munson, Marty. “Big bursa.” Prevention (May 1996): 63-65.
GALE ENCYCLOPEDIA OF MEDICINE 2 621BursitisGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 621

OTHER
“Bursitis.” HealthAnswers.com. 1998 <http://www.health
answers.com>.
Bypass surgery seeCoronary artery bypass
graft surgery
Byssinosis
Byssinosis is a chronic, asthma-like narrowing of the
airways. Also called brown lung disease, byssinosis resultsfrom inhaling particles of cotton, flax, hemp, or jute.
Although inhaling cotton dust was identified as a

source of respiratory disease more than 300 years ago,byssinosis has been recognized as an occupational haz-ard for textile workers for less than 50 years. More than800,000 workers in the cotton, flax, and rope-makingindustries are exposed in the workplace to airborne parti-cles that can cause byssinosis. Only workers in mills thatmanufacture yarn, thread, or fabric have a significant riskof dying of this disease.

In the United States, byssinosis is almost completely
limited to workers who handle unprocessed cotton. Morethan 35,000 textile workers have been disabled by byssi-nosis and 183 died between 1979 and 1992. Most of thepeople whose deaths were due to byssinosis lived in thetextile-producing regions of North and South Carolina.
Wheezing ,shortness of breath , and a feeling of

tightness in the chest occur occasionally during the earlystages of the disease. Symptoms are usually more pro-nounced when returning to work after a weekend, holi-day, or vacation and subside as the worker becomes reac-customed to the environment.
As many as 25% of workers with byssinosis have

symptoms that continue or recur throughout the work-week. More severe breathing problems seem to resultboth from exposure to high levels of dust and fromlonger dust exposure. Workers who also smoke cigarettessuffer the most severe impairment.Diagnosis
Tests that detect decreasing lung capacity during the
workday are used to diagnose byssinosis. Obstructivepatterns are likely in patients who have had recurrentsymptoms for more than 10 years.

Treatment
Therapy for early-stage byssinosis focuses on
reversing airway narrowing. Antihistamines may be pre-
scribed to reduce tightness in the chest. Bronchodilators
(drugs used to relax breathing passages and improve airflow) may be used with an inhaler or taken in tablet form.Reducing exposure is essential. Any worker who hassymptoms of byssinosis or who has trouble breathingshould transfer to a less-contaminated area.
Prognosis
Smoking , impaired lung function, and a history of

respiratory allergy increase a textile worker’s risk of devel-oping byssinosis. Prolonged exposure makes patientswheeze more often and can cause chronic bronchitis . It
does not lead to permanently disabling lung disease.
Eliminating exposure to textile dust is the surest way

to prevent byssinosis. Using exhaust hoods, improvingventilation, and employing wetting procedures are verysuccessful methods of controlling dust levels to preventbyssinosis. Protective equipment required during certainprocedures also prevents exposure to levels of contami-nation that exceed the current United States standard forcotton dust exposure.
Resources
BOOKS

Stephen McPhee, et al. Stamford: Appleton & Lange,1995.
GALE ENCYCLOPEDIA OF MEDICINE 2 622ByssinosisKEY TERMS
Wheeze —A whistling sound made by the flow of
high-velocity air through narrowed airways.Wheezing is a symptom of several respiratory dis-eases including byssinosis and asthma.GEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 622

OTHER
“Occupational Lung Disease.” American Lung Association
Page .27 May 1998 <http://www.lungusa.org>.
“1996 World Surveillance Report: Selected Data Highlights.”
Centers for Disease Control .27 May 1998. 27 May 1998

<http://www.cdc.gov/niosh/w7_high.html>.
GALE ENCYCLOPEDIA OF MEDICINE 2 623ByssinosisGEM -0433 to 0624 - B  10/22/03 6:09 PM  Page 623