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Sorsbys fundus dystrophy | Sorsbys fundus dystrophy (SFD) is a very rare genetic disorder characterized by the loss of central vision. It was first described by Sorsby and Mason in 1949.
Signs and symptoms
Patients typically become symptomatic in their 40s due to loss of central vision. However, tests of rod photoreceptor function (i.e., night vision tests) show dysfunction at an earlier age. One of the most sensitive visual function parameters for early SFD is a prolongation of rod-mediated dark adaptation. High-resolution structural imaging of the Bruchs membrane and of the underlying choriocapillaris – the capillary plexus nourishing the outer retina – also shows early alterations.
Genetics
The inheritance pattern is autosomal dominant. It is related to a mutation in the TIMP3 gene.
Diagnosis
Treatment
References
External links
Sorsbys fundus dystrophy at OMIM
Sorsbys fundus dystrophy at Orpha.net |
Granulomatous meningoencephalitis | Granulomatous meningoencephalitis (GME) is an inflammatory disease of the central nervous system (CNS) of dogs and, rarely, cats. It is a form of meningoencephalitis. GME is likely second only to encephalitis caused by canine distemper virus as the most common cause of inflammatory disease of the canine CNS. The disease is more common in female dogs of young and middle age. It has a rapid onset. The lesions of GME exist mainly in the white matter of the cerebrum, brainstem, cerebellum, and spinal cord. The cause is only known to be noninfectious and is considered at this time to be idiopathic. Because lesions resemble those seen in allergic meningoencephalitis, GME is thought to have an immune-mediated cause, but it is also thought that the disease may be based on an abnormal response to an infectious agent. One study searched for viral DNA from canine herpesvirus, canine adenovirus, and canine parvovirus in brain tissue from dogs with GME, necrotizing meningoencephalitis, and necrotizing leukoencephalitis (see below for the latter two conditions), but failed to find any.
Types of GME
Disseminated – This is a diffuse disease throughout the CNS. It was previously known as inflammatory reticulosis. There is an accumulation of mononuclear cells and neutrophils around the blood vessels (perivascular) of the CNS. Meningitis is seen with this form of GME and causes fever and neck pain. It has an acute progression over a few weeks. Symptoms include incoordination, nystagmus, head tilt, seizures, and depression.
Focal – The disease presents as a granuloma, which mimics a tumor. It usually is found in the cerebrum or cerebellopontine angle. Symptoms may be acute or develop slowly over several months and depend on the location of the lesion.
Ocular – This is an uncommon form of GME and is characterized by sudden blindness caused by optic neuritis. The disease is bilateral. Ocular GME is considered to be an extension of CNS disease. The blood vessels of the posterior segment of the eye and anterior uvea have the same infiltrates of inflammatory cells as the intracranial vessels. Uveitis, retinal detachment, and secondary glaucoma may be seen.
Diagnosis and treatment
Cerebrospinal fluid (CSF) analysis shows a large number of white blood cells. Typically small mature lymphocytes are the majority of cells seen, with monocytes and neutrophils making up the rest. Definitive diagnosis is based on histopathology, either a brain biopsy or post-mortem evaluation (necropsy). A CT scan or MRI will show patchy, diffuse, or multifocal lesions. For a number of years, the basic treatment was some type of corticosteroid in combination with one or more immunosuppressive drugs, typically cytosine arabinoside and/or cyclosporine or other medications such as azathioprine, cyclophosphamide, or procarbazine, of which were usually added one at a time to the corticosteroid until a successful combination was found. There is evidence that treatment with radiation therapy for focal GME provides the longest periods of remission.
Pug dog encephalitis
Pug dog encephalitis (PDE) is an idiopathic inflammatory disease primarily affecting the prosencephalon (forebrain and thalamus). It is also known as necrotizing meningoencephalitis. The disease may be inherited in Pugs and Maltese and has been diagnosed in other breeds as well (Yorkies, Chihuahuas). The prevalence of PDE in pugs is about 1%. It differs in pathology from GME by more tissue breakdown and increased eosinophils (white blood cells). CSF analysis is also unique among inflammatory CNS diseases in dogs in that the cells are predominantly lymphocytes, instead of a mixed population of mononuclear cells. In Maltese and Pugs, there is extensive necrosis and inflammation of the gray matter of the cerebrum and subcortical white matter. The most common early symptoms are related to forebrain disease and include seizures and dementia, and later circling, head tilt, and blindness with normal pupillary light reflexes may be seen. PDE has a poor prognosis.
Necrotizing leukoencephalitis
In Yorkshire Terriers there can be severe mononuclear inflammation of the brainstem and periventricular cerebral white matter. Because the condition in this breed frequently affects only the white matter, it has been called necrotizing leukoencephalitis. Symptoms of brainstem and central vestibular disease predominate.
Other types of noninfectious meningoencephalitis
Steroid-responsive meningoencephalitis is any noninfectious meningoencephalitis that responds well to corticosteroids and usually has an excellent prognosis. This could represent mild forms of GME or PDE, but there are two separate conditions recognized also.
Steroid-responsive meningitis/arteritis, also known as necrotizing vasculitis, is seen most commonly in Beagles, Boxers, Bernese Mountain Dogs, and German Shorthaired Pointers younger than two years of age. Many cases have fever, loss of appetite, and severe neck pain without other neurologic symptoms, although long-term cases may have incoordination and limb weakness or paralysis. CSF analysis shows predominantly neutrophils. In Beagles this condition is also known as Beagle pain syndrome.
Eosinophilic meningoencephalomyelitis is seen mainly in Golden Retrievers. CSF analysis shows predominantly eosinophils.
An acute progressive pyogranulomatous meningoencephalomyelitis is seen in mature Pointer dogs. There is monocytic and neutrophilic infiltration of the leptomeninges. Symptoms include incoordination, reluctance to move, and neck rigidity.
See also
Encephalitis
Meningitis
== References == |
1q21.1 deletion syndrome | 1q21.1 deletion syndrome is a rare aberration of chromosome 1. A human cell has one pair of identical chromosomes on chromosome 1. With the 1q21.1 deletion syndrome, one chromosome of the pair is not complete, because a part of the sequence of the chromosome is missing. One chromosome has the normal length and the other is too short.
In 1q21.1, the 1 stands for chromosome 1, the q stands for the long arm of the chromosome and 21.1 stands for the part of the long arm in which the deletion is situated.
The syndrome is a form of the 1q21.1 copy number variations, and it is a deletion in the distal area of the 1q21.1 part. The CNV leads to a very variable phenotype, and the manifestations in individuals are quite variable. Some people who have the syndrome can function in a normal way, while others have symptoms of intellectual impairment and various physical anomalies.1q21.1 microdeletion is a very rare chromosomal condition. Only 46 individuals with this deletion have been reported in medical literature as of August 2011.
Symptoms and signs
Recognised symptoms are:
Only one set of genes on the two chromosomes function (haploinsufficiency)
Thrombocytopenia-absent radius (TAR syndrome), in case of a class II-deletion
Neurological-psychiatric problems: schizophrenia; epilepsy; learning problems; cognitive disabilities — mild to moderate; developmental delay — mild to moderate (milestones like sitting, standing and walking; come at a later period in childhood); children show an ataxic gait and fall down a lot
Dysmorphism: slightly unusual facial appearance; disturbed growth; skeletal malformations; small head (microcephaly); prominent forehead; bulbous nose; deep-set eyes; broad thumbs; broad toes; squint; very flexible joints; clavicular pseudoarthrosis (the collarbone doesnt develop normally) (class II-deletion); an extra transverse crease of the fifth finger (class II-deletion)); problems with the development of the vagina (Müllerian aplasia)
Eyes: cataracts
Heart abnormalities and cardiovascular anomalies (30% of the cases): anomalous origin of the coronary artery (Class II-deletion)
Kidneys: missing kidney or floating kidneys
Cancer: neuroblastoma
Sleep disturbancesIt is not clear whether the list of symptoms is complete. Very little information is known about the syndrome. The syndrome can have completely different effects on members of the same family.A common deletion is between 1.0–1.9Mb. Mefford states that the standard for a deletion is 1.35Mb. The largest deletion seen on a living human is over 5 Mb.
Cause
Meiosis is the process of dividing cells in humans. In meiosis, the chromosome pairs split and a representative of each pair goes to one daughter cell. In this way the number of chromosomes will be halved in each cell, while all the parts on the chromosome (genes) remain, after being randomized. Which information of the parent cell ends up in the daughter cell is purely decided by chance. Besides this random process, there is a second random process. In this second random process the DNA will be scrambled in a way that pieces are omitted (deletion), added (duplication), moved from one place to another (translocation) and inverted (inversion). This is a common process, which leads to about 0.4% variation in the DNA.A problem of the second random process is that genetic mistakes can occur. Because of the deletion and duplication process, the chromosomes that come together in a new cell may be shorter or longer. The result of this spontaneous change in the structure of DNA is a so-called copy number variation. Due to the copy number variation chromosomes of different sizes can be combined in a new cell. If this occurs around conception, the result will be a first cell of a human with a genetic variation. This can be either positive or negative. In positive cases this new human will be capable of a special skill that is assessed positively, for example, in sports or science. In negative cases, you have to deal with a syndrome or a severe disability, as in this case the 1q21.1 deletion syndrome.Based on the meiotic process, the syndrome may occur in two ways.
a spontaneous deviation (a de novo situation): two chromosomes come together of which one has a copy number variation as a result of the meiosis process.
a parent is unknowingly the carrier of a chromosome with a copy number variation and passes it at conception to the child, with different consequences for the child.Due to this genetic misprint, the embryo may experience problems in the development during the first months of pregnancy. Approximately 20 to 40 days after fertilization, something goes wrong in the construction of the body parts and brain, which leads to a chain reaction.
Genetics
The structure of 1q21.1
The structure of 1q21.1 is complex. The area has a size of approximately 6 Megabase (Mb) (from 141.5 Mb to 147.9 Mb). Within 1q21.1 there are two areas where the CNVs can be found: the proximal area or TAR area (144.1 to 144.5) and the distal area (144.7 to 145.9). The 1q21.1 deletion syndrome will commonly be found in the distal area, but an overlap with the TAR-area is possible. 1q21.1 has multiple repetitions of the same structure (areas with the same color in the picture have equal structures) Only 25% of the structure is not duplicated. There are several gaps in the sequence. There is no further information available about the DNA-sequence in those areas up until now. The gaps represent approximately 700 Kilobase. New genes are expected in the gaps. Because the gaps are still a topic of research, it is hard to find the exact start and end markers of a deletion. The area of 1q21.1 is one of the most difficult parts of the human genome to map.Because of the repetitions in 1q21.1, there is a larger chance of an unequal crossing-over during meiosis. CNVs occur due to non-allelic homologous recombination mediated by low copy repeats (sequentially similar regions).
Typing
A common deletion is restricted to the distal area. This is a Class I-deletion.In some cases the deletion is so large that the proximal area is involved as well, the so-called Class II-deletion. There are some complex cases in which both the proximal area and the distal area are affected, while the area in between is normal. There are also some a-typical variants.
Related genes
Genes related to 1q21.1 deletion in the distal area are PDE4DIP, HYDIN2, PRKAB2, PDIA3P, FMO5, CHD1L, BCL9, ACP6, GJA5, GJA8, NBPF10, GPR89B, GPR89C, PDZK1P1 and NBPF11.
Diagnostics
A de novo-situation appears in about 75% of the cases. In 25% of the cases, one of the parents is carrier of the syndrome, without any effect on the parent. Sometimes adults have mild problems with the syndrome. To find out whether either of the parents carries the syndrome, both parents have to be tested. In several cases, the syndrome was identified with the child, because of a developmental disorder or another problem, and later it appeared that the parent was affected as well. In families where both parents have tested negative for the syndrome, chances of a second child with the syndrome are extremely low. If the syndrome was found in the family, chances of a second child with the syndrome are 50%, because the syndrome is autosomal dominant. The effect of the syndrome on the child cannot be predictedThe syndrome can be detected with fluorescence in situ hybridization. For parents with a child with the syndrome, it is advisable to consult a physician before another pregnancy.
Management
Treatment of cause: Due to the genetic cause, no treatment of the cause is possible.Treatment of manifestations: routine treatment of ophthalmologic, cardiac, and neurologic findings; speech, occupational, and physical therapies as appropriate; specialized learning programs to meet individual needs; antiepileptic drugs or antipsychotic medications as needed.Surveillance: routine pediatric care; routine developmental assessments; monitoring of specific identified medical issues.
Prevalence
As of October 2012, Unique, an international rare chromosome disorder group and registry, has 64 genetically confirmed cases of this deletion worldwide.
Research
On several locations in the world people are studying on the subject of 1q21.1 deletion syndrome. The syndrome was identified for the first time with people with heart abnormalities. The syndrome has later been found in patients with schizophrenia. Research is done on patients with a symptom of the syndrome, to find more patients with the syndrome.There may be a relation between autism and schizophrenia. Literature shows that nine locations have been found on the DNA where the syndromes related to autism or schizophrenia can be found, the so-called "hotspots": 1q21.1, 3q29, 15q13.3, 16p11.2, 16p13.1, 16q21, 17p12, 21q11.2 and 21q13.3. With a number of hotspots, either autism and schizophrenia were observed depending on the copy-number variation (CNV) at that location.Statistical research showed that schizophrenia is more common in combination with 1q21.1 deletion syndrome. On the other side, autism is significantly more common with 1q21.1 duplication syndrome. Further research confirmed that the odds on a relation between schizophrenia and deletions at 1q21.1, 3q29, 15q13.3, 22q11.21 en Neurexin 1 (NRXN1) and duplications at 16p11.2 are at 7.5% or higher.
Common variations in the BCL9 gene, which is in the distal area, confer risk of schizophrenia and may also be associated with bipolar disorder and major depressive disorder.Research is done on 10–12 genes on 1q21.1 that produce DUF1220-locations. DUF1220 is an unknown protein, which is active in the neurons of the brain near the neocortex. Based on research on apes and other mammals, it is assumed that DUF1220 is related to cognitive development (man: 212 locations; chimpanzee: 37 locations; monkey: 30 locations; mouse: 1 location). It appears that the DUF1220-locations on 1q21.1 are in areas that are related to the size and the development of the brain. The aspect of the size and development of the brain is related to autism (macrocephaly) and schizophrenia (microcephaly). It has been proposed that a deletion or duplication of a gene that produces DUF1220-areas might cause growth and development disorders in the brain Another relation between macrocephaly with duplications and microcephaly with deletions has been seen in research on the HYDIN Paralog or HYDIN2. This part of 1q21.1 is involved in the development of the brain. It is assumed to be a dosage-sensitive gene. When this gene is not available in the 1q21.1 area, it leads to microcephaly. HYDIN2 is a recent duplication (found only in humans) of the HYDIN gene found on 16q22.2.
Research on the genes CHD1L and PRKAB2 within lymphoblast cells lead to the conclusion that anomalies appear with the 1q21.1-deletion syndrome:
CHD1L is an enzyme which is involved in untangling the chromatides and the DNA repair system. With 1q21.1 deletion syndrome a disturbance occurs, which leads to increased DNA breaks. The role of CHD1L is similar to that of helicase with the Werner syndrome
PRKAB2 is involved in maintaining the energy level of cells. With 1q21.1-deletion syndrome this function was attenuated.GJA5 has been identified as the gene that is responsible for the phenotypes observed with congenital heart diseases on the 1q21.1 location. In case of a duplication of GJA5 tetralogy of Fallot is more common. In case of a deletion other congenital heart diseases than tetralogy of Fallot are more common.
References
Further reading
External links
DECIPHER database entry for 1q21.1 deletion syndrome
1q21.1 deletion, GeneReviews NCBI Bookshelf
Orpha.net |
Community-acquired pneumonia | Community-acquired pneumonia (CAP) refers to pneumonia (any of several lung diseases) contracted by a person outside of the healthcare system. In contrast, hospital-acquired pneumonia (HAP) is seen in patients who have recently visited a hospital or who live in long-term care facilities. CAP is common, affecting people of all ages, and its symptoms occur as a result of oxygen-absorbing areas of the lung (alveoli) filling with fluid. This inhibits lung function, causing dyspnea, fever, chest pains and cough.
CAP, the most common type of pneumonia, is a leading cause of illness and death worldwide. Its causes include bacteria, viruses, fungi and parasites. CAP is diagnosed by assessing symptoms, performing a physical examination, by x-ray or by sputum examination. Patients with CAP sometimes require hospitalization, and it is treated primarily with antibiotics, antipyretics and cough medicine. Some forms of CAP can be prevented by vaccination and by abstaining from tobacco products.
Signs and symptoms
Common symptoms
Coughing which produces greenish or yellow sputum
A high fever, accompanied by sweating, chills and shivering
Sharp, stabbing chest pains
Rapid, shallow, often painful breathing
Less-common symptoms
Coughing up blood (hemoptysis)
Headaches, including migraines
Loss of appetite
Excessive fatigue
Bluish skin (cyanosis)
Nausea
Vomiting
Diarrhea
Joint pain (arthralgia)
Muscle aches (myalgia)
Rapid heartbeat
Dizziness or lightheadedness
In the elderly
New or worsening confusion
Hypothermia
Poor coordination, which may lead to falls
In infants
Unusual sleepiness
Yellowing of the skin (jaundice)
Difficulty feeding
Complications
Major complications of CAP include:
Sepsis - A life-threatening reaction to infection. A common cause of sepsis is bacterial pneumonia, frequently the result of infection with streptococcus pneumoniae. Patients with sepsis require intensive care with blood pressure monitoring and support against hypotension. Sepsis can cause liver, kidney and heart damage.
Respiratory failure - CAP patients often have dyspnea, which may require support. Non-invasive machines (such as bilevel positive airway pressure), a tracheal tube or a ventilator may be used.
Pleural effusion and empyema - Microorganisms from the lung may trigger fluid collection in the pleural cavity, or empyema. Pleural fluid, if present, should be collected with a needle and examined. Depending on the results, complete drainage of the fluid with a chest tube may be necessary to prevent proliferation of the infection. Antibiotics, which do not penetrate the pleural cavity well, are less effective.
Abscess - A pocket of fluid and bacteria may appear on X-ray as a cavity in the lung. Abscesses, typical of aspiration pneumonia, usually contain a mixture of anaerobic bacteria. Although antibiotics can usually cure abscesses, sometimes they require drainage by a surgeon or radiologist.
Causes
Many different microorganisms can cause CAP. However, the most common cause is Streptococcus pneumoniae. Certain groups of people are more susceptible to CAP-causing pathogens - infants, adults with chronic conditions (such as chronic obstructive pulmonary disease), and senior citizens. Alcoholics and others with compromised immune systems are more likely to develop CAP from Haemophilus influenzae or Pneumocystis jirovecii. A definitive cause is identified in only half the cases.
Neonates and infants
It is possible for a fetus to develop a lung infection before birth by aspirating infected amniotic fluid or through a blood-borne infection which crossed the placenta. Infants can also inhale contaminated fluid from the vagina at birth. The most prevalent pathogen causing CAP in newborns is Streptococcus agalactiae, also known as group-B streptococcus (GBS). GBS causes more than half of CAP in the first week after birth. Other bacterial causes of neonatal CAP include Listeria monocytogenes and a variety of mycobacteria. CAP-causing viruses may also be transferred from mother to child; herpes simplex virus, the most common, is life-threatening, and adenoviridae, mumps and enterovirus can also cause pneumonia. Another cause of neonatal CAP is Chlamydia trachomatis, which, though acquired at birth, does not cause pneumonia until two to four weeks later. It usually presents with no fever and a characteristic, staccato cough.
CAP in older infants reflects increased exposure to microorganisms, with common bacterial causes including Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumoniae, Moraxella catarrhalis and Staphylococcus aureus. Maternally-derived syphilis is also a cause of CAP in infants. Viral causes include human respiratory syncytial virus (RSV), human metapneumovirus, adenovirus, human parainfluenza viruses, influenza and rhinovirus, and RSV is a common source of illness and hospitalization in infants. CAP caused by fungi or parasites is not usually seen in otherwise-healthy infants.
Children
Although children older than one month tend to be at risk for the same microorganisms as adults, children under five years of age are much less likely to have pneumonia caused by Mycoplasma pneumoniae, Chlamydophila pneumoniae or Legionella pneumophila than older children. In contrast, older children and teenagers are more likely to acquire Mycoplasma pneumoniae and Chlamydophila pneumoniae than adults.
Adults
A full spectrum of microorganisms is responsible for CAP in adults, and patients with certain risk factors are more susceptible to infections by certain groups of microorganisms. Identifying people at risk for infection by these organisms aids in appropriate treatment.
Many less-common organisms can cause CAP in adults; these may be determined by identifying specific risk factors, or when treatment for more common causes fails.
Risk factors
Some patients have an underlying problem which increases their risk of infection. Some risk factors are:
Obstruction - When part of the airway (bronchus) leading to the alveoli is obstructed, the lung cannot eliminate fluid; this can lead to pneumonia. One cause of obstruction, especially in young children, is inhalation of a foreign object such as a marble or toy. The object lodges in a small airway, and pneumonia develops in the obstructed area of the lung. Another cause of obstruction is lung cancer, which can block the flow of air.
Lung disease - Patients with underlying lung disease are more likely to develop pneumonia. Diseases such as emphysema and habits such as smoking result in more frequent and more severe bouts of pneumonia. In children, recurrent pneumonia may indicate cystic fibrosis or pulmonary sequestration.
Immune problems - Immune-deficient patients, such as those with HIV/AIDS, are more likely to develop pneumonia. Other immune problems that increase the risk of developing pneumonia range from severe childhood immune deficiencies, such as Wiskott–Aldrich syndrome, to the less severe common variable immunodeficiency.
Pathophysiology
The symptoms of CAP are the result of lung infection by microorganisms and the response of the immune system to the infection. Mechanisms of infection are different for viruses and other microorganisms.
Viruses
Up to 20 percent of CAP cases can be attributed to viruses. The most common viral causes are influenza, parainfluenza, human respiratory syncytial virus, human metapneumovirus and adenovirus. Less common viruses which may cause serious illness include chickenpox, SARS, avian flu and hantavirus.Typically, a virus enters the lungs through the inhalation of water droplets and invades the cells lining the airways and the alveoli. This leads to cell death; the cells are killed by the virus or they self-destruct. Further lung damage occurs when the immune system responds to the infection. White blood cells, particularly lymphocytes, activate chemicals known as cytokines which cause fluid to leak into the alveoli. The combination of cell destruction and fluid-filled alveoli interrupts the transportation of oxygen into the bloodstream. In addition to their effects on the lungs, many viruses affect other organs. Viral infections weaken the immune system, making the body more susceptible to bacterial infection, including bacterial pneumonia.
Bacteria and fungi
Although most cases of bacterial pneumonia are caused by Streptococcus pneumoniae, infections by atypical bacteria such as Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Legionella pneumophila can also cause CAP. Enteric gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, are a group of bacteria that typically live in the large intestine; contamination of food and water by these bacteria can result in outbreaks of pneumonia. Pseudomonas aeruginosa, an uncommon cause of CAP, is a difficult bacteria to treat.
Bacteria and fungi typically enter the lungs by inhalation of water droplets, although they can reach the lung through the bloodstream if an infection is present. In the alveoli, bacteria and fungi travel into the spaces between cells and adjacent alveoli through connecting pores. The immune system responds by releasing neutrophil granulocytes, white blood cells responsible for attacking microorganisms, into the lungs. The neutrophils engulf and kill the microorganisms, releasing cytokines which activate the entire immune system. This response causes fever, chills and fatigue, common symptoms of CAP. The neutrophils, bacteria and fluids leaked from surrounding blood vessels fill the alveoli, impairing oxygen transport. Bacteria may travel from the lung to the bloodstream, causing septic shock (very low blood pressure which damages the brain, kidney, and heart).
Parasites
A variety of parasites can affect the lungs, generally entering the body through the skin or by being swallowed. They then travel to the lungs through the blood, where the combination of cell destruction and immune response disrupts oxygen transport.
Diagnosis
Patients with symptoms of CAP require evaluation. Diagnosis of pneumonia is made clinically, rather than on the basis of a particular test. Evaluation begins with a physical examination by a health provider, which may reveal fever, an increased respiratory rate (tachypnea), low blood pressure (hypotension), a fast heart rate (tachycardia) and changes in the amount of oxygen in the blood. Palpating the chest as it expands and tapping the chest wall to identify dull, non-resonant areas can identify stiffness and fluid, signs of CAP. Listening to the lungs with a stethoscope (auscultation) can also reveal signs associated with CAP. A lack of normal breath sounds or the presence of crackles can indicate fluid consolidation. Increased vibration of the chest when speaking, known as tactile fremitus, and increased volume of whispered speech during auscultation can also indicate the presence of fluid.Several tests can identify the cause of CAP. Blood cultures can isolate bacteria or fungi in the bloodstream. Sputum Gram staining and culture can also reveal the causative microorganism. In severe cases, bronchoscopy can collect fluid for culture. Special tests, such as urinalysis, can be performed if an uncommon microorganism is suspected.
Chest X-rays and X-ray computed tomography (CT) can reveal areas of opacity (seen as white), indicating consolidation. CAP does not always appear on x-rays, sometimes because the disease is in its initial stages or involves a part of the lung not clearly visible on x-ray. In some cases, chest CT can reveal pneumonia not seen on x-rays. However, congestive heart failure or other types of lung damage can mimic CAP on x-ray.When signs of pneumonia are discovered during evaluation, chest X-rays and examination of the blood and sputum for infectious microorganisms may be done to support a diagnosis of CAP. The diagnostic tools employed will depend on the severity of illness, local practices and concern about complications of the infection. All patients with CAP should have their blood oxygen monitored with pulse oximetry. In some cases, arterial blood gas analysis may be required to determine the amount of oxygen in the blood. A complete blood count (CBC) may reveal extra white blood cells, indicating infection.
Prevention
CAP may be prevented by treating underlying illnesses that increasing its risk, by smoking cessation, and by vaccination. Vaccination against haemophilus influenzae and streptococcus pneumoniae in the first year of life has been protective against childhood CAP. A vaccine against streptococcus pneumoniae, available for adults, is recommended for healthy individuals over 65 and all adults with COPD, heart failure, diabetes mellitus, cirrhosis, alcoholism, cerebrospinal fluid leaks or who have had a splenectomy. Re-vaccination may be required after five or ten years.Patients who have been vaccinated against streptococcus pneumoniae, health professionals, nursing-home residents and pregnant women should be vaccinated annually against influenza. During an outbreak, drugs such as amantadine, rimantadine, zanamivir and oseltamivir have been demonstrated to prevent influenza.
Treatment
CAP is treated with an antibiotic that kills the infecting microorganism; treatment also aims at managing complications. If the causative microorganism is unidentified, which is often the case, the laboratory identifies the most effective antibiotic; this may take several days.
Health professionals consider a persons risk factors for various organisms when choosing an initial antibiotic. Additional consideration is given to the treatment setting; most patients are cured by oral medication, while others must be hospitalized for intravenous therapy or intensive care.
Current treatment guidelines recommend a beta lactam, like amoxicillin and a macrolide, like azithromycin or clarithromycin, or a quinolone, such as levofloxacin. Doxycycline is the antibiotic of choice in the UK for atypical bacteria, due to increased clostridium difficile colitis in hospital patients linked to the increased use of clarithromycin.
Ceftriaxone and azithromycin are often used to treat community acquired pneumonia, which usually present with a few days of cough, fever, and shortness of breath. Chest x-ray typically reveals a lobar infiltrate (rather than diffuse).
Newborns
Most newborn infants with CAP are hospitalized, receiving IV ampicillin and gentamicin for at least ten days to treat the common causative agents streptococcus agalactiae, listeria monocytogenes and escherichia coli. To treat the herpes simplex virus, IV acyclovir is administered for 21 days.
Children
Treatment of CAP in children depends on the childs age and the severity of illness. Children under five are not usually treated for atypical bacteria. If hospitalization is not required, a seven-day course of amoxicillin is often prescribed, with co-trimaxazole as an alternative when there is allergy to penicillins. Further studies are needed to confirm the efficacy of newer antibiotics. With the increase in drug-resistant Streptococcus pneumoniae, antibiotics such as cefpodoxime may become more popular. Hospitalized children receive intravenous ampicillin, ceftriaxone or cefotaxime, and a recent study found that a three-day course of antibiotics seems sufficient for most mild-to-moderate CAP in children.
Adults
In 2001 the American Thoracic Society, drawing on the work of the British and Canadian Thoracic Societies, established guidelines for the management of adult CAP by dividing patients into four categories based on common organisms:
Healthy outpatients without risk factors: This group (the largest) is composed of otherwise-healthy patients without risk factors for DRSP, enteric gram-negative bacteria, pseudomonas or other, less common, causes of CAP. Primary microorganisms are viruses, atypical bacteria, penicillin-sensitive streptococcus pneumoniae and haemophilus influenzae. Recommended drugs are macrolide antibiotics, such as azithromycin or clarithromycin, for seven to ten days. A shorter course of these antibiotics has been investigated, however, there is not sufficient evidence to make recommendations.
Outpatients with underlying illness or risk factors: Although this group does not require hospitalization, they have underlying health problems such as emphysema or heart failure or are at risk for DRSP or enteric gram-negative bacteria. They may be treated with a quinolone active against streptococcus pneumoniae (such as levofloxacin) or a β-lactam antibiotic (such as cefpodoxime, cefuroxime, amoxicillin or amoxicillin/clavulanic acid) and a macrolide antibiotic, such as azithromycin or clarithromycin, for seven to ten days.
Hospitalized patients without risk for pseudomonas: This group requires intravenous antibiotics, with a quinolone active against streptococcus pneumoniae (such as levofloxacin), a β-lactam antibiotic (such as cefotaxime, ceftriaxone, ampicillin/sulbactam or high-dose ampicillin plus a macrolide antibiotic (such as azithromycin or clarithromycin) for seven to ten days.
Intensive-care patients at risk for pseudomonas aeruginosa: These patients require antibiotics targeting this difficult-to-eradicate bacterium. One regimen is an intravenous antipseudomonal beta-lactam such as cefepime, imipenem, meropenem or piperacillin/tazobactam, plus an IV antipseudomonal fluoroquinolone such as levofloxacin. Another is an IV antipseudomonal beta-lactam such as cefepime, imipenem, meropenem or piperacillin/tazobactam, plus an aminoglycoside such as gentamicin or tobramycin, plus a macrolide (such as azithromycin) or a nonpseudomonal fluoroquinolone such as ciprofloxacin.For mild-to-moderate CAP, shorter courses of antibiotics (3–7 days) seem to be sufficient.Some patients with CAP will be at increased risk of death despite antimicrobial treatment. A key reason for this is the hosts exaggerated inflammatory response. There is a tension between controlling the infection on one hand and minimizing damage to other tissues on the other. Some recent research focuses on immunomodulatory therapy that can modulate the immune response in order to reduce injury to the lung and other affected organs such as the heart. Although the evidence for these agents has not resulted in their routine use, their potential benefits are promising.
Hospitalization
Some CAP patients require intensive care, with clinical prediction rules such as the pneumonia severity index and CURB-65 guiding the decision whether or not to hospitalize. Factors increasing the need for hospitalization include:
Age greater than 65
Underlying chronic illnesses
Respiratory rate greater than 30 per minute
Systolic blood pressure less than 90 mmHg
Heart rate greater than 125 per minute
Temperature below 35 or over 40 °C
Confusion
Evidence of infection outside the lungLaboratory results indicating hospitalization include:
Arterial oxygen tension less than 60 mm Hg
Carbon dioxide over 50 mmHg or pH under 7.35 while breathing room air
Hematocrit under 30 percent
Creatinine over 1.2 mg/dl or blood urea nitrogen over 20 mg/dl
White-blood-cell count under 4 × 10^9/L or over 30 × 10^9/L
Neutrophil count under 1 x 10^9/LX-ray findings indicating hospitalization include:
Involvement of more than one lobe of the lung
Presence of a cavity
Pleural effusion
Prognosis
The CAP outpatient mortality rate is less than one percent, with fever typically responding within the first two days of therapy, and other symptoms abating in the first week. However, X-rays may remain abnormal for at least a month. Hospitalized patients have an average mortality rate of 12 percent, with the rate rising to 40 percent for patients with bloodstream infections or those who require intensive care. Factors increasing mortality are identical to those indicating hospitalization.
When CAP does not respond to treatment, this may indicate a previously unknown health problem, a treatment complication, inappropriate antibiotics for the causative organism, a previously unsuspected microorganism (such as tuberculosis) or a condition mimicking CAP (such as granuloma with polyangiitis). Additional tests include X-ray computed tomography, bronchoscopy or lung biopsy.
Epidemiology
CAP is common worldwide, and is a major cause of death in all age groups. In children, most deaths (over two million a year) occur in the newborn period. According to a World Health Organization estimate, one in three newborn deaths result from pneumonia. Mortality decreases with age until late adulthood, with the elderly at risk for CAP and its associated mortality.
More CAP cases occur during the winter than at other times of the year. CAP is more common in males than females, and more common in black people than Caucasians. Patients with underlying illnesses (such as Alzheimers disease, cystic fibrosis, COPD, tobacco smoking, alcoholism or immune-system problems) have an increased risk of developing pneumonia.
See also
Bacterial pneumonia
Viral pneumonia
Fungal pneumonia
Parasitic pneumonia
References
Mandell LA, Wunderink RG, Anzueto A, et al. (March 2007). "Infectious Diseases Society of America/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults". Clinical Infectious Diseases. 44 (Suppl 2): S27–72. doi:10.1086/511159. PMID 17278083.
External links
Infectious Diseases Society of America/American Thoracic Society Consensus Guidelines on the Management of Community-Acquired Pneumonia in Adults PDF |
Myxoid cyst | A myxoid cyst is a cutaneous condition often characterized by nail plate depression and grooves.
See also
Scleroderma
List of cutaneous conditions
List of radiographic findings associated with cutaneous conditions
== References == |
Parakeratosis | Parakeratosis is a mode of keratinization characterized by the retention of nuclei in the stratum corneum. In mucous membranes, parakeratosis is normal. In the skin, this process leads to the abnormal replacement of annular squames with nucleated cells. Parakeratosis is associated with the thinning or loss of the granular layer and is usually seen in diseases of increased cell turnover, whether inflammatory or neoplastic. Parakeratosis is seen in the plaques of psoriasis and in dandruff.
Granular parakeratosis (originally termed axillary granular parakeratosis) is an idiopathic, benign, nondisabling cutaneous disease that manifests with intertriginous erythematous, brown or red, scaly or keratotic papules and plaques. It presents in all age groups and has no established clinical associations.
See also
Skin lesion
Skin disease
List of skin diseases
== References == |
Mitochondrial encephalomyopathy | A mitochondrial encephalomyopathy is a form of encephalomyopathy that is associated with a mitochondrial disease.
MELAS syndrome
Examples include MELAS syndrome and MERRF syndrome. These conditions can sometimes present together.KSS is sometimes included in this category, but it is not included in this category in MeSH.
References
== External links == |
Pycnodysostosis | Pycnodysostosis (from Greek: πυκνός (puknos) meaning "dense", dys ("defective"), and ostosis ("condition of the bone")), is a lysosomal storage disease of the bone caused by a mutation in the gene that codes the enzyme cathepsin K. It is also known as PKND and PYCD.
History
The disease was first described by Maroteaux and Lamy in 1962 at which time it was defined by the following characteristics: dwarfism; osteopetrosis; partial agenesis of the terminal digits of the hands and feet; cranial anomalies, such as persistence of fontanelles and failure of closure of cranial sutures; frontal and occipital bossing; and hypoplasia of the angle of the mandible. The defective gene responsible for the disease was discovered in 1996. The French painter Henri de Toulouse Lautrec (1864-1901) is believed to have had the disease.
Signs and symptoms
Pycnodysostosis causes the bones to be abnormally dense; the last bones of the fingers (the distal phalanges) to be unusually short; and delays the normal closure of the connections (sutures) of the skull bones in infancy, so that the "soft spot" (fontanelle) on top of the head remains widely open. Because of the bone denseness, those with the syndrome suffer from fractures.Those with the syndrome have brittle bones which easily break, especially in the legs and feet.
Other abnormalities involve the head and face, teeth, collar bones, skin, and nails. The front and back of the head are prominent. Within the open sutures of the skull, there may be many small bones (called wormian bones). The midface is less full than usual. The nose is prominent. The jaw can be small. The palate is narrow and grooved. There will be delay in fall of milk teeth. The permanent teeth can also be slow to appear. The permanent teeth are commonly irregular and teeth may be missing (hypodontia). The collar bones are often underdeveloped and malformed. The nails are flat, grooved, and dysplastic. High bone density, Acro-osteolysis and obtuse mandibular angle are the characteristic radiological findings of this disorder.Pycnodysostosis also causes problems that may become evident with time. Aside from the broken bones, the distal phalanges and the collar bone can undergo slow progressive deterioration. Vertebral defects may permit the spine to curve laterally resulting in scoliosis. The dental problems often require orthodontic care and cavities are common.
Patients with PYCD are at a high risk of severe obstructive sleep apnea (OSA) due to upper airway obstructions. OSA must be managed to prevent long term pulmonary complications.Amongst infrequent complications, attention should be paid to maxillofacial anomalies. Snoring can be one of the presenting complaints and this needs early evaluation and management of obstructive sleep apnea if present to prevent long term pulmonary complications.
Genetics
PYCD is a rare autosomal recessive disorder. The molecular basis of pycnodysostosis was elucidated in 1996 by Gelb and collaborators and the disorder results from biallelic pathogenic mutation in CTSK gene (OMIM * 601105). This gene codes for cathepsin K, a lysosomal cysteine protease that is highly expressed in osteoclasts and plays a significant role in bone remodelling by degenerating the bone matrix proteins such as type I collagen, osteopontin, and osteonectin. Defective function of cathepsin K therefore results in failure of normal degradation of the accumulated collagen fibres in the resorptive microenvironment by osteoclasts despite normal generation of ruffled membranes and mobilization of bone minerals.
If both parents of a diagnosed individual are heterozygous for a CTSK pathogenic variant, siblings of the individual have a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier.
Diagnosis
Pycnodysostosis is one of those disorders which has a typical facial gestalt and can be clinically identified in the majority of cases. Skeletal surveys can also aid in clinical diagnosis and characteristic features include high bone density, acro-osteolysis and obtuse mandibular angle. Molecular testing will be the final resort to confirm the diagnosis. Due to the limited number of exons of the CTSK gene that causes pycnodysostosis, a cheaper genetic testing called Sanger sequencing can be employed to confirm the diagnosis.
Treatment and management
The treatment of pycnodysostosis is currently based on symptomatic management and no active trials are in place for a curative approach. The comorbidities like short stature, fracture and maxillofacial issues can be easily managed when identified earlier, which can improve the quality of life of these individuals.
Management can include physical, medical, and psychological care including:
Growth hormone therapy
Environmental and/or occupational modifications
Orthopedic care for fractures and scoliosis
Sleep medicine to address sleep apnea
Dental and orthodontic carePatients are likely to have annual physical exams with doctors and specialists to monitor all symptoms.
Epidemiology
Its incidence is estimated to be 1.7 per 1 million births.
Differences from osteopetrosis
Many of the radiological findings of PYCD are similar to those of osteopetrosis, a disease that causes bone density due to a defect in bone reabsorption; however, the two diagnoses differ in several ways. In PYCD, there is also:
Wormian bones
Delayed closure of sutures and fontanels
Obtuse mandibular angle
Gracile clavicles that are hypoplastic at the lateral ends
Partial absence of the hyoid bone
Hypoplasia or aplasia of the distal phalanges and ribs
References
== External links == |
Hyperdontia | Hyperdontia is the condition of having supernumerary teeth, or teeth that appear in addition to the regular number of teeth (32 in the average adult). They can appear in any area of the dental arch and can affect any dental organ. The opposite of hyperdontia is hypodontia, where there is a congenital lack of teeth, which is a condition seen more commonly than hyperdontia. The scientific definition of hyperdontia is "any tooth or odontogenic structure that is formed from tooth germ in excess of usual number for any given region of the dental arch." The additional teeth, which may be few or many, can occur on any place in the dental arch. Their arrangement may be symmetrical or non-symmetrical.
Signs and symptoms
The presence of a supernumerary tooth, particularly when seen in young children, is associated with a disturbance of the maxillary incisor region. This commonly results in the impaction of the incisors during the mixed dentition stage. The study debating this also considered many other factors such as: the patients age, number, morphology, growth orientation and position of the supernumerary tooth. Alongside this issue, the presence of an extra tooth can impede the eruption of adjacent additional or normal teeth. Therefore, the presence of a supernumerary tooth when found must be approached with the appropriate treatment plan, incorporating the likelihood of incisal crowding. In some individuals, the additional teeth can erupt far from the dental arch, within the maxillary sinus. The extra teeth may also migrate to a different location after development. In some cases, supernumerary teeth can lead to the formation of cysts. Crowding is also frequently seen in people with hyperdontia.
Causes
There is evidence of hereditary factors along with some evidence of environmental factors leading to this condition. While a single excess tooth is relatively common, multiple hyperdontia is rare in people with no other associated diseases or syndromes. Many supernumerary teeth never erupt, but they may delay eruption of nearby teeth or cause other dental or orthodontic problems. Molar-type extra teeth are the most common type. Dental X-rays are often used to diagnose hyperdontia.
It is suggested that supernumerary teeth develop from a third tooth bud arising from the dental lamina near the regular tooth bud or possibly from splitting the regular tooth bud itself. Supernumerary teeth in deciduous (baby) teeth are less common than in permanent teeth.
Related conditions
Hyperdontia is seen in a number of disorders, including Gardners syndrome and cleidocranial dysostosis, where multiple supernumerary teeth are seen that are usually impacted.Other associated conditions are: Cleidocranial dysplasia, Ehlers–Danlos syndrome Type III, Ellis–van Creveld syndrome, Gardners syndrome, Goldenhar syndrome, Hallermann–Streiff syndrome, Orofaciodigital syndrome type I, Incontinentia pigmenti, Marfan syndrome, Nance–Horan syndrome, and Tricho-rhino-phalangeal syndrome Type 1.
Diagnosis
Supernumerary teeth may be detected by taking two different dental X-rays at different angles. Examples of this may be an intra-oral X-ray (one that is taken inside the mouth) and a panoramic radiograph. However, these X-rays are 2D and therefore do not accurately portray the 3D view of the teeth.
Types
Supernumerary teeth can be classified by shape and by position. The shapes include the following:
Supplemental (where the tooth has a normal shape for the teeth in that series);
Tuberculate (also called barrel shaped);
Conical (also called peg shaped);
Compound odontoma (multiple small tooth-like forms);
Complex odontoma (a disorganized mass of dental tissue)When classified by position, a supernumerary tooth may be referred to as a mesiodens, a paramolar, or a distomolar. Occasionally, these teeth do not erupt into the oral cavity but manifest as a malocclusion.The most common supernumerary tooth is a mesiodens, which is a malformed, peg-like tooth that occurs between the maxillary central incisors.
Fourth and fifth molars that form behind the third molars are another kind of supernumerary teeth.
Treatment
Although these teeth are usually asymptomatic and pose no threat to the individual, they are often extracted for aesthetic reasons, to allow the eruption of other teeth, orthodontic reasons and/or suspected pathology. This is done particularly if the mesiodens is positioned in the maxillary central incisor region. The traditional method of removal is done by using bone chisels, although a more advanced technique has been found to be more beneficial, especially if surgery is required. Through the use of piezoelectricity, piezoelectric ultrasonic bone surgery may be more time-consuming than the traditional method but it seems to reduce the post-operative bleeding and associated complications quite significantly.
Epidemiology
It is evident that hyperdontia is more common in the permanent dentition than in the primary. There is a considerable difference between males and females in the prevalence of these teeth in permanent dentition; hyperdontia is twice as common in males as in females. However, this approximation varies in terms of location, other associating syndromes that may be present, and the ethnicity of the individual. In terms of ethnicity, it can be seen that hyperdontia is in fact less common in European than in Asian populations. There is evidence to show that an individual is more likely to have hyperdontia if other members of their family also have the condition.
References
== External links == |
Metamorphopsia | Metamorphopsia is a type of distorted vision in which a grid of straight lines appears wavy and parts of the grid may appear blank. People can first notice they suffer with the condition when looking at mini-blinds in their home. For example, straight lines might be wavy or bendy. Things may appear closer or further than they are.
Initially characterized in the 1800s, metamorphopsia was described as one of the primary and most notable indications of myopic and senile maculopathies. Metamorphopsia can present itself as unbalanced vision, resulting from small unintentional movements of the eye as it tries to stabilize the field of vision. Metamorphopsia can also lead to the misrepresentation of an object’s size or shape.It is mainly associated with macular degeneration, particularly age-related macular degeneration with choroidal neovascularization. Other conditions that can present with complaints of metamorphopsia include: pathological myopia, presumed ocular histoplasmosis syndrome, choroidal rupture and multifocal choroiditis.
Pathology
The mechanisms that result in the development of metamorphopsia involve structural changes in the retina of the eye (retinal mechanism) as well as processing changes in the cerebral cortex of the brain (cortical mechanism). The retinal mechanism involves the displacement of retinal layers which results in the mislocation of light on the retina. The cortical mechanism, which was discovered after the retinal mechanism, is affected by perceptual “filling-in” and visual crowding effects. The cortical mechanism was found to work in combination with the retinal mechanism to contribute to metamorphopsia in long-standing maculopathy or after the treatment of macular disorders.
Causes of Metamorphopsia
Metamorphopsia can be a symptom of a number of eye disorders involving the retina or macula. Some of these conditions include the following:
Age-related macular degeneration
Epiretinal membrane and vitreomacular traction
Posterior vitreous detachment
Macular hole
Diagnosis
Tests used for diagnosis of Metamorphopsia mostly make use of subjective assessments of how a person views regular patterns. Many of these tests have a poor ability to accurately diagnose or identify a person with the disease (i.e.,poor sensitivity). The use of assessments such as a psychophysical test called preferential hyperacuity perimetry, which assesses a person’s ability to any misalignments of visual objects, may permit a more sensitive diagnosis of Metamorphopsia.
Treatment and Prognosis
Metamorphopsia is a symptom of several common retinal and macular diseases, therefore treating the underlying disorder can improve symptoms. For people who have conditions such as Epiretinal membrane (ERM), Macular Holes and Retinal Detachment, decreased metamorphopsia is associated with an increase in visual acuity. Quantitative evaluation of metamorphopsia is an important step in understanding visual functions of individuals with macular disorders and is an essential tool for physicians in evaluating treatment results.
Types
Dry (non-exudative, > 80%)—deposition of yellowish extracellular material in and between Bruchs membrane and retinal pigment epithelium (“drusen”) with gradual loss in vision.Wet (exudative, 10–15%)—rapid loss of vision due to bleeding secondary to choroidal neovascularization.
Etymology
Gk, meta + morphe, form, opsis, sight
See also
Dysmorphopsia
Hallucination
== References == |
Asteroid hyalosis | Asteroid hyalosis is a degenerative condition of the eye involving small white opacities in the vitreous humor. It is known to occur in humans, dogs, cats, horses, and chinchillas. Clinically, these opacities are quite refractile, giving the appearance of stars (or asteroids) shining in the night sky—except that ocular asteroids are often quite mobile. Ocular asteroids must be distinguished from the more common typical vitreous floaters, which are usually fibrillar or cellular condensates. The cause of asteroid hyalosis is unknown, but it has been associated with diabetes mellitus, hypertension, hypercholesterolemia, and, in certain animals, tumors of the ciliary body. In dogs, asteroid hyalosis is considered to be an age related change. The asteroid bodies are made up of hydroxylapatite, which in turn consists of calcium and phosphates or phospholipids. While asteroid hyalosis does not usually severely affect vision, the floating opacities can be quite annoying, and may interfere significantly with visualization and testing of the retina. While treatment of asteroid hyalosis is usually unnecessary, vitrectomy may occasionally be indicated, for both diagnostic and therapeutic purposes.
See also
Synchysis scintillans
References
== External links == |
Corneal ectatic disorders | Corneal ectatic disorders or corneal ectasia are a group of uncommon, noninflammatory, eye disorders characterised by bilateral thinning of the central, paracentral, or peripheral cornea.
Types
Keratoconus, a progressive, noninflammatory, bilateral, asymmetric disease, characterized by paraxial stromal thinning and weakening that leads to corneal surface distortion.
Keratoglobus, a rare noninflammatory corneal thinning disorder, characterised by generalised thinning and globular protrusion of the cornea.
Pellucid marginal degeneration, a bilateral, noninflammatory disorder, characterized by a peripheral band of thinning of the inferior cornea.
Posterior keratoconus, a rare condition, usually congenital, which causes a nonprogressive thinning of the inner surface of the cornea, while the curvature of the anterior surface remains normal. Usually only a single eye is affected.
Post-LASIK ectasia, a complication of LASIK eye surgery.
Terriens marginal degeneration, a painless, noninflammatory, unilateral or asymmetrically bilateral, slowly progressive thinning of the peripheral corneal stroma.
Diagnosis
Usually diagnosed clinically by several clinical tests. Although some investigations might needed for confirming the diagnosis and to differentiate different types of corneal ectatic diseases.
Corneal topography
Corneal tomography
Treatment
Treatment options include contact lenses and intrastromal corneal ring segments for correcting refractive errors caused by irregular corneal surface, corneal collagen cross-linking to strengthen a weak and ectatic cornea, or corneal transplant for advanced cases.
References
External links
International Journal of Keratoconus and Ectatic Corneal Diseases |
Anagen effluvium | Anagen effluvium is the pathologic loss of anagen or growth-phase hairs. Classically, it is caused by radiation therapy to the head and systemic chemotherapy, especially with alkylating agents.: 753–4 Anagen effluvium is due to an acute injury to the hair follicles by an endogenous or exogenous cause, resulting in sudden diffuse shedding of structurally damaged hairs. Diffuse alopecia (hair loss) may occur over a period of days. The alopecia is non-scarring.
Pathophysiology
Any insult that impairs mitosis of hair follicle keratinocytes can cause anagen effluvium. Disruption to cell division in the hair matrix makes the hair narrowed at its base and susceptible to breakage just above the zone of keratinisation. The necrotic matrix forms plugs consisting of melanin, keratin and inner root sheath which are extruded through the follicular opening. This process is known as trichomalacia. The main causes of anagen effluvium are an infection, a drug, a toxin, radiation or an autoimmune disease.Toxins that can interrupt hair growth include:
Chemotherapy agents, usually prescribed to treat cancer, especially when multiple drugs are used or they are in high dose. Severe hair loss is reported from doxorubicin, the nitrosoureas, and cyclophosphamide. Other causes are bleomycin, dactinomycin, daunorubicin, systemic fluorouracil, and high-dose methotrexate.
Other medicines such as colchicine and ciclosporin (ciclosporin more often causes increased hair growth)
Poisons such as thallium, arsenic, gold and bismuth.
Evaluation
A biopsy is rarely necessary, as a diagnosis can usually be made on history and physical exam findings alone. If a biopsy is requested or necessary for diagnosis, it can help exclude telogen effluvium. In anagen effluvium, histopathologic evaluation of a punch biopsy of the scalp will exhibit a normal anagen-to-telogen ratio, which is less than 15% telogen hair follicles. If greater than 15% of the hair follicles are in the telogen phase, this more supports a diagnosis of telogen effluvium.
Treatment
The management of anagen effluvium should be aimed at limiting the amount of time the patient has alopecia. To date, several agents have been studied; unfortunately, no treatment appears to be effective in preventing or stopping the hair loss. Although the results have not been impressive in stopping or preventing hair loss, it has been postulated that topical minoxidil is effective in reducing the period of baldness by an average of fifty days. Several studies have described limiting drug delivery to the scalp by using a scalp tourniquet during chemotherapy. If scalp or brain metastases are a possibility, this method should not be used to allow penetration of the chemotherapeutic agent. Another method that has shown success is inducing scalp hypothermia (by keeping ice over the scalp) to a scalp temperature of fewer than 24° Celsius during chemotherapy with daunorubicin, doxorubicin, paclitaxel, vincristine, vinblastine, mechlorethamine, actinomycin D, and epirubicin.As pharmacologic agents successful in treating and preventing anagen effluvium have not been found, patient education and aesthetic advice on managing hair loss are fundamental to managing androgen effluvium. Expectations should be managed so that patients understand the unfortunate inevitability of the disorder; however, they should also be assured that most cases of anagen effluvium are reversible and they will grow hair once chemotherapy is ceased. Patients should be instructed to avoid chemical trauma to the hair. This includes hot appliances, bleach, or color treatments in the time leading up to and during chemotherapy. If possible, patients should be given resources to obtain hairpieces or protective scarves before hair loss and educated on the benefits such garments offer, including cold protection in addition to the aesthetic component.
Differential Diagnosis
The differential diagnosis for anagen effluvium includes other nonscarring alopecias such as telogen effluvium, trichotillomania, and androgenetic alopecia. These entities can be distinguished by history, hair pull test, and trichoscopy. A thorough review of systems should be completed to exclude other causes of hair loss such as nutritional deficiencies, metabolic and endocrine disorders, and infections.
See also
Telogen effluvium
Noncicatricial alopecia
List of cutaneous conditions
References
== External links == |
Hypophosphatemia | Hypophosphatemia is an electrolyte disorder in which there is a low level of phosphate in the blood. Symptoms may include weakness, trouble breathing, and loss of appetite. Complications may include seizures, coma, rhabdomyolysis, or softening of the bones.Causes include alcohol use disorder, refeeding in those with malnutrition, recovery from diabetic ketoacidosis, burns, hyperventilation, and certain medications. It may also occur in the setting of hyperparathyroidism, hypothyroidism, and Cushing syndrome. It is diagnosed based on a blood phosphate concentration of less than 0.81 mmol/L (2.5 mg/dL). When levels are below 0.32 mmol/L (1.0 mg/dL) it is deemed to be severe.Treatment depends on the underlying cause. Phosphate may be given by mouth or by injection into a vein. Hypophosphatemia occurs in about 2% of people within hospital and 70% of people in the intensive care unit (ICU).
Signs and symptoms
Muscle dysfunction and weakness – This occurs in major muscles, but also may manifest as: diplopia, low cardiac output, dysphagia, and respiratory depression due to respiratory muscle weakness.
Mental status changes – This may range from irritability to gross confusion, delirium, and coma.
White blood cell dysfunction, causing worsening of infections.
Instability of cell membranes due to low adenosine triphosphate (ATP) levels – This may cause rhabdomyolysis with increased serum levels of creatine phosphokinase, and also hemolytic anemia.
Increased affinity for oxygen in the blood caused by decreased production of 2,3-bisphosphoglyceric acid.
Causes
Refeeding syndrome – This causes a demand for phosphate in cells due to the action of hexokinase, an enzyme that attaches phosphate to glucose to begin metabolism of glucose. Also, production of ATP when cells are fed and recharge their energy supplies requires phosphate. A similar mechanism is seen in the treatment of diabetic ketoacidosis, which can be complicated by respiratory failure in these cases due to respiratory muscle weakness.
Respiratory alkalosis – Any alkalemic condition moves phosphate out of the blood into cells. This includes most common respiratory alkalemia (a higher than normal blood pH from low carbon dioxide levels in the blood), which in turn is caused by any hyperventilation (such as may result from sepsis, fever, pain, anxiety, drug withdrawal, and many other causes). This phenomenon is seen because in respiratory alkalosis carbon dioxide (CO2) decreases in the extracellular space, causing intracellular CO2 to freely diffuse out of the cell. This drop in intracellular CO2 causes a rise in cellular pH which has a stimulating effect on glycolysis. Since the process of glycolysis requires phosphate (the end product is adenosine triphosphate), the result is a massive uptake of phosphate into metabolically active tissue (such as muscle) from the serum. However, that this effect is not seen in metabolic alkalosis, for in such cases the cause of the alkalosis is increased bicarbonate rather than decreased CO2. Bicarbonate, unlike CO2, has poor diffusion across the cellular membrane and therefore there is little change in intracellular pH.
Alcohol use disorder – Alcohol impairs phosphate absorption. People who excessively consume alcohol are usually also malnourished with regard to minerals. In addition, alcohol treatment is associated with refeeding, which further depletes phosphate, and the stress of alcohol withdrawal may create respiratory alkalosis, which exacerbates hypophosphatemia (see above).
Malabsorption – This includes gastrointestinal damage, and also failure to absorb phosphate due to lack of vitamin D, or chronic use of phosphate binders such as sucralfate, aluminum-containing antacids, and (more rarely) calcium-containing antacids.
Intravenous iron (usually for anemia) may cause hypophosphatemia. The loss of phosphate is predominantly the result of renal wasting.Primary hypophosphatemia is the most common cause of non-nutritional rickets. Laboratory findings include low-normal serum calcium, moderately low serum phosphate, elevated serum alkaline phosphatase, and low serum 1,25 dihydroxy-vitamin D levels, hyperphosphaturia, and no evidence of hyperparathyroidism.Hypophosphatemia decreases 2,3-bisphosphoglycerate (2,3-BPG) causing a left shift in the oxyhemoglobin curve.Other rarer causes include:
Certain blood cancers such as lymphoma or leukemia
Hereditary causes
Liver failure
Tumor-induced osteomalacia
Pathophysiology
Hypophosphatemia is caused by the following three mechanisms:
Inadequate intake (often unmasked in refeeding after long-term low phosphate intake)
Increased excretion (e.g. in hyperparathyroidism, hypophosphatemic rickets)
Shift of phosphorus from the extracellular to the intracellular space. This can be seen in treatment of diabetic ketoacidosis, refeeding, short-term increases in cellular demand (e.g. hungry bone syndrome) and acute respiratory alkalosis.
Diagnosis
Hypophosphatemia is diagnosed by measuring the concentration of phosphate in the blood. Concentrations of phosphate less than 0.81 mmol/L (2.5 mg/dL) are considered diagnostic of hypophosphatemia, though additional tests may be needed to identify the underlying cause of the disorder.
Treatment
Standard intravenous preparations of potassium phosphate are available and are routinely used in malnourished people and people who consume excessive amounts of alcohol. Supplementation by mouth is also useful where no intravenous treatment are available. Historically one of the first demonstrations of this was in people in concentration camp who died soon after being re-fed: it was observed that those given milk (high in phosphate) had a higher survival rate than those who did not get milk.Monitoring parameters during correction with IV phosphate
Phosphorus levels should be monitored after 2 to 4 hours after each dose, also monitor serum potassium, calcium and magnesium. Cardiac monitoring is also advised.
See also
X-linked hypophosphatemia
References
== External links == |
Umbilical cord prolapse | Umbilical cord prolapse is when the umbilical cord comes out of the uterus with or before the presenting part of the baby. The concern with cord prolapse is that pressure on the cord from the baby will compromise blood flow to the baby. It usually occurs during labor but can occur anytime after the rupture of membranes.The greatest risk factors are an abnormal position of the baby within the uterus and a premature or small baby. Other risk factors include a multiple pregnancy, more than one previous delivery, and too much amniotic fluid. Whether medical rupture of the amniotic sac is a risk is controversial. The diagnosis should be suspected if there is a sudden decrease in the babys heart rate during labor. Seeing or feeling the cord confirms the diagnosis.Management focuses on quick delivery, usually by cesarean section. Filling the bladder or pushing up the baby by hand is recommended until this can take place. Sometimes women will be placed in a knee-chest position or the Trendelenburg position in order to help prevent further cord compression. With appropriate management, the majority of cases have good outcomes.Umbilical cord prolapse occurs in about 1 in 500 pregnancies. The risk of death of the baby is about 10%. However, much of this risk is due to congenital anomalies or prematurity. It is considered an emergency.
