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Bepotastine	Bepotastine (Talion, Bepreve) is a 2nd generation antihistamine. It was approved in Japan for use in the treatment of allergic rhinitis and urticaria/pruritus in July 2000 and January 2002, respectively. It is currently marketed in the United States as an eye drop under the brand-name Bepreve, by ISTA Pharmaceuticals, a subsidiary of Bausch + Lomb. Pharmacology Bepotastine is available as an ophthalmic solution and oral tablet. It is a direct H1-receptor antagonist that inhibits the release of histamine from mast cells. The ophthalmic formulation has shown minimal systemic absorption, between 1 and 1.5% in healthy adults. Common side effects are eye irritation, headache, unpleasant taste, and nasopharyngitis. The main route of elimination is urinary excretion, 75-90% excreted unchanged. Marketing history It is marketed in Japan by Tanabe Seiyaku under the brand name Talion. Talion was co-developed by Tanabe Seiyaku and Ube Industries, the latter of which discovered bepotastine. In 2001, Tanabe Seiyaku granted Senju, now owned by Allergan, exclusive worldwide rights, with the exception of certain Asian countries, to develop, manufacture and market bepotastine for ophthalmic use. Senju, in turn, has granted the United States rights for the ophthalmic preparation to ISTA Pharmaceuticals. Sales and patents In 2011, ISTA pharmaceuticals experienced a 2.4% increase in net revenues from 2010, which was driven by the sales of Bepreve. Their net revenue for 2011 was $160.3 million. ISTA Pharmaceuticals was acquired by Bausch & Lomb in March 2012 for $500 million. Bausch & Lomb hold the patent for bepotastine besilate (https://www.accessdata.fda.gov/scripts/cder/ob/docs/temptn.cfm. On November 26, 2014, Bausch & Lomb sued Micro Labs USA for patent infringement. Bausch & Lomb was recently bought out by Valeant Pharmaceuticals in May 2013 for $8.57 billion, Valeants largest acquisition to date, causing the companys stock to rise 25% when the deal was announced. Clinical trials A Phase III clinical trial was carried out in 2010 to evaluate the effectiveness of bepotastine besilate ophthalmic solutions 1.0% and 1.5%. These solutions were compared to a placebo and evaluated for their ability to reduce ocular itchiness. The study was carried out with 130 individuals and evaluated after 15 minutes, 8 hours, or 16 hours. There was a reduction in itchiness at all-time points for both ophthalmic solutions. The study concluded that bepotastine besilate ophthalmic formulations reduced ocular itchiness for at least 8 hours after dosing compared to placebo. Phase I and II trials were carried out in Japan. Studies have been performed in animals and bepotastine besilate was not found to be teratogenic in rats during fetal development, even at 3,300 times more that typical use in humans. Evidence of infertility was seen in rats at 33,000 times the typical ocular dose in humans. The safety and efficacy has not been established in patients under 2 years of age and has been extrapolated from adults for patients under 10 years of age. == References ==
Vecuronium bromide	Vecuronium bromide, sold under the brand name Norcuron among others, is a medication used as part of general anesthesia to provide skeletal muscle relaxation during surgery or mechanical ventilation. It is also used to help with endotracheal intubation; however, suxamethonium (succinylcholine) is generally preferred if this needs to be done quickly. It is given by injection into a vein. Effects are greatest at about 4 minutes and last for up to an hour.Side effects may include low blood pressure and prolonged paralysis. Allergic reactions are rare. It is unclear if use in pregnancy is safe for the baby. Vecuronium is in the aminosteroid neuromuscular-blocker family of medications and is of the non-depolarizing type. It works by blocking the action of acetylcholine on skeletal muscles.Vecuronium was approved for medical use in the United States in 1984. It is on the World Health Organizations List of Essential Medicines. Vecuronium is available as a generic medication. The effects may be reversed with a combination of neostigmine and atropine. Mechanism of action Vecuronium operates by competing for the cholinoceptors at the motor end plate, thereby exerting its muscle-relaxing properties, which are used adjunctively to general anesthesia. Under balanced anesthesia, the time to recovery to 25% of control (clinical duration) is approximately 25 to 40 minutes after injection and recovery is usually 95% complete approximately 45 to 65 minutes after injection of an intubating dose. The neuromuscular blocking action of vecuronium is slightly enhanced in the presence of potent inhalation anesthetics. If vecuronium is first administered more than 5 minutes after the start of the inhalation of enflurane, isoflurane, or halothane, or when a steady state has been achieved, the intubating dose of vecuronium may be decreased by approximately 15%. Vecuronium has an active metabolite, 3-desacetyl-vecuronium, that has 80% of the effect of vecuronium. Accumulation of this metabolite, which is cleared by the kidneys, can prolong the duration of action of the drug, particularly when an infusion is used in a person with kidney failure.Reversal of vecuronium can be accomplished by administration of sugammadex which is a γ-cyclodextrin which encapsulates vecuronium preventing it from binding to receptors. Reversal can also be accomplished with neostigmine or other cholinesterase inhibitors, but their efficacy is lower than that of sugammadex. History As long ago as 1862, adventurer Don Ramon Paez described a Venezuelan poison, guachamaca, which the indigenous peoples used to lace sardines as bait for herons and cranes. If the head and neck of a bird so killed was cut off, the remainder of the flesh could be eaten safely. Paez also described the attempt of a Llanero woman to murder a rival to her lovers affections with guachamaca and unintentionally killed 10 other people when her husband shared his food with their guests. It is probable that the plant was Malouetia nitida or Malouetia schomburgki.The genus Malouetia (family Apocynaceae) is found in both South America and Africa. The botanist Robert E. Woodson Jr comprehensively classified the American species of Malouetia in 1935. At that time, only one African species of Malouetia was recognized, but the following year Woodson described a second: Malouetia bequaertiana, from the Belgian Congo.In 1960, scientists reported the isolation of malouetine from the roots and bark of Malouetia bequaertiana Woodson by means of an ion exchange technique. Optimization of the aminosteroid nucleus led to a sequence of synthesized derivatives, ultimately leading to pancuronium bromide in 1964. The name was derived from p(iperidino)an(drostane)cur(arising)-onium.A paper published in 1973 discussed the structure-activity relationships of a series of aminosteroid muscle relaxants, including the mono-quaternary analogue of pancuronium, later called vecuronium. Society and culture It is commercially available as ampoules containing 4 or 10 mg of the drug in powder form which needs to be dissolved in distilled water prior to being given. Non-medical use Vecuronium bromide has been used as part of a drug cocktail that prisons in the United States use as a means to put a condemned prisoner to death. Vecuronium is used to paralyze the prisoner and stop his or her breathing, in conjunction with a sedative and potassium chloride to stop the prisoners heart. Injections of vecuronium bromide without proper sedation allow the person to be fully awake but unable to move in response to pain.In 2001, Japanese nurse Daisuke Mori was reported to have murdered 10 patients using vecuronium bromide. He was convicted of murder and was sentenced to life imprisonment. References External links "Vecuronium Bromide". Drug Information Portal. U.S. National Library of Medicine.
Bendamustine	Bendamustine, sold under the brand name Treanda among others, is a chemotherapy medication used in the treatment of chronic lymphocytic leukemia (CLL), multiple myeloma, and non-Hodgkins lymphoma. It is given by injection into a vein.Common side effects include low blood cell counts, fever, nausea, diarrhea, loss of appetite, cough, and rash. Other severe side effects include allergic reactions and increased risk of infection. Use in pregnancy is known to harm the baby. Bendamustine is in the alkylating agents family of medication. It works by interfering with the function of DNA and RNA.Bendamustine was approved for medical use in the United States in 2008. It is on the World Health Organizations List of Essential Medicines. The cost in the United Kingdom for the NHS is about 275.81 pounds per 100 mg vial. It was originally made from nitrogen mustard. Medical uses Bendamustine has been used both as sole therapy and in combination with other agents including etoposide, fludarabine, mitoxantrone, methotrexate, prednisone, rituximab, vincristine and 90Y-ibritumomab tiuxetan. Lymphomas One combination for stage III/IV relapsed or refractory indolent lymphomas and mantle cell lymphoma (MCL), with or without prior rituximab-containing chemoimmunotherapy treatment, is bendamustine with mitoxantrone and rituximab. In Germany in 2012 it has become the first line treatment of choice for indolent lymphoma. After trial results released in June 2012 showed that it more than doubled disease progression-free survival when given along with rituximab. The combination also left patients with fewer side effects than the older R-CHOP treatment. Adverse effects Common adverse reactions are typical for the class of nitrogen mustards, and include nausea, fatigue, vomiting, diarrhea, fever, constipation, loss of appetite, cough, headache, unintentional weight loss, difficulty breathing, rashes, and stomatitis, as well as immunosuppression, anemia, and low platelet counts. Notably, this drug has a low incidence of hair loss (alopecia) unlike most other chemotherapy drugs. Warning Bendamustine solution is not compatible with Closed System Transfer Devices (CSTD) Situation: *Most CSTD vendors have adapted their system to become compatible. FDA issued a warning on March 11, 2015, not to use bendamustine solution with CSTDs, adapters and syringes which contain either polycarbonate or acrylonitrile-butadiene-styrene (ABS) due to the incompatibility with N,N-dimethylacetamide (DMA).Background: PhaSealR & SpirosR CSTDs contain either polycarbonate or ABS can dissolve when coming into contact with bendamustine (which contains DMA).Assessment: This can lead to device failure, possible product contamination, and potential serious adverse health consequences, including skin reactions in health care professionals preparing and administering this product and the risk of small blood vessel blockage in patients.Recommendations: Immediately, stop using all PhaSealR &/or SpirosR products including adapters when preparing & administering bendamustine. Only use polypropylene syringes with bendamustine. These syringes are translucent in appearance. Continue to use all universal PPE & safety precautions for hazardous drugs when preparing & administering bendamustine. Pharmacology Bendamustine is a white, water-soluble microcrystalline powder with amphoteric properties. It acts as an alkylating agent causing intra-strand and inter-strand cross-links between DNA bases. After intravenous infusion it is extensively metabolised in the liver by cytochrome p450. More than 95% of the drug is bound to protein – primarily albumin. Only free bendamustine is active. Elimination is biphasic with a half-life of 6–10 minutes and a terminal half-life of approximately 30 minutes. It is eliminated primarily through the kidneys. History Bendamustine was first made in 1963 by Ozegowski and Krebs in East Germany (the former German Democratic Republic). Until 1990 it was available only in East Germany. East German researchers found that it was useful for treating chronic lymphocytic leukemia, Hodgkins disease, non-Hodgkins lymphoma, multiple myeloma and lung cancer. Bendamustine received its first marketing approval in Germany, where it is marketed under the tradename Ribomustin, by Astellas Pharma GmbHs licensee, Mundipharma International Corporation Limited. It is indicated as a single-agent or in combination with other anti-cancer agents for indolent non-Hodgkins lymphoma, multiple myeloma, and chronic lymphocytic leukemia. SymBio Pharmaceuticals Ltd. holds exclusive rights to develop and market bendamustine HCl in Japan and selected Asia Pacific Rim countries. In March 2008, Cephalon received approval from the United States Food and Drug Administration to market bendamustine in the US, where it is sold under the tradename Treanda, for treatment of chronic lymphocytic leukemia.In October 2008, the FDA granted further approval to market Treanda for the treatment of indolent B-cell non-Hodgkins lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Research It is also being studied for the treatment of sarcoma. It is also being investigated in phase II trials for the non-cancer treatment of AL amyloidosis. References External links "Bendamustine". Drug Information Portal. U.S. National Library of Medicine.
Tobramycin/dexamethasone	Tobramycin/dexamethasone, sold under the brand name Tobradex, is a fixed-dose combination medication in the form of eye drops and eye ointment, marketed by Alcon. The active ingredients are tobramycin (an antibiotic) and dexamethasone (a corticosteroid). It is prescribed for the treatment of pink eye in combination with bacterial infections. Contraindications It is contraindicated with herpetic and other viral eye infections. Other contraindications include fungal and mycobacterial infections because tobramycin is inactive against those, and the corticoid acts as an immunosuppressive agent, preventing the bodys immune system from dealing with the infection. The drops are also contraindicated in patients with corneal lesions. Side effects Similarly to other corticosteroid eye drops, side effects include hypersensitivity and, especially after long-term use, secondary eye infections, cataract (clouding of the eye lens) and increased intraocular pressure, leading to glaucoma. Consequently, the drug should not be applied longer than 24 days without further medical evaluation. Interactions Anticholinergic eye drops potentiate the risk of increased intraocular pressure. Systemic aminoglycoside antibiotics increase toxicity for ears, nerves and kidney. Brand names Tobrason is a brand name in Jordan. References External links "Dexamethasone mixture with tobramycin". Drug Information Portal. U.S. National Library of Medicine.
Etravirine	Etravirine (ETR, brand name Intelence, formerly known as TMC125) is a drug used for the treatment of HIV. Etravirine is a non-nucleoside reverse transcriptase inhibitor (NNRTI). Unlike the currently available agents in the class, resistance to other NNRTIs does not seem to confer resistance to etravirine. Etravirine is marketed by Janssen, a subsidiary of Johnson & Johnson. In January 2008, the Food and Drug Administration approved its use for patients with established resistance to other drugs, making it the 30th anti-HIV drug approved in the United States and the first to be approved in 2008. It was also approved for use in Canada on April 1, 2008.Etravirine is licensed in the United States, Canada, Israel, Russia, Australia and the European Union, and is under regulatory review in Switzerland. Indications and dosage Etravirine, in combination with other anti-retrovirals, is indicated for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in antiretroviral treatment-experienced adult patients, who have evidence of viral replication and HIV-1 strains resistant to a non-nucleoside reverse transcriptase inhibitor (NNRTI) and other antiretroviral agents. The recommended dose of etravirine is 200 mg (2 x 100 mg tablets, or 1 x 200 mg tablet as of 03/18/2011) taken twice daily following a meal. The type of food does not affect the exposure to etravirine. Contraindication Each 100 mg etravirine tablet contains 160 mg of lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine. Mechanism of action Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), designed to be active against HIV with mutations that confer resistance to the two most commonly prescribed first-generation NNRTIs, mutation K103N for efavirenz and Y181C for nevirapine. This potency appears to be related to etravirines flexibility as a molecule. Etravirine is a diarylpyrimidine (DAPY), a type of organic molecule with some conformational isomerism that can bind the enzyme reverse transcriptase in multiple conformations, allowing for a more robust interaction between etravirine and the enzyme, even in the presence of mutations. Other diarylpyrimidine-analogues are currently being used as anti-HIV agents, notably rilpivirine. Warnings and risks In 2009, the prescribing information for etravirine was modified to include "postmarketing reports of cases of Stevens–Johnson syndrome, toxic epidermal necrolysis and erythema multiforme, as well as hypersensitivity reactions characterized by rash, constitutional findings, and sometimes organ dysfunction, including liver failure. Intelence therapy should be immediately discontinued when signs and symptoms of severe skin or hypersensitivity reactions develop." Repositioning Etravine has been studied for use in a drug repositioning application. In a paper published in the medical journal Movement Disorders, etravirine was shown to cause an increase in frataxin production. Frataxin deficiency is a key component to Friedreichs ataxia, a genetically inherited disease that causes the progressive loss of coordination and muscle strength leading to motor incapacitation and the full-time use of a wheelchair. Chemistry Etravine forms as colourless orthorhombic crystals in space group Pna21. The structures of these and of a number of solvate and salt forms have been reported. References External links "Etravirine". Drug Information Portal. U.S. National Library of Medicine.
Naproxen/pseudoephedrine	Naproxen/pseudoephedrine, sold under the brand name Aleve-D among others, is a fixed-dose combination medication used for the treatment of nasal congestion and other symptoms of the common cold. It contains naproxen, as the sodium salt, a nonsteroidal anti-inflammatory drug (NSAID); and pseudoephedrine, as the hydrochloride, a nasal decongestant. References External links "Naproxen mixture with pseudoephedrine hydrochloride". Drug Information Portal. U.S. National Library of Medicine.
Sotrovimab	Sotrovimab, sold under the brand name Xevudy, is a human neutralizing monoclonal antibody with activity against severe acute respiratory syndrome coronavirus 2, known as SARS-CoV-2. It is under development by GlaxoSmithKline and Vir Biotechnology, Inc. Sotrovimab is designed to attach to the spike protein of SARS-CoV-2.The most common side effects include hypersensitivity (allergic) reactions and infusion-related reactions. Medical uses In the European Union, sotrovimab is indicated for the treatment of COVID-19 in people aged twelve years of age and older and weighing at least 40 kilograms (88 lb) who do not require supplemental oxygen and who are at increased risk of the disease becoming severe.Sotrovimab is given by intravenous infusion, preferably within 5 days of onset of COVID-19 symptoms. Development and mechanism of action Sotrovimabs development began in December 2019, at Vir Biotechnology when Vir scientists first learned of the initial COVID-19 outbreak in China. Vir subsidiary Humabs BioMed had already compiled a library of frozen blood samples from patients infected with viral diseases, including two samples from patients infected with SARS-CoV-1. Vir scientists obtained samples of the novel SARS-CoV-2 virus and mixed them with various antibodies recovered from the old SARS-CoV-1 blood samples. The objective was to identify antibodies effective against both SARS-CoV-1 and SARS-CoV-2. This would imply that the antibodies were targeting highly conserved sequences and in turn would be more likely to remain effective against future variants of SARS-CoV-2. In April 2020, Lawrence Berkeley National Laboratory conducted a X-ray crystallography study at Virs request to investigate how such antibodies bind to SARS-CoV-2 at the molecular level. The Berkeley Lab data helped Vir identify candidates for further study, and Vir eventually settled on a single candidate antibody, S309. Vir collaborated with GlaxoSmithKline to make various refinements to S309, resulting in sotrovimab.Sotrovimab has been engineered to possess an Fc LS mutation (M428L/N434S) that confers enhanced binding to the neonatal Fc receptor resulting in an extended half-life and potentially enhanced drug distribution to the lungs.Sotrovimab has demonstrated activity via two antiviral mechanisms in vitro, antibody-dependent cellular cytotoxicity (ADCC) and antibody-dependent cellular phagocytosis (ADCP). Clinical efficacy The pivotal COMET-ICE study is an ongoing, randomized, double-blind, placebo-controlled study to assess the safety and efficacy of sotrovimab in adults with confirmed COVID-19 (mild, early disease with less than five days of symptoms) at risk of disease progression.An interim analysis of this study reported that sotrovimab reduced the risk of hospitalization for more than 24 hours or death by 85% compared with placebo. Overall 1% of people receiving sotrovimab died or required hospitalization for more than 24 hours compared to 7% of people treated with placebo. The study is ongoing and preliminary results have been published in the New England Journal of Medicine.The full analysis of the COMET-ICE trial was published in JAMA and it showed that sotrovimab reduced risk of hospitalization for more than 24 hours or death by 79% compared to placebo (1% for sotrovoimab group and 6% for the placebo group). The trial involved 1057 participants and took place before the omicron variant was prevalent. Manufacturing Sotrovimab is a biologic product which takes six months to manufacture in living cells. It is produced in Chinese hamster ovary cells. At product launch in May 2021, sotrovimabs active pharmaceutical ingredient was produced by WuXi Biologics in China and sent to a GlaxoSmithKline plant in Parma, Italy for further processing into the finished product. In January 2022, the spread of the SARS-CoV-2 Omicron variant began to render other monoclonal antibodies obsolete and caused global demand for sotrovimab to skyrocket. In response, Vir and GlaxoSmithKline announced they were working with Samsung Biologics on manufacturing sotrovimab at an additional site in South Korea. Society and culture Economics In 2021, the United States government agreed to purchase 1.5 million doses of the drug at $2,100 per dose. Legal status In May 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) completed its review on the use of sotrovimab for the treatment of COVID-19. It concluded that sotrovimab can be used to treat confirmed COVID-19 in adults and adolescents (aged twelve years and above and weighing at least 40 kilograms (88 lb)) who do not require supplemental oxygen and who are at risk of progressing to severe COVID-19. On 16 December 2021, the CHMP recommended authorizing sotrovimab for use in the EU and authorization was granted the next day.In May 2021, the U.S. Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for sotrovimab for the treatment of mild-to-moderate COVID-19 in people aged aged twelve years and above weighing at least 40 kilograms (88 lb) with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death.In August 2021, sotrovimab was granted provisional approval for the treatment of COVID-19 in Australia.In September 2021, sotrovimab was granted special exception authorization in Japan.In December 2021, the Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom approved sotrovimab for use in people aged twelve years of age and over who weigh more than 40 kilograms (88 lb).In March 2022, the FDA withdrew the EUA for sotrovimab in Connecticut, Maine, Massachusetts, New Hampshire, Rhode Island, Vermont, New Jersey, New York, Puerto Rico, the Virgin Islands, Illinois, Indiana, Michigan, Minnesota, Ohio, Wisconsin, Arizona, California, Hawaii, Nevada, American Samoa, Commonwealth of the Northern Mariana Islands, Federated States of Micronesia, Guam, Marshall Islands, Republic of Palau, Alaska, Idaho, Oregon, and Washington due to the high frequency of the Omicron BA.2 sub-variant and data showing that the authorized dose of sotrovimab is unlikely to be effective against that sub-variant. In April 2022, the FDA withdrew the EUA for sotrovimab. Research Sotrovimab is being evaluated in the following clinical trials: Clinical trial number NCT04545060 for "COMET-ICE" at ClinicalTrials.gov Clinical trial number NCT04779879 for "COMET-PEAK" at ClinicalTrials.gov Clinical trial number NCT04501978 for "ACTIV-3-TICO" at ClinicalTrials.gov Clinical trial number NCT04634409 for "BLAZE-4" at ClinicalTrials.govIn March 2022, Australian virologists observed that sotrovimab may cause a drug-resistant mutation. References External links "Sotrovimab". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT04545060 for "VIR-7831 for the Early Treatment of COVID-19 in Outpatients (COMET-ICE)" at ClinicalTrials.gov Australian Public Assessment Report: Sotrovimab. Therapeutic Goods Administration (TGA) (Report). 20 August 2021.