Signs and symptoms
The first sign of umbilical cord prolapse is usually a sudden and severe decrease in fetal heart rate that does not immediately resolve. On fetal heart tracing (a linear recording of the fetal heart rate) this would usually look like moderate to severe variable decelerations. In overt cord prolapse, the cord can be seen or felt on the vulva or vagina.A majority of umbilical cord prolapse cases happen during the second stage of labor.
Risk factors
Risk factors that are associated with umbilical cord prolapse tend to make it difficult for the baby from appropriately engaging and filling the maternal pelvis or are related to abnormalities of the umbilical cord. The two major categories of risk factors are spontaneous and iatrogenic (those that result from medical intervention).
spontaneous factors:
fetal malpresentation: abnormal fetal lie tends to result in space below the baby in the maternal pelvis, which can then be occupied by the cord.
polyhydramnios, or an abnormally high amount of amniotic fluid
prematurity: likely related to increased chance of malpresentation and relative polyhydramnios.
low birth weight: usually described as <2500g at birth, though some studies will use <1500g. Cause is likely similar to those for prematurity.
multiple gestation, or being pregnant with more than one baby at a given time: more likely to occur in the baby that is not born first.
spontaneous rupture of membranes: about half of prolapses occur within 5 minutes of membrane rupture, two-thirds within 1 hour, 95% within 24 hours.
treatment associated factors:
artificial rupture of membranes
placement of internal monitors (for example, internal scalp electrode or intrauterine pressure catheter)
manual rotation of fetal head
Diagnosis
Umbilical cord prolapse should always be considered a possibility when there is a sudden decrease in fetal heart rate or variable decelerations, particularly after the rupture of membranes. With overt prolapses, the diagnosis can be confirmed if the cord can be felt on vaginal examination. Without overt prolapse, the diagnosis can only be confirmed after a cesarean section, though even then it will not always be evident at time of procedure.
Classification
There are three types of umbilical prolapse that can occur:
overt umbilical cord prolapse: descent of the umbilical cord past the presenting fetal part. In this case, the cord is through the cervix and into or beyond the vagina. Overt umbilical cord prolapse requires rupture of membranes. This is the most common type of cord prolapse.
occult umbilical prolapse: descent of the umbilical cord alongside the presenting fetal part, but has not advanced past the presenting fetal part. Occult umbilical prolapse can occur with both intact or ruptured membranes.
funic (cord) presentation: presence of the umbilical cord between the presenting fetal part and fetal membranes. In this case, the cord has not passed the opening of the cervix. In funic presentation, the membranes are not yet ruptured.
Management
The typical treatment of umbilical cord prolapse in the setting of a viable pregnancy involves immediate delivery by the quickest and safest route possible. This usually requires cesarean section, especially if the woman is in early labor. Occasionally, vaginal delivery will be attempted if clinical judgment determines that is a safer or quicker method.Other interventions during management of cord prolapse are typically used to decrease the chance of complications while preparations for delivery are being made. These interventions are focused on reducing pressure on the cord to prevent fetal complications from cord compression. The following maneuvers are among those used in clinical practice:
Manual elevation of the presenting fetal part.
Repositioning of the mother to be in the knee-chest position or Trendelenburg position (head down with feet elevated), lying on left side is usually preferred.
Filling of the bladder using a foley catheter can help elevate the presenting fetal part and lift it off the cord.
Use of tocolytics (medications to suppress labor) have been proposed, usually done in addition to bladder filling rather than as a stand-alone intervention.If the mother is far from delivery, funic reduction (manually placing the cord back into the uterine cavity) has been attempted, with successful cases reported. However, this is not currently recommended by the Royal College of Obstetricians and Gynaecologists (RCOG), as there is insufficient evidence to support this maneuver.
Outcomes
The primary concern with umbilical cord prolapse is inadequate blood supply, and thus oxygen, to the baby if the cord becomes compressed. The cord can become compressed either due to mechanical pressure (usually from the presenting fetal part) or from sudden contraction of the vessels due to decreased temperatures in the vagina in comparison to the uterus. This can lead to death of the baby or other complications.
Historically, the rate of fetal death in the setting of cord prolapse has been as high 40%. However, these estimates occurred in the context of home or births outside of the hospital. When considering cord prolapses that have occurred in inpatient labor and delivery settings, the rate drops to as low as 0-3%, though the mortality rate remains higher than for babies without cord prolapse. The reduction in mortality for hospital births is likely due to the ready availability of immediate cesarean section.
Many other fetal outcomes have been studied, including Apgar score (a quick assessment of a newborns health status) at 5 minutes and length of hospitalization after delivery. While both measures are worse for newborns delivered after cord prolapse, it is unclear what effect this has in the long-term. Relatively large studies that have tried to quantify long-term effects of cord prolapse on children found that less than 1% (1 in 120 studied) had a major neurologic disability, and less than 1% (110 in 16,675) had diagnosed cerebral palsy.
Epidemiology
Rates of umbilical cord prolapse ranges from 0.1 to 0.6% of all pregnancies. This rate has remained stable over time. A recent study estimates 77% of cord prolapses occur in singleton pregnancies (where there is only one baby). In twin pregnancies, cord prolapses occur more frequently in the second twin to be delivered, with 9% in the first twin and 14% in the second twin.
References
== External links == |
Coronary artery disease | Coronary artery disease (CAD), also called coronary heart disease (CHD), ischemic heart disease (IHD), myocardial ischemia, or simply heart disease, involves the reduction of blood flow to the heart muscle due to build-up of atherosclerotic plaque in the arteries of the heart. It is the most common of the cardiovascular diseases. Types include stable angina, unstable angina, myocardial infarction, and sudden cardiac death. A common symptom is chest pain or discomfort which may travel into the shoulder, arm, back, neck, or jaw. Occasionally it may feel like heartburn. Usually symptoms occur with exercise or emotional stress, last less than a few minutes, and improve with rest. Shortness of breath may also occur and sometimes no symptoms are present. In many cases, the first sign is a heart attack. Other complications include heart failure or an abnormal heartbeat.Risk factors include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, and excessive alcohol consumption. A number of tests may help with diagnoses including: electrocardiogram, cardiac stress testing, coronary computed tomographic angiography, and coronary angiogram, among others.Ways to reduce CAD risk include eating a healthy diet, regularly exercising, maintaining a healthy weight, and not smoking. Medications for diabetes, high cholesterol, or high blood pressure are sometimes used. There is limited evidence for screening people who are at low risk and do not have symptoms. Treatment involves the same measures as prevention. Additional medications such as antiplatelets (including aspirin), beta blockers, or nitroglycerin may be recommended. Procedures such as percutaneous coronary intervention (PCI) or coronary artery bypass surgery (CABG) may be used in severe disease. In those with stable CAD it is unclear if PCI or CABG in addition to the other treatments improves life expectancy or decreases heart attack risk.In 2015, CAD affected 110 million people and resulted in 8.9 million deaths. It makes up 15.6% of all deaths, making it the most common cause of death globally. The risk of death from CAD for a given age decreased between 1980 and 2010, especially in developed countries. The number of cases of CAD for a given age also decreased between 1990 and 2010. In the United States in 2010, about 20% of those over 65 had CAD, while it was present in 7% of those 45 to 64, and 1.3% of those 18 to 45; rates were higher among men than women of a given age.
Signs and symptoms
The narrowing of coronary arteries reduces the supply of oxygen-rich blood flowing to the heart, which becomes more pronounced during strenuous activities during which the heart beats faster. For some, this causes severe symptoms, while others experience no symptoms at all.The most common symptom is chest pain or discomfort that occurs regularly with activity, after eating, or at other predictable times; this phenomenon is termed stable angina and is associated with narrowing of the arteries of the heart. Angina also includes chest tightness, heaviness, pressure, numbness, fullness, or squeezing. Angina that changes in intensity, character or frequency is termed unstable. Unstable angina may precede myocardial infarction. In adults who go to the emergency department with an unclear cause of pain, about 30% have pain due to coronary artery disease. Angina, shortness of breath, sweating, nausea or vomiting, and lightheadedness are signs of a heart attack, or myocardial infarction, and immediate emergency medical services are crucial.
Symptoms in women
Symptoms in women can differ from those in men, and the most common symptom reported by women of all races is shortness of breath. Other symptoms more commonly reported by women than men are extreme fatigue, sleep disturbances, indigestion, and anxiety. However, some women do experience irregular heartbeat, dizziness, sweating, and nausea. Burning, pain, or pressure in the chest or upper abdomen that can travel to the arm or jaw can also be experienced in women, but it is less commonly reported by women than men. On average, women experience symptoms 10 years later than men. Women are less likely to recognize symptoms and seek treatment.
Risk factors
Coronary artery disease has a number of well determined risk factors. Some of these include high blood pressure, smoking, diabetes, lack of exercise, obesity, high blood cholesterol, poor diet, depression, family history, psychological stress and excessive alcohol. About half of cases are linked to genetics. Smoking and obesity are associated with about 36% and 20% of cases, respectively. Smoking just one cigarette per day about doubles the risk of CAD. Lack of exercise has been linked to 7–12% of cases. Exposure to the herbicide Agent Orange may increase risk. Rheumatologic diseases such as rheumatoid arthritis, systemic lupus erythematosus, psoriasis, and psoriatic arthritis are independent risk factors as well.Job stress appears to play a minor role accounting for about 3% of cases. In one study, women who were free of stress from work life saw an increase in the diameter of their blood vessels, leading to decreased progression of atherosclerosis. In contrast, women who had high levels of work-related stress experienced a decrease in the diameter of their blood vessels and significantly increased disease progression. Having a type A behavior pattern, a group of personality characteristics including time urgency, competitiveness, hostility, and impatience, is linked to an increased risk of coronary disease.
Blood fats
High blood cholesterol (specifically, serum LDL concentrations; also referred to as LDL-C to denote low-density lipoprotien cholesterol). HDL (high density lipoprotein) has a protective effect over development of coronary artery disease.
High blood triglycerides may play a role.
High levels of lipoprotein(a), a compound formed when LDL cholesterol combines with a protein known as apolipoprotein(a).Dietary cholesterol does not appear to have a significant effect on blood cholesterol and thus recommendations about its consumption may not be needed. Saturated fat is still a concern.
Genetics
The heritability of coronary artery disease has been estimated between 40% and 60%. Genome-wide association studies have identified over 160 genetic susceptibility loci for coronary artery disease.
Other
Endometriosis in women under the age of 40.
Depression and hostility appear to be risks.
The number of categories of adverse childhood experiences (psychological, physical, or sexual abuse; violence against mother; or living with household members who used substances, mentally ill, suicidal, or incarcerated) showed a graded correlation with the presence of adult diseases including coronary artery (ischemic heart) disease.
Hemostatic factors: High levels of fibrinogen and coagulation factor VII are associated with an increased risk of CAD.
Low hemoglobin.
In the Asian population, the b fibrinogen gene G-455A polymorphism was associated with the risk of CAD.
Pathophysiology
Limitation of blood flow to the heart causes ischemia (cell starvation secondary to a lack of oxygen) of the hearts muscle cells. The hearts muscle cells may die from lack of oxygen and this is called a myocardial infarction (commonly referred to as a heart attack). It leads to damage, death, and eventual scarring of the heart muscle without regrowth of heart muscle cells. Chronic high-grade narrowing of the coronary arteries can induce transient ischemia which leads to the induction of a ventricular arrhythmia, which may terminate into a dangerous heart rhythm known as ventricular fibrillation, which often leads to death.Typically, coronary artery disease occurs when part of the smooth, elastic lining inside a coronary artery (the arteries that supply blood to the heart muscle) develops atherosclerosis. With atherosclerosis, the arterys lining becomes hardened, stiffened, and accumulates deposits of calcium, fatty lipids, and abnormal inflammatory cells – to form a plaque. Calcium phosphate (hydroxyapatite) deposits in the muscular layer of the blood vessels appear to play a significant role in stiffening the arteries and inducing the early phase of coronary arteriosclerosis. This can be seen in a so-called metastatic mechanism of calciphylaxis as it occurs in chronic kidney disease and hemodialysis. Although these people have kidney dysfunction, almost fifty percent of them die due to coronary artery disease. Plaques can be thought of as large "pimples" that protrude into the channel of an artery, causing partial obstruction to blood flow. People with coronary artery disease might have just one or two plaques, or might have dozens distributed throughout their coronary arteries. A more severe form is chronic total occlusion (CTO) when a coronary artery is completely obstructed for more than 3 months.Cardiac syndrome X is chest pain (angina pectoris) and chest discomfort in people who do not show signs of blockages in the larger coronary arteries of their hearts when an angiogram (coronary angiogram) is being performed. The exact cause of cardiac syndrome X is unknown. Explanations include microvascular dysfunction or epicardial atherosclerosis. For reasons that are not well understood, women are more likely than men to have it; however, hormones and other risk factors unique to women may play a role.
Diagnosis
For symptomatic people, stress echocardiography can be used to make a diagnosis for obstructive coronary artery disease. The use of echocardiography, stress cardiac imaging, and/or advanced non-invasive imaging is not recommended on individuals who are exhibiting no symptoms and are otherwise at low risk for developing coronary disease.The diagnosis of "Cardiac Syndrome X" – the rare coronary artery disease that is more common in women, as mentioned, is a diagnosis of exclusion. Therefore, usually, the same tests are used as in any person with the suspected of having coronary artery disease:
Baseline electrocardiography (ECG)
Exercise ECG – Stress test
Exercise radioisotope test (nuclear stress test, myocardial scintigraphy)
Echocardiography (including stress echocardiography)
Coronary angiography
Intravascular ultrasound
Magnetic resonance imaging (MRI)The diagnosis of coronary disease underlying particular symptoms depends largely on the nature of the symptoms. The first investigation is an electrocardiogram (ECG/EKG), both for "stable" angina and acute coronary syndrome. An X-ray of the chest and blood tests may be performed.
Stable angina
In "stable" angina, chest pain with typical features occurring at predictable levels of exertion, various forms of cardiac stress tests may be used to induce both symptoms and detect changes by way of electrocardiography (using an ECG), echocardiography (using ultrasound of the heart) or scintigraphy (using uptake of radionuclide by the heart muscle). If part of the heart seems to receive an insufficient blood supply, coronary angiography may be used to identify stenosis of the coronary arteries and suitability for angioplasty or bypass surgery.Stable coronary artery disease (SCAD) is also often called stable ischemic heart disease (SIHD). A 2015 monograph explains that "Regardless of the nomenclature, stable angina is the chief manifestation of SIHD or SCAD." There are U.S. and European clinical practice guidelines for SIHD/SCAD.
Acute coronary syndrome
Diagnosis of acute coronary syndrome generally takes place in the emergency department, where ECGs may be performed sequentially to identify "evolving changes" (indicating ongoing damage to the heart muscle). Diagnosis is clear-cut if ECGs show elevation of the "ST segment", which in the context of severe typical chest pain is strongly indicative of an acute myocardial infarction (MI); this is termed a STEMI (ST-elevation MI) and is treated as an emergency with either urgent coronary angiography and percutaneous coronary intervention (angioplasty with or without stent insertion) or with thrombolysis ("clot buster" medication), whichever is available. In the absence of ST-segment elevation, heart damage is detected by cardiac markers (blood tests that identify heart muscle damage). If there is evidence of damage (infarction), the chest pain is attributed to a "non-ST elevation MI" (NSTEMI). If there is no evidence of damage, the term "unstable angina" is used. This process usually necessitates hospital admission and close observation on a coronary care unit for possible complications (such as cardiac arrhythmias – irregularities in the heart rate). Depending on the risk assessment, stress testing or angiography may be used to identify and treat coronary artery disease in patients who have had an NSTEMI or unstable angina.
Risk assessment
There are various risk assessment systems for determining the risk of coronary artery disease, with various emphasis on different variables above. A notable example is Framingham Score, used in the Framingham Heart Study. It is mainly based on age, gender, diabetes, total cholesterol, HDL cholesterol, tobacco smoking, and systolic blood pressure. When it comes to predicting risk in younger adults (18–39 years old), Framingham Risk Score remains below 10-12% for all deciles of baseline-predicted risk.Polygenic score is another way of risk assessment. In one study the relative risk of incident coronary events was 91% higher among participants at high genetic risk than among those at low genetic risk.
Prevention
Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. Prevention involves adequate physical exercise, decreasing obesity, treating high blood pressure, eating a healthy diet, decreasing cholesterol levels, and stopping smoking. Medications and exercise are roughly equally effective. High levels of physical activity reduce the risk of coronary artery disease by about 25%. Life’s Essential 8 are the key measures for improving and maintaining cardiovascular health, as defined by the American Heart Association. AHA added sleep as a factor influencing heart health in 2022.Most guidelines recommend combining these preventive strategies. A 2015 Cochrane Review found some evidence that counseling and education to bring about behavioral change might help in high-risk groups. However, there was insufficient evidence to show an effect on mortality or actual cardiovascular events.In diabetes mellitus, there is little evidence that very tight blood sugar control improves cardiac risk although improved sugar control appears to decrease other problems such as kidney failure and blindness. The World Health Organization (WHO) recommends "low to moderate alcohol intake" to reduce risk of coronary artery disease while high intake increases the risk.
Diet
A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death. Vegetarians have a lower risk of heart disease, possibly due to their greater consumption of fruits and vegetables. Evidence also suggests that the Mediterranean diet and a high fiber diet lower the risk.The consumption of trans fat (commonly found in hydrogenated products such as margarine) has been shown to cause a precursor to atherosclerosis and increase the risk of coronary artery disease.Evidence does not support a beneficial role for omega-3 fatty acid supplementation in preventing cardiovascular disease (including myocardial infarction and sudden cardiac death). There is tentative evidence that intake of menaquinone (Vitamin K2), but not phylloquinone (Vitamin K1), may reduce the risk of CAD mortality.
Secondary prevention
Secondary prevention is preventing further sequelae of already established disease. Effective lifestyle changes include:
Weight control
Smoking cessation
Avoiding the consumption of trans fats (in partially hydrogenated oils)
Decreasing psychosocial stress
ExerciseAerobic exercise, like walking, jogging, or swimming, can reduce the risk of mortality from coronary artery disease. Aerobic exercise can help decrease blood pressure and the amount of blood cholesterol (LDL) over time. It also increases HDL cholesterol.Although exercise is beneficial, it is unclear whether doctors should spend time counseling patients to exercise. The U.S. Preventive Services Task Force found "insufficient evidence" to recommend that doctors counsel patients on exercise but "it did not review the evidence for the effectiveness of physical activity to reduce chronic disease, morbidity, and mortality", only the effectiveness of counseling itself. The American Heart Association, based on a non-systematic review, recommends that doctors counsel patients on exercise.Psychological symptoms are common in people with CHD, and while many psychological treatments may be offered following cardiac events, there is no evidence that they change mortality, the risk of revascularization procedures, or the rate of non-fatal myocardial infarction.Antibiotics for secondary prevention of coronary heart disease
Antibiotics may help patients with coronary disease to reduce the risk of heart attacks and strokes. However, the latest evidence suggests that antibiotics for secondary prevention of coronary heart disease are harmful with increased mortality and occurrence of stroke. So, the use of antibiotics is not currently supported for preventing secondary coronary heart disease.
Neuropsychological Assessment
A thorough systematic review found that indeed there is a link between a CHD condition and brain dysfunction in females/women. Consequently, since research is showing that cardiovascular diseases, like CHD, can play a role as a precursor for dementia, like Alzheimers disease, individuals with CHD should have a neuropsychological assessment.
Treatment
There are a number of treatment options for coronary artery disease:
Lifestyle changes
Medical treatment – commonly prescribed drugs (e.g., cholesterol lowering medications, beta-blockers, nitroglycerin, calcium channel blockers, etc.);
Coronary interventions as angioplasty and coronary stent;
Coronary artery bypass grafting (CABG)
Medications
Statins, which reduce cholesterol, reduce the risk of coronary artery disease
Nitroglycerin
Calcium channel blockers and/or beta-blockers
Antiplatelet drugs such as aspirinIt is recommended that blood pressure typically be reduced to less than 140/90 mmHg. The diastolic blood pressure however should not be lower than 60 mmHg. Beta blockers are recommended first line for this use.
Aspirin
In those with no previous history of heart disease, aspirin decreases the risk of a myocardial infarction but does not change the overall risk of death. It is thus recommended only in adults who are at increased risk for coronary artery disease where increased risk is defined as "men older than 90 years of age, postmenopausal women, and younger persons with risk factors for coronary artery disease (for example, hypertension, diabetes, or smoking) who are at increased risk for heart disease and may wish to consider aspirin therapy". More specifically, high-risk persons are "those with a 5-year risk ≥ 3%".
Anti-platelet therapy
Clopidogrel plus aspirin (dual anti-platelet therapy) reduces cardiovascular events more than aspirin alone in those with a STEMI. In others at high risk but not having an acute event, the evidence is weak. Specifically, its use does not change the risk of death in this group. In those who have had a stent, more than 12 months of clopidogrel plus aspirin does not affect the risk of death.
Surgery
Revascularization for acute coronary syndrome has a mortality benefit. Percutaneous revascularization for stable ischaemic heart disease does not appear to have benefits over medical therapy alone. In those with disease in more than one artery, coronary artery bypass grafts appear better than percutaneous coronary interventions. Newer "anaortic" or no-touch off-pump coronary artery revascularization techniques have shown reduced postoperative stroke rates comparable to percutaneous coronary intervention. Hybrid coronary revascularization has also been shown to be a safe and feasible procedure that may offer some advantages over conventional CABG though it is more expensive.
Epidemiology
As of 2010, CAD was the leading cause of death globally resulting in over 7 million deaths. This increased from 5.2 million deaths from CAD worldwide in 1990. It may affect individuals at any age but becomes dramatically more common at progressively older ages, with approximately a tripling with each decade of life. Males are affected more often than females.It is estimated that 60% of the worlds cardiovascular disease burden will occur in the South Asian subcontinent despite only accounting for 20% of the worlds population. This may be secondary to a combination of genetic predisposition and environmental factors. Organizations such as the Indian Heart Association are working with the World Heart Federation to raise awareness about this issue.Coronary artery disease is the leading cause of death for both men and women and accounts for approximately 600,000 deaths in the United States every year. According to present trends in the United States, half of healthy 40-year-old men will develop CAD in the future, and one in three healthy 40-year-old women. It is the most common reason for death of men and women over 20 years of age in the United States.
Society and culture
Names
Other terms sometimes used for this condition are "hardening of the arteries" and "narrowing of the arteries". In Latin it is known as morbus ischaemicus cordis (MIC).
Support groups
The Infarct Combat Project (ICP) is an international nonprofit organization founded in 1998 which tries to decrease ischemic heart diseases through education and research.
Industry influence on research
In 2016 research into the archives of theSugar Association, the trade association for the sugar industry in the US, had sponsored an influential literature review published in 1965 in the New England Journal of Medicine that downplayed early findings about the role of a diet heavy in sugar in the development of CAD and emphasized the role of fat; that review influenced decades of research funding and guidance on healthy eating.
Research
Research efforts are focused on new angiogenic treatment modalities and various (adult) stem-cell therapies. A region on chromosome 17 was confined to families with multiple cases of myocardial infarction. Other genome-wide studies have identified a firm risk variant on chromosome 9 (9p21.3). However, these and other loci are found in intergenic segments and need further research in understanding how the phenotype is affected.A more controversial link is that between Chlamydophila pneumoniae infection and atherosclerosis. While this intracellular organism has been demonstrated in atherosclerotic plaques, evidence is inconclusive as to whether it can be considered a causative factor. Treatment with antibiotics in patients with proven atherosclerosis has not demonstrated a decreased risk of heart attacks or other coronary vascular diseases.Since the 1990s the search for new treatment options for coronary artery disease patients, particularly for so called "no-option" coronary patients, focused on usage of angiogenesis and (adult) stem cell therapies. Numerous clinical trials were performed, either applying protein (angiogenic growth factor) therapies, such as FGF-1 or VEGF, or cell therapies using different kinds of adult stem cell populations. Research is still going on – with first promising results particularly for FGF-1 and utilization of endothelial progenitor cells.
Myeloperoxidase has been proposed as a biomarker.Plant-based nutrition has been suggested as a way to reverse coronary artery disease, but strong evidence is still lacking for claims of potential benefits.
References
External links
Risk Assessment of having a heart attack or dying of coronary artery disease, from the American Heart Association.
"Coronary Artery Disease". MedlinePlus. U.S. National Library of Medicine. |
Multiple endocrine neoplasia type 2 | Multiple endocrine neoplasia type 2 (also known as "Pheochromocytoma and amyloid producing medullary thyroid carcinoma", "PTC syndrome," and "Sipple syndrome") is a group of medical disorders associated with tumors of the endocrine system. The tumors may be benign or malignant (cancer). They generally occur in endocrine organs (e.g. thyroid, parathyroid, and adrenals), but may also occur in endocrine tissues of organs not classically thought of as endocrine.MEN2 is a sub-type of MEN (multiple endocrine neoplasia) and itself has sub-types, as discussed below.
Signs and symptoms
MEN2 can present with a sign or symptom related to a tumor or, in the case of multiple endocrine neoplasia type 2b, with characteristic musculoskeletal and/or lip and/or gastrointestinal findings. Medullary thyroid carcinoma (MTC) represents the most frequent initial diagnosis. Occasionally pheochromocytoma or primary hyperparathyroidism may be the initial diagnosis.Pheochromocytoma occurs in 33-50% of MEN2 cases. In MEN2A, primary hyperparathyroidism occurs in 10–50% of cases and is usually diagnosed after the third decade of life. Rarely, it may present in childhood or be the sole clinical manifestation of this syndrome.MEN2A associates medullary thyroid carcinoma with pheochromocytoma in about 20–50% of cases and with primary hyperparathyroidism in 5–20% of cases. MEN2B associates medullary thyroid carcinoma with pheochromocytoma in 50% of cases, with marfanoid habitus and with mucosal and digestive neurofibromatosis.In familial isolated medullary thyroid carcinoma the other components of the disease are absent.
In a review of 85 patients 70 had MEN2A and 15 had MEN2B. The initial manifestation of MEN2 was medullary thyroid carcinoma in 60% of patients, medullary thyroid carcinoma synchronous with pheochromocytoma in 34% and pheochromocytoma alone in 6%. 72% had bilateral pheochromocytomas.
Causes
The table in the multiple endocrine neoplasia article lists the genes involved in the various MEN syndromes. Most cases of MEN2 derive from a variation in the RET proto-oncogene, and are specific for cells of neural crest origin. A database of MEN-implicated RET mutations is maintained by the University of Utah Department of Physiology.The protein produced by the RET gene plays an important role in the TGF-beta (transforming growth factor beta) signaling system. Because the TGF-beta system operates in nervous tissues throughout the body, variations in the RET gene can have effects in nervous tissues throughout the body. MEN2 generally results from a gain-of-function variant of a RET gene. Other diseases, such as Hirschsprung disease, result from loss-of-function variants. OMIM # 164761 lists the syndromes associated with the RET gene.
Genetics
When inherited, multiple endocrine neoplasia type 2 is transmitted in an autosomal dominant pattern, which means affected people have one affected parent, and possibly affected siblings and children. Some cases, however, result from spontaneous new mutations in the RET gene. These cases occur in people with no family history of the disorder. In MEN2B, for example, about half of all cases arise as spontaneous new mutations.
Diagnosis
Diagnosis is suspected when a patient with family history of two of the three classical tumors (medullary thyroid cancer, pheochromocytoma, parathyroid adenoma) or MEN2 presents with one of the classical tumors. It is confirmed by genetic testing for mutation in RET gene.
Differences in presentation
As noted, all types of MEN2 include pheochromocytoma and medullary thyroid carcinoma.
MEN2A is additionally characterized by the presence of parathyroid hyperplasia.
MEN2B is additionally characterized by the presence of mucocutaneous neuroma, gastrointestinal symptoms (e.g. constipation and flatulence), and muscular hypotonia.
MEN2B can present with a Marfanoid habitus.
Classification
Before gene testing was available, the type and location of tumors determined which type of MEN2 a person had. Gene testing now allows a diagnosis before tumors or symptoms develop.
A table in the multiple endocrine neoplasia article compares the various MEN syndromes. MEN2 and MEN1 are distinct conditions, despite their similar names. MEN2 includes MEN2A, MEN2B and familial medullary thyroid cancer (FMTC).The common feature among the three sub-types of MEN2 is a high propensity to develop medullary thyroid carcinoma.
A variant of MEAs 2A was described in 1989. This variant also has patches of cutaneous amyloidosis in the mid/upper back and is inherited in an autosomal dominant fashion.
Management
Management of MEN2 patients includes thyroidectomy including cervical central and bilateral lymph nodes dissection for MTC, unilateral adrenalectomy for unilateral pheochromocytoma or bilateral adrenalectomy when both glands are involved and selective resection of pathologic parathyroid glands for primary hyperparathyroidism. Familial genetic screening is recommended to identify at risk subjects who will develop the disease, permitting early management by performing prophylactic thyroidectomy, giving them the best chance of cure.
Prognosis
Prognosis of MEN2 is mainly related to the stage-dependant prognosis of MTC indicating the necessity of a complete thyroid surgery for index cases with MTC and the early thyroidectomy for screened at risk subjects.
See also
Multiple endocrine neoplasia
Multiple endocrine neoplasia type 1
Multiple endocrine neoplasia type 2b
Multiple mucosal neuromata
References
External links
MEN2 (RET) gene variant database
GeneReview/NIH/UW entry on Multiple Endocrine Neoplasia Type 2 |
Dependent personality disorder | Dependent personality disorder (DPD) is characterized by a pervasive psychological dependence on other people. This personality disorder is a long-term condition in which people depend on others to meet their emotional and physical needs, with only a minority achieving normal levels of independence. Dependent personality disorder is a cluster C personality disorder, which is characterized by excessive fear and anxiety. It begins prior to early adulthood, and it is present in a variety of contexts and is associated with inadequate functioning. Symptoms can include anything from extreme passivity, devastation or helplessness when relationships end, avoidance of responsibilities and severe submission.
Signs and symptoms
People who have dependent personality disorder are overdependent on other people when it comes to making decisions. They cannot make a decision on their own as they need constant approval from other people. Consequently, individuals diagnosed with DPD tend to place needs and opinions of others above their own as they do not have the confidence to trust their decisions. This kind of behaviour can explain why people with DPD tend to show passive and clingy behaviour. These individuals display a fear of separation and cannot stand being alone. When alone, they experience feelings of isolation and loneliness due to their overwhelming dependence on other people. Generally people with DPD are also pessimistic: they expect the worst out of situations or believe that the worst will happen. They tend to be more introverted and are more sensitive to criticism and fear rejection.
Risk factors
People with a history of neglect and an abusive upbringing are more susceptible to develop DPD, specifically those involved in long-term abusive relationships. Those with overprotective or authoritarian parents are also more at risk to develop DPD. Having a family history of anxiety disorder can play a role in the development of DPD as a 2004 twin study found a 0.81 heritability for personality disorders collectively.
Causes
The exact cause of dependent personality disorder is unknown. A study in 2012 estimated that between 55% and 72% of the risk of the condition is inherited from ones parents. The difference between a "dependent personality" and a "dependent personality disorder" is somewhat subjective, which makes diagnosis sensitive to cultural influences such as gender role expectations.
Dependent traits in children tended to increase with parenting behaviours and attitudes characterized by overprotectiveness and authoritarianism. Thus the likelihood of developing dependent personality disorder increased, since these parenting traits can limit them from developing a sense of autonomy, rather teaching them that others are powerful and competent.Traumatic or adverse experiences early in an individuals life, such as neglect and abuse or serious illness, can increase the likelihood of developing personality disorders, including dependent personality disorder, later on in life. This is especially prevalent for those individuals who also experience high interpersonal stress and poor social support.There is a higher frequency of the disorder seen in women than men, hence expectations relating to gender role may contribute to some extent.
Diagnosis
Clinicians and clinical researchers conceptualize dependent personality disorder in terms of four related components:
Cognitive: a perception of oneself as powerless and ineffectual, coupled with the belief that other people are comparatively powerful and potent.
Motivational: a desire to obtain and maintain relationships with protectors and caregivers.
Behavioral: a pattern of relationship-facilitating behavior designed to strengthen interpersonal ties and minimize the possibility of abandonment and rejection.
Emotional: fear of abandonment, fear of rejection, and anxiety regarding evaluation by figures of authority.
American Psychiatric Association and DSM
The Diagnostic and Statistical Manual of Mental Disorders (DSM) contains a dependent personality disorder diagnosis. It refers to a pervasive and excessive need to be taken care of which leads to submissive and clinging behavior and fears of separation. This begins prior to early adulthood and can be present in a variety of contexts.In the DSM Fifth Edition (DSM-5), there is one criterion by which there are eight features of dependent personality disorder. The disorder is indicated by at least five of the following factors:
Has difficulty making everyday decisions without an excessive amount of advice and reassurance from others.
Needs others to assume responsibility for most major areas of their life.
Has difficulty expressing disagreement with others because of fear of loss of support or approval.
Has difficulty initiating projects or doing things on their own (because of a lack of self confidence in judgment or abilities rather than a lack of motivation or energy).
Goes to excessive lengths to obtain nurturance and support from others, to the point of volunteering to do things that are unpleasant.
Feels uncomfortable or helpless when alone because of exaggerated fears of being unable to care for themselves.
Urgently seeks another relationship as a source of care and support when a close relationship ends.
Is unrealistically preoccupied with fears of being left to take care of themselves.The diagnosis of personality disorders in the fourth edition Diagnostic and Statistical Manual of Mental Disorders, including dependent personality disorder, was found to be problematic due to reasons such as excessive diagnostic comorbidity, inadequate coverage, arbitrary boundaries with normal psychological functioning, and heterogeneity among individuals within the same categorial diagnosis.
World Health Organization
The World Health Organizations ICD-10 lists dependent personality disorder as F60.7 Dependent personality disorder:
It is characterized by at least 4 of the following:
Encouraging or allowing others to make most of ones important life decisions;
Subordination of ones own needs to those of others on whom one is dependent, and undue compliance with their wishes;
Unwillingness to make even reasonable demands on the people one depends on;
Feeling uncomfortable or helpless when alone, because of exaggerated fears of inability to care for oneself;
Preoccupation with fears of being abandoned by a person with whom one has a close relationship, and of being left to care for oneself;
Limited capacity to make everyday decisions without an excessive amount of advice and reassurance from others.Associated features may include perceiving oneself as helpless, incompetent, and lacking stamina.
Includes:
Asthenic, inadequate, passive, and self-defeating personality (disorder)
It is a requirement of ICD-10 that a diagnosis of any specific personality disorder also satisfies a set of general personality disorder criteria.
SWAP-200
The SWAP-200 is a diagnostic tool that was proposed with the goal of overcoming limitations, such as limited external validity for the diagnostic criteria for dependent personality disorder, to the DSM. It serves as a possible alternative nosological system that emerged from the efforts to create an empirically based approach to personality disorders – while also preserving the complexity of clinical reality. Dependent personality disorder is considered a clinical prototype in the context of the SWAP-200. Rather than discrete symptoms, it provides composite description characteristic criteria – such as personality tendencies.Based on the Q-Sort method and prototype matching, the SWAP-200 is a personality assessment procedure relying on an external observers judgment. It provides:
A personality diagnosis expressed as the matching with ten prototypical descriptions of DSM-IV personality disorders.
A personality diagnosis based on the matching of the patient with 11 Q-factors of personality derived empirically.
A dimensional profile of healthy and adaptive functioning.The traits that define dependent personality disorder according to SWAP-200 are:
They tend to become attached quickly and/or intensely, developing feelings and expectations that are not warranted by the history or context of the relationship.
Since they tend to be ingratiating and submissive, people with DPD tend to be in relationships in which they are emotionally or physically abused.
They tend to feel ashamed, inadequate, and depressed.
They also feel powerless and tend to be suggestible.
They are often anxious and tend to feel guilty.
These people have difficulty acknowledging and expressing anger and struggle to get their own needs and goals met.
Unable to soothe or comfort themselves when distressed, they require involvement of another person to help regulate their emotions.
Psychodynamic Diagnostic Manual
The Psychodynamic Diagnostic Manual (PDM) approaches dependent personality disorder in a descriptive, rather than prescriptive sense and has received empirical support. The Psychodynamic Diagnostic Manual includes two different types of dependent personality disorder:
Passive-aggressive
Counter-dependent The PDM-2 adopts and applies a prototypic approach, using empirical measures like the SWAP-200. It was influenced by a developmental and empirically grounded perspective, as proposed by Sidney Blatt. This model is of particular interest when focusing on dependent personality disorder, claiming that psychopathology comes from distortions of two main coordinates of psychological development:
The anaclitic/introjective dimension.
The relatedness/self-definition dimension.The anaclitic personality organization in individuals exhibits difficulties in interpersonal relatedness, exhibiting the following behaviours:
Preoccupation with relationships
Fear of abandonment and of rejection
Seeking closeness and intimacy
Difficulty managing interpersonal boundaries
Tend to have an anxious-preoccupied attachment style.Introjective personality style is associated with problems in self-definition.
Differential diagnosis
There are similarities between individuals with dependent personality disorder and individuals with borderline personality disorder, in that they both have a fear of abandonment. Those with dependent personality disorder do not exhibit impulsive behaviour, unstable affect, and poor self-image experienced by those with borderline personality disorder, differentiating the two disorders.
Treatment
People who have DPD are generally treated with psychotherapy. The main goal of this therapy is to make the individual more independent and help them form healthy relationships with the people around them. This is done by improving their self-esteem and confidence.Medication can be used to treat patients with depression or anxiety because of their DPD, but this does not treat the core problems caused by DPD.
Epidemiology
Based on a recent survey of 43,093 Americans, 0.49% of adults meet diagnostic criteria for DPD (National Epidemiologic Survey on Alcohol and Related Conditions; NESARC; Grant et al., 2004).
Traits related to DPD, like most personality disorders, emerge in childhood or early adulthood. Findings from the NESArC study found that 18 to 29 year olds have a greater chance of developing DPD. DPD is more common among women compared to men as 0.6% of women have DPD compared to 0.4% of men.A 2004 twin study suggests a heritability of 0.81 for developing dependent personality disorder. Because of this, there is significant evidence that this disorder runs in families.Children and adolescents with a history of anxiety disorders and physical illnesses are more susceptible to acquiring this disorder.
Millons subtypes
Psychologist Theodore Millon identified five adult subtypes of dependent personality disorder. Any individual dependent may exhibit none or one of the following:
History
The conceptualization of dependency, within classical psychoanalytic theory, is directly related to Freuds oral psychosexual stage of development. Frustration or over-gratification was said to result in an oral fixation and in an oral type of character, characterized by feeling dependent on others for nurturance and by behaviours representative of the oral stage. Later psychoanalytic theories shifted the focus from a drive-based approach of dependency to the recognition of the importance of early relationships and establishing separation from these early caregivers, in which the exchanges between the caregiver and the child become internalized, and the nature of these interactions becomes part of the concepts of the self and of others.
References
Sources
Beck, Aaron T; Freeman, Arthur (1990). Cognitive Therapy of Personality Disorders. New York: Guilford Press. ISBN 978-0-89862-434-2.
Millon, Theodore; Davis, Roger Dale (1996). Disorders of Personality: DSM-IV and Beyond. New York: Wiley. ISBN 978-0-471-01186-6.
Millon, Theodore (1981). Disorders of Personality: DSM-III, Axis II. New York: Wiley. ISBN 978-0-471-06403-9.
Perry, J. C. (1996). "Dependent personality disorder". In Gabbard, Glen O.; Atkinson, Sarah D. (eds.). Synopsis of Treatments of Psychiatric Disorders. American Psychiatric Press. pp. 995–998. ISBN 978-0-88048-859-4.
Gjerde, L. C.; Czajkowski, N.; Røysamb, E.; Ørstavik, R. E.; Knudsen, G. P.; Østby, K.; Torgersen, S.; Myers, J.; Kendler, K. S.; Reichborn-Kjennerud, T. (2012). "The heritability of avoidant and dependent personality disorder assessed by personal interview and questionnaire". Acta Psychiatrica Scandinavica. 126 (6): 448–457. doi:10.1111/j.1600-0447.2012.01862.x. PMC 3493848. PMID 22486635.
Millon, Theodore; Millon, Carrie M.; Meagher, Sarah; Grossman, Seth; Ramnath, Rowena (2004). Personality Disorders in Modern Life. Wiley. ISBN 978-0-471-66850-3.
Millon, Theodore (2006). "Personality Subtypes".
Kantor, Martin (1992). Diagnosis and Treatment of the Personality Disorders. Ishiyaku EuroAmerica. ISBN 978-0-912791-89-0.
Ellison, J. M.; Adler, D. A. (1990). "A strategy for the pharmacotherapy of personality disorders". In Adler, David A. (ed.). Treating Personality Disorders. San Francisco: Jossey-Bass. pp. 43–63. ISBN 978-1-55542-811-2.
Adler, David A., ed. (1990). Treating Personality Disorders. San Francisco: Jossey-Bass. ISBN 978-1-55542-811-2.
Richards, Henry Jay (1993). Therapy of the Substance Abuse Syndromes. New York: Jason Aronson. ISBN 978-0-87668-539-6.
Zimmerman, Mark (1994). Diagnosing DSM-IV-R Psychiatric Disorders in Primary Care Settings: An Interview Guide for the Nonpsychiatrist Physician. Psych Products. ISBN 978-0-9633821-3-9.
Ekleberry, Sharon (2014). "Dependent Personality Disorder (DPD)". Treating Co-Occurring Disorders. pp. 63–64. ISBN 978-1-317-82549-4.
Oldham, John M.; Morris, Lois B. (1990). The Personality Self-portrait: Why You Think, Work, Love, and Act the Way You Do. Bantam. ISBN 978-0-553-05757-7.
Sperry, Len (1995). Psychopharmacology and Psychotherapy: Strategies for Maximizing Treatment Outcomes. Psychology Press. ISBN 978-0-87630-787-8.
Stone, Michael H. (1993). Abnormalities of Personality: Within and Beyond the Realm of Treatment. Norton. ISBN 978-0-393-70127-2.
Benjamin, Lorna Smith (1993). Interpersonal Diagnosis and Treatment of Personality Disorders. Guilford Press. ISBN 978-0-89862-990-3.
Benjamin, Lorna Smith (1996). "Dependent Personality Disorder". Interpersonal Diagnosis and Treatment of Personality Disorders. Guilford Press. pp. 221–239. ISBN 978-0-89862-990-3.
External links
J. Christopher Perry, M.P.H., M.D., 2005 (Dependent Personality Disorder)
Diagnostic Features, Complications, Prevalence, Associated Laboratory Findings
MedlinePlus Medical Encyclopedia: Dependent personality disorder |
Nasal septum perforation | A nasal septum perforation is a medical condition in which the nasal septum, the bony/cartilaginous wall dividing the nasal cavities, develops a hole or fissure.
This may be brought on directly, as in the case of nasal piercings, or indirectly, as by long-term topical drug application, including intranasal ethylphenidate, methamphetamine, cocaine, crushed prescription pills, or decongestant nasal sprays, chronic epistaxis, excessive nose picking and as a complication of nasal surgery like septoplasty or rhinoplasty. Much less common causes for perforated nasal septums include rare granulomatous inflammatory conditions like granulomatosis with polyangiitis. It has been reported as a side effect of anti-angiogenesis drugs like bevacizumab.
Signs and symptoms
A perforated septum can vary in size and location, and is usually found deep inside the nose. It may be asymptomatic, or cause a variety of signs and symptoms. Small perforations can cause a whistling noise when breathing. Larger perforations usually have more severe symptoms. These can be a combination of crusting, blood discharge, difficulty breathing, nasal pressure and discomfort. The closer the perforation is to the nostrils, the more likely it is to cause symptoms.
Cause
Infective causes include syphilis, leprosy, and rhinoscleroma. Non-infective causes include cocaine abuse, an in situ foreign body, chronic use of topical nasal decongestants, methamphetamine, facial trauma, or may develop as a consequence of nasal surgery.
Treatment
Septal perforations are managed with a multitude of options. The treatment often depends on the severity of symptoms and the size of the perforations. Generally speaking anterior septal perforations are more bothersome and symptomatic. Posterior septal perforations, which mainly occur iatrogenically, are often managed with simple observation and are at times intended portions of skull base surgery. Septal perforations that are not bothersome can be managed with simple observation. While no septal perforation will spontaneously close, for the majority of septal perforations that are unlikely to get larger observation is an appropriate form of management. For perforations that bleed or are painful, initial management should include humidification and application of salves to the perforation edges to promote healing. Mucosalization of the perforation edges will help prevent pain and recurrent epistaxis and majority of septal perforations can be managed without surgery.
For perforations in which anosmia, or the loss of smell, and a persistent whistling are a concern, the use of a silicone septal button is a treatment option. These can be placed while the patient is awake and usually in the clinic setting. While complications of button insertion are minimal, the presence of the button can be bothersome to most patients.
For patients who desire definitive close, surgery is the only option. Prior to determining candidacy for surgical closure, the etiology of the perforation must be determined. Often this requires a biopsy of the perforation to rule out autoimmune causes. If a known cause such as cocaine is the offending agent, it must be ensured that the patient is not still using the irritant.
For those that are determined to be medically cleared for surgery, the anatomical location and size of the perforation must be determined. This is often done with a combination of a CT scan of the sinuses without contrast and an endoscopic evaluation by an Ear Nose and Throat doctor. Once dimensions are obtained the surgeon will decide if it is possible to close the perforation. Multiple approaches to access the septum have been described in the literature. While sublabial and midfacial degloving approaches have been described, the most popular today is the rhinoplasty approach. This can include both open and closed methods. The open method results in a scar on the columella, however, it allows for more visibility to the surgeon. The closed method utilizes an incision all on the inside of the nose. The concept behind closure includes bringing together the edges of mucosa on each side of the perforation with minimal tension. An interposition graft is also often used. The interposition graft provides extended stability and also structure to the area of the perforation. Classically, a graft from the scalp utilizing temporalis fascia was used. Kridel, et al., first described the usage of acellular dermis so that no further incisions are required; they reported an excellent closure rate of over 90 percent. Overall perforation closure rates are variable and often determined by the skill of the surgeon and technique used. Often surgeons who claim a high rate of closure choose perforations that are easier to close. An open rhinoplasty approach also allows for better access to the nose to repair any concurrent nasal deformities, such as saddle nose deformity, that occur with a septal perforation.
See also
Nasal septum deviation
References
Different surgical treatments for nasal septal perforation and their outcomes
Septal Perforation Closure Utilizing the External Septorhinoplasty Approach
A Review of 25-Year Experience of Nasal Septal Perforation Repair
== External links == |
Robinow syndrome | Robinow syndrome is an extremely rare genetic disorder characterized by short-limbed dwarfism, abnormalities in the head, face, and external genitalia, as well as vertebral segmentation. The disorder was first described in 1969 by human geneticist Meinhard Robinow, along with physicians Frederic N. Silverman and Hugo D. Smith, in the American Journal of Diseases of Children. By 2002, over 100 cases had been documented and introduced into medical literature.Two forms of the disorder exist, dominant and recessive, of which the former is more common. Patients with the dominant version often suffer moderately from the aforementioned symptoms. Recessive cases, on the other hand, are usually more physically marked, and individuals may exhibit more skeletal abnormalities. The recessive form is particularly frequent in Turkey. However, this can likely be explained by a common ancestor, as these patients families can be traced to a single town in Eastern Turkey. Clusters of the autosomal recessive form have also been documented in Oman and Czechoslovakia.The syndrome is also known as Robinow-Silverman-Smith syndrome, Robinow dwarfism, fetal face, fetal face syndrome, fetal facies syndrome, acral dysostosis with facial and genital abnormalities, or mesomelic dwarfism-small genitalia syndrome. The recessive form was previously known as Covesdem syndrome.
Signs and symptoms
Robinow noted the resemblance of affected patients faces to that of a fetus, using the term "fetal facies" to describe the appearance of a small face and widely spaced eyes. Clinical features also may include a short, upturned nose, a prominent forehead, and a flat nasal bridge. The upper lip may be "tented", exposing dental crowding, "tongue tie", or gum hypertrophy.
Though the eyes do not protrude, abnormalities in the lower eyelid may give that impression. Surgery may be necessary if the eyes cannot close fully. In addition, the ears may be set low on the head or have a deformed pinna.Patients suffer from dwarfism, short lower arms, small feet, and small hands. Fingers and toes may also be abnormally short and laterally or medially bent. The thumb may be displaced and some patients, notably in Turkey, experience ectrodactyly. All patients often suffer from vertebral segmentation abnormalities. Those with the dominant variant have, at most, a single butterfly vertebra. Those with the recessive form, however, may suffer from hemivertebrae, vertebral fusion, and rib anomalies. Some cases resemble Jarcho-Levin syndrome or spondylocostal dysostosis.Genital defects characteristically seen in males include a micropenis with a normally developed scrotum and testes. Sometimes, testicles may be undescended, or the patient may suffer from hypospadias. Female genital defects may include a reduced size clitoris and underdeveloped labia minora. Infrequently, the labia majora may also be underdeveloped. Some research has shown that females may experience vaginal atresia or haematocolpos.The autosomal recessive form of the disorder tends to be much more severe. Examples of differences are summarized in the following table:
Associated conditions
Medical conditions include frequent ear infection, hearing loss, hypotonia, developmental problems, respiratory problems, eating difficulties, light sensitivity, and esophageal reflux.Data on fertility and the development of secondary sex characteristics is relatively sparse. It has been reported that both male and female patients have had children. Males who have reproduced have all had the autosomal dominant form of the disorder; the fertility of those with the recessive variant is unknown.Researchers have also reported abnormalities in the renal tract of affected patients. Hydronephrosis is a relatively common condition, and researchers have theorized that this may lead to urinary tract infections. In addition, a number of patients have suffered from cystic dysplasia of the kidney.A number of other conditions are often associated with Robinow syndrome. About 15% of reported patients suffer from congenital heart defects. Though there is no clear pattern, the most common conditions include pulmonary stenosis and atresia. In addition, though intelligence is generally normal, around 15% of patients show developmental delays.
Genetics
Genetic studies have linked the autosomal recessive form of the disorder to the ROR2 gene on position 9 of the long arm of chromosome 9. The gene is responsible for aspects of bone and cartilage growth. This same gene is involved in causing autosomal dominant brachydactyly B.
The autosomal dominant form has been linked to three genes - WNT5A, Segment polarity protein dishevelled homolog DVL-1 (DVL1) and Segment polarity protein dishevelled homolog DVL-3 (DVL3). This form is often caused by new mutations and is generally less severe than the recessive form. Two further genes have been linked to this disorder - Frizzled-2 (FZD2) and Nucleoredoxin (NXN gene). All of these genes belong to the same metabolic pathway - the WNT system. This system is involved in secretion for various compounds both in the fetus and in the adult.
A fetal ultrasound can offer prenatal diagnosis 19 weeks into pregnancy. However, the characteristics of a fetus suffering from the milder dominant form may not always be easy to differentiate from a more serious recessive case. Genetic counseling is an option given the availability of a family history.
Diagnosis
Robinow syndrome is suspected by clinical findings and family history and confirmed by typical ROR-2 biallelic pathogenic variants identified by molecular genetic testing.
Treatment
Treatment of the various manifestations will usually be addressed by a multidisciplinary team.
History
The disorder was first described in 1969 by the German-American Human Geneticist Meinhard Robinow (1909–1997), along with physicians Frederic N. Silverman and Hugo D. Smith, in the American Journal of Diseases of Children. By 2002, over 100 cases had been documented and introduced into medical literature.
References
Further reading
White, Janson; Mazzeu, Juliana F; Hoischen, Alexander; Jhangiani, Shalini N; Gambin, Tomasz; Alcino, Michele Calijorne; Penney, Samantha; Saraiva, Jorge M; Hove, Hanne; Skovby, Flemming; Kayserili, Hülya; Estrella, Elicia; Vulto-Van Silfhout, Anneke T; Steehouwer, Marloes; Muzny, Donna M; Sutton, V. Reid; Gibbs, Richard A; Lupski, James R; Brunner, Han G; Van Bon, Bregje W.M; Carvalho, Claudia M.B (2015). "DVL1 Frameshift Mutations Clustering in the Penultimate Exon Cause Autosomal-Dominant Robinow Syndrome". The American Journal of Human Genetics. 96 (4): 612–22. doi:10.1016/j.ajhg.2015.02.015. PMC 4385180. PMID 25817016.
External links
GeneReview/NCBI/NIH/UW entry on ROR2-Related Robinow Syndrome
Disease ID 5704 at NIHs Office of Rare Diseases |
Metageria | Metageria is a cutaneous condition characterized by premature aging.
See also
Hutchinson–Gilford syndrome
List of cutaneous conditions
References
== External links == |
Hashimotos encephalopathy | Hashimotos encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a neurological condition characterized by encephalopathy, thyroid autoimmunity, and good clinical response to corticosteroids. It is associated with Hashimotos thyroiditis, and was first described in 1966. It is sometimes referred to as a neuroendocrine disorder, although the conditions relationship to the endocrine system is widely disputed. It is recognized as a rare disease by the NIH Genetic and Rare Diseases Information Center.Up to 2005, almost 200 case reports of this disease were published. Between 1990 and 2000, 43 cases were published. Since that time, research has expanded and numerous cases are being reported by scientists around the world, suggesting that this rare condition is likely to have been significantly undiagnosed in the past. Over 100 scientific articles on Hashimotos encephalopathy were published between 2000 and 2013.
Signs and symptoms
The onset of symptoms tends to be fairly gradual and to occur over 1-12 years.Symptoms of Hashimotos encephalopathy may include:
Personality changes
Aggression
Delusional behavior
Concentration and memory problems
Coma
Disorientation
Headaches
Jerks in the muscles (myoclonus – 65% of cases)
Lack of coordination (ataxia – 65% of cases)
Partial paralysis on the right side
Psychosis
Seizures (60% of cases)
Sleep abnormalities (55% of cases)
Speech problems (transient aphasia – 80% of cases)
Status epilepticus (20% of cases)
Tremors (80% of cases)
Pathogenesis
The mechanism of pathogenesis is not known, but is thought to be an autoimmune disorder, similar to Hashimotos thyroiditis, as its name suggests.Consistent with this hypothesis, autoantibodies to alpha-enolase have been found to be associated with Hashimotos encephalopathy. Since enolase is the penultimate step in glycolysis, if it were inhibited (for example by being bound by autoantibodies), one would expect decreased energy production by each cell, leading to resulting atrophy of the affected organ.This would occur most likely through each cell shrinking in size in response to the energy deficit (and/or in extreme situations from some cells dying via either apoptosis or necrosis, depending on location). This may occur as a result of enough ATP not being available to maintain cellular functions - notably, failure of the Na/K ATPase, resulting in a loss of the gradient to drive the Na/Ca antiporter, which normally keeps Ca+2 out of cells so it does not build to toxic levels that will rupture cell lysosomes leading to apoptosis. An additional feature of a low-energy state is failure to maintain axonal transport via dynein/kinesin ATPases, which in many diseases results in neuronal injury to both the brain and/or periphery.
Pathology
Very little is known about the pathology of Hashimotos encephalopathy. Post mortem studies of some individuals have shown lymphocytic vasculitis of venules and veins in the brain stem and a diffuse gliosis involving gray matter more than white matter.As mentioned above, autoantibodies to alpha-enolase associated with Hashimotos encephalopathy have thus far been the most hypothesized mechanism of injury.
Diagnosis
Laboratory and radiological findings
Increased liver enzyme levels (55% cases)
Increased thyroid-stimulating hormone (55% cases)
Increased erythrocyte sedimentation rate (25% cases)Cerebrospinal fluid findings:
Raised protein (25% cases)
Negative for 14–3–3 protein
May contain antithyroid antibodies
Magnetic resonance imaging abnormalities consistent with encephalopathy (26% f cases)
Single photon emission computed tomography shows focal and global hypoperfusion (75% of cases)
Cerebral angiography is normalThyroid hormone abnormalities are common (>80% of cases):
Subclinical hypothyroidism (35% of cases)
Overt hypothyroidism (20% of cases)
Hyperthyroidism (5% of cases)
Euthyroid on levothyroxine (10% of cases)
Euthyroid not on levothyroxine (20% of cases)Thyroid antibodies – both antithyroid peroxidase antibodies (anti-TPO, antithyroid microsomal antibodies, anti-M) and antithyroglobulin antibodies (anti-Tg) – in the disease are elevated, but their levels do not correlate with the severity.Electroencephalogram studies, while almost always abnormal (98% of cases), are usually not diagnostic. The most common findings are diffuse or generalized slowing or frontal intermittent rhythmic delta activity. Prominent triphasic waves, focal slowing, epileptiform abnormalities, and photoparoxysmal and photomyogenic responses may be seen.A study from 2006 suggested the following diagnostic criteria:
Encephalopathy with cognitive impairment and at least one of the following features:
neuropsychiatric symptoms (e.g. hallucination, delusion or paranoia)
Myoclonus, generalised tonic-clonic or partial seizures
focal-neurological deficits
Elevated titres of thyroid tissue antibodies (TPO-ab or microsomal)
Euthyroidism (potentially achieved by treatment with L-T4 or L-T3) or mild hypothyroidism with TSH concentration below 20 mIU/L
No evidence for infectious, toxic, metabolic or neoplastic processes in blood, urine or CSF analyses
No serological evidence for neuronal antibodies (e.g. voltage-gated calcium channel, voltage-gated potassium channel, or other currently recognized paraneoplastic antibodies) to support another diagnosis
In imaging studies no evidence for vascular, neoplastic or structural lesions that might explain the symptoms
Complete or nearly complete remission after initiation of glucocorticoid therapy.
Definition
A relapsing encephalopathy occurs in association with autoimmune (Hashimotos or Ords thyroiditis), with high titers of antithyroid antibodies. Clinically, the condition may present one or more symptoms. Onset is often gradual and may go unnoticed by the patient and close associates to the patients. Symptoms sometimes resolve themselves within days to weeks, leaving a patient undiagnosed. For many other patients, the condition may result in ongoing problems with a variety of manifestations, often confusing clinicians due to the diffuse nature of symptoms.
Differential diagnosis
Alzheimers disease
Cerebrovascular accidents (stroke)
Creutzfeldt–Jakob disease
Epilepsy
Migraine (including basilar, hemiplegic, and retinal types)
Other forms of autoimmune encephalitis, including forms of limbic encephalitis such as anti-NMDA receptor encephalitis
Schizophrenia
Spontaneous cerebrospinal fluid leak
Viral encephalitis
Transient ischemic attack
Treatment
Because most patients respond to corticosteroids or immunosuppressant treatment, this condition is now also referred to as steroid-responsive encephalopathy.Initial treatment is usually with oral prednisone (50–150 mg/day) or high-dose intravenous methylprednisolone (1 g/day) for 3–7 days. Thyroid hormone treatment is also included if required.Failure of some patients to respond to this first-line treatment has produced a variety of alternative treatments, including azathioprine, cyclophosphamide, chloroquine, methotrexate, periodic intravenous immunoglobulin, and plasma exchange. No controlled trials have been conducted, so the optimal treatment is not known.Seizures, if present, are controlled with typical antiepileptic agents.
Prognosis
Duration of treatment is usually between 2 and 25 years. Earlier reports suggested that 90% of cases stay in remission after discontinuation of treatment, but this is at odds with more recent studies, which suggest that relapse commonly occurs after initial high-dose steroid treatment. Left untreated, this condition can result in coma and death.
Epidemiology
The prevalence has been estimated to be 2.1/100,000 with a male-to-female ratio of 1:4. The mean age of onset is 44 with 20% of cases presenting before the age of 18 years. Most reported cases occur during the patients fifth decade of life.
History
The first case of HE was described by Brain et al. in 1966. The patient was a 48-year-old man with hypothyroidism, multiple episodes of encephalopathy, stroke-like symptoms, and Hashimotos thyroiditis confirmed by elevated antithyroid antibodies.
Alternative names
Steroid-responsive encephalopathy associated with autoimmune thyroiditis, SREAT
Nonvasculitic autoimmune meningoencephalitis, NAIM
Encephalopathy associated with autoimmune thyroid disease, EAATD
References
Further reading
Hashimotos Encephalopathy SREAT Alliance (2013). Understanding Hashimotos Encephalopathy: A Guide for Patients, Families, and Caregivers, Featuring Stories of HE Patients from Around the World. North Charleston, SC: CreateSpace Independent Publishing Platform. ISBN 9781484883099. OCLC 890816771.
Schiess N, Pardo CA (October 2008). "Hashimotos encephalopathy". Annals of the New York Academy of Sciences. 1142 (1): 254–65. Bibcode:2008NYASA1142..254S. doi:10.1196/annals.1444.018. PMID 18990131. S2CID 1312798.
Taylor SE, Garalda ME, Tudor-Williams G, Martinez-Alier N (February 2003). "An organic cause of neuropsychiatric illness in adolescence". The Lancet. 361 (9357): 572. doi:10.1016/S0140-6736(03)12517-2. PMID 12598143. S2CID 35053683. |
Aschers syndrome | Aschers syndrome, is a rare disorder first described in 1920. It is characterized by repeated episodes of lip and eyelid edema and occasionally euthyroid goiter. The syndrome generally occurs within the first 20 years of life. About 100 cases had been described by 1998.
Signs and Symptoms
Blepharochalasis : Recurrent episodes of swelling cause stretching and atrophy of the upper eyelid skin. This results in the relaxation of the tarsal fold allowing tissue to slack over the palpebral fissure. In severe cases, the lower eyelid is also involved.
Double Upper Lip : Swelling causes duplication between the inner and outer parts of the upper lip. Occasionally the lower lip is involved.
Euthyroid Goiter : Occurs in 10% of cases. It is not usually associated with toxic symptoms. Goiter usually presents several years after initial eyelid and lip edema.
Diagnosis
Treatment
Cosmetic surgery is generally the treatment of choice.
References
== External links == |
Triparesis | Triparesis is a medical condition, similar to triplegia, but the major difference between the two is primarily that triplegia is total loss of function in three limbs, and triparesis denotes weakening of three limbs.
== References == |
Distal trisomy 10q | Distal trisomy 10 is a rare chromosomal disorder that causes several physical defects and intellectual disability.Humans, like all sexually reproducing species, have somatic cells that are in diploid [2N] state, meaning that N represent the number of chromosomes, and 2 the number of their copies. In humans, there are 23 chromosomes, but there are two sets of them, one from mother and one from father, totaling in 46, that are arranged according to their size, function and genes they carry. Each cell is supposed to have two of each, but sometimes due to mutations or malfunctions during cell division, mistakes are made that cause serious health problems. One such error is the cause of Distal trisomy 10q disorder.Each chromosome has two arms, labeled p (for petite, or short) and q (for long). If both arms are equal in length, the chromosome is said to be metacentric. If arms lengths are unequal, chromosome is said to be submetacentric, and if p arm is so short that is hard to observe, but still present, then the chromosome is acrocentric. In Distal Trisomy 10q disorder, end or distal portion of the q (long) arm of the chromosome number 10 appears to be present three times, rather than two times as it is supposed to be. This extra arm results in chromosome 10 trisomy, meaning that three arms are present. Depending on the length of the aberrant arm, the severity can vary from case to case. Often the source of this chromosomal error is a translocation in one of the parents. Sometimes it occurs spontaneously, in which case it is termed de novo.This syndrome has a large range of outcomes depending on how much chromosomal material is involved. Outcomes include: very slow postnatal growth, hypotonia, lack of coordination skills and mild to severe cases of intellectual disability, digestive issues, and heart and kidney problems. Individuals with this disorder can also be distinguished by their facial features. Number of support groups do exist in the United States, where affected families can meet and discuss problems they encounter, possible treatments and can find emotional support.
See also
Down syndrome
Turner syndrome
Klinefelters syndrome
References
== External links == |
Ventricular dyssynchrony | In cardiology, ventricular dyssynchrony is a difference in the timing, or lack of synchrony, of contractions in different ventricles in the heart. Large differences in timing of contractions can reduce cardiac efficiency and is correlated with heart failure.
Types of dyssynchrony
Three chief presentations of dyssynchrony can occur:
Atrioventricular (AV) dyssynchrony occurs when there is an unfavorable difference in timing between atrial and ventricular contractions.
Interventricular dyssynchrony occurs when there is a difference in timing between right ventricular (RV) and left ventricular (LV) Systole.
Intraventricular dyssynchrony occurs when the timing in a sequence of activations and contractions of segments of the LV wall becomes abnormal. In all three types, changes in timing lead to changes in the dynamic behavior of the myocardial tissues, leading to mechanical dyssynchrony. All three presentations allow distinct and easily reproducible electrical signatures as illustrated by left and right bundle branch blocks, hemiblocks, etc. The concise measurement of the time and morphology of the QRS interval allows the interventional ability to manipulate this interval with biventricular pacemakers.
It is important to distinguish ventricular dyssynchrony from ventricular dyssynergy. Dyssynergy refers to changes in relative strength of contractions, whereas dyssynchrony is a change in relative timing of contractions. Once again the terms inotropy and chronotropy apply to the pathology under examination. Biventricular pacing strongly favors chronotropy over inotropy.
Diagnosis
Echocardiography and tissue Doppler echocardiography are both needed to fully diagnose the different types of ventricular dyssynchrony.
Treatment
Recent studies suggest that cardiac resynchronization therapy can reduce the incidence of ventricular dyssynchrony and thus increase cardiac efficiency.
See also
Bundle branch block
Ejection fraction
Pacemaker syndrome
Speckle tracking echocardiography
Transthoracic echocardiogram
== References == |
Hemolytic jaundice | Hemolytic jaundice, also known as prehepatic jaundice, is a type of jaundice arising from hemolysis or excessive destruction of red blood cells, when the byproduct bilirubin is not excreted by the hepatic cells quickly enough. Unless the patient is concurrently affected by hepatic dysfunctions or is experiencing hepatocellular damage, the liver does not contribute to this type of jaundice.As one of the three categories of jaundice, the most obvious sign of hemolytic jaundice is the discolouration or yellowing of the sclera and the skin of the patient, but additional symptoms may be observed depending on the underlying causes of hemolysis. Hemolytic causes associated with bilirubin overproduction are diverse and include disorders such as sickle cell anemia, hereditary spherocytosis, thrombotic thrombocytopenic purpura, autoimmune hemolytic anemia, hemolysis secondary to drug toxicity, thalassemia minor, and congenital dyserythropoietic anemias. Pathophysiology of hemolytic jaundice directly involves the metabolism of bilirubin, where overproduction of bilirubin due to hemolysis exceeds the livers ability to conjugate bilirubin to glucuronic acid.Diagnosis of hemolytic jaundice is based mainly on visual assessment of the yellowing of the patients skin and sclera, while the cause of hemolysis must be determined using laboratory tests. Treatment of the condition is specific to the cause of hemolysis, but intense phototherapy and exchange transfusion can be used to help the patient excrete accumulated bilirubin. Complications related to hemolytic jaundice include hyperbilirubinemia and chronic bilirubin encephalopathy, which may be deadly without proper treatment.
Signs and symptoms
The signs and symptoms additional to the development of a yellowish colour in the sclera and skin are specific to the causes of hemolysis.
For example, if the patient has hemolytic jaundice resulting from sickle cell disease, vaso-occlusive phenomena like acute vaso-occlusive pain and acute chest syndrome may be observed in the acute phases, while in anemia, neurologic deficits and various pulmonary conditions may manifest in the chronic phase.Regardless of the causes, laboratory-confirmed elevation is predominantly seen in unconjugated bilirubin. Serum bilirubin concentration rarely exceeds 4 mg/dL, unless the patient has concurrent liver disease.
Causes
The underlying causes of hemolytic jaundice, as its name suggests, are disorders associated with hemolysis. Such disorders are manifold and the common causes include:
Sickle cell disease, in which a mutation in the globin gene causes the formation of sickle hemoglobin. This disease is marked by the manifestation of chronic compensated hemolytic anemia, with laboratory findings not limited to unconjugated hyperbilirubinemia but also elevated serum lactate dehydrogenase and low serum haptoglobin.
Thrombotic thrombocytopenic purpura, in which the reduced activity of the von Willebrand factor-cleaving protease ADAMTS13 causes a thrombotic microangiopathy. This disease, acquired or hereditary, is marked by very severe microangiopathic hemolytic anemia, with laboratory findings including extremely high serum lactate dehydrogenase and negative anti-RBC antibodies and Coombs test. Clinically, dark urine from hemoglobinuria may be observed because the hemolysis is intravascular (see Pathophysiology below).
Autoimmune hemolytic anemia (AIHA), in which autoantibodies react with self red blood cells and cause their destruction. This disease is marked by increased extravascular hemolysis, with laboratory findings including increased lactate dehydrogenase and decreased or absent haptoglobin in both warm and cold AIHA, and positive Coombs test. Clinically, jaundice or dark urine present in approximately one-third of the cases, and most of the symptoms are related to anemia.Other less commonly observed causes of hemolysis include:
Hemolysis secondary to drug toxicity
Thalassemia minor
Congenital dyserythropoietic anemiaThe above list is not exhaustive, and rare causes of hemolysis such as Bartonella infection, hemolysis due to transfusion reactions, and microangiopathic hemolytic anemia should be suspected when symptoms specific to those causes manifest.
Pathophysiology
Bilirubin overproduction
The mechanisms by which bilirubin is overproduced in hemolytic jaundice can be understood in relation to the two major sites of hemolysis: intravascular and extravascular.During intravascular hemolysis, red blood cells are broken down within the vasculature, allowing hemoglobin from the ruptured red blood cells to form haptoglobin-hemoglobin complexes with haptoglobin, which will be internalized and degraded by hepatocytes and the spleen. If the degree of hemolysis is abnormally high, the unbound hemoglobin is converted to methemoglobin from which the heme moiety is bound to hemopexin or to albumin, and both heme-hemopexin and heme-bound albumin are internalized by hepatocytes and subsequently degraded to bilirubin.
During extravascular hemolysis, red blood cells are destroyed by phagocytosis by macrophages in the reticuloendothelial system and digested by phagosomes. Hemoglobin within red blood cells are then degraded to release heme, which will be converted by microsomal heme oxygenase to iron, carbon monoxide and biliverdin, and are immediately reduced to unconjugated bilirubin by biliverdin reductase and released into the plasma.
Affinity of unconjugated bilirubin to albumin
In both settings of hemolysis mentioned above, only low levels of conjugated bilirubin may accumulate in the serum, with the amount falling within the normal limits of 4 percent of total bilirubin as conjugated bilirubin can be efficiently excreted in bile through being secreted across canalicular membrane. Increased levels of conjugated bilirubin will only be observed with coexisting hepatobiliary abnormalities. Only when the canalicular excretion capacity is exceeded, conjugated bilirubin will accumulate in the plasma. As unconjugated bilirubin has a high affinity to albumin, at high level it is not efficiently cleared through glomerular filtration and it binds to the elastic tissue of the skin and sclera, where high albumin content can be found. This explains the yellow discolouration observed in these tissues in hemolytic jaundice.
Diagnosis
Symptoms of jaundice can be observed superficially, thus visual methods are used to identify the condition. However, underlying causes of jaundice must be diagnosed through laboratory testing.
Visual assessment
In both newborns and adults, yellowing of the skin is a marker for jaundice. As most cases of jaundice are observed in newborns, healthcare workers use visual methods to identify the presence of this condition. A clinical jaundice scale, an adapted version of the Kramers scale, is used to quantify the severity of jaundice through the spread of skin discoloration from zone 1, the head, to zone 5, the palms and soles of the neonates body. Cephalocaudal progression of jaundice to zone 4 and 5 of the Kramers scale shows a significant positive correlation with serum bilirubin concentration of at least 11.0 mg per 100 ml, indicating the need for treatment.
Jaundice Eye Colour Index (JECI)
Conjunctival icterus can be quantified by the Jaundice Eye Colour Index (JECI) through digital photography of the sclera, where a JECI of 0 indicates a white colour, and a JECI of 0.1 indicates an intense yellow colour, which is a sign of hemolytic jaundice.
Screening laboratory tests
Multiple tests can be used to diagnose jaundice, but results of different parameters must be compared to determine its etiology.
When a patient shows signs of jaundice such as the yellowing of the skin and sclera, a urine test is performed to check the levels of urobilinogen present. The presence of urobilinogen and its increased levels indicate that there are more than normal amounts of bilirubin in the intestine, showing that jaundice observed is not due to the blockage of bile flow, and is of pre-hepatic or hepatic causes. Normal colour of the patients urine indicates the absence of unconjugated bilirubin.Results from the urine test should be confirmed by a complete blood count (CBC) and serum testing for total serum bilirubin and fractionated bilirubin. Increased reticulocytes and the presence of schistocytes in the blood smear of the patient observed during CBC indicates hemolysis. If the patient has hemolytic jaundice, serum testing will show that conjugated bilirubin will only account for less than 15% of the total serum bilirubin due to the increase of unconjugated bilirubin.Analysis of liver biopsies will show the levels of alkaline phosphatase, aspartate transaminase, and alanine transaminase in the patient, which has a negative correlation with liver function. Normal levels of these enzymes indicate that there is no significant hepatocellular damage.When an infant is suspected to have hemolytic jaundice, abnormal morphologies of erythrocytes can be analyzed to find out the causes of hemolysis. A Coombs test should be performed, and end-tidal carbon monoxide concentration should be monitored to understand the rate of hemolysis in the infants body. If chronic hemolytic jaundice is diagnosed in a newborn, development of anemia and bilirubin cholelithiasis should be monitored as well.
Haptoglobin testing
If other symptoms of anemia is present, the amount of serum haptoglobin in the patient can be measured to test for hemolysis. During hemolysis, hemoglobin in blood dissociates and forms complexes with haptoglobins in the plasma, which are then catabolized. Low levels of haptoglobin resulting from the test shows that there are large amounts of free hemoglobin in the blood to be bound, acting as an indicator of hemolysis.
Treatment
As jaundice is not common in adults, most treatment methods for this condition are centered around neonates, of which 50% develop jaundice.
Neonates
Intensive phototherapy at saturation dose is used as a first-line clinical treatment which decreases the amount of accumulated unconjugated bilirubin in the infants serum by the addition of oxygen, thus allowing it to dissolve in water so the liver can more easily convert it into products which can be excreted without further metabolism. For infants with hemolytic jaundice, severe and prolonged cases of hyperbilirubinemia, or high serum bilirubin that does not decrease after phototherapy, blood exchange transfusion is carried out at the umbilical venous catheter to mechanically remove bilirubin. In cases of immune hemolytic jaundice, intravenous immunoglobulin therapy may be used to treat the condition. Administration of intravenous immunoglobulin can block monocyte Fc-receptors, preventing or reducing further hemolysis.
Adults
In adults, hemolytic jaundice is uncommon, and medical treatment methods should be determined by recognizing the underlying causes of hemolysis in the patient.
Complications
In cases where patients receive poor or no treatment of jaundice, neurodevelopmental complications may follow the condition, eventually leading to hearing loss, visual impairment, and in severe cases, mortality.
Hyperbilirubinemia
Hyperbilirubinemia may be observed when hemolysis produces too much bilirubin through the excessive breakdown of red blood cells, and the bilirubin builds up in the patients blood and tissue fluids without proper excretion. Untreated or inadequately treated hyperbilirubinemia will lead to other complications such as kernicterus.
Kernicterus
Chronic bilirubin encephalopathy, also known as kernicterus, is a brain-damaging complication associated with both preterm and full term infants with jaundice, where the large amounts of unconjugated bilirubin in the infants become neurotoxic. Kernicterus affects mainly the basal ganglia, and its effects can spread to the hippocampus, geniculate nuclei, and cranial nerve nuclei. Symptoms of kernicterus include athetoid cerebral palsy and in severe cases, may lead to death of the patient. Most cases of kernicterus develop in infants following early hospital discharge from phototherapy.
== References == |
Histoplasmosis | Histoplasmosis is a fungal infection caused by Histoplasma capsulatum. Symptoms of this infection vary greatly, but the disease affects primarily the lungs. Occasionally, other organs are affected; called disseminated histoplasmosis, it can be fatal if left untreated.
Histoplasmosis is common among AIDS patients because of their suppressed immunity. In immunocompetent individuals, past infection results in partial protection against ill effects if reinfected.
Histoplasma capsulatum is found in soil, often associated with decaying bat guano or bird droppings. Disruption of soil from excavation or construction can release infectious elements that are inhaled and settle into the lung.
From 1938 to 2013 in the US, 105 outbreaks were reported in a total of 26 states plus Puerto Rico. In 1978 to 1979 during a large urban outbreak in which 100,000 people were exposed to the fungus in Indianapolis, victims had pericarditis, rheumatological syndromes, esophageal and vocal cord ulcers, parotitis, adrenal insufficiency, uveitis, fibrosing mediastinitis, interstitial nephritis, intestinal lymphangiectasia, and epididymitis. Histoplasmosis mimics colds, pneumonia, and the flu, and can be shed by bats in their feces.
Signs and symptoms
If symptoms of histoplasmosis infection occur, they start within 3 to 17 days after exposure; the typical time is 12–14 days. Most affected individuals have clinically silent manifestations and show no apparent ill effects. The acute phase of histoplasmosis is characterized by nonspecific respiratory symptoms, often cough or flu-like. Chest X-ray findings are normal in 40–70% of cases. Chronic histoplasmosis cases can resemble tuberculosis; disseminated histoplasmosis affects multiple organ systems and is fatal unless treated.While histoplasmosis is the most common cause of mediastinitis, this remains a relatively rare disease. Severe infections can cause hepatosplenomegaly, lymphadenopathy, and adrenal enlargement. Lesions often left calcification nodules as they are healed.Presumed ocular histoplasmosis syndrome causes chorioretinitis, where the choroid and retina of the eyes are scarred, resulting in a loss of vision not unlike macular degeneration. Despite its name, the relationship to Histoplasma is controversial. Distinct from POHS, acute ocular histoplasmosis may rarely occur in immunodeficiency.
Complications
In absence of proper treatment and especially in immunocompromised individuals, complications can arise. These include recurrent pneumonia, respiratory failure, fibrosing mediastinitis, superior vena cava syndrome, pulmonary vessel obstruction, and progressive fibrosis of lymph nodes. Fibrosing mediastinitis is a serious complication and can be fatal. Smokers with structural lung disease have higher probability of developing chronic cavitary histoplasmosis.After healing of lesions, hard, calcified lymph nodes can erode the walls of the airway, causing hemoptysis.
Mechanisms
H. capsulatum grows in soil and material contaminated with bird or bat droppings (guano). The fungus has been found in poultry-house litter, caves, areas harboring bats, and bird roosts (particularly those of starlings). The fungus is thermally dimorphic; in the environment, it grows as a brownish mycelium, and at body temperature (37°C in humans), it morphs into a yeast. Histoplasmosis is not contagious but is contracted by inhalation of the spores from disturbed soil or guano. The inoculum is represented principally by microconidia. These are inhaled and reach the alveoli. In the alveoli, macrophages ingest these microconidia. They survive inside the phagosome. As the fungus is thermally dimorphic, these microconidia are transformed into yeast. They grow and multiply inside the phagosome. The macrophages travel in lymphatic circulation and can spread the disease to different organs.Within the phagosome, the fungus has an absolute requirement for thiamine. Cell-mediated immunity for histoplasmosis develops within 2 weeks. If the patient has strong cellular immunity, macrophages, epithelial cells, and lymphocytes surround the organisms and contain them, and eventually calcify. In immunocompromised individuals, the organisms disseminate to different organs such as bone, spleen, liver, adrenal glands, and mucocutaneous membranes, resulting in progressive disseminated histoplasmosis. Chronic lung disease can manifest.
Diagnosis
Clinically, a wide spectrum of disease manifestations occurs, making diagnosis somewhat difficult. More severe forms include the chronic pulmonary form, often occurring in the presence of underlying pulmonary disease, and a disseminated form, which is characterized by the progressive spread of infection to extrapulmonary sites. Oral manifestations have been reported as the main complaint of the disseminated forms, leading the patient to seek treatment, whereas pulmonary symptoms in disseminated disease may be mild or even misinterpreted as flu. Histoplasmosis can be diagnosed by samples containing the fungus taken from sputum (via bronchoalveolar lavage), blood, or infected organs. It can also be diagnosed by detection of antigens in blood or urine samples by ELISA or polymerase chain reaction. Antigens can cross-react with antigens of African histoplasmosis (caused by Histoplasma duboisii), blastomycosis, coccidioidomycosis, paracoccidioidomycosis, and talaromycosis infection. Histoplasmosis can also be diagnosed by a test for antibodies against Histoplasma in the blood. Histoplasma skin tests indicate whether persons have been exposed, but do not indicate whether they have the disease. Formal histoplasmosis diagnoses are often confirmed only by culturing the fungus directly. Sabouraud agar is one agar growth medium on which the fungus can be cultured. Cutaneous manifestations of disseminated disease are diverse and often present as a nondescript rash with systemic complaints. Diagnosis is best established by urine antigen testing, as blood cultures may take up to 6 weeks for diagnostic growth to occur and serum antigen testing often comes back with a false negative before 4 weeks of disseminated infection.
Types
Histoplasmosis may be divided into these types:: 316–317
Primary pulmonary histoplasmosis
Progressive disseminated histoplasmosis
Primary cutaneous histoplasmosis
African histoplasmosis
Prevention
Testing or decontaminating most sites that may be contaminated with H. capsulatum is impractical, but the sources below list environments where histoplasmosis is common, and precautions to reduce a persons risk of exposure, in the three parts of the world where the disease is prevalent. Precautions common to all geographical locations would be to avoid accumulations of bird or bat droppings.The US National Institute for Occupational Safety and Health provides information on work practices and personal protective equipment that may reduce the risk of infection.A review paper includes information on locations in which Histoplasma has been found in Africa (in chicken runs, on bats, in the caves bats inhabit, and in soil), and a thorough reference list including English, French, and Spanish language references.
Treatment
In the majority of immunocompetent individuals, histoplasmosis resolves without any treatment. Antifungal medications are used to treat severe cases of acute histoplasmosis and all cases of chronic and disseminated disease. Typical treatment of severe disease first involves treatment with amphotericin B, followed by oral itraconazole.Liposomal preparations of amphotericin B are more effective than deoxycholate preparations. The liposomal preparation is preferred in patients who might be at risk of nephrotoxicity, although all preparations of amphotericin B have risk of nephrotoxicity. Individuals taking amphotericin B are monitored for renal function. Liposomal amphotericin B is better at treating people with progressive disseminated Histoplasmosis and underlying HIV when compared to deoxycholate amphotericin B. Meanwhile, fluconazole performs poorly when compared to other azoles.Treatment with itraconazole must continue for at least a year in severe cases, while in acute pulmonary Histoplasmosis, 6 to 12 weeks treatment is sufficient. Alternatives to itraconazole are posaconazole, voriconazole, and fluconazole. Individuals taking itraconazole are monitored for hepatic function.
Prognosis
About 90% of patients with normal immune systems regain health without any intervention. Less than 5% need serious treatments.
Epidemiology
H. capsulatum is found throughout the world. It is endemic in certain areas of the United States, particularly in states bordering the Ohio River valley and the lower Mississippi River. The humidity and acidity patterns of soil are associated with endemicity. Bird and bat droppings in soil promote the growth of Histoplasma. Contact with such soil aerosolizes the microconidia, which can infect humans. It is also common in caves in Southern and East Africa. Positive Histoplasmin skin tests occur in as many as 90% of the people living in areas where H. capsulatum is common, such as the eastern and central United States.In Canada, the St. Lawrence River Valley is the site of the most frequent infections, with 20–30% of the population testing positive. A review of reported cases in 2018 showed disease presence throughout Southeast Asia, In India, the Gangetic West Bengal is the site of most frequent infections, with 9.4% of the population testing positive. H. c. capsulatum was isolated from the local soil proving endemicity of Histoplasmosis in West Bengal.
History
Histoplasma was discovered in 1905 by Samuel T. Darling, but only in the 1930s was it discovered to be a widespread infection. Before then, many cases of histoplasmosis were mistakenly attributed to tuberculosis, and patients were mistakenly admitted to tuberculosis sanatoria. Some patients contracted tuberculosis in these sanatoriums.
Society and culture
Johnny Cash included a reference to the disease, even correctly noting its source in bird droppings, in the song "Beans for Breakfast".
Bob Dylan was hospitalized due to Histoplasmosis in 1997, causing the cancellation of concerts in the United Kingdom and Switzerland.
In episode 21 of season three of the television series House M.D., a patient was diagnosed with Histoplasmosis.
In episode five of season one of the television series Dexter, Vince Masuka gets worried about getting Histoplasmosis from the dust in the air and the hair of the rats.
In episode 5 of season 5 of Monsters Inside Me, a video game programmer, Cody Fry was infected with the disease.
In the BBC drama Call The Midwifes 9th season, a character is diagnosed with the disease after initial confusion regarding whether his symptoms were more indicative of tuberculosis. He contracts it from the droppings of pet pigeons he keeps in his home.
References
External links
CDC Disease Info histoplasmosis |
Hip fracture | A hip fracture is a break that occurs in the upper part of the femur (thigh bone). Symptoms may include pain around the hip, particularly with movement, and shortening of the leg. Usually the person cannot walk.They most often occur as a result of a fall. (Femoral head fractures are a rare kind of hip fracture that may also be the result of a fall but are more commonly caused by more violent incidents such as traffic accidents.) Risk factors include osteoporosis, taking many medications, alcohol use, and metastatic cancer. Diagnosis is generally by X-rays. Magnetic resonance imaging, a CT scan, or a bone scan may occasionally be required to make the diagnosis.Pain management may involve opioids or a nerve block. If the persons health allows, surgery is generally recommended within two days. Options for surgery may include a total hip replacement or stabilizing the fracture with screws. Treatment to prevent blood clots following surgery is recommended.About 15% of women break their hip at some point in life; women are more often affected than men. Hip fractures become more common with age. The risk of death in the year following a fracture is about 20% in older people.
Signs and symptoms
The classic clinical presentation of a hip fracture is an elderly patient who sustained a low-energy fall and now has groin pain and is unable to bear weight. Pain may be referred to the supracondylar knee. On examination, the affected extremity is often shortened and externally rotated compared to the unaffected leg.
Complications
Nonunion, failure of the fracture to heal, is common in fractures of the neck of the femur, but much more rare with other types of hip fracture. Avascular necrosis of the femoral head occurs frequently (20%) in intracapsular hip fractures, because the blood supply is interrupted.Malunion, healing of the fracture in a distorted position, is very common. The thigh muscles tend to pull on the bone fragments, causing them to overlap and reunite incorrectly. Shortening, varus deformity, valgus deformity, and rotational malunion all occur often because the fracture may be unstable and collapse before it heals. This may not be as much of a concern in patients with limited independence and mobility.Hip fractures rarely result in neurological or vascular injury.
Medical
Many people are unwell before breaking a hip; it is common for the break to have been caused by a fall due to some illness, especially in the elderly. Nevertheless, the stress of the injury, and a likely surgery, increases the risk of medical illness including heart attack, stroke, and chest infection.Hip fracture patients are at considerable risk for thromboemoblism, blood clots that dislodge and travel in the bloodstream. Deep venous thrombosis (DVT) is when the blood in the leg veins clots and causes pain and swelling. This is very common after hip fracture as the circulation is stagnant and the blood is hypercoagulable as a response to injury. DVT can occur without causing symptoms. A pulmonary embolism (PE) occurs when clotted blood from a DVT comes loose from the leg veins and passes up to the lungs. Circulation to parts of the lungs is cut off which can be very dangerous. Fatal PE may have an incidence of 2% after hip fracture and may contribute to illness and mortality in other cases.Mental confusion is extremely common following a hip fracture. It usually clears completely, but the disorienting experience of pain, immobility, loss of independence, moving to a strange place, surgery, and drugs combine to cause delirium or accentuate pre-existing dementia.
Urinary tract infection (UTI) can occur. Patients are immobilized and in bed for many days; they are frequently catheterised, commonly causing infection.
Prolonged immobilization and difficulty moving make it hard to avoid pressure sores on the sacrum and heels of patients with hip fractures. Whenever possible, early mobilization is advocated; otherwise, alternating pressure mattresses should be used.
Risk factors
Hip fracture following a fall is likely to be a pathological fracture. The most common causes of weakness in bone are:
Osteoporosis.
Other metabolic bone diseases such as Pagets disease, osteomalacia, osteopetrosis and osteogenesis imperfecta. Stress fractures may occur in the hip region with metabolic bone disease.
Elevated levels of homocysteine, a toxic natural amino acid.
Benign or malignant primary bone tumors are rare causes of hip fractures.
Metastatic cancer deposits in the proximal femur may weaken the bone and cause a pathological hip fracture.
Infection in the bone is a rare cause of hip fracture.
Tobacco smoking (associated with osteoporosis).
Mechanism
Functional anatomy
The hip joint is a ball-and-socket joint. The femur connects at the acetabulum of the pelvis and projects laterally before angling medially and inferiorly to form the knee. Although this joint has three degrees of freedom, it is still stable due to the interaction of ligaments and cartilage. The labrum lines the circumference of the acetabulum to provide stability and shock absorption. Articular cartilage covers the concave area of acetabulum, providing more stability and shock absorption. Surrounding the entire joint itself is a capsule secured by the tendon of the psoas muscle and three ligaments. The iliofemoral, or Y, ligament is located anteriorly and serves to prevent hip hyperextension. The pubofemoral ligament is located anteriorly just underneath the iliofemoral ligament and serves primarily to resist abduction, extension, and some external rotation. Finally the ischiofemoral ligament on the posterior side of the capsule resists extension, adduction, and internal rotation. When considering the biomechanics of hip fractures, it is important to examine the mechanical loads the hip experiences during low energy falls.
Biomechanics
The hip joint is unique in that it experiences combined mechanical loads. An axial load along the shaft of the femur results in compressive stress. Bending load at the neck of the femur causes tensile stress along the upper part of the neck and compressive stress along the lower part of the neck. While osteoarthritis and osteoporosis are associated with bone fracture as we age, these diseases are not the cause of the fracture alone. Low energy falls from standing are responsible for the majority of fractures in the elderly, but fall direction is also a key factor. Elderly tend to fall to the side as instead of forward, and the lateral hip and strikes the ground first. During a sideways fall, the chances of hip fracture see a 15-fold and 12-fold increase in elderly males and females, respectively.
Neurological factors
Elderly individuals are also predisposed to hip fractures due to many factors that can compromise proprioception and balance, including medications, vertigo, stroke, and peripheral neuropathy.
Diagnosis
Physical examination
Displaced fractures of the trochanter or femoral neck will classically cause external rotation and shortening of the leg when the patient is laying supine.
Imaging
Typically, radiographs are taken of the hip from the front (AP view), and side (lateral view). Frog leg views are to be avoided, as they may cause severe pain and further displace the fracture. In situations where a hip fracture is suspected but not obvious on x-ray, an MRI is the next test of choice. If an MRI is not available or the patient can not be placed into the scanner a CT may be used as a substitute. MRI sensitivity for radiographically occult fracture is greater than CT. Bone scan is another useful alternative however substantial drawbacks include decreased sensitivity, early false negative results and decreased conspicuity of findings due to age-related metabolic changes in the elderly.A case demonstrating a possible order of imaging in initially subtle findings:
As the patients most often require an operation, full pre-operative general investigation is required. This would normally include blood tests, ECG and chest x-ray.
Types
X-rays of the affected hip usually make the diagnosis obvious; AP (anteroposterior) and lateral views should be obtained.
Trochanteric fractures are subdivided into either intertrochanteric (between the greater and lesser trochanter) or pertrochanteric (through the trochanters) by the Müller AO Classification of fractures. Practically, the difference between these types is minor. The terms are often used synonymously. An isolated trochanteric fracture involves one of the trochanters without going through the anatomical axis of the femur, and may occur in young individuals due to forceful muscle contraction. Yet, an isolated trochanteric fracture may not be regarded as a true hip fracture because it is not cross-sectional.
Prevention
The majority of hip fractures are the result of a fall, particularly in the elderly. Therefore, identifying why the fall occurred, and implementing treatments or changes, is key to reducing the occurrence of hip fractures. Multiple contributing factors are often identified. These can include environmental factors and medical factors (such as postural hypotension or co-existing disabilities from disease such as Stroke or Parkinsons disease which cause visual and/or balance impairments). A recent study has identified a high incidence of undiagnosed cervical spondylotic myelopathy (CSM) amongst patients with a hip fracture. This is relatively unrecognised consequent of CSM.Additionally, there is some evidence to systems designed to offer protection in the case of a fall. Hip protectors, for example appear to decrease the number of hip fractures among the elderly, but they are often not used.
Management
Most hip fractures are treated surgically by implanting a prosthesis. Surgical treatment outweighs the risks of nonsurgical treatment which requires extensive bedrest. Prolonged immobilization increases risk of thromboembolism, pneumonia, deconditioning, and decubitus ulcers. Regardless, the surgery is a major stress, particularly in the elderly. Pain is also significant, and can also result in immobilization, so patients are encouraged to become mobile as soon as possible, often with the assistance of physical therapy. Skeletal traction pending surgery is not supported by the evidence. Regional nerve blocks are useful for pain management in hip fractures. Peripheral nerve blocks may reduce pain on movement and acute confusional state, may improve time to first mobilisation, and may reduce the risk of postoperative lower respiratory tract infection. Surgery can be performed under general anaesthesia or with neuraxial techniques – choice is based on surgical and patient factors, as outcomes such as mortality and post-procedure complications including pneumonia, MI, stroke or confusion, are not affected by anaesthetic technique.Red blood cell transfusion is common for people undergoing hip fracture surgery due to the blood loss sustained during surgery and from the injury. The benefits of giving blood when the hemoglobin is less than 10 g/dL versus less than 8 g/dL are not clear. Waiting until the hemoglobin was less than 8 g/dL or the person had symptoms may increase the risk of heart problems.If operative treatment is refused or the risks of surgery are considered to be too high the main emphasis of treatment is on pain relief. Skeletal traction may be considered for long-term treatment. Aggressive chest physiotherapy is needed to reduce the risk of pneumonia and skilled rehabilitation and nursing to avoid pressure sores and DVT/pulmonary embolism Most people will be bedbound for several months. Non-operative treatment is now limited to only the most medically unstable or demented patients or those who are nonambulatory at baseline with minimal pain during transfers.Surgery on the same day or day following the break is estimated to reduce postoperative mortality in people who are medically stable.
Intracapsular fractures
For low-grade fractures (Garden types 1 and 2), standard treatment is fixation of the fracture in situ with screws or a sliding screw/plate device. This treatment can also be offered for displaced fractures after the fracture has been reduced.Fractures managed by closed reduction can possibly be treated by percutaneously inserted screws.In elderly patients with displaced or intracapsular fractures many surgeons prefer to undertake a hemiarthroplasty, replacing the broken part of the bone with a metal implant. However, in elderly people who are medically well and still active, a total hip replacement may be indicated. Independently mobile older adults with hip fractures may benefit from a total hip replacement instead of hemiarthroplasty.Traction is contraindicated in femoral neck fractures due to it affecting blood flow to the head of the femur.The latest evidence suggests that there may be little or no difference between screws and fixed angle plates as internal fixation implants for intracapsular hip fractures in older adults. The findings are based on low quality evidence that cant firmly conclude major difference in hip function, quality of life, and additional surgery.
Trochanteric fracture
A trochanteric fracture, below the neck of the femur, has a good chance of healing.
Closed reduction may not be satisfactory and open reduction then becomes necessary. The use of open reduction has been reported as 8-13% among pertrochanteric fractures, and 52% among intertrochanteric fractures. Both intertrochanteric and pertrochanteric fractures may be treated by a dynamic hip screw and plate, or an intramedullary rod.The fracture typically takes 3–6 months to heal. As it is only common in elderly, removal of the dynamic hip screw is usually not recommended to avoid unnecessary risk of second operation and the increased risk of re-fracture after implant removal. The most common cause for hip fractures in the elderly is osteoporosis; if this is the case, treatment of the osteoporosis can well reduce the risk of further fracture. Only young patients tend to consider having it removed; the implant may function as a stress riser, increasing the risk of a break if another accident occurs.
Subtrochanteric fractures
Subtrochanteric fractures may be treated with an intramedullary nail or a screw-plate construction and may require traction pre-operatively, though this practice is uncommon. It is unclear if any specific type of nail results in different outcomes than any other type of nail.A lateral incision over the trochanter is made and a cerclage wire is placed around the fracture for reduction. Once reduction has been achieved a guide canal for the nail is made through the proximal cortex and medullary. The nail is inserted through the canal and is fixated proximally and distally with screws. X-rays are obtained to ensure proper reduction and placement of the nail and screws are achieved.
Rehabilitation
Rehabilitation has been proven to increase daily functional status. Forty percent of individuals with hip fractures are also diagnosed with dementia or mild cognitive impairment which often results in poorer post-surgical outcomes. In such cases enhanced rehabilitation and care models have been shown to have limited positive effects in reducing delirium and hospital length of stay. It is unclear if the use of anabolic steroids effects recovery.There is not enough evidence to ascertain what are the best strategies to promote walking after hip fracture surgery. On the other hand, there is moderate-certaintly evidence that rehabilitation after hip fracture surgery, when delivered by a multidisciplinary team and supervised by an appropriate medical specialist, results in fewer cases of poor outcome, like death and deterioration in residential status.
Nutrition supplementation
Oral supplements with non-protein energy, protein, vitamins and minerals started before or early after surgery may prevent complications during the first year after hip fracture in aged adults; without seemingly effects on mortality.
Surgical complications
Deep or superficial wound infection has an approximate incidence of 2%. It is a serious problem as superficial infection may lead to deep infection. This may cause infection of the healing bone and contamination of the implants. It is difficult to eliminate infection in the presence of metal foreign bodies such as implants. Bacteria inside the implants are inaccessible to the bodys defence system and to antibiotics. The management is to attempt to suppress the infection with drainage and antibiotics until the bone is healed. Then the implant should be removed, following which the infection may clear up.
Implant failure may occur; the metal screws and plate can break, back out, or cut out superiorly and enter the joint. This occurs either through inaccurate implant placement or if the fixation does not hold in weak and brittle bone. In the event of failure, the surgery may be redone or changed to a total hip replacement. Mal-positioning: The fracture can be fixed and subsequently heal in an incorrect position; especially rotation. This may not be a severe problem or may require subsequent osteotomy surgery for correction.
Prognosis
Hip fractures are very dangerous episodes, especially for elderly and frail patients. The risk of dying from the stress of the surgery and the injury in the first thirty days is about 10%. At one year after fracture, this may reach 30%. If the condition is untreated the pain and immobility imposed on the patient increase that risk. Problems such as pressure sores and chest infections are all increased by immobility. The prognosis of untreated hip fractures is very poor.
Post operation
Among those affected over the age of 65, 40% are transferred directly to long-term care facilities, long-term rehabilitation facilities, or nursing homes; most of those affected require some sort of living assistance from family or home-care providers. 50% permanently require walkers, canes, or crutches for mobility; all require some sort of mobility assistance throughout the healing process. Most of the recovery of walking ability and activities of daily living occurs within 6 months of the fracture. After the fracture about half of older people recover their pre-fracture level of mobility and ability to perform instrumental activities of daily living, while 40–70% regain their level of independence for basic activities of daily living.Among those affected over the age of 50, approximately 25% die within the next year due to complications such as blood clots (deep venous thrombosis, pulmonary embolism), infections, and pneumonia.Patients with hip fractures are at high risk for future fractures including hip, wrist, shoulder, and spine. After treatment of the acute fracture, the risk of future fractures should be addressed. Currently, only 1 in 4 patients after a hip fracture receives treatment and work up for osteoporosis, the underlying cause of most of the fractures. Current treatment standards include the starting of a bisphosphonate to reduce future fracture risk by up to 50%.
Epidemiology
Hip fractures are seen globally and are a serious concern at the individual and population level. By 2050, it is estimated that there will be six million cases of hip fractures worldwide. One study published in 2001 found that in the US alone, 310,000 individuals were hospitalized due to hip fractures, which can account for 30% of Americans who were hospitalized that year. Another study found that in 2011, femur neck fractures were among the most expensive conditions seen in US hospitals, with an aggregated cost of nearly $4.9 billion for 316,000 inpatient hospitalizations. Rates of hip fractures are declining in the United States, possibly due to increased use of bisphosphonates and risk management. Falling, poor vision, weight, and height are all seen as risk factors. Falling is one of the most common risk factors for hip fractures. Approximately 90% of hip fractures are attributed to falls from standing height.Given the high morbidity and mortality associated with hip fractures and the cost to the health system, in England and Wales, the National Hip Fracture Database is a mandatory nationwide audit of care and treatment of all hip fractures.
Population
All populations experience hip fractures but numbers vary with race, gender, and age. Women have three times as many hip fractures as men. In a lifetime, men have an estimated 6% risk whereas postmenopausal women have an estimated 14% risk of having a hip fracture. These statistics provide insight over a lifespan, and conclude that women are twice as likely to have a hip fracture. The overwhelming majority of hip fractures occur in white individuals, while blacks and Hispanics have a lower rate of them. This may be due to their generally greater bone density and also because whites have longer overall lifespan and higher likelihood of reaching an advanced age where the risk of breaking a hip goes up. Deprivation is also a key factor: in England, it has been found that people in the poorest parts of the country are more likely to fracture a hip and less likely to recover well than those in the least deprived areas.
Age related
Age is the most dominant factor in hip fracture injuries, with most cases occurring in people over 75. The increase of age is related to the increase of the incidence of hip fracture, which is the most frequent cause of hospitalization in centenarians, overcoming congestive heart failure and respiratory infection. Falls are the most common cause of hip fractures; around 30–60% of older adults fall each year. This increases the risk for hip fracture and leads to the increased risk of death in older individuals, the rate of one year mortality is seen from 12 to 37%. For those remaining patients, half of them need assistance and cannot live independently. Also, older adults sustain hip fractures because of osteoporosis, which is a degenerative disease due to age and decrease in bone mass. The average age for sustaining a hip fracture is 77 years old for women and 72 years old for men.
References
External links
Fractures of the Femoral Neck Wheeless Textbook of Orthopaedics
Intertrochanteric Fractures Wheeless Textbook of Orthopaedics |
Acute cutaneous lupus erythematosus | Acute cutaneous lupus erythematosus is a cutaneous condition characterized by a bilateral malar rash (also known as a "butterfly rash") and lesions that tend to be transient, and that follow sun exposure. The acute form is distinct from chronic and subacute cutaneous lupus erythematosus, which may have different types of skin lesions. Cutaneous lupus erythematosus is associated with both lupus erythematosus-specific lesions and cutaneous manifestations that are not specific to lupus erythematosus, such as oral ulcers and urticaria. Because of the diagnostic criteria used to diagnose systemic lupus erythematosus, a patient with only cutaneous manifestations may be diagnosed with the systemic form of the disease.
Forms
Acute cutaneous lupus erythematosus can be either localized or generalized.
Localized form
The localized form of the disease is most commonly associated with the malar rash and normally develops in a patients twenties. The localized form occurs only above the patients neck and is not associated with rashes in other parts of the body.
Generalized form
Generalized acute cutaneous lupus erythematosus includes skin below the patients neck and is described as a macropapular rash or photosensitive lupus dermatitis. Symptoms include similar erythematic lesions as seen in the localized form, but forms a symmetrical rash and can be mistaken for a drug rash.
See also
Lupus erythematosus
List of cutaneous conditions
== References == |
Primary myelofibrosis | Primary myelofibrosis (PMF) is a rare bone marrow blood cancer. It is classified by the World Health Organization (WHO) as a type of myeloproliferative neoplasm, a group of cancers in which there is growth of abnormal cells in the bone marrow. This is most often associated with a somatic mutation in the JAK2, CALR, or MPL gene markers. In PMF, the healthy marrow is replaced by scar tissue (fibrosis), resulting in a lack of production of normal blood cells. Symptoms include anemia, increased infection and an enlarged spleen (splenomegaly).
In 2016, prefibrotic primary myelofibrosis was formally classified as a distinct condition that progresses to overt PMF in many patients, the primary diagnostic difference being the grade of fibrosis.
Signs and symptoms
The primary feature of primary myelofibrosis is bone marrow fibrosis, but it is often accompanied by:
Abdominal fullness related to an enlarged spleen (splenomegaly).
Bone pain
Bruising and easy bleeding due to inadequate numbers of platelets
Cachexia (loss of appetite, weight loss, and fatigue)
Enlargement of both the liver and spleen
Fatigue
Gout and high uric acid levels
Increased susceptibility to infection, such as pneumonia
Pallor and shortness of breath due to anemia
In rarer cases, a raised red blood cell volume
Cutaneous myelofibrosis is a rare skin condition characterized by dermal and subcutaneous nodules.: 746
Causes
The underlying cause of PMF is unknown (idiopathic disease). There is an association between mutations to the JAK2, CALR, or MPL gene and myelofibrosis. Approximately 90% of those with myelofibrosis have one of these mutations and 10% carry none of these mutations. These mutations are not specific to myelofibrosis, and are linked to other myeloproliferative neoplasms, specifically polycythemia vera and essential thrombocythemia.The V617F mutation to the JAK2 protein is found in approximately half of individuals with primary myelofibrosis. The V617F mutation is a change of valine to phenylalanine at the 617 position. Janus kinases (JAKs) are non-receptor tyrosine kinases essential for the activation of signaling that is mediated by cytokine receptors lacking catalytic activity. These include receptors for erythropoietin, thrombopoietin, most interleukins and interferon. JAK2 mutations are significant because JAK2 plays a role in controlling production of blood cells from hematopoietic stem cells. The V617F mutation appears to make hematopoietic cells more sensitive to growth factors that need JAK2 for signal transduction, which include erythropoietin and thrombopoietin.The MPL gene codes for a protein that acts as a receptor for thrombopoietin. A mutation in that gene, known as a W515 mutation, leads to the production of an abnormal thrombopoietin receptor protein, which results in the overproduction of abnormal megakaryocytes. The abnormal megakaryocytes stimulate other cells, the fibroblasts, to produce collagen in the bone marrow, by secreting PDGF and TGF-β1.
Mechanism
Myelofibrosis is a clonal neoplastic disorder of hematopoiesis, the formation of blood cellular components. It is one of the myeloproliferative disorders, diseases of the bone marrow in which excess cells are produced at some stage. Production of cytokines such as fibroblast growth factor by the abnormal hematopoietic cell clone (particularly by megakaryocytes) leads to replacement of the hematopoietic tissue of the bone marrow by connective tissue via collagen fibrosis. The decrease in hematopoietic tissue impairs the patients ability to generate new blood cells, resulting in progressive pancytopenia, a shortage of all blood cell types. However, the proliferation of fibroblasts and deposition of collagen is a secondary phenomenon, and the fibroblasts themselves are not part of the abnormal cell clone.In primary myelofibrosis, progressive scarring, or fibrosis, of the bone marrow occurs, for the reasons outlined above. The result is extramedullary hematopoiesis, i.e. blood cell formation occurring in sites other than the bone marrow, as the hemopoietic cells are forced to migrate to other areas, particularly the liver and spleen. This causes an enlargement of these organs. In the liver, the abnormal size is called hepatomegaly. Enlargement of the spleen is called splenomegaly, which also contributes to causing pancytopenia, particularly thrombocytopenia and anemia. Another complication of extramedullary hematopoiesis is poikilocytosis, or the presence of abnormally shaped red blood cells.Myelofibrosis can be a late complication of other myeloproliferative disorders, such as polycythemia vera, and less commonly, essential thrombocythemia. In these cases, myelofibrosis occurs as a result of somatic evolution of the abnormal hematopoietic stem cell clone that caused the original disorder. In some cases, the development of myelofibrosis following these disorders may be accelerated by the oral chemotherapy drug hydroxyurea.
Sites of hematopoiesis
The principal site of extramedullary hematopoiesis in myelofibrosis is the spleen, which is usually markedly enlarged, sometimes weighing as much as 4000 g. As a result of massive enlargement of the spleen, multiple subcapsular infarcts often occur in the spleen, meaning that due to interrupted oxygen supply to the spleen partial or complete tissue death happens. On the cellular level, the spleen contains red blood cell precursors, granulocyte precursors and megakaryocytes, with the megakaryocytes prominent in their number and in their bizarre shapes. Megakaryocytes are believed to be involved in causing the secondary fibrosis seen in this condition, as discussed under "Mechanism" above. Sometimes unusual activity of the red blood cells, white blood cells, or platelets is seen. The liver is often moderately enlarged, with foci of extramedullary hematopoiesis. Microscopically, lymph nodes also contain foci of hematopoiesis, but these are insufficient to cause enlargement.There are also reports of hematopoiesis taking place in the lungs. These cases are associated with hypertension in the pulmonary arteries.The bone marrow in a typical case is hypercellular and diffusely fibrotic. Both early and late in disease, megakaryocytes are often prominent and are usually dysplastic.
Diagnosis
Epidemiologically, the disorder usually develops slowly and is mainly observed in people over the age of 50.Diagnosis is made on the basis of bone marrow biopsy. Fibrosis grade 2 or 3 defines overt PMF whereas grade 0 or 1 defines prefibrotic primary myelofibrosis.A physical exam of the abdomen may reveal enlargement of the spleen, the liver, or both.Blood tests are also used in diagnosis. Primary myelofibrosis can begin with a blood picture similar to that found in polycythemia vera or chronic myeloid leukemia. Most people with myelofibrosis have moderate to severe anemia. Eventually thrombocytopenia, a decrease of blood platelets develops. When viewed through a microscope, a blood smear will appear markedly abnormal, with presentation of pancytopenia, which is a reduction in the number of all blood cell types: red blood cells, white blood cells, and platelets. Red blood cells may show abnormalities including bizarre shapes, such as teardrop-shaped cells, and nucleated red blood cell precursors may appear in the blood smear (leukoerythroblastic reaction). Normally, mature red blood cells in adults do not have a cell nucleus, and the presence of nucleated red blood cells suggests that immature cells are being released into the bloodstream in response to a very high demand for the bone marrow to produce new red blood cells. Immature white cells and platelets (large megakaryocytes) are also seen in blood samples, and basophil counts are increased. When late in the disease progression an attempt is made to take a sample of bone marrow by aspiration, it may result in a dry tap, meaning that where the needle can normally suck out a sample of semi-liquid bone marrow, it produces no sample because the marrow has been replaced with collagen fibers. A bone marrow biopsy will reveal collagen fibrosis, replacing the marrow that would normally occupy the space.
Treatment
The one known curative treatment is allogeneic stem cell transplantation, but this approach involves significant risks.
Other treatment options are largely supportive, and do not alter the course of the disorder (with the possible exception of ruxolitinib, as discussed below). These options may include regular folic acid, allopurinol or blood transfusions. Dexamethasone, alpha-interferon and hydroxyurea (also known as hydroxycarbamide) may play a role.Lenalidomide and thalidomide may be used in its treatment, though peripheral neuropathy is a common troublesome side-effect.Frequent blood transfusions may also be required. If the patient is diabetic and is taking a sulfonylurea, this should be stopped periodically to rule out drug-induced thrombocytopenia.Splenectomy is sometimes considered as a treatment option for patients with myelofibrosis in whom massive splenomegaly is contributing to anaemia because of hypersplenism, particularly if they have a heavy requirement for blood transfusions. However, splenectomy in the presence of massive splenomegaly is a high-risk procedure, with a mortality risk as high as 3% in some studies.In November 2011, the U.S. Food and Drug Administration (FDA) approved ruxolitinib (Jakafi) as a treatment for intermediate or high-risk myelofibrosis. Ruxolitinib serves as an inhibitor of JAK 1 and 2.
The New England Journal of Medicine (NEJM) published results from two Phase III studies of ruxolitinib. These data showed that the treatment significantly reduced spleen volume, improved symptoms of myelofibrosis, and was associated with much improved overall survival rates compared to placebo. However, the beneficial effect of ruxolitinib on survival has been recently questioned.In August 2019, the FDA approved fedratinib (Inrebic) as a treatment for adults with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis (MF).In March 2022, the FDA approved pacritinib (Vonjo) with an indication to treat adults who have intermediate or high-risk primary or secondary myelofibrosis and who have platelet (blood clotting cells) levels below 50,000/µL.
History
Myelofibrosis was first described in 1879 by Gustav Heuck. Eponyms for the disease are Heuck-Assmann disease or Assmanns Disease, for Herbert Assmann, who published a description under the term "osteosclerosis" in 1907.It was characterised as a myeloproliferative condition in 1951 by William Dameshek.The disease was also known as myelofibrosis with myeloid metaplasia and agnogenic myeloid metaplasia The World Health Organization utilized the name chronic idiopathic myelofibrosis until 2008, when it adopted the name of primary myelofibrosis.
In 2016, the WHO revised their classification of myeloproliferative neoplasms to define Prefibrotic primary myelofibrosis as a distinct clinical entity from overt PMF.
References
== External links == |
Craniodiaphyseal dysplasia | Craniodiaphyseal dysplasia (CDD), also known as lionitis, is an extremely rare autosomal recessive bone disorder that causes calcium to build up in the skull, disfiguring the facial features and reducing life expectancy.
These calcium deposits decrease the size of cranial foramina, and can decrease the circumference of the cervical spinal canal. In the few cases recorded, most died in childhood.
Cause
The underlying genetics are uncertain.
Diagnosis
Among the medical signs are dacryocystitis, seizures, intellectual disability, and paralysis, each of which is a complication resulting from the diminutive foramina. A common sign reported as a result of the disease has been widely spaced eyes.
Society
Peter Bogdanovichs 1985 drama film Mask drew public attention to the case of Roy L. "Rocky" Dennis, an American boy who died of the disorder in 1978.In the American medical drama Greys Anatomy episode "Yesterday", Jesse Plemons plays a teenage boy with lionitis. The main character of the two-issue comic book miniseries Friday the 13th: How I Spent My Summer Vacation by Wildstorm Productions is a 13-year-old boy with the disorder. In the anthology television series American Horror Story season 1, Beauregard, the brother of Tate and Adelaide, had lionitis.
See also
Leontiasis ossea
References
External links
Craniodiaphyseal dysplasia at orpha.net |
X-linked endothelial corneal dystrophy | X-linked endothelial corneal dystrophy (XECD) is a rare form of corneal dystrophy described first in 2006, based on a 4-generation family of 60 members with 9 affected males and 35 trait carriers, which led to mapping the XECD locus to Xq25. It manifests as severe corneal opacification or clouding, sometimes congenital, in the form of a ground glass, milky corneal tissue, and moon crater-like changes of corneal endothelium. Trait carriers manifest only endothelial alterations resembling moon craters.As of December 2014, the molecular basis for this disease remained unknown, although 181 genes were known to be within the XECD locus, of which 68 were known to be protein-coding.
References
== External links == |
Sinusoidal hemangioma | Sinusoidal hemangioma is a condition, by something of a misnomer, a term for a lesion that is a vascular malformation with various clinical presentations. This condition may present as nodules, often in the breast area or extremities, or as large firm bulging facial masses beneath normal-appearing skin; the latter have an aggressive and invasive course.
See also
Sinus pericranii
List of cutaneous conditions
== References == |
Sick building syndrome | Sick building syndrome (SBS) is a condition in which people in a building develop symptoms of illness or become infected with chronic disease from the building in which they work or reside. The outbreaks may or may not be a direct result of inadequate cleaning or inappropriate cleaning methods. SBS has also been used to describe staff concerns in post-war buildings with misplanned building aerodynamics, defects in the construction materials or assembly process and-or inadequate maintenance. Certain symptoms tend to increase in severity with the time people spend in the building; often improving over time or even disappearing when people are away from the building. SBS is also used interchangeably with "building-related symptoms", which orients the name of the condition around patients symptoms rather than a "sick" building. A 1984 World Health Organization (WHO) report suggested up to 30% of new and remodeled buildings worldwide may be subject of complaints related to poor indoor air quality.
Other causes have been attributed to contaminants produced by outgassing of some types of building materials, volatile organic compounds (VOC), improper exhaust ventilation of ozone (byproduct of some office machinery), light industrial chemicals used within, or lack of adequate fresh-air intake/air filtration (see minimum efficiency reporting value).The main identifying observation is an increased incidence of complaints of symptoms such as headache, eye, nose, and throat irritation, fatigue, and dizziness and nausea. In fact the 1989 Oxford English Dictionary defines SBS in that way. The World Health Organization created a 484-page tome on indoor air quality back in 1984 when SBS was attributed only to non-organic causes, and suggested that the book might form a basis for legislation or litigation.Case studies can contribute to a better understanding and management of sick building syndrome. Sick building causes are frequently pinned down to flaws in the heating, ventilation, and air conditioning (HVAC) systems. However, there have been inconsistent findings on whether air conditioning systems result in SBS or not.More recently, sick building was confirmed as a vector for the transmission of SARS in 2003. Norovirus has also been linked with buildings because of "the small inoculum required to produce infection (<100 viral particles), prolonged viral shedding, and its ability to survive in the environment." Many norovirus outbreaks have been traced back to cruise ships with food service in unsanitary conditions, or filthy personal hygiene around the toilet.
Signs and symptoms
Human exposure to aerosols has been documented to give rise to a variety of adverse health effects. Building occupants complain of symptoms such as sensory irritation of the eyes, nose, or throat; neurotoxic or general health problems; skin irritation; nonspecific hypersensitivity reactions; infectious diseases; and odor and taste sensations. Exposure to poor lighting conditions has led to general malaise.Extrinsic allergic alveolitis has been associated with the presence of fungi and bacteria in the moist air of residential houses and commercial offices. A study in 2017 correlated several inflammatory diseases of the respiration tract with objective evidence of damp-caused damage in homes.The WHO has classified the reported symptoms into broad categories, including: mucous membrane irritation (eye, nose, and throat irritation), neurotoxic effects (headaches, fatigue, and irritability), asthma and asthma-like symptoms (chest tightness and wheezing), skin dryness and irritation, gastrointestinal complaints and more.Several sick occupants may report individual symptoms which do not appear to be connected. The key to discovery is the increased incidence of illnesses in general with onset or exacerbation within a fairly close time frame – usually within a period of weeks. In most cases, SBS symptoms will be relieved soon after the occupants leave the particular room or zone. However, there can be lingering effects of various neurotoxins, which may not clear up when the occupant leaves the building. In some cases – particularly in sensitive individuals – there can be long-term health effects.