Alka-Seltzer	Alka-Seltzer is an effervescent antacid and pain reliever first marketed by the Dr. Miles Medicine Company of Elkhart, Indiana, United States. Alka-Seltzer contains three active ingredients: aspirin (acetylsalicylic acid) (ASA), sodium bicarbonate, and anhydrous citric acid. The aspirin is a pain reliever and anti-inflammatory, the sodium bicarbonate is an antacid, and the citric acid reacts with the sodium bicarbonate and water to form effervescence.It was developed by head chemist Maurice Treneer. Alka-Seltzer is marketed for relief of minor aches, pains, inflammation, fever, headache, heartburn, stomachache, indigestion, acid reflux and hangovers, while neutralizing excess stomach acid. It was launched in 1931.Its sister product, Alka-Seltzer Plus, treats cold and flu symptoms. A wide variety of formulae, many using acetaminophen (paracetamol) instead of aspirin, are available under the sister brand. Product information Alka-Seltzer is a combination of sodium bicarbonate, aspirin, and anhydrous citric acid, used for the relief of heartburn, acid indigestion, and stomach aches.Alka-Seltzer is sold in foil packets, each containing two tablets. Prior to 1984, it was also available stacked in glass tubes. It is available in many different flavors. It was once marketed as a cure-all; at one time, its ads even suggested taking it for "the blahs". Subsequent promotion has taken into consideration that aspirin is a drug that is not tolerated by everyone, and the product is no longer advertised in this fashion. Chemistry of the effervescence Though important to the overall effect of the medication, the aspirin (acetylsalicylic acid) is not required to produce the effervescent action of Alka-Seltzer; the effervescence is produced by the baking soda (sodium bicarbonate) and citric acid reacting to form sodium citrate and carbon dioxide gas. Marketing The product has been extensively advertised since its launch in the United States. It was originally marketed by Mikey Wiseman, a company scientist of Dr. Miles Medicine Company, who also helped direct its development. Print advertising was used immediately, and in 1932 the radio show Alka-Seltzer Comedy Star of Hollywood began, with National Barn Dance following in 1933, along with many more. The radio sponsorships continued into the 1950s, with the Alka-Seltzer Time show airing from 1949 to 1957. In 1951, the "Speedy" character was introduced. The character was conceived by creative director George Pal of the Wade Advertising agency and designed by illustrator Wally Wood. Originally named Sparky, the name was changed to Speedy by sales manager Perry L. Shupert to align with that years promotional theme, "Speedy Relief." Speedy appeared in over 200 TV commercials between 1954 and 1964. His body was one Alka-Seltzer tablet, while he wore another as a hat. Buster Keaton appeared along with the animated Speedy Alka-Seltzer figure in a series of 1950s commercials based on the product slogan, "Relief is just a swallow away." Speedy Alka-Seltzer was voiced by Dick Beals. Speedy was revived for a "Plop, plop, fizz, fizz" song spot in 1976. In his 1976 revival Beals proclaimed Alka-Seltzers virtues and sang the "Plop, plop, fizz, fizz, oh what a relief it is" song in his iconic high, squeaky voice. In the early 1960s, a commercial showing two tablets dropping into a glass of water instead of the usual one caused sales to double.Alka-Seltzer TV ads from the 1960s and 1970s in the US were among the most popular of the 20th century, ranking number 13, according to Advertising Age. To increase sales in a relatively flat business, Bayer revived several of the vintage spots.Paul Margulies (father of actress Julianna Margulies) created the famous "Plop, plop, fizz, fizz" ad campaign when he worked as a Madison Avenue ad executive. The ubiquitous jingle was composed by Tom Dawes—a former member of The Cyrkle. The slogan was altered to "Plink, plink, fizz" in the United Kingdom.During the race for space in the early 1960s before the moon landing, there was a commercial with Speedy in a space suit and a jingle with the lyrics "On Mans first trip through space, I only hope that Im aboard, securely strapped in place. Theyll track our ship with radar and telescopes and soon, imagine seeing Speedy Alka-Seltzer on the moon!"George Raft starred in the 1969 Alka-Seltzer commercial "The Unfinished Lunch". It consisted of Raft incarcerated in a prison lunchroom. He takes a bite of the prison food and recoils. Suddenly he bangs his cup on the steel table. It ripples throughout the room. He starts intoning "Alka-Seltzer, Alka-Seltzer..." Soon, the other hundreds of inmates do the same. (The commercial became so popular that several weeks later, Raft appeared as a guest on The Tonight Show Starring Johnny Carson. Raft told Carson that it took more than 7 hours to tape the 30-second commercial. Raft was enraged by the end of the day, thus making his inmate portrayal that much more convincing for the final editing. The film crew gave Raft his crumpled tin cup, which he showed to Carson and the audience.An animated mid-1960s commercial, animated by R. O. Blechman, shows a man and his own stomach sitting opposite each other in chairs, having an argument moderated by their therapist in a voiceover. The stomach (voiced by Gene Wilder) accuses the man of purposely trying to irritate it. The man accuses his stomach of complaining too much about the foods he likes. The therapist suggests Alka-Seltzer, and further suggests that the two must take care of each other. The closing words are of the stomach saying to the man: "Well, Ill try — if you will."Alka-Seltzer had a series of commercials during the mid-1960s that used a song called "No Matter What Shape (Your Stomachs In)". A different version was recorded by The T-Bones and was released as a single, which became a hit in 1966. The ads featured only the midsections (no faces) of people of all shapes and sizes. A clip of the ad can be seen briefly in the 1988 motion picture The In Crowd, immediately before the movies first live broadcast of the fictitious "Perry Parkers Dance Party." In an Alka-Seltzer commercial from 1969, an actor (played by Jack Somack) in a commercial for the fictional product "Magdalinis Meatballs" has to eat a meatball and then say "Mamma mia, thats-a spicy meat-a ball-a!" in an ersatz Italian accent. Take after take is ruined by some comedic trial or another (comedian Ronny Graham dropping the clapperboard). By the commercials end, Jack has eaten so many meatballs that its "Alka-Seltzer to the rescue." With his stomach settled, Jack does a perfect take, except that the oven door falls off. The director (off-camera) sighs and says, "OK, lets break for lunch."A 1970 commercial shows a newlywed couple in the bedroom after the woman (played by Alice Playten) has finished serving her husband (played by Terry Kiser) a giant dumpling; the implication is that her cooking skills are severely lacking, despite her husbands lament, "I cant believe I ate that whole thing!", the commercials catchphrase. She lies on the bed in delusional triumph. She offers her beleaguered husband a heart-shaped meatloaf; he disappears to take some Alka-Seltzer. When she hears the fizzy noise coming from the bathroom, he quickly covers the glass of dissolving Alka-Seltzer as she wonders aloud if it is raining. Just when he has recovered his well-being, he hears her misreading recipes for dinner the next night: "Marshmallowed meatballs," "medium salad snails," and "pouched (actually poached) oysters". He returns to the bathroom for more Alka-Seltzer. The catchphrase, Howie Cohen told the Los Angeles Times, was inspired when he ate too much of the food at a London commercial shoot because "I am a nice Jewish kid from the Bronx, so I ate everything," and when he told his wife "I cant believe I ate the whole thing", she said, "Theres your next Alka-Seltzer commercial."A 1971 commercial featured another catch-phrase from Cohen (along with Bob Pasqualina), "Try it, youll like it!" It was remade with Kathy Griffin in 2006. In 1972, an actor (Milt Moss) spent the commercial moaning, "I cant believe I ate that who-o-o-o-o-ole thing," while his wife (Lynn Whinic) made sarcastic comments and finally advised him to take some Alka-Seltzer. In 2005, this ad was also remade, featuring Peter Boyle and Doris Roberts from the 1996–2005 TV sitcom Everybody Loves Raymond.Sammy Davis, Jr. recorded two versions of the "Plop Plop Fizz Fizz" jingle in 1978, one of which (the "big band" version) was featured on a television commercial. Both the big band and rock versions had additional lyrics (with at least one verse unique to each song) written by Tom Dawes, former lead singer of The Cyrkle who wrote the original jingle. In 2009, the brand was featured in television commercials supporting the United States Ski Team that included alpine skier Lindsey Vonn and Nordic combined skier Bill Demong. Miniature figures of the Speedy mascot were shown with each. Alka-Seltzer products are sold in nighttime and daytime, or non drowsy, formulas. The non-drowsy claims have recently been questioned.In December 2010, Alka-Seltzer began a series of new commercials featuring Speedy, using a CGI character, created by Animation Director David Hulin, to recreate the stop-motion puppetry of the 1950s and 1960s, with Speedy voiced by Debi Derryberry. See also Carbonated water Brioschi References External links Official website
Aspirin	Aspirin, also known as acetylsalicylic acid (ASA), is a nonsteroidal anti-inflammatory drug (NSAID) used to reduce pain, fever, and/or inflammation, and as an anticoagulant. Specific inflammatory conditions which aspirin is used to treat include Kawasaki disease, pericarditis, and rheumatic fever.Aspirin is also used long-term to help prevent further heart attacks, ischaemic strokes, and blood clots in people at high risk. For pain or fever, effects typically begin within 30 minutes. Aspirin works similarly to other NSAIDs but also suppresses the normal functioning of platelets.One common adverse effect is an upset stomach. More significant side effects include stomach ulcers, stomach bleeding, and worsening asthma. Bleeding risk is greater among those who are older, drink alcohol, take other NSAIDs, or are on other blood thinners. Aspirin is not recommended in the last part of pregnancy. It is not generally recommended in children with infections because of the risk of Reye syndrome. High doses may result in ringing in the ears.A precursor to aspirin found in the bark of the willow tree (genus Salix) has been used for its health effects for at least 2,400 years. In 1853, chemist Charles Frédéric Gerhardt treated the medicine sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time. Over the next 50 years, other chemists established the chemical structure and devised more efficient production methods.: 69–75 Aspirin is available without medical prescription as a proprietary or generic medication in most jurisdictions. It is one of the most widely used medications globally, with an estimated 40,000 tonnes (44,000 tons) (50 to 120 billion pills) consumed each year, and is on the World Health Organizations List of Essential Medicines. In 2020, it was the 36th most commonly prescribed medication in the United States, with more than 17 million prescriptions. Brand vs. generic name In 1897, scientists at the Bayer company began studying acetylsalicylic acid as a less-irritating replacement medication for common salicylate medicines.: 69–75 By 1899, Bayer had named it "Aspirin" and sold it around the world.Aspirins popularity grew over the first half of the 20th century, leading to competition between many brands and formulations. The word Aspirin was Bayers brand name; however, their rights to the trademark were lost or sold in many countries. The name is ultimately a blend of the prefix a(cetyl) + spir Spiraea, the meadowsweet plant genus from which the acetylsalicylic acid was originally derived at Bayer + -in, the common chemical suffix. Chemical properties Aspirin decomposes rapidly in solutions of ammonium acetate or the acetates, carbonates, citrates, or hydroxides of the alkali metals. It is stable in dry air, but gradually hydrolyses in contact with moisture to acetic and salicylic acids. In solution with alkalis, the hydrolysis proceeds rapidly and the clear solutions formed may consist entirely of acetate and salicylate.Like flour mills, factories producing aspirin tablets must control the amount of the powder that becomes airborne inside the building, because the powder-air mixture can be explosive. The National Institute for Occupational Safety and Health (NIOSH) has set a recommended exposure limit in the United States of 5 mg/m3 (time-weighted average). In 1989, the Occupational Safety and Health Administration (OSHA) set a legal permissible exposure limit for aspirin of 5 mg/m3, but this was vacated by the AFL-CIO v. OSHA decision in 1993. Synthesis The synthesis of aspirin is classified as an esterification reaction. Salicylic acid is treated with acetic anhydride, an acid derivative, causing a chemical reaction that turns salicylic acids hydroxyl group into an ester group (R-OH → R-OCOCH3). This process yields aspirin and acetic acid, which is considered a byproduct of this reaction. Small amounts of sulfuric acid (and occasionally phosphoric acid) are almost always used as a catalyst. This method is commonly demonstrated in undergraduate teaching labs. Reaction mechanism Formulations containing high concentrations of aspirin often smell like vinegar because aspirin can decompose through hydrolysis in moist conditions, yielding salicylic and acetic acids. Physical properties Aspirin, an acetyl derivative of salicylic acid, is a white, crystalline, weakly acidic substance, with a melting point of 136 °C (277 °F), and a boiling point of 140 °C (284 °F). Its acid dissociation constant (pKa) is 3.5 at 25 °C (77 °F). Polymorphism Polymorphism, or the ability of a substance to form more than one crystal structure, is important in the development of pharmaceutical ingredients. Many drugs receive regulatory approval for only a single crystal form or polymorph. For a long time, only one crystal structure for aspirin was known. That aspirin might have a second crystalline form was suspected since the 1960s. The elusive second polymorph was first discovered by Vishweshwar and coworkers in 2005, and fine structural details were given by Bond et al. A new crystal type was found during experiments after co-crystallization of aspirin and levetiracetam from hot acetonitrile. The form II is only stable at 100 K and reverts to form I at ambient temperature. In the (unambiguous) form I, two salicylic molecules form centrosymmetric dimers through the acetyl groups with the (acidic) methyl proton to carbonyl hydrogen bonds, and in the newly claimed form II, each salicylic molecule forms the same hydrogen bonds with two neighboring molecules instead of one. With respect to the hydrogen bonds formed by the carboxylic acid groups, both polymorphs form identical dimer structures. Mechanism of action Discovery of the mechanism In 1971, British pharmacologist John Robert Vane, then employed by the Royal College of Surgeons in London, showed aspirin suppressed the production of prostaglandins and thromboxanes. For this discovery he was awarded the 1982 Nobel Prize in Physiology or Medicine, jointly with Sune Bergström and Bengt Ingemar Samuelsson. Prostaglandins and thromboxanes Aspirins ability to suppress the production of prostaglandins and thromboxanes is due to its irreversible inactivation of the cyclooxygenase (COX; officially known as prostaglandin-endoperoxide synthase, PTGS) enzyme required for prostaglandin and thromboxane synthesis. Aspirin acts as an acetylating agent where an acetyl group is covalently attached to a serine residue in the active site of the PTGS enzyme (Suicide inhibition). This makes aspirin different from other NSAIDs (such as diclofenac and ibuprofen), which are reversible inhibitors. Low-dose aspirin use irreversibly blocks the formation of thromboxane A2 in platelets, producing an inhibitory effect on platelet aggregation during the lifetime of the affected platelet (8–9 days). This antithrombotic property makes aspirin useful for reducing the incidence of heart attacks in people who have had a heart attack, unstable angina, ischemic stroke or transient ischemic attack. 40 mg of aspirin a day is able to inhibit a large proportion of maximum thromboxane A2 release provoked acutely, with the prostaglandin I2 synthesis being little affected; however, higher doses of aspirin are required to attain further inhibition.Prostaglandins, local hormones produced in the body, have diverse effects, including the transmission of pain information to the brain, modulation of the hypothalamic thermostat, and inflammation. Thromboxanes are responsible for the aggregation of platelets that form blood clots. Heart attacks are caused primarily by blood clots, and low doses of aspirin are seen as an effective medical intervention to prevent a second acute myocardial infarction. COX-1 and COX-2 inhibition At least two different types of cyclooxygenases, COX-1 and COX-2, are acted on by aspirin. Aspirin irreversibly inhibits COX-1 and modifies the enzymatic activity of COX-2. COX-2 normally produces prostanoids, most of which are proinflammatory. Aspirin-modified PTGS2 (prostaglandin-endoperoxide synthase 2) produces lipoxins, most of which are anti-inflammatory. Newer NSAID drugs, COX-2 inhibitors (coxibs), have been developed to inhibit only PTGS2, with the intent to reduce the incidence of gastrointestinal side effects.Several COX-2 inhibitors, such as rofecoxib (Vioxx), have been withdrawn from the market, after evidence emerged that PTGS2 inhibitors increase the risk of heart attack and stroke. Endothelial cells lining the microvasculature in the body are proposed to express PTGS2, and, by selectively inhibiting PTGS2, prostaglandin production (specifically, PGI2; prostacyclin) is downregulated with respect to thromboxane levels, as PTGS1 in platelets is unaffected. Thus, the protective anticoagulative effect of PGI2 is removed, increasing the risk of thrombus and associated heart attacks and other circulatory problems. Since platelets have no DNA, they are unable to synthesize new PTGS once aspirin has irreversibly inhibited the enzyme, an important difference as compared with reversible inhibitors. Furthermore, aspirin, while inhibiting the ability of COX-2 to form pro-inflammatory products such as the prostaglandins, converts this enzymes activity from a prostaglandin-forming cyclooxygenase to a lipoxygenase-like enzyme: aspirin-treated COX-2 metabolizes a variety of polyunsaturated fatty acids to hydroperoxy products which are then further metabolized to specialized proresolving mediators such as the aspirin-triggered lipoxins, aspirin-triggered resolvins, and aspirin-triggered maresins. These mediators possess potent anti-inflammatory activity. It is proposed that this aspirin-triggered transition of COX-2 from cyclooxygenase to lipoxygenase activity and the consequential formation of specialized proresolving mediators contributes to the anti-inflammatory effects of aspirin. Additional mechanisms Aspirin has been shown to have at least three additional modes of action. It uncouples oxidative phosphorylation in cartilaginous (and hepatic) mitochondria, by diffusing from the inner membrane space as a proton carrier back into the mitochondrial matrix, where it ionizes once again to release protons. Aspirin buffers and transports the protons. When high doses are given, it may actually cause fever, owing to the heat released from the electron transport chain, as opposed to the antipyretic action of aspirin seen with lower doses. In addition, aspirin induces the formation of NO-radicals in the body, which have been shown in mice to have an independent mechanism of reducing inflammation. This reduced leukocyte adhesion is an important step in the immune response to infection; however, evidence is insufficient to show aspirin helps to fight infection. More recent data also suggest salicylic acid and its derivatives modulate signalling through NF-κB. NF-κB, a transcription factor complex, plays a central role in many biological processes, including inflammation.Aspirin is readily broken down in the body to salicylic acid, which itself has anti-inflammatory, antipyretic, and analgesic effects. In 2012, salicylic acid was found to activate AMP-activated protein kinase, which has been suggested as a possible explanation for some of the effects of both salicylic acid and aspirin. The acetyl portion of the aspirin molecule has its own targets. Acetylation of cellular proteins is a well-established phenomenon in the regulation of protein function at the post-translational level. Aspirin is able to acetylate several other targets in addition to COX isoenzymes. These acetylation reactions may explain many hitherto unexplained effects of aspirin. Pharmacokinetics Acetylsalicylic acid is a weak acid, and very little of it is ionized in the stomach after oral administration. Acetylsalicylic acid is quickly absorbed through the cell membrane in the acidic conditions of the stomach. The increased pH and larger surface area of the small intestine causes aspirin to be absorbed more slowly there, as more of it is ionized. Owing to the formation of concretions, aspirin is absorbed much more slowly during overdose, and plasma concentrations can continue to rise for up to 24 hours after ingestion.About 50–80% of salicylate in the blood is bound to human serum albumin, while the rest remains in the active, ionized state; protein binding is concentration-dependent. Saturation of binding sites leads to more free salicylate and increased toxicity. The volume of distribution is 0.1–0.2 L/kg. Acidosis increases the volume of distribution because of enhancement of tissue penetration of salicylates.As much as 80% of therapeutic doses of salicylic acid is metabolized in the liver. Conjugation with glycine forms salicyluric acid, and with glucuronic acid to form two different glucuronide esters. The conjugate with the acetyl group intact is referred to as the acyl glucuronide; the deacetylated conjugate is the phenolic glucuronide. These metabolic pathways have only a limited capacity. Small amounts of salicylic acid are also hydroxylated to gentisic acid. With large salicylate doses, the kinetics switch from first-order to zero-order, as metabolic pathways become saturated and renal excretion becomes increasingly important.Salicylates are excreted mainly by the kidneys as salicyluric acid (75%), free salicylic acid (10%), salicylic phenol (10%), and acyl glucuronides (5%), gentisic acid (< 1%), and 2,3-dihydroxybenzoic acid. When small doses (less than 250 mg in an adult) are ingested, all pathways proceed by first-order kinetics, with an elimination half-life of about 2.0 h to 4.5 h. When higher doses of salicylate are ingested (more than 4 g), the half-life becomes much longer (15 h to 30 h), because the biotransformation pathways concerned with the formation of salicyluric acid and salicyl phenolic glucuronide become saturated. Renal excretion of salicylic acid becomes increasingly