Cause
ASHRAE has recognized that polluted urban air, designated within the United States Environmental Protection Agency (EPA)s air quality ratings as unacceptable, requires the installation of treatment such as filtration for which the HVAC practitioners generally apply carbon-impregnated filters and their likes. Different toxins will aggravate the human body in different ways. Some people are more allergic to mold, while others are highly sensitive to dust. Inadequate ventilation will exaggerate small problems (such as deteriorating fiberglass insulation or cooking fumes) into a much more serious indoor air quality problem. Common products such as paint, insulation, rigid foam, Particle Board, plywood, duct liners, exhaust fumes and other chemical contaminants from indoor or outdoor sources, and biological contaminants can be trapped inside by the HVAC AC system. As this air is recycled using fan coils the overall oxygenation ratio drops and becomes harmful. When combined with other stress factors such as traffic noise, poor lighting, inhabitants of buildings located in a polluted urban area can quickly become ill as their immune system is overwhelmed. Certain VOCs, considered toxic chemical contaminants to humans, are used as adhesives in all common building construction products. These aromatic carbon rings / VOCs can cause acute and chronic health effects on the occupants of a building, including cancer, paralysis, lung failure, and others. Bacterial spores, fungal spores, mold spores, pollen, and viruses are types of biological contaminants and can all cause allergic reactions or illness described as SBS. In addition, pollution from outdoors, such as motor vehicle exhaust, can infiltrate into poorly designed buildings and contribute to poor indoor air quality, high ppm of CO and CO2. Adult SBS symptoms were associated with a history of allergic rhinitis, eczema and asthma.A 2015 study concerning the association of SBS and indoor air pollutants in office buildings in Iran found that, as carbon dioxide levels increase in a building, symptoms like nausea, headaches, nasal irritation, dyspnea, and throat dryness have also been shown to increase. Certain work conditions have been found to be correlated with specific symptoms. For example, higher light intensity was significantly related to skin dryness, eye pain, and malaise. Higher temperature has also been found to correlate with symptoms such as sneezing, skin redness, itchy eyes and headache, while lower relative humidity has been associated with sneezing, skin redness, and pain of the eyes.In 1973, in response to the oil crisis and conservation concerns, ASHRAE Standards 62-73 and 62-81 reduced required ventilation from 10 cubic feet per minute (4.7 L/s) per person to 5 cubic feet per minute (2.4 L/s) per person, but this was found to be a contributing factor to sick building syndrome. As of the 2016 revision, ASHRAE ventilation standards call for 5 to 10 cubic feet per minute of ventilation per occupant (depending on the occupancy type) in addition to ventilation based on the zone floor area delivered to the breathing zone.
Psychological factors
One study looked at commercial buildings and their employees, comparing some environmental factors suspected of inducing SBS to a self-reported survey of the occupants, finding that the measured psycho-social circumstances appeared more influential than the tested environmental factors. The authors of that study pointed to the self-reported nature of the observations as a limitation of the research.Research has shown that SBS shares several symptoms common in other conditions thought to be at least partially caused by psychosomatic tendencies. The umbrella term "autoimmune/inflammatory syndrome induced by adjuvants" has been suggested. Other members of the suggested group include silicosis, macrophagic myofascitis, Gulf War syndrome, and post-vaccination phenomena.
Workplace
Greater effects were found with features of the psycho-social work environment including high job demands and low support. The report concluded that the physical environment of office buildings appears to be less important than features of the psycho-social work environment in explaining differences in the prevalence of symptoms. However, there is still a relationship between sick building syndrome and symptoms of workers regardless of workplace stress.Excessive work stress or dissatisfaction, poor interpersonal relationships and poor communication are often seen to be associated with SBS, recent studies show that a combination of environmental sensitivity and stress can greatly contribute to sick building syndrome.Specific work-related stressors are related with specific SBS symptoms. Workload and work conflict are significantly associated with general symptoms (headache, abnormal tiredness, sensation of cold or nausea). While crowded workspaces and low work satisfaction are associated with upper respiratory symptoms. Work productivity has been associated with ventilation rates, a contributing factor to SBS, and theres a significant increase in production as ventilation rates increase, by 1.7% for every two-fold increase of ventilation rate. Printer effluent, released into the office air as ultra-fine particles (UFPs) as toner is burned during the printing process, may lead to certain SBS symptoms. Printer effluent may contain a variety of toxins to which a subset of office workers are sensitive, triggering SBS symptoms.Specific careers are also associated with specific SBS symptoms. Transport, communication, healthcare, and social workers have highest prevalence of general symptoms. Skin symptoms such as eczema, itching, and rashes on hands and face are associated with technical work. Forestry, agriculture, and sales workers have the lowest rates of sick building syndrome symptoms.From the assessment done by Fisk and Mudarri, 21% of asthma cases in the United States were caused by wet environments with mold that exist in all indoor environments, such as schools, office buildings, houses and apartments. Also found the exposure to the mold increases the chances of respiratory issues by 30 to 50 percent. Additionally, studies showing that health effects with dampness and mold in indoor environments found that increased risk of adverse health effects occurs with dampness or visible mold environments.Milton et al. determined the cost of sick leave specific for one business was an estimated $480 per employee, and about five days of sick leave per year could be attributed to low ventilation rates. When comparing low ventilation rate areas of the building to higher ventilation rate areas, the relative risk of short-term sick leave was 1.53 times greater in the low ventilation areas.
Home
Sick building syndrome can also occur due to factors of the home. Laminate flooring can cause more exposure to chemicals and more resulting SBS symptoms compared to stone, tile, and cement flooring. Recent redecorating and new furnishings within the last year were also found to be associated with increased symptoms, along with dampness and related factors, having pets, and the presence of cockroaches. The presence of mosquitoes was also a factor related to more symptoms, though it is unclear whether it was due to the presence of mosquitoes or the use of repellents.
Mold
Some studies have found that Sick building syndrome may be associated with indoor mould or mycotoxin contamination. However, the attribution of sick building syndrome to mould is controversial and supported by little evidence.
Reducing the dampness in all indoor environment will prevent all the respiratory issues caused by dampness and mold in indoor environment.
Indoor temperature
Indoor temperature under 18 °C (64 °F) has been shown to be associated with increased respiratory and cardiovascular diseases, increased blood levels, and increased hospitalization.
Diagnosis
While sick building syndrome (SBS) encompasses a multitude of non-specific symptoms, building-related illness (BRI) comprises specific, diagnosable symptoms caused by certain agents (chemicals, bacteria, fungi, etc.). These can typically be identified, measured, and quantified. There are usually 4 causal agents in BRI; 1.) Immunologic, 2.) Infectious, 3.) toxic, and 4.) irritant. For instance, Legionnaires disease, usually caused by Legionella pneumophila, involves a specific organism which could be ascertained through clinical findings as the source of contamination within a building.
Prevention
Regular inspections to indicate for presence of mold or other toxins
Adequate maintenance of all building mechanical systems
Toxin-absorbing plants, such as sansevieria
Roof shingle non-pressure cleaning for removal of algae, mold, and Gloeocapsa magma
Using ozone to eliminate the many sources, such as VOCs, molds, mildews, bacteria, viruses, and even odors. However, numerous studies identify high-ozone shock treatment as ineffective despite commercial popularity and popular belief.
Replacement of water-stained ceiling tiles and carpeting
Only using paints, adhesives, solvents, and pesticides in well-ventilated areas or only using these pollutant sources during periods of non-occupancy
Increasing the number of air exchanges; the American Society of Heating, Refrigeration and Air-Conditioning Engineers recommend a minimum of 8.4 air exchanges per 24-hour period
Increased ventilation rates that are above the minimum guidelines
Proper and frequent maintenance of HVAC systems
UV-C light in the HVAC plenum
Installation of HVAC air cleaning systems or devices to remove VOCs and bioeffluents (people odors)
Central vacuums that completely remove all particles from the house including the ultrafine particles (UFPs) which are less than 0.1 μm
Regular vacuuming with a HEPA filter vacuum cleaner to collect and retain 99.97% of particles down to and including 0.3 micrometers
Placing bedding in sunshine, which is related to a study done in a high-humidity area where damp bedding was common and associated with SBS
Lighting in the workplace should be designed to give individuals control, and be natural when possible
Relocating office printers outside the air conditioning boundary, perhaps to another building
Replacing current office printers with lower emission rate printers
Identification and removal of products containing harmful ingredients
Management
SBS, as a non specific blanket term, does not have any specific cause or cure. Any known cure would be associated with the specific eventual disease that was cause by exposure to known contaminants. In all cases, alleviation consists of removing the affected person from the building associated. BRI, on the other hand, utilizes treatment appropriate for the contaminant identified within the building (e.g., antibiotics for Legionnaires disease).In most cases, simply improving the indoor air quality (IAQ) of a particular building will attenuate, or even eliminate, the continued exposure to toxins. For the individual, the recovery may be a process involved with targeting the acute symptoms of a specific illness, as in the case of mold toxins. Treating various building-related illnesses is vital to the overall understanding of SBS. Careful analysis by certified building professionals and Medical Doctors can help to identify the exact cause of the BRI, and help to illustrate a causal path to infection. With this knowledge one can, theoretically, remediate a building of contaminants and rebuild the structure with new materials. Office BRI may more likely than not be explained by three events: "Wide range in the threshold of response in any population (susceptibility), a spectrum of response to any given agent, or variability in exposure within large office buildings." Isolating any one of the three aspects of office BRI can be a great challenge, which is why those who find themselves with BRI should take three steps, history, examinations, and interventions. History describes the action of continually monitoring and recording the health of workers experiencing BRI, as well as obtaining records of previous building alterations or related activity. Examinations go hand in hand with monitoring employee health. This step is done by physically examining the entire workspace and evaluating possible threats to health status among employees. Interventions follow accordingly based on the results of the Examination and History report.
Epidemiology
Some studies have found that women have higher reports of SBS symptoms than men. It is not entirely clear, however, if this is due to biological, social, or occupational factors.
A 2001 study published in the Journal Indoor Air, gathered 1464 office-working participants to increase the scientific understanding of gender differences under the Sick Building Syndrome phenomenon. Using questionnaires, ergonomic investigations, building evaluations, as well as physical, biological, and chemical variables, the investigators obtained results that compare with past studies of SBS and gender. The study team found that across most test variables, prevalence rates were different in most areas, but there was also a deep stratification of working conditions between genders as well. For example, mens workplaces tend to be significantly larger and have all-around better job characteristics. Secondly, there was a noticeable difference in reporting rates, specifically that women have higher rates of reporting roughly 20% higher than men. This information was similar to that found in previous studies, thus indicating a potential difference in willingness to report.There might be a gender difference in reporting rates of sick building syndrome, because women tend to report more symptoms than men do. Along with this, some studies have found that women have a more responsive immune system and are more prone to mucosal dryness and facial erythema. Also, women are alleged by some to be more exposed to indoor environmental factors because they have a greater tendency to have clerical jobs, wherein they are exposed to unique office equipment and materials (example: blueprint machines, toner-based printers), whereas men often have jobs based outside of offices.
History
In the late 1970s, it was noted that nonspecific symptoms were reported by tenants in newly constructed homes, offices, and nurseries. In media it was called "office illness". The term "sick building syndrome" was coined by the WHO in 1986, when they also estimated that 10–30% of newly built office buildings in the West had indoor air problems. Early Danish and British studies reported symptoms.
Poor indoor environments attracted attention. The Swedish allergy study (SOU 1989:76) designated "sick building" as a cause of the allergy epidemic as was feared. In the 1990s, therefore, extensive research into "sick building" was carried out. Various physical and chemical factors in the buildings were examined on a broad front.
The problem was highlighted increasingly in media and was described as a "ticking time bomb". Many studies were performed in individual buildings.
In the 1990s "sick buildings" were contrasted against "healthy buildings". The chemical contents of building materials were highlighted. Many building material manufacturers were actively working to gain control of the chemical content and to replace criticized additives. The ventilation industry advocated above all more well-functioning ventilation. Others perceived ecological construction, natural materials, and simple techniques as a solution.
At the end of the 1990s came an increased distrust of the concept of "sick building". A dissertation at the Karolinska Institutet in Stockholm 1999 questioned the methodology of previous research, and a Danish study from 2005 showed these flaws experimentally. It was suggested that sick building syndrome was not really a coherent syndrome and was not a disease to be individually diagnosed, but a collection of as many as to dozen semi related diseases. In 2006 the Swedish National Board of Health and Welfare recommended in the medical journal Läkartidningen that "sick building syndrome" should not be used as a clinical diagnosis. Thereafter, it has become increasingly less common to use terms such as "sick buildings" and "sick building syndrome" in research. However, the concept remains alive in popular culture and is used to designate the set of symptoms related to poor home or work environment engineering. "Sick building" is therefore an expression used especially in the context of workplace health.
Sick building syndrome made a rapid journey from media to courtroom where professional engineers and architects became named defendants and were represented by their respective professional practice insurers. Proceedings invariably relied on expert witnesses, medical and technical experts along with building managers, contractors and manufacturers of finishes and furnishings, testifying as to cause and effect. Most of these actions resulted in sealed settlement agreements, none of these being dramatic. The insurers needed a defense based upon Standards of Professional Practice to meet a court decision that declared that in a modern, essentially sealed building, the HVAC systems must produce breathing air for suitable human consumption. ASHRAE (American Society of Heating, Refrigeration and Air Conditioning Engineers, currently with over 50,000 international members) undertook the task of codifying its indoor air quality (IAQ) standard.
ASHRAE empirical research determined that "acceptability" was a function of outdoor (fresh air) ventilation rate and used carbon dioxide as an accurate measurement of occupant presence and activity. Building odors and contaminants would be suitably controlled by this dilution methodology. ASHRAE codified a level of 1,000 ppm of carbon dioxide and specified the use of widely available sense-and-control equipment to assure compliance. The 1989 issue of ASHRAE 62.1-1989 published the whys and wherefores and overrode the 1981 requirements that were aimed at a ventilation level of 5,000 ppm of carbon dioxide, (the OAHA workplace limit), federally set to minimize HVAC system energy consumption. This apparently ended the SBS epidemic.
Over time, building materials changed with respect to emissions potential. Smoking vanished and dramatic improvements in ambient air quality, coupled with code compliant ventilation and maintenance, per ASHRAE standards have all contributed to the acceptability of the indoor air environment.
See also
Aerotoxic syndrome
Havana syndrome
Healthy building
Multiple chemical sensitivity
NASA Clean Air Study
Nosocomial infection
Somatization disorder
Fan death
References
Further reading
Martín-Gil J., Yanguas M. C., San José J. F., Rey-Martínez and Martín-Gil F. J. "Outcomes of research into a sick hospital". Hospital Management International, 1997, pp. 80–82. Sterling Publications Limited.
Åke Thörn, The Emergence and preservation of sick building syndrome, KI 1999.
Charlotte Brauer, The sick building syndrome revisited, Copenhagen 2005.
Michelle Murphy, Sick Building Syndrome and the Problem of Uncertainty, 2006.
Johan Carlson, "Gemensam förklaringsmodell för sjukdomar kopplade till inomhusmiljön finns inte" [Unified explanation for diseases related to indoor environment not found]. Läkartidningen 2006/12.
Research Committee Report on Diagnosis and Treatment of Chronic Inflammatory Response Syndrome Caused by Exposure to the Interior Environment of Water-Damaged Buildings (PDF).
Bulletin of the Transilvania University of Braşov, Series I: Engineering Sciences • Vol. 5 (54) No. 1 2012 "Impact of Indoor Environment Quality on Sick Building Syndrome in Indian Leed Certified Buildings". by Jagannathan Mohan
== External links == |
Dysexecutive syndrome | Dysexecutive syndrome (DES) consists of a group of symptoms, usually resulting from brain damage, that fall into cognitive, behavioural and emotional categories and tend to occur together. The term was introduced by Alan Baddeley to describe a common pattern of dysfunction in executive functions, such as planning, abstract thinking, flexibility and behavioural control. It is thought to be Baddeleys hypothesized working memory system and the central executive that are the hypothetical systems impaired in DES. The syndrome was once known as frontal lobe syndrome; however dysexecutive syndrome is preferred because it emphasizes the functional pattern of deficits (the symptoms) over the location of the syndrome in the frontal lobe, which is often not the only area affected.
Classification code in ICD-10 - F07
Symptoms and signs
Symptoms of DES fall into three broad categories: cognitive, emotional and behavioural. Many of the symptoms can be seen as a direct result of impairment to the central executive component of working memory, which is responsible for attentional control and inhibition. Although many of the symptoms regularly co-occur, it is common to encounter patients who have several, but not all symptoms. The accumulated effects of the symptoms have a large impact on daily life.
Cognitive symptoms
Cognitive symptoms refer to a persons ability to process thoughts. Cognition primarily refers to memory, the ability to learn new information, speech, and reading comprehension. Deficits within this area cause many problems with everyday life decisions.One of the main difficulties for an individual with DES is planning and reasoning. Impaired planning and reasoning affect the individuals ability to realistically assess and manage the problems of everyday living. New problems and situations may be especially poorly handled because of the inability to transfer previous knowledge to the new event. An individual that has DES may have a short attention span due to impairment in attentional control. This may alter the individuals ability to focus, and as such have difficulty with reading and following a storyline or conversation. For instance, they can easily lose track of conversations which can make it difficult to hold a meaningful conversation and may result in avoiding social interactions.Individuals with DES will have very poor working memory and short term memory due to executive dysfunction. The dysfunction can range from mild and subtle to severe and obvious. There is a tremendous variability in the manifestations of executive dysfunction with strong influences often apparent from the affected persons personality, life experiences and intellect. Individuals with DES may experience confabulation, which is the spontaneous reporting of events that never happened. This can affect their autobiographical memory. It is thought that patients may not be able to assess the accuracy of memory retrieval and therefore elaborate on implausible memories.Individuals with dementia, delirium or other severe psychiatric illnesses combined with DES often have disturbed sleep patterns. Some will not recognize that it is night-time and may become upset when someone tries to correct them.
Emotional symptoms
The emotional symptoms that individuals with DES experience may be quite extreme and can cause extensive problems. They may have difficulty inhibiting many types of emotions such as anger, excitement, sadness, or frustration. Due to multiple impairments of cognitive functioning, there can be much more frustration when expressing certain feelings and understanding how to interpret everyday situations. Individuals with DES may have higher levels of aggression or anger because they lack abilities that are related to behavioural control. They can also have difficulty understanding others points of view, which can lead to anger and frustration.
Behavioural symptoms
Behavioural symptoms are evident through an individuals actions. People with DES often lose their social skills because their judgments and insights into what others may be thinking are impaired. They may have trouble knowing how to behave in group situations and may not know how to follow social norms. The central executive helps control impulses; therefore when impaired, patients have poor impulse control. This can lead to higher levels of aggression and anger. DES can also cause patients to appear self-centered and stubbornUtilization behaviour is when a patient automatically uses an object in the appropriate manner, but at an inappropriate time. For example, if a pen and paper are placed in front of an individual with DES they will start to write or if there is a deck of cards they will deal them out. Patients showing this symptom will begin the behaviour in the middle of conversations or during auditory tests. Utilization behaviour is thought to occur because an action is initiated when an object is seen, but patients with DES lack the central executive control to inhibit acting it out at inappropriate times.Perseveration is also often seen in patients with DES. Perseveration is the repetition of thoughts, behaviours, or actions after they have already been completed. For instance, continually blowing out a match, after it is no longer lit is an example of perseveration behaviour. There are three types of perseveration: continuous perseveration, stuck-in-set perseveration, and recurrent perseveration. Stuck-in-set perseveration is most often seen in dysexecutive syndrome. This type of perseveration refers to when a patient cannot get out of a specific frame of mind, such as when asked to name animals they can only name one. If you ask them to then name colours, they may still give you animals. Perseveration may explain why some patients appear to have obsessive-compulsive disorder.
Comorbid disorders
DES often occurs with other disorders, which is known as comorbidity. Many studies have examined the presence of DES in patients with schizophrenia. Results of schizophrenic patients on the Behavioural Assessment of the Dysexecutive Syndrome (BADS) test (discussed below) are comparable to brain injured patients. Further, results of BADS have been shown to correlate with phases of schizophrenia. Patients in the chronic phase of the disorder have significantly lower scores than those who are acute. This is logical due to the similarities in executive disruptions that make everyday life difficult for those with schizophrenia and symptoms that form DES.
Patients with Alzheimers disease and other forms of dementia have been shown to exhibit impairment in executive functioning as well. The effects of DES symptoms on the executive functions and working memory, such as attentiveness, planning and remembering recently learned things, are some of the earliest indicators of Alzheimers disease and dementia with Lewy bodies.
Studies have also indicated that chronic alcoholism (see Korsakoffs syndrome) can lead to a mild form of DES according to results of BADS.
Causes
The most frequent cause of the syndrome is brain damage to the frontal lobe. Brain damage leading to the dysexecutive pattern of symptoms can result from physical trauma such as a blow to the head or a stroke or other internal trauma.
It is important to note that frontal lobe damage is not the only cause of the syndrome. It has been shown that damage, such as lesions, in other areas of the brain may indirectly affect executive functions and lead to similar symptoms (such as ventral tegmental area, basal ganglia and thalamus). There is not one specific pattern of damage that leads to DES, as multiple affected brain structures and locations have led to the symptoms. This is one reason why the term frontal lobe syndrome is not preferred.
Diagnosis
Assessment of patients with DES can be difficult because traditional tests generally focus on one specific problem for a short period of time. People with DES can do fairly well on these tests because their problems are related to integrating individual skills into everyday tasks. The lack of everyday application of traditional tests is known as low ecological validity.
Behavioural
The Behavioural Assessment of the Dysexecutive Syndrome (BADS) was designed to address the problems of traditional tests and evaluate the everyday problems arising from DES. BADS is designed around six subtests and ends with the Dysexecutive Questionnaire (DEX). These tests assess executive functioning in more complex, real-life situations, which improves their ability to predict day-to-day difficulties of DES.
The six tests are as follows:Rule Shift Cards - Assesses the subjects ability to ignore a prior rule after being given a new rule to follow.
Action Program - This test requires the use of problem solving to accomplish a new, practical task.
Key Search - This test reflects the real-life situation of needing to find something that has been lost. It assesses the patients ability to plan how to accomplish the task and monitor their own progress.
Temporal Judgment - Patients are asked to make estimated guesses to a series of questions such as, "how fast do racehorses gallop?". It tests the ability to make sensible guesses.
Zoo Map - Tests the ability to plan while following a set of rules.
Modified Six Elements - This test assesses the subjects ability to plan, organize and monitor behaviour.The Dysexecutive Questionnaire (DEX) is a 20-item questionnaire designed to sample emotional, motivational, behavioural and cognitive changes in a subject with DES. One version is designed for the subject to complete and another version is designed for someone who is close to the individual, such as a relative or caregiver. Instructions are given to the participant to read 20 statements describing common problems of everyday life and to rate them according to their personal experience. Each item is scored on a 5-point scale according to its frequency from never (0 point) to very often (4 points).
Treatment
There is no cure for individuals with DES, but there are therapies to help them cope with their symptoms. DES can affect a number of functions in the brain and vary from person to person. Because of this variance, it is suggested that the most successful therapy would include multiple methods. Researchers suggest that a number of factors in the executive functioning need to be improved, including self-awareness, goal setting, planning, self-initiation, self-monitoring, self-inhibition, flexibility, and strategic behaviour.
One method for individuals to improve in these areas is to help them plan and carry out actions and intentions through a series of goals and sub-goals. To accomplish this, therapists teach patients a three-step model called the General Planning Approach. The first step is Information and Awareness, in which the patients are taught about their own problems and shown how this affects their lives. The patients are then taught to monitor their executive functions and begin to evaluate them. The second stage, Goal Setting and Planning, consists of patients making specific goals, as well as devising a plan to accomplish them. For example, patients may decide they will have lunch with a friend (their goal). They are taught to write down which friend it may be, where they are going for lunch, what time they are going, how they will get there, etc. (sub-goals). They are also taught to make sure the steps go in the correct order. The final stage, named Initiation, Execution, and Regulation, requires patients to implement their goals in their everyday lives. Initiation can be taught through normal routines. The first step can cue the patient to go to the next step in their plan. Execution and regulation are put into action with reminders of how to proceed if something goes wrong in the behavioural script. This treatment method has resulted in improved daily executive functioning, however no improvements were seen on formal executive functioning tests.
Since planning is needed in many activities, different techniques have been used to improve this deficit in patients with DES. Autobiographical memories can be used to help direct future behaviour. You can draw on past experiences to know what to do in the future. For example, when you want to take a bus, you know from past experience that you have to walk to the bus stop, have the exact amount of change, put the change in the slot, and then you can go find a seat. Patients with DES seem to not be able to use this autobiographical memory as well as a normal person. Training for DES patients asks them to think of a specific time when they did an activity previously. They are then instructed to think about how they accomplished this activity. An example includes "how would you plan a holiday". Patients are taught to think of specific times they went on a holiday and then to think how they may have planned these holidays. By drawing on past experiences patients were better able to make good decisions and plans.
Cognitive Analytic Therapy (CAT) has also been used to help those with DES. Because individuals with this syndrome have trouble integrating information into their actions it is often suggested that they have programmed reminders delivered to a cell phone or pager. This helps them remember how they should behave and discontinue inappropriate actions. Another method of reminding is to have patients write a letter to themselves. They can then read the letter whenever they need to. To help patients remember how to behave, they may also create a diagram. The diagram helps organize their thoughts and shows the patient how they can change their behaviour in everyday situations.The use of auditory stimuli has been examined in the treatment of DES. The presentation of auditory stimuli causes an interruption in current activity, which appears to aid in preventing "goal neglect" by increasing the patients ability to monitor time and focus on goals. Given such stimuli, subjects no longer performed below their age group average IQ.
Controversy
Some researchers have suggested that DES is mislabelled as a syndrome because it is possible for the symptoms to exist on their own. Also, there is not a distinct pattern of damage that leads to the syndrome. Not all patients with frontal lobe damage have DES and some patients with no damage at all to the frontal lobe exhibit the necessary pattern of symptoms. This has led research to investigate the possibility that executive functioning is broken down into multiple processes that are spread throughout the frontal lobe. Further disagreement comes from the syndrome being based on Baddeley and Hitchs model of working memory and the central executive, which is a hypothetical construct.The vagueness of some aspects of the syndrome has led researchers to test for it in a non-clinical sample. The results show that some dysexecutive behaviours are part of everyday life, and the symptoms exist to varying degrees in everyone. For example, absent-mindedness and lapses in attention are common everyday occurrences for most people. However, for the majority of the population such inattentiveness is manageable, whereas patients with DES experience it to such a degree that daily tasks become difficult.
See also
ADHD
Schizophrenia
== References == |
Nasolacrimal duct obstruction | Nasolacrimal duct obstruction is the obstruction of the nasolacrimal duct and may be either congenital or acquired. Obstruction of the nasolacrimal duct leads to the excess overflow of tears called epiphora.
Sign and symptoms
Excessive tearing is the most common complaint of patients with nasolacrimal duct obstruction, followed by acute or chronic infections. Pain at the side of the nose suggests dacryocystitis.
Nasolacrimal duct obstruction is more common with increasing age and more common in females than males.
Cause
Involutional stenosis
Involutional stenosis is probably the most common cause of nasolacrimal duct obstruction in older people. It affects women twice as frequently as men. Although the inciting event in this process is unknown, clinicopathologic study suggests that compression of the lumen of the nasolacrimal duct is caused by inflammatory infiltrates and edema. This may be the result of an unidentified infection or possibly an autoimmune disease.
Dacryolith
Dacryoliths or cast formation, within the lacrimal sac can also produce obstruction of the nasolacrimal duct.
Sinus disease
Sinus disease often occurs in conjunction with, and in other instances may contribute to the development of nasolacrimal duct obstruction. Patients should be asked about previous sinus surgery, as the nasolacrimal duct is sometimes damaged when the maxillary sinus ostium is being enlarged anteriorly.
Trauma
Naso-orbital fractures may involve the nasolacrimal duct. Early treatment by fracture reduction with stenting of the entire lacrimal drainage system should be considered. However, such injuries are often not recognized or are initially neglected as more serious injuries are managed. In such cases, late treatment of persistent epiphora usually requires dacryocystorhinostomy.
Inflammatory disease
Granulomatous disease, including sarcoidosis, granulomatosis with polyangiitis, and midline granuloma, may also lead to nasolacrimal duct obstruction.
Lacrimal plugs
As with similar cases of canalicular obstruction, dislodged punctual and canalicular plugs can migrate to and occlude the nasolacrimal duct.
Neoplasm
Neoplasm should be considered in any patient presenting with nasolacrimal duct obstruction. In patients with atypical presentations, including younger age and male gender, further workup is appropriate. Bloody punctual discharge or lacrimal sac distension above the medial canthal tendon is also highly suggestive of neoplasm.
Congenital
Congenital nasolacrimal duct obstruction, or dacryostenosis, occurs when the lacrimal duct has failed to open at the time of birth, most often due to an imperforate membrane at the valve of Hasner. Around 6% of infants have congenital nasolacrimal duct obstruction, or dacryostenosis, usually experiencing a persistent watery eye even when not crying. If a secondary infection occurs (Dacryocystitis), purulent (yellow / green) discharge may be present.
Most cases resolve spontaneously, with antibiotics reserved only if conjunctivitis occurs. Lacrimal sac massage has been proposed as helping to open the duct, though this is not always successful. The aim of massage is to generate enough hydrostatic pressure (downward, toward the nose) to "pop" open any obstruction. Additional massage may then be performed up toward the lacrimal punctum, in order to express any infectious material out of the nasolacrimal sac. When discharge or crusting is present, the lids should be gently cleaned using cooled pre-boiled water or saline.
Referral to an ophthalmologist is indicated if symptoms are still present at 12 months, or sooner if significant symptoms or recurrent infections occur. Nasolacrimal duct probing may be performed in the office setting (usually from 4 to 8 months of age) or under general anesthesia in an operating room for older patients. The success rate of probing is higher for younger children. A silastic tube or stent may be employed along with probing to maintain tear duct patency. A systematic review comparing immediate probing with deferred probing found that in children with unilateral nasolacrimal duct obstruction, immediate probing resulted in a higher success rate of treatment compared to deferred probing.
Diagnosis
Evaluation is in the form of a dye disappearance test followed by irrigation test. By using this sequence (with modifications) as a guide, the physician can frequently streamline diagnostic testing.
Dye disappearance test
The dye disappearance test is useful for assessing the presence or absence of adequate lacrimal outflow, especially in unilateral cases. It is more heavily relied upon in children, in whom lacrimal irrigation is impossible without deep sedation. Using a drop of sterile 2% fluorescein solution or a moistened fluorescein strip, the examiner instills fluorescein into the conjunctival fornices of each eye and then observes the tear film, preferably with the cobalt blue filter of the slit lamp. Persistence of significant dye and, particularly asymmetric clearance of the dye from the tear meniscus over a 5-minute period indicate an obstruction. If the dye disappearance test result is normal, severe lacrimal drainage dysfunction is highly unlikely. The Jones tests are variations of the dye disappearance test.
Irrigation test
In irrigation test, a lacrimal irrigation cannula is passed into the punctum and advanced through the canaliculus to the lacrimal fossa. Clear water or saline is then irrigated through the cannula. If fluid passes into the nose without reflux out of the opposite canaliculus, the system is patent. If no fluid passes but it all comes back through either punctum, nasolacrimal duct obstruction is present.
Management
Intubation and stenting
Some clinicians believe that partial stenosis of the nasolacrimal duct with symptomatic epiphora sometimes responds to surgical intubation of the entire lacrimal drainage system. This procedure should be performed only if the tubes can be passed easily. In complete nasolacrimal duct obstruction, intubation alone is not effective, and a dacryocystorhinostomy should be considered.
Dacryocystorhinostomy
A dacryocystorhinostomy is the treatment of choice for most patients with acquired nasolacrimal duct obstruction. Surgical indications include recurrent dacryocystitis, chronic mucoid reflux, painful distension of the lacrimal sac, and bothersome epiphora. For patients with dacryocystitis, active infection should be cleared, if possible, before a dacryocystorhinostomy is performed.
See also
Nasolacrimal duct
Lacrimal apparatus
Imperforate lacrimal punctum
References
== External links == |
Bronchocele | A bronchocele is a segment of bronchus that is filled with mucus and completely enclosed so the mucus cannot drain out. This segment is usually dilated. It is also called bronchial mucocele. If there is no obstruction to the flow of mucus, it is called mucoid impaction of bronchus. A bronchocele results from obstruction of the bronchus. Overproduction of mucus can also contribute. Obstruction may occur due to scarring, a tumor, or congenital atresia. |
Hypertrophic osteoarthropathy | Hypertrophic osteoarthropathy is a medical condition combining clubbing and periostitis of the small hand joints, especially the distal interphalangeal joints and the metacarpophalangeal joints. Distal expansion of the long bones as well as painful, swollen joints and synovial villous proliferation are often seen. The condition may occur alone (primary), or it may be secondary to diseases like lung cancer. Among patients with lung cancer, it is most associated with adenocarcinoma and least associated with small cell lung cancer. These patients often get clubbing and increased bone deposition on long bones. Their presenting signs and symptoms are sometimes only clubbing and painful ankles.
Cause
Hypertrophic osteoarthropathy is one of many distant effect disorders due to cancer, with lung cancer being the most common cause but also occurring with ovarian or adrenal malignancies. A distant effect disorder, or a paraneoplastic syndrome, affects distant areas and thus is not related to local compression or obstruction effects from the tumor. Other paraneoplastic syndromes include hypercalcemia, SIADH, Cushings syndrome and a variety of neurological disorders.
Thought to be due to fibrovascular proliferation caused by accumulation of megakaryocytes in the digital vessels which are normally filtered by the lungs.
Diagnosis
People with hypertrophic osteoarthropathy may have bone scans showing parallel lines of activity along the cortex of the shafts and ends of tibiae, femurs and radii; especially around the knees, ankles and wrists. This activity may decrease after treatment of the underlying cause.
Treatment
Non-steroidal anti-inflammatory drugs (NSAIDs) can give significant relief of the symptoms. Treatment of lung cancer or other causes of hypertrophic osteoarthropathy results in regression of symptoms for some patients.
Etymology
The eponymous Bamberger–Marie syndrome is named for Austrian internist Eugen von Bamberger and French neurologist Pierre Marie.
See also
Periosteal reaction
Hypertrophic osteopathy
References
== External links == |
Epidermal nevus syndrome | Epidermal nevus syndrome (also known as "Feuerstein and Mims syndrome", and "Solomons syndrome": 775 ) is a rare disease that was first described in 1968 and consists of extensive epidermal nevi with abnormalities of the central nervous system (CNS), skeleton, skin, cardiovascular system, genitourinary system and eyes.: 634 However, since the syndromes first description, a broader concept for the "epidermal nevus" syndrome has been proposed, with at least six types being described:: 776
Schimmelpenning syndrome
Nevus comedonicus syndrome
Pigmented hairy epidermal nevus syndrome
Proteus syndrome
CHILD syndrome
Phakomatosis pigmentokeratotica
See also
Epidermis
List of cutaneous conditions
References
== External links == |
Sacroiliac joint dysfunction | Sacroiliac joint dysfunction generally refers to pain in the sacroiliac joint region that is caused by abnormal motion in the sacroiliac joint, either too much motion or too little motion.
Signs and symptoms
Common symptoms include lower back pain, buttocks pain, sciatic leg pain, groin pain, hip pain (for explanation of leg, groin, and hip pain, see referred pain), urinary frequency, and "transient numbness, prickling, or tingling." Pain can range from dull aching to sharp and stabbing and increases with physical activity. Symptoms also worsen with prolonged or sustained positions (i.e., sitting, standing, lying). Bending forward, stair climbing, hill climbing, and rising from a seated position can also provoke pain. Pain can increase during menstruation in women. People with severe and disabling sacroiliac joint dysfunction can develop insomnia and depression. Sacral torsion that is untreated over a long period of time can cause severe Achilles tendinosis.
Causes
Hypermobility
Sacroiliac joint dysfunction is an outcome of either extra-articular dysfunction or from intraarticular dysfunction.
SI joint dysfunction is sometimes referred to as "sacroiliac joint instability" or "sacroiliac joint insufficiency" due to the support the once strong and taut ligaments can no longer sustain. When the joint is hypermobile or loose, it is classified as an extra-articular dysfunction because abnormal joint movement and alignment is a consequence of weakened, injured, or sprained ligaments, while the joint itself is structurally normal and healthy. The sacroiliac joint itself often will not show degenerative changes, such as arthritis, until many years of the dysfunction being allowed to continue. Injury to the ligaments that hold the sacroiliac joints in proper support is thought to be caused by a torsion or high impact injury (such as an automobile accident) or a hard fall, resulting in the hypermobility. As many as 58% of people diagnosed with sacroiliac joint pain had some inciting traumatic injury based on clinical examination findings. The joint that was once stabilized by strong ligaments, now overly stretched, sprained, or torn, will move beyond its normal range. This is thought to result in the ilium and sacral surfaces "locking" in an incongruent or asymmetrical fashion (one innominate bone is tilted anteriorly; the other innominate bone is tilted posteriorly) causing pain that can be debilitating.Hormone imbalances, particularly those associated with pregnancy and the hormone relaxin, can also cause a ligamentous laxity resulting in the weakening of the sacroiliac structure.
During pregnancy, relaxin serves as natures way of allowing the female pelvis to achieve distention of the birthing canal. Pelvic joint pain in post pregnancy women is thought to be derived from the inability of the stretched out ligaments to return to normal tautness. Women who have delivered large babies or who have had extended labors also are prone to developing chronic sacroiliac joint pain and instability.In some people, the sacroiliac joints reverse the normal concave-convex locking relationship, which can lead to rotational misalignment. The variation in joint configuration results in some sacroiliac joints being inherently weaker or more prone to misalignment.Certain biomechanical or muscle length imbalances may ultimately predispose a person to sacroiliac dysfunction and pain. Likely, this is a result of altered gait patterns and repetitive stress to the SI joint and related structures. These conditions exist in persons with leg-length inequality, scoliosis, a history of polio, poor-quality footwear, and hip osteoarthritis.There is also a notable incidence of lumbar spinal fusion patients that present with sacroiliac pain and hypermobility, potentially due to the adjacent lumbar joints being fixed and unable to move. Clinical studies have found up to 75% of post-lumbar fusion patients develop SI joint degeneration within five years of surgery.
Hypomobility
Pathological hypomobility (too little movement) of the sacroiliac joint is an intra-articular disorder in which the joint locks due to wearing down with age or degenerative joint disease.Hypomobility of this kind can also occur with an inflammatory disease such as ankylosing spondylitis, rheumatoid arthritis, or an infection.
Pathophysiology
The sacroiliac joint is a true diarthrodial joint that joins the sacrum to the pelvis. The sacrum connects on the right and left sides to the ilia (pelvic bones) to form the sacroiliac joints. The pelvic girdle is made up of two innominate bones (the iliac bones) and the sacrum. The innominate bones join in the front of the pelvis to form the pubic symphysis, and at back of the sacrum to form the sacroiliac (SI) joints. Each innominate bone (ilium) joins the femur (thigh bone) to form the hip joint; thus the sacroiliac joint moves with walking and movement of the torso.In this joint, hyaline cartilage on the sacral side moves against fibrocartilage on the iliac side. The sacroiliac joint contains numerous ridges and depressions that function in stability. Studies have documented that motion does occur at the joint; therefore, slightly subluxed and even locked positions can occur.Muscles and ligaments surround and attach to the SI joint in the front and back, primarily on the ilial or sacral surfaces. These can all be a source of pain and inflammation if the SI joint is dysfunctional. The sacroiliac joint is highly dependent on its strong ligamentous structure for support and stability. The most commonly disrupted and/or torn ligaments are the iliolumbar ligament and the posterior sacroiliac ligament. The ligamentous structures offer resistance to shear and loading. The deep anterior, posterior, and interosseous ligaments resist the load of the sacrum relative to the ilium. More superficial ligaments (e.g., the sacrotuberous ligament) react to dynamic motions (such as straight-leg raising during physical motion). The long dorsal sacroiliac ligament can become stretched in periods of increased lumbar lordosis (e.g., during pregnancy).
Affected muscle groups
Many large and small muscles have relationships with the ligaments of the sacroiliac joint including the piriformis (see "piriformis syndrome", a condition often related with sacroiliac joint dysfunction), rectus femoris, gluteus maximus and minimus, erector spinae, latissimus dorsi, thoracolumbar fascia, and iliacus. Any of these muscles can be involved or spasm with a painful and dysfunctional sacroiliac joint. The SI joint is a pain-sensitive structure richly innervated by a combination of unmyelinated free nerve endings and the posterior primary rami of spinal segments L2-S3. The wide possibility of innervation may explain why pain originating from the joint can manifest in so many various ways, with different and unique referral patterns (see "referred pain") for individual patients. Patients with sacroiliac joint dysfunction can also develop tightness and dysfunction in the hamstring, quadriceps, iliotibial tract (see "iliotibial band syndrome") and hip flexors, including the psoas muscle. Individuals with severe and long-standing sacroiliac joint dysfunction can develop muscle deconditioning and atrophy throughout the body due to limitation of activities and exercise that bring about pain in the low back.
Diagnosis
Perhaps the biggest reason for misdiagnosis or lack of diagnosis of sacroiliac joint dysfunction is based on the inability of common radiological imaging to discern the disorder. Diagnostic testing, such as X-ray, CT scan, or MRI, do not usually reveal abnormalities; therefore, they cannot reliably be used for diagnosis of sacroiliac joint dysfunction. There is a new imaging test SPECT/CT which can sometimes detect sacroiliac joint dysfunction. There is also a lack of evidence that sacroiliac joint mobility maneuvers (Gillet, Standing flexion test, and Seated Flexion test) detect motion abnormalities. Given the inherent technical limitations of the visible and palpable signs from these sacroiliac joint mobility maneuvers another broad category of clinical signs have been described called provocative maneuvers. These maneuvers are designed to reproduce or increase pain emanating within the sacroiliac joint.A clinician (i.e., a spine surgeon, orthopedic surgeon, sports medicine doctor, athletic trainer, medical massage therapist, physical therapist, physiatrist, osteopath or chiropractor) can develop a probable diagnosis of sacroiliac joint dysfunction by using a hands on approach through palpating the painful areas and performing the following provocative maneuvers below:
Gaenslen test - This pain provocation test applies torsion to the joint. With one hip flexed onto the abdomen, the other leg is allowed to dangle off the edge of the table. Pressure should then be directed downward on the leg in order to achieve hip extension and stress the sacroiliac joint.
Iliac Gapping Test - Distraction can be performed to the anterior sacroiliac ligaments by applying pressure to the anterior superior iliac spine.
Iliac Compression Test - Apply compression to the joint with the patient lying on his or her side. Pressure is applied downward to the uppermost iliac crest.
FABER or Patrick test - To identify if pain may come from the sacroiliac joint during flexion, abduction, and external rotation, the clinician externally rotates the hip while the patient lies supine. Then, downward pressure is applied to the medial knee stressing both the hip and sacroiliac joint.
Thigh Thrust - This test applies anteroposterior shear stress on the SI joint. The patient lies supine with one hip flexed to 90 degrees. The examiner stands on the same side as the flexed leg. The examiner provides either a quick thrust or steadily increasing pressure through the line of the femur. The pelvis is stabilized at the sacrum or at the opposite ASIS with the hand of the examinerCautious interpretation is warranted because there are no biomechanical studies showing that the Thigh Thrust test isolates forces in the SIJ when performed at 90 degrees and due to intra-individual variation in body type, hip flexibility, general flexibility of the trunk and pelvis.
In all the tests, pain along the typical area raises suspicion for sacroiliac joint dysfunction. However no single test is very reliable in the diagnosis of sacroiliac joint dysfunction. It is important to remember true neurogenic weakness, numbness, or loss of reflex should alert the clinician to consider nerve root pathology.The current "gold standard" for diagnosis of sacroiliac joint dysfunction emanating within the joint is sacroiliac joint injection confirmed under fluoroscopy or CT-guidance using a local anesthetic solution. The diagnosis is confirmed when the patient reports a significant change in relief from pain and the diagnostic injection is performed on 2 separate visits. Published studies have used at least a 75 percent change in relief of pain before a response is considered positive and the sacroiliac joint deemed the source of pain.
However, several other injection studies have compared intra-articular with extra-articular injection, and indicate that the ligament injection behind the joint is oftentimes superior to injection in the joint and seems to be a very underutilized diagnostic tool.
Misdiagnosis
In the early 1900s, dysfunction of the sacroiliac joint was a common diagnosis associated with low back and sciatic nerve pain. However, research by Danforth and Wilson in 1925 concluded that the sacroiliac joint could not cause sciatic nerve pain because the joint does not have a canal in which the nerves can be entrapped against the joint. The biomechanical relationship between the sacroiliac joint, the piriformis muscle (see "piriformis syndrome"), and the sciatic nerve had not yet been discovered.In 1934, the work of Mixter and Barr shifted all emphasis in research and treatment from the sacroiliac to the herniated intervertebral disc, namely lumbar discs. Medical focus on herniated discs was further forwarded by the invention of the MRI in 1977. Over-diagnosis and attention on herniated discs has led to the SI joint becoming an underappreciated pain generator in an estimated 15% to 25% of patients with axial low back pain.The ligaments in the sacroiliac are among the strongest in the body and are not suspected by many clinicians to be susceptible to spraining or tearing. Skepticism of the existence of sacroiliac joint dysfunction within the medical community is furthered by the debate on how little or much the sacroiliac joint moves. A discrepancy as large as 2-17 degrees has been reported in clinical findings.
Treatment
Treatment is often dependent on the duration and severity of the pain and dysfunction. In the acute phase (first 1–2 weeks) for a mild sprain of the sacroiliac, it is typical for the patient to be prescribed rest, ice/heat, spinal manipulation, and physical therapy; anti-inflammatory medicine can also be helpful.If the pain does not resolve in the first 1–2 weeks, then the patient may benefit from a steroid and anesthetic mixture fluoroscopically injected into the joint (this also serves in confirming diagnosis), as well as manipulative or manual therapy. For the most severe and chronic forms of sacroiliac dysfunction, treatment should proceed with the support of a sacroiliac belt, injection therapy, and finally, surgery. The anti-inflammatory effect of injection therapy is not permanent, and the injections do not offer an opportunity to stabilize an incompetent joint. Surgery is often considered a last resort, but for some patients, it is the only method of effectively stabilizing the loose joint. A fixation of the joint (screws or similar hardware only, without the use of bone grafting) is more common than a spinal fusion, as it is much less invasive, surgically straightforward, and results in a quicker recovery time for the patient. Some experts in the field believe that it is important to make sure the sacroiliac joint is in an anatomically correct position prior to fixation or fusion, but published research contradicts this belief.Platelet-rich plasma (PRP) injections have shown positive results as a treatment for Sacroiliac Joint Dysfunction, with randomized trials & case reports showing them to be more effective over periods of 3 months than steroid injections. Studies have also shown PRP injections into the sacroiliac joint are able to provide complete relief of symptoms, lasting as long as 4 years.Dextrose prolotherapy injections performed either intraarticularly or into the dorsal sacroiliac ligaments is sometimes performed as an alternative treatment option. This is a controversial therapy but it does have research evidence to support its use. Kim et al. in 2010 published a randomized controlled trial evaluating the effect of intraarticular prolotherapy injections versus intraarticular steroid injections in proven sacroiliac joint pain. The two interventions were equal in the short term at 3 months, but the prolotherapy group had superior pain relief at the 15 month mark at the end of follow up. This type of trial is considered high level evidence in medical circles. Hoffman et al. in 2018 published a prospective cohort study with positive results in the treatment of those with sacroiliac joint dysfunction.
See also
Pelvic floor dysfunction
Pelvic pain
Sacroiliitis
== References == |
Warty dyskeratoma | Warty dyskeratoma, also known as an Isolated dyskeratosis follicularis,: 777 is a benign epidermal proliferation with distinctive histologic findings that may mimic invasive squamous cell carcinoma and commonly manifests as an umbilicated (Having a central mark or depression resembling a navel) lesion with a keratotic plug, WD have some histopathologic similarities to viral warts but its not caused by HPV and the majority of these lesions display overall histopathologic features consistent with a follicular adnexal neoplasm. Usually limited to the head, neck, scalp or face and vulva. Lesions are generally solitary and sporadic and may be associated with a follicular unit. Oral involvement, particularly the hard palate, and genital involvement have been reported. it can also be thought of as one of the manifestations of focal acantholytic dyskeratosis, an epidermal reaction pattern that can be seen in several disorders, including Dariers disease and Grovers disease.: 639 But the main Difference between Darier disease and Warty dyskeratoma, is that Darier disease inherited dermatosis (autosomal dominant) consisting of multiple keratotic papules on the face, trunk, and extremities, while WD occurs as an isolated, noninherited, single keratotic nodule mainly confined to the head and neck as mentioned earlier.
Differential Diagnosis
Warty dyskeratoma must be differentiated from vulvar dysplasia, Bowenoid papulosis, squamous carcinoma, condyloma, and other viral-induced squamous lesions.
See also
Keratosis follicularis (disambiguation)
Stucco keratosis
List of cutaneous conditions
== References == |
Urethral hypermobility | Urethral hypermobility is a condition of excessive movement of the female urethra due to a weakened urogenital diaphragm. It describes the instability of the urethra in relation to the pelvic floor muscles. A weakened pelvic floor muscle fails to adequately close the urethra and hence can cause stress urinary incontinence. This condition can be measured with anterior compartment descent. It is sometimes treated with urethral bulking injections.
== References == |
Acrodysostosis | Acrodysostosis is a rare congenital malformation syndrome which involves shortening of the interphalangeal joints of the hands and feet, intellectual disability in approximately 90% of affected children, and peculiar facies. Other common abnormalities include short head (as measured front to back), small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur.Other common abnormalities include short head (as measured front to back), small broad upturned nose with flat nasal bridge, protruding jaw, increased bone age, intrauterine growth retardation, juvenile arthritis and short stature. Further abnormalities of the skin, genitals, teeth, and skeleton may occur.
Signs and Symptoms
Acrodysostosis presents with a wide spectrum of clinical manifestations. The following is a list of conditions and complications associated with acrodysostosis.
Bone issues
Skeletal dysplasia (dwarfism, short stature)
Brachydactyly
Advanced bone age
Bone plate fusing
Scoliosis
Pain – joint, hip, lower back, wrist
Endocrine
Hypothyroidism
Hypoparathyroidism
Pseudohypoparathyroidism
Vitamin D deficiency
Thyroid cysts
Type 1 diabetes
Behavioural / Developmental / Emotional
Autism Spectrum Disorder (ASD)
Childhood Apraxia of Speech
Cognitive impairment
Sensory issues
Gross motor delays
Fine motor delays
Craniofacial and dental
Cranial frontal nasal syndrome Midface hypoplasia
Depressed nasal bridge
Retrognathia
Glossoptosis
High palate
Mandibular distraction surgery Jaw surgery
Underbite
Chalky teeth
Overcrowded teeth
Early eruption of adult teeth
Small, unaligned teeth
Cardiology
Hypertension
Atrial Septal Defect (ASD)
Aortic Coarctation
Middle Aortic Syndrome (MAS) Coarctation of abdominal aorta Bradycardia
Bicuspid aortic valve
Causes
Acrodysostosis is believed to be caused by mutations in the PRKAR1A gene (type 1) or the PDE4D gene (type 2). It has been suggested that the condition might be genetically related i.e. in an autosomal dominant mode of transmission. Both males and females are affected. The disorder has been associated with the older age of parents at the time of conception.
A PRKAR1A mutation has been identified in acrodysostosis with hormone resistance.
Diagnosis
Treatment
There are currently no approved treatments or standardised treatment guidelines for acrodysostosis. Management of acrodysostosis typically focuses on addressing specific symptoms that occur in each individual and may include surgery, physical therapy and special education.
Research
A number of transgenic mouse models have been generated that harbour genetic mutations within genes linked to the condition in humans. These mouse models exhibit phenotypes similar to that observed in Acrodysostosis in humans.
Media
The actress Olivia Colman partnered with the charity Acrodysostosis Support and Research to raise awareness for the disease. She participated in a promotional video campaign in December 2020.
References
External links
"Acrodysostosis: Support and Research".
"Acrodysostosis: Disease Information from NORD". National Organization for Rare Disorders.
Acrodysostosis at NIHs Office of Rare Diseases |
Pemphigus herpetiformis | Pemphigus herpetiformis is a cutaneous condition, a clinical variant of pemphigus that combines the clinical features of dermatitis herpetiformis with the immunopathologic features of pemphigus.
Pathophysiology
Pemphigus Herpetiformis is an IGg mediated autoantibodies that affect the epidermal layer of the skin.
Diagnosis
See also
Adult linear IgA disease
List of cutaneous conditions
== References == |
Papular mucinosis | Papular mucinosis (also known as scleromyxedema, "generalized lichen myxedematosus" and "sclerodermoid lichen myxedematosus") is a rare skin disease. Localized and disseminated cases are called papular mucinosis or lichen myxedematosus while generalized, confluent papular forms with sclerosis are called scleromyxedema. Frequently, all three forms are regarded as papular mucinosis. However, some authors restrict it to only mild cases. Another form, acral persistent papular mucinosis is regarded as a separate entity.
Presentation
Papular mucinosis is chronic and may be progressive. The dermal layer of the skin breaks out into small and solid bumps, usually conical in shape and measured from 2 to 4 mm or sometimes flat-topped papules. Unlike pustules, these bumps do not contain pus. Instead they contain mucin, a waxy substance of mucus, the bodys natural and protective lubricant found in saliva and epithelial cells in lungs and the sensitive part of the nose. They usually come in clusters such as linear arrays. Less frequently, urticarial, nodular, or sometimes annular lesions may be appreciated. The dorsal aspect of the hands, face, elbows, and extensor portions of the extremities are most frequently affected. Mucosal lesions are absent. The coalescence of papules on the face, particularly on the glabella, results in longitudinal folding and gives the appearance of a leonine facies.
In scleromyxedema, symptoms can occur on larger part of the body. Redness and scleroderma-like induration occurs on the skin. In addition, the mobility of the lips, hands, arms, and legs is reduced. Proximal myopathy, inflammatory polyarthritis, central nervous system symptoms, esophageal aperistalsis, and hoarseness are among the notable systemic symptoms. If viscera is involved, the disease will be fatal. The dermatoneuro syndrome is a rare neurological complication of the disease presenting with fever, seizures and altered mental status.
Diagnosis
Classification
Papular mucinosis may be divided into several types or variants:
Acral persistent papular mucinosis
Self-healing papular mucinosis
Papular mucinosis of infancy
Cutaneous mucinosis of infancy
Nodular lichen myxedematosus
Localized lichen myxedematosus
Discrete papular lichen myxedematosus
Treatment
There is no effective treatment for this condition. It has been reported that clearance of lesions can be done with melphalan and cyclophosphamide alone or in combination with prednisone. Both isotretinoin and etretinate have also been shown to improve the conditions. All medications listed can cause adverse symptoms, with isotretinoin and etretinate particularly dangerous since they are both teratogens. Other attempted treatments include interferon-alpha, cyclosporine, PUVA photochemotherapy, electron-beam therapy, IVIg and dermabrasion. However, the overall prognosis for the disease is poor. There are reported instances of remission of the disease when treated with a combination of Revlimid and Dexamethasone over a 24-month period.
Incidence
Papular mucinosis affects adults of both sexes equally and appears between ages 30 and 80. Recently, it has been reported in patients infected with the HIV/AIDS virus. It has also been associated with certain paraproteinemias such as IgG lambda paraproteinemia.
See also
List of cutaneous conditions
Notes
References
"What is Papular mucinosis?", The Star (Malaysia), December 20, 2006.
"Papular Mucinosis", Dermatology Online Journal Vol. 7 No. 2.
== External links == |
Epstein syndrome | Epstein syndrome is a rare genetic disease characterized by a mutation in the MYH9 gene in nonmuscle myosin. This disease affects the patients renal system and can result in kidney failure. Epstein Syndrome was first discovered in 1972 when two families had similar symptoms to Alport syndrome. Epstein syndrome and other Alport-like disorders were seen to be caused by mutations in the MYH9 (myosin heavy chain 9) gene, however, Epstein syndrome differs as it was more specifically linked to a mutation on the R702 codon on the MYH9 gene. Diseases with mutations on the MYH9 gene also include May–Hegglin anomaly, Sebastian syndrome and Fechtner syndrome.
Signs and symptoms
Initial symptoms are often described as bleeding tendency and thrombocytopenia. Bleeding tendency may be observed in epistaxis and purpura. Other symptoms may include macrothrombocytopenia, proteinuria, nephropathy, sensorineural hearing loss, low platelet count, oral lesions and cataracts. The most common symptoms include macrothrombocytopenia, mild sensorineural hearing loss and nephritis. The symptoms and the severity of these symptoms vary between patients where most patients experience nephritis in childhood and then progress to kidney failure in adolescence. In macrothrombocytopenia platelet sizes can reach to approximately 6.6 um compared to a normal platelet size of 2.5 um where 30% platelets can reach the size of an erythrocytes. This large platelet size can be compared with MYH9 disorders where platelet size can vary between 4.5 um and the 6.6 um that is found in Epstein Syndrome with mutations on the R207 codon.
Causes
Epstein Syndrome is caused by a mutation in MYH9 gene. This mutation is autosomal dominant and is thereby inherited if one or both parents carry the mutated gene. However, there have been cases where Epstein Syndrome has been sporadic or non-congenital. Mutations are found in the nonmuscle myosin heavy chain IIA and is associated with chromosome 22. The MYH9 gene encodes for tissues including platelets, cochlea, renal cells, neutrophils and eyes.
Pathophysiology
The main symptom in Epstein Syndrome is thrombocytopaenia. Thrombocytopaenia is generally inherited as an autosomal dominant gene and platelets are found to aggregate with either epinephrine or collagen. Platelets assist in blood clotting and coagulate when there are damages blood vessels. This coagulation attempts to cease bleeding. Thrombocytopaenia means there is low platelet volume in the blood. This means there are less platelets to coagulate in presence of a damaged blood vessel, which can result in bleeding problems. The platelets are large (macrothrombocytopenia) and often consist of neutrophil inclusions. The large size of platelets may be due to excess microtubule coils and tublin. This large size of the platelets also affects their ability to bind to each other to seal damaged blood vessels and stop bleeding.Nephritis involves the inflammation of the kidney and this inflammation results in a reduced ability to filter blood and remove nitrogenous wastes. This excessive accumulation of wastes will result in a continued build-up of wastes including urea which interferes with metabolism.One of the kidneys functions include osmoregulation which involves the regulation of osmotic pressure in the blood by regulating the water content in blood pressure. Through osmosis (water movement from a low solute concentration to an area of high solute concentration) water is reabsorbed back into the blood from nephron tubules in the kidney. This maintenance of water concentration in the blood is essential for maintaining blood pressure and is affected in nephritis.
Diagnosis
The cardinal symptom in Epstein syndrome is thrombocytopaenia with giant platelets (macrothrombocytopenia). A peripheral blood smear is taken from the patient and a light microscope is used to these identify giant platelets. Leukocyte inclusions are also examined for, because approximately 41.1% of R207 mutations have leukocyte inclusions. These are often abnormal neutrophils with a small size of approximately less than 0.7 um and have an abnormallocation on the non-muscle myosin heavy chain IIA (NMMHC-II). These inclusion bodies have RNA and no DNA. RNA in these inclusion bodies can be located in immunofluorescence analysis with the anti nonmuscle heavy chain IIA antibody.Hematology analysers or a hemocytometer can be used to determine the amount of platelets. A sample of blood is drawn from a patients arm. A small amount of platelets in blood smears compared to the normal range of 150,000 to 450,000 platelets in microliter of blood suggest thrombocytopaenia, which is a common symptom in Epstein syndrome.A urine sample is often collected where a urinalysis can be used to determine the volume of proteins excreted in urine. Abnormal amounts of protein detected means the patient has proteinuria. Patients with Epstein syndrome often have large proteinuria where they excrete above 3.5g of protein in their urine in a day. This is one of the initial signs of renal disease.Easy bruising and abnormal bleeding tendencies are also described in initial diagnosis. This supports the common misdiagnosis for chronic idiopathic thrombocytopaenia purpura in patients with Epstein syndrome. These symptoms are often noticed in early childhood due to the congenital cause of the disease.
Treatment
Epstein syndrome is regarded as a refractory disease. Treatments include renal transplantation, however, this may become problematic as patients low platelet count (thrombocytopaenia) increase the risks of complications in surgery. Successful Renal transplants can arise from cadavers or from live donors. To minimize the risk of patients losing too much blood during the perioperative period, HLA-matched platelet infusions can be used to maintain satisfactory platelet levels. Nephritis involves the inflammation of the kidney and this inflammation results in a reduced ability to filter blood. In order to ensure the transplanted kidney is recognised as ‘self’ by Major Histocompatibility cells, immunosuppression drugs are used post operation. Immunosuppression medication may include calcineurin inhibitor, antimetabolite and methylprednisolone and assist in suppressing the immune systems response to the transplanted kidney
Maintenance
As a result of nephritis, a healthy blood pressure becomes difficult to maintain and hence medication including vasopressin may be prescribed to maintain blood pressure. Severe nephritis may mean kidney dialysis is required to ensure the blood is being filtered. This may include either peritoneal dialysis or haemodialysis, however, haemodialysis is most common as Epstein syndrome patients will often eventually have renal transplants. Peritoneal dialysis involves blood being filtered through a membrane in the abdomen (peritoneum). Whereas haemodialysis involves blood being filtered through a dialyser, which consists of a semi-permeable membrane where toxins including urea are removed from the blood. Haemodialysis also filters blood quicker than peritoneal dialysis.Intravenous immunoglobin treatments can be used to support the patients immune system as well as medication with Prednisolone to reduce inflammation.Sensorineural hearing loss is a common symptom in Epstein syndrome and can be treated with cochlea implants. Cochlea implants have four main parts including the electrode array, the transmitter, the receiver/stimulator and the microphone. The microphone is positioned behind the ear and receives sound waves, the processor then converts the sound into electrical signals. These electrical signals are further converted into electrical impulses in the cochlea where the transmitter is located, which in turn sends the signal to the auditory nerve. This results in a nervous impulse sent to the brain where the ‘sound’ is deciphered.
Prognosis
In most case Epstein syndrome patients will endure early-onset end-stage renal disease (ESRD) at the end of adolescence. Expected kidney failure means patients will need renal transplants in the near future.
Notable cases
In a study which investigated suitable management for severe Epstein syndrome, four patients were observed. Patient 1 demonstrated a common background and symptoms for Epstein syndrome. Patient 1 was a male who was initially diagnosed with chronic idiopathic thrombocytopaenia purpura in early childhood and then macrothrobocytopaenia. He progressed to kidney failure and began haemodialysis at seventeen years old. Patient 1 was only diagnosed with Epstein syndrome at the age of thirty-three where the mutation in the nonmuscle myosin was noticed. His eldest son also carried the same mutation.An Epstein syndrome patient with oral lesions was recorded to be the first with this symptom. The patient was a twenty-six-year-old female who was diagnosed with thrombocytopaenia with purpura at age four. She was then finally diagnosed with Epstein syndrome at twenty-two years old when she developed symptoms for hearing loss as well as proteinuria and hematuria revealing poor kidney function. After an oral examination, palatal purpua in her mouth was observed.A Japanese male was diagnosed with sporadic Epstein syndrome where both his parents did not have the R702H mutation. He was initially diagnosed with chronic macrothrombocytopaenia at three years old and throughout childhood symptoms for hearing loss and proteinuria were observed. At 24 years old his kidney failure had severely progressed as well as his hearing loss and thrombocytopenia. A genetic test confirmed he had the R702H mutation despite having no familial record of Epstein syndrome.
References
== External links == |
Bufotoxin | Bufotoxins are a family of toxic steroid lactones or substituted Tryptamines of which some may or may not be toxic. They occur in the parotoid glands, skin and poison of many toads (genus Bufo) and other amphibians, and in some plants and mushrooms. The exact composition varies greatly with the specific source of the toxin. It can contain 5-MeO-DMT, bufagins, bufalin, bufotalin, bufotenin, bufothionine, dehydrobufotenine, epinephrine, norepinephrine, and serotonin. Some authors have also used the term bufotoxin to describe the conjugate of a bufagin with suberylarginine.The toxic substances found in toads can be divided by chemical structure in two groups:
bufadienolides, which are cardiac glycosides (e.g., bufotalin, bufogenin)
tryptamine-related substances (e.g., bufotenin)Toads known to secrete bufotoxin include the following:
Bufo alvarius
Bufo americanus
Bufo arenarum
Bufo asper
Bufo blombergi
Bufo boreas
Bufo bufo
Bufo bufo gargarizans
Sclerophrys gutturalis (syn. Bufo gutturalis)
Bufo formosus
Bufo fowleri
Rhinella marina (formerly Bufo marinus)
Bufo melanostictus
Bufo peltocephalus
Bufo quercicus
Bufo regularis
Bufo valliceps
Bufo viridis
Bufo vulgaris
Extraction
Extract from the skin of certain Asian toads, such as Bufo bufo gargarizans and Bufo melanostictus, is often found in certain Chinese folk remedies. The Pharmacopoeia of the Peoples Republic of China (ChP) considers the two species valid sources of toad venom (Chinese: 蟾酥; pinyin: Chánsū; Latin: bufonis venenum), and requires the dry product to contain at least 6% of cinobufagin and resibufogenin combined by weight. The extract is obtained by squeezing the parotoid glands of caught, washed toads for a white venom and drying; the final dried venom is usually brown, with a chunk or flake form.
Human poisoning
Toad‐venom poisoning is rare but can kill. It can occur when someone drinks toad soup, eats toad meat or toad eggs, or swallows live toads on a bet. It can also happen when someone deliberately takes commercial substances made with toad toxins. These go under names including "Kyushin", "Chan Su" (marketed as a painkiller, topical anesthetic or cardiac treatment), "Rockhard" and "Love Stone" (marketed as aphrodisiacs)."Chan Su" (literally "toad venom") is often adulterated with standard painkillers, such as paracetamol, promethazine and diclofenac. It may be ingested or injected.
References
External links
Anaxyrus boreas boreas - Boreal Toad, californiaherps.com
Toad Toxins, erowid.com |
Palpation thyroiditis | Palpation thyroiditis refers to the development of thyroid inflammation due to mechanical damage to thyroid follicles. This can occur by vigorous repeated palpation (as with thyroid examination) or surgical manipulation (as can occur with radical neck dissection). It is a type of subacute thyroiditis. Pathology shows multifocal granulomatous folliculitis. T cells predominate compared to B cells. There may be initial transient hyperthyroidism due to leakage of preformed thyroid hormone in blood.
== References == |
Syringobulbia | Syringobulbia is a medical condition in which syrinxes, or fluid-filled cavities, affect the brainstem (usually the lower brainstem). The exact cause is often unknown, but may be linked to a widening of the central canal of the spinal cord. This may affect one or more cranial nerves, resulting in various kinds of facial palsies. Sensory and motor nerve pathways may be affected by interruption or compression of nerves. This disorder is associated with syringomyelia, a syrinx limited to the spinal cord. It can be diagnosed using magnetic resonance imaging. Symptoms may be treated with tricyclic antidepressants.
Signs and symptoms
Syringobulbia usually causes pain. It may also cause a loss of sense of temperature. Alveolar hypoventilation (insufficient breathing, a type of central hypoventilation syndrome) may occur, with hypercapnia (excess blood CO2), stridor (an unusual breathing sound), and irregular breathing.
Cause
Syringobulbia may be caused by a birth defect, trauma or tumor growth. The exact trigger is unknown, but may be linked to a widening of the central canal of the spinal cord.
Mechanism
Syringobulbia affects the lower part of the brainstem. The central canal of the spinal cord may be widened. A fluid-filled lesion forms, known as a syrinx. This can vary in size significantly between patients. Nerve fibres may be compressed where they cross the midline, or in other parts of the spinal cord. Cranial nerves may be affected.Syringobulbia may be associated with syringomyelia, a syrinx limited to the spinal cord.
Diagnosis
Syringobulbia may be diagnosed using magnetic resonance imaging.
Treatment
The pain caused by syringobulbia may be treated with tricyclic antidepressants.
See also
Syrinx
Syringomyelia
References
External links
14-182d. at Merck Manual of Diagnosis and Therapy Professional Edition |
Hypochondriasis | Hypochondriasis or hypochondria is a condition in which a person is excessively and unduly worried about having a serious illness. An old concept, the meaning of hypochondria has repeatedly changed. It has been claimed that this debilitating condition results from an inaccurate perception of the condition of body or mind despite the absence of an actual medical diagnosis. An individual with hypochondriasis is known as a hypochondriac. Hypochondriacs become unduly alarmed about any physical or psychological symptoms they detect, no matter how minor the symptom may be, and are convinced that they have, or are about to be diagnosed with, a serious illness.Often, hypochondria persists even after a physician has evaluated a person and reassured them that their concerns about symptoms do not have an underlying medical basis or, if there is a medical illness, their concerns are far in excess of what is appropriate for the level of disease. It is also referred to hypochondriaism which is the act of being in a hypochondriatic state, acute hypochondriaism. Many hypochondriacs focus on a particular symptom as the catalyst of their worrying, such as gastro-intestinal problems, palpitations, or muscle fatigue. To qualify for the diagnosis of hypochondria the symptoms must have been experienced for at least 6 months.International Classification of Diseases (ICD-10) classifies hypochondriasis as a mental and behavioral disorder. In the Diagnostic and Statistical Manual of Mental Disorders, DSM-IV-TR defined the disorder, "Hypochondriasis", as a somatoform disorder and one study has shown it to affect about 3% of the visitors to primary care settings. The 2013 DSM-5 replaced the diagnosis of hypochondriasis with the diagnoses of somatic symptom disorder (75%) and illness anxiety disorder (25%).Hypochondria is often characterized by fears that minor bodily or mental symptoms may indicate a serious illness, constant self-examination and self-diagnosis, and a preoccupation with ones body. Many individuals with hypochondriasis express doubt and disbelief in the doctors diagnosis, and report that doctors’ reassurance about an absence of a serious medical condition is unconvincing, or short-lasting. Additionally, many hypochondriacs experience elevated blood pressure, stress, and anxiety in the presence of doctors or while occupying a medical facility, a condition known as "white coat syndrome". Many hypochondriacs require constant reassurance, either from doctors, family, or friends, and the disorder can become a debilitating challenge for the individual with hypochondriasis, as well as their family and friends. Some individuals with hypochondria completely avoid any reminder of illness, whereas others frequently visit medical facilities, sometimes obsessively. Some may never speak about it.
Signs and symptoms
Hypochondriasis is categorized as a somatic amplification disorder—a disorder of "perception and cognition"—that involves a hyper-vigilance of situation of the body or mind and a tendency to react to the initial perceptions in a negative manner that is further debilitating. Hypochondriasis manifests in many ways. Some people have numerous intrusive thoughts and physical sensations that push them to check with family, friends, and physicians. For example, a person who has a minor cough may think that they have tuberculosis. Or sounds produced by organs in the body, such as those made by the intestines, might be seen as a sign of a very serious illness to patients dealing with hypochondriasis.Other people are so afraid of any reminder of illness that they will avoid medical professionals for a seemingly minor problem, sometimes to the point of becoming neglectful of their health when a serious condition may exist and go undiagnosed. Yet others live in despair and depression, certain that they have a life-threatening disease and no physician can help them. Some consider the disease as a punishment for past misdeeds.Hypochondriasis is often accompanied by other psychological disorders. Bipolar disorder, clinical depression, obsessive-compulsive disorder (OCD), phobias, and somatization disorder,
panic disorder are the most common accompanying conditions in people with hypochondriasis, as well as a generalized anxiety disorder diagnosis at some point in their life.Many people with hypochondriasis experience a cycle of intrusive thoughts followed by compulsive checking, which is very similar to the symptoms of obsessive-compulsive disorder. However, while people with hypochondriasis are afraid of having an illness, patients with OCD worry about getting an illness or of transmitting an illness to others. Although some people might have both, these are distinct conditions.Patients with hypochondriasis often are not aware that depression and anxiety produce their own physical symptoms, and mistake these symptoms for manifestations of another mental or physical disorder or disease. For example, people with depression often experience changes in appetite and weight fluctuation, fatigue, decreased interest in sex, and motivation in life overall. Intense anxiety is associated with rapid heartbeat, palpitations, sweating, muscle tension, stomach discomfort, dizziness, shortness of breath, and numbness or tingling in certain parts of the body (hands, forehead, etc.).If a person is ill with a medical disease such as diabetes or arthritis, there will often be psychological consequences, such as depression. Some even report being suicidal. In the same way, someone with psychological issues such as depression or anxiety will sometimes experience physical manifestations of these affective fluctuations, often in the form of medically unexplained symptoms. Common symptoms include headaches; abdominal, back, joint, rectal, or urinary pain; nausea; fever and/or night sweats; itching; diarrhea; dizziness; or balance problems. Many people with hypochondriasis accompanied by medically unexplained symptoms feel they are not understood by their physicians, and are frustrated by their doctors’ repeated failure to provide symptom relief.
Cause
The genetic contribution to hypochondriasis is probably moderate, with heritability estimates around 10-37%. Non-shared environmental factors (i.e., experiences that differ between twins in the same family) explain most of the variance in key components of the condition such as the fear of illness and disease conviction. In contrast, the contribution of shared environmental factors (i.e., experiences shared by twins in the same family) to hypochondriasis is approximately zero.Although little is known about exactly which non-shared environmental factors typically contribute to causing hypochondriasis, certain factors such as exposure to illness-related information are widely believed to lead to short-term increases in health anxiety and to have contributed to hypochondriasis in individual cases. Overly protective caregivers and an excessive focus on minor health concerns have also been implicated as potential causes of hypochondriasis.In the media and on the Internet, articles, TV shows, and advertisements regarding serious illnesses such as cancer and multiple sclerosis often portray these diseases as being random, obscure, and somewhat inevitable. In the short term, inaccurate portrayal of risk and the identification of non-specific symptoms as signs of serious illness may contribute to exacerbating fear of illness. Major disease outbreaks or predicted pandemics can have similar effects.
Anecdotal evidence suggests that some individuals become hypochondriac after experiencing major medical diagnosis or death of a family member or friend. Similarly, when approaching the age of a parents premature death from disease, many otherwise healthy, happy individuals fall prey to hypochondria. These individuals believe they have the same disease that caused their parents death, sometimes causing panic attacks with corresponding symptoms.
Diagnosis
The ICD-10 defines hypochondriasis as follows:
A. Either one of the following:
A persistent belief, of at least six months duration, of the presence of a minimum of two serious physical diseases (of which at least one must be specifically named by the patient).
A persistent preoccupation with a presumed deformity or disfigurement (body dysmorphic disorder).B. Preoccupation with the belief and the symptoms causes persistent distress or interference with personal functioning in daily living and leads the patient to seek medical treatment or investigations (or equivalent help from local healers).C. Persistent refusal to accept medical advice that there is no adequate physical cause for the symptoms or physical abnormality, except for short periods of up to a few weeks at a time immediately after or during medical investigations.D. Most commonly used exclusion criteria: not occurring only during any of the schizophrenia and related disorders (F20–F29, particularly F22) or any of the mood disorders (F30–F39).The DSM-IV defines hypochondriasis according to the following criteria:
A. Preoccupation with fears of having, or the idea that one has, a serious disease based on the persons misinterpretation of bodily symptoms.
B. The preoccupation persists despite appropriate medical evaluation and reassurance.
C. The belief in Criterion A is not of delusional intensity (as in Delusional Disorder, Somatic Type) and is not restricted to a circumscribed concern about appearance (as in Body Dysmorphic Disorder).
D. The preoccupation causes clinically significant distress or impairment in
social, occupational, or other important areas of functioning.
E. The duration of the disturbance is at least 6 months.
F. The preoccupation is not better accounted for by Generalized Anxiety Disorder, Obsessive-Compulsive Disorder, Panic Disorder, a Major Depressive Episode, Separation Anxiety, or another Somatoform Disorder.
In the fifth version of the DSM (DSM-5), most who met criteria for DSM-IV hypochondriasis instead meet criteria for a diagnosis of somatic symptom disorder (SSD) or illness anxiety disorder (IAD).
Classification
The classification of hypochondriasis in relation to other psychiatric disorders has long been a topic of scholarly debate and has differed widely between different diagnostic systems and influential publications.
In the case of the DSM, the first and second versions listed hypochondriasis as a neurosis, whereas the third and fourth versions listed hypochondriasis as a somatoform disorder. The current version of the DSM (DSM-5) lists somatic symptom disorder (SSD) under the heading of "somatic symptom and related disorders", and illness anxiety disorder (IAD) under both this heading and as an anxiety disorder.
The ICD-10, like the third and fourth versions of the DSM, lists hypochondriasis as a somatoform disorder. The ICD-11, however, lists hypochondriasis under the heading of "obsessive-compulsive or related disorders".
There are also numerous influential scientific publications that have argued for other classifications of hypochondriasis. Notably, since the early 1990s, it has become increasingly common to regard hypochondriasis as an anxiety disorder, and to refer to the condition as "health anxiety" or "severe health anxiety".
Treatment
Approximately 20 randomized controlled trials and numerous observational studies indicate that cognitive behavioral therapy (CBT) is an effective treatment for hypochondriasis. Typically, about two-thirds of patients respond to treatment, and about 50% of patients achieve remission, i.e., no longer have hypochondriasis after treatment. CBT for hypochondriasis and health anxiety may be offered in various formats, including as face-to-face individual or group therapy, via telephone, or as guided self-help with information conveyed via a self-help book or online treatment platform. Effects are typically sustained over time.There is also evidence that antidepressant medications such as selective serotonin reuptake inhibitors can reduce symptoms. In some cases, hypochondriasis responds well to antipsychotics, particularly the newer atypical antipsychotic medications.
Etymology
Among the regions of the abdomen, the hypochondrium is the uppermost part. The word derives from the Greek term ὑποχόνδριος hypokhondrios, meaning "of the soft parts between the ribs and navel" from ὑπό hypo ("under") and χόνδρος khondros, or cartilage (of the sternum). Hypochondria in Late Latin meant "the abdomen".The term hypochondriasis for a state of disease without real cause reflected the ancient belief that the viscera of the hypochondria were the seat of melancholy and sources of the vapor that caused morbid feelings. Until the early 18th century, the term referred to a "physical disease caused by imbalances in the region that was below your rib cage" (i.e., of the stomach or digestive system). For example, Robert Burtons The Anatomy of Melancholy (1621) blamed it "for everything from too much spittle to rumbling in the guts".
Immanuel Kant discussed hypochondria in his 1798 book, Anthropology from a Pragmatic Point of View, like this: The disease of the hypochondriac consists in this: that certain bodily sensations do not so much indicate a really existing disease in the body as rather merely excite apprehensions of its existence: and human nature is so constituted – a trait which the animal lacks – that it is able to strengthen or make permanent local impressions simply by paying attention to them, whereas an abstraction – whether produced on purpose or by other diverting occupations – lessens these impressions, or even effaces them altogether.
Anthropology by Immanuel Kant, 1798 Journal of Speculative Philosophy Vol. XVI edited by William Torrey Harris p. 395-396
See also
References
Further reading
External links
Hypochondriasis at Curlie |
Femoral nerve | The femoral nerve is a nerve in the thigh that supplies skin on the upper thigh and inner leg, and the muscles that extend the knee.
Structure
The femoral nerve is the major nerve supplying the anterior compartment of the thigh. It is the largest branch of the lumbar plexus, and arises from the dorsal divisions of the ventral rami of the second, third, and fourth lumbar nerves (L2, L3, and L4).The nerve enters Scarpas triangle by passing beneath the inguinal ligament, just lateral to the femoral artery. In the thigh, the nerve lies in a groove between iliacus muscle and psoas major muscle, outside the femoral sheath, and lateral to the femoral artery. After a short course of about 4 cm in the thigh, the nerve is divided into anterior and posterior divisions, separated by lateral femoral circumflex artery. The branches are shown below:
Muscular branches
The nerve to the pectineus muscle arises immediately above the inguinal ligament from the medial side of the femoral nerve, and passes behind the femoral sheath to enter the anterior surface of the muscle.
Anterior division supplies the sartorius muscle
Posterior division supplies the rectus femoris muscle, the three vasti (vastus medialis muscle, vastus lateralis muscle, and vastus intermedius muscle), and articularis genus muscle. The articularis genus is supplied by a branch of the nerve to vastus intermedius.
Cutaneous branches
The anterior division gives off anterior cutaneous branches: The anterior cutaneous branches are: the intermediate femoral cutaneous nerve and the medial femoral cutaneous nerve.
The posterior division gives off only one branch, which is the saphenous nerve.
Articular branches
Hip joint is supplied by nerve to the rectus femoris.
Knee joint is supplied by the nerves to the three vasti. The nerve to vastus medialis is particularly thick because it contains the proprioceptive fibres from the knee joint. This is in accordance to the Hiltons law.
Vascular branches
Branches to the femoral artery and its branches.
Clinical significance
Signals from the femoral nerve and its branches can be blocked to interrupt transmission of pain signal from the innervation area, by performing a regional nerve blockage. Some of the nerve blocks that work by affecting the femoral nerve are the femoral nerve block, the fascia iliac block and the 3-in-1 nerve block. Femoral nerve blocks are very effective.During pelvic surgery and abdominal surgery, the femoral nerve must be identified early on to protect it from iatrogenic nerve injury.The femoral nerve stretch test can be performed to identify the compression of spinal nerve roots. The test is positive if thigh pain increases.
Additional images
See also
Femoral nerve stretch test
References
This article incorporates text in the public domain from page 955 of the 20th edition of Grays Anatomy (1918)
External links
Femoral nerve at the Duke University Health Systems Orthopedics program
MedlinePlus Encyclopedia: 000687 - "Femoral nerve dysfunction" (includes illustration)
Anatomy photo:40:17-0202 at the SUNY Downstate Medical Center - "Posterior Abdominal Wall: Nerves of the Lumbar Plexus"
Cross section image: pembody/body15a—Plastination Laboratory at the Medical University of Vienna
Cross section image: pelvis/pelvis-e12-15—Plastination Laboratory at the Medical University of Vienna
arteries-nerves%20LE/nerves1 at the Dartmouth Medical Schools Department of Anatomy |
Tay–Sachs disease | Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord. The most common form is infantile Tay–Sachs disease, which becomes apparent around three to six months of age, with the baby losing the ability to turn over, sit, or crawl. This is then followed by seizures, hearing loss, and inability to move, with death usually occurring by the age of three to five. Less commonly, the disease may occur in later childhood or adulthood (juvenile or late-onset). These forms tend to be less severe, but the juvenile form typically results in death by age 15.Tay–Sachs disease is caused by a genetic mutation in the HEXA gene on chromosome 15, which codes form a subunit of the hexosaminidase enzyme known as hexosaminidase A. It is inherited from a persons parents in an autosomal recessive manner. The mutation disrupts the activity of the enzyme, which results in the build-up of the molecule GM2 ganglioside within cells, leading to toxicity. Diagnosis may be supported by measuring the blood hexosaminidase A level or genetic testing. Tay–Sachs disease is a type of GM2 gangliosidosis and sphingolipidosis.The treatment of Tay–Sachs disease is supportive in nature. This may involve multiple specialities as well as psychosocial support for the family. The disease is rare in the general population. In Ashkenazi Jews, French Canadians of southeastern Quebec, the Old Order Amish of Pennsylvania, and the Cajuns of southern Louisiana, the condition is more common. Approximately 1 in 3,600 Ashkenazi Jews at birth are affected.The disease is named after British ophthalmologist Waren Tay, who in 1881 first described a symptomatic red spot on the retina of the eye; and American neurologist Bernard Sachs, who described in 1887 the cellular changes and noted an increased rate of disease in Ashkenazi Jews. Carriers of a single Tay–Sachs allele are typically normal. It has been hypothesized that being a carrier may confer protection from tuberculosis, explaining the persistence of the allele in certain populations. Researchers are looking at gene therapy or enzyme replacement therapy as possible treatments.
Signs and symptoms
Tay–Sachs disease is typically first noticed in infants around 6 months old displaying an abnormally strong response to sudden noises or other stimuli, known as the "startle response". There may also be listlessness or muscle stiffness (hypertonia). The disease is classified into several forms, which are differentiated based on the onset age of neurological symptoms.
Infantile
Infants with Tay–Sachs disease appear to develop normally for the first six months after birth. Then, as neurons become distended with GM2 gangliosides, a relentless deterioration of mental and physical abilities begins. The child may become blind, deaf, unable to swallow, atrophied, and paralytic. Death usually occurs before the age of four.
Juvenile
Juvenile Tay–Sachs disease is rarer than other forms of Tay–Sachs, and usually is initially seen in children between two and ten years old. People with Tay–Sachs disease experience cognitive and motor skill deterioration, dysarthria, dysphagia, ataxia, and spasticity. Death usually occurs between the ages of five and fifteen years.
Late-onset
A rare form of this disease, known as Adult-Onset or Late-Onset Tay–Sachs disease, usually has its first symptoms during the 30s or 40s. In contrast to the other forms, late-onset Tay–Sachs disease is usually not fatal as the effects can stop progressing. It is frequently misdiagnosed. It is characterized by unsteadiness of gait and progressive neurological deterioration. Symptoms of late-onset Tay–Sachs – which typically begin to be seen in adolescence or early adulthood – include speech and swallowing difficulties, unsteadiness of gait, spasticity, cognitive decline, and psychiatric illness, particularly a schizophrenia-like psychosis. People with late-onset Tay–Sachs may become full-time wheelchair users in adulthood.Until the 1970s and 1980s, when the diseases molecular genetics became known, the juvenile and adult forms of the disease were not always recognized as variants of Tay–Sachs disease. Post-infantile Tay–Sachs was often misdiagnosed as another neurological disorder, such as Friedreichs ataxia.
Genetics
Tay–Sachs disease is an autosomal recessive genetic disorder, meaning that when both parents are carriers, there is a 25% risk of giving birth to an affected child with each pregnancy. The affected child would have received a mutated copy of the gene from each parent. If one parent has this Genetic disorder and is passed down to the child, then the child becomes a carrier.Tay–Sachs results from mutations in the HEXA gene on chromosome 15, which encodes the alpha-subunit of beta-N-acetylhexosaminidase A, a lysosomal enzyme. By 2000, more than 100 different mutations had been identified in the human HEXA gene. These mutations have included single base insertions and deletions, splice phase mutations, missense mutations, and other more complex patterns. Each of these mutations alters the genes protein product (i.e., the enzyme), sometimes severely inhibiting its function. In recent years, population studies and pedigree analysis have shown how such mutations arise and spread within small founder populations. Initial research focused on several such founder populations:
Ashkenazi Jews. A four base pair insertion in exon 11 (1278insTATC) results in an altered reading frame for the HEXA gene. This mutation is the most prevalent mutation in the Ashkenazi Jewish population, and leads to the infantile form of Tay–Sachs disease.
Cajuns. The same 1278insTATC mutation found among Ashkenazi Jews occurs in the Cajun population of southern Louisiana. Researchers have traced the ancestry of carriers from Louisiana families back to a single founder couple – not known to be Jewish – who lived in France in the 18th century.
French Canadians. Two mutations, unrelated to the Ashkenazi/Cajun mutation, are absent in France but common among certain French-Canadian communities living in southeastern Quebec and Acadians from the Province of New Brunswick. Pedigree analysis suggests the mutations were uncommon before the late 17th century.In the 1960s and early 1970s, when the biochemical basis of Tay–Sachs disease was first becoming known, no mutations had been sequenced directly for genetic diseases. Researchers of that era did not yet know how common polymorphisms would prove to be. The "Jewish Fur Trader Hypothesis," with its implication that a single mutation must have spread from one population into another, reflected the knowledge at the time. Subsequent research, however, has proven that a large variety of different HEXA mutations can cause the disease. Because Tay–Sachs was one of the first genetic disorders for which widespread genetic screening was possible, it is one of the first genetic disorders in which the prevalence of compound heterozygosity has been demonstrated.Compound heterozygosity ultimately explains the diseases variability, including the late-onset forms. The disease can potentially result from the inheritance of two unrelated mutations in the HEXA gene, one from each parent. Classic infantile Tay–Sachs disease results when a child has inherited mutations from both parents that completely stop the biodegradation of gangliosides. Late onset forms occur due to the diverse mutation base – people with Tay–Sachs disease may technically be heterozygotes, with two differing HEXA mutations that both inactivate, alter, or inhibit enzyme activity. When a patient has at least one HEXA copy that still enables some level of hexosaminidase A activity, a later onset disease form occurs. When disease occurs because of two unrelated mutations, the patient is said to be a compound heterozygote.Heterozygous carriers (individuals who inherit one mutant allele) show abnormal enzyme activity but manifest no disease symptoms. This phenomenon is called dominance; the biochemical reason for wild-type alleles dominance over nonfunctional mutant alleles in inborn errors of metabolism comes from how enzymes function. Enzymes are protein catalysts for chemical reactions; as catalysts, they speed up reactions without being used up in the process, so only small enzyme quantities are required to carry out a reaction. Someone homozygous for a nonfunctional mutation in the enzyme-encoding gene has little or no enzyme activity, so will manifest the abnormal phenotype. A heterozygote (heterozygous individual) has at least half of the normal enzyme activity level, due to the expression of the wild-type allele. This level is normally enough to enable normal function and thus prevent phenotypic expression.
Pathophysiology
Tay–Sachs disease is caused by insufficient activity of the enzyme hexosaminidase A. Hexosaminidase A is a vital hydrolytic enzyme, found in the lysosomes, that breaks down sphingolipids. When hexosaminidase A is no longer functioning properly, the lipids accumulate in the brain and interfere with normal biological processes. Hexosaminidase A specifically breaks down fatty acid derivatives called gangliosides; these are made and biodegraded rapidly in early life as the brain develops. Patients with and carriers of Tay–Sachs can be identified by a simple blood test that measures hexosaminidase A activity.The hydrolysis of GM2-ganglioside requires three proteins. Two of them are subunits of hexosaminidase A; the third is a small glycolipid transport protein, the GM2 activator protein (GM2A), which acts as a substrate-specific cofactor for the enzyme. Deficiency in any one of these proteins leads to ganglioside storage, primarily in the lysosomes of neurons. Tay–Sachs disease (along with AB-variant GM2-gangliosidosis and Sandhoff disease) occurs because a mutation inherited from both parents deactivates or inhibits this process. Most Tay–Sachs mutations probably do not directly affect protein functional elements (e.g., the active site). Instead, they cause incorrect folding (disrupting function) or disable intracellular transport.
Diagnosis
In patients with a clinical suspicion for Tay–Sachs disease, with any age of onset, the initial testing involves an enzyme assay to measure the activity of hexosaminidase in serum, fibroblasts, or leukocytes. Total hexosaminidase enzyme activity is decreased in individuals with Tay–Sachs as is the percentage of hexosaminidase A. After confirmation of decreased enzyme activity in an individual, confirmation by molecular analysis can be pursued. All patients with infantile onset Tay–Sachs disease have a "cherry red" macula in the retina, easily observable by a physician using an ophthalmoscope. This red spot is a retinal area that appears red because of gangliosides in the surrounding retinal ganglion cells. The choroidal circulation is showing through "red" in this foveal region where all retinal ganglion cells are pushed aside to increase visual acuity. Thus, this cherry-red spot is the only normal part of the retina; it shows up in contrast to the rest of the retina. Microscopic analysis of the retinal neurons shows they are distended from excess ganglioside storage. Unlike other lysosomal storage diseases (e.g., Gaucher disease, Niemann–Pick disease, and Sandhoff disease), hepatosplenomegaly (liver and spleen enlargement) is not seen in Tay–Sachs.
Prevention
Three main approaches have been used to prevent or reduce the incidence of Tay–Sachs:
Prenatal diagnosis. If both parents are identified as carriers, prenatal genetic testing can determine whether the fetus has inherited a defective gene copy from both parents. Chorionic villus sampling (CVS), the most common form of prenatal diagnosis, can be performed between 10 and 14 weeks of gestation. Amniocentesis is usually performed at 15–18 weeks. These procedures have risks of miscarriage of 1% or less.
Preimplantation genetic diagnosis. By retrieving the mothers eggs for in vitro fertilization, it is possible to test the embryo for the disorder prior to implantation. Healthy embryos are then selected and transferred into the mothers womb, while unhealthy embryos are discarded. In addition to Tay–Sachs disease, preimplantation genetic diagnosis has been used to prevent cystic fibrosis and sickle cell anemia among other genetic disorders.
Mate selection. In Orthodox Jewish circles, the organization Dor Yeshorim carries out an anonymous screening program so that carriers for Tay–Sachs and other genetic disorders can avoid marrying each other.
Management
As of 2010 there was no treatment that addressed the cause of Tay–Sachs disease or could slow its progression; people receive supportive care to ease the symptoms and extend life by reducing the chance of contracting infections. Infants are given feeding tubes when they can no longer swallow. In late-onset Tay–Sachs, medication (e.g., lithium for depression) can sometimes control psychiatric symptoms and seizures, although some medications (e.g., tricyclic antidepressants, phenothiazines, haloperidol, and risperidone) are associated with significant adverse effects.
Outcomes
As of 2010, even with the best care, children with infantile Tay–Sachs disease usually die by the age of 4. Children with the juvenile form are likely to die between the ages 5–15, while the lifespans of those with the adult form will probably not be affected.
Epidemiology
Ashkenazi Jews have a high incidence of Tay–Sachs and other lipid storage diseases. In the United States, about 1 in 27 to 1 in 30 Ashkenazi Jews is a recessive carrier. The disease incidence is about 1 in every 3,500 newborn among Ashkenazi Jews. French Canadians and the Cajun community of Louisiana have an occurrence similar to the Ashkenazi Jews. Irish Americans have a 1 in 50 chance of being a carrier. In the general population, the incidence of carriers as heterozygotes is about 1 in 300. The incidence is approximately 1 in 320,000 newborns in the general population in the United States.Three general classes of theories have been proposed to explain the high frequency of Tay–Sachs carriers in the Ashkenazi Jewish population:
Heterozygote advantage. When applied to a particular allele, this theory posits that mutation carriers have a selective advantage, perhaps in a particular environment.
Reproductive compensation. Parents who lose a child because of disease tend to "compensate" by having additional children following the loss. This phenomenon may maintain and possibly even increase the incidence of autosomal recessive disease.
Founder effect. This hypothesis states that the high incidence of the 1278insTATC chromosomes is the result of an elevated allele frequency that existed by chance in an early founder population.Tay–Sachs disease was one of the first genetic disorders for which epidemiology was studied using molecular data. Studies of Tay–Sachs mutations using new molecular techniques such as linkage disequilibrium and coalescence analysis have brought an emerging consensus among researchers supporting the founder effect theory.
History
Waren Tay and Bernard Sachs were two physicians. They described the diseases progression and provided differential diagnostic criteria to distinguish it from other neurological disorders with similar symptoms.Both Tay and Sachs reported their first cases among Ashkenazi Jewish families. Tay reported his observations in 1881 in the first volume of the proceedings of the British Ophthalmological Society, of which he was a founding member. By 1884, he had seen three cases in a single family. Years later, Bernard Sachs, an American neurologist, reported similar findings when he reported a case of "arrested cerebral development" to other New York Neurological Society members.Sachs, who recognized that the disease had a familial basis, proposed that the disease should be called amaurotic familial idiocy. However, its genetic basis was still poorly understood. Although Gregor Mendel had published his article on the genetics of peas in 1865, Mendels paper was largely forgotten for more than a generation – not rediscovered by other scientists until 1899. Thus, the Mendelian model for explaining Tay–Sachs was unavailable to scientists and doctors of the time. The first edition of the Jewish Encyclopedia, published in 12 volumes between 1901 and 1906, described what was then known about the disease:
It is a curious fact that amaurotic family idiocy, a rare and fatal disease of children, occurs mostly among Jews. The largest number of cases has been observed in the United States—over thirty in number. It was at first thought that this was an exclusively Jewish disease because most of the cases at first reported were between Russian and Polish Jews; but recently there have been reported cases occurring in non-Jewish children. The chief characteristics of the disease are progressive mental and physical enfeeblement; weakness and paralysis of all the extremities; and marasmus, associated with symmetrical changes in the macula lutea. On investigation of the reported cases, they found that neither consanguinity nor syphilitic, alcoholic, or nervous antecedents in the family history are factors in the etiology of the disease. No preventive measures have as yet been discovered, and no treatment has been of benefit, all the cases having terminated fatally.
Jewish immigration to the United States peaked in the period 1880–1924, with the immigrants arriving from Russia and countries in Eastern Europe; this was also a period of nativism (hostility to immigrants) in the United States. Opponents of immigration often questioned whether immigrants from southern and eastern Europe could be assimilated into American society. Reports of Tay–Sachs disease contributed to a perception among nativists that Jews were an inferior race.In 1969, Shintaro Okada and John S. OBrien showed that Tay–Sachs disease was caused by an enzyme defect; they also proved that Tay–Sachs patients could be diagnosed by an assay of hexosaminidase A activity. The further development of enzyme assays demonstrated that levels of hexosaminidases A and B could be measured in patients and carriers, allowing the reliable detection of heterozygotes. During the early 1970s, researchers developed protocols for newborn testing, carrier screening, and pre-natal diagnosis. By the end of 1979, researchers had identified three variant forms of GM2 gangliosidosis, including Sandhoff disease and the AB variant of GM2-gangliosidosis, accounting for false negatives in carrier testing.
Society and culture
Since carrier testing for Tay–Sachs began in 1971, millions of Ashkenazi Jews have been screened as carriers. Jewish communities embraced the cause of genetic screening from the 1970s on. The success with Tay–Sachs disease has led Israel to become the first country that offers free genetic screening and counseling for all couples and opened discussions about the proper scope of genetic testing for other disorders in Israel.Because Tay–Sachs disease was one of the first autosomal recessive genetic disorders for which there was an enzyme assay test (prior to polymerase chain reaction testing methods), it was intensely studied as a model for all such diseases, and researchers sought evidence of a selective process. A continuing controversy is whether heterozygotes (carriers) have or had a selective advantage. The presence of four different lysosomal storage disorders in the Ashkenazi Jewish population suggests a past selective advantage for heterozygous carriers of these conditions."This controversy among researchers has reflected three debates among geneticists at large:
Dominance versus overdominance. In applied genetics (selective and agricultural breeding), this controversy has reflected the century-long debate over whether dominance or overdominance provides the best explanation for heterosis (hybrid vigor).
The classical/balance controversy. The classical hypothesis of genetic variability, often associated with Hermann Muller, maintains that most genes are of a normal wild type, and that most individuals are homozygous for that wild type, while most selection is purifying selection that operates to eliminate deleterious alleles. The balancing hypothesis, often associated with Theodosius Dobzhansky, states that heterozygosity will be common at loci, and that it frequently reflects either directional selection or balancing selection.
Selectionists versus neutralists. In theoretical population genetics, selectionists emphasize the primacy of natural selection as a determinant of evolution and of variation within a population, while neutralists favor a form of Motoo Kimuras neutral theory of molecular evolution, which emphasizes the role of genetic drift.
Research directions
Enzyme replacement therapy
Enzyme replacement therapy techniques have been investigated for lysosomal storage disorders, and could potentially be used to treat Tay–Sachs as well. The goal would be to replace the nonfunctional enzyme, a process similar to insulin injections for diabetes. However, in previous studies, the HEXA enzyme itself has been thought to be too large to pass through the specialized cell layer in the blood vessels that forms the blood–brain barrier in humans.Researchers have also tried directly instilling the deficient enzyme hexosaminidase A into the cerebrospinal fluid (CSF) which bathes the brain. However, intracerebral neurons seem unable to take up this physically large molecule efficiently even when it is directly by them. Therefore, this approach to treatment of Tay–Sachs disease has also been ineffective so far.
Jacob sheep model
Tay–Sachs disease exists in Jacob sheep. The biochemical mechanism for this disease in the Jacob sheep is virtually identical to that in humans, wherein diminished activity of hexosaminidase A results in increased concentrations of GM2 ganglioside in the affected animal. Sequencing of the HEXA gene cDNA of affected Jacobs sheep reveal an identical number of nucleotides and exons as in the human HEXA gene, and 86% nucleotide sequence identity. A missense mutation (G444R) was found in the HEXA cDNA of the affected sheep. This mutation is a single nucleotide change at the end of exon 11, resulting in that exons deletion (before translation) via splicing. The Tay–Sachs model provided by the Jacob sheep is the first to offer promise as a means for gene therapy clinical trials, which may prove useful for disease treatment in humans.
Substrate reduction therapy
Other experimental methods being researched involve substrate reduction therapy, which attempts to use alternative enzymes to increase the brains catabolism of GM2 gangliosides to a point where residual degradative activity is sufficient to prevent substrate accumulation. One experiment has demonstrated that using the enzyme sialidase allows the genetic defect to be effectively bypassed, and as a consequence, GM2 gangliosides are metabolized so that their levels become almost inconsequential. If a safe pharmacological treatment can be developed – one that increases expression of lysosomal sialidase in neurons without other toxicity – then this new form of therapy could essentially cure the disease.Another metabolic therapy under investigation for Tay–Sachs disease uses miglustat. This drug is a reversible inhibitor of the enzyme glucosylceramide synthase, which catalyzes the first step in synthesizing glucose-based glycosphingolipids like GM2 ganglioside.
Increasing β-hexosaminidase A activity
As Tay–Sachs disease is a deficiency of β-hexosaminidase A, deterioration of affected individuals could be slowed or stopped through the use of a substance that increases its activity. However, since in infantile Tay–Sachs disease there is no β-hexosaminidase A, the treatment would be ineffective, but for people affected by Late-Onset Tay–Sachs disease, β-hexosaminidase A is present, so the treatment may be effective. The drug pyrimethamine has been shown to increase activity of β-hexosaminidase A. However, the increased levels of β-hexosaminidase A still fall far short of the desired "10% of normal HEXA", above which the phenotypic symptoms begin to disappear.
Cord blood transplant
This is a highly invasive procedure which involves destroying the patients blood system with chemotherapy and administering cord blood. Of five people who had received the treatment as of 2008, two were still alive after five years and they still had a great deal of health problems.Critics point to the procedures harsh nature—and the fact that it is unapproved. Other significant issues involve the difficulty in crossing the blood–brain barrier, as well as the great expense, as each unit of cord blood costs $25,000, and adult recipients need many units.
Gene therapy
On 10 February 2022, the first ever gene therapy was announced, it uses an adeno-associated virus (AAV) to deliver the correct instruction for the HEXA gene on brain cells which causes the disease. Only two children were part of a compassionate trial presenting improvements over the natural course of the disease and no vector-related adverse events.
References
External links
GeneReviews/NCBI/NIH/UW entry on hexosaminidase A deficiency, Tay–Sachs disease
NINDS Tay–Sachs Disease Information Page
Tay–Sachs disease at NLM Genetics Home Reference
Tay–Sachs on NCBI |
Congenital rubella syndrome | Congenital rubella syndrome (CRS) can occur in a developing fetus of a pregnant woman who has contracted rubella, usually in the first trimester. If infection occurs 0–28 days before conception, the infant has a 43% risk of being affected. If the infection occurs 0–12 weeks after conception, the risk increases to 81%. If the infection occurs 13–26 weeks after conception, the risk is 54% of the infant being affected by the disease. Infants are not generally affected if rubella is contracted during the third trimester, or 26–40 weeks after conception. Problems rarely occur when rubella is contracted by the mother after 20 weeks of gestation and continues to disseminate the virus after birth.
It was discovered in 1941 by Australian Norman McAlister Gregg.
Signs and symptoms
The classic triad for congenital rubella syndrome is:
Sensorineural deafness (58% of patients)
Eye abnormalities—especially retinopathy, cataract, glaucoma, and microphthalmia (43% of patients)
Congenital heart disease—especially pulmonary artery stenosis and patent ductus arteriosus (50% of patients)Other manifestations of CRS may include:
Spleen, liver, or bone marrow problems (some of which may disappear shortly after birth)
Intellectual disability
Small head size (microcephaly)
Low birth weight
Thrombocytopenic purpura
Extramedullary hematopoiesis (presents as a characteristic blueberry muffin rash)
Enlarged liver
Small jaw size
Skin lesions Children who have been exposed to rubella in the womb should also be watched closely as they age for any indication of:
Developmental delay
Autism
Schizophrenia
Growth retardation
Learning disabilities
Diabetes mellitus
Diagnosis
Prevention
Vaccinating the majority of the population is effective at preventing congenital rubella syndrome. For women who plan to become pregnant, the MMR (measles mumps, rubella) vaccination is highly recommended, at least 28 days prior to conception. The vaccine should not be given to women who are already pregnant as it contains live viral particles.Other preventative actions can include the screening and vaccinations of high-risk personnel, such as medical and child care professions.
== References == |
Balanitis | Balanitis is inflammation of the glans penis. When the foreskin is also affected, the proper term is balanoposthitis. Balanitis on boys still in diapers must be distinguished from redness caused by ammoniacal dermatitis. The word balanitis is from the Greek βάλανος balanos, literally meaning acorn, used because of the similarity in shape to the glans penis.
Signs and symptoms
Small red erosions on the glans (first sign)
Redness of the foreskin
Redness of the penis
Other rashes on the head of the penis
Foul smelling discharge
Painful foreskin and penis
Complications
Recurrent bouts of balanitis may cause scarring of the preputial orifice; the reduced elasticity may lead to pathologic phimosis. Further complications may include:
Stricture of urethral meatus
Phimosis
Paraphimosis
Cause
Inflammation has many possible causes, including irritation by environmental substances, physical trauma, and infection such as bacterial, viral, or fungal. Some of these infections are sexually transmitted diseases.
It is less common among people who are circumcised, as in many cases, a dysfunction of the foreskin is a causal or contributing factor. Both not enough cleaning and too much cleaning can cause problems. Diabetes can make balanitis more likely, especially if the blood sugar is poorly controlled.It is important to exclude other causes of similar symptoms such as penile cancer.
Diagnosis
Diagnosis may include careful identification of the cause with the aid of a good patient history, swabs and cultures, and pathological examination of a biopsy.
Types
Zoons balanitis, also known as Balanitis Circumscripta Plasmacellularis or plasma cell balanitis (PCB), is an idiopathic, rare, benign penile dermatosis for which circumcision is often the preferred treatment. Zoons balanitis has been successfully treated with the carbon dioxide laser; and more recently, Albertini and colleagues report the avoidance of circumcision and successful treatment of Zoons balanitis with an Er:YAG laser. Another study, by Retamar and colleagues, found that 40 percent of those treated with CO2 laser relapsed.
Circinate balanitis, also known as balanitis circinata, is a serpiginous annular dermatitis associated with reactive arthritis.
Pseudoepitheliomatous keratotic and micaceous balanitis
Treatment
Initial treatment in adults often involves simply pulling back the foreskin and cleaning the penis.
However, some topical antibiotic and fungal ointments may be used for treatment for mild cases.
Depending upon severity, hydrocortisone and other steroidal creams may be used upon consultation.
Epidemiology
Balanitis "is a common condition affecting 11% of adult men seen in urology clinics and 3% of children" in the United States; globally, balanitis "may occur in up to 3% of uncircumcised males".
Other animals
In dogs, balanoposthitis is caused by a disruption in the integumentary system, such as a wound or intrusion of a foreign body. A dog with this condition behaves normally, with the exception of excessive licking at the prepuce, and a yellow green, pus-like discharge is usually present.
In sheep (rams/wethers), ulcerative enzootic balanoposthitis is caused by the Corynebacterium renale group (C. renale, C. pilosum & C. cystidis).
For the condition in bulls, caused by a virus see Bovine herpesvirus 1.
Balanoposthitis is believed to have contributed to the decline to near-extinction of Gilberts potoroo.
References
Further reading
Edwards S. (for the Clinical Effectiveness Group) National guideline on the management of balanitis. Association for Genitourinary Medicine (UK) and the Medical Society for the Study of Venereal Diseases (UK), 2001.
External links
Zoons Balanitis at eMedicine
Dermatological atlas |
Scleredema | Scleredema is a rare, self-limiting skin condition defined by progressive thickening and hardening of the skin, usually on the areas of the upper back, neck, shoulders and face. The skin may also change color to red or orange. The disease was discovered by Abraham Buschke. Although the cause of scleredema is unknown, it is usually associated with a disease, usually diabetes, a viral illness or strep throat. It is usually not fatal, but it may cause death if the disease spreads to the internal organs. It may also cause an infection.
Diagnosis
The scleredema is usually proposed as a diagnosis based on the appearance of the skin and the patients medical history. To confirm the diagnosis, the doctor performs a skin biopsy, in which hematoxylin and eosin staining will show a thick reticular dermis with thick collagen bundles separated by clear spaces. The patients blood may be examined for diseases that may appear after the onset of symptoms, such as multiple myeloma.
Treatment
Although many types of medications have been tried as treatments, none of them have been proven effective in treating scleredema. Those treatments, such as corticosteroids, may benefit the patient, but will not cure their condition. If the affected area is infected, it is usually treated immediately. The symptoms of the condition usually resolve within six months to two years after onset. However, patients whose condition was associated to diabetes may suffer for longer periods of time.Myocarditis resulting as a complication from the disease has been successfully treated with penicillin and steroids.
See also
Necrobiosis lipoidica
References
== External links == |
Zygomycosis | Zygomycosis is the broadest term to refer to infections caused by bread mold fungi of the zygomycota phylum. However, because zygomycota has been identified as polyphyletic, and is not included in modern fungal classification systems, the diseases that zygomycosis can refer to are better called by their specific names: mucormycosis (after Mucorales), phycomycosis (after Phycomycetes) and basidiobolomycosis (after Basidiobolus). These rare yet serious and potentially life-threatening fungal infections usually affect the face or oropharyngeal (nose and mouth) cavity. Zygomycosis type infections are most often caused by common fungi found in soil and decaying vegetation. While most individuals are exposed to the fungi on a regular basis, those with immune disorders (immunocompromised) are more prone to fungal infection. These types of infections are also common after natural disasters, such as tornadoes or earthquakes, where people have open wounds that have become filled with soil or vegetative matter.The condition may affect the gastrointestinal tract or the skin, often beginning in the nose and paranasal sinuses. It is one of the most rapidly spreading fungal infections in humans. Treatment consists of prompt and intensive antifungal drug therapy and surgery to remove the infected tissue.
Causes
Pathogenic zygomycosis is caused by species in two orders: Mucorales or Entomophthorales, with the former causing far more disease than the latter. These diseases are known as "mucormycosis" and "entomophthoramycosis", respectively.
Order Mucorales (mucormycosis)
Family Mucoraceae
Absidia (Absidia corymbifera)
Apophysomyces (Apophysomyces elegans and Apophysomyces trapeziformis)
Mucor (Mucor indicus)
Rhizomucor (Rhizomucor pusillus)
Rhizopus (Rhizopus oryzae)
Family Cunninghamellaceae
Cunninghamella (Cunninghamella bertholletiae)
Family Thamnidiaceae
Cokeromyces (Cokeromyces recurvatus)
Family Saksenaeaceae
Saksenaea (Saksenaea vasiformis)
Family Syncephalastraceae
Syncephalastrum (Syncephalastrum racemosum)
Order Entomophthorales (entomophthoramycosis)
Family Basidiobolaceae
Basidiobolus (Basidiobolus ranarum)
Family Ancylistaceae
Conidiobolus (Conidiobolus coronatus/Conidiobolus incongruus)
Epidemiology
Zygomycosis has been found in survivors of the 2004 Indian Ocean earthquake and tsunami and in survivors of the 2011 Joplin, Missouri tornado.
Symptoms
In the primary cutaneous form, the lesions are usually painful and necrotic, with black eschar, accompanied by a fever. Patients will usually present with a history of poorly controlled diabetes or malignancy. Myocutaneous infections may lead to amputation. Pulmonary tract infections seen with lung transplant patients, who are at high risk for fatal invasive mycoses. Rhinocerebral infection is characterized by paranasal swelling with necrotic tissues. Patient may have hemorrhagic exudates (tissue fluid from lesions tinged with blood) from the nose and eyes as the fungi penetrate through blood vessels and other anatomical structures.
Diagnosis
Diagnosis is done with potassium hydroxide (KOH) preparation in tissue. On light microscopy, there will be broad, ribbon-like septate hyphae with 90 degree angles on branches. KOH wet mount of the black eschar will show aseptate fungal hyphae with right angle branching. Periodic Acid Schiff (PAS) staining will reveal similar broad hyphae in the dermis and cutis. Fungal culture can also confirm the organism. Diagnosis remains difficult due to the lack of laboratory tests as mortality remains high. In 2005, a multiplex PCR test was able to identify five species of Rhizopus and may prove useful as a screening method for visceral mucormycosis in the future.The clinical approach to diagnosis includes radiologic, where more than ten nodules and pleural effusion are associated to pulmonary forms of the disease. In CT, a reverse halo sign is noted. Direct microscopy and histopathology, and cultures remain the gold standards for diagnoses. Zygomycophyta share close clinical and radiological features to Aspergillosis. Invasive procedures such as bronchial endoscopy and lung biopsy may be necessary to confirm pulmonary diagnosis are no validated indirect tests are available. Quantitative polymerase chain reaction to detect serum DNA of the pathogen shows promise.
Treatment
The condition may affect the gastrointestinal tract or the skin In non-trauma cases, it usually begins in the nose and paranasal sinuses and is one of the most rapidly spreading fungal infections in humans. Common symptoms include thrombosis and tissue necrosis.Due to the organisms rapid growth and invasion, zygomycosis presents with a high fatality rate. Treatment must begin immediately with debridement of the necrotic tissue plus Amphotericin B. Complete excision of the infectious tissue may be required as suspected dead tissue must be excised aggressively. Documented case of conservative surgical drainage, intravenous amphotericin B in an insulin-dependent diabetic have proven effective in sino-orbital infection. The prognosis varies vastly depending upon an individual patients circumstances.
Other animals
The term oomycosis is used to describe oomycete infections. These are more common in animals, notably dogs and horses. These are heterokonts, not true fungi. Types include pythiosis (caused by Pythium insidiosum) and lagenidiosis.
Zygomycosis has been described in a cat, where fungal infection of the tracheobronchus led to respiratory disease requiring euthanasia.
References
== External links == |
Diethylstilbestrol | Diethylstilbestrol (DES), also known as stilbestrol or stilboestrol, is a nonsteroidal estrogen medication, which is presently rarely used. In the past, it was widely used for a variety of indications, including pregnancy support for women with a history of recurrent miscarriage, hormone therapy for menopausal symptoms and estrogen deficiency in women, treatment of prostate cancer in men and breast cancer in women, and other uses. By 2007, it was only used in the treatment of prostate cancer and breast cancer. In 2011, Hoover and colleagues reported on adverse health outcomes linked to DES including infertility, miscarriage, ectopic pregnancy, preeclampsia, preterm birth, stillbirth, infant death, menopause prior to age 45, breast cancer, cervical cancer, and vaginal cancer. While most commonly taken by mouth, DES was available for use by other routes as well, for instance, vaginal, topical, and by injection.
DES is an estrogen, or an agonist of the estrogen receptors, the biological target of estrogens like estradiol. It is a synthetic and nonsteroidal estrogen of the stilbestrol group, and differs from the natural estrogen estradiol in various ways. Compared to estradiol, DES has greatly improved bioavailability when taken by mouth, is more resistant to metabolism, and shows relatively increased effects in certain parts of the body like the liver and uterus. These differences result in DES having an increased risk of blood clots, cardiovascular issues, and certain other adverse effects.DES was discovered in 1938 and introduced for medical use in 1939. From about 1940 to 1971, the medication was given to pregnant women in the incorrect belief that it would reduce the risk of pregnancy complications and losses. In 1971, DES was shown to cause clear-cell carcinoma, a rare vaginal tumor, in girls and women who had been exposed to this medication in utero. The United States Food and Drug Administration subsequently withdrew approval of DES as a treatment for pregnant women. Follow-up studies have indicated that DES also has the potential to cause a variety of significant adverse medical complications during the lifetimes of those exposed.The United States National Cancer Institute recommends women born to mothers who took DES to undergo special medical exams on a regular basis to screen for complications as a result of the medication. Individuals who were exposed to DES during their mothers pregnancies are commonly referred to as "DES daughters" and "DES sons". Since the discovery of the toxic effects of DES, it has largely been discontinued and is now mostly no longer marketed.
Medical uses
DES has been used in the past for the following indications:
Recurrent miscarriage in pregnancy
Menopausal hormone therapy for the treatment of menopausal symptoms such as hot flashes and vaginal atrophy
Hormone therapy for hypoestrogenism (e.g., gonadal dysgenesis, premature ovarian failure, and after oophorectomy)
Postpartum lactation suppression to prevent or reverse breast engorgement
Gonorrheal vaginitis (discontinued following the introduction of the antibiotic penicillin)
Prostate cancer and breast cancer
Prevention of tall stature in tall adolescent girls
Treatment of acne in girls and women
As an emergency postcoital contraceptive
As a means of chemical castration for hypersexuality and paraphilias in men and sex offenders
Prevention of the testosterone flare at the start of gonadotropin-releasing hormone agonist (GnRH agonist) therapy
Feminizing hormone therapy for transgender womenDES was used at a dosage of 0.2 to 0.5 mg/day in menopausal hormone therapy.Interest in the use of DES to treat prostate cancer in men continues today. However, use of bioidentical parenteral estrogens like polyestradiol phosphate has been advocated in favor of oral synthetic estrogens like DES due to their much lower risk of cardiovascular toxicity. In addition to prostate cancer, some interest in the use of DES to treat breast cancer in women continues today as well. However, similarly to the case of prostate cancer, arguments have been made for the use of bioidentical estrogens like estradiol instead of DES for breast cancer.Oral DES at 0.25 to 0.5 mg/day is effective in the treatment of hot flashes in men undergoing androgen deprivation therapy for prostate cancer.Although DES was used to support pregnancy, it was later found not to be effective for this use.