important as the metabolic pathways become saturated, because it is extremely sensitive to changes in urinary pH. A 10- to 20-fold increase in renal clearance occurs when urine pH is increased from 5 to 8. The use of urinary alkalinization exploits this particular aspect of salicylate elimination. It was found that short-term aspirin use in therapeutic doses might precipitate reversible acute kidney injury when the patient was ill with glomerulonephritis or cirrhosis. Aspirin for some patients with chronic kidney disease and some children with congestive heart failure was contraindicated. History Medicines made from willow and other salicylate-rich plants appear in clay tablets from ancient Sumer as well as the Ebers Papyrus from ancient Egypt.: 8–13 Hippocrates referred to the use of salicylic tea to reduce fevers around 400 BC, and willow bark preparations were part of the pharmacopoeia of Western medicine in classical antiquity and the Middle Ages. Willow bark extract became recognized for its specific effects on fever, pain, and inflammation in the mid-eighteenth century. By the nineteenth century, pharmacists were experimenting with and prescribing a variety of chemicals related to salicylic acid, the active component of willow extract.: 46–55 In 1853, chemist Charles Frédéric Gerhardt treated sodium salicylate with acetyl chloride to produce acetylsalicylic acid for the first time;: 46–48 in the second half of the 19th century, other academic chemists established the compounds chemical structure and devised more efficient methods of synthesis. In 1897, scientists at the drug and dye firm Bayer began investigating acetylsalicylic acid as a less-irritating replacement for standard common salicylate medicines, and identified a new way to synthesize it.: 69–75 By 1899, Bayer had dubbed this drug Aspirin and was selling it globally.: 27 The word Aspirin was Bayers brand name, rather than the generic name of the drug; however, Bayers rights to the trademark were lost or sold in many countries. Aspirins popularity grew over the first half of the 20th century leading to fierce competition with the proliferation of aspirin brands and products.Aspirins popularity declined after the development of acetaminophen/paracetamol in 1956 and ibuprofen in 1962. In the 1960s and 1970s, John Vane and others discovered the basic mechanism of aspirins effects,: 226–231 while clinical trials and other studies from the 1960s to the 1980s established aspirins efficacy as an anti-clotting agent that reduces the risk of clotting diseases.: 247–257 The initial large studies on the use of low-dose aspirin to prevent heart attacks that were published in the 1970s and 1980s helped spur reform in clinical research ethics and guidelines for human subject research and US federal law, and are often cited as examples of clinical trials that included only men, but from which people drew general conclusions that did not hold true for women.Aspirin sales revived considerably in the last decades of the 20th century, and remain strong in the 21st century with widespread use as a preventive treatment for heart attacks and strokes.: 267–269 Trademark Bayer lost its trademark for Aspirin in the United States in actions taken between 1918 and 1921 because it had failed to use the name for its own product correctly and had for years allowed the use of "Aspirin" by other manufacturers without defending the intellectual property rights. Today, aspirin is a generic trademark in many countries. Aspirin, with a capital "A", remains a registered trademark of Bayer in Germany, Canada, Mexico, and in over 80 other countries, for acetylsalicylic acid in all markets, but using different packaging and physical aspects for each. Compendial status United States Pharmacopeia British Pharmacopoeia Medical use Aspirin is used in the treatment of a number of conditions, including fever, pain, rheumatic fever, and inflammatory conditions, such as rheumatoid arthritis, pericarditis, and Kawasaki disease. Lower doses of aspirin have also been shown to reduce the risk of death from a heart attack, or the risk of stroke in people who are at high risk or who have cardiovascular disease, but not in elderly people who are otherwise healthy. There is some evidence that aspirin is effective at preventing colorectal cancer, though the mechanisms of this effect are unclear. In the United States, the selective initiation of low-dose aspirin, based on an individualised assessment, has been deemed reasonable for the primary prevention of cardiovascular disease in people aged between 40 and 59 who have a 10% or greater risk of developing cardiovascular disease over the next 10 years and are not at an increased risk of bleeding. Pain Aspirin is an effective analgesic for acute pain, although it is generally considered inferior to ibuprofen because aspirin is more likely to cause gastrointestinal bleeding. Aspirin is generally ineffective for those pains caused by muscle cramps, bloating, gastric distension, or acute skin irritation. As with other NSAIDs, combinations of aspirin and caffeine provide slightly greater pain relief than aspirin alone. Effervescent formulations of aspirin relieve pain faster than aspirin in tablets, which makes them useful for the treatment of migraines. Topical aspirin may be effective for treating some types of neuropathic pain.Aspirin, either by itself or in a combined formulation, effectively treats certain types of a headache, but its efficacy may be questionable for others. Secondary headaches, meaning those caused by another disorder or trauma, should be promptly treated by a medical provider. Among primary headaches, the International Classification of Headache Disorders distinguishes between tension headache (the most common), migraine, and cluster headache. Aspirin or other over-the-counter analgesics are widely recognized as effective for the treatment of tension headache. Aspirin, especially as a component of an aspirin/paracetamol/caffeine combination, is considered a first-line therapy in the treatment of migraine, and comparable to lower doses of sumatriptan. It is most effective at stopping migraines when they are first beginning. Fever Like its ability to control pain, aspirins ability to control fever is due to its action on the prostaglandin system through its irreversible inhibition of COX. Although aspirins use as an antipyretic in adults is well established, many medical societies and regulatory agencies, including the American Academy of Family Physicians, the American Academy of Pediatrics, and the Food and Drug Administration, strongly advise against using aspirin for treatment of fever in children because of the risk of Reyes syndrome, a rare but often fatal illness associated with the use of aspirin or other salicylates in children during episodes of viral or bacterial infection. Because of the risk of Reyes syndrome in children, in 1986, the US Food and Drug Administration (FDA) required labeling on all aspirin-containing medications advising against its use in children and teenagers. Inflammation Aspirin is used as an anti-inflammatory agent for both acute and long-term inflammation, as well as for treatment of inflammatory diseases, such as rheumatoid arthritis. Heart attacks and strokes Aspirin is an important part of the treatment of those who have had a heart attack. It is generally not recommended for routine use by people with no other health problems, including those over the age of 70.The 2009 Antithrombotic Trialists Collaboration published in Lancet evaluated the efficacy and safety of low dose aspirin in secondary prevention. In those with prior ischaemic stroke or acute myocardial infarction, daily low dose aspirin was associated with a 19% relative risk reduction of serious cardiovascular events (non-fatal myocardial infarction, non-fatal stroke, or vascular death). This did come at the expense of a 0.19% absolute risk increase in gastrointestinal bleeding; however, the benefits outweigh the hazard risk in this case. Data from early trials of aspirin in primary prevention suggested low dose aspirin is more beneficial for people <70 kg and high dose aspirin is more beneficial for those ≥70 kg. However, more recent trials have suggested lower dose aspirin is not more efficacious in people with a low body weight and more evidence is required to determine the effect of higher dose aspirin in people with a high body weight. The United States Preventive Services Task Force (USPSTF), in 2016, recommended initiating low-dose aspirin use for the primary prevention of cardiovascular disease and colon cancer in adults aged 50 to 59 years who have a 10% or greater 10-year cardiovascular disease (CVD) risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years. However, in 2021, the USPSTF recommended against the routine use of daily aspirin for primary prevention in adults in their 40s and 50s, citing the fact that the risk of side effects outweighs the potential benefits. In April 2022, the USPSTF said "people ages 40 to 59 who are at higher risk for CVD should decide with their clinician whether to start taking aspirin; people 60 or older should not start taking aspirin to prevent a first heart attack or stroke."The status of the use of aspirin for the primary prevention in cardiovascular disease is conflicting and inconsistent. The ASCEND study demonstrated that in high-bleeding risk diabetics with no prior cardiovascular disease, there is no overall clinical benefit (12% decrease in risk of ischaemic events v/s 29% increase in GI bleeding) of low dose aspirin in preventing the serious vascular events over a period of 7.4 years. Similarly, the results of the ARRIVE study also showed no benefit of same dose of aspirin in reducing the time to first cardiovascular outcome in patients with moderate risk of cardiovascular disease over a period of five years.Aspirin appears to offer little benefit to those at lower risk of heart attack or stroke—for instance, those without a history of these events or with pre-existing disease. Some studies recommend aspirin on a case-by-case basis, while others have suggested the risks of other events, such as gastrointestinal bleeding, were enough to outweigh any potential benefit, and recommended against using aspirin for primary prevention entirely. Aspirin has also been suggested as a component of a polypill for prevention of cardiovascular disease.Complicating the use of aspirin for prevention is the phenomenon of aspirin resistance. For people who are resistant, aspirins efficacy is reduced. Some authors have suggested testing regimens to identify people who are resistant to aspirin.After percutaneous coronary interventions (PCIs), such as the placement of a coronary artery stent, a U.S. Agency for Healthcare Research and Quality guideline recommends that aspirin be taken indefinitely. Frequently, aspirin is combined with an ADP receptor inhibitor, such as clopidogrel, prasugrel, or ticagrelor to prevent blood clots. This is called dual antiplatelet therapy (DAPT). Duration of DAPT was advised in the United States and European Union guidelines after the CURE and PRODIGY studies. In 2020, the systematic review and network meta-analysis from Khan et al. showed promising benefits of short-term (< 6 months) DAPT followed by P2Y12 inhibitors in selected patients, as well as the benefits of extended-term (> 12 months) DAPT in high risk patients. In conclusion, the optimal duration of DAPT after PCIs should be personalized after outweighing each patients risks of ischemic events and risks of bleeding events with consideration of multiple patient-related and procedure-related factors. Moreover, aspirin should be continued indefinitely after DAPT is complete. Cancer prevention Aspirin may reduce the overall risk of both getting cancer and dying from cancer. There is substantial evidence for lowering the risk of colorectal cancer (CRC), but must be taken for at least 10–20 years to see this benefit. It may also slightly reduce the risk of endometrial cancer, breast cancer, and prostate cancer.Some conclude the benefits are greater than the risks due to bleeding in those at average risk. Others are unclear if the benefits are greater than the risk. Given this uncertainty, the 2007 United States Preventive Services Task Force (USPSTF) guidelines on this topic recommended against the use of aspirin for prevention of CRC in people with average risk. Nine years later however, the USPSTF issued a grade B recommendation for the use of low-dose aspirin (75 to 100 mg/day) "for the primary prevention of CVD [cardiovascular disease] and CRC in adults 50 to 59 years of age who have a 10% or greater 10-year CVD risk, are not at increased risk for bleeding, have a life expectancy of at least 10 years, and are willing to take low-dose aspirin daily for at least 10 years".A meta-analysis through 2019 said that there was an association between taking aspirin and lower risk of cancer of the colorectum, esophagus, and stomach.In 2021, the U.S. Preventive services Task Force raised questions about the use of aspirin in cancer prevention. It notes the results of the 2018 ASPREE (Aspirin in Reducing Events in the Elderly) Trial, in which the risk of cancer-related death was higher in the aspirin-treated group than
Aspirin	in the placebo group. Psychiatry Bipolar disorder Aspirin, along with several other agents with anti-inflammatory properties, has been repurposed as an add-on treatment for depressive episodes in subjects with bipolar disorder in light of the possible role of inflammation in the pathogenesis of severe mental disorders. However, meta-analytic evidence is based on very few studies and does not suggest any efficacy of aspirin in the treatment of bipolar depression. Thus, notwithstanding the biological rationale, the clinical perspectives of aspirin and anti-inflammatory agents in the treatment of bipolar depression remain uncertain. Dementia Although cohort and longitudinal studies have shown low-dose aspirin has a greater likelihood of reducing the incidence of dementia, numerous randomised controlled trials have not validated this. Other uses Aspirin is a first-line treatment for the fever and joint-pain symptoms of acute rheumatic fever. The therapy often lasts for one to two weeks, and is rarely indicated for longer periods. After fever and pain have subsided, the aspirin is no longer necessary, since it does not decrease the incidence of heart complications and residual rheumatic heart disease. Naproxen has been shown to be as effective as aspirin and less toxic, but due to the limited clinical experience, naproxen is recommended only as a second-line treatment.Along with rheumatic fever, Kawasaki disease remains one of the few indications for aspirin use in children in spite of a lack of high quality evidence for its effectiveness.Low-dose aspirin supplementation has moderate benefits when used for prevention of pre-eclampsia. This benefit is greater when started in early pregnancy. Resistance For some people, aspirin does not have as strong an effect on platelets as for others, an effect known as aspirin-resistance or insensitivity. One study has suggested women are more likely to be resistant than men, and a different, aggregate study of 2,930 people found 28% were resistant. A study in 100 Italian people found, of the apparent 31% aspirin-resistant subjects, only 5% were truly resistant, and the others were noncompliant. Another study of 400 healthy volunteers found no subjects who were truly resistant, but some had "pseudoresistance, reflecting delayed and reduced drug absorption". Meta-analysis and systematic reviews have concluded that laboratory confirmed aspirin resistance confers increased rates of poorer outcomes in cardiovascular and neurovascular diseases. Although the majority of research conducted has surrounded cardiovascular and neurovascular, there is emerging research into the risk of aspirin resistance after orthopaedic surgery where aspirin is used for venous thromboembolism prophylaxis. Aspirin resistance in orthopaedic surgery, specifically after total hip and knee arthroplasties, is of interest as risk factors for aspirin resistance are also risk factors for venous thromboembolisms and osteoarthritis; the sequalae of requiring a total hip or knee arthroplasty. Some of these risk factors include obesity, advancing age, diabetes mellitus, dyslipidaemia and inflammatory diseases. Dosages Adult aspirin tablets are produced in standardised sizes, which vary slightly from country to country, for example 300 mg in Britain and 325 mg (or 5 grains) in the United States. Smaller doses are based on these standards, e.g., 75 mg and 81 mg tablets. The 81-milligram (1+1⁄4-grain) tablets are commonly called "baby aspirin" or "baby-strength", because they were originally – but no longer – intended to be administered to infants and children. No medical significance occurs due to the slight difference in dosage between the 75 mg and the 81 mg tablets. The dose required for benefit appears to depend on a persons weight. For those weighing less than 70 kilograms (154 lb), low dose is effective for preventing cardiovascular disease; for patients above this weight, higher doses are required.In general, for adults, doses are taken four times a day for fever or arthritis, with doses near the maximal daily dose used historically for the treatment of rheumatic fever. For the prevention of myocardial infarction (MI) in someone with documented or suspected coronary artery disease, much lower doses are taken once daily.March 2009 recommendations from the USPSTF on the use of aspirin for the primary prevention of coronary heart disease encourage men aged 45–79 and women aged 55–79 to use aspirin when the potential benefit of a reduction in MI for men or stroke for women outweighs the potential harm of an increase in gastrointestinal hemorrhage. The WHI study of postmenopausal women found that aspirin resulted in a 25% lower risk of death from cardiovascular disease and a 14% lower risk of death from any cause, though there was no significant difference between 81 mg and 325 mg aspirin doses. The 2021 ADAPTABLE study also showed no significant difference in cardiovascular events or major bleeding between 81 mg and 325 mg doses of aspirin in patients (both men and women) with established cardiovascular disease.Low-dose aspirin use was also associated with a trend toward lower risk of cardiovascular events, and lower aspirin doses (75 or 81 mg/day) may optimize efficacy and safety for people requiring aspirin for long-term prevention.In children with Kawasaki disease, aspirin is taken at dosages based on body weight, initially four times a day for up to two weeks and then at a lower dose once daily for a further six to eight weeks. Adverse effects In October 2020, the US Food and Drug Administration (FDA) required the drug label to be updated for all nonsteroidal anti-inflammatory medications to describe the risk of kidney problems in unborn babies that result in low amniotic fluid. They recommend avoiding NSAIDs in pregnant women at 20 weeks or later in pregnancy. One exception to the recommendation is the use of low-dose 81 mg aspirin at any point in pregnancy under the direction of a health care professional. Contraindications Aspirin should not be taken by people who are allergic to ibuprofen or naproxen, or who have salicylate intolerance or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Owing to its effect on the stomach lining, manufacturers recommend people with peptic ulcers, mild diabetes, or gastritis seek medical advice before using aspirin. Even if none of these conditions is present, the risk of stomach bleeding is still increased when aspirin is taken with alcohol or warfarin. People with hemophilia or other bleeding tendencies should not take aspirin or other salicylates. Aspirin is known to cause hemolytic anemia in people who have the genetic disease glucose-6-phosphate dehydrogenase deficiency, particularly in large doses and depending on the severity of the disease. Use of aspirin during dengue fever is not recommended owing to increased bleeding tendency. People with kidney disease, hyperuricemia, or gout should not take aspirin because it inhibits the kidneys ability to excrete uric acid, thus may exacerbate these conditions. Aspirin should not be given to children or adolescents to control cold or influenza symptoms, as this has been linked with Reyes syndrome. Gastrointestinal Aspirin use has been shown to increase the risk of gastrointestinal bleeding. Although some enteric-coated formulations of aspirin are advertised as being "gentle to the stomach", in one study, enteric coating did not seem to reduce this risk. Combining aspirin with other NSAIDs has also been shown to further increase this risk. Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper gastrointestinal bleeding.Blockade of COX-1 by aspirin apparently results in the upregulation of COX-2 as part of a gastric defense. Several trials suggest that the simultaneous use of a COX-2 inhibitor with aspirin may increase the risk of gastrointestinal injury. However, currently available evidence has been unable to prove that this effect is consistently repeatable in everyday clinical practice. More dedicated research is required to provide greater clarity on the subject. Therefore, caution should be exercised if combining aspirin with any "natural" supplements with COX-2-inhibiting properties, such as garlic extracts, curcumin, bilberry, pine bark, ginkgo, fish oil, resveratrol, genistein, quercetin, resorcinol, and others.In addition to enteric coating, "buffering" is the other main method companies have used to try to mitigate the problem of gastrointestinal bleeding. Buffering agents are intended to work by preventing the aspirin from concentrating in the walls of the stomach, although the benefits of buffered aspirin are disputed. Almost any buffering agent used in antacids can be used; Bufferin, for example, uses magnesium oxide. Other preparations use calcium carbonate. Gas-forming agents in effervescent tablet and powder formulations can also double as a buffering agent, one example being sodium bicarbonate found in Alka-Seltzer.Taking it with vitamin C has been investigated as a method of protecting the stomach lining. Taking equal doses of vitamin C and aspirin may decrease the amount of stomach damage that occurs compared to taking aspirin alone. Retinal vein occlusion It is a widespread habit among eye specialists (ophthalmologists) to prescribe aspirin as an add-on medication for patients with retinal vein occlusion (RVO), such as central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO). The reason of this widespread use is the evidence of its proven effectiveness in major systemic venous thrombotic disorders, and it has been assumed that may be similarly beneficial in various types of retinal vein occlusion. However, a large-scale investigation based on data of nearly 700 patients showed "that aspirin or other antiplatelet aggregating agents or anticoagulants adversely influence the visual outcome in patients with CRVO and hemi-CRVO, without any evidence of protective or beneficial effect". Several expert groups, including the Royal College of Ophthalmologists, recommended against the use of antithrombotic drugs (incl. aspirin) for patients with RVO. Central effects Large doses of salicylate, a metabolite of aspirin, cause temporary tinnitus (ringing in the ears) based on experiments in rats, via the action on arachidonic acid and NMDA receptors cascade. Reyes syndrome Reyes syndrome, a rare but severe illness characterized by acute encephalopathy and fatty liver, can occur when children or adolescents are given aspirin for a fever or other illness or infection. From 1981 to 1997, 1207 cases of Reyes syndrome in people younger than 18 were reported to the US Centers for Disease Control and Prevention (CDC). Of these, 93% reported being ill in the three weeks preceding the onset of Reyes syndrome, most commonly with a respiratory infection, chickenpox, or diarrhea. Salicylates were detectable in 81.9% of children for whom test results were reported. After the association between Reyes syndrome and aspirin was reported, and safety measures to prevent it (including a Surgeon Generals warning, and changes to the labeling of aspirin-containing drugs) were implemented, aspirin taken by children declined considerably in the United States, as did the number of reported cases of Reyes syndrome; a similar decline was found in the United Kingdom after warnings against pediatric aspirin use were issued. The US Food and Drug Administration recommends aspirin (or aspirin-containing products) should not be given to anyone under the age of 12 who has a fever, and the UK National Health Service recommends children who are under 16 years of age should not take aspirin, unless it is on the advice of a doctor. Skin For a small number of people, taking aspirin can result in symptoms including hives, swelling, and headache. Aspirin can exacerbate symptoms among those with chronic hives, or create acute symptoms of hives. These responses can be due to allergic reactions to aspirin, or more often due to its effect of inhibiting the COX-1 enzyme. Skin reactions may also tie to systemic contraindications, seen with NSAID-precipitated bronchospasm, or those with atopy.Aspirin and other NSAIDs, such as ibuprofen, may delay the healing of skin wounds. Earlier findings from two small, low-quality trials suggested a benefit with aspirin (alongside compression therapy) on venous leg ulcer healing time and leg ulcer size, however larger, more recent studies of higher quality have been unable to corroborate these outcomes. As such, further research is required to clarify the role of aspirin in this context. Other adverse effects Aspirin can induce swelling of skin tissues in some people. In one study, angioedema appeared one to six hours after ingesting aspirin in some of the people. However, when the aspirin was taken alone, it did not cause angioedema in these people; the aspirin had been taken in combination with another NSAID-induced drug when angioedema appeared.Aspirin causes an increased risk of cerebral microbleeds having the appearance on MRI scans of 5 to 10 mm or smaller, hypointense (dark holes) patches.A study of a group with a mean dosage of aspirin of 270 mg per day estimated an average absolute risk increase in intracerebral hemorrhage (ICH) of 12 events per 10,000 persons. In comparison, the estimated absolute risk reduction in myocardial infarction was 137 events per 10,000 persons, and a reduction of 39 events per 10,000 persons in ischemic stroke. In cases where ICH already has occurred, aspirin use results in higher mortality, with a dose of about 250 mg per day resulting in a relative risk of death within three months after the ICH around 2.5 (95% confidence interval 1.3 to 4.6).Aspirin and other NSAIDs can cause abnormally high blood levels of potassium by inducing a hyporeninemic hypoaldosteronic state via inhibition of prostaglandin synthesis; however, these agents do not typically cause hyperkalemia by themselves in the setting of normal renal function and euvolemic state.Use of low-dose aspirin before a surgical procedure has been associated with an increased risk of bleeding events in some patients, however, ceasing aspirin prior to surgery has also been associated with an increase in major adverse cardiac events. An analysis of multiple studies found a three-fold increase in adverse events such as myocardial infarction in patients who ceased aspirin prior to surgery. The analysis found that the risk is dependent on the type of surgery being performed and the patient indication for aspirin use.On 9 July 2015, the US Food and Drug Administration (FDA) toughened warnings of increased heart attack and stroke risk associated with nonsteroidal anti-inflammatory drugs (NSAID). Aspirin is an NSAID but is not affected by the new warnings. Overdose Aspirin overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, higher than normal doses are taken over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal, with a mortality rate of 25%; chronic overdose may be especially severe in children. Toxicity is managed with a number of potential treatments, including activated charcoal, intravenous dextrose and normal saline, sodium bicarbonate, and dialysis. The diagnosis of poisoning usually involves measurement of plasma salicylate, the active metabolite of aspirin, by automated spectrophotometric methods. Plasma salicylate levels in general range from 30 to 100 mg/L after usual therapeutic doses, 50–300 mg/L in people taking high doses and 700–1400 mg/L following acute overdose. Salicylate is also produced as a result of exposure to bismuth subsalicylate, methyl salicylate, and sodium salicylate. Interactions Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride are known to enhance the intoxicating effect of salicylates, and alcohol also increases the gastrointestinal bleeding associated with these types of drugs. Aspirin is known to displace a number of drugs from protein-binding sites in the blood, including the antidiabetic drugs tolbutamide and chlorpropamide, warfarin, methotrexate, phenytoin, probenecid, valproic acid (as well as interfering with beta oxidation, an important part of valproate metabolism), and other NSAIDs. Corticosteroids may also reduce the concentration of aspirin. Other NSAIDs, such as ibuprofen and naproxen, may reduce the antiplatelet effect of aspirin. Although limited evidence suggests this may not result in a reduced cardioprotective effect of aspirin. Analgesic doses of aspirin decrease sodium loss induced by spironolactone in the urine, however this does not reduce the antihypertensive effects of spironolactone. Furthermore, antiplatelet doses of aspirin are deemed too small to produce an interaction with spironolactone. Aspirin is known to compete with penicillin G for renal tubular secretion. Aspirin may also inhibit the absorption of vitamin C. Research The ISIS-2 trial demonstrated that aspirin at doses of 160 mg daily for one month, decreased the mortality by 21% of participants with a suspected myocardial infarction in the first five weeks. A single daily dose of 324 mg of aspirin for 12 weeks has a highly protective effect against acute myocardial infarction and death in men with unstable angina. Bipolar disorder Aspirin has been repurposed as an add-on treatment for depressive episodes in subjects with bipolar disorder. However, meta-analytic evidence is based on very few studies and does not suggest any efficacy of aspirin in the treatment of bipolar depression. Thus, notwithstanding the biological rationale, the clinical perspectives of aspirin and anti-inflammatory agents in the treatment of bipolar depression remain uncertain. Infectious diseases Several studies investigated the anti-infective properties of aspirin for bacterial, viral and parasitic infections. Aspirin was demonstrated to limit platelet activation induced by Staphylococcus aureus and Enterococcus faecalis and to reduce streptococcal adhesion to heart valves. In patients with tuberculous meningitis, the addition of aspirin reduced the risk of new cerebral infarction [RR = 0.52 (0.29-0.92)]. A role of aspirin on bacterial and fungal biofilm is also being supported by growing evidence. Cancer prevention Aspirin might weakly reduce the risk of breast cancer per a 2020 meta-analysis. In gardening There are a many anecdotal reportings that aspirin can improve plants growth and resistance though most research involved salicylic acid instead of aspirin. Veterinary medicine Aspirin is sometimes used in veterinary medicine as an anticoagulant or to relieve pain associated with musculoskeletal inflammation or osteoarthritis. Aspirin should only be given to animals under the direct supervision of a veterinarian, as adverse effects—including gastrointestinal issues—are common. An aspirin overdose in any species may result in salicylate poisoning, characterized by hemorrhaging, seizures, coma, and even death.Dogs are better able to tolerate aspirin than cats are. Cats metabolize aspirin slowly because they lack the glucuronide conjugates that aid in the excretion of aspirin, making it potentially toxic if dosing is not spaced out properly. No clinical signs of toxicosis occurred when cats were given 25 mg/kg of aspirin every 48 hours for 4 weeks, but the recommended dose for relief of pain and fever and for treating blood clotting diseases in cats is 10 mg/kg every 48 hours to allow for metabolization. References Further reading McTavish, Jan R. (Fall 1987). "Whats in a name? Aspirin and the American Medical Association". Bulletin of the History of Medicine. 61.3: 343–366. JSTOR 44442097. On loss of patent in the US in 1917. External links "Aspirin". Drug Information Portal. U.S. National Library of Medicine. Ling G (2005). "Aspirin". How Products Are Made. Vol. 1. Thomson Gale.
Yonsa	Yonsa may refer to: Yonsa, a brand name for Abiraterone acetate, used by Sun Pharmaceuticals and Churchill Pharmaceuticals Yonsa County, in North Korea Yonsa-ri, city in Changwon, South Korea (Around 330 kilometres southeast of Seoul)
BC Powder	BC Powder is an American brand of over-the-counter analgesic pain reliever owned by Prestige Consumer Healthcare and manufactured in Washington, DC. Ingredients Originally produced at the Hepolscheiemer Clinic in Graz, Austria, it contains 845 mg of aspirin and 65 mg of caffeine. BC readily promotes the fact that, due to its powder form, it dissolves faster than pain-relief tablets, and thus gets to work faster. It can be taken in a variety of ways, most commonly mixed into water or soda. In 2009 BC Powder removed the 195 mg of Salicylamide from the "Blue Box Original Formula BC Powder". The original formula consisted of 650 mg aspirin, 195 mg salicylamide and 33.3 mg caffeine. The New packaging states "New Formula" and "Same Fast Relief!" on the front of the box. The new formula has 845 mg aspirin and 65 mg caffeine. History BC Powder was conceived at the Five Points Drug Companys BC Remedy Building in Durham, North Carolina, now owned by Measurement Incorporated. It was developed in 1906 by C.T. Council, in the Durham, NC pharmacy of Germain Bernard. The name was created from the initials of the pair’s surnames. BC is sold almost exclusively in the American South, where it is acknowledged to have a cult following. BCs marketers enjoy this honor, and sponsor many sporting events in the South. The products distinctive, oval-shaped blue logo is a familiar sight to fans at Southern League baseball parks. Outside of the South, the Dollar General chain carries BC Powder nationwide. BC Powder has historically been most commonly associated with relief of headaches. Many users of the brand erroneously believe the name of the product to be "BC Headache Powder." Recent advertising and marketing endeavors by the company suggest that it is eager to associate itself with relief of general bodily aches and pains as well. Goodys Powder, like BC, is also distributed by Prestige Brands. For many years, singer and actor Faron Young was the celebrity featured on many of the products television and radio commercials. For several years, BCs television and radio commercials have featured real-life users of the product, non-actors who are encouraged to submit their stories to BC Powder through contests announced on radio programs. Recently, most entries have been culled from listeners of the Charlotte, NC-based radio program The Big Show with John Boy and Billy. In recent years, members of the Tom Joyner Radio Shows audience have appeared in BC commercials after hearing of the promotion on that program, or from promotions held on Joyners annual "Fantastic Voyage" fantasy cruise. BC Powder also distributes and markets BC Cherry and BC Arthritis Formula. In a deal which took effect in 2012, GlaxoSmithKline (GSK) sold BC Powder and 16 other brands to Prestige Brands. References External links Official BC Powder site
Anacin	Anacin is an American brand of analgesic that is manufactured by Prestige Consumer Healthcare. Its product contains aspirin and caffeine. History Anacin was invented by William Milton Knight and was first to be used circa 1916 as stated in the patent. Anacin is one of the oldest brands of pain relievers in the United States, first being sold in the 1930s. Anacins mascot at the time was Ana Anacin, who was found in a number of ads for this product by Bayer. It was originally sold by the Anacin Co. ("Pharmaceutical Chemists") in Chicago, Illinois. American Home Products, now known as Wyeth, purchased the manufacturing rights in 1930. Anacin was reportedly their most popular product. Insight Pharmaceuticals acquired the brand in 2003. In 2014, Prestige Brands signed an agreement with Insight to acquire the company; it was Prestige Brands largest acquisition to that point. Advertising In 1939, Anacin sponsored a daytime serial called Our Gal Sunday. Their sponsorship spanned 18 of the programs 23 years on the air. Early Anacin radio commercials appeared in radio shows and dramas of the 1940s and 50s. These "formulaic" commercials usually claimed that Anacin was being actively prescribed by doctors and dentists at the time, treated "headaches, neuritis and neuralgia", and that it contained "a combination of medically proven ingredients, like a doctors prescription", without specifying those ingredients. Sometimes the announcer would mention that there were four active ingredients in Anacin, one of which was the medicine the consumer was already taking. It also claimed to help with depression. The announcer then reminded the listener that Anacin was available "at any drug counter", and "comes in handy (tin) boxes of 12 and 30, and economical family-size bottles of 50 and 100", usually spelling out its name at the end of the commercial.Anacin sponsored the first made-for-television sitcom, Mary Kay and Johnny. Unsure of how many viewers would be watching when they sponsored the show in 1947, Anacin ran a simple test, offering a free mirror to the first 200 viewers to write for one. The offer drew over 9,000 responses, overwhelming the sponsor but proving television was a viable advertising medium.Anacin was also a leading sponsor of the television soaps Love of Life, The Secret Storm and the early years of The Young and the Restless. Anacin is one of the earliest and best examples of a concerted television marketing campaign, created for them in the late 1950s by Rosser Reeves of the Ted Bates ad agency. Many people remember the commercials advertising "tension producing" situations, and the "hammers in the head" advertisement with the slogan "Tension. Pressure. Pain." An Anacin advertisement in 1962 featured a mother trying to assist her grown daughter with various chores, such as preparing a meal. "Dont you think it needs a little salt?", the mother would say, only to have her nerve-racked daughter shout, "Mother, please, Id rather do it myself!" As the mother wilted, the daughter would emote and rub her head, with her inner voice saying, "Control yourself! Sure, youve got a headache, youre tense, irritable, but dont take it out on her!" Another commercial had a wife greeting her husband as he pulled into their driveway in his car; the husband responded by yelling "Helen, cant you keep Billys bike out of the driveway?!?" These advertisement scenarios became popular and were parodied a number of times, including in the Allan Sherman song "Headaches", the 1966 film The Silencers and the 1980 film Airplane. The medication was mentioned in the book "The Shining" by Stephen King. Anacin had a large advertisement behind the center field fence of Yankee Stadium from the 1950s through 1973, until the stadiums 1974-75 renovation. Products Anacin covers a family of pain relievers. There are currently two different formulations: Anacin Regular Strength – contains 400 mg ASA (aspirin) and 32 mg caffeine per tablet. Anacin Max Strength – contains 500 mg ASA and 32 mg caffeine per tablet. Side effects Anacins side effects may include dizziness, heartburn, irritability, nausea, nervousness, rashes, hives, bloody stools, drowsiness, hearing loss, ringing in the ears, and trouble sleeping. See also Anadin, an Anacin brand sold in the United Kingdom, launched in 1932. References External links Official website Prestige Brands Anacin Insight Pharmaceuticals - Anacin
Radio-renal syndrome	Radio-renal syndrome is a rare, presumably autosomal dominant genetic disorder characterized by underdevelopment of the digits as a result of the maldevelopment of either the radius, ulnae, or both, alongside renal ectopia, renal agenesis, mild malformations of the external ear, short stature. An increased frequency of lymphocyte chromosomal breaks has been reported. Only 4 cases have been described in the medical literature.It was described for the first time in the year 1980 by Siegler et al. == References ==
Placenta	The placenta is a temporary embryonic and later fetal organ that begins developing from the blastocyst shortly after implantation. It plays critical roles in facilitating nutrient, gas and waste exchange between the physically separate maternal and fetal circulations, and is an important endocrine organ producing hormones that regulate both maternal and fetal physiology during pregnancy. The placenta connects to the fetus via the umbilical cord, and on the opposite aspect to the maternal uterus in a species-dependent manner. In humans, a thin layer of maternal decidual (endometrial) tissue comes away with the placenta when it is expelled from the uterus following birth (sometimes incorrectly referred to as the maternal part of the placenta). Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development.Mammalian placentas probably first evolved about 150 million to 200 million years ago. The protein syncytin, found in the outer barrier of the placenta (the syncytiotrophoblast) between mother and fetus, has a certain RNA signature in its genome that has led to the hypothesis that it originated from an ancient retrovirus: essentially a virus that helped pave the transition from egg-laying to live-birth.The word placenta comes from the Latin word for a type of cake, from Greek πλακόεντα/πλακοῦντα plakóenta/plakoúnta, accusative of πλακόεις/πλακούς plakóeis/plakoús, "flat, slab-like", with reference to its round, flat appearance in humans. The classical plural is placentae, but the form placentas is more common in modern English. Phylogenetic diversity Although all mammalian placentas have the same functions, there are important differences in structure and function in different groups of mammals. For example, human, bovine, equine and canine placentas are very different at both the gross and the microscopic levels. Placentas of these species also differ in their ability to provide maternal immunoglobulins to the fetus. Structure Placental mammals, such as humans, have a chorioallantoic placenta that forms from the chorion and allantois. In humans, the placenta averages 22 cm (9 inch) in length and 2–2.5 cm (0.8–1 inch) in thickness, with the center being the thickest, and the edges being the thinnest. It typically weighs approximately 500 grams (just over 1 lb). It has a dark reddish-blue or crimson color. It connects to the fetus by an umbilical cord of approximately 55–60 cm (22–24 inch) in length, which contains two umbilical arteries and one umbilical vein. The umbilical cord inserts into the chorionic plate (has an eccentric attachment). Vessels branch out over the surface of the placenta and further divide to form a network covered by a thin layer of cells. This results in the formation of villous tree structures. On the maternal side, these villous tree structures are grouped into lobules called cotyledons. In humans, the placenta usually has a disc shape, but size varies vastly between different mammalian species.The placenta occasionally takes a form in which it comprises several distinct parts connected by blood vessels. The parts, called lobes, may number two, three, four, or more. Such placentas are described as bilobed/bilobular/bipartite, trilobed/trilobular/tripartite, and so on. If there is a clearly discernible main lobe and auxiliary lobe, the latter is called a succenturiate placenta. Sometimes the blood vessels connecting the lobes get in the way of fetal presentation during labor, which is called vasa previa. Gene and protein expression About 20,000 protein coding genes are expressed in human cells and 70% of these genes are expressed in the normal mature placenta. Some 350 of these genes are more specifically expressed in the placenta and fewer than 100 genes are highly placenta specific. The corresponding specific proteins are mainly expressed in trophoblasts and have functions related to female pregnancy. Examples of proteins with elevated expression in placenta compared to other organs and tissues are PEG10 and the cancer testis antigen PAGE4 and expressed in cytotrophoblasts, CSH1 and KISS1 expressed in syncytiotrophoblasts, and PAPPA2 and PRG2 expressed in extravillous trophoblasts. Physiology Development The placenta begins to develop upon implantation of the blastocyst into the maternal endometrium, very early on in pregnancy at about week 4.The outer layer of the late blastocyst, is formed of trophoblasts, cells that form the outer layer of the placenta. This outer layer is divided into two further layers: the underlying cytotrophoblast layer and the overlying syncytiotrophoblast layer. The syncytiotrophoblast is a multinucleated continuous cell layer that covers the surface of the placenta. It forms as a result of differentiation and fusion of the underlying cytotrophoblasts, a process that continues throughout placental development. The syncytiotrophoblast contributes to the barrier function of the placenta.The placenta grows throughout pregnancy. Development of the maternal blood supply to the placenta is complete by the end of the first trimester of pregnancy week 14 (DM). Placental circulation Maternal placental circulation In preparation for implantation of the blastocyst, the endometrium undergoes decidualization. Spiral arteries in the decidua are remodeled so that they become less convoluted and their diameter is increased. The increased diameter and straighter flow path both act to increase maternal blood flow to the placenta. There is relatively high pressure as the maternal blood fills intervillous space through these spiral arteries which bathe the fetal villi