Side effects
At more than 1 mg/day, DES is associated with high rates of side effects including nausea, vomiting, abdominal discomfort, headache, and bloating (incidence of 15–50%).
Breast changes and feminization
The pigmentation of the breast areolae are often very dark and almost black with DES therapy. The pigmentation that occurs with synthetic estrogens such as DES is much greater than with natural estrogens such as estradiol. The mechanism of the difference is unknown. Progestogens like hydroxyprogesterone caproate have been reported to reduce the nipple hyperpigmentation induced by high-dose estrogen therapy.In men treated with it for prostate cancer, DES has been found to produce high rates of gynecomastia (breast development) of 41 to 77%.
Blood clots and cardiovascular issues
In studies of DES as a form of high-dose estrogen therapy for men with prostate cancer, it has been associated with considerable cardiovascular morbidity and mortality. The risk is dose-dependent. A dosage of 5 mg/day DES has been associated with a 36% increase in non-cancer-related (mostly cardiovascular) deaths. In addition, there is an up to 15% incidence of venous thromboembolism. A 3 mg/day dosage of DES has been associated with an incidence of thromboembolism of 9.6 to 17%, with an incidence of cardiovascular complications of 33.3%. A lower dosage of 1 mg/day DES has been associated with a rate of death due to cardiovascular events of 14.8% (relative to 8.3% for orchiectomy alone).
Other long-term effects
DES has been linked to a variety of long-term adverse effects, such as increased risk of
vaginal clear-cell adenocarcinoma
vaginal adenosis
T-shaped uterus
uterine fibroids
cervical weakness
breast cancer
infertility
hypogonadism
intersexual gestational defects
depression,
and others,in women who were treated with it during pregnancy, and/or in their offspring.A comprehensive animal study in 1993 found a plethora of adverse effects from DES such as (but not limited to)
genotoxicity (due to quinone metabolite)
teratogenicity
penile and testicular hypoplasia
cryptorchidism (in rats and rhesus monkeys),
liver and renal cancer (in hamsters), ovarian papillary carcinoma (in canines), and
malignant uterine mesothelioma (in squirrel monkeys). Evidence was also found linking ADHD to F2 generations, demonstrating that there is at least some neurological and transgenerational effects in addition to the carcinogenic.Rodent studies reveal female reproductive tract cancers and abnormalities reaching to the F2 generation, and there is evidence of adverse effects such as irregular menstrual cycles intersexual in grandchildren of DES mothers. Additionally, evidence also points to transgenerational effects in F2 sons, such as hypospadias.
At this time however, the extent of DES transgenerational effects in humans is not fully understood.
Overdose
DES has been assessed in the past in clinical studies at extremely high doses of as much as 1,500 to 5,000 mg/day.
Pharmacology
Pharmacodynamics
Estrogenic activity
DES is an estrogen; specifically, it is a highly potent full agonist of both of the estrogen receptors (ERs). It has approximately 468% and 295% of the affinity of estradiol at the ERα and ERβ, respectively. However, EC50 values of 0.18 nM and 0.06 nM of DES for the ERα and ERβ, respectively, have been reported, suggesting, in spite of its binding affinity for the two receptors, several-fold preference for activation of the ERβ over the ERα. In addition to the nuclear ERs, DES is an agonist of the G protein-coupled estrogen receptor (GPER), albeit with relatively low affinity (~1,000 nM). DES produces all of the same biological effects attributed to natural estrogens like estradiol. This includes effects in the uterus, vagina, mammary glands, pituitary gland, and other tissues.A dosage of 1 mg/day DES is approximately equivalent to a dosage of 50 µg/day ethinylestradiol in terms of systemic estrogenic potency. Similarly to ethinylestradiol, DES shows a marked and disproportionately strong effect on liver protein synthesis. Whereas its systemic estrogenic potency was about 3.8-fold of that of estropipate (piperazine estrone sulfate), which has similar potency to micronized estradiol, the hepatic estrogenic potency of DES was 28-fold that of estropipate (or about 7.5-fold stronger potency for a dosage with equivalent systemic estrogenic effect).DES has at least three mechanisms of action in the treatment of prostate cancer in men. It suppresses gonadal androgen production and hence circulating androgen levels due to its antigonadotropic effects; it stimulates hepatic sex hormone-binding globulin (SHBG) production, thereby increasing circulating levels of SHBG and decreasing the free fraction of testosterone and dihydrotestosterone (DHT) in the circulation; and it may have direct cytotoxic effects in the testes and prostate gland. DES has also been found to decrease DNA synthesis at high doses.DES is a long-acting estrogen, with a nuclear retention of around 24 hours.
Antigonadotropic effects
Due to its estrogenic activity, DES has antigonadotropic effects. That is, it exerts negative feedback on the hypothalamic–pituitary–gonadal axis (HPG axis), suppresses the secretion of the gonadotropins, luteinizing hormone (LH) and follicle-stimulating hormone (FSH), and suppresses sex hormone production as well as gamete production or maturation in the gonads. A study of ovulation inhibition in women found that 5 mg/day oral DES was 92% effective, with ovulation occurring in only a single cycle. DES consistently suppresses testosterone levels in men into the castrate range (<50 ng/dL) within 1 to 2 weeks at doses of 3 mg/day and above. Conversely, a dosage of 1 mg/day DES is unable to fully suppress testosterone levels into the castrate range in men, which instead often stabilize at just above castrate levels (>50 ng/dL). However, it has also been reported that 1 mg/day DES results in approximately 50% suppression of testosterone levels, albeit with wide interindividual variability. It has been said that doses of DES of less than 1 mg/day have no effect on testosterone levels. However, the addition of an "extremely low" dosage of 0.1 mg/day DES to cyproterone acetate has been found to result in a synergistic antigonadotropic effect and to suppress testosterone levels into the castrate range in men. DES at 3 mg/day has similar testosterone suppression to a dose of 300 mg/day, suggesting that suppression of testosterone levels is maximal by 3 mg/day.
Other activities
In addition to the ERs, an in vitro study found that DES also possesses activity, albeit relatively weak, at a variety of other steroid hormone receptors. Whereas the study found EC50 values of 0.18 nM and 0.06 nM of DES for the ERα and ERβ, respectively, the medication showed significant glucocorticoid activity at a concentration of 1 μM that surpassed that of 0.1 nM dexamethasone, as well as significant antagonism of the androgen, progesterone, and mineralocorticoid receptors (75%, 85%, and 50% inhibition of positive control stimulation, respectively, all at a concentration of 1 μM). It also showed approximately 25% inhibition of the activation of PPARγ and LXRα at a concentration of 10 μM. The researchers stated that, to the best of their knowledge, they were the first to report such actions of DES, and hypothesized that these actions could be involved in the clinical effects of DES, for instance, in prostate cancer (notably in which particularly high dosages of DES are employed). However, they also noted that the importance of the activities requires further study in animal models at pharmacologically relevant doses.DES has been identified as an antagonist of all three isotypes of the estrogen-related receptors (ERRs), the ERRα, ERRβ, and ERRγ. Half-maximal inhibition occurs at a concentration of about 1 μM.
Pharmacokinetics
DES is well-absorbed with oral administration. With an oral dosage of 1 mg/day DES, plasma levels of DES at 20 hours following the last dose ranged between 0.9 and 1.9 ng/mL (3.4 to 7.1 nmol/L). Sublingual administration of DES appears to have about the same estrogenic potency of oral DES in women. Intrauterine DES has been studied for the treatment of uterine hypoplasia. Oral DES is thought to have about 17 to 50% of the clinical estrogenic potency of DES by injection.The distribution half-life of DES is 80 minutes. It has no affinity for SHBG or corticosteroid-binding globulin, and hence is not bound to these proteins in the circulation. The plasma protein binding of DES is greater than 95%.Hydroxylation of the aromatic rings of DES and subsequent conjugation of the ethyl side chains accounts for 80 to 90% of DES metabolism, while oxidation accounts for the remaining 10 to 20% and is dominated by conjugation reactions. Conjugation of DES consists of glucuronidation, while oxidation includes dehydrogenation into (Z,Z)-dienestrol. The medication is also known to produce paroxypropione as a metabolite. DES produces transient quinone-like reactive intermediates that cause cellular and genetic damage, which may help to explain the known carcinogenic effects of DES in humans. However, other research indicates that the toxic effects of DES may simply be due to overactivation of the ERs. In contrast to estradiol, the hydroxyl groups of DES do not undergo oxidation into an estrone-like equivalent.The elimination half-life of DES is 24 hours. The metabolites of DES are excreted in urine and feces.
Chemistry
DES belongs to the stilbestrol (4,4-dihydroxystilbene) group of compounds. It is a nonsteroidal open-ring analogue of the steroidal estrogen estradiol. DES can be prepared from anethole, which also happens to be weakly estrogenic. Anethole was demethylated to form anol and anol then spontaneously dimerized into dianol and hexestrol, with DES subsequently being synthesized via structural modification of hexestrol. As shown by X-ray crystallography, the molecular dimensions of DES are almost identical to those of estradiol, particularly in regards to the distance between the terminal hydroxyl groups.
History
Synthesis
DES was first synthesized in early 1938 by Leon Golberg, then a graduate student of Sir Robert Robinson at the Dyson Perrins Laboratory at the University of Oxford. Golbergs research was based on work by Wilfrid Lawson at the Courtauld Institute of Biochemistry, (led by Sir Edward Charles Dodds at Middlesex Hospital Medical School now part of University College London). A report of its synthesis was published in Nature on 5 February 1938.DES research was funded by the UK Medical Research Council (MRC), which had a policy against patenting drugs discovered using public funds. Because it was not patented, DES was produced by more than 200 pharmaceutical and chemical companies worldwide.
Clinical use
DES was first marketed for medical use in 1939. It was approved by the United States Food and Drug Administration (FDA) on September 19, 1941, in tablets up to 5 mg for four indications: gonorrheal vaginitis, atrophic vaginitis, menopausal symptoms, and postpartum lactation suppression to prevent breast engorgement. The gonorrheal vaginitis indication was dropped when the antibiotic penicillin became available. From its very inception, the drug was highly controversial.In 1941, Charles Huggins and Clarence Hodges at the University of Chicago found estradiol benzoate and DES to be the first effective drugs for the treatment of metastatic prostate cancer. DES was the first cancer drug.Orchiectomy or DES or both were the standard initial treatment for symptomatic advanced prostate cancer for over 40 years, until the GnRH agonist leuprorelin was found to have efficacy similar to DES without estrogenic effects and was approved in 1985.From the 1940s until the late 1980s, DES was FDA-approved as estrogen replacement therapy for estrogen deficiency states such as ovarian dysgenesis, premature ovarian failure, and after oophorectomy.
In the 1940s, DES was used off-label to prevent adverse pregnancy outcomes in women with a history of miscarriage. On July 1, 1947, the FDA approved the use of DES for this indication. The first such approval was granted to Bristol-Myers Squibb, allowing use of 25 mg (and later 100 mg) tablets of DES during pregnancy. Approvals were granted to other pharmaceutical companies later in the same year. The recommended regimen started at 5 mg per day in the seventh and eighth weeks of pregnancy (from first day of last menstrual period), increased every other week by 5 mg per day through the 14th week, and then increased every week by 5 mg per day from 25 mg per day in the 15th week to 125 mg per day in the 35th week of pregnancy.
DES was originally considered effective and safe for both the pregnant woman and the developing baby. It was aggressively marketed and routinely prescribed. Sales peaked in 1953.
In the early 1950s, a double-blind clinical trial at the University of Chicago assessed pregnancy outcomes in women who were assigned to either receive or not receive DES. The study showed no benefit of taking DES during pregnancy; adverse pregnancy outcomes were not reduced in the women who were given DES. By the late 1960s, six of seven leading textbooks of obstetrics said DES was ineffective at preventing miscarriage.Despite an absence of evidence supporting the use of DES to prevent adverse pregnancy outcomes, DES continued to be given to pregnant women through the 1960s. In 1971, a report published in the New England Journal of Medicine showed a probable link between DES and vaginal clear cell adenocarcinoma in girls and young women who had been exposed to this drug in utero. Later in the same year, the FDA sent an FDA Drug Bulletin to all U.S. physicians advising against the use of DES in pregnant women. The FDA also removed prevention of miscarriage as an indication for DES use and added pregnancy as a contraindication for DES use. On February 5, 1975, the FDA ordered 25 mg and 100 mg tablets of DES withdrawn, effective February 18, 1975. The number of persons exposed to DES during pregnancy or in utero during the period of 1940 to 1971 is unknown, but may be as high as 2 million in the United States. DES was also used in other countries, most notably France, the Netherlands, and Great Britain.
From the 1950s through the beginning of the 1970s, DES was prescribed to prepubescent girls to begin puberty and thus stop growth by closing growth plates in the bones. Despite its clear link to cancer, doctors continued to recommend the hormone for "excess height".In 1960, DES was found to be more effective than androgens in the treatment of advanced breast cancer in postmenopausal women. DES was the hormonal treatment of choice for advanced breast cancer in postmenopausal women until 1977, when the FDA approved tamoxifen, a selective estrogen receptor modulator with efficacy similar to DES but fewer side effects.Several sources from medical literature in the 1970s and 1980s indicate that DES was used as a component of hormone therapy for transgender women.In 1973, in an attempt to restrict off-label use of DES as a postcoital contraceptive (which had become prevalent at many university health services following publication of an influential study in 1971 in JAMA) to emergency situations such as rape, an FDA Drug Bulletin was sent to all U.S. physicians and pharmacists that said the FDA had approved, under restricted conditions, postcoital contraceptive use of DES.In 1975, the FDA said it had not actually given (and never did give) approval to any manufacturer to market DES as a postcoital contraceptive, but would approve that indication for emergency situations such as rape or incest if a manufacturer provided patient labeling and special packaging as set out in a FDA final rule published in 1975. To discourage off-label use of DES as a postcoital contraceptive, the FDA in 1975 removed DES 25 mg tablets from the market and ordered the labeling of lower doses (5 mg and lower) of DES still approved for other indications changed to state: "This drug product should not be used as a postcoital contraceptive" in block capital letters on the first line of the physician prescribing information package insert and in a prominent and conspicuous location of the container and carton label. In the 1980s, off-label use of the Yuzpe regimen of certain regular combined oral contraceptive pills superseded off-label use of DES as a postcoital contraceptive.In 1978, the FDA removed postpartum lactation suppression to prevent breast engorgement from their approved indications for DES and other estrogens. In the 1990s, the only approved indications for DES were treatment of advanced prostate cancer and treatment of advanced breast cancer in postmenopausal women. The last remaining U.S. manufacturer of DES, Eli Lilly, stopped making and marketing it in 1997.
Trials
Diethylstilbestrol has been used countless times in studies on rats. Once it was discovered that DES was causing vaginal cancer, experiments began on both male and female rats. Many of these male rats were injected with DES while other male rats were injected with olive oil, and they were considered the control group. Each group received the same dosage on the same days, and the researchers performed light microscopy, electron microscopy, and confocal laser microscopy. With both the electron and confocal laser microscopy, it was prevalent that the Sertoli cells, which is a somatic cell where spermatids develop in the testes, was formed thirty-six years later in the rats who were injected with Diethylstilbestrol compared to the rats in the control group. Proceeding the completion of the trial, it was understood that rats of older age who were injected with DES experienced delay in sertoli cell maturation, underdeveloped epididymides, and drastic decrease in weight compared to its counterparts.The female rats used were inbred and most of them were given DES combined in their food. These rats were divided into three groups, one group who received no diethylstilbestrol, one group who had DES mixed into their diet, and the third group who had DES administered into their diet after day 13 of being pregnant. Some rats who were given DES unfortunately died before delivering their pup. The group that received DES in their food for 13 days while being pregnant resulted in early abortion and delivery failure. These outcomes showed that DES had a detrimental effect on pregnancy when administered as often as it was. Providing the dosing of diethylstilbestrol later in the pregnancy term also made visible the occurrence of abortions among the rats. Overall, any interaction with DES in female rats concluded in the rats experiencing abortions, improper fetal growth, and the increase in sterility.A review of people who had been treated or exposed to DES was done to find out how long-term effects would show. People for a long time had been treated during their pregnancy with DES and there have been known to be toxic and adverse effects to the hormone therapy. "Exposure to DES has been associated with an increased risk for breast cancer in DES mothers (relative risk, <2.0) and with a lifetime risk of clear-cell cervicovaginal cancer in DES daughters of 1/1000 to 1/10 000." Side effects of DES are proving to be long-term as it can cause increased risks to cancer after use. There will be continued work to see how far the adverse effects of DES will go after previous therapy as many women had used this during pregnancy and there is a long line to see how it will effect offspring and the mothers longer-term.
Regulations
In 1938, the ability to test the safety of DES on animals was first obtained by the FDA. The results from the preliminary tests showed that DES harmed the reproductive systems of animals. The application of these results to humans could not be determined, so the FDA could not act in a regulatory manner.New Drug Applications for DES approval were withdrawn in 1940 in a decision made by the FDA based on scientific uncertainty. However, this decision resulted in significant political pressure, so the FDA came to a compromise. The compromise meant that DES would be available only by prescription and would have to have warnings about its effects on the bottle, but the warning was dropped in 1945. In 1947, DES finally gained FDA approval for prescription to pregnant women who had diabetes as a method of preventing miscarriages. This led to the widespread prescription of DES to all pregnant women.In 1971, the FDA recommended against the prescription of DES to pregnant women. As a result, DES then began to see a withdraw from the US market starting in 1972 and in the European market starting in 1978, but the FDA still did not withdraw its approval for the use of DES in humans.DES was classified as a Group 1 carcinogen by the International Agency for Research on Cancer. After classification as a carcinogen, DES had its FDA approval withdrawn in 2000. DES is currently only in use for veterinary practices and in research trials as allowed by the FDA.Medical Ethics
Medical Ethics in regard to the approval and use of Diethylstilbestrol have been dismissed because of the actions of the FDA and pharmaceutical companies that were making DES at the time of its use. The Vice President of the American Drug Manufacturers Association, Carson Frailey, was employed by drug companies creating DES in order to help get it approved by the Food and Drug Administration (FDA). Nancy Langston, the author of The Retreat from Precaution: Regulating Diethylstilbestrol (DES), Endocrine Disruptors, and Environmental Health, states that "Frailey persuaded fifty-four doctors from around the country to write to the FDA, describing their clinical experiences with a total of more than five thousand patients. Only four of these fifty-four doctors felt that DES should not be approved, and the result was that, against the concerns of many of the FDA medical staff, the FDAs drug chief Theodore Klumpp recommended that the FDA approve DES." This excerpt describes how DES was unethically approved and shows that the motivation behind its approval was for the benefit of drug companies rather than the people who were going to use the drug. This approval of DES violates the values of medical ethics, autonomy, non-maleficence, beneficence, and justice as there was little thought put into how DES would affect its users. The decisions made by the FDA leaders to approve DES without further study and convince doctors to dissimulate their opinions on the use of DES is unethical. Once DES was approved for public consumption the "warnings [for DES were] made available only on a separate circular that patients would not see. Doctors could get this warning circular only by writing to the drug companies and requesting it. Letters between companies and FDA regulators reveal that both groups feared that if a woman ever saw how many potential risks DES might present, she might refuse to take the drug—or else she might sue the company and the prescribing doctors if she did get cancer or liver damage after taking the drug." Women were not informed about the possible effects of DES because doctors and FDA regulators were afraid DES would fail |
Diethylstilbestrol | and never be approved costing the drug companies millions of dollars. The act of distributing potentially dangerous medicine to patients regardless of the affect and harm it may do solely for monetary gain is unethical.
Lawsuits
In the 1970s, the negative publicity surrounding the discovery of DESs long-term effects resulted in a huge wave of lawsuits in the United States against its manufacturers. These culminated in a landmark 1980 decision of the Supreme Court of California, Sindell v. Abbott Laboratories, in which the court imposed a rebuttable presumption of market share liability upon all DES manufacturers, proportional to their share of the market at the time the drug was consumed by the mother of a particular plaintiff.
Eli Lilly, a pharmaceutical company manufacturing DES, and the University of Chicago, had an action filed against them in regard to clinical trials from the 1950s. Three women filed the claim that their daughters had developments of abnormal cervical cellular formations as well as reproductive abnormalities in themselves and their sons. The plaintiffs had asked the courts to certify their case as a class action but were declined by the courts. However, the courts issued an opinion that their case had merit. The court held that Eli Lilly had a duty to notify about the risks of DES once they became aware of them or should have become aware of them. Under Illinois tort law, for the plaintiffs to recover under theories of breach of duty to warn and strict liability, the plaintiffs must have alleged injury to themselves. Ultimately, under their claims of breach of duty to warn and strict liability due to the plaintiffs citing risk of physical injury to others, not physical injury to themselves, the case was dismissed by the courts. Although the case was not certified as class action and their claims of breach of duty to warn and strict liability was dismissed, the courts did not dismiss the battery allegations. The issue was then to determine whether the University of Chicago had committed battery against these women but the case was settled before trial. Part of the settlement agreement for this case, Mink v. University of Chicago, attorneys for the plaintiffs negotiated for the university to provide free medical exams for all offspring exposed to DES in utero during the 1950 experiments as well as treat the daughters of any women involved who develop DES-associated vaginal or cervical cancer.As of February 1991, there were over a thousand pending legal actions against DES manufacturers. There are over 300 companies that manufactured DES according to the same formula and the largest barrier to recovery is determining which manufacturer supplied the drug in each particular case. Many of the successful cases have relied on joint or several parties holding liability.
A lawsuit was filed in Boston Federal Court by 53 DES daughters who say their breast cancers were the result of DES being prescribed to their mothers while pregnant with them. Their cases survived a Daubert hearing. In 2013, the Fecho sisters who initiated the breast cancer/DES link litigation agreed to an undisclosed settlement amount on the second day of trial. The remaining litigants have received various settlements.The advocacy group DES Action USA helped provide information and support for DES-exposed persons engaged in lawsuits.
Society and culture
Alan Turing, the ground-breaking cryptographer, founder of computing science and programmable computers, who also proposed the actual theoretical model of biological morphogenesis, was forced onto this medication to induce chemical castration as a punitive and discredited "treatment" for homosexual behaviour, shortly before he died in ambiguous circumstances.James Herriot describes a case regarding treating a small dogs testicular Sertoli cell tumor in his 1974 book All Things Bright and Beautiful. Herriot decided to prescribe a high dose of the new drug Stilboestrol for the recurring tumor, with the amusing side effect that the male dog became "attractive to other male dogs", who followed the terrier around the village for a few weeks. Herriot comments in the story that he knew "The new drug was said to have a feminising effect, but surely not to that extent."
Veterinary use
Canine incontinence
DES has been very successful in treating female canine incontinence stemming from poor sphincter control. It is still available from compounding pharmacies, and at the low (1 mg) dose, does not have the carcinogenic properties that were so problematic in humans. It is generally administered once a day for seven to ten days and then once every week as needed.
Livestock growth promotion
The greatest usage of DES was in the livestock industry, used to improve feed conversion in beef and poultry. During the 1960s, DES was used as a growth hormone in the beef and poultry industries. It was later found to cause cancer by 1971, but was not phased out until 1979. Although DES was discovered to be harmful to humans, its veterinary use was not immediately halted. As of 2011, DES was still being used as a growth promoter in terrestrial livestock or fish in some parts of the world including China.
References
Further reading
External links
Diethylstilbestrol (DES) and Cancer National Cancer Institute
DES Update from the U.S. Centers for Disease Control and Prevention
DES Action USA national consumer organization providing comprehensive information for DES-exposed individuals
DES Booklets from the U.S. National Institutes of Health (c. 1980)
DES Follow-up Study National Cancer Institutes longterm study of DES-exposed persons (including the DES-AD Project)
University of Chicago DES Registry of patients with CCA (clear cell adenocarcinoma) of the vagina and/or cervix
DES Diethylstilbestrol Provides resources and social media links for general DES awareness |
Hereditary pyropoikilocytosis | Hereditary pyropoikilocytosis (HPP) is an autosomal recessive form of hemolytic anemia characterized by an abnormal sensitivity of red blood cells to heat and erythrocyte morphology similar to that seen in thermal burns or from prolonged exposure of a healthy patients blood sample to high ambient temperatures. Patients with HPP tend to experience severe hemolysis and anemia in infancy that gradually improves, evolving toward typical elliptocytosis later in life. However, the hemolysis can lead to rapid sequestration and destruction of red cells. Splenectomy is curative when this occurs.
HPP has been associated with a defect of the erythrocyte membrane protein spectrin and with spectrin deficiency. It was characterized in 1975. It is considered a severe form of hereditary elliptocytosis.
Causes
Mutations of the alphaspectrin gene causes this disease.
HPP can be considered as a subset of hereditary elliptocytosis.
Diagnosis
Genetic testing for the presence of mutations in protein molecules is considered to be a confirmatory testing technique. It is important to know the risks regarding the transmission and dangers of HPP.
Treatment
Splenectomy is a possible treatment
See also
Erythrocyte
Poikilocytosis
List of hematologic conditions
References
== External links == |
Exercise-induced bronchoconstriction | Exercise-induced asthma, or E.I.A., occurs when the airways narrow as a result of exercise. The preferred term for this condition is exercise-induced bronchoconstriction (EIB). While exercise does not cause asthma, it is frequently an asthma trigger.It might be expected that people with E.I.B. would present with shortness of breath, and/or an elevated respiratory rate and wheezing, consistent with an asthma attack. However, many will present with decreased stamina, or difficulty in recovering from exertion compared to team members, or paroxysmal coughing from an irritable airway. Similarly, examination may reveal wheezing and prolonged expiratory phase, or may be quite normal. Consequently, a potential for under-diagnosis exists. Measurement of airflow, such as peak expiratory flow rates, which can be done inexpensively on the track or sideline, may prove helpful. In athletes, symptoms of bronchospasm such as chest discomfort, breathlessness, and fatigue are often falsely attributed to the individual being “out of shape”, having asthma, or possessing a hyperreactive airway rather than E.I.B.
Cause
While the potential triggering events for E.I.B. are well recognized, the underlying pathogenesis is poorly understood. It usually occurs after at least several minutes of vigorous, aerobic activity, which increases oxygen demand to the point where breathing through the nose (nasal breathing) must be supplemented by mouth breathing. The resultant inhalation of air that has not been warmed and humidified by the nasal passages seems to generate increased blood flow to the linings of the bronchial tree, resulting in edema. Constriction of these small airways then follows, worsening the degree of obstruction to airflow. There is increasing evidence that the smooth muscle that lines the airways becomes progressively more sensitive to changes that occur as a result of injury to the airways from dehydration. The chemical mediators that provoke the muscle spasm appear to arise from mast cells.
Diagnosis
Exercise-induced bronchoconstriction can be difficult to diagnose clinically given the lack of specific symptoms and frequent misinterpretation as manifestations of vigorous exercise. There are many mimics that present with similar symptoms, such as vocal cord dysfunction, cardiac arrhythmias, cardiomyopathies, and gastroesophageal reflux disease. It is also important to distinguish those who have asthma with exercise worsening, and who consequently will have abnormal testing at rest, from true exercise-induced bronchoconstriction, where there will be normal baseline results. Because of the wide differential diagnosis of exertional respiratory complaints, the diagnosis of exercise-induced bronchoconstriction based on history and self-reported symptoms alone has been shown to be inaccurate and will result in an incorrect diagnosis more than 50% of the time. An important and often over-looked differential diagnosis is exercise-induced laryngeal obstruction EILO. The latter can co-exist with EIB and is best differentiated using objective testing and continuous laryngoscopy during exercise (CLE) testing.
Spirometry
Objective testing should begin with spirometry at rest. In true exercise-induced bronchoconstriction, the results should be within normal limits. Should resting values be abnormal, then asthma, or some other chronic lung condition, is present. There is, of course, no reason why asthma and exercise-induced bronchoconstriction should not co-exist but the distinction is important because without successful treatment of underlying asthma, treatment of an exercise component will likely be unsuccessful. If baseline testing is normal, some form of exercise or pharmacologic stress will be required, either on the sideline or practice venue, or in the laboratory.
Exercise testing
Treadmill or ergometer-based testing in lung function laboratories are effective methods for diagnosing exercise-induced bronchoconstriction, but may result in false negatives if the exercise stimulus is not intense enough.
Field-exercise challenge
Field-exercise challenge tests that involve the athlete performing the sport in which they are normally involved and assessing FEV1 after exercise are helpful if abnormal but have been shown to be less sensitive than eucapnic voluntary hyperventilation.
Eucapnic voluntary hyperventilation challenge
The International Olympic Committee recommends the eucapnic voluntary hyperventilation (EVH) challenge as the test to document exercise-induced asthma in Olympic athletes. In the EVH challenge, the patient voluntarily, without exercising, rapidly breathes dry air enriched with 5% CO2 for six minutes. The presence of the enriched CO2 compensates for the CO2 losses in the expired air, not matched by metabolic production, that occurs during hyperventilation, and so maintains CO2 levels at normal.
Medication challenge
Medication challenge tests, such as the methacholine challenge test, have a lower sensitivity for detection of exercise-induced bronchoconstriction in athletes and are also not a recommended first-line approach in the evaluation of exercise-induced asthma.Mannitol inhalation has been recently approved for use in the United States.
A relatively recent review of the literature has concluded that there is currently insufficient available evidence to conclude that either mannitol inhalation or eucapnic voluntary hyperventilation are suitable alternatives to exercise challenge testing to detect exercise-induced bronchoconstriction and that additional research is required.
Treatment
Lifestyle
The best treatment is avoidance of conditions predisposing to attacks, when possible. In athletes who wish to continue their sport or do so in adverse conditions, preventive measures include altered training techniques and medications.
Some take advantage of the refractory period by precipitating an attack by "warming up," and then timing competition such that it occurs during the refractory period. Step-wise training works in a similar fashion. Warm up occurs in stages of increasing intensity, using the refractory period generated by each stage to reach a full workload.
Medication
There is no evidence supporting different treatment for EIB in asthmatic athletes and nonathletes. The most common medication used is a beta agonist taken about 20 minutes before exercise. Some physicians prescribe inhaled anti-inflammatory mists such as corticosteroids or leukotriene antagonists, and mast cell stabilizers have also proven effective.In May 2013, the American Thoracic Society issued the first treatment guidelines for EIB, recommending use of "a short-acting β2-agonist before exercise in all patients with EIB. For patients who continue to have symptoms of EIB despite the administration of a short-acting β2-agonist before exercise, strong recommendations were made for a daily inhaled corticosteroid, a daily leukotriene receptor antagonist, or a mast cell stabilizing agent before exercise."
Research
A crossover study compared oral montelukast with inhaled salmeterol, both given two hours before exercise, showing that the drugs had similar benefit.A meta-analysis of preliminary research indicated that vitamin C may be useful to relieve respiratory symptoms such as cough during exercise.
Prognosis
As evidenced by many professional athletes who have overcome EIB using some combination of accepted treatments, the prognosis is usually very good. Olympic swimmers Tom Dolan, Amy Van Dyken, and Nancy Hogshead, Olympic track star Jackie Joyner-Kersee, baseball Hall of Famer Catfish Hunter, and American football player Jerome Bettis are among the many who have done so. Tour de France winner Chris Froome reported that he suffers from the condition, after being spotted using a nasal inhaler during race. Other athletes with EIB include racing cyclist Simon Yates, distance runner Paula Radcliffe and cross-country skier Marit Bjørgen. Research by sports scientist John Dickinson found that 70 percent of UK-based members of the British swimming team had some form of asthma, as did a third of Team Sky cyclists, compared to a national asthma rate of eight to ten percent, whilst a study by the United States Olympic Committee in 2000 found that half of cross-country skiers had EIB.
References
External links
"Tips to Remember: Exercise-induced asthma". American Academy of Allergy, Asthma, and Immunology. Retrieved 2007-04-12.
Fact sheet: Exercise-induced asthma |
Central pontine myelinolysis | Central pontine myelinolysis is a neurological condition involving severe damage to the myelin sheath of nerve cells in the pons (an area of the brainstem). It is predominately iatrogenic (treatment-induced), and is characterized by acute paralysis, dysphagia (difficulty swallowing), dysarthria (difficulty speaking), and other neurological symptoms.
Central pontine myelinolysis was first described as a disorder in 1959. The original paper described four cases with fatal outcomes, and the findings on autopsy. The disease was described as a disease of alcoholics and malnutrition. Central pontine indicated the site of the lesion and myelinolysis was used to emphasise that myelin was affected. The authors intentionally avoided the term demyelination to describe the condition, in order to differentiate this condition from multiple sclerosis and other neuroinflammatory disorders.Since this original description, demyelination in other areas of the central nervous system associated with osmotic stress has been described outside the pons (extrapontine). Osmotic demyelination syndrome is the term used for both central pontine myelinolysis and extrapontine myelinolysis.Central pontine myelinolysis, and osmotic demyelination syndrome, present most commonly as a complication of treatment of patients with profound hyponatremia (low sodium), which can result from a varied spectrum of conditions, based on different mechanisms. It occurs as a consequence of a rapid rise in serum tonicity following treatment in individuals with chronic, severe hyponatremia who have made intracellular adaptations to the prevailing hypotonicity.
Signs and symptoms
Symptoms depend on the regions of the brain involved. Prior to its onset, patients may present with the neurological signs and symptoms of hyponatraemic encephalopathy such as nausea and vomiting, confusion, headache and seizures. These symptoms may resolve with normalisation of the serum sodium concentration. Three to five days later, a second phase of neurological manifestations occurs correlating with the onset of myelinolysis. Observable immediate precursors may include seizures, disturbed consciousness, gait changes, and decrease or cessation of respiratory function.The classical clinical presentation is the progressive development of spastic quadriparesis, pseudobulbar palsy, and emotional lability (pseudobulbar affect), with other more variable neurological features associated with brainstem damage. These result from a rapid myelinolysis of the corticobulbar and corticospinal tracts in the brainstem.In about ten per cent of people with central pontine myelinolysis, extrapontine myelinolysis is also found. In these cases symptoms of Parkinsons disease may be generated.
Causes
The most common cause is overly-rapid correction of low blood sodium levels (hyponatremia). Apart from rapid correction of hyponatraemia, there are case reports of central pontine myelinolysis in association with hypokalaemia, anorexia nervosa when feeding is started, patients undergoing dialysis and burn victims. There is a case report of central pontine myelinolysis occurring in the context of refeeding syndrome, in the absence of hyponatremia.It has also been known to occur in patients suffering withdrawal symptoms of chronic alcoholism. In these instances, occurrence may be entirely unrelated to hyponatremia or rapid correction of hyponatremia. It could affect patients who take some prescription medicines that are able to cross the blood-brain barrier and cause abnormal thirst reception - in this scenario the central pontine myelinolysis is caused by polydipsia leading to low blood sodium levels (hyponatremia).In schizophrenic patients with psychogenic polydipsia, inadequate thirst reception leads to excessive water intake, severely diluting serum sodium. With this excessive thirst combined with psychotic symptoms, brain damage such as central pontine myelinolysis may result from hyperosmolarity caused by excess intake of fluids, (primary polydipsia) although this is difficult to determine because such patients are often institutionalised and have a long history of mental health conditions.It has been observed following hematopoietic stem cell transplantation.Central pontine myelinolysis may also occur in patients prone to hyponatremia affected by:
Severe liver disease (e.g., cirrhosis)
Liver transplant
Alcoholism
Hypokalemia
People with serum sodium <105 mEq/L
Severe burns
Malnutrition
Anorexia nervosa
Severe electrolyte disorders
HIV/AIDS
hyperemesis gravidarum
Hyponatremia due to peritoneal dialysis
Wernicke encephalopathy
Pathophysiology
The currently accepted theory states that the brain cells adjust their osmolarities by changing levels of certain osmolytes like inositol, betaine, and glutamine in response to varying serum osmolality. In the context of chronic low plasma sodium (hyponatremia), the brain compensates by decreasing the levels of these osmolytes within the cells, so that they can remain relatively isotonic with their surroundings and not absorb too much fluid. The reverse is true in hypernatremia, in which the cells increase their intracellular osmolytes so as not to lose too much fluid to the extracellular space.With correction of the hyponatremia with intravenous fluids, the extracellular tonicity increases, followed by an increase in intracellular tonicity. When the correction is too rapid, not enough time is allowed for the brains cells to adjust to the new tonicity, namely by increasing the intracellular osmoles mentioned earlier. If the serum sodium levels rise too rapidly, the increased extracellular tonicity will continue to drive water out of the brains cells. This can lead to cellular dysfunction and central pontine myelinolysis.
Diagnosis
It can be diagnosed clinically in the appropriate context, but may be difficult to confirm radiologically using conventional imaging techniques. Changes are more prominent on MRI than on CT, but often take days or weeks after acute symptom onset to develop. Imaging by MRI typically demonstrates areas of hyperintensity on T2-weighted images.
Treatment
To minimise the risk of this condition developing from its most common cause, overly rapid reversal of hyponatremia, the hyponatremia should be corrected at a rate not exceeding 10 mmol/L/24 h or 0.5 mEq/L/h; or 18 mEq/L/48hrs; thus avoiding demyelination. No large clinical trials have been performed to examine the efficacy of therapeutic re-lowering of serum sodium, or other interventions sometimes advocated such as steroids or plasma exchange.
Alcoholic patients should receive vitamin supplementation and a formal evaluation of their nutritional status.Once osmotic demyelination has begun, there is no cure or specific treatment. Care is mainly supportive. Alcoholics are usually given vitamins to correct for other deficiencies. The favourable factors contributing to the good outcome in central pontine myelinolysis without hyponatremia were: concurrent treatment of all electrolyte disturbances, early intensive care unit involvement at the advent of respiratory complications, early introduction of feeding including thiamine supplements with close monitoring of the electrolyte changes and input.Research has led to improved outcomes. Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia. Further study is required before using inositol in humans for this purpose.
Prognosis
Though traditionally the prognosis is considered poor, a good functional recovery is possible. All patients at risk of developing refeeding syndrome should have their electrolytes closely monitored, including sodium, potassium, magnesium, glucose and phosphate.
Recent data indicate that the prognosis of critically ill patients may even be better than what is generally considered, despite severe initial clinical manifestations and a tendency by the intensivists to underestimate a possible favorable evolution.
While some patients die, most survive and of the survivors, approximately one-third recover; one-third are disabled but are able to live independently; one-third are severely disabled. Permanent disabilities range from minor tremors and ataxia to signs of severe brain damage, such as spastic quadriparesis and locked-in syndrome. Some improvements may be seen over the course of the first several months after the condition stabilizes.The degree of recovery depends on the extent of the original axonal damage.
References
External links
MedPix Images of Osmotic Myelinolysis |
Epiblepharon | Epiblepharon is a condition characterised by a congenital horizontal fold of skin near the margin of the upper or lower eyelid caused by the abnormal insertion of muscle fibres. This extra fold of skin redirects the lashes into a vertical position, where they may contact the globe of the eye. This is found most commonly in Asian individuals, especially children. One estimate puts the percentage of affected Asian children aged 7–14 years old at 12.6%.
References
== External links == |
Chlamydia | Chlamydia, or more specifically a chlamydia infection, is a sexually transmitted infection caused by the bacterium Chlamydia trachomatis. Most people who are infected have no symptoms. When symptoms do appear they may occur only several weeks after infection; the incubation period between exposure and being able to infect others is thought to be on the order of two to six weeks. Symptoms in women may include vaginal discharge or burning with urination. Symptoms in men may include discharge from the penis, burning with urination, or pain and swelling of one or both testicles. The infection can spread to the upper genital tract in women, causing pelvic inflammatory disease, which may result in future infertility or ectopic pregnancy.Chlamydia infections can occur in other areas besides the genitals, including the anus, eyes, throat, and lymph nodes. Repeated chlamydia infections of the eyes that go without treatment can result in trachoma, a common cause of blindness in the developing world.Chlamydia can be spread during vaginal, anal, or oral sex, and can be passed from an infected mother to her baby during childbirth. The eye infections may also be spread by personal contact, flies, and contaminated towels in areas with poor sanitation. Infection by the bacterium Chlamydia trachomatis only occurs in humans. Diagnosis is often by screening which is recommended yearly in sexually active women under the age of twenty-five, others at higher risk, and at the first prenatal visit. Testing can be done on the urine or a swab of the cervix, vagina, or urethra. Rectal or mouth swabs are required to diagnose infections in those areas.Prevention is by not having sex, the use of condoms, or having sex with only one other person, who is not infected. Chlamydia can be cured by antibiotics with typically either azithromycin or doxycycline being used. Erythromycin or azithromycin is recommended in babies and during pregnancy. Sexual partners should also be treated, and infected people should be advised not to have sex for seven days and until symptom free. Gonorrhea, syphilis, and HIV should be tested for in those who have been infected. Following treatment people should be tested again after three months.Chlamydia is one of the most common sexually transmitted infections, affecting about 4.2% of women and 2.7% of men worldwide. In 2015, about 61 million new cases occurred globally. In the United States about 1.4 million cases were reported in 2014. Infections are most common among those between the ages of 15 and 25 and are more common in women than men. In 2015 infections resulted in about 200 deaths. The word chlamydia is from the Greek χλαμύδα, meaning "cloak".
Signs and symptoms
Genital disease
Women
Chlamydial infection of the cervix (neck of the womb) is a sexually transmitted infection which has no symptoms for around 70% of women infected. The infection can be passed through vaginal, anal, or oral sex. Of those who have an asymptomatic infection that is not detected by their doctor, approximately half will develop pelvic inflammatory disease (PID), a generic term for infection of the uterus, fallopian tubes, and/or ovaries. PID can cause scarring inside the reproductive organs, which can later cause serious complications, including chronic pelvic pain, difficulty becoming pregnant, ectopic (tubal) pregnancy, and other dangerous complications of pregnancy.
Chlamydia is known as the "silent epidemic", as at least 70% of genital C. trachomatis infections in women (and 50% in men) are asymptomatic at the time of diagnosis, and can linger for months or years before being discovered. Signs and symptoms may include abnormal vaginal bleeding or discharge, abdominal pain, painful sexual intercourse, fever, painful urination or the urge to urinate more often than usual (urinary urgency).
For sexually active women who are not pregnant, screening is recommended in those under 25 and others at risk of infection. Risk factors include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, and inconsistent condom use. Guidelines recommend all women attending for emergency contraceptive are offered chlamydia testing, with studies showing up to 9% of women aged <25 years had chlamydia.
Men
In men, those with a chlamydial infection show symptoms of infectious inflammation of the urethra in about 50% of cases. Symptoms that may occur include: a painful or burning sensation when urinating, an unusual discharge from the penis, testicular pain or swelling, or fever. If left untreated, chlamydia in men can spread to the testicles causing epididymitis, which in rare cases can lead to sterility if not treated. Chlamydia is also a potential cause of prostatic inflammation in men, although the exact relevance in prostatitis is difficult to ascertain due to possible contamination from urethritis.
Eye disease
Trachoma is a chronic conjunctivitis caused by Chlamydia trachomatis. It was once the leading cause of blindness worldwide, but its role diminished from 15% of blindness cases by trachoma in 1995 to 3.6% in 2002. The infection can be spread from eye to eye by fingers, shared towels or cloths, coughing and sneezing and eye-seeking flies. Symptoms include mucopurulent ocular discharge, irritation, redness, and lid swelling. Newborns can also develop chlamydia eye infection through childbirth (see below). Using the SAFE strategy (acronym for surgery for in-growing or in-turned lashes, antibiotics, facial cleanliness, and environmental improvements), the World Health Organization aims for the global elimination of trachoma by 2020 (GET 2020 initiative).
Joints
Chlamydia may also cause reactive arthritis—the triad of arthritis, conjunctivitis and urethral inflammation—especially in young men. About 15,000 men develop reactive arthritis due to chlamydia infection each year in the U.S., and about 5,000 are permanently affected by it. It can occur in both sexes, though is more common in men.
Infants
As many as half of all infants born to mothers with chlamydia will be born with the disease. Chlamydia can affect infants by causing spontaneous abortion; premature birth; conjunctivitis, which may lead to blindness; and pneumonia. Conjunctivitis due to chlamydia typically occurs one week after birth (compared with chemical causes (within hours) or gonorrhea (2–5 days)).
Other conditions
A different serovar of Chlamydia trachomatis is also the cause of lymphogranuloma venereum, an infection of the lymph nodes and lymphatics. It usually presents with genital ulceration and swollen lymph nodes in the groin, but it may also manifest as rectal inflammation, fever or swollen lymph nodes in other regions of the body.
Transmission
Chlamydia can be transmitted during vaginal, anal, or oral sex, or direct contact with infected tissue such as conjunctiva. Chlamydia can also be passed from an infected mother to her baby during vaginal childbirth. It is assumed that the probability of becoming infected is proportionate to the number of bacteria one is exposed to.
Pathophysiology
Chlamydiae have the ability to establish long-term associations with host cells. When an infected host cell is starved for various nutrients such as amino acids (for example, tryptophan), iron, or vitamins, this has a negative consequence for Chlamydiae since the organism is dependent on the host cell for these nutrients. Long-term cohort studies indicate that approximately 50% of those infected clear within a year, 80% within two years, and 90% within three years.The starved chlamydiae enter a persistent growth state wherein they stop cell division and become morphologically aberrant by increasing in size. Persistent organisms remain viable as they are capable of returning to a normal growth state once conditions in the host cell improve.There is debate as to whether persistence has relevance. Some believe that persistent chlamydiae are the cause of chronic chlamydial diseases. Some antibiotics such as β-lactams have been found to induce a persistent-like growth state.
Diagnosis
The diagnosis of genital chlamydial infections evolved rapidly from the 1990s through 2006. Nucleic acid amplification tests (NAAT), such as polymerase chain reaction (PCR), transcription mediated amplification (TMA), and the DNA strand displacement amplification (SDA) now are the mainstays. NAAT for chlamydia may be performed on swab specimens sampled from the cervix (women) or urethra (men), on self-collected vaginal swabs, or on voided urine. NAAT has been estimated to have a sensitivity of approximately 90% and a specificity of approximately 99%, regardless of sampling from a cervical swab or by urine specimen. In women seeking an sexually transmitted infection (STI) clinic and a urine test is negative, a subsequent cervical swab has been estimated to be positive in approximately 2% of the time.At present, the NAATs have regulatory approval only for testing urogenital specimens, although rapidly evolving research indicates that they may give reliable results on rectal specimens.
Because of improved test accuracy, ease of specimen management, convenience in specimen management, and ease of screening sexually active men and women, the NAATs have largely replaced culture, the historic gold standard for chlamydia diagnosis, and the non-amplified probe tests. The latter test is relatively insensitive, successfully detecting only 60–80% of infections in asymptomatic women, and often giving falsely-positive results. Culture remains useful in selected circumstances and is currently the only assay approved for testing non-genital specimens. Other methods also exist including: ligase chain reaction (LCR), direct fluorescent antibody resting, enzyme immunoassay, and cell culture.Rapid point-of-care tests are, as of 2020, not thought to be effective for diagnosing chlamydia in men of reproductive age and nonpregnant women because of high false-negative rates.
Prevention
Prevention is by not having sex, the use of condoms, or having sex with only one other person, who is not infected.
Screening
For sexually active women who are not pregnant, screening is recommended in those under 25 and others at risk of infection. Risk factors include a history of chlamydial or other sexually transmitted infection, new or multiple sexual partners, and inconsistent condom use. For pregnant women, guidelines vary: screening women with age or other risk factors is recommended by the U.S. Preventive Services Task Force (USPSTF) (which recommends screening women under 25) and the American Academy of Family Physicians (which recommends screening women aged 25 or younger). The American College of Obstetricians and Gynecologists recommends screening all at risk, while the Centers for Disease Control and Prevention recommend universal screening of pregnant women. The USPSTF acknowledges that in some communities there may be other risk factors for infection, such as ethnicity. Evidence-based recommendations for screening initiation, intervals and termination are currently not possible. For men, the USPSTF concludes evidence is currently insufficient to determine if regular screening of men for chlamydia is beneficial. They recommend regular screening of men who are at increased risk for HIV or syphilis infection. A Cochrane review found that the effects of screening are uncertain in terms of chlamydia transmission but that screening probably reduces the risk of pelvic inflammatory disease in women.In the United Kingdom the National Health Service (NHS) aims to:
Prevent and control chlamydia infection through early detection and treatment of asymptomatic infection;
Reduce onward transmission to sexual partners;
Prevent the consequences of untreated infection;
Test at least 25 percent of the sexually active under 25 population annually.
Retest after treatment.
Treatment
C. trachomatis infection can be effectively cured with antibiotics. Guidelines recommend azithromycin, doxycycline, erythromycin, levofloxacin or ofloxacin. In men, doxycycline (100 mg twice a day for 7 days) is probably more effective than azithromycin (1 g single dose) but evidence for the relative effectiveness of antibiotics in women is very uncertain. Agents recommended during pregnancy include erythromycin or amoxicillin.An option for treating sexual partners of those with chlamydia or gonorrhea includes patient-delivered partner therapy (PDT or PDPT), which is the practice of treating the sex partners of index cases by providing prescriptions or medications to the patient to take to his/her partner without the health care provider first examining the partner.Following treatment people should be tested again after three months to check for reinfection.
Epidemiology
Globally, as of 2015, sexually transmitted chlamydia affects approximately 61 million people. It is more common in women (3.8%) than men (2.5%). In 2015 it resulted in about 200 deaths.In the United States about 1.6 million cases were reported in 2016. The CDC estimates that if one includes unreported cases there are about 2.9 million each year. It affects around 2% of young people. Chlamydial infection is the most common bacterial sexually transmitted infection in the UK.Chlamydia causes more than 250,000 cases of epididymitis in the U.S. each year. Chlamydia causes 250,000 to 500,000 cases of PID every year in the United States. Women infected with chlamydia are up to five times more likely to become infected with HIV, if exposed.
References
External links
Chlamydia at Curlie
Chlamydia Fact Sheet from the CDC |
Developmental regression | Developmental regression is when a child who has reached a certain developmental stage begins to lose previously acquired milestones. It differs from developmental delay in that a child experiencing developmental delay is either not reaching developmental milestones or not progressing to new developmental milestones, while a child experiencing developmental regression will lose milestones and skills after acquiring them. Developmental regression is associated with diagnoses of autism spectrum disorder, childhood disintegrative disorder, Rett syndrome, Landau-Kleffner syndrome, and neuro-degenerative diseases. The loss of motor, language, and social skills can be treated with occupational therapy, physical therapy, and speech therapy.
Associated Diagnoses
Developmental regression is typically a symptom of neurological disorder.
Autism Spectrum Disorder
Autism spectrum disorder is a developmental disorder in which a childs communication and social skills are affected. Children with autism spectrum disorder can experience a loss of their previously acquired language and social skills. This is often reported by the childs parents. Children can experience loss of vocabulary and language understanding, as well as no longer make eye contact or play social and imitative games when they previously had. They can also experience a loss of motor and basic skills like toileting or feeding themselves. In autism spectrum disorder, this regression occurs in the first few years of development.
Childhood Disintegrative Disorder
Childhood disintegrative disorder (CDD) is a developmental disorder in which children experience a regression of social language, and motor functioning skills. CDD was merged with autism spectrum disorder in the DSM-V in 2013. Children with CDD can experience a loss of expressive and receptive language skills, social and self-care skills, play skills, and/or motor skills. Regression commonly occurs at around 3 or 4 years old, but after at least two years of normal development and before age 10.
Rett Syndrome
Rett syndrome is a neurodevelopmental disorder caused by a genetic mutation. It occurs almost exclusively in girls. A child with Rett syndrome experiences a loss of previously had intentional hand skills, and can experience a loss of language skills. Children can also experience a loss of social skills and autism-like symptoms. The regression typically occurs between 1–4 years of age.
Landau-Kleffner Syndrome
Landau-Kleffner syndrome is a form of epilepsy associated with a loss of language skills. Those with LKS lose their ability to understand spoken language and to verbally express themselves. LKS typically has an onset of between the ages of 2 and 8 years old.
Neuro-degenerative diseases
Neuro-degenerative diseases (disorders like Batten disease) can result in a child losing previously acquired motor, language, and speech skills.
Signs and symptoms
Children with developmental regression lose developmental milestones they have previously gained. These can be motor, social, or language skills. The loss of motor skills could include loss of the ability to purposefully use hands, loss of the ability to feed oneself, loss of the ability to walk, loss of the ability to bathe oneself, and loss of the ability to dress oneself. The loss of social skills could include loss of the ability/desire to play, loss of the ability to make appropriate eye contact, and loss of interest in playing social games. The loss of language skills could include the loss of a childs ability to understand spoken speech and sounds (receptive language skills) and/or the loss of a childs ability to use words/spoken language (expressive language skills).
Diagnosis
The American Academy of Pediatrics recommends that most children receive a developmental screening at their 9-month, 18 month, and 30 month physical exams. Physicians also screen children for autism spectrum disorder at their 18-month and 2 year appointments. If the screening indicates a potential problem, a physician would then perform a developmental evaluation to identify the specific developmental areas affected and assess the childs needs. Parents can also monitor their children and inform their provider if their child has lost previously reached developmental milestones.
Treatment
For treatment of regression of motor skills, occupational and physical therapy can be used. Occupational therapy can help children regain some of their lost fine motor skills. An occupational therapist can help a child improve their fine motor skills and hand-eye coordination so they can complete basic life tasks like bathing or feeding themselves, and fine motor skill tasks like writing. Physical therapy can be used to treat regression of gross motor skills. Physical therapists can help a child with skills like walking or mobility issues.Speech therapy is often used for treatment of regression of language skills. Speech therapists will help a child restore as much of their lost language skills as possible, and help a child learn to communicate, potentially with the use of communication aids.Social skills training can be used to treat a regression of social skills. Children who receive social skills training are taught age-appropriate social skills like problem solving and peer interaction skills.For regression related to seizures, medication can be used to treat the seizures.
See also
Developmental disorder
== References == |
Pashayan syndrome | Pashayan syndrome, also known as Pashayan–Pruzansky Syndrome and blepharo-naso-facial syndrome, is a rare syndrome with Mendelian autosomal dominant inheritance with variable expression. An article describing a family with this syndrome was first published in 1973 in The American Journal of Diseases of Children by Drs Hermine Pashayan, Samuel Pruzansky and Allen Putterman from Abraham Lincoln School of Medicine, University of Illinois in Chicago. Facial abnormalities characterise this syndrome as well as malformation of extremities. Specific characteristics would be a bulky, flattened nose, where the face has a mask like appearance and the ears are also malformed.A subset of Pashayan syndrome has also been described, known as "cerebrofacioarticular syndrome", "Van Maldergem syndrome" or "Van Maldergem–Wetzburger–Verloes syndrome". Similar symptoms are noted in these cases as in Pashayan syndrome.
References
== External links == |
Fibrous dysplasia of bone | Fibrous dysplasia is a disorder where normal bone and marrow is replaced with fibrous tissue, resulting in formation of bone that is weak and prone to expansion. As a result, most complications result from fracture, deformity, functional impairment, and pain. Disease occurs along a broad clinical spectrum ranging from asymptomatic, incidental lesions, to severe disabling disease. Disease can affect one bone (monostotic), multiple (polyostotic), or all bones (panostotic) and may occur in isolation or in combination with café au lait skin macules and hyperfunctioning endocrinopathies, termed McCune–Albright syndrome. More rarely, fibrous dysplasia may be associated with intramuscular myxomas, termed Mazabrauds syndrome. Fibrous dysplasia is very rare, and there is no known cure. Fibrous dysplasia is not a form of cancer.
Presentation
Fibrous dysplasia is a mosaic disease that can involve any part or combination of the craniofacial, axillary, and/or appendicular skeleton. The type and severity of the complications therefore depend on the location and extent of the affected skeleton. The clinical spectrum is very broad, ranging from an isolated, asymptomatic monostotic lesion discovered incidentally, to severe disabling disease involving practically the entire skeleton and leading to loss of vision, hearing, and/or mobility.Individual bone lesions typically manifest during the first few years of life and expand during childhood. The vast majority of clinically significant bone lesions are detectable by age 10 years, with few new and almost no clinically significant bone lesions appearing after age 15 years. Total body scintigraphy is useful to identify and determine the extent of bone lesions, and should be performed in all patients with suspected fibrous dysplasia.Children with fibrous dysplasia in the appendicular skeleton typically present with limp, pain, and/or pathologic fractures. Frequent fractures and progressive deformity may lead to difficulties with ambulation and impaired mobility. In the craniofacial skeleton, fibrous dysplasia may present as a painless “lump” or facial asymmetry. Expansion of craniofacial lesions may lead to progressive facial deformity. In rare cases, patients may develop vision and/or hearing loss due to compromise of the optic nerves and/or auditory canals, which is more common in patients with McCune-Albright syndrome associated growth hormone excess. Fibrous dysplasia commonly involves the spine, and may lead to scoliosis, which in rare instances may be severe. Untreated, progressive scoliosis is one of the few features of fibrous dysplasia that can lead to early fatality.
Bone pain is a common complication of fibrous dysplasia. It may present at any age, but most commonly develops during adolescence and progresses into adulthood.
Bone marrow stromal cells in fibrous dysplasia produce excess amounts of the phosphate-regulating hormone fibroblast growth factor-23 (FGF23), leading to loss of phosphate in the urine. Patients with hypophosphatemia may develop rickets/osteomalacia, increased fractures, and bone pain.
Pathophysiology
Fibrous dysplasia is a mosaic disease resulting from post-zygotic activating mutations of the GNAS locus at 20q13.2-q13.3, which codes for the α subunit of the Gs G protein-coupled receptor. In bone, constitutive Gsα signaling results in impaired differentiation and proliferation of bone marrow stromal cells. Proliferation of these cells causes replacement of normal bone and marrow with fibrous tissue. The bony trabeculae are abnormally thin and irregular, and often likened to Chinese characters (bony spicules on biopsy).Fibrous dysplasia is not hereditary, and there has never been a case of genetic inheritance from parent to child.
Diagnosis
On x-ray, fibrous dysplasia appears as bubbly lytic lesions, or a ground glass appearance. Computerized tomography (CT) or magnetic resonance imaging (MRI) scans may be used to determine how extensively bones are affected. CT can better demonstrate the typical "ground glass" appearance, which is a highly specific radiological finding, while MRI can show cystic areas with fluid contents. A bone scan uses radioactive tracers, which are injected into your bloodstream. The damaged parts of bones take up more of the tracer, which show up more brightly on the scan. A biopsy, which uses a hollow needle to remove a small piece of the affected bone for laboratory analysis, can diagnose fibrous dysplasia definitely.
Treatment
Treatment in fibrous dysplasia is mainly palliative, and is focused on managing fractures and preventing deformity. There are no medications capable of altering the disease course. Intravenous bisphosphonates may be helpful for treatment of bone pain, but there is no clear evidence that they strengthen bone lesions or prevent fractures. Surgical techniques that are effective in other disorders, such as bone grafting, curettage, and plates and screws, are frequently ineffective in fibrous dysplasia and should be avoided. Intramedullary rods are generally preferred for management of fractures and deformity in the lower extremities. Progressive scoliosis can generally be managed with standard instrumentation and fusion techniques. Surgical management in the craniofacial skeleton is complicated by frequent post-operative FD regrowth, and should focus on correction of functional deformities. Prophylactic optic nerve decompression increases the risk of vision loss and is contraindicated.Managing endocrinopathies is a critical component of management in FD. All patients with fibrous dysplasia should be evaluated and treated for endocrine diseases associated with McCune–Albright syndrome. In particular untreated growth hormone excess may worsen craniofacial fibrous dysplasia and increase the risk of blindness. Untreated hypophosphatemia increases bone pain and risk of fractures.