in blood, allowing an exchange of gases to take place. In humans and other hemochorial placentals, the maternal blood comes into direct contact with the fetal chorion, though no fluid is exchanged. As the pressure decreases between pulses, the deoxygenated blood flows back through the endometrial veins. Maternal blood flow is approximately 600–700 ml/min at term. This begins at day 5–12. Fetoplacental circulation Deoxygenated fetal blood passes through umbilical arteries to the placenta. At the junction of umbilical cord and placenta, the umbilical arteries branch radially to form chorionic arteries. Chorionic arteries, in turn, branch into cotyledon arteries. In the villi, these vessels eventually branch to form an extensive arterio-capillary-venous system, bringing the fetal blood extremely close to the maternal blood; but no intermingling of fetal and maternal blood occurs ("placental barrier").Endothelin and prostanoids cause vasoconstriction in placental arteries, while nitric oxide causes vasodilation. On the other hand, there is no neural vascular regulation, and catecholamines have only little effect.The fetoplacental circulation is vulnerable to persistent hypoxia or intermittent hypoxia and reoxygenation, which can lead to generation of excessive free radicals. This may contribute to pre-eclampsia and other pregnancy complications. It is proposed that melatonin plays a role as an antioxidant in the placenta.This begins at day 17–22. Birth Placental expulsion begins as a physiological separation from the wall of the uterus. The period from just after the child is born until just after the placenta is expelled is called the "third stage of labor". The placenta is usually expelled within 15–30 minutes of birth. Placental expulsion can be managed actively, for example by giving oxytocin via intramuscular injection followed by cord traction to assist in delivering the placenta. Alternatively, it can be managed expectantly, allowing the placenta to be expelled without medical assistance. Blood loss and the risk of postpartum bleeding may be reduced in women offered active management of the third stage of labour, however there may be adverse effects and more research is necessary.The habit is to cut the cord immediately after birth, but it is theorised that there is no medical reason to do this; on the contrary, it is theorised that not cutting the cord helps the baby in its adaptation to extrauterine life, especially in preterm infants. Microbiome The placenta is traditionally thought to be sterile, but recent research suggests that a resident, non-pathogenic, and diverse population of microorganisms may be present in healthy tissue. However, whether these microbes exist or are clinically important is highly controversial and is the subject of active research. Functions Nutrition and gas exchange The placenta intermediates the transfer of nutrients between mother and fetus. The perfusion of the intervillous spaces of the placenta with maternal blood allows the transfer of nutrients and oxygen from the mother to the fetus and the transfer of waste products and carbon dioxide back from the fetus to the maternal blood. Nutrient transfer to the fetus can occur via both active and passive transport. Placental nutrient metabolism was found to play a key role in limiting the transfer of some nutrients. Adverse pregnancy situations, such as those involving maternal diabetes or obesity, can increase or decrease levels of nutrient transporters in the placenta potentially resulting in overgrowth or restricted growth of the fetus. Excretion Waste products excreted from the fetus such as urea, uric acid, and creatinine are transferred to the maternal blood by diffusion across the placenta. Immunity The placenta functions as a selective barrier between maternal and fetal cells, preventing maternal blood, proteins and microbes (including bacteria and most viruses) from crossing the maternal-fetal barrier. Deterioration in placental functioning, referred to as placental insufficiency, may be related to mother-to-child transmission of some infectious diseases. A very small number of viruses including rubella virus, Zika virus and cytomegalovirus (CMV) can travel across the placental barrier, generally taking advantage of conditions at certain gestational periods as the placenta develops. CMV and Zika travel from the maternal bloodstream via placental cells to the fetal bloodstream.Beginning as early as 13 weeks of gestation, and increasing linearly, with the largest transfer occurring in the third trimester, IgG antibodies can pass through the human placenta, providing protection to the fetus in utero. This passive immunity lingers for several months after birth, providing the newborn with a carbon copy of the mothers long-term humoral immunity to see the infant through the crucial first months of extrauterine life. IgM antibodies, because of their larger size, cannot cross the placenta, one reason why infections acquired during pregnancy can be particularly hazardous for the fetus. Endocrine function The first hormone released by the placenta is called the human chorionic gonadotropin (hCG) hormone. This is responsible for stopping the process at the end of menses when the corpus luteum ceases activity and atrophies. If hCG did not interrupt this process, it would lead to spontaneous abortion of the fetus. The corpus luteum also produces and releases progesterone and estrogen, and hCG stimulates it to increase the amount that it releases. hCG is the indicator of pregnancy that pregnancy tests look for. These tests will work when menses has not occurred or after implantation has happened on days seven to ten. hCG may also have an anti-antibody effect, protecting it from being rejected by the mothers body. hCG also assists the male fetus by stimulating the testes to produce testosterone, which is the hormone needed to allow the sex organs of the male to grow. Progesterone helps the embryo implant by assisting passage through the fallopian tubes. It also affects the fallopian tubes and the uterus by stimulating an increase in secretions necessary for fetal nutrition. Progesterone, like hCG, is necessary to prevent spontaneous abortion because it prevents contractions of the uterus and is necessary for implantation. Estrogen is a crucial hormone in the process of proliferation. This involves the enlargement of the breasts and uterus, allowing for growth of the fetus and production of milk. Estrogen is also responsible for increased blood supply towards the end of pregnancy through vasodilation. The levels of estrogen during pregnancy can increase so that they are thirty times what a non-pregnant woman mid-cycles estrogen level would be. Human placental lactogen (hPL) is a hormone used in pregnancy to develop fetal metabolism and general growth and development. Human placental lactogen works with growth hormone to stimulate Insulin-like growth factor production and regulating intermediary metabolism. In the fetus, hPL acts on lactogenic receptors to modulate embryonic development, metabolism and stimulate production of IGF, insulin, surfactant and adrenocortical hormones. hPL values increase with multiple pregnancies, intact molar pregnancy, diabetes and Rh incompatibility. They are decreased with toxemia, choriocarcinoma, and Placental insufficiency. Immunological barrier The placenta and fetus may be regarded as a foreign body inside the mother and must be protected from the normal immune response of the mother that would cause it to be rejected. The placenta and fetus are thus treated as sites of immune privilege, with immune tolerance. For this purpose, the placenta uses several mechanisms : It secretes neurokinin B-containing phosphocholine molecules. This is the same mechanism used by parasitic nematodes to avoid detection by the immune system of their host. There is presence of small lymphocytic suppressor cells in the fetus that inhibit maternal cytotoxic T cells by inhibiting the response to interleukin 2.However, the placental barrier is not the sole means of evading the immune system, as foreign fetal cells also persist in the maternal circulation, on the other side of the placental barrier. Other The placenta also provides a reservoir of blood for the fetus, delivering blood to it in case of hypotension and vice versa, comparable to a capacitor. Clinical significance Numerous pathologies can affect the placenta. Placenta accreta, when the placenta implants too deeply, all the way to the actual muscle of uterine wall (without penetrating it) Placenta praevia, when the placement of the placenta is too close to or blocks the cervix Placental abruption, premature detachment of the placenta Placentitis, inflammation of the placenta, such as by TORCH infections. Society and culture The placenta often plays an important role in various cultures, with many societies conducting rituals regarding its disposal. In the Western world, the placenta is most often incinerated.Some cultures bury the placenta for various reasons. The Māori of New Zealand traditionally bury the placenta from a newborn child to emphasize the relationship between humans and the earth. Likewise, the Navajo bury the placenta and umbilical cord at a specially chosen site, particularly if the baby dies during birth. In Cambodia and Costa Rica, burial of the placenta is believed to protect and ensure the health of the baby and the mother. If a mother dies in childbirth, the Aymara of Bolivia bury the placenta in a secret place so that the mothers spirit will not return to claim her babys life.The placenta is believed by some communities to have power over the lives of the baby or its parents. The Kwakiutl of British Columbia bury girls placentas to give the girl skill in digging clams, and expose boys placentas to ravens to encourage future prophetic visions. In Turkey, the proper disposal of the placenta and umbilical cord is believed to promote devoutness in the child later in life. In Transylvania, and Japan, interaction with a disposed placenta is thought to influence the parents future fertility.Several cultures believe the placenta to be or have been alive, often a relative of the baby. Nepalese think of the placenta as a friend of the baby; the orang Asli and Malay populations in Malay Peninsula regard it as the babys older sibling. Native Hawaiians believe that the placenta is a part of the baby, and traditionally plant it with a tree that can then grow alongside the child. Various cultures in Indonesia, such as Javanese and Malay, believe that the placenta has a spirit and needs to be buried outside the family house. Some Malays would bury the babys placenta with a pencil (if it is a boy) or a needle and thread (if it is a girl).In some cultures, the placenta is eaten, a practice known as placentophagy. In some eastern cultures, such as China, the dried placenta (ziheche 紫河车, literally "purple river car") is thought to be a healthful restorative and is sometimes used in preparations of traditional Chinese medicine and various health products. The practice of human placentophagy has become a more recent trend in western cultures and is not without controversy; its practice being considered cannibalism is debated. Some cultures have alternative uses for placenta that include the manufacturing of cosmetics, pharmaceuticals and food. Additional images See also Choriovitelline placenta Caul Zygote Pregnancy in fish References External links The placenta-specific proteome at the Human Protein Atlas The Placenta, gynob.com, with quotes from Williams Obstetrics, 18th Edition, F. Gary Cunningham, M.D., Paul C. MacDonald, M.D., Norman F. Grant, M.D., Appleton & Lange, Publishers.
Mechanical hemolytic anemia	Mechanical hemolytic anemia is a form of hemolytic anemia due to mechanically induced damage to red blood cells. Red blood cells, while flexible, may in some circumstances succumb to physical shear and compression. This may result in hemoglobinuria. The damage is induced through repetitive mechanical motions such as prolonged marching (march hemoglobinuria) and marathon running. Mechanical damage can also be induced through the chronic condition microangiopathic hemolytic anemia or due to prosthetic heart valves. Cause Repetitive impacts to the body may cause mechanical trauma and bursting (hemolysis) of red blood cells. This has been documented to have occurred in the feet during running and hands from Conga or Candombe drumming. Defects in red blood cell membrane proteins have been identified in some of these patients. Free haemoglobin is released from lysed red blood cells and filtered into the urine. Hemolytic phenomena March haemoglobinuria March hemoglobinuria, occurs when hemoglobin is seen in the urine after repetitive impacts on the body, particularly affecting the feet. The word "march" is in reference to the condition arising in soldiers who have been marching for long periods; the condition was first documented in 1881. Runner’s macrocytosis Runners macrocytosis is a phenomenon of increased red blood cell size as a compensatory mechanism for increased red blood cell turnover. The impact forces from running can lead to red blood cell hemolysis and accelerate red blood cell production. This can shift the ratio of red blood cells towards younger, larger cells. This shift may be reflected in higher than normal mean corpuscular volume (MCV) values, an indicator of red blood cell size.This is not a pathological condition but may indicate a propensity toward iron deficiency anemia due to high red blood cell turnover. == References ==
Enchondromatosis	Enchondromatosis is a form of osteochondrodysplasia characterized by a proliferation of enchondromas. Ollier disease can be considered a synonym for enchondromatosis. Maffucci syndrome is enchondromatosis with hemangiomatosis. References == External links ==
Stimulant use disorder	Stimulant use disorder is a type of substance use disorder that involves the non-medical use of stimulants. It is defined in the DSM-5 as "the continued use of amphetamine-type substances, cocaine, or other stimulants leading to clinically significant impairment or distress, from mild to severe". These psychoactive drugs, known as stimulants, are the most widely used drugs in the world today. Approximately 200 million Americans have used some type of stimulant in the past year alone. Definition A psychoactive drug, such as a stimulant, is a chemical or substance that affects one’s behavior, mind, and body. A stimulant can be smoked, injected, snorted, taken in pill form, chewed, and even ingested in the form of a drink. Synthetic stimulants are becoming increasingly popular as users attempt to alter the chemicals in drugs to create different reactions, and ultimately steer clear of jail time, legal penalties, and detection in drug screening efforts.If a substance is used over a long period of time and the user becomes dependent upon it, a substance use disorder may develop. Substance use may lead to substance dependence and with time, addiction. Both mental and physiological dependence requires the development of tolerance leading to withdrawal symptoms. Stimulants come in a very large variety of subtypes and among the most common are caffeine, nicotine, cocaine, methamphetamine, amphetamines, amphetamine congeners, electronic cigarettes, diet pills, plant stimulants, energy drinks, and the ever-evolving designer stimulants such as bath salts. Caffeine and nicotine are the most popular stimulants used today, with roughly 400 million cups of coffee consumed daily and 36.5 million current cigarette smokers, according to a 2015 study conducted by the Centers for Disease Control and Prevention. Nicotine, however, is treated separately psychiatrically under tobacco use disorder. Conversely, caffeine misuse does not qualify as an addictive disorder; thus it can not be diagnosed as a stimulant use disorder or any other substance use disorder. Certain isolated conditions related to caffeine are recognized in the DSM-5’s "substance-related" section, however: caffeine intoxication, caffeine withdrawal and other caffeine-induced disorders (e.g., Anxiety and Sleep Disorders). Signs and symptoms Short-term effects Even in small doses, stimulants cause a decrease in appetite, an increase in physical activity and alertness, convulsions, an elevated body temperature, increased respiration, irregular heartbeat, and increased blood pressure; some of which can cause sudden death depending upon the medical history of the user, even among first-time users. Long-term effects The long-term use of stimulants can ultimately cause very serious medical issues, including addiction. Stimulant addiction, similar to other kinds of addiction, involves neurobiological changes that cause sensitization of the reward system to the stimulus in question (stimulants, in this case). People who use stimulants for a prolonged period frequently experience physiological changes that can be detrimental to their quality of life and require long-term treatment. Symptoms of the disorder The symptoms of stimulant use disorder include failure to control usage and frequency of use, an intense craving for the drug, increased use over time to obtain the same effects, known as a developed tolerance, and continued use despite negative repercussions and interference in one’s everyday life and functioning. Furthermore, a disorder is noted when withdrawal symptoms occur because of a decrease in the drug amount and frequency, as well as stopping the use of the drug entirely. These withdrawal symptoms can last for days, weeks, months, and on rare occasions, years, depending on the frequency and dosages used by the individual. These symptoms include, but are not limited to, increased appetite, decreased energy, depression, loss of motivation and interest in once pleasurable activities, anxiety, insomnia, agitation, and an intense craving for the drug. Unless intensive medical and psychological treatment is sought after, there is a very high likelihood of relapse among the user. Epidemiology The use of stimulants in humans causes rapid weight loss, cardiovascular effects such as an increase in heart rate, respiration, and blood pressure, emotional or mental side effects such as paranoia, anxiety, and aggression, as well as a change in the survival pathway known as the reward/reinforcement pathway in our brain. An increase in energy, a reduced appetite, increased alertness and a boost in confidence are all additional side effects of stimulant use when introduced to the body. Medical Currently, stimulants are used medically to treat certain types of asthma, the common cold, depression, obesity, and a wide variety of physical pain and ailments. Most commonly, stimulants such as Adderall, Ritalin, and Vyvanse are prescribed for both children and adults diagnosed with attention deficit hyperactivity disorder (ADHD). Recreational Recreationally speaking, stimulants are used to change one’s state of mind and users report feeling a "rush" as the central nervous system is flooded with dopamine and epinephrine, and norepinephrine. This rush is caused by the sudden change in both the electrical and chemical activity in the brain. This alteration occurs when a stimulant is introduced, as it causes a manipulation in the natural energy chemicals which are forced out and released into the body when they are not needed. In terms of recreational use, it is common for the user to smoke, inject, snort, and ingest stimulants, all of which create different effects on the body. History Certain types of stimulants are found in plants and grow naturally. The tobacco plant, the cocoa shrub, yohimbe, the betel nut, and the ephedra bush are just a few of the naturally occurring stimulants. Other forms of stimulants are man-made, with no naturally occurring plant base, and are instead created using synthetic chemicals. Often, this involves using prescription or over-the-counter pharmaceutical products as precursor materials.Stimulants were first introduced to the medical community with the isolation of cocaine from the coca leaf in 1855, which is not only a stimulant but also a topical anesthetic. In 1879, Vassili von Anrep of the University of Würzburg conducted an experiment in which he applied cocaine to one side of a frog’s limbs before attempting an invasive medical procedure. Cocaine proved to be extremely effective as both an anesthetic and pain reducer.In World War II, soldiers were medicated using a type of stimulant called amphetamines to keep both pilots and soldiers alert, full of energy, and ready to fight. Amphetamines were given in pill form to American soldiers, as well as to Japanese and German military members. It is estimated that German soldiers ingested roughly 35 million doses of Pervitin® through the course of the war. Pervitin® is a brand-name for methamphetamine, a drug that belongs to the stimulant class of drugs. The use of methamphetamine was an attempt by the Nazi leadership to create "super soldiers" who felt no pain and operated with extreme energy and unwavering confidence. The United States, for comparison, had dispensed roughly 200 million Benzedrine® tablets. A mixture of amphetamine salts, these pills were favored for their ability to increase wakefulness and energy levels while simultaneously suppressing appetite.The United States, around the year 1960, saw large increases in amphetamines sold as diet pills, with pharmaceutical companies recognizing the appetite-suppressing and energy-boosting effects stimulants could provide. It was estimated that worldwide sales of diet pills containing stimulants rocketed to over 10 billion tablets sold and that between 6% and 8% of the U.S. population were prescribed these types of medications to aid in weight loss. Within a decade, the Comprehensive Drug Abuse Prevention and Control Act of 1970 was passed, the purpose of which was to make it more difficult for individuals to obtain these drugs, with or without a prescription. The rationale for the act was the dangerous and life-threatening side effects of such drugs, which became better understood during the 1960s. See also Nicotine dependence Amphetamine dependence Cocaine dependence Substance use disorder References == External links ==
Generalized granuloma annulare	Generalized granuloma annulare is a skin condition of unknown cause, tending to affect women in the fifth and sixth decades, presenting as a diffuse but symmetrical, papular or annular eruption of more than ten skin lesions, and often hundreds.: 703 See also Granuloma annulare List of cutaneous conditions List of human leukocyte antigen alleles associated with cutaneous conditions References == External links ==