See also
Cherubism
Dysplasia
McCune–Albright syndrome
References
Further reading
GeneReviews entry for Fibrous Dysplasia/McCune-Albright Syndrome
== External links == |
Congenital hemolytic anemia | Congenital hemolytic anemia refers to hemolytic anemia which is primarily due to congenital disorders.
Types
Basically classified by causative mechanism, types of congenital hemolytic anemia include:
Genetic conditions of RBC Membrane
Hereditary spherocytosis
Hereditary elliptocytosis
Genetic conditions of RBC metabolism (enzyme defects). This group is sometimes called congenital nonspherocytic (hemolytic) anemia, which is a term for a congenital hemolytic anemia without spherocytosis, and usually excluding hemoglobin abnormalities as well, but rather encompassing defects of glycolysis in the erythrocyte.Glucose-6-phosphate dehydrogenase deficiency (G6PD or favism)
Pyruvate kinase deficiency
Aldolase A deficiency
Hemoglobinopathies/genetic conditions of hemoglobin
Sickle cell anemia
Congenital dyserythropoietic anemia
Thalassemia
See also
Hematopoietic ulcer
List of circulatory system conditions
References
== External links == |
Fibrofolliculoma | Fibrofolliculomas are 2 to 4 mm in diameter, dome-shaped, yellowish or skin-colored papules usually located on the head, neck, and upper trunk. They are characteristically seen in Birt–Hogg–Dubé syndrome.: 674
See also
List of cutaneous conditions
List of cutaneous neoplasms associated with systemic syndromes
Trichodiscoma
== References == |
Septic arthritis | Acute septic arthritis, infectious arthritis, suppurative arthritis, osteomyelitis, or joint infection is the invasion of a joint by an infectious agent resulting in joint inflammation. Generally speaking, symptoms typically include redness, heat and pain in a single joint associated with a decreased ability to move the joint. Onset is usually rapid. Other symptoms may include fever, weakness and headache. Occasionally, more than one joint may be involved, especially in neonates and younger children. In neonates, infants during the first year of life, and toddlers, the signs and symptoms of septic arthritis can be deceptive and mimic other infectious and non-infectious disorders.In children, septic arthritis is usually caused by non-specific bacterial infection and commonly hematogenous, i.e., spread through the bloodstream. Septic arthritis and/or acute hematogenous osteomyelitis usually occurs in children with no co-occurring health problems. Other routes of infection include direct trauma and spread from a nearby abscess. Other less common cause include specific bacteria as mycobacterium tuberculosis, viruses, fungi and parasites. In children, however, there are certain groups that are specifically vulnerable to such infections namely preterm infants, neonates in general, children and adolescence with hematologic disorders, renal osteodystrophy and immune-compromised status. In adults vulnerable groups include an artificial joint, prior arthritis, diabetes and poor immune function. Diagnosis is generally based on accurate correlation between history-taking and clinical examination findings and basic laboratory and imaging findings like joint ultrasound.In children septic arthritis can have serious consequences if not treated appropriately and timely. Initial treatment typically includes antibiotics such as vancomycin, ceftriaxone or ceftazidime. Surgery in the form of joint drainage is the gold standard management in large joints like the hip and shoulder. Without early treatment, long-term joint problems may occur, such as irreversible joint destruction and dislocation.
Signs and symptoms
Children
In children septic arthritis usually affects the larger joints like the hips, knees and shoulders. The early signs and symptoms of septic arthritis in children and adolescence can be confused with limb injury. Among the signs and symptoms of septic arthritis are: acutely swollen, red, painful joint with fever. Kocher criteria have been suggested to predict the diagnosis of septic arthritis in children.Importantly, observation of active limb motion or kicking in the lower limb can provide valuable clues to septic arthritis of hip or knee. In neonates/new born and infants the hip joint is characteristically held in abduction flexion and external rotation. This position helps the infant accommodate maximum amount of septic joint fluid with the least tension possible. The tendency to have multiple joint involvements in septic arthritis of neonates and young children should be closely considered.
Adults
In adults, septic arthritis most commonly causes pain, swelling and warmth at the affected joint. Therefore, those affected by septic arthritis will often refuse to use the extremity and prefer to hold the joint rigidly. Fever is also a symptom; however, it is less likely in older people. In adults the most common joint affected is the knee. Hip, shoulder, wrist and elbow joints are less commonly affected. Spine, sternoclavicular and sacroiliac joints can also be involved. The most common cause of arthritis in these joints is intravenous drug use. Usually, only one joint is affected. More than one joint can be involved if bacteria are spread through the bloodstream.
Prosthetic joint
For those with artificial joint implants, there is a chance of 0.86 to 1.1% of getting infected in a knee joint and 0.3 to 1.7% of getting infected in a hip joint. There are three phases of artificial joint infection: early, delayed and late.
Early – infection occurs in less than 3 months. Usual signs and symptoms are fever and joint pain, with redness and warmth over the joint operation site. The mode of infection is during the joint implant surgery. The usual bacteria involved are Staphylococcus aureus and gram negative bacilli.
Delayed – infection occurs between 3 and 24 months. There would be persistent joint pain, due to loosening of the implant. The mode of infection is during the implant surgery. Common bacteria are coagulase-negative Staphylococcus and Cutibacterium acnes.
Late – more than 24 months. It is usually presented with a sudden onset of joint pain and fever. The mode of infection is through the bloodstream. The bacteria involved are the same as those in septic arthritis of a normal joint.
Cause
Septic arthritis is most commonly caused by a bacterial infection. Bacteria can enter the joint by:
The bloodstream from an infection elsewhere (most common)
Direct penetration into the joint (arthrocentesis, arthroscopy, trauma)
A surrounding infection in the bone or tissue (uncommon, from osteomyelitis, septic bursitis, abscess).Microorganisms in the blood may come from infections elsewhere in the body such as wound infections, urinary tract infections, meningitis or endocarditis. Sometimes, the infection comes from an unknown location. Joints with preexisting arthritis, such as rheumatoid arthritis, are especially prone to bacterial arthritis spread through the blood. In addition, some treatments for rheumatoid arthritis can also increase a persons risk by causing an immunocompromised state. Intravenous drug use can cause endocarditis that spreads bacteria in the bloodstream and subsequently causes septic arthritis. Bacteria can enter the joint directly from prior surgery, intraarticular injection, trauma or joint prosthesis.
Risk factors
In children, although septic arthritis occurs in healthy children and adolescents with no co-occurring health issues, there are certain risk factors that may increase the likelihood of acquiring septic arthritis. For example, children with renal osteodystrophy or renal bone disease, certain hematological disorders and diseases causing immune suppression are risk factors for childhood septic arthritis.The rate of septic arthritis varies from 4 to 29 cases per 100,000 person-years, depending on the underlying medical condition and the joint characteristics. For those with a septic joint, 85% of the cases have an underlying medical condition while 59% of them had a previous joint disorder. Having more than one risk factor greatly increases risk of septic arthritis.
Age over 80 years
Diabetes mellitus
Osteoarthritis
Rheumatoid arthritis. Risk of septic arthritis increases with anti-tumor necrosis factor alpha treatment.
Immunosuppressive medication
Intravenous drug abuse
Recent joint surgery
Hip or knee prosthesis and skin infection
HIV infection
Other causes of sepsis
Organisms
Most cases of septic arthritis involve only one organism; however, polymicrobial infections can occur, especially after large open injuries to the joint. Septic arthritis is usually caused by bacteria, but may be caused by viral, mycobacterial, and fungal pathogens as well. It can be broadly classified into three groups: non-gonococcal arthritis, gonococcal arthritis, and others.
Non-gonococcal arthritis – These bacteria account for over 80% of septic arthritis cases and are usually staphylococci or streptococci. Such infections most commonly come from drug abuse, cellulitis, abscesses, endocarditis, and chronic osteomyelitis. Methicillin-resistant Staphylococcus aureus (MRSA) may affect 5 to 25% of the cases while gram negative bacilli affects 14 to 19% of the septic arthritis cases. Gram negative infections are usually acquired through urinary tract infections, drug abuse, and skin infections. Older people who are immunocompromised are also prone to get gram negative infections. Common gram negative organisms are: Pseudomonas aeruginosa and Escherichia coli. Both gram positive and gram negative infections are commonly spread through the blood from an infective source; but can be introduced directly into the joint or from surrounding tissue. It often affects older people, and often happens suddenly, involving only one joint. Joint aspiration cultures are positive in 90% of cases, while only 50% of blood cultures yield any organisms.
Gonococcal arthritis – Neisseria gonorrhoeae is a common cause of septic arthritis in people who are sexually active and under 40 years old. The bacteria is spread through the blood to the joint following sexual transmission. Other symptoms of disseminated gonococcal infection can include migration of joint pain, tenosynovitis and dermatitis. Synovial fluid cultures are positive in 25 to 70% of the cases while blood cultures are seldom positive. Apart from blood and joint cultures, swabs from urethra, rectum, pharynx, and cervix should also be taken. Polymerase chain reaction (PCR) is another useful way of identifying gonococcal infections if diagnosis is difficult and clinical presentation is similar to reactive arthritis.
Others – Fungal and mycobacterial infections are rare causes of septic arthritis and usually have a slow onset of joint symptoms. Mycobacterial joint infection most commonly affects hip and knee joints, caused by reactivation of past mycobacterial infections, with or without signs and symptoms of tuberculosis in lungs. Synovial fluid cultures will be positive in 80% of the cases. However, acid fast smears are not useful. Histology is not specific to myocobacterial infection as there are other granulomatous diseases that can show similar histology. Borrelia burgdorferi, a bacterium that causes lyme disease, can affect multiple large joints such as the knee. Confirmation of Lyme disease is done through enzyme-linked immunosorbent assay (ELISA) followed by confirmation using Western Blot test. It cannot be cultured from synovial fluid. However, PCR testing yields 85% positive result from synovial fluid. Viruses such as rubella, parvovirus B19, chikungunya, and HIV infection can also cause septic arthritis.
Prosthetic joint infection – Artificial joint infection are usually caused by coagulase negative Staphylococci, Staphylococcus aureus, and gram negative bacilli. Concurrent infections by multiple organisms is also reported in 20% of the cases. The risk factors of prosthetic joint infections are: previous fracture, seropositive rheumatoid arthritis, obesity, revision arthroplasty, and surgical site infections.
List of organisms
Staphylococci (40%)Staphylococcus aureus – the most common cause in most age groups. Can be caused by skin infection, previously damaged joint, prosthetic joint or intravenous drug use.
coagulase-negative staphylococci – usually due to prosthetic joint
Streptococci – the second-most common cause (28%)Streptococcus pyogenes – a common cause in children under 5
Streptococcus pneumoniae
Group B streptococci – a common cause in infants
Haemophilus influenzae
Neisseria gonorrhoeae – the most common cause of septic arthritis in young, sexually active adults. Multiple macules or vesicles seen over the trunk are a pathognomonic feature.
Neisseria meningitidis
Escherichia coli – in the elderly, IV drug users and the seriously ill
Pseudomonas aeruginosa – IV drug users or penetrating trauma through the shoe
M. tuberculosis, Salmonella spp. and Brucella spp. – cause septic spinal arthritis
Eikenella corrodens – human bites
Pasteurella multocida, bartonella henselae, capnocytophaga – animal bites or scratches
Fungal species – immunocompromised state
Borrelia burgdorferi – ticks, causes lyme disease
Spirillum minus, Streptobacillus moniliformis– rat bites
Diagnosis
Septic arthritis should be considered whenever a person has rapid onset pain in a swollen joint, regardless of fever. One or multiple joints can be affected at the same time.Laboratory studies such as blood cultures, white blood cell count with differential, ESR, and CRP should also be included. However, white cell count, ESR, and CRP are nonspecific and could be elevated due to infection elsewhere in the body. Serologic studies should be done if lyme disease is suspected. Blood cultures can be positive in 25 to 50% of those with septic arthritis due to spread of infection from the blood. CRP more than 20 mg/L and ESR greater than 20 mm/hour together with typical signs and symptoms of septic arthritis should prompt arthrocentesis from the affected joint for synovial fluid examination.The synovial fluid should be collected before the administration of antibiotics and should be sent for gram stain, culture, leukocyte count with differential, and crystal studies. This can include NAAT testing for N. gonorrhoeae if suspected in a sexually active person.In children, the Kocher criteria is used for diagnosis of septic arthritis.
Differential diagnosis
The differential diagnosis of septic arthritis is broad and challenging. First, it has to be differentiated from acute hematogenous osteomyelitis. This is because the treatment lines of both conditions are not identical. Noteworthy, septic arthritis and acute hematogenous osteomyelitis can co-occur. Especially in the hip and shoulder joints their co-occurrence is likely and represents a diagnostic challenge. Therefore, physicians should have a high suspicion index in that regard. This is because in both the hip and shoulder joints the metaphysis is intra-articular which in turn facilitates the spread of hematogenous osteomyelitis into the joint cavity. Conversely, joint sepsis may spread to the metaphysis and induce osteomyelitis.
Acute exacerbation of juvenile idiopathic arthritis and transient synovitis of the hip both of which are non-septic conditions may mimic septic arthritis. More serious and life-threatening disorders as bone malignancies e.g. Ewing sarcoma and osteosarcoma may mimic septic arthritis associated with concurrent acute hematogenous osteomyelitis. In this regard, Magnetic resonance imaging may play an important role in the differential diagnosis.
Joint aspiration
In children, joint synovial fluid aspiration techniques aim at isolating the infectious organism by culture and sensitivity analysis. Cytological analysis of the joint aspirate can point to septic arthritis. However, a negative culture and sensitivity test does not rule out the presence of septic arthritis. Various clinical scenarios and technique-related factors may impact the validity of results of the culture and sensitivity. Additionally, results of cytological analysis, though important, should not be interpreted in isolation of the clinical settings.
In the joint fluid, the typical white blood cell count in septic arthritis is over 50,000-100,000 cells per 10−6/l (50,000-100,000 cell/mm3); where more than 90% are neutrophils is suggestive of septic arthritis. For those with prosthetic joints, white cell count more than 1,100 per mm3 with neutrophil count greater than 64% is suggestive of septic arthritis. However, septic synovial fluid can have white blood cell counts as low as a few thousand in the early stages. Therefore, differentiation of septic arthritis from other causes is not always possible based on cell counts alone. Synovial fluid PCR analysis is useful in finding less common organisms such as Borrelia species. However, measuring protein and glucose levels in joint fluid is not useful for diagnosis.The Gram stain can rule in the diagnosis of septic arthritis, however, cannot exclude it.Synovial fluid cultures are positive in over 90% of nongonoccocal arthritis; however, it is possible for the culture to be negative if the person received antibiotics prior to the joint aspiration. Cultures are usually negative in gonoccocal arthritis or if fastidious organisms are involved.If the culture is negative or if a gonococcal cause is suspected, NAAT testing of the synovial fluid should be done.Positive crystal studies do not rule out septic arthritis. Crystal-induced arthritis such as gout can occur at the same time as septic arthritis.A lactate level in the synovial fluid of greater than 10 mmol/L makes the diagnosis very likely.
Blood tests
Laboratory testing includes white blood cell count, ESR and CRP. These values are usually elevated in those with septic arthritis; however, these can be elevated by other infections or inflammatory conditions and are, therefore, nonspecific. Procalcitonin may be more useful than CRP.Blood cultures can be positive in up to half of people with septic arthritis.
Imaging
Imaging such as x-ray, CT, MRI or ultrasound are nonspecific. They can help determine areas of inflammation but cannot confirm septic arthritis.When septic arthritis is suspected, x-rays should generally be taken. This is used to assess any problems in the surrounding structures such as bone fractures, chondrocalcinosis, and inflammatory arthritis which may predispose to septic arthritis. While x-rays may not be helpful early in the diagnosis/treatment, they may show subtle increase in joint space and tissue swelling. Later findings include joint space narrowing due to destruction of the joint.Ultrasound is effective at detecting joint effusions.CT and MRI are not required for diagnosis; but if the diagnosis is unclear or the joints are hard to examine (ie.sacroiliac or hip joints); they can help to assess for inflammation/infection in or around the joint (i.e. Osteomyelitis), bone erosions, and bone marrow oedema. Both CT and MRI scans are helpful in guiding arthrocentesis of the joints.
Differential diagnosis
Crystal induced arthritis such as gout or pseudogout
Inflammatory arthritisRheumatoid arthritis
Seronegative spondyloarthropathy such as ankylosing spondylitis or reactive arthritis
Traumatic arthritis due to hemarthrosis, fracture or foreign body
Osteoarthritis
Treatment
Treatment is usually with intravenous antibiotics, analgesia and washout and/or aspiration of the joint. Draining the pus from the joint is important and can be done either by needle (arthrocentesis) or opening the joint surgically (arthrotomy).Empiric antibiotics for suspected bacteria should be started. This should be based on Gram stain of the synovial fluid as well as other clinical findings. General guidelines are as follows:
Gram positive cocci – vancomycin
Gram negative cocci – Ceftriaxone
Gram negative bacilli – Ceftriaxone, cefotaxime, or ceftazidime
Gram stain negative and immunocompetent – vancomycin
Gram stain negative and immunocompromised – vancomycin + third generation cephalosphorin
IV drug use (possible pseudomonas aeruginosa) – ceftazidime +/- an aminoglycosideOnce cultures are available, antibiotics can be changed to target the specific organism. After a good response to intravenous antibiotics, people can be switched to oral antibiotics. The duration of oral antibiotics varies, but is generally for 1–4 weeks depending on the offending organism. Repeated daily joint aspiration is useful in the treatment of septic arthritis. Every aspirate should be sent for culture, gram stain, white cell count to monitor the progress of the disease. Both open surgery and arthroscopy are helpful in the drainage of the infected joint. During surgery, lysis of the adhesions, drainage of pus, and debridement of the necrotic tissues are done. Close follow up with physical exam & labs must be done to make sure the person is no longer feverish, pain has resolved, has improved range of motion, and lab values are normalized.In infection of a prosthetic joint, a biofilm is often created on the surface of the prosthesis which is resistant to antibiotics. Surgical debridement is usually indicated in these cases. A replacement prosthesis is usually not inserted at the time of removal to allow antibiotics to clear infection of the region. People that cannot have surgery may try long-term antibiotic therapy in order to suppress the infection. The use of prophylactic antibiotics before dental, genitourinary, gastrointestinal procedures to prevent infection of the implant is controversial.Low-quality evidence suggests that the use of corticosteroids may reduce pain and the number of days of antibiotic treatment in children.
Outcomes
Risk of permanent impairment of the joint varies greatly. This usually depends on how quickly treatment is started after symptoms occur as longer lasting infections cause more destruction to the joint. The involved organism, age, preexisting arthritis, and other comorbidities can also increase this risk. Gonococcal arthritis generally does not cause long term impairment. For those with Staphylococcus aureus septic arthritis, 46 to 50% of the joint function returns after completing antibiotic treatment. In pneumococcal septic arthritis, 95% of the joint function will return if the person survives. One-third of people are at risk of functional impairment (due to amputation, arthrodesis, prosthetic surgery, and deteriorating joint function) if they have an underlying joint disease or a synthetic joint implant. Mortality rates generally range from 10 to 20%. These rates increase depending on the offending organism, advanced age, and comorbidities such as rheumatoid arthritis.
Epidemiology
In children and adolescence septic arthritis and acute hematogenous osteomyelitis occurs in about 1.34 to 82 per 100,000 per annual hospitalization rates. In adults septic arthritis occurs in about 5 people per 100,000 each year. It occurs more commonly in older people. With treatment, about 15% of people die, while without treatment 66% die.
References
== External links == |
Benign paroxysmal vertigo of childhood | Benign paroxysmal vertigo of childhood is an uncommon neurological disorder which presents with recurrent episodes of dizziness. The presentation is usually between the ages of 2 years and 7 years of age and is characterised by short episodes of vertigo of sudden onset when the child appears distressed and unwell. The child may cling to something or someone for support. The episode lasts only minutes and resolves suddenly and completely. It is a self-limiting condition and usually resolves after about eighteen months, although many go on to experience migrainous vertigo (or vestibular migraine) when older.Benign paroxysmal vertigo of childhood is a migrainous phenomenon with more than 50% of those affected having a family history of migraines affecting a first-degree relative. It has no relationship to benign paroxysmal positional vertigo which is a different condition entirely.
== References == |
Spastic quadriplegia | Spastic quadriplegia, also known as spastic tetraplegia, is a subset of spastic cerebral palsy that affects all four limbs (both arms and legs).
Compared to quadriplegia, spastic tetraplegia is defined by spasticity of the limbs as opposed to strict paralysis. It is distinguishable from other forms of cerebral palsy in that those afflicted with the condition display stiff, jerky movements stemming from hypertonia of the muscles.Spastic quadriplegia, while affecting all four limbs more or less equally, can still present parts of the body as stiffer than others, such as one arm being tighter than another arm, and so forth. Spastic triplegia, meanwhile, involves three limbs (such as one arm and two legs, or one leg and two arms, etc.); spastic diplegia affects two limbs (commonly just the legs), spastic hemiplegia affects one or another entire side of the body (left or right); and spastic monoplegia involves a single limb.
Symptoms and signs
Spastic quadriplegia can be detected by the abnormal development of motor skills in children. Symptoms can present themselves as early as three months but are generally seen before the child reaches two years of age. Some warning signs include: a child of more than two months who has stiff legs that scissor and is unable to control his or her head, and a child of more than twelve months who has not developed the ability to crawl or stand.Spastic quadriplegia also presents a range of symptoms that affect the musculature. Many experience contractures, which are defined as joints that cannot be stretched or moved. Clonus is another symptom that is characterized by alternating, rapid muscle contraction and relaxation. This presents itself as tremors and scissoring of the limbs. Distonia, or lasting muscle contractions and tightness, is also often experienced by those affected by spastic quadriplegia. These involuntary muscle contractions may affect the development of structural muscle around the hip and lead to hip dysplasia and dislocation, making it difficult to sit. The combination of these symptoms often makes it difficult for the patients to walk as well. Although the arms and legs of patients are often stiff, the neck is usually limp due to the lack of voluntary muscle control.
Causes
Spastic quadriplegia is generally caused by brain damage or disruptions in normal brain development preceding birth. According to the National Institutes of Health, there are four types of brain damage that can cause spastic quadriplegia. These include, damage to the white matter (periventricular leukomalacia), abnormal brain development (cerebral dysgenesis), bleeding in the brain (intracranial hemorrhage), and brain damage due to lack of oxygen (hypoxic-ischemic encephalopathy or intrapartum asphyxia).The white matter of the brain is especially vulnerable between the 26th and 34th weeks of maturation, and damage to the white matter can interfere with the brain’s ability to transmit signals to the rest of the body. Spastic quadriplegia can be caused by a condition known as periventricular leukomalacia which results in the formation of lesions and holes in the white matter of the brain.Prior to the 26th week of maturation, the fetal brain is particularly susceptible to various toxins whose effects can ultimately hinder normal development. Exposure of the brain to infectious agents is especially dangerous because they can trigger immune responses that activate cytokines and lead to inflammation of the brain. Some infections that have been linked to the development of spastic quadriplegia include meningitis, herpes, rubella, and encephalitis. A difference in blood types between the mother and the fetus can also initiate a problematic immune response and cause brain damage. Severe jaundice, can also lead to brain damage and spastic quadriplegia due to a buildup of bilirubin in the blood.Bleeding in the brain caused by fetal strokes, blood clots, weak and malformed blood vessels, or high maternal blood pressure may also lead to brain damage causing spastic quadriplegia. Maternal infection, most specifically pelvic inflammatory disease, has been shown to increase the risk of fetal stroke.Hypoxia, lack of oxygen to the brain, can also cause damage in the cerebral motor cortex and other brain regions. This lack of oxygen can be the result of placenta malfunction, womb rupture, umbilical cord damage, low maternal blood pressure or asphyxia during labor and delivery.Children who experienced many complications during birth, such as, prematurity, insufficient oxygen, low birthweight, aspiration, head injury, or bleeding in the brain have a greater risk of developing spastic quadriplegia. Children whose mothers were ill during the pregnancy or did not receive adequate nutrition are also more likely to develop the disease.
Diagnosis
Spastic quadriplegia can be diagnosed as early as age one after a noticed delay in development, particularly a delay in rolling, crawling, sitting, or walking. However, depending on the severity, signs may not show up until the age of three. Muscle tone is sometimes used to make the diagnosis for spastic quadriplegia as affected children often appear to be either too stiff or too floppy.Another important diagnostic factor is the persistence of primitive reflexes past the age at which they should have disappeared (6–12 months of age). These reflexes include the rooting reflex, the sucking reflex, and the Moro reflex, among others.Magnetic resonance imaging (MRI) or a computed tomography scan (CT scan) may be used to locate the cause of the symptoms. Ultrasound may be used for the same function in premature babies.Because cerebral palsy refers to a group of disorders, it is important to have a clear and systematic naming system. These disorders must be non-progressive, non-transient, and not due to injury to the spinal cord. Disorders within the group are classified based on two characteristics- the main physiological symptom, and the limbs that are affected. For a disorder to be diagnosed as spastic quadriplegia, an individual must show spastic symptoms (as opposed to athetotic, hypertonic, ataxic, or atonic symptoms) and it must be present in all four limbs (as opposed to hemiplegic, diplegic, or triplegic cases).While a diagnosis may be able to be made shortly after birth based on family history and observation of the infant, it is often postponed until after the child is between 18–24 months old in order to monitor the possible regression or progression of symptoms.
Scientific classification
The scientific classifications for these types include:
Management
Research
Doublecortin positive cells, similar to stem cells, are extremely adaptable and, when extracted from a brain, cultured and then re-injected in a lesioned area of the same brain, they can help repair and rebuild it. The treatment using them would take some time to be available for general public use, as it has to clear regulations and trials.
Notes
== External links == |
Bruns nystagmus | Bruns nystagmus is an unusual type of bilateral nystagmus most commonly occurring in patients with cerebellopontine angle tumours. It is caused by the combination of slow, large amplitude nystagmus (gaze paretic nystagmus) when looking towards the side of the lesion, and rapid, small amplitude nystagmus (vestibular nystagmus) when looking away from the side of the lesion. It occurs in 11% of patients with vestibular schwannoma, and occurs mainly in patients with larger tumours (67% of patients with tumours over 3.5 cm diameter). Bruns nystagmus is also associated with an increased incidence of balance disturbance in patients with vestibular schwannoma. It may be caused by the compression of both flocculi, the vestibular part of the cerebellum, and improvement in both the nystagmus and balance problems occur commonly after removal of the tumour.Bruns nystagmus is named for Ludwig Bruns (1858 – 1915).
== References == |
Pseudopelade of Brocq | Pseudopelade of Brocq is a flesh- to pink-colored, irregularly shaped alopecia that may begin in a moth-eaten pattern with eventual coalescence into larger patches of alopecia.: 648 : 761
See also
Cicatricial alopecia
Louis-Anne-Jean Brocq
List of cutaneous conditions
References
== External links == |
Manganese deficiency | Manganese deficiency may refer to:
Manganese deficiency (medicine)
Manganese deficiency (plant) |
Lisch epithelial corneal dystrophy | Lisch epithelial corneal dystrophy (LECD), also known as band-shaped and whorled microcystic dystrophy of the corneal epithelium, is a rare form of corneal dystrophy first described in 1992 by Lisch et al. In one study it was linked to chromosomal region Xp22.3, with as yet unknown candidate genes.The main features of this disease are bilateral or unilateral gray band-shaped and feathery opacities. They sometimes take on a form of a whirlpool, repeating the known pattern of corneal epithelium renewal. Abrasion of the epithelium in 3 patients brought only temporary relief, with abnormal epithelium regrowth in several months.Epithelial cells in the zones of opacity were shown to have diffuse cytoplasmic vacuoles with as yet unestablished content.
References
== External links == |
Carney complex | Carney complex and its subsets LAMB syndrome and NAME syndrome are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity. It is distinct from Carneys triad. Approximately 7% of all cardiac myxomas are associated with Carney complex.
Presentation
The spotty skin pigmentation and lentigines occur most commonly on the face, especially on the lips, eyelids, conjunctiva and oral mucosa. Cardiac myxomas may lead to embolic strokes and heart failure and may present with fever, joint pain, shortness of breath, diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may manifest as disorders such as Cushing syndrome. The most common endocrine gland manifestation is an ACTH-independent Cushings syndrome due to primary pigmented nodular adrenocortical disease (PPNAD).
The LAMB acronym refers to lentigines, atrial myxomas, and blue nevi. NAME refers to nevi, atrial myxoma, myxoid neurofibromas, and ephelides.Testicular cancer, particularly Sertoli cell type, is associated with Carney syndrome. Thyroid and pancreas cancer may also occur.Although J Aidan Carney also described Carneys triad it is entirely different.
Pathophysiology
Carney complex is most commonly caused by mutations in the PRKAR1A gene on chromosome 17 (17q23-q24)
which may function as a tumor-suppressor gene. The encoded protein is a type 1A regulatory subunit of protein kinase A. Inactivating germline mutations of this gene are found in 70% of people with Carney complex.Less commonly, the molecular pathogenesis of Carney complex is a variety of genetic changes at chromosome 2 (2p16).Both types of Carney complex are autosomal dominant. Despite dissimilar genetics, there appears to be no phenotypic difference between PRKAR1A and chromosome 2p16 mutations.
Treatment
Cardiac myxomas can be difficult to manage surgically because of recurrence within the heart, often far away from the site of the initial tumor.
History
In 1914 an American neurosurgeon, Harvey Cushing, reported on a patient with a pituitary tumour on whom he had operated. The post mortem findings as reported were consistent with Carney complex, though at the time this condition had yet to be described. In 2017 archived tissue from the operation in Cushings report was subjected to DNA sequencing, revealing an Arg74His (arginine to histidine: guanine (G)-> adenosine (A) transition in the second codon position of the 74th codon in the protein) mutation in the PRKAR1A gene, confirming a diagnosis of Carney complex. Therefore, Cushings paper appears to be the first report of this complex.
See also
Epithelioid blue nevus
List of cutaneous neoplasms associated with systemic syndromes
References
External links
GeneReview/UW/NIH entry on Carney complex |
Chemical colitis | Chemical colitis is a type of colitis, an inflammation of the large intestine or colon, caused by the introduction of harsh chemicals to the colon by an enema or other procedure. Chemical colitis can resemble ulcerative colitis, infectious colitis and pseudomembranous colitis endoscopically.Prior to 1950, hydrogen peroxide enemas were commonly used for certain conditions. This practice will often result in chemical colitis.Soap enemas may also cause chemical colitis.
Harsh chemicals, such as compounds used to clean colonoscopes, are sometimes accidentally introduced into the colon during colonoscopy or other procedures. This can also lead to chemical colitis.Chemical colitis may trigger a flare of ulcerative colitis or Crohns colitis. Symptoms of colitis are assessed using the Simple Clinical Colitis Activity Index.
== References == |
3-Methylglutaconic aciduria | 3-Methylglutaconic aciduria (MGA) is any of at least five metabolic disorders that impair the bodys ability to make energy in the mitochondria. As a result of this impairment, 3-methylglutaconic acid and 3-methylglutaric acid build up and can be detected in the urine.
3-Methylglutaconic acid is an organic acid. The double carboxylic acid functions are the principal cause of the strength of this acid. 3-methylglutaconic acid can be detected by the presence of the acid function and the double connection that involves reactivity with some specific substances.
Genetics
The inheritance patterns of 3-methylglutaconic aciduria differ depending on the gene involved.
Types I and III are inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.
Type II is inherited in an X-linked recessive pattern. A condition is considered X-linked if the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation must be present in both copies of the gene to cause the disorder. Males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.
The inheritance pattern of 3-methylglutaconic aciduria type IV is unknown.
Diagnosis
Diagnosis is typically post-mortem.
Classification
There are five known subgroups of MGA; MGA type I, II, III, IV & V.
The characteristic features of 3-methylglutaconic aciduria type I include speech delay, delayed development of both mental and motor skills (psychomotor delay), elevated levels of acid in the blood and tissues (metabolic acidosis), abnormal muscle tone (dystonia), and spasms and weakness affecting the arms and legs (spastic quadriparesis). Fewer than 20 cases of 3-methylglutaconic aciduria type I have been reported.
Barth syndrome is a common name for 3-methylglutaconic aciduria type II. The main features of Barth syndrome include a weakened and enlarged heart (dilated cardiomyopathy), recurrent infections due to low numbers of white blood cells (neutropenia), skeletal problems, and delayed growth. The incidence of 3-methylglutaconic aciduria type II is approximately 1 in 200,000 male infants.
Costeff syndrome is another name for 3-methylglutaconic aciduria type III. This disorder is characterized mainly by the degeneration of the optic nerves, which carry information from the eyes to the brain. Sometimes other nervous system problems occur, such as an inability to maintain posture, poor muscle tone, the development of certain involuntary movements (extrapyramidal dysfunction), and a general decrease in brain function (cognitive deficit). The incidence of 3-methylglutaconic aciduria type III is about 1 in 10,000 newborns in the Iraqi Jewish population. This disorder is extremely rare in all other populations.
The signs and symptoms of 3-methylglutaconic aciduria type IV are variable and overlap with types I-III. The incidence of 3-methylglutaconic aciduria type IV is unknown.
Treatment
There is no known treatment or cure.
Epidemiology
3-Methylglutaconic aciduria seems to be most prevalent amongst the Jewish population of Iraq. However, a high concentration of one type is found in the Saguenay-Lac-Saint-Jean region of Canada. This suggests that the disease is more frequent in insular areas where there is more likelihood that both parents are carriers, a higher birth rate, and a greater frequency of consanguineous marriages. As all types of 3-Methylglutaconic aciduria are known to be genetic diseases and show a recessive inheritance pattern, consanguineous marriages (in which both partners may have inherited the mutation from the same ancestor) increase the chances of having a baby with the condition.
References
External links
"3-METHYLGLUTACONIC ACIDURIA". Datagenno.
Anikster Y (2020). Adam MP, Ardinger HH, Pagon RA, et al. (eds.). "Costeff Syndrome". GeneReviews® [Internet]. University of Washington. PMID 20301646. NBK1473.
3-Methylglutaconic aciduria at NLM Genetics Home Reference |
Waterhouse–Friderichsen syndrome | Waterhouse–Friderichsen syndrome (WFS) is defined as adrenal gland failure due to bleeding into the adrenal glands, commonly caused by severe bacterial infection. Typically, it is caused by Neisseria meningitidis.The bacterial infection leads to massive bleeding into one or (usually) both adrenal glands. It is characterized by overwhelming bacterial infection meningococcemia leading to massive blood invasion, organ failure, coma, low blood pressure and shock, disseminated intravascular coagulation (DIC) with widespread purpura, rapidly developing adrenocortical insufficiency and death.
Signs and symptoms
Waterhouse-Friderichsen syndrome can be caused by a number of different organisms (see below). When caused by Neisseria meningitidis, WFS is considered the most severe form of meningococcal sepsis. The onset of the illness is nonspecific with fever, rigors, vomiting, and headache. Soon a rash appears; first macular, not much different from the rose spots of typhoid, and rapidly becoming petechial and purpuric with a dusky gray color. Low blood pressure (hypotension) develops and rapidly leads to septic shock. The cyanosis of extremities can be extreme and the patient is very prostrated or comatose. In this form of meningococcal disease, meningitis generally does not occur. Low levels of blood glucose and sodium, high levels of potassium in the blood, and the ACTH stimulation test demonstrate the acute adrenal failure. Leukocytosis need not be extreme and in fact leukopenia may be seen and it is a very poor prognostic sign. C-reactive protein levels can be elevated or almost normal. Thrombocytopenia is sometimes extreme, with alteration in prothrombin time (PT) and partial thromboplastin time (PTT) suggestive of disseminated intravascular coagulation (DIC). Acidosis and acute kidney failure can be seen as in any severe sepsis. Meningococci can be readily cultured from blood or cerebrospinal fluid, and can sometimes be seen in smears of cutaneous lesions. Difficulty swallowing, atrophy of the tongue, and cracks at the corners of the mouth are also characteristic features.
Causes
Multiple species of bacteria can be associated with the condition:
Meningococcus is another term for the bacterial species Neisseria meningitidis; blood infection with said species usually underlies WFS. While many infectious agents can infect the adrenals, an acute, selective infection is usually meningococcus.
Pseudomonas aeruginosa can also cause WFS.
WFS can also be caused by Streptococcus pneumoniae infections, a common bacterial pathogen typically associated with meningitis in the adult and elderly population.
Mycobacterium tuberculosis could also cause WFS. Tubercular invasion of the adrenal glands could cause hemorrhagic destruction of the glands and cause mineralocorticoid deficiency.
Staphylococcus aureus has recently also been implicated in pediatric WFS.
It can also be associated with Haemophilus influenzae.Viruses may also be implicated in adrenal problems:
Cytomegalovirus can cause adrenal insufficiency, especially in the immunocompromised.
Ebola virus infection may also cause similar acute adrenal failure.
Diagnosis
Diagnostic criteria are based on clinical features of adrenal insufficiency as well as identifying the causal agent. If the causal agent is suspected to be meningitis a lumbar puncture is performed. If the causal agent is suspected to be bacterial a blood culture and complete blood count is performed. An adrenocorticotropic hormone stimulation test can be performed to assess adrenal function.
Prevention
Routine vaccination against meningococcus is recommended by the Centers for Disease Control and Prevention for all 11- to 18-year-olds and people who have poor splenic function (who, for example, have had their spleen removed or who have sickle-cell disease which damages the spleen), or who have certain immune disorders, such as a complement deficiency.
Treatment
Fulminant infection from meningococcal bacteria in the bloodstream is a medical emergency and requires emergent treatment with vasopressors, fluid resuscitation, and appropriate antibiotics. Benzylpenicillin was once the drug of choice with chloramphenicol as a good alternative in allergic patients. Ceftriaxone is an antibiotic commonly employed today. Hydrocortisone can sometimes reverse the adrenal insufficiency. Amputations, reconstructive surgery, and tissue grafting are sometimes needed as a result of tissue necrosis (typically of the extremities) caused by the infection.
History
Waterhouse–Friderichsen syndrome is named after Rupert Waterhouse (1873–1958), an English physician, and Carl Friderichsen (1886–1979), a Danish pediatrician, who wrote papers on the syndrome, which had been previously described.
References
== External links == |
Diastasis (pathology) | In pathology, diastasis is the separation of parts of the body that are normally joined, such as the separation of certain abdominal muscles during pregnancy, or of adjacent bones without fracture.
See also
Diastasis recti
Diastasis symphysis pubisCompare with:
Diastasis (physiology)
== References == |
Selenium deficiency | Selenium deficiency occurs when an organism lacks the required levels of selenium, a critical nutrient in many species. Deficiency, although relatively rare in healthy well-nourished individuals, can have significant negative results, affecting the health of the heart and the nervous system; contributing to depression, anxiety, and dementia; and interfering with reproduction and gestation.
Signs and symptoms
Selenium deficiency in combination with Coxsackievirus infection can lead to Keshan disease, which is potentially fatal. Selenium deficiency also contributes (along with iodine deficiency) to Kashin-Beck disease. The primary symptom of Keshan disease is myocardial necrosis, leading to weakening of the heart. Kashin-Beck disease results in atrophy, degeneration and necrosis of cartilage tissue. Keshan disease also makes the body more susceptible to illness caused by other nutritional, biochemical, or infectious diseases.
Selenium is also necessary for the conversion of the thyroid hormone thyroxine (T4) into its more active counterpart triiodothyronine (T3), and as such a deficiency can cause symptoms of hypothyroidism, including extreme fatigue, mental slowing, goiter, cretinism, and recurrent miscarriage.
Causes
It can occur in patients with severely compromised intestinal function, those undergoing total parenteral nutrition, those who have had gastrointestinal bypass surgery, and also in persons of advanced age (i.e., over 90).People dependent on food grown from selenium-deficient soil may be at risk for deficiency. Increased risk for developing various diseases has also been noted, even when certain individuals lack optimal amounts of selenium, but not enough to be classified as deficient.For some time now, it has been reported in medical literature that a pattern of side-effects possibly associated with cholesterol-lowering drugs (e.g., statins) may resemble the pathology of selenium deficiency.
Diagnosis
Reference ranges
The European Food Safety Authority (EFSA) recommends a dietary allowance of 70 μg per day selenium intake for adults. In the US, the Dietary Reference Intake for adults is 55 µg/day. In the UK it is 75 µg/day for adult males and 60 µg/day for adult females. 55 µg/day recommendation is based on full expression of plasma glutathione peroxidase. Selenoprotein P is a better indicator of selenium nutritional status, and full expression of it would require more than 66 µg/day.
Epidemiology and prevention
Selenium deficiency is uncommon, but regions in China, Europe, Russia and New Zealand have low levels of selenium in croplands and diet. The worldwide prevalence of selenium deficiency is however predicted to rise under climate change due to the loss of selenium from croplands. These diseases are most common in certain parts of China where the intake is low because the soil is extremely deficient in selenium. Studies in Jiangsu Province of China have indicated a reduction in the prevalence of these diseases by taking selenium supplements. In Finland, selenium salts are added to chemical fertilizers, as a way to increase selenium in soils. Dietary supplements may utilize sodium selenite, L-selenomethionine or selenium-enriched yeast.
In non-human animals
In some regions (e.g. much of the northeastern and northwestern US and adjacent Canada, and the southeastern US), selenium deficiency in some animal species is common unless supplementation is carried out. Selenium deficiency is responsible (either alone or together with vitamin E deficiency) for many of the cases of WMD ("white muscle disease"), evidenced at slaughter or during necropsy by whitish appearance of striated muscle tissue due to bleaching by peroxides and hydroperoxides. Although this degenerative disease can occur in foals, pigs and other animal species, ruminants are particularly susceptible. In general, absorption of dietary selenium is lower in ruminants than in non-ruminants, and is lower from forages than from grain. Sheep are more susceptible than cattle to WMD, and goats are more susceptible than sheep. Because of seleniums role in certain peroxidases (converting hydroperoxides to alcohols) and because of the antioxidant role of vitamin E (preventing hydroperoxide formation), a low level of Se can be somewhat (but not wholly) compensated by a high level of vitamin E. (In the animal, localization of peroxidases and vitamin E differs, partly because of the fat-solubility of vitamin E.) Some studies have indicated that about 0.12 or 0.23 mg Se per kg of dry matter intake may be sufficient for avoiding Se deficiency in sheep in some circumstances. However, somewhat higher Se intake may be required for avoidance of WMD where certain legumes are consumed. The cyanogenic glycosides in some white clover (Trifolium repens) varieties may influence the Se requirement, presumably because of cyanide from the aglycone released by glucosidase activity in the rumen and inactivation of glutathione peroxidases by the effect of absorbed cyanide on the glutathione moiety.In areas where selenium deficiency in livestock is a concern, selenium (as selenite) may be supplemented in feed. In some countries, e.g. the US and Canada, such supplementation is regulated. Neonate ruminants at risk of WMD may be administered both Se and vitamin E by injection; some of the WMD myopathies respond only to Se, some only to vitamin E, and some to either.
References
== External links == |
Protothecosis | Protothecosis, otherwise known as Algaemia, is a disease found in dogs, cats, cattle, and humans caused by a type of green alga known as Prototheca that lacks chlorophyll and enters the human or animal bloodstream. It and its close relative Helicosporidium are unusual in that they are actually green algae that have become parasites. The two most common species are Prototheca wickerhamii and Prototheca zopfii. Both are known to cause disease in dogs, while most human cases are caused by P. wickerhami. Prototheca is found worldwide in sewage and soil. Infection is rare despite high exposure, and can be related to a defective immune system. In dogs, females and Collies are most commonly affected.The first human case was identified in 1964 in Sierra Leone.
Cause
Prototheca has been thought to be a mutant of Chlorella, a type of single-celled green alga. However, while Chlorella contains galactose and galactosamine in the cell wall, Prototheca lacks these. Also, Chlorella obtains its energy through photosynthesis, while Prototheca is saprotrophic, feeding on dead and decaying organic matter. When Prototheca was first isolated from slime flux of trees in 1894, it was thought to be a type of fungus. Its size varies from 2 to 15 micrometres.
Treatment
Treatment with amphotericin B has been reported.
In cattle
Cattle can be affected by protothecal enteritis and mastitis. Protothecal mastitis is endemic worldwide, although most cases of infected herds have been reported in Germany, the United States, and Brazil.
In dogs
Disseminated protothecosis is most commonly seen in dogs. The algae enters the body through the mouth or nose and causes infection in the intestines. From there it can spread to the eye, brain, and kidneys. Symptoms can include diarrhea, weight loss, weakness, inflammation of the eye (uveitis), retinal detachment, ataxia, and seizures.Dogs with acute blindness and diarrhea that develop exudative retinal detachment should be assessed for protothecosis. Diagnosis is through culture or finding the organism in a biopsy, cerebrospinal fluid, vitreous humour, or urine. Treatment of the disseminated form in dogs is very difficult, although use of antifungal medication has been successful in a few cases. Prognosis for cutaneous protothecosis is guarded and depends on the surgical options. Prognosis for the disseminated form is grave. This may be due to delayed recognition and treatment.
See also
Progressive disseminated histoplasmosis
List of cutaneous conditions
Chlorellosis
References
== External links == |
Myhre syndrome | Myhre syndrome is a rare genetic disorder inherited in an autosomal dominant fashion. It is caused by mutation in SMAD4 gene.
Signs and symptoms
The clinical presentation is variable but includes
developmental and growth delay
athletic muscular built
skeletal anomalies
joint stiffness
characteristic facial appearance
deafness
variable cognitive deficits
tracheal stenosis
aortic stenosis
pyloric stenosisThe facial abnormalities include:
blepharophimosis (an abnormally narrow gap between the upper and lower eyelids)
maxillary hypoplasia (underdevelopment of the upper jaw)
prognathism (prominent lower jaw)The skeletal abnormalities include:
short stature
square body shape
broad ribs
iliac hypoplasia
brachydactyly
flattened vertebrae
thickened calvariaCongenital heart disease and undescended testes have also been reported in association with this syndrome.
Genetics
Myhre syndrome is due to mutations in the SMAD4 gene. This gene encodes a protein - transducer mediating transforming growth factor beta. Some researchers believe that the SMAD4 gene mutations that cause Myhre syndrome impair the ability of the SMAD4 protein to attach (bind) properly with the other proteins involved in the signaling pathway. Other studies have suggested that these mutations result in an abnormally stable SMAD4 protein that remains active in the cell longer. Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome.The patients of this disease exhibit hypertrophic phenotype in their muscle tissues. Myostatin target genes are found to be downregulated while bone morphogenetic protein (BMP) target genes display both upregulated and downregulated genotypes.
Diagnosis
Treatment
History
This disorder was first reported in 1981.
It has many similarities to LAPS Syndrome and they both arise from the same mutations in the SMAD4 gene. It is believed that they are the same syndrome.
References
This article incorporates text from the United States National Library of Medicine ([1]), which is in the public domain.
== External links == |
Mesenteric pseudocyst | Mesenteric pseudocyst (Pseudomesenteric cyst) is a mass in the abdomen that is devoid of any epithelial lining. They are caused either due to trauma or infection. The term mesenteric pseudocyst was first used by Ros et al in 1987. Mesenteric pseudocysts are very rare, making up only about less than one in 250,000 hospital admissions.
== References == |
Optic nerve glioma | Optic nerve glioma (or optic glioma), a form of glioma which affects the optic nerve, is often one of the central nervous system manifestations of neurofibromatosis 1.Optic gliomas are usually pilocytic tumors, and can involve the optic nerve or optic chiasm. Optic gliomas are usually associated with neurofibromatosis type 1 in 30% of people with the condition.Optic nerve gliomas have low mortality but extremely high prevalence of vision loss & eye-bulging exophthalmos) in children. As of 2014, approximately 1000 cases had been reported.
Diagnosis
Optic nerve gliomas are diagnosed using magnetic resonance imaging (MRI) and CT scans. The tumor adopts a fusiform appearance, appearing wider in the middle and tapered at the ends. Enlargement of the optic nerve along with a downward kink in the mid-orbit is usually observed. While CT scans allow for optic nerve evaluation, MRI allows for intracranial evaluation to observe if the tumor has extended to other regions such as the optic chiasm & hypothalamus.
Treatment
The main goal of treating optic gliomas is to preserve vision for as long as possible. The tumor’s slow & self-limiting growth indicates that it is not immediately problematic in most benign cases, with long-term studies showing that people with optic glioma may still have stable functional vision without intervention. As a result, the first & preferred course of action is usually observation of optic glioma over time.Once the first signs of visual deterioration and/or tumor progression are observed, interventional treatments will then commence. These include radiation therapy, [[chemotherapy and surgical excision. While being the most effective therapy, radiation has shown damaging effects on the already compromised intellect as well as an increase in vascular issues & second tumor formation in children with neurofibromatosis 1. However, fractionated stereotactic radiation therapy (FSRT) is gaining traction as the most preferred interventional treatment for optic nerve glioma due to its combination of the therapeutic efficiency of radiation therapy without the negative side effects. Chemotherapy has also been shown to be a safer alternative to most radiation therapies & surgery for very young children (under the age of 3). However, the optimal chemotherapeutic therapy has not been defined, with risks of different toxicities still observed in older children. Surgery is considered the final choice of treatment, due to the high risk of blindness & damage to the affected eye. It is considered in only certain scenarios, such as relieving a cosmetically unappealing bulging eye (exophthalmos), removing an enlarging and/or expanding tumor or a combination of both.
Prognosis
Optic gliomas alternate between periods of inactivity and growth, making their clinical presentation variable & clinical course unpredictable. Once the optic chiasm is involved, the prognosis for life & vision worsens.
References
External links
00724 at CHORUS |
Da Costas syndrome | Da Costas syndrome (also known as "soldiers heart", cardiac neurosis, chronic asthenia, effort syndrome, functional cardiovascular disease, neurocirculatory asthenia, primary neurasthenia, subacute asthenia and irritable heart) is a psychiatric syndrome which presents a set of symptoms similar to those of heart disease. These include fatigue upon exertion, shortness of breath, palpitations, sweating, and chest pain.
While a physical examination does not reveal any gross physiological abnormalities, orthostatic intolerance has been noted. It was originally thought to be a cardiac condition, and treated with a predecessor to modern cardiac drugs. While the condition was eventually recategorized as psychiatric, in modern times, it is known to represent several disorders, some of which now have a known medical basis. For stress-related combat disorders generally, see post-traumatic stress disorder.
Historically, similar forms of this disorder have been noticed in various wars, like the American Civil War and Crimean war, and among British troops who colonized India. The condition was named after Jacob Mendes Da Costa who investigated and described the disorder in 1871.
Signs and symptoms
Symptoms of Da Costas syndrome include fatigue upon exertion, weakness induced by minor activity, shortness of breath, palpitations, sweating, and chest pain.
Causes
Da Costas syndrome was originally considered to be heart failure or other cardiac condition, and was later recategorized to be psychiatric. The term is no longer in common use by any medical agencies and has generally been superseded by more specific diagnoses, some of which have a medical basis.
Diagnosis
Although it is listed in the ICD-9 (306.2) and ICD-10 (F45.8) under "somatoform autonomic dysfunction", the term is no longer in common use by any medical agencies and has generally been superseded by more specific diagnoses.
The orthostatic intolerance observed by Da Costa has since also been found in patients diagnosed with chronic fatigue syndrome, postural orthostatic tachycardia syndrome (POTS) and mitral valve prolapse syndrome. In the 21st century, this intolerance is classified as a neurological condition. Exercise intolerance has since been found in many organic diseases.
Classification
There are many names for the syndrome, which has variously been called soldiers heart, cardiac neurosis, chronic asthenia, effort syndrome, functional cardiovascular disease, neurocirculatory asthenia, primary neurasthenia, and subacute asthenia. Da Costa himself called it irritable heart and the term soldiers heart was in common use both before and after his paper. Most authors use these terms interchangeably, but some authors draw a distinction between the different manifestations of this condition, preferring to use different labels to highlight the predominance of psychiatric or non-psychiatric complaints. For example, Oglesby Paul writes that "Not all patients with neurocirculatory asthenia have a cardiac neurosis, and not all patients with cardiac neurosis have neurocirculatory asthenia." None of these terms have widespread use.
Treatment
The report of Da Costa shows that patients recovered from the more severe symptoms when removed from the strenuous activity or sustained lifestyle that caused them. A reclined position and forced bed rest were the most beneficial.Other treatments evident from the previous studies were improving physique and posture, appropriate levels of exercise where possible, wearing loose clothing about the waist, and avoiding postural changes such as stooping, or lying on the left or right side, or the back in some cases, which relieved some of the palpitations and chest pains, and standing up slowly can prevent the faintness associated with postural or orthostatic hypotension in some cases.
Pharmacological intervention came in the form of digitalis, a group of glycoside drugs derived from the foxglove (Digitalis purpurea), which is now known to act as a sodium-potassium ATPase inhibitor, increasing stroke volume and decreasing heart rate; at the time it was used for the latter effect in patients with palpitations.
History
Da Costas syndrome is named for the surgeon Jacob Mendes Da Costa, who first observed it in soldiers during the American Civil War. At the time it was proposed, Da Costas syndrome was seen as a very desirable physiological explanation for "soldiers heart". Use of the term "Da Costas syndrome" peaked in the early 20th century. Towards the mid-century, the condition was generally re-characterized as a form of neurosis. It was initially classified as "F45.3" (under somatoform disorder of the heart and cardiovascular system) in ICD-10, and is now classified under "somatoform autonomic dysfunction".
Da Costas syndrome involves a set of symptoms which include left-sided chest pains, palpitations, breathlessness, and fatigue in response to exertion. Earl de Grey who presented four reports on British soldiers with these symptoms between 1864 and 1868, and attributed them to the heavy weight of military equipment being carried in knapsacks which were tightly strapped to the chest in a manner which constricted the action of the heart. Also in 1864, Henry Harthorme observed soldiers in the American Civil War who had similar symptoms which were attributed to “long-continued overexertion, with deficiency of rest and often nourishment”, and indefinite heart complaints were attributed to lack of sleep and bad food. In 1870 Arthur Bowen Myers of the Coldstream Guards also regarded the accoutrements as the cause of the trouble, which he called neurocirculatory asthenia and cardiovascular neurosis.J. M. Da Costas study of 300 soldiers reported similar findings in 1871 and added that the condition often developed and persisted after a bout of fever or diarrhoea. He also noted that the pulse was always greatly and rapidly influenced by position, such as stooping or reclining. A typical case involved a man who was on active duty for several months or more and contracted an annoying bout of diarrhoea or fever, and then, after a short stay in hospital, returned to active service. The soldier soon found that he could not keep up with his comrades in the exertions of a soldiers life as previously, because he would get out of breath, and would get dizzy, and have palpitations and pains in his chest, yet upon examination some time later he appeared generally healthy. In 1876 surgeon Arthur Davy attributed the symptoms to military foot drill where “over-expanding the chest, caused dilatation of the heart, and so induced irritability".During World War I, Sir Thomas Lewis (who had been a member of staff of the Medical Research Committee) studied many soldiers who had been referred to the Military Heart Hospitals in Hampstead and Colchester with disordered action of the heart or valvular disease of the heart. In 1918 he published a monograph summarizing his findings, which showed that the vast majority did not have structural heart disease, as evidenced by the diagnostic methods available at the time. In it, he reviewed the difference in symptoms between effort syndrome and structural heart disease, examined possible causes of effort syndrome, the diagnosis of structural heart disease in soldiers, its outlook and treatment, and lessons learned by the Army.
Since then, a variety of similar or partly similar conditions named above have been described.
See also
Shell shock
Combat fatigue
Takotsubo cardiomyopathy
Postural orthostatic tachycardia syndrome
Soldiers Heart (novel)
References
== External links == |
Fontanelle | A fontanelle (or fontanel) (colloquially, soft spot) is an anatomical feature of the infant human skull comprising soft membranous gaps (sutures) between the cranial bones that make up the calvaria of a fetus or an infant. Fontanelles allow for stretching and deformation of the neurocranium both during birth and later as the brain expands faster than the surrounding bone can grow. Premature complete ossification of the sutures is called craniosynostosis.
After infancy, the anterior fontanelle is known as the bregma.
Structure
An infants skull consists of five main bones: two frontal bones, two parietal bones, and one occipital bone. These are joined by fibrous sutures, which allow movement that facilitates childbirth and brain growth.
Posterior fontanelle is triangle-shaped. It lies at the junction between the sagittal suture and lambdoid suture. At birth, the skull features a small posterior fontanelle with an open area covered by a tough membrane, where the two parietal bones adjoin the occipital bone (at the lambda). The posterior fontanelles ossify within 6–8 weeks after birth. This is called intramembranous ossification. The mesenchymal connective tissue turns into bone tissue.
Anterior fontanelle is a diamond-shaped membrane-filled space located between the two frontal and two parietal bones of the developing fetal skull. It persists until approximately 18 months after birth. It is at the junction of the coronal suture and sagittal suture. The fetal anterior fontanelle may be palpated until 18 months. In cleidocranial dysostosis, however, it is often late in closing at 8–24 months or may never close. Examination of an infant includes palpating the anterior fontanelle.
Two smaller fontanelles are located on each side of the head, more anteriorly the sphenoidal or anterolateral fontanelle (between the sphenoid, parietal, temporal, and frontal bones) and more posteriorly the mastoid or posterolateral fontanelle (between the temporal, occipital, and parietal bones).During birth, fontanelles enable the bony plates of the skull to flex, allowing the childs head to pass through the birth canal. The ossification of the bones of the skull causes the anterior fontanelle to close over by 9 to 18 months. The sphenoidal and posterior fontanelles close during the first few months of life. The closures eventually form the sutures of the neurocranium. Other than the anterior and posterior fontanelles, the mastoid fontanelle and the sphenoidal fontanelle are also significant.
Closure
In humans, the sequence of fontanelle closure is as follows:
The posterior fontanelle generally closes 2 to 3 months after birth;
The sphenoidal fontanelle is the next to close around 6 months after birth;
The mastoid fontanelle closes next from 6 to 18 months after birth; and
The anterior fontanelle is generally the last to close between 12 and 18 months.
Clinical significance
The fontanelle may pulsate, and although the precise cause of this is not known, it is normal and seems to echo the heartbeat, perhaps via the arterial pulse within the brain vasculature, or in the meninges. This pulsating action is how the soft spot got its name – fontanelle is borrowed from the old French word fontenele, which is a diminutive of fontaine, meaning "spring". It is assumed that the term spring is used because of the analogy of the dent in a rock or earth where a spring arises.Parents may worry that their infant may be more prone to injury at the fontanelles. In fact, although they may colloquially be called "soft-spots", the membrane covering the fontanelles is extremely tough and difficult to penetrate.Fontanelles allow the infant brain to be imaged using ultrasonography. Once they are closed, most of the brain is inaccessible to ultrasound imaging, because the bony skull presents an acoustic barrier.