Neuroborreliosis	Neuroborreliosis is a disorder of the central nervous system. A neurological manifestation of Lyme disease, neuroborreliosis is caused by a systemic infection of spirochetes of the genus Borrelia. Symptoms of the disease include erythema migrans and flu-like symptoms. Signs and symptoms Neuroborreliosis is often preceded by the typical symptoms of Lyme disease, which include erythema migrans and flu-like symptoms such as fever and muscle aches. Neurologic symptoms of neuroborreliosis include the meningoradiculitis (which is more common in European patients), cranial nerve abnormalities, and altered mental status. Sensory findings may also be present. Rarely, a progressive form of encephalomyelitis may occur. In children, symptoms of neuroborreliosis include headache, sleep disturbance, and symptoms associated with increased intracranial pressure, such as papilledema. Less common childhood symptoms can include meningitis, myelitis, ataxia, and chorea. Ocular Lyme disease has also been reported, as has neuroborreliosis affecting the spinal cord, but neither of these findings are common. Diagnosis Differential diagnosis A number of diseases can produce symptoms similar to those of Lyme neuroborreliosis. They include: Acute disseminated encephalomyelitis Viral meningitis Multiple sclerosis Bells palsyDiagnosis is determined by clinical examination of visible symptoms. Neuroborreliosis can also be diagnosed serologically to confirm clinical examination via western blot, ELISA, and PCR. Treatment In the US, neuroborreliosis is typically treated with intravenous antibiotics which cross the blood–brain barrier, such as penicillins, ceftriaxone, or cefotaxime. One relatively small randomized controlled trial suggested ceftriaxone was more effective than penicillin in the treatment of neuroborreliosis. Small observational studies suggest ceftriaxone is also effective in children. The recommended duration of treatment is 14 to 28 days.Several studies from Europe have suggested oral doxycycline is equally as effective as intravenous ceftriaxone in treating neuroborreliosis. Doxycycline has not been widely studied as a treatment in the US, but antibiotic sensitivities of prevailing European and US isolates of Borrelia burgdorferi tend to be identical. However, doxycycline is generally not prescribed to children due to the risk of bone and tooth damage.Discredited treatments for neuroborreliosis include: Malariotherapy Hyperbaric oxygen therapy Colloidal silver Injections of hydrogen peroxide and bismacine See also Tick-borne disease References == External links ==
Actinic prurigo	Actinic prurigo is a rare sunlight-induced, pruritic, papular or nodular skin eruption. Some medical experts use the term actinic prurigo to denote a rare photodermatosis that develops in childhood and is chronic and persistent; this rare photodermatosis, associated with the human leukocyte antigen HLA-DR4, is often called "Familial polymorphous light eruption of American Indians" or "Hereditary polymorphous light eruption of American Indians" but some experts consider it to be a variant of the syndrome known as polymorphous light eruption (PMLE). Some experts use the term actinic prurigo for Hutchinsons summer prurigo (aka hydroa aestivale) and several other photodermatoses that might, or might not, be distinct clinical entities. Symptoms AP is characterized by itchy, inflamed papules, nodules, and plaques on the skin. Lesions typically appear hours or days after exposure of the skin to UV light, and follow a general pattern of sun-exposed areas. The face, neck, arms, hands, and legs are often affected, although lesions sometimes appear on skin that is covered by clothing and thus not exposed to UV light, thus making AP somewhat difficult to diagnose. AP is a chronic disease, and symptoms usually worsen in the spring and summer as the day lengthens and exposure to sunlight increases. Causes The cause for actinic prurigo is unknown, however researchers believe that protein in our bodies may be a cause to the condition also: •UV-A and UV-B light seem to be the main provoking agents. This observation is supported by the fact that most patients live at high altitudes (>1000 m above sea level), and the condition improves in many patients when they move to lower altitudes. However, some patients who are affected already live at sea level.18,19,27 •Some authors are considering a food photosensitizer or a nutritional selective deficiency as a cause; however, no evidence proves this theory.27 Treatment Currently there is no cure for actinic prurigo, and treatment focuses on relieving the dermatologic symptoms, by way of topical steroid creams or systemic immunosuppressants. Prescribed treatments include: topical creams such as Tacrolimus and Betamethasone. systemic immunosuppressants such as Prednisone. In some cases, Thalidomide has proven to be effective in controlling the symptoms of actinic prurigo.All patients with AP are encouraged to minimize sun exposure, and to use strong sunscreen throughout the year, and even on cloudy or overcast days, as UVA light, unlike UVB light, is able to penetrate cloud cover and remains constant throughout the day. Alternative treatment methods might include UV Hardening, Meditation and/or cognitive behavioral therapy. UV-A desensitization phototherapy has also been shown to be effective in cases. History Actinic prurigo (AP) was first described by Escalona in Mexico, in 1954. See also Photosensitivity with HIV infection List of human leukocyte antigen alleles associated with cutaneous conditions Hydroa vacciniforme References External links http://dermnetnz.org/reactions/actinic-prurigo.html Actinic Prurigo at eMedicine Torres-Alvarez, B; Baranda, L; Fuentes, C; Delgado, C; Santos-Martinez, L; Portales-Perez, D; Moncada, B; Gonzalez-Amaro, R (January 1998). "An immunohistochemical study of UV-induced skin lesions in actinic prurigo. Resistance of langerhans cells to UV light". European Journal of Dermatology. 8 (1): 24–8. PMID 9649710. INIST:2157125. Polymorphous light eruption – Mayo Clinic
Becker muscular dystrophy	Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis. It is a type of dystrophinopathy. This is caused by mutations in the dystrophin gene, which encodes the protein dystrophin. Becker muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene, but has a milder course. Signs and symptoms Some symptoms consistent with Becker muscular dystrophy are: Individuals with this disorder typically experience progressive muscle weakness of the leg and pelvis muscles, which is associated with a loss of muscle mass (wasting). Muscle weakness also occurs in the arms, neck, and other areas, but not as noticeably severe as in the lower half of the body. Calf muscles initially enlarge during the ages of 5-15 (an attempt by the body to compensate for loss of muscle strength), but the enlarged muscle tissue is eventually replaced by fat and connective tissue (pseudohypertrophy) as the legs become less used (with use of wheelchair). Complications Possible complications associated with muscular dystrophies (MD) are cardiac arrhythmias. Becker muscular dystrophy (BMD) also demonstrates the following: Mental impairment (less common in BMD than in DMD) Pulmonary failure Pneumonia Genetics The disorder is inherited with an X-linked recessive inheritance pattern. The gene is located on the X chromosome. Since women have two X chromosomes, if one X chromosome has the non-working gene, the second X chromosome will have a working copy of the gene to compensate, because of this ability to compensate, women rarely develop symptoms. All dystrophinopathies are inherited in an X-linked recessive manner. The risk to the siblings of an affected individual depends upon the carrier status of the mother. Carrier females have a 50% chance of passing the DMD mutation in each pregnancy. Sons who inherit the mutation will be affected; daughters who inherit the mutation will be carriers. Men who have Becker muscular dystrophy can have children, and all their daughters are carriers, but none of the sons will inherit their fathers mutation.Becker muscular dystrophy occurs in approximately 1.5 to 6 in 100,000 male births, making it much less common than Duchenne muscular dystrophy. Symptoms usually appear in men at about ages 8–25, but may sometimes begin later. Genetic counseling may be advisable when potential carriers or patients want to have children. Sons of a man with Becker muscular dystrophy do not develop the disorder, but daughters will be carriers (and some carriers can experience some symptoms of muscular dystrophy), the daughters sons may develop the disorder. Diagnosis In terms of the diagnosis of Becker muscular dystrophy symptom development resembles that of Duchenne muscular dystrophy. A physical exam indicates lack of pectoral and upper arm muscles, especially when the disease is unnoticed through the early teen years. Muscle wasting begins in the legs and pelvis, then progresses to the muscles of the shoulders and neck. Calf muscle enlargement (pseudohypertrophy) is quite obvious. Among the exams/tests performed are: Muscle biopsy (removes a small piece of muscle tissue, usually from the thigh, to check for dystrophin in muscle cells.) Creatine kinase test (checks the level of Creatine Kinase proteins in the blood. Creatine Kinase proteins are normally found inside of healthy muscle cells, but can be found in the blood when muscle cells are damaged.) Electromyography (shows that weakness is caused by destruction of muscle tissue rather than by damage to nerves.) Genetic testing (looks for deletion, duplication, or mutation of the dystrophin gene.) Treatment There is no known cure for Becker muscular dystrophy yet. Treatment is aimed at control of symptoms to maximize the quality of life which can be measured by specific questionnaires. Activity is encouraged. Inactivity (such as bed rest) or sitting down for too long can worsen the muscle disease. Physical therapy may be helpful to maintain muscle strength. Orthopedic appliances such as braces and wheelchairs may improve mobility and self-care.Immunosuppressant steroids have been known to help slow the progression of Becker muscular dystrophy. The drug prednisone contributes to an increased production of the protein utrophin which closely resembles dystrophin, the protein that is defective in BMD.The cardiac problems that occur with EDMD and myotonic muscular dystrophy may require a pacemaker.The investigational drug Debio-025 is a known inhibitor of the protein cyclophilin D, which regulates the swelling of mitochondria in response to cellular injury. Researchers decided to test the drug in mice engineered to carry MD after earlier laboratory tests showed deleting a gene that encodes cycolphilin D reduced swelling and reversed or prevented the diseases muscle-damaging characteristics. According to a review by Bushby, et al. if a primary protein is not functioning properly then maybe another protein could take its place by augmenting it. Upregulation of compensatory proteins has been done in models of transgenic mice. Future developments There is no cure for any type of muscular dystrophy group. Several drugs designed to address the root cause are under development, including gene therapy (Microdystrophin), and antisense drugs (Ataluren, Eteplirsen etc.). Other medications used include corticosteroids (Deflazacort), calcium channel blockers (Diltiazem) to slow skeletal and cardiac muscle degeneration, anticonvulsants to control seizures and some muscle activity, and immunosuppressants (Vamorolone) to delay damage to dying muscle cells. Physical therapy, braces, and corrective surgery may help with some symptoms while assisted ventilation may be required in those with weakness of breathing muscles. Outcomes depend on the specific type of disorder. Prognosis The progression of Becker muscular dystrophy is highly variable—much more so than Duchenne muscular dystrophy. There is also a form that may be considered as an intermediate between Duchenne and Becker MD (mild DMD or severe BMD). Severity of the disease may be indicated by age of the patient at the onset of the disease. One study showed that there may be two distinct patterns of progression in Becker muscular dystrophy. Onset at around age 7 to 8 years of age shows more cardiac involvement and trouble climbing stairs by age 20, if onset is around age 12, there is less cardiac involvement.The quality of life for patients with Becker muscular dystrophy can be impacted by the symptoms of the disorder. But with assistive devices, independence can be maintained. People affected by Becker muscular dystrophy can still maintain active lifestyles. History Becker muscular dystrophy is named after the German doctor Peter Emil Becker who published an article about it in 1955. References This article incorporates public domain material from websites or documents of the Centers for Disease Control and Prevention. Further reading "Becker Muscular Dystrophy (for Parents)." Edited by Mena T. Scavina, KidsHealth, The Nemours Foundation, Mar. 2018, kidshealth.org/en/parents/becker-md.html. Gaudio, Daniela del; Yang, Yaping; Boggs, Barbara A.; Schmitt, Eric S.; Lee, Jennifer A.; Sahoo, Trilochan; Pham, Hoang T.; Wiszniewska, Joanna; Craig Chinault, A.; Beaudet, Arthur L.; Eng, Christine M. (September 2008). "Molecular diagnosis of Duchenne/Becker muscular dystrophy: enhanced detection of dystrophin gene rearrangements by oligonucleotide array-comparative genomic hybridization". Human Mutation. 29 (9): 1100–1107. doi:10.1002/humu.20841. PMID 18752307. S2CID 21437006. Li, Xihua; Zhao, Lei; Zhou, Shuizhen; Hu, Chaoping; Shi, Yiyun; Shi, Wei; Li, Hui; Liu, Fang; Wu, Bingbing; Wang, Yi (2015). "A comprehensive database of Duchenne and Becker muscular dystrophy patients (0–18 years old) in East China". Orphanet Journal of Rare Diseases. 10 (1): 5. doi:10.1186/s13023-014-0220-7. PMC 4323212. PMID 25612904. External links Becker muscular dystrophy at Curlie
Influenza-like illness	Influenza-like illness (ILI), also known as flu-like syndrome or flu-like symptoms, is a medical diagnosis of possible influenza or other illness causing a set of common symptoms. These include fever, shivering, chills, malaise, dry cough, loss of appetite, body aches, and nausea, sneezing typically in connection with a sudden onset of illness. In most cases, the symptoms are caused by cytokines released by immune system activation, and are thus relatively non-specific. Common causes of ILI include the common cold and influenza, which tends to be less common but more severe than the common cold. Less common causes include side effects of many drugs and manifestations of many other diseases. Definition The term ILI can be used casually, but when used in the surveillance of influenza cases, can have a strict definition. The World Health Organization defines an illness as an ILI if the patient has a fever greater than or equal to 38 C° and a cough, which began in the last 10 days. If the patient requires hospitalisation, the illness is classified instead as a severe acute respiratory infection (SARI). Other organisations may have different definitions. For instance, the CDC defines it as a 100 °F (38 °C) fever or greater, and a cough or sore throat. Causes The causes of influenza-like illness range from benign self-limited illnesses such as gastroenteritis, rhinoviral disease, and influenza, to severe, sometimes life-threatening, diseases such as meningitis, sepsis, and leukemia. Influenza Technically, any clinical diagnosis of influenza is a diagnosis of ILI, not of influenza. This distinction usually is of no great concern because, regardless of cause, most cases of ILI are mild and self-limiting. Furthermore, except perhaps during the peak of a major outbreak of influenza, most cases of ILI are not due to influenza. ILI is very common: in the United States each adult can average 1–3 episodes per year and each child can average 3–6 episodes per year.Influenza in humans is subject to clinical surveillance by a global network of more than 110 National Influenza Centers. These centers receive samples obtained from patients diagnosed with ILI, and test the samples for the presence of an influenza virus. Not all patients diagnosed with ILI are tested, and not all test results are reported. Samples are selected for testing based on severity of ILI, and as part of routine sampling, and at participating surveillance clinics and laboratories. The United States has a general surveillance program, a border surveillance program, and a hospital surveillance program, all devoted to finding new outbreaks of influenza.In most years, in the majority of samples tested, the influenza virus is not present (see figure above). In the United States during the 2008–9 influenza season through 18 April, out of 183,839 samples tested and reported to the CDC, only 25,925 (14.1%) were positive for influenza. The percent positive reached a maximum of about 25%. The percent positive increases with the incidence of infection, peaking with the peak incidence of influenza (see figure). During an epidemic, 60–70% of patients with a clear influenza-like illness actually have influenza.Samples are respiratory samples, usually collected by a physician, nurse, or assistant, and sent to a hospital laboratory for preliminary testing. There are several methods of collecting a respiratory sample, depending on requirements of the laboratory that will test the sample. A sample may be obtained from around the nose simply by wiping with a dry cotton swab. Other causes Infectious diseases causing ILI include respiratory syncytial virus, malaria, acute HIV/AIDS infection, herpes, hepatitis C, Lyme disease, rabies, myocarditis, Q fever, dengue fever, poliomyelitis, pneumonia, measles, SARS, COVID-19, and many others. Pharmaceutical drugs that may cause ILI include many biologics such as interferons and monoclonal antibodies. Chemotherapeutic agents also commonly cause flu-like symptoms. Other drugs associated with a flu-like syndrome include bisphosphonates, caspofungin, and levamisole. A flu-like syndrome can also be caused by an influenza vaccine or other vaccines, and by opioid withdrawal in physically dependent individuals. Diagnosis Influenza-like illness is a nonspecific respiratory illness characterized by fever, fatigue, cough, and other symptoms that stop within a few days. Most cases of ILI are caused not by influenza but by other viruses (e.g., rhinoviruses, coronaviruses, human respiratory syncytial virus, adenoviruses, and human parainfluenza viruses). Less common causes of ILI include bacteria such as Legionella, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Streptococcus pneumoniae. Influenza, RSV, and certain bacterial infections are particularly important causes of ILI because these infections can lead to serious complications requiring hospitalization. Physicians who examine persons with ILI can use a combination of epidemiologic and clinical data (information about recent other patients and the individual patient) and, if necessary, laboratory and radiographic tests to determine the cause of the ILI. The use of multiplexed point-of-care testing such as CRP (C-reactive protein) along with an examination by a doctor may help to identify a bacterial and avoid an unnecessary antibiotic prescription.During the 2009 flu pandemic, many thousands of cases of ILI were reported in the media as suspected swine flu. Most were false alarms. A differential diagnosis of probable swine flu requires not only symptoms but also a high likelihood of swine flu due to the persons recent history. During the 2009 flu pandemic in the United States, the CDC advised physicians to "consider swine influenza infection in the differential diagnosis of patients with acute febrile respiratory illness who have either been in contact with persons with confirmed swine flu, or who were in one of the five U.S. states that have reported swine flu cases or in Mexico during the 7 days preceding their illness onset." A diagnosis of confirmed swine flu required laboratory testing of a respiratory sample (a simple nose and throat swab). In rare cases If a person with ILI also has either a history of exposure or an occupational or environmental risk of exposure to Bacillus anthracis (anthrax), then a differential diagnosis requires distinguishing between ILI and anthrax. Other rare causes of ILI include leukemia and metal fume fever. In horses ILI occurs in some horses after intramuscular injection of vaccines. For these horses, light exercise speeds resolution of the ILI. Non-steroidal anti-inflammatory drugs (NSAIDs) may be given with the vaccine. See also Attack rate Disease surveillance == References ==
Migraine	Migraine (UK:, US: ) is a common neurological disorder characterized by recurrent headaches. Typically, the associated headache affects one side of the head, is pulsating in nature, may be moderate to severe in intensity, and could last from a few hours to three days. Non-headache symptoms may include nausea, vomiting, and sensitivity to light, sound, or smell. The pain is generally made worse by physical activity during an attack, although regular physical exercise may prevent future attacks. Up to one-third of people affected have aura: typically, it is a short period of visual disturbance that signals that the headache will soon occur. Occasionally, aura can occur with little or no headache following, but not everyone has this symptom.Migraine is believed to be due to a mixture of environmental and genetic factors. About two-thirds of cases run in families. Changing hormone levels may also play a role, as migraine affects slightly more boys than girls before puberty and two to three times more women than men. The risk of migraine usually decreases during pregnancy and after menopause. The underlying mechanisms are not fully known. They are, however, believed to involve the nerves and blood vessels of the brain.Initial recommended treatment is with simple pain medication such as ibuprofen and paracetamol (acetaminophen) for the headache, medication for the nausea, and the avoidance of triggers. Specific medications such as triptans or ergotamines may be used in those for whom simple pain medications are not effective. Caffeine in combination with other analgesics is safe and effective in treatment of acute migraine. A number of medications are useful to prevent attacks including metoprolol, valproate, and topiramate.Globally, approximately 15% of people are affected by migraine. In the Global Burden of Disease Study of 2010, it was ranked as the third most prevalent disorder in the world. It most often starts at puberty and is worst during middle age. As of 2016, it is one of the most common causes of disability. An early description consistent with migraines is contained in the Ebers papyrus, written around 1500 BC in ancient Egypt. The word migraine is from the Greek ἡμικρᾱνίᾱ (hēmikrāníā), pain in half of the head, from ἡμι- (hēmi-), half and κρᾱνίον (krāníon), skull. Signs and symptoms Migraine typically presents with self-limited, recurrent severe headache associated with autonomic symptoms. About 15–30% of people living with migraine experience episodes with aura, and they also frequently experience episodes without aura. The severity of the pain, duration of the headache, and frequency of attacks are variable. A migraine attack lasting longer than 72 hours is termed status migrainosus. There are four possible phases to a migraine attack, although not all the phases are necessarily experienced: The prodrome, which occurs hours or days before the headache The aura, which immediately precedes the headache The pain phase, also known as headache phase The postdrome, the effects experienced following the end of a migraine attackMigraine is associated with major depression, bipolar disorder, anxiety disorders, and obsessive–compulsive disorder. These psychiatric disorders are approximately 2–5 times more common in people without aura, and 3–10 times more common in people with aura. Prodrome phase Prodromal or premonitory symptoms occur in about 60% of those with migraines, with an onset that can range from two hours to two days before the start of pain or the aura. These symptoms may include a wide variety of phenomena, including altered mood, irritability, depression or euphoria, fatigue, craving for certain food(s), stiff muscles (especially in the neck), constipation or diarrhea, and sensitivity to smells or noise. This may occur in those with either migraine with aura or migraine without aura. Neuroimaging indicates the limbic system and hypothalamus as the origin of prodromal symptoms in migraine. Aura phase Aura is a transient focal neurological phenomenon that occurs before or during the headache. Aura appears gradually over a number of minutes (usually occurring over 5–60 minutes) and generally lasts less than 60 minutes. Symptoms can be visual, sensory or motoric in nature, and many people experience more than one. Visual effects occur most frequently: they occur in up to 99% of cases and in more than 50% of cases are not accompanied by sensory or motor effects.Visual disturbances often consist of a scintillating scotoma (an area of partial alteration in the field of vision which flickers and may interfere with a persons ability to read or drive). These typically start near the center of vision and then spread out to the sides with zigzagging lines which have been described as looking like fortifications or walls of a castle. Usually the lines are in black and white but some people also see colored lines. Some people lose part of their field of vision known as hemianopsia while others experience blurring.Sensory aura are the second most common type; they occur in 30–40% of people with auras. Often a feeling of pins-and-needles begins on one side in the hand and arm and spreads to the nose–mouth area on the same side. Numbness usually occurs after the tingling has passed with a loss of position sense. Other symptoms of the aura phase can include speech or language disturbances, world spinning, and less commonly motor problems. Motor symptoms indicate that this is a hemiplegic migraine, and weakness often lasts longer than one hour unlike other auras. Auditory hallucinations or delusions have also been described. Pain phase Classically the headache is unilateral, throbbing, and moderate to severe in intensity. It usually comes on gradually and is aggravated by physical activity during a migraine attack. However, the effects of physical activity on migraine are complex, and some researchers have concluded that, while exercise can trigger migraine attacks, regular exercise may have a prophylactic effect and decrease frequency of attacks. The feeling of pulsating pain is not in phase with the pulse. In more than 40% of cases, however, the pain may be bilateral (both sides of the head), and neck pain is commonly associated with it. Bilateral pain is particularly common in those who have migraine without aura. Less commonly pain may occur primarily in the back or top of the head. The pain usually lasts 4 to 72 hours in adults; however, in young children frequently lasts less than 1 hour. The frequency of attacks is variable, from a few in a lifetime to several a week, with the average being about one a month.The pain is frequently accompanied by nausea, vomiting, sensitivity to light, sensitivity to sound, sensitivity to smells, fatigue and irritability. Many thus seek a dark and quiet room. In a basilar migraine, a migraine with neurological symptoms related to the brain stem or with neurological symptoms on both sides of the body, common effects include a sense of the world spinning, light-headedness, and confusion. Nausea occurs in almost 90% of people, and vomiting occurs in about one-third. Other symptoms may include blurred vision, nasal stuffiness, diarrhea, frequent urination, pallor, or sweating. Swelling or tenderness of the scalp may occur as can neck stiffness. Associated symptoms are less common in the elderly. Silent migraine Sometimes, aura occurs without a subsequent headache. This is known in modern classification as a typical aura without headache, or acephalgic migraine in previous classification, or commonly as a silent migraine. However, silent migraine can still produce debilitating symptoms, with visual disturbance, vision loss in half of both eyes, alterations in color perception, and other sensory problems, like sensitivity to light, sound, and odors, and aura sudden outbreak without headache can be scary. It can last from 15 to 30 minutes, usually no longer than 60 minutes, and it can recur or appear as an isolated event. Postdrome The migraine postdrome could be defined as that constellation of symptoms occurring once the acute headache has settled. Many report a sore feeling in the area where the migraine was, and some report impaired thinking for a few days after the headache has passed. The person may feel tired or "hung over" and have head pain, cognitive difficulties, gastrointestinal symptoms, mood changes, and weakness. According to one summary, "Some people feel unusually refreshed or euphoric after an attack, whereas others note depression and malaise." For some individuals this can vary each time. Cause The underlying causes of migraines are unknown. However, they are believed to be related to a mix of environmental and genetic factors. They run in families in about two-thirds of cases and rarely occur due to a single gene defect. While migraines were once believed to be more common in those of high intelligence, this does not appear to be true. A number of psychological conditions are associated, including depression, anxiety, and bipolar disorder, as are many biological events or triggers. Genetics Studies of twins indicate a 34% to 51% genetic influence of likelihood to develop migraine. This genetic relationship is stronger for migraine with aura than for migraines without aura. A number of specific variants of genes increase the risk by a small to moderate amount.Single gene disorders that result in migraines are rare. One of these is known as familial hemiplegic migraine, a type of migraine with aura, which is inherited in an autosomal dominant fashion. Four genes have been shown to be involved in familial hemiplegic migraine. Three of these genes are involved in ion transport. The fourth is an axonal protein associated with the exocytosis complex. Another genetic disorder associated with migraine is CADASIL syndrome or cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy. One meta-analysis found a protective effect from angiotensin converting enzyme polymorphisms on migraine. The TRPM8 gene, which codes for a cation channel, has been linked to migraines. Triggers Migraine may be induced by triggers, with some reporting it as an influence in a minority of cases and others the majority. Many things such as fatigue, certain foods, alcohol, and weather have been labeled as triggers; however, the strength and significance of these relationships are uncertain. Most people with migraines report experiencing triggers. Symptoms may start up to 24 hours after a trigger. Physiological aspects Common triggers quoted are stress, hunger, and fatigue (these equally contribute to tension headaches). Psychological stress has been reported as a factor by 50 to 80% of people. Migraine has also been associated with post-traumatic stress disorder and abuse. Migraine episodes are more likely to occur around menstruation. Other hormonal influences, such as menarche, oral contraceptive use, pregnancy, perimenopause, and menopause, also play a role. These hormonal influences seem to play a greater role in migraine without aura. Migraine episodes typically do not occur during the second and third trimesters of pregnancy, or following menopause. Dietary aspects Between 12 and 60% of people report foods as triggers.There are many reports that tyramine – which is naturally present in chocolate, alcoholic beverages, most cheeses, processed meats, and other foods – can trigger migraine symptoms in some individuals. Likewise, monosodium glutamate (MSG) is frequently reported as a trigger for migraine symptoms. Environmental aspects A 2009 review on potential triggers in the indoor and outdoor environment concluded that while there were insufficient studies to confirm environmental factors as causing migraine, "migraineurs worldwide consistently report similar environmental triggers". The article suggests that people living with migraine take some preventive measures related to indoor air quality and lighting. Pathophysiology Migraine is believed to be primarily a neurological disorder, while others believe it to be a neurovascular disorder with blood vessels playing the key role, although current evidence does not support this completely. Others believe both are likely important. One theory is related to increased excitability of the cerebral cortex and abnormal control of pain neurons in the trigeminal nucleus of the brainstem. Aura Cortical spreading depression, or spreading depression according to Leão, is a burst of neuronal activity followed by a period of inactivity, which is seen in those with migraines with aura. There are a number of explanations for its occurrence, including activation of NMDA receptors leading to calcium entering the cell. After the burst of activity, the blood flow to the cerebral cortex in the area affected is decreased for two to six hours. It is believed that when depolarization travels down the underside of the brain, nerves that sense pain in the head and neck are triggered. Pain The exact mechanism of the head pain which occurs during a migraine episode is unknown. Some evidence supports a primary role for central nervous system structures (such as the brainstem and diencephalon), while other data support the role of peripheral activation (such as via the sensory nerves that surround blood vessels of the head and neck). The potential candidate vessels include dural arteries, pial arteries and extracranial arteries such as those of the scalp. The role of vasodilatation of the extracranial arteries, in particular, is believed to be significant. Neuromodulators Adenosine, a neuromodulator, may be involved. Released after the progressive cleavage of adenosine triphosphate (ATP), adenosine acts on adenosine receptors to put the body and brain in a low activity state by dilating blood vessels and slowing the heart rate, such as before and during the early stages of sleep. Adenosine levels have been found to be high during migraine attacks. Caffeines role as an inhibitor of adenosine may explain its effect in reducing migraine. Low levels of the neurotransmitter serotonin, also known as 5-hydroxytryptamine (5-HT), are also believed to be involved.Calcitonin gene-related peptides (CGRPs) have been found to play a role in the pathogenesis of the pain associated with migraine, as levels of it become elevated during an attack. Diagnosis The diagnosis of a migraine is based on signs and symptoms. Neuroimaging tests are not necessary to diagnose migraine, but may be used to find other causes of headaches in those whose examination and history do not confirm a migraine diagnosis. It is believed that a substantial number of people with the condition remain undiagnosed.The diagnosis of migraine without aura, according to the International Headache Society, can be made according to the following criteria, the "5, 4, 3, 2, 1 criteria": Five or more attacks—for migraine with aura, two attacks are sufficient for diagnosis. Four hours to three days in duration Two or more of the following: Unilateral (affecting one side of the head) Pulsating Moderate or severe pain intensity Worsened by or causing avoidance of routine physical activity One or more of the following: Nausea and/or vomiting Sensitivity to both light (photophobia) and sound (phonophobia)If someone experiences two of the following: photophobia, nausea, or inability to work or study for a day, the diagnosis is more likely. In those with four out of five of the following: pulsating headache, duration of 4–72 hours, pain on one side of the head, nausea, or symptoms that interfere with the persons life, the probability that this is a migraine attack is 92%. In those with fewer than three of these symptoms, the probability is 17%. Classification Migraine was first comprehensively classified in 1988. The International Headache Society updated their classification of headaches in 2004. A third version was published in 2018. According to this classification, migraine is a primary headache disorder along with tension-type headaches and cluster headaches, among others.Migraine is divided into seven subclasses (some of which include further subdivisions): Migraine without aura, or "common migraine", involves migraine headaches that are not accompanied by aura. Migraine with aura, or "classic migraine", usually involves migraine headaches accompanied by aura. Less commonly, aura can occur without a headache, or with a nonmigraine headache. Two other varieties are familial hemiplegic migraine and sporadic hemiplegic migraine, in which a person has migraine with aura and with accompanying motor weakness. If a close relative has had the same condition, it is called "familial", otherwise it is called "sporadic". Another variety is basilar-type migraine, where a headache and aura are accompanied by difficulty speaking, world spinning, ringing in ears, or a number of other brainstem-related symptoms, but not motor weakness. This type was initially believed to be due to spasms of the basilar artery, the artery that supplies the brainstem. Now that this mechanism is not believed to be primary, the symptomatic term migraine with brainstem aura (MBA) is preferred. Childhood periodic syndromes that are commonly precursors of migraine include cyclical vomiting (occasional intense periods of vomiting), abdominal migraine (abdominal pain, usually accompanied by nausea), and benign paroxysmal vertigo of childhood (occasional attacks of vertigo). Retinal migraine involves migraine headaches accompanied by visual disturbances or even temporary blindness in one eye. Complications of migraine describe migraine headaches and/or auras that are unusually long or unusually frequent, or associated with a seizure or brain lesion. Probable migraine describes conditions that have some characteristics of migraines, but where there is not enough evidence to diagnose it as a migraine with certainty (in the presence of concurrent medication overuse). Chronic migraine is a complication of migraines, and is a headache that fulfills diagnostic criteria for migraine headache and occurs for a greater time interval. Specifically, greater or equal to 15 days/month for longer than 3 months. Abdominal migraine The diagnosis of abdominal migraine is controversial. Some evidence indicates that recurrent episodes of abdominal pain in the absence of a headache may be a type of migraine or are at least a precursor to migraines. These episodes of pain may or may not follow a migraine-like prodrome and typically last minutes to hours. They often occur in those with either a personal or family history of typical migraine. Other syndromes that are believed to be precursors include cyclical vomiting syndrome and benign paroxysmal vertigo of childhood. Differential diagnosis Other conditions that can cause similar symptoms to a migraine headache include temporal arteritis, cluster headaches, acute glaucoma, meningitis and subarachnoid hemorrhage. Temporal arteritis typically occurs in people over 50 years old and presents with tenderness over the temple, cluster headache presents with one-sided nose stuffiness, tears and severe pain around the orbits, acute glaucoma is associated with vision problems, meningitis with fevers, and subarachnoid hemorrhage with a very fast onset. Tension headaches typically occur on both sides, are not pounding, and are less disabling.Those with stable headaches that meet criteria for migraines should not receive neuroimaging to look for other intracranial disease. This requires that other concerning findings such as papilledema (swelling of the optic disc) are not present. People with migraines are not at an increased risk of having another cause for severe headaches. Prevention Preventive treatments of migraine include medications, nutritional supplements, lifestyle alterations, and surgery. Prevention is recommended in those who have headaches more than two days a week, cannot tolerate the medications used to treat acute attacks, or those with severe attacks that are not easily controlled. Recommended lifestyle changes include stopping tobacco use and reducing behaviors that interfere with sleep.The goal is to reduce the frequency, painfulness, and duration of migraine episodes, and to increase the effectiveness of abortive therapy. Another reason for prevention is to avoid medication overuse headache. This is a common problem and can result in chronic daily headache. Medication Preventive migraine medications are considered effective if they reduce the frequency or severity of the migraine attacks by at least 50%. Due to few medications being approved specifically for the preventative treatment of migraine headaches; many medications such as beta-blockers, anticonvulsive agents such as topiramate or sodium valproate, antidepressants such as amitriptyline and calcium channel blockers such as flunarizine are used off label for the preventative treatment of migraine headaches. Guidelines are fairly consistent in rating the anticonvulsants topiramate and divalproex/sodium valproate, and the beta blockers propranolol and metoprolol as having the highest level of evidence for first-line use for migraine prophylaxis in adults. Propranolol and topiramate have the best evidence in children; however, evidence only supports short-term benefit as of 2020.The beta blocker timolol is also effective for migraine prevention and in reducing migraine attack frequency and severity. While beta blockers are often used for first-line treatment, other antihypertensives also have a proven efficiency in migraine prevention, namely the calcium channel blocker verapamil and the angiotensin receptor blocker candesartan.Tentative evidence also supports the use of magnesium supplementation. Increasing dietary intake may be better. Recommendations regarding effectiveness varied for the anticonvulsants gabapentin and pregabalin. Frovatriptan is effective for prevention of menstrual migraine.The antidepressants amitriptyline and venlafaxine are probably also effective. Angiotensin inhibition by either an angiotensin-converting enzyme inhibitor or angiotensin II receptor antagonist may reduce attacks.Medications in the anti-calcitonin gene-related peptide, including eptinezumab, erenumab, fremanezumab, and galcanezumab, appear to decrease the frequency of migraines by one to two per month. They are, however, expensive: a year of erenumab costs $6,900 as of 2019. Alternative therapies Acupuncture has a small effect in reducing migraine frequency, compared to sham acupuncture, a practice where needles are placed randomly or do not penetrate the skin. Physiotherapy, massage and relaxation, and chiropractic manipulation might be as effective as propranolol or topiramate in the prevention of migraine headaches; however, the research had some problems with methodology. Another review, however, found evidence to support spinal manipulation to be poor and insufficient to support its use.Tentative evidence supports the use of stress reduction techniques such as cognitive behavioral therapy, biofeedback, and relaxation techniques. Regular physical exercise may decrease the frequency. Numerous psychological approaches have been developed that are aimed at preventing or reducing the frequency of migraine in adults including educational approaches, relaxation techniques, assistance in developing coping strategies, strategies to change the way one thinks of a migraine attack, and strategies to reduce symptoms. The medical evidence supporting the effectiveness of these types of psychological approaches is very limited.Among alternative medicines, butterbur has the best evidence for its use. However, unprocessed butterbur contains chemicals called pyrrolizidine alkaloids (PAs) which can cause liver damage, however there are versions that are PA free. In addition, butterbur may cause allergic reactions in people who are sensitive to plants such as ragweed. There is tentative evidence that coenzyme Q10 reduces migraine frequency.Feverfew has traditionally been used as a treatment for fever, headache and migraine, womens conditions such as difficulties in labour and regulation of menstruation, relief of stomach ache, toothache and insect bites. During the last decades, it has mainly been used for headache and as a preventive treatment for migraine. The plant parts used for medicinal use are the dried leaves or the dried aerial parts. Several historical data supports feverfews traditional medicinal uses. In addition, several clinical studies have been performed assessing the efficacy and safety of feverfew monotherapy in the prevention of migraine. The majority of the clinical trials favoured feverfew over placebo. The data also suggest that feverfew is associated with only mild and transient adverse effects. The frequency of migraine was positively affected after treatment with feverfew. Reduction of migraine severity was also reported after intake of feverfew and incidence of nausea and vomiting decreased significantly. No effect of feverfew was reported in one study.There is tentative evidence for melatonin as an add-on therapy for prevention and treatment of migraine. The data on melatonin are mixed and certain studies have had negative results. The reasons for the mixed findings are unclear but may stem from differences in study design and dosage. Melatonins possible mechanisms of action in migraine are not completely clear, but may include improved sleep, direct action on melatonin receptors in the brain, and anti-inflammatory properties. Devices and surgery Medical devices, such as biofeedback and neurostimulators, have some advantages in migraine prevention, mainly when common anti-migraine medications are contraindicated or in case of medication overuse. Biofeedback helps people be conscious of some physiological parameters so as to control them and try to relax and may be efficient for migraine treatment. Neurostimulation uses noninvasive or implantable neurostimulators similar to pacemakers for the treatment of intractable chronic migraine with encouraging results for severe cases. A transcutaneous electrical nerve stimulator and a transcranial magnetic stimulator are approved in the United States for the prevention of migraines. There is also tentative evidence for transcutaneous electrical nerve stimulation decreases the frequency of migraines. Migraine surgery, which involves decompression of certain nerves around the head and neck, may be an option in certain people who do not improve with medications. Management There are three main aspects of treatment: trigger avoidance, acute symptomatic control, and medication for prevention. Medications are more effective if used earlier in an attack. The frequent use of medications may result in medication overuse headache, in which the headaches become more severe and more frequent. This may occur with triptans, ergotamines, and analgesics, especially opioid analgesics. Due to these concerns simple analgesics are recommended to be used less than three days per week at most. Analgesics Recommended initial treatment for those with mild to moderate symptoms are simple analgesics such as nonsteroidal anti-inflammatory drugs (NSAIDs) or the combination of paracetamol (also known as acetaminophen), aspirin, and caffeine. Several NSAIDs, including diclofenac and ibuprofen have evidence to support their use. Aspirin (900 to 1000 mg) can relieve moderate to severe migraine pain, with an effectiveness similar to sumatriptan. Ketorolac is available in intravenous and intramuscular formulations.Paracetamol, either alone or in combination with metoclopramide, is another effective treatment with a low risk of adverse effects. Intravenous metoclopramide is also effective by itself. In pregnancy, paracetamol and metoclopramide are deemed safe as are NSAIDs until the third trimester.Naproxen by itself may not be effective as a stand-alone medicine to stop a migraine headache as it is only weakly better than a placebo medication in clinical trials. Antiemetics Triptans Triptans such as sumatriptan are medications used to stop an active migraine headache (an abortive medication). Triptans are the initially recommended treatments for those with moderate to severe pain from an acute migraine headache or those with milder symptoms who do not respond to simple analgesics. Triptans have been shown to be effective for both pain and nausea in up to 75% of people. There are different methods or routes of administration to take sumatriptan including oral (by mouth), injectable (subcutaneous), rectal, nasal spray, and oral dissolving tablets. For people with migraine symptoms such as nausea or vomiting, taking the abortive medicine by mouth or through the nose may be difficult. All route of administration have been shown to be effective at reducing migraine symptoms, however, nasal and injectable subcutaneous administration may result in more side effects. The adverse effects associated with rectal administration have not been well studied. Some people may find that they respond to one type of sumatriptan better than another.Most side effects are mild, including flushing; however, rare cases of myocardial ischemia have occurred. They are thus not recommended for people with cardiovascular disease, who have had a stroke, or have migraines that are accompanied by neurological problems. In addition, triptans should be prescribed with caution for those with risk factors for vascular disease. While historically not recommended in those with basilar migraines there is no specific evidence of harm from their use in this population to support this caution. Triptans are not addictive, but may cause medication-overuse headaches if used more than 10 days per month.Sumatriptan does not prevent other migraine headaches from starting in the future. For increased effectiveness at stopping migraine symptoms, a combined