Disorders
Bulging
A very tense or bulging anterior fontanelle indicates raised intracranial pressure. Increased cranial pressure in infants may cause the fontanelles to bulge or the head to begin to enlarge abnormally. It can occur due to:
Craniosynostosis – premature fusion of the cranial sutures
Encephalitis – swelling (inflammation) of the brain, most often due to infections
Hydrocephalus – a buildup of fluid inside the skull
Meningitis – infection of the membranes covering the brain
Shaken baby syndrome
Sunken
A sunken (also called "depressed") fontanelle indicates dehydration or malnutrition.
Enlarged
The fontanelles may be enlarged, may be slow to close, or may never close, most commonly due to causes like:
Down syndrome
Hydrocephalus
Intrauterine growth restriction (IUGR)
Premature birthRarer causes include:
Achondroplasia
Apert syndrome
Cleidocranial dysostosis
Congenital rubella
Neonatal hypothyroidism
Osteogenesis imperfecta
Rickets
Third
Sometimes there is a third bigger fontanelle other than posterior and anterior ones in a newborn. In one study, the frequency of third fontanelles in an unselected population of newborn infants was 6.3%. It is very common in Down syndrome and some congenital infections. If present, the physician should rule out serious conditions associated with the third fontanelle.
Other animals
Primates
In apes the fontanelles fuse soon after birth. In chimpanzees the anterior fontanelle is fully closed by 3 months of age.
Dogs
One of the more serious problems that can affect canines is known as an "open fontanelle", which occurs when the skull bones at the top of the head fail to close. The problem is often found in conjunction with hydrocephalus, which is a condition in which too much fluid is found within and around the brain, placing pressure on the brain and surrounding tissues. Often the head will appear dome-shaped, and the open fontanelle is noticeable as a "soft spot" on the top of the dogs head. The fluid-filled spaces within the brain, known as ventricles, also become swollen. The increased pressure damages or prevents the development of brain tissue.Not all open fontanelles are connected with hydrocephalus. In many young dogs the skull bones are not fused at birth, but instead will close slowly over a three- to six-month period. Occasionally these bones fail to close, but the dog is still healthy. In these cases, however, the dogs owners need to be very careful, since any injury or bumps to the animals head could cause significant brain damage, as well as conditions like epilepsy.
An open fontanelle, known as a "molera", is a recognized feature of the Chihuahua breed. The American Kennel Club breed standard states that the skull of the Chihuahua should be domed, with or without the molera being present. However, the Fédération Cynologique Internationale (FCI) standard for the Chihuahua lists an open fontanelle as a disqualification.
Additional images
== References == |
Bolivian hemorrhagic fever | Bolivian hemorrhagic fever (BHF), also known as black typhus or Ordog Fever, is a hemorrhagic fever and zoonotic infectious disease originating in Bolivia after infection by Machupo mammarenavirus.BHF was first identified in 1963 as an ambisense RNA virus of the Arenaviridae family, by a research group led by Karl Johnson. The mortality rate is estimated at 5 to 30 percent. Due to its pathogenicity, Machupo virus requires Biosafety Level Four conditions, the highest level.During the period between February and March 2007, some 20 suspected BHF cases (3 fatal) were reported to the Servicio Departamental de Salud (SEDES) in Beni Department, Bolivia. In February 2008, at least 200 suspected new cases (12 fatal) were reported to SEDES. In November 2011, a second case was confirmed near the departmental capital of Trinidad, and a serosurvey was conducted to determine the extent of Machupo virus infections in the department. A SEDES expert involved in the survey expressed his concerns about the expansion of the virus to other provinces outside the endemic regions of Mamoré and Iténez provinces.
Epidemiology
History
The disease was first encountered in 1962, in the Bolivian village of San Joaquín, hence the name "Bolivian" Hemorrhagic Fever. When initial investigations failed to find an arthropod carrier, other sources were sought before finally determining that the disease was carried by infected mice. Although mosquitoes were not the cause as originally suspected, the extermination of mosquitoes using DDT to prevent malaria proved to be indirectly responsible for the outbreak in that the accumulation of DDT in various animals along the food chain led to a shortage of cats in the village; subsequently, a mouse plague erupted in the village, leading to an epidemic.
Vectors
The vector is the large vesper mouse (Calomys callosus), a rodent indigenous to northern Bolivia. Infected animals are asymptomatic and shed the virus in excreta, thereby infecting humans. Evidence of person-to-person transmission of BHF exists but is believed to be rare.
Symptoms
The infection has a slow onset with fever, malaise, headache and myalgia, very similar to Malaria symptoms. Petechiae (blood spots) on the upper body and bleeding from the nose and gums are observed when the disease progresses to the hemorrhagic phase, usually within seven days of onset. Severe hemorrhagic or neurologic symptoms are observed in about one third of patients. Neurologic symptoms involve tremors, delirium, and convulsions. The mortality rate is about 25%.
Prevention
Measures to reduce contact between the vesper mouse and humans may have contributed to limiting the number of outbreaks, with no cases identified between 1973 and 1994. Although there are no cures or vaccine for the disease, a vaccine developed for the genetically related Junín virus which causes Argentine hemorrhagic fever has shown evidence of cross-reactivity to Machupo virus, and may therefore be an effective prophylactic measure for people at high risk of infection. Post infection (and providing that the person survives the infection), those that have contracted BHF are usually immune to further infection of the disease.
Weaponization
Bolivian hemorrhagic fever was one of three hemorrhagic fevers and one of more than a dozen agents that the United States researched as potential biological weapons before the nation suspended its biological weapons program in 1969. Albert Nickel, a 53-year old animal caretaker at Fort Detrick, died in 1964 from the disease after being bitten by an infected mouse. Nickel Place, on Fort Detrick, is named in his honor. It was also under research by the Soviet Union, under the Biopreparat bureau.
Vaccine research
Investigational vaccines exist for Argentine hemorrhagic fever and RVF; however, neither is approved by FDA or commonly available in the United States.The structure of the attachment glycoprotein has been determined by X-ray crystallography and this glycoprotein is likely to be an essential component of any successful vaccine.
References
Bibliography
Medical Microbiology 2nd Edition Mims et al. Mosby Publishing 1998 p 371
== External links == |
Abscess of thymus | An abscess of the thymus (also known as "Dubois abscesses") is a condition that is one of many possible causes of cysts in the mediastinum.
It can present with chest pain behind the sternum.It can be associated with congenital syphilis.Although the thymus is usually classified with the immune system, thymic diseases are classified with endocrine disorders in ICD-9 and ICD-10.
References
== External links == |
Bouffée délirante | Bouffée délirante (BD) is an acute and transient psychotic disorder. It is a uniquely French psychiatric diagnostic term with a long history in France and various French speaking nations: Caribbean, e.g. Haiti, Guadeloupe, Antilles and Francophone Africa. The term BD was originally coined and described by Valentin Magnan (1835–1916), fell into relative disuse and was later revived by Henri Ey (1900–1977).
Terminology
The French word bouffée is often translated as a puff or waft (as of air), but can also mean a flash, rush or surge. Chabrol translates the word délirante as "delusional". Other common dictionary definitions include less useful meanings such as "crazy" or "incoherent". A reasonable English translation of the term bouffée délirante is "delusional flash".
Description
Bouffée délirante is "an acute, brief nonorganic psychosis that typically presents with a sudden onset of fully formed, thematically variable delusions and hallucinations against a background of some degree of clouding of consciousness, unstable and fluctuating affect, and spontaneous recovery with some probability of relapse." The following criteria have been suggested for a diagnosis of BD: a) abrupt onset, b) polymorphic delusions, emotional changes, mood swings, depersonalization, derealization and/or hallucinations, c) complete remission within weeks or a few months, d) exclusion of organic causation, alcohol or drug use, e) no psychiatric antecedents with the exception of a previous episode of bouffée délirante. American academic investigators proposed the following definition in 2011: "The French concept of bouffée délirante refers to conditions with a sudden onset marked by prominent delusions with hallucinations, confusion, anxiety and affective symptoms. Symptoms vary rapidly, perhaps even by the hour, and there is a rapid return to the premorbid state of health." A frequently quoted authority on BD, P. Pichot (Hôpital Sainte Anne, Paris) provides this description of BD:
sudden onset: a bolt from the blue.
manifold delusions without recognizable structure and cohesiveness with/without hallucinations.
clouding of consciousness associated with emotional instability.
absence of physical signs.
rapid return to pre-morbid level of functioning.Pichots criteria can be refined further with these typical clinical characteristics:
age: usually between 20 and 40 years of age.
onset: acute without prior mental illness (with the exception of previous episodes of bouffée délirante).
past history: no chronic mental disturbance after resolution of the BD episode.
typical symptoms: delusions and/or hallucinations of any type. Depersonalization/derealization and/or confusion
depression and/or elation.
symptoms quite variable from day to day and even hour to hour.
not due to alcohol, drug use, or organic mental disorder.
Formal classification
In 1968 the French national organization INSERM (Institut National de la Santé et de la Recherche Médicale) classification of mental illness referenced two types of BD in their category acute delusional psychoses and confusional states viz. reactive bouffée délirante and bouffée délirante (Magnans type). This classification scheme has been largely replaced by the two nosological systems discussed below.
The World Health Organization edition of the International Classification of Diseases 10th edition:version 2019 (ICD-10, CIM-10 en français), lists BD as the subentry "Bouffée délirante without symptoms of schizophrenia or unspecified" under diagnosis code F23: Acute and Transient Psychotic Disorders subsection, F23.0: Acute polymorphic psychotic disorder without symptoms of schizophrenia. It is likely that the use of the term BD in French clinical psychiatry will decline further with the proposed 2022 implementation of ICD-11 (which was released in May 2019.) In contrast to the ICD-10, the term BD does not appear anywhere in ICD-11. The closest clinical match for BD in the ICD-11 is code 6A23, Acute and transient psychotic disorder which is defined as
acute onset of psychotic symptoms that emerge without a prodrome and reach their maximal severity within two weeks. Symptoms may include delusions, hallucinations, disorganization of thought processes, perplexity or confusion, and disturbances of affect and mood. Catatonia-like psychomotor disturbances may be present. Symptoms typically change rapidly, both in nature and intensity, from day to day, or even within a single day. The duration of the episode does not exceed 3 months, and most commonly lasts from a few days to 1 month. The symptoms are not a manifestation of another health condition (e.g., a brain tumor) and are not due to the effect of a substance or medication on the central nervous system (e.g., corticosteroids), including withdrawal (e.g., alcohol withdrawal).
The Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) diagnostic category brief psychotic disorder is probably the closest analog of BD. The French term BD is nowhere mentioned in DSM-5. The diagnosis of Bouffée Délirante is still in use in the Classification Française des Troubles Mentaux (French Classification of Mental Disorder, CFTM) under the name Bouffée délirante aiguë.
Incidence
The frequency of BD diagnoses in French hospitals has been declining due to the widespread acceptance of international classification systems such as the ICD-10 and DSM-5. However, the BD diagnosis has been used as recently as 2019 in Le Groupe Hospitalier Universitaire Paris psychiatrie & neurosciences (GHU Paris), Maison Blanche Bichat XVIII. Older estimates of the incidence of BD in psychiatric hospitalizations ranges from 1–5%. Psychiatric admission reviews show that 2–7% of first episode psychotic episodes are due to brief psychotic disorder; here serving as a surrogate diagnosis for BD. Some authors state that the diagnostic category of BD can be eliminated because it can be fully integrated into the Polymorphic subgroup of Acute and Transient Psychotic Disorders of the ICD-10.
Treatment
There are no current published guidelines in the English language psychiatric literature that discuss treatment for BD. A 2019 case of BD from GHU Paris treated the patient with largactil (chlorpromazine). Assuming that BPD is an equivalent diagnosis, treatment depends on the severity of the episode. Mildly affected patients may receive supportive management and observation with additional outpatient therapy. More severe illness may require inpatient hospitalization and pharmacologic treatment with benzodiazepines and/or antipsychotic medication, for example: risperidone, though no clinical trials have examined the efficacy of therapy for BPD.
Prognosis
It is difficult to firmly establish the prognosis of first episode BD patients with respect to progression to other psychiatric illness or relapse to another psychotic episode. This is due to the fact that high quality follow-up studies of large cohorts of BD patients are unavailable in part because of the uncommon nature of the illness and non-standardization of diagnostic methods. Investigators attempting to define the prognosis in BD have used data from similar conditions, i.e. acute transient psychotic disorder (ATPD) and brief psychotic disorder (BPD). A meta-analysis involving 11,000 patients estimated the rate of recurrent psychotic episodes in ATPD and BPD patients was 51% at 30 months compared to first episode schizophrenia patients who had an 84% recurrence rate at 36 months. As suggested by the various definitions of BD discussed above, rapid recovery and return to pre-morbid level of function is expected, though quantitative data is lacking.
Society
Psychiatric illnesses comparable to the unique French BD can be seen in the cycloid psychosis of German speaking countries and the psychogenic psychosis in Scandinavia. It has been argued that acute and transient psychoses are more common in African and Afro-Caribbean populations and may be attributable to socio-cultural factors. This has led to the term "culture-bound syndrome." It must be stressed that the term BD long predates any such socio-cultural, ethnic, or regional uses. The African and Caribbean nuances of the diagnosis and presentation of BD has been extensively reviewed by Henry MB Murphy. Note that DSM-5 does not use the term culture-bound and the term BD is not listed in the "Glossary of Cultural Concepts of Distress" in DSM-5.
Summary
BD is a psychotic disorder of short duration generally considered to have a relatively good prognosis. The diagnosis has undergone numerous changes and re-evaluations since its description by Magnan in 1886. Though becoming replaced by more internationally recognized terminology, BD as a diagnostic category is still in use in France and other French speaking nations.
See also
Brief psychotic disorder
== References == |
Vitamin A deficiency | Vitamin A deficiency (VAD) or hypovitaminosis A is a lack of vitamin A in blood and tissues. It is common in poorer countries, especially among children and women of reproductive age, but is rarely seen in more developed countries. Nyctalopia (night blindness) is one of the first signs of VAD, as the vitamin has a major role in phototransduction. Xerophthalmia, keratomalacia, and complete blindness can follow if the deficiency is more severe.Vitamin A deficiency is the worlds leading cause of preventable childhood blindness, and is critical to achieving Millennium Development Goal 4 to reduce child mortality. About 250,000 to 500,000 malnourished children in the developing world go blind each year from a deficiency of vitamin A, around half of whom die within a year of becoming blind. The United Nations Special Session on Children in 2002 set a goal of the elimination of VAD by 2010.The prevalence of night blindness due to VAD is also high among pregnant women in many developing countries. VAD also contributes to maternal mortality and other poor outcomes in pregnancy and lactation.VAD also diminishes the ability to fight infections. In countries where children are not immunized, infectious diseases such as measles have higher fatality rates. As elucidated by Alfred Sommer, even mild, subclinical deficiency can also be a problem, as it may increase childrens risk of developing respiratory and diarrheal infections, decrease growth rate, slow bone development, and decrease likelihood of survival from serious illness.VAD is estimated to affect about one-third of children under the age of five around the world. It is estimated to claim the lives of 670,000 children under five annually. Around 250,000–500,000 children in developing countries become blind each year owing to VAD, with the highest prevalence in Southeast Asia and Africa. According to the World Health Organization (WHO), VAD is under control in the United States, but in developing countries, VAD is a significant concern. Globally, 65% of all children aged 6 to 59 months received two doses of vitamin A in 2013, fully protecting them against VAD (80% in the least developed countries).
Signs and symptoms
The most common cause of blindness in developing countries is Vitamin A deficiency. The WHO estimated in 1995 that 13.8 million children had some degree of visual loss related to VAD. Night blindness and its worsened condition, xerophthalmia, are markers of Vitamin A deficiency, collections of keratin in the conjunctiva, known as Bitots spots, and ulceration and necrosis of cornea keratomalacia can be seen. Conjunctival epithelial defects occur around lateral aspect of the limbus in the subclinical stage of VAD. These conjunctival epithelial defects are not visible on a biomicroscope, but they take up black stain and become readily visible after instillation of kajal (surma); this is called "Imtiazs sign".
Night blindness
Night blindness is the difficulty for the eyes to adjust to dim light. Affected individuals have poor vision in the darkness but see normally when adequate light is present.
A process called dark adaptation typically causes an increase in photopigment amounts in response to low levels of illumination. This occurs to an enormous magnitude, increasing light sensitivity by up to 100,000 times its sensitivity in normal daylight conditions. VAD affects vision by inhibiting the production of rhodopsin, the photopigment responsible for sensing low-light situations. Rhodopsin is found in the retina and is composed of retinal (an active form of vitamin A) and opsin (a protein). When VAD prevents the body from producing sufficient amounts of retinal, a decreased amount of rhodopsin is produced and night blindness results.
Night blindness caused by VAD has been associated with the loss of goblet cells in the conjunctiva, a membrane covering the outer surface of the eye. Goblet cells are responsible for secretion of mucus, and their absence results in xerophthalmia, a condition where the eyes fail to produce tears. Dead epithelial and microbial cells accumulate on the conjunctiva and form debris that can lead to infection and possibly blindness.Decreasing night blindness requires the improvement of vitamin A status in at-risk populations. Supplements and fortification of food have been shown to be effective interventions. Supplement treatment for night blindness includes massive doses of vitamin A (200,000 IU) in the form of retinyl palmitate to be taken by mouth, which is administered two to four times a year. Intramuscular injections are poorly absorbed and are ineffective in delivering sufficient bioavailable vitamin A. Fortification of food with vitamin A is costly, but can be done in wheat, sugar, and milk. Households may circumvent expensive fortified food by altering dietary habits. Consumption of yellow-orange fruits and vegetables rich in carotenoids, specifically beta-carotene, provides provitamin A precursors that can prevent VAD-related night blindness. However, the conversion of carotene to retinol varies from person to person and bioavailability of carotene in food varies.
Infection
Along with poor diet, infection and disease are common in many developing communities. Infection depletes vitamin A reserves which in turn make the affected individual more susceptible to further infection. Increased incidence of xerophthalmia has been observed after an outbreak of measles, with mortality correlated with severity of eye disease. In longitudinal studies of preschool children, susceptibility to disease increased substantially when severe VAD was present.The reason for the increased infection rate in vitamin A deficient individuals is that T-killer cells require the retinol metabolite retinoic acid to proliferate correctly. Retinoic acid is a ligand for nuclear retinoic acid receptors that bind the promoter regions of specific genes, thus activating transcription and stimulating T cell replication. Vitamin A deficiency will often entail deficient retinol intake, resulting in a reduced number of T-cells and lymphocytes, leading to an inadequate immune response and consequently a greater susceptibility to infections. In the presence of dietary deficiency of vitamin A, VAD and infections reciprocally aggravate each other.
Causes
In addition to dietary problems, other causes of VAD are known. Iron deficiency can affect vitamin A uptake; other causes include fibrosis, pancreatic insufficiency, inflammatory bowel disease, and small-bowel bypass surgery. Protein energy malnutrition is often seen in VAD; suppressed synthesis of retinol binding protein (RBP) due to protein deficiency leads to reduced retinol uptake. Excess alcohol consumption can deplete vitamin A, and a stressed liver may be more susceptible to vitamin A toxicity. People who consume large amounts of alcohol should seek medical advice before taking vitamin A supplements. In general, people should also seek medical advice before taking vitamin A supplements if they have any condition associated with fat malabsorption such as pancreatitis, cystic fibrosis, tropical sprue, and biliary obstruction. Other causes of vitamin A deficiency are inadequate intake, fat malabsorption, or liver disorders. Deficiency impairs immunity and hematopoiesis and causes rashes and typical ocular effects (e.g., xerophthalmia, night blindness).
Diagnosis
Initial assessment may be made based on clinical signs of VAD. Conjunctival impression cytology can be used to assess the presence of xerophthalmia which is strongly correlated with VAD status (and can be used to monitor recovery progress). Several methods of assessing bodily vitamin A levels are available, with HPLC the most reliable. Measurement of plasma retinol levels is a common laboratory assay used to diagnose VAD. Other biochemical assessments include measuring plasma retinyl ester levels, plasma and urinary retonioic acid levels, and vitamin A in breast milk.
Prevention and treatment
Treatment of VAD can be undertaken with both oral vitamin A and injectable forms, generally as vitamin A palmitate.
As an oral form, the supplementation of vitamin A is effective for lowering the risk of morbidity, especially from severe diarrhea, and reducing mortality from measles and all-cause mortality. Vitamin A supplementation of children under five who are at risk of VAD can reduce all‐cause mortality by 23%. Some countries where VAD is a public-health problem address its elimination by including vitamin A supplements available in capsule form with national immunization days (NIDs) for polio eradication or measles. Additionally, the delivery of vitamin A supplements, during integrated child health events such as child health days, have helped ensure high coverage of vitamin A supplementation in a large number of least developed countries. Child health events enable many countries in West and Central Africa to achieve over 80% coverage of vitamin A supplementation. According to UNICEF data, in 2013 worldwide, 65% of children between the ages of 6 and 59 months were fully protected with two high-dose vitamin A supplements. Vitamin A capsules cost about US$0.02. The capsules are easy to handle; they do not need to be stored in a refrigerator or vaccine carrier. When the correct dosage is given, vitamin A is safe and has no negative effect on seroconversion rates for oral polio or measles vaccines. However, because the benefit of vitamin A supplements is transient, children need them regularly every four to six months. Since NIDs provide only one dose per year, NIDs-linked vitamin A distribution must be complemented by other programs to maintain vitamin A in children Maternal high supplementation benefits both mother and breast-fed infant: high-dose vitamin A supplementation of the lactating mother in the first month postpartum can provide the breast-fed infant with an appropriate amount of vitamin A through breast milk. However, high-dose supplementation of pregnant women should be avoided because it can cause miscarriage and birth defects.
Food fortification is also useful for improving VAD. A variety of oily and dry forms of the retinol esters, retinyl acetates, and retinyl palmitate are available for food fortification of vitamin A. Margarine and oil are the ideal food vehicles for vitamin A fortification. They protect vitamin A from oxidation during storage and prompt absorption of vitamin A. Beta-carotene and retinyl acetate or retinyl palmitate are used as a form of vitamin A for vitamin A fortification of fat-based foods. Fortification of sugar with retinyl palmitate as a form of vitamin A has been used extensively throughout Central America. Cereal flours, milk powder, and liquid milk are also used as food vehicles for vitamin A fortification.
Separated from fortification via addition of synthetic vitamin A to foods, means of fortifying foods via genetic engineering have been explored. Research on rice began in 1982. The first field trials of golden rice cultivars were conducted in 2004. The result was "Golden Rice", a variety of Oryza sativa rice produced through genetic engineering to biosynthesize beta-carotene, a precursor of retinol, in the edible parts of rice. In May 2018, regulatory agencies in the United States, Canada, Australia and New Zealand had concluded that Golden Rice met food safety standards. On 21 July 2021, the Philippines became the first country to officially issue the biosafety permit for commercially propagating Golden Rice. Researchers at the U.S. Agricultural Research Service have been able to identify genetic sequences in corn that are associated with higher levels of beta-carotene, the precursor to vitamin A. They found that breeders can cross certain variations of corn to produce a crop with an 18-fold increase in beta-carotene.
Dietary diversification can also reduce risk of VAD. Non-animal sources of vitamin A like fruits and vegetables contain preformed vitamin A and account for greater than 80% of intake for most individuals in the developing world. The increase in consumption of vitamin A-rich foods of animal origin has beneficial effects on VAD.
Global initiatives
Global efforts to support national governments in addressing VAD are led by the Global Alliance for Vitamin A (GAVA), which is an informal partnership between Nutrition International, Helen Keller International, UNICEF, WHO, and CDC. About 75% of the vitamin A required for supplementation of preschool-aged children in low- and middle-income countries is supplied through a partnership between Nutrition International and UNICEF, with support from Global Affairs Canada. An estimated 1.25 million deaths due to vitamin A deficiency have been averted in 40 countries since 1998. In 2013, the prevalence of vitamin A deficiency was 29% in low-income and middle-income countries, remaining highest in sub-Saharan Africa and South Asia. A 2017 review (updated in 2022) found that vitamin A supplementation in children five years old and younger in 70 countries was associated with a 12% reduction in mortality rate. The review reported that synthetic vitamin A supplementation may not be the best long‐term solution for vitamin A deficiency, but rather food fortification, improved food distribution programs, and crop improvement, such as for fortified rice or vitamin A-rich sweet potato, may be more effective in eradicating vitamin A deficiency.
References
Further reading
UNICEF, Vitamin A Supplementation: A Decade of Progress, UNICEF, New York, 2007.
Flour Fortification Initiative, GAIN, Micronutrient Initiative, USAID, The World Bank, UNICEF, Investing in the Future: A United Call to Action on Vitamin and Mineral Deficiencies, 2009.
UNICEF, Improving Child Nutrition: The achievable imperative for global progress, UNICEF, New York, 2013.
External links
Nutrition International
Global Alliance for Vitamin A
UNICEF Data on Vitamin A Deficiency and Supplementation
Helen Keller International
A2Z
World Health Organization Database on Vitamin A Deficiency
Vitamin A Deficiency on IAPB |
Auricular hypertrichosis | Auricular hypertrichosis (hypertrichosis lanuginosa acquisita, hypertrichosis pinnae auris) is a genetic condition expressed as long and strong hairs growing from the helix of the pinna.
Presentation
Ear hair generally refers to the terminal hair arising from follicles inside the external auditory meatus in humans. In its broader sense, ear hair may also include the fine vellus hair covering much of the ear, particularly at the prominent parts of the anterior ear, or even the abnormal hair growth as seen in hypertrichosis and hirsutism. Medical research on the function of ear hair is currently very scarce.
Hair growth within the ear canal is often observed to increase in older men, together with increased growth of nose hair. Excessive hair growth within or on the ear is known medically as auricular hypertrichosis. Some men, particularly in the male population of India, have coarse hair growth along the lower portion of the helix, a condition referred to as "having hairy pinnae" (hypertrichosis lanuginosa acquisita).
Genetics
The genetic basis of auricular hypertrichosis has not been settled. Some researchers have proposed a Y-linked pattern of inheritance and others have suggested an autosomal gene is responsible. A third hypothesis predicts the phenotype results from the interaction of two loci, one on the homologous part of the X and Y and one on the nonhomologous sequence of the Y. These hypotheses are not mutually exclusive, and there may be a variety of genetic mechanisms underlying this phenotype.
Lee et al. (2004), using Y-chromosomal DNA binary-marker haplotyping, suggested that a cohort of southern Indian hairy-eared males carried Y chromosomes from many haplogroup. The hypothesis of Y- linkage would require multiple independent mutations within a single population. No significant difference between the Y-haplogroup frequencies of hairy-eared males and those of a geographically matched control sample of unaffected males was established. The study concluded that auricular hypertrichosis is not Y-linked in southern India, though this result may not apply to all to all populations.
See also
Ear hair
Hypertrichosis
== References == |
Velopharyngeal inadequacy | Velopharyngeal inadequacy is a malfunction of a velopharyngeal mechanism which is responsible for directing the transmission of sound energy and air pressure in both the oral cavity and the nasal cavity. When this mechanism is impaired in some way, the valve does not fully close, and a condition known as velopharyngeal inadequacy can develop. VPI can either be congenital or acquired later in life.
Presentation
Relationship to cleft palate
A cleft palate is one of the most common causes of VPI. Cleft palate is an anatomical abnormality that occurs in utero and is present at birth. This malformation can affect the lip and palate, or the palate only. A cleft palate can affect the mobility of the velopharyngeal valve, thereby resulting in VPI.
Causes
While cleft is the most common cause of VPI, other significant etiologies exist. These other causes are outlined in the chart below:
Diagnosis
Classification
The most frequent types of cleft palates are overt, submucous, and occult submucous.
Treatment
A common method to treat Velopharyngeal insufficiency is pharyngeal flap surgery, where tissue from the back of the mouth is used to close part of the gap. Other ways of treating velopharyngeal insufficiency is by placing a posterior nasopharyngeal wall implant (commonly cartilage or collagen) or type of soft palate lengthening procedure (i.e. VY palatoplasty).
Inadequacy, insufficiency and incompetency
Velopharyngeal insufficiency or incompetency are related labels for this phenomenon, in addition to most common generic- velopharyngeal inadequacy. Velopharyngeal insufficiency is the inability of the velopharyngeal sphincter to sufficiently separate the nasal cavity from the oral cavity during speech. Velopharyngeal incompetency occurs when the soft palate and the lateral/posterior pharyngeal walls fail to separate the oral cavity from the nasal cavity during speech. Although the definitions are similar, the etiologies correlated with each term differ slightly. However, in the field of medical professionals these terms are typically used interchangeably.
References
Conley SF, Gosain AK, Marks SM, Larson DL (1997). "Identification and assessment of velopharyngeal inadequacy". Am J Otolaryngol. 18 (1): 38–46. doi:10.1016/S0196-0709(97)90047-8. PMID 9006676.
Johns DF, Rohrich RJ, Awada M (2003). "Velopharyngeal incompetence: a guide for clinical evaluation". Plast. Reconstr. Surg. 112 (7): 1890–7, quiz 1898, 1982. doi:10.1097/01.PRS.0000091245.32905.D5. PMID 14663236.
McWilliams, Betty Jane; Peterson-Falzone, Sally J.; Hardin-Jones, Mary A.; Karnell, Michael P. (2001). Cleft palate speech. St. Louis: Mosby. ISBN 0-8151-3153-4.
Hardin-Jones, Mary A.; Peterson-Falzone, Sally J.; Judith Trost-Cardamone; Karnell, Michael P. (2005). The Clinicians Guide to Treating Cleft Palate Speech. St. Louis: Mosby-Year Book. ISBN 0-323-02526-9.
Willging JP (1999). "Velopharyngeal insufficiency". Int. J. Pediatr. Otorhinolaryngol. 49 Suppl 1: S307–9. doi:10.1016/S0165-5876(99)00182-2. PMID 10577827.
== External links == |
Gastroptosis | Gastroptosis is the abnormal downward displacement of the stomach. It is not a life-threatening condition. The condition frequently causes digestive symptoms and constipation. It is much more prominent in women than men. Gastroptosis is diagnosed with x-ray using barium contrast.
See also
Visceroptosis
References
== External links == |
Relative energy deficiency in sport | Relative energy deficiency in sport (RED-S) is a syndrome in which disordered eating (or low energy availability), amenorrhoea/oligomenorrhoea (in women), and decreased bone mineral density (osteoporosis and osteopenia) are present. It is caused by eating too little food to support the amount of energy being expended by an athlete, often at the urging of a coach or other authority figure who believes that athletes are more likely to win competitions when they have an extremely lean body type. RED-S is a serious illness with lifelong health consequences and can potentially be fatal.RED-S is the broader, more comprehensive name for what was formerly known as the female athlete triad (or simply the triad), which was a condition seen in females participating in sports that emphasize leanness or low body weight. As the non-menstrual components are also seen in males, the name was changed to the comprehensive term RED-S.
Classification
Formerly known as the female athlete triad, RED-S is a syndrome of three interrelated conditions. Thus, if an athlete is suffering from one element of the triad, it is likely that they are suffering from the other two components of the triad as well.With the increase in female participation in sports, the incidence of a triad of disorders particular to women—the female athlete triad—has also increased. The female athlete triad and its relationship with athletics was identified in the 1980s as the prevalence increased during this period, and symptoms, risk factors, causes, and treatments were studied in depth and their relatedness evaluated. The condition is most common in sports that emphasize leanness, such as cross country running, gymnastics, and figure skating. Many of those who suffer from the triad are involved in some sort of athletics, in order to promote weight loss and leanness. The competitive sports that promote this physical leanness may result in disordered eating and be responsible for the origin of the female athlete triad.
For some women, the disorder can have major health consequences. In addition, for some competitive female athletes, problems such as low self-esteem, a tendency toward perfectionism, and family stress place them at risk for disordered eating.
Signs and symptoms
Clinical symptoms of RED-S may include disordered eating, fatigue, hair loss, cold hands and feet, dry skin, noticeable weight loss, increased healing time from injuries (e.g., lingering bruises), increased incidence of bone fracture and cessation of menses. Affected athletes may also struggle with low self-esteem and depression.
Upon physical examination, a physician may also note the following symptoms: elevated carotene in the blood, anemia, orthostatic hypotension, electrolyte irregularities, hypoestrogenism, vaginal atrophy, and bradycardia.An athlete may show signs of restrictive eating, but not meet the clinical criteria for an eating disorder. They may also display subtle menstrual disturbances, such as a change in menstrual cycle length, anovulation, or luteal phase defects, but not yet have developed complete amenorrhea. Likewise, an athletes bone density may decrease, but may not yet have dropped below her age-matched normal range. These signs can be considered "occult," as no one symptom may be severe enough to seek medical attention, leaving the triad to go unnoticed or untreated.
Disordered eating
Energy availability is defined as energy intake minus energy expended. Energy is taken in through food consumption. Bodies expend energy through normal functioning as well as through exercise. In the case of RED-S, low energy availability may be due to eating disorders, but not necessarily so. Athletes may experience low energy availability by exercising more without a concomitant change in eating habits, or they may increase their energy expenditure while also eating less. Disordered eating is defined among this situation due to the low caloric intake or low energy availability.
While most athletes do not meet the clinical criteria to be diagnosed with an eating disorder such as anorexia nervosa or bulimia nervosa, many will exhibit disordered eating habits such as fasting, as well as avoiding certain types of food the athlete thinks are "bad" (such as foods containing fat). There are multiple factors that play in encouraging athletes to aim for a more lean body type, such as the culture and the individual. More severe examples of disordered eating habits may include binge-eating; purging; and the use of diet-pills, laxatives, diuretics, and enemas.By restricting their diet, the athlete may worsen their problem of low energy availability. Having low dietary energy from excessive exercise or dietary restrictions leaves too little energy for the body to carry out normal functions such as maintaining a regular menstrual cycle or healthy bone density.
Amenorrhea
Amenorrhea, defined as the cessation of a woman’s menstrual cycle for more than three months, is the second disorder in the triad. Weight fluctuations from dietary restrictions and/or excessive exercise affect the hypothalamus’s output of gonadotropic hormones. Gonadotropic hormones “stimulate growth of the gonads and the secretion of sex hormones.” (e.g. gonadotropin-releasing hormone, lutenizing hormone and follicle stimulating hormone.) These gonadotropic hormones play a role in stimulating estrogen release from the ovaries. Without estrogen release, the menstrual cycle is disrupted. Exercising intensely and not eating enough calories can lead to decreases in estrogen, the hormone that helps to regulate the menstrual cycle. As a result, periods may become irregular or stop altogether.There are two types of amenorrhea. A woman who has been having her period and then stops menstruating for ninety days or more is said to have secondary amenorrhea. In the case of RED-S, the majority of secondary amenorrhea cases are attributed to functional hypothalamic amenorrhea (FHA), an adaptive mechanism to preserve energy for survival and vital processes rather than reproduction when energy balance is low. Primary amenorrhea is characterized by delayed menarche (the onset of menses during puberty). Delayed menarche may be associated with delay of the development of secondary sexual characteristics.
Osteoporosis
Osteoporosis is defined by the National Institutes of Health as ‘‘a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture.’’ Low estrogen levels and poor nutrition, especially low calcium intake, can lead to osteoporosis, the third aspect of the triad. This condition can ruin a female athletes career because it may lead to stress fractures and other injuries.Patients with RED-S get osteoporosis due to hypoestrogenemia, or low estrogen levels. With estrogen deficiency, the osteoclasts live longer and are therefore able to resorb more bone. In response to the increased bone resorption, there is increased bone formation and a high-turnover state develops which leads to bone loss and perforation of the trabecular plates. As osteoclasts break down bone, patients see a loss of bone mineral density. Low bone mineral density renders bones more brittle and hence susceptible to fracture. Because athletes are active and their bones must endure mechanical stress, the likelihood of experiencing bone fracture is particularly high.Additionally, because those suffering with RED-S are also restricting their diet, they may also not be consuming sufficient amounts vitamins and minerals which contribute to bone density; not getting enough calcium or vitamin D further exacerbates the problem of weak bones.Bone mass is now thought to peak between the ages of 18-25. Thus, behaviors which result in low bone density in youth could be detrimental to an athlete’s bone health throughout her lifetime.In addition, ovulation is the primary way that females create the hormone progesterone. When an ovum is released from the ovary, the structure that remains develops into the corpus luteum. The corpus luteum emits the hormone progesterone during the 10–16 days of the luteal phase. Without experiencing regular, ovulatory menstrual cycles, the female is not secreting the hormone progesterone during the luteal phase of her cycle. Progesterone directly stimulates osteoblasts to make new bone. Therefore if the woman is not ovulating, she is not creating progesterone, and misses out on this opportunity to stimulate new bone growth.
Causes
Gymnastics, figure skating, ballet, diving, swimming, and long distance running are examples of sports which emphasize low body weight. The triad is seen more often in aesthetic sports such as these versus ball game sports. Women taking part in these sports may be at an increased risk for developing RED-S.Athletes at greatest risk for low energy availability are those who restrict dietary energy intake, who exercise for prolonged periods, who are vegetarian, and who limit the types of food they will eat. Many factors appear to contribute to disordered eating behaviors and clinical eating disorders. Dieting is a common entry point and interest has focused on the contribution of environmental and social factors, psychological predisposition, low self-esteem, family dysfunction, abuse, biological factors, and genetics. Additional factors for athletes include early start of sport-specific training and dieting, injury, and a sudden increase in training volume. Surveys show more negative eating attitude scores in athletic disciplines favoring leanness. Disordered eating behaviors are risk factors for eating disorders.
Treatment
The underlying cause of the RED-S is an imbalance between energy taken into the body (through nutrition) and energy used by the body (through exercise). The treatment includes correcting this imbalance by either increasing calories in a diet or by decreasing calories burned by exercise for 12 months or longer. Persons with RED-S should get treatment from a multi-disciplinary team that includes a physician, dietitian, and mental health counselor, and seek support from family, friends, and their coach.Because a symptom of the RED-S is menstrual dysfunction, some physicians may recommend oral contraceptives because those pills will regulate the menstrual cycle. However, the underlying cause of the menstrual disorder is an energy imbalance, and using pills to regulate the menstrual cycle without changes in diet and behavior is likely to mask the food deficiency and delay appropriate treatment. A woman taking contraceptives to treat menstrual dysfunction without correcting this energy imbalance will continue to lose bone density.
Less exercise
Continued participation in training and competition depends on the physical and mental health of the athlete. Athletes who weigh less than 80 percent of their ideal body weight may not be able to safely participate.Persons with RED-S are often asked by health care providers to reduce the amount of time they spend exercising by 10-12 percent.
Eating more
Low energy availability with or without eating disorders, functional hypothalamic amenorrhea, and osteoporosis, alone or in combination, pose significant health risks to physically active girls and women. Prevention, recognition, and treatment of these clinical conditions should be a priority of those who work with female athletes to ensure that they maximize the benefits of regular exercise.Patients are recommended to work with a dietician who can monitor their nutritional status and help the patient work towards a healthy goal weight. Patients should also meet with a psychiatrist or psychologist to address the psychological aspects of the triad. Therefore, it is important that trainers and coaches are made aware of the athlete’s condition and be part of her recovery.
Medicine
Patients are also sometimes treated pharmacologically. To both induce menses and improve bone density, doctors may prescribe cyclic estrogen or progesterone as is used to treat post-menopausal women. Patients may also be put on oral contraceptives to stimulate regular periods. In addition to hormone therapy, nutrition supplements may be recommended. Doctors may prescribe calcium supplements. Vitamin D supplements may be also used because this vitamin aids in calcium absorption. Bisphosphonates and calcitonin, used to treat adults with osteoporosis, may be prescribed, although their effectiveness in adolescents has not yet been established. Finally, if indicated by a psychiatric examination, the affected athlete may be prescribed anti-depressants and in some cases benzodiazepines to help in alleviating severe distress at mealtimes.
Prognosis
Sustained low energy availability, with or without disordered eating, can impair health. Psychological problems associated with eating disorders include low self-esteem, depression, and anxiety disorders. Medical complications involve the cardiovascular, endocrine, reproductive, skeletal, gastrointestinal, renal, and central nervous systems. The prognosis for anorexia nervosa is grave with a six-fold increase in standard mortality rates compared to the general population. In one study, 5.4% of athletes with eating disorders reported suicide attempts. Although 83% of anorexia nervosa patients partially recover, the rate of sustained recovery of weight, menstrual function and eating behavior is only 33%.Amenorrheic women can be infertile, due to the absence of ovarian follicular development, ovulation, and luteal function. Consequences of hypoestrogenism seen in amenorrheic athletes include impaired endothelium-dependent arterial vasodilation, which reduces the perfusion of working muscle, impaired skeletal muscle oxidative metabolism, elevated low-density lipoprotein cholesterol levels, and vaginal dryness.Due to low bone mineral density that declines as the number of missed menstrual cycles accumulates, and the loss of BMD may not be fully reversible. Stress fractures occur more commonly in physically active women with menstrual irregularities and/or low BMD with a relative risk for stress fracture two to four times greater in amenorrheic than eumenorrheic athletes. Fractures also occur in the setting of nutritional deficits and low BMD.
Society and culture
The American Academy of Pediatrics and the AAFP contend that exercise is important and should be promoted in girls for health and enjoyment; however, pediatricians should be wary of health problems that may occur in female athletes. The health related issues concerning this topic are grave and can lead to numerous health issues as previously demonstrated. The treatment plan will depend on the severity of the disorder, however some form of treatment has been shown as helpful to produce successful progress towards a better health condition. Clearly, many health problems arise due to disordered eating.
Coaches are discouraged from active participation in the treatment of eating disorders. In addition to conflicts of interest, coaches may be perceived to pressure athletes and potentially perpetuate components of RED-S. For example, in maintaining a place on the team or continued scholarship support, a female athlete may feel compelled to overtrain or restrict eating.
See also
Body dysmorphic disorder
Gonadotropin
List of medical triads, tetrads, and pentads
References
External links
American Academy of Family Physicians: The Female Athlete Triad |
Confluent and reticulated papillomatosis | Confluent and reticulated papillomatosis of Gougerot and Carteaud is an uncommon but distinctive acquired ichthyosiform dermatosis characterized by persistent dark, scaly, papules and plaques that tend to be localized predominantly on the central trunk.
Eponym
Henri Gougerot and Alexandre Carteaud originally described the condition in 1927. The cause remains unknown, but the observation that the condition may clear with Minocycline turned attention to an infectious agent. Actinomycete Dietzia strain X was isolated from one individual. Other antibiotics found useful include azithromycin, fusidic acid, clarithromycin, erythromycin, tetracycline and cefdinir.
See also
Ichthyosis
Acquired ichthyosis
List of cutaneous conditions
References
== External links == |
Warsaw breakage syndrome | Warsaw breakage syndrome is a rare genetic condition. Fewer than 10 cases have been reported by 2018. Its clinical manifestations affect several organ systems.
Presentation
These include
Severe pre- and postnatal growth retardation
Microcephaly
Intellectual disability
Dysmorphic features
Small and elongated face
Narrow bifrontal diameter
Prominent cheeks
Small nares
Flat philtrum
Relatively large mouth
Bilateral epicanthal folds
High arched palate
Microretrognathism
Coloboma of the optic disc
Strabismus
Cup-shaped ears
Sensorineural deafness
Short neck
Jugular hypoplasia
Cardiac features
Ventricular septal defect
Tetralogy of Fallot
Sketelal features
Clinodactyly of the fifth fingers
Syndactyly of the second and third toes
Small thumbs
Small fibulae
Others
Abnormal skin pigmentation
Single palmar crease
Genetics
This condition is caused by mutations in the DDX11 gene which is located on the short arm of chromosome 12 (12p11).
This gene encodes an iron-sulfur containing DNA helicase that belongs to the superfamily 2 of helicases. This protein interacts with the 9-1-1 checkpoint complex protein.The inheritance pattern is not yet clear.
Diagnosis
The diagnosis may be suspected on clinical grounds and can be confirmed by sequencing the DDX11 gene.
Differential diagnosis
The DDX should be based on the following:
Bloom syndrome
Cornelia de Lange syndrome
Fanconi anemia
Nijmegen breakage syndrome
Roberts syndrome
Xeroderma pigmentosum
Treatment
There is no known curative treatment for this condition presently. Management is supportive.
History
This condition was first described in 2010.
== References == |
Disruptive mood dysregulation disorder | Disruptive mood dysregulation disorder (DMDD) is a mental disorder in children and adolescents characterized by a persistently irritable or angry mood and frequent temper outbursts that are disproportionate to the situation and significantly more severe than the typical reaction of same-aged peers. DMDD was added to the DSM-5 as a type of depressive disorder diagnosis for youths. The symptoms of DMDD resemble those of attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), anxiety disorders, and childhood bipolar disorder .DMDD first appeared as a disorder in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) in 2013 and is classified as a mood disorder. Treatments include medication to manage mood symptoms as well as individual and family therapy to address emotion-regulation skills. Children with DMDD are at risk for developing depression and anxiety later in life.
Signs and symptoms
Children with DMDD show severe and recurrent temper outbursts three or more times per week. These outbursts can be verbal or behavioral. Verbal outbursts often are described by observers as "rages", "fits", or "tantrums". Children may scream, yell, and cry for excessively long periods of time, sometimes with little provocation. Physical outbursts may be directed toward people or property. Children may throw objects; hit, slap, or bite others; destroy toys or furniture; or otherwise act in a harmful or destructive manner.
Children with DMDD also display persistently irritable or angry mood that is observable by others. Parents, teachers, and classmates describe these children as habitually angry, touchy, grouchy, or easily "set off". Unlike the irritability that can be a symptom of other childhood disorders, such as ODD, anxiety disorders, and major depressive disorder, the irritability displayed by children with DMDD is not episodic or situation-dependent. In DMDD, the irritability or anger is severe and is shown most of the day, nearly every day in multiple settings, lasting for one or more years.
Note
DMDD is a newly classified disorder, first appearing in the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) in 2013. The DSM is used for the assessment and diagnosis of mental disorders; it does not include specific guidelines for the treatment of any disorder.
Researchers at the National Institute of Mental Health (NIMH) developed the DMDD diagnosis to diagnose more accurately youth who may have been previously diagnosed with pediatric bipolar disorder (despite not experiencing the symptoms needed for a diagnosis of bipolar disorder).The DSM-5 includes several additional diagnostic criteria which describe the duration, setting, and onset of the disorder: the outbursts must be present for at least 12 months and occur in at least two settings (e.g. home and school), and it must be severe in at least one setting. Symptoms appear before the age of 10, and diagnosis must be made between ages 6 and 18.
Comorbidity
The core features of DMDD—temper outbursts and chronic irritability—are sometimes seen in children and adolescents with other psychiatric conditions. Differentiating DMDD from these other conditions can be difficult. Three disorders that most closely resemble DMDD are attention deficit hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and bipolar disorder in children.
ADHD
ADHD is a neurodevelopmental disorder characterized by problems with inattention and/or hyperactivity-impulsivity.
ODD
ODD is a disruptive behavior disorder characterized by oppositional, defiant, and sometimes hostile actions directed towards others. The DSM-5 considers DMDD a severe manifestation of symptoms associated with ODD. A diagnosis of both DMDD and ODD is not permitted or necessary; individuals who meet the diagnostic requirements for DMDD also meet the requirements for ODD.
Bipolar disorder
One of the main differences between DMDD and bipolar disorder is that the irritability and anger outbursts associated with DMDD are not episodic; symptoms of DMDD are chronic and displayed constantly on an almost daily basis. On the other hand, bipolar disorder is characterized by distinct manic or hypomanic episodes usually lasting a few days, or a few weeks at most, that parents should be able to differentiate from their childs typical mood and behavior in between episodes. The DSM precludes a dual diagnosis of DMDD and bipolar disorder. Bipolar disorder alone should be used for youths who show classic symptoms of episodic mania or hypomania.Prior to adolescence, DMDD is much more common than bipolar disorder. Most children with DMDD see a decrease in symptoms as they enter adulthood, whereas individuals with bipolar disorder typically display symptoms for the first time as teenagers and young adults. Children with DMDD are more at risk for developing major depressive disorder or generalized anxiety disorder when theyre older rather than bipolar disorder.
Conduct Disorder
Conduct disorder is a behavior disorder characterized by repeated, persistent patterns of behavior that violate the rights of others and disregard major societal norms and rules. While both DMDD and conduct disorder are associated with argumentative and defiant behavior, DMDD is distinctly differentiated from conduct disorder by the DSM. Individuals with DMDD experience severe emotional dysregulation not seen in conduct disorder. Additionally, conduct disorder is described by a distinct lack of remorse and repeated physical harm and threats of harm to people and/or animals. Evidence of conduct disorder during childhood is one of the criteria for an adult diagnosis of antisocial personality disorder, however adults with a continued diagnosis of conduct disorder do not necessarily have antisocial personality disorder.
Causes
Youth with DMDD have difficulty attending, processing, and responding to negative emotional stimuli and social experiences in their everyday lives. For example, some studies have shown youths with DMDD to have problems interpreting the social cues and emotional expressions of others. These youths may be especially bad at judging others negative emotional displays, such as feelings of sadness, fearfulness, and anger. Functional MRI studies suggest that under-activity of the amygdala, the brain area that plays a role in the interpretation and expression of emotions and novel stimuli, is associated with these deficits. Deficits in interpreting social cues may predispose children to instances of anger and aggression in social settings with little provocation. For examples, youths with DMDD may selectively attend to negative social cues (e.g., others scowling, teasing) and minimize all other information about the social events. They may also misinterpret the emotional displays of others, believing others benign actions to be hostile or threatening. Consequently, they may be more likely than their peers to act in impulsive and angry ways.Children with DMDD may also have difficulty regulating negative emotions once they are elicited. To study these problems with emotion regulation, researchers asked children with DMDD to play computer games that are rigged so that children will lose. While playing these games, children with DMDD report more agitation and negative emotional arousal than their typically developing peers. Furthermore, youths with DMDD showed markedly greater activity in the medial frontal gyrus and anterior cingulate cortex compared to other youths. These brain regions are important because they are involved in evaluating and processing negative emotions, monitoring ones own emotional state, and selecting an effective response when upset, angry, or frustrated. Altogether, these findings suggest that youths with DMDD are more strongly influenced by negative events than other youths. They may become more upset and select less effective and socially acceptable ways to deal with negative emotions when they arise.
Treatment
Medication
Evidence for treatment is weak, and treatment is determined based on the physicians response to the symptoms that people with DMDD present. Because the mood stabilizing medication, lithium, is effective in treating adults with bipolar disorder, some physicians have used it to treat DMDD although it has not been shown to be better than placebo in alleviating the signs and symptoms of DMDD. DMDD is treated with a combination of medications that target the childs symptom presentation. For youths with DMDD alone, antidepressant medication is sometimes used to treat underlying problems with irritability or sadness. For youths with unusually strong temper outbursts, an atypical antipsychotic medication, such as risperidone, may be warranted. Both medications, however, are associated with significant side effects in children. Finally, for children with both DMDD and ADHD, stimulant medication is sometimes used to reduce symptoms of impulsivity.
Psychosocial
Several cognitive-behavioral interventions have been developed to help youths with chronic irritability and temper outbursts. Because many youths with DMDD show problems with ADHD and oppositional-defiant behavior, experts initially tried to treat these children using contingency management. This type of intervention involves teaching parents to reinforce childrens appropriate behavior and extinguish (usually through systematic ignoring or time out) inappropriate behavior. Although contingency management can be helpful for ADHD and ODD symptoms, it does not seem to reduce the most salient features of DMDD, namely, irritability and anger.
Epidemiology
There are not good estimates of the prevalence of DMDD, but primary studies have found a rate of 0.8 to 3.3%. Epidemiological studies show that approximately 3.2% of children in the community have chronic problems with irritability and temper, the essential features of DMDD. These problems are probably more common among clinic-referred youths. Parents report that approximately 30% of children hospitalized for psychiatric problems meet diagnostic criteria for DMDD; 15% meet criteria based on the observations of hospital staff.
What is the difference between typical irritability and severe irritability?
All children can become irritable sometimes. It’s a normal reaction to frustration. Children experiencing severe irritability (as observed in DMDD) have difficulty tolerating frustration and have outbursts that are out of proportion for the situation at hand. These outbursts occur more often and are more severe than what you would typically expect for children of this age.
For example, a parent tells the child to stop playing a game and do their homework. Any child might be frustrated or annoyed. But a child with DMDD may become extremely upset and emotional and have an intense temper outburst with yelling or hitting. A child with DMDD experiences these intense temper outbursts a few times a week.
History
Beginning in the 1990s, some clinicians began observing children with hyperactivity, irritability, and severe temper outbursts. These symptoms greatly interfered with their lives at home, school, and with friends. Because other diagnoses, like ADHD and ODD, did not capture the severity of childrens irritability and anger, many of these children were diagnosed with bipolar disorder. Longitudinal studies showed that children with chronic irritability and temper outbursts often developed later problems with anxiety and depression, and rarely developed bipolar disorder in adolescence or adulthood. Consequently, the developers of DSM-5 created a new diagnostic label, DMDD, to describe children with persistent irritability and angry outbursts. In 2013, the American Psychiatric Association (APA) added DMDD to the DSM-5 and classified it as a depressive disorder.
== References == |
Intervertebral disc | An intervertebral disc (or intervertebral fibrocartilage) lies between adjacent vertebrae in the vertebral column. Each disc forms a fibrocartilaginous joint (a symphysis), to allow slight movement of the vertebrae, to act as a ligament to hold the vertebrae together, and to function as a shock absorber for the spine.
Structure
Intervertebral discs consist of an outer fibrous ring, the anulus fibrosus disci intervertebralis, which surrounds an inner gel-like center, the nucleus pulposus. The anulus fibrosus consists of several layers (laminae) of fibrocartilage made up of both type I and type II collagen. Type I is concentrated toward the edge of the ring, where it provides greater strength. The stiff laminae can withstand compressive forces. The fibrous intervertebral disc contains the nucleus pulposus and this helps to distribute pressure evenly across the disc. This prevents the development of stress concentrations which could cause damage to the underlying vertebrae or to their endplates. The nucleus pulposus contains loose fibers suspended in a mucoprotein gel. The nucleus of the disc acts as a shock absorber, absorbing the impact of the bodys activities and keeping the two vertebrae separated. It is the remnant of the notochord.There is one disc between each pair of vertebrae, except for the first cervical segment, the atlas. The atlas is a ring around the roughly cone-shaped extension of the axis (second cervical segment). The axis acts as a post around which the atlas can rotate, allowing the neck to swivel. There are 23 discs in the human spine: 6 in the neck (cervical) region, 12 in the middle back (thoracic) region, and 5 in the lower back (lumbar) region Discs are named by the vertebral body above and below. For example, the disc between the fifth and sixth cervical vertebrae is designated "C5-6".
Development
During development and at birth, vertebral discs have some vascular supply to the cartilage endplates and the anulus fibrosus. These quickly deteriorate leaving almost no direct blood supply in healthy adults.
Intervertebral disc space
The intervertebral disc space is typically defined on an X-ray photograph as the space between adjacent vertebrae. In healthy patients, this corresponds to the size of the intervertebral disc. The size of the space can be altered in pathological conditions such as discitis (infection of the intervertebral disc).
Function
The intervertebral disc functions to separate the vertebrae from each other and provides the surface for the shock-absorbing gel of the nucleus pulposus. The nucleus pulposus of the disc functions to distribute hydraulic pressure in all directions within each intervertebral disc under compressive loads. The nucleus pulposus consists of large vacuolated notochord cells, small chondrocyte-like cells, collagen fibrils, and aggrecan, a proteoglycan that aggregates by binding to hyaluronan. Attached to each aggrecan molecule are glycosaminoglycan (GAG) chains of chondroitin sulfate and keratan sulfate. Increasing the amount of negatively charged aggrecan increases oncotic pressure, resulting in a shift of extracellular fluid from the outside to the inside of the nucleus pulposus. The amount of glycosaminoglycans (and hence water) decreases with age and degeneration.
Clinical significance
Anything arising from the intervertebral disc may be termed discogenic in particular when referring to associated pain as discogenic pain.
Herniation
A spinal disc herniation, commonly referred to as a slipped disc, can happen when unbalanced mechanical pressures substantially deform the anulus fibrosus, allowing part of the nucleus to obtrude. These events can occur during peak physical performance, during traumas, or as a result of chronic deterioration (typically accompanied with poor posture), and has been associated with a Propionbacterium acnes infection. Both the deformed anulus and the gel-like material of the nucleus pulposus can be forced laterally or posteriorly, distorting local muscle function and putting pressure on the nearby nerve. This can give symptoms typical of nerve root entrapment, which can vary between paresthesia, numbness, chronic and/or acute pain, either locally or along the dermatome served by the entrapped nerve, loss of muscle tone and decreased homeostatic performance. The disc is not physically slipped; it bulges, usually in just one direction.
Another kind of herniation, of the nucleus pulposus, can happen as a result of the formation of Schmorls nodes on the intervertebral disc. This is referred to as vertical disc herniation.
Degeneration
Before age 40, approximately 25% of people show evidence of disc degeneration at one or more levels. Beyond age 40, more than 60% of people show evidence of disc degeneration at one or more levels on magnetic resonance imaging (MRI). These degenerative changes are a normal part of the ageing process and do not correlate to pain.
One effect of aging and disc degeneration is that the nucleus pulposus begins to dehydrate and the concentration of proteoglycans in the matrix decreases, thus limiting the ability of the disc to absorb shock. This general shrinking of disc size is partially responsible for the common decrease in height as humans age. The anulus fibrosus also becomes weaker with age and has an increased risk of tearing. In addition, the cartilage endplates begin thinning, fissures begin to form, and there is sclerosis of the subchondral bone. Since the fissures are formed in the anulus fibrosus due to osteo-arthritic bones or degeneration in general, the inner nucleus pulposus can seep out and put pressure on any number of vertebral nerves. A herniated disc can cause mild to severe pain such as sciatica and treatment for herniated discs range from physical therapy to surgery.(see also: Intervertebral disc arthroplasty) Other degeneration of the vertebral column includes diffuse idiopathic skeletal hyperostosis (DISH) which is the calcification or ossification of the ligaments surrounding the vertebrae. This degeneration causes stiffness and sometimes even curvature in the lumbar and thoraco-lumbar spinal region.
Burgeoning evidence suggests that long-term running may mitigate age-related degeneration within lumbar intervertebral discs
Scoliosis
While this may not cause pain in some people, in others it may cause chronic pain. Other spinal disorders can affect the morphology of intervertebral discs. For example, patients with scoliosis commonly have calcium deposits (ectopic calcification) in the cartilage endplate and sometimes in the disc itself.
Herniated discs are also found to have a higher degree of cellular senescence than non-herniated discs. In addition to scoliosis, which is the lateral S curvature of the spine, the fused vertebrae can also experience other abnormalities such as kyphosis (hunchback) which shows in old age, or lordosis (swayback), which is often present in pregnancy and obesity.
Etymology
The Latin word anulus means "little ring"; it is the diminutive of anus ("ring"). The misspelling annulus is also common.
Additional images
See also
Back pain
Degenerative disc disease
Spinal decompression
Lumbar spinal stenosis
References
External links
Intervertebral Discs
Spinal Disc Summary
Cross section image: pembody/body12a—Plastination Laboratory at the Medical University of Vienna |
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