Migraine	therapy that includes sumatriptan and naproxen may be suggested. CGRP receptor antagonists CGRP receptor antagonists target calcitonin gene-related peptide or its receptor to prevent migraine headaches or reduce their severity. CGRP is a signaling molecule as well as a potent vasodilator that is involved in the development of a migraine headache. There are four injectable monoclonal antibodies that target CGRP or its receptor (eptinezumab, erenumab, fremanezumab and galcanezumab) and the medications have demonstrated efficacy in the preventative treatment of episodic and chronic migraine headaches in phase 3 randomized clinical trials. Eptinezumab is available as an infusion every three months, Erenumab and galcanezumab are once monthly injections and fremanezumab is a monthly or quarterly injection. Ergotamines Ergotamine and dihydroergotamine are older medications still prescribed for migraines, the latter in nasal spray and injectable forms. They appear equally effective to the triptans and experience adverse effects that typically are benign. In the most severe cases, such as those with status migrainosus, they appear to be the most effective treatment option. They can cause vasospasm including coronary vasospasm and are contraindicated in people with coronary artery disease. Magnesium Magnesium is recognized as an inexpensive, over-the-counter supplement which some studies have shown to be effective in both preventing and treating migraine in intravenous form. Other Intravenous metoclopramide, intravenous prochlorperazine, or intranasal lidocaine are other potential options. Metoclopramide or prochlorperazine are the recommended treatment for those who present to the emergency department. Haloperidol may also be useful in this group. A single dose of intravenous dexamethasone, when added to standard treatment of a migraine attack, is associated with a 26% decrease in headache recurrence in the following 72 hours. Spinal manipulation for treating an ongoing migraine headache is not supported by evidence. It is recommended that opioids and barbiturates not be used due to questionable efficacy, addictive potential, and the risk of rebound headache. There is tentative evidence that propofol may be useful if other measures are not effective.Occipital nerve stimulation, may be effective but has the downsides of being cost-expensive and has a significant amount of complications.There is modest evidence for the effectiveness of non-invasive neuromodulatory devices, behavioral therapies and acupuncture in the treatment of migraine headaches. There is little to no evidence for the effectiveness of physical therapy, chiropractic manipulation and dietary approaches to the treatment of migraine headaches. Behavioral treatment of migraine headaches may be helpful for those who may not be able to take medications (for example pregnant women).Feverfew is registered as a traditional herbal medicine in the Nordic countries under the brand name Glitinum, only powdered feverfew is approved in the Herbal community monograph issued by European Medicines Agency (EMA). Sexual activity, particularly orgasm, may provide relief for some migraineurs. Children Ibuprofen helps decrease pain in children with migraines and is the initially recommended treatment. Paracetamol does not appear to be effective in providing pain relief. Triptans are effective, though there is a risk of causing minor side effects like taste disturbance, nasal symptoms, dizziness, fatigue, low energy, nausea, or vomiting. Ibuprofen should be used less than half the days in a month and triptans less than a third of the days in a month to decrease the risk of medication overuse headache. Chronic migraine Topiramate and botulinum toxin (Botox) have evidence in treating chronic migraine. Botulinum toxin has been found to be useful in those with chronic migraine but not those with episodic ones. The anti-CGRP monoclonal antibody erenumab was found in one study to decrease chronic migraines by 2.4 days more than placebo. Prognosis "Migraine exists on a continuum of different attack frequencies and associated levels of disability." For those with occasional, episodic migraine, a "proper combination of drugs for prevention and treatment of migraine attacks" can limit the diseases impact on patients personal and professional lives. But fewer than half of people with migraine seek medical care and more than half go undiagnosed and undertreated. "Responsive prevention and treatment of migraine is incredibly important" because evidence shows "an increased sensitivity after each successive attack, eventually leading to chronic daily migraine in some individuals." Repeated migraine results in "reorganization of brain circuitry," causing "profound functional as well as structural changes in the brain." "One of the most important problems in clinical migraine is the progression from an intermittent, self-limited inconvenience to a life-changing disorder of chronic pain, sensory amplification, and autonomic and affective disruption. This progression, sometimes termed chronification in the migraine literature, is common, affecting 3% of migraineurs in a given year, such that 8% of migraineurs have chronic migraine in any given year." Brain imagery reveals that the electrophysiological changes seen during an attack become permanent in people with chronic migraine; "thus, from an electrophysiological point of view, chronic migraine indeed resembles a never-ending migraine attack." Severe migraine ranks in the highest category of disability, according to the World Health Organization, which uses objective metrics to determine disability burden for the authoritative annual Global Burden of Disease report. The report classifies severe migraine alongside severe depression, active psychosis, quadriplegia, and terminal-stage cancer.Migraine with aura appears to be a risk factor for ischemic stroke doubling the risk. Being a young adult, being female, using hormonal birth control, and smoking further increases this risk. There also appears to be an association with cervical artery dissection. Migraine without aura does not appear to be a factor. The relationship with heart problems is inconclusive with a single study supporting an association. Migraine does not appear to increase the risk of death from stroke or heart disease. Preventative therapy of migraines in those with migraine with aura may prevent associated strokes. People with migraine, particularly women, may develop higher than average numbers of white matter brain lesions of unclear significance. Epidemiology Worldwide, migraine affects nearly 15% or approximately one billion people. It is more common in women at 19% than men at 11%. In the United States, about 6% of men and 18% of women experience a migraine attack in a given year, with a lifetime risk of about 18% and 43% respectively. In Europe, migraines affect 12–28% of people at some point in their lives with about 6–15% of adult men and 14–35% of adult women getting at least one yearly. Rates of migraine are slightly lower in Asia and Africa than in Western countries. Chronic migraine occurs in approximately 1.4 to 2.2% of the population.These figures vary substantially with age: onset of migraine is most commonly between 15 and 24 years of age, and occur most frequently in those 35 to 45 years of age. In children, about 1.7% of 7 year olds and 3.9% of those between 7 and 15 experience migraine, with the condition being slightly more common in boys before puberty. Children as young as two years may be affected. During adolescence, migraine becomes more common among women and this persists for the rest of the lifespan, being twice as common among elderly females than males. In women migraine without aura are more common than migraine with aura; however in men the two types occur with similar frequency.During perimenopause symptoms often get worse before decreasing in severity. While symptoms resolve in about two thirds of the elderly, in 3 to 10% they persist. History An early description consistent with migraine is contained in the Ebers papyrus, written around 1500 BCE in ancient Egypt. In 200 BCE, writings from the Hippocratic school of medicine described the visual aura that can precede the headache and a partial relief occurring through vomiting.A second-century description by Aretaeus of Cappadocia divided headaches into three types: cephalalgia, cephalea, and heterocrania. Galen of Pergamon used the term hemicrania (half-head), from which the word migraine was eventually derived. He also proposed that the pain arose from the meninges and blood vessels of the head. Migraine was first divided into the two now used types – migraine with aura (migraine ophthalmique) and migraine without aura (migraine vulgaire) in 1887 by Louis Hyacinthe Thomas, a French Librarian. The mystical visions of Hildegard von Bingen, which she described as “reflections of the living light", are consistent with the visual aura experienced during migraines. Trepanation, the deliberate drilling of holes into a skull, was practiced as early as 7,000 BCE. While sometimes people survived, many would have died from the procedure due to infection. It was believed to work via "letting evil spirits escape". William Harvey recommended trepanation as a treatment for migraines in the 17th century.While many treatments for migraine have been attempted, it was not until 1868 that use of a substance which eventually turned out to be effective began. This substance was the fungus ergot from which ergotamine was isolated in 1918. Methysergide was developed in 1959 and the first triptan, sumatriptan, was developed in 1988. During the 20th century with better study-design, effective preventive measures were found and confirmed. Society and culture Migraine is a significant source of both medical costs and lost productivity. It has been estimated that migraine is the most costly neurological disorder in the European Community, costing more than €27 billion per year. In the United States, direct costs have been estimated at $17 billion, while indirect costs — such as missed or decreased ability to work — is estimated at $15 billion. Nearly a tenth of the direct cost is due to the cost of triptans. In those who do attend work during a migraine attack, effectiveness is decreased by around a third. Negative impacts also frequently occur for a persons family. Research Potential prevention mechanisms Transcranial magnetic stimulation shows promise as does transcutaneous supraorbital nerve stimulation. There is preliminary evidence that a ketogenic diet may help prevent episodic and long-term migraine. Potential gender dependency While no definitive proof has been found linking migraine to gender, statistical data indicates that women may be more prone to having migraine, showing migraine incidence three times higher among women than men. The Society for Womens Health Research has also mentioned hormonal influences, mainly estrogen, as having a considerable role in provoking migraine pain. Studies and research related to the gender dependencies of migraine are still ongoing, and conclusions have yet to be achieved. References Notes Olesen J (2006). The headaches (3 ed.). Philadelphia: Lippincott Williams & Wilkins. ISBN 9780781754002. Further reading Ashina M (November 2020). Ropper AH (ed.). "Migraine". The New England Journal of Medicine. 383 (19): 1866–1876. doi:10.1056/nejmra1915327. PMID 33211930. S2CID 227078662. Oskoui M, Pringsheim T, Billinghurst L, Potrebic S, Gersz EM, Gloss D, et al. (September 2019). "Practice guideline update summary: Pharmacologic treatment for pediatric migraine prevention: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology. 93 (11): 500–509. doi:10.1212/WNL.0000000000008105. PMC 6746206. PMID 31413170. Oskoui M, Pringsheim T, Holler-Managan Y, Potrebic S, Billinghurst L, Gloss D, et al. (September 2019). "Practice guideline update summary: Acute treatment of migraine in children and adolescents: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Headache Society". Neurology. 93 (11): 487–499. doi:10.1212/WNL.0000000000008095. PMID 31413171. S2CID 199662718. External links Migraine at Curlie
Arsenical keratosis	An arsenical keratosis is a growth of keratin on the skin caused by arsenic,: 725 which occurs naturally in the earths crust and is widely distributed in the environment, Arsenical compounds are used in industrial, agricultural, and medicinal substances. Arsenic is also found to be an environmental contaminant in drinking water (well water) and an occupational hazard for miners and glass workers.: 640 Arsenic may also causes other conditions including: Bowens disease, cardiovascular diseases, developmental abnormalities, neurologic and neurobehavioral disorders, diabetes, hearing loss, hematologic disorders, and various types of cancer. Arsenical keratoses may persist indefinitely, and some may develop into invasive squamous cell carcinoma. Metastatic arsenic squamous cell carcinoma and arsenic-induced malignancies in internal organs such as the bladder, kidney, skin, liver, and colon, may result in death. Signs and symptoms Books talk about diffuse ketarosic neoformations in palms and plants, which can evolve into basal cell carcinoma. These neoformations are usually yellowish. Pathophysiology Arsenite impairs nucleotide excision repair, and it may also affect gene expression by increasing or decreasing DNA methylation. The high affinity of arsenic for sulfhydryl groups makes keratin-rich cells (e.g., epidermal keratinocytes) a sensitive target for arsenic-induced toxicity. Arsenic has been shown to alter epidermal keratinocyte differentiation processes, induce overexpression of growth factors, and enhance proliferation of human keratinocytes. Treatment A chelating agent (e.g., dimercaprol) may be helpful to correct acute arsenic exposure, but it has minimal or no effect for patients who had arsenic exposure a long time ago. Oral retinoids (e.g., acitretin, etretinate) may be helpful in treating arsenic-induced cutaneous lesions and in reducing the risk of cutaneous and internal malignancy formation, especially in Bowmans disease. Topical 5-fluorouracil cream or 5% imiquimod cream may be useful in treating arsenical keratoses and Bowens disease. == References ==
Stress (biology)	Stress, either physiological, biological or psychological, is an organisms response to a stressor such as an environmental condition. Stress is the bodys method of reacting to a condition such as a threat, challenge or physical and psychological barrier. There are two hormones that an individual produces during a stressful situation, these are well known as adrenaline and cortisol. Stimuli that alter an organisms environment are responded to by multiple systems in the body. In humans and most mammals, the autonomic nervous system and hypothalamic-pituitary-adrenal (HPA) axis are the two major systems that respond to stress.The sympathoadrenal medullary (SAM) axis may activate the fight-or-flight response through the sympathetic nervous system, which dedicates energy to more relevant bodily systems to acute adaptation to stress, while the parasympathetic nervous system returadrenaliney to homeostasis. The second major physiological stress-response center, the HPA axis, regulates the release of cortisol, which influences many bodily functions such as metabolic, psychological and immunological functions. The SAM and HPA axes are regulated by several brain regions, including the limbic system, prefrontal cortex, amygdala, hypothalamus, and stria terminalis.Through these mechanisms, stress can alter memory functions, reward, immune function, metabolism and susceptibility to diseases. Disease risk is particularly pertinent to mental illnesses, whereby chronic or severe stress remains a common risk factor for several mental illnesses. One system suggests there are five types of stress labeled "acute time-limited stressors", "brief naturalistic stressors", "stressful event sequences", "chronic stressors", and "distant stressors". An acute time-limited stressor involves a short-term challenge, while a brief natural stressor involves an event that is normal but nevertheless challenging. A stressful event sequence is a stressor that occurs, and then continues to yield stress into the immediate future. A chronic stressor involves exposure to a long-term stressor, and a distant stressor is a stressor that is not immediate. Psychology Acute stressful situations where the stress experienced is severe is a cause of change psychologically to the detriment of the well-being of the individual, such that symptomatic derealization and depersonalization, and anxiety and hyperarousal, are experienced. The International Classification of Diseases includes a group of mental and behavioral disorders which have their aetiology in reaction to severe stress and the consequent adaptive response. Chronic stress, and a lack of coping resources available, or used by an individual, can often lead to the development of psychological issues such as delusions, depression and anxiety (see below for further information).Chronic stressors may not be as intense as acute stressors such as natural disaster or a major accident, but persist over longer periods of time, tend to have a more negative effect on health because they are sustained and thus require the bodys physiological response to occur daily. This depletes the bodys energy more quickly and usually occurs over long periods of time, especially when these microstressors cannot be avoided (i.e. stress of living in a dangerous neighborhood). See allostatic load for further discussion of the biological process by which chronic stress may affect the body. For example, studies have found that caregivers, particularly those of dementia patients, have higher levels of depression and slightly worse physical health than non-caregivers.When humans are under chronic stress, permanent changes in their physiological, emotional, and behavioral responses may occur. Chronic stress can include events such as caring for a spouse with dementia, or may result from brief focal events that have long term effects, such as experiencing a sexual assault. Studies have also shown that psychological stress may directly contribute to the disproportionately high rates of coronary heart disease morbidity and mortality and its etiologic risk factors. Specifically, acute and chronic stress have been shown to raise serum lipids and are associated with clinical coronary events.However, it is possible for individuals to exhibit hardiness—a term referring to the ability to be both chronically stressed and healthy. Even though psychological stress is often connected with illness or disease, most healthy individuals can still remain disease-free after being confronted with chronic stressful events. This suggests that there are individual differences in vulnerability to the potential pathogenic effects of stress; individual differences in vulnerability arise due to both genetic and psychological factors. In addition, the age at which the stress is experienced can dictate its effect on health. Research suggests chronic stress at a young age can have lifelong effects on the biological, psychological, and behavioral responses to stress later in life. Etymology and historical usage The term "stress" had none of its contemporary connotations before the 1920s. It is a form of the Middle English destresse, derived via Old French from the Latin stringere, "to draw tight". The word had long been in use in physics to refer to the internal distribution of a force exerted on a material body, resulting in strain. In the 1920s and 30s, biological and psychological circles occasionally used the term to refer to a mental strain or to a harmful environmental agent that could cause illness.Walter Cannon used it in 1926 to refer to external factors that disrupted what he called homeostasis. But "...stress as an explanation of lived experience is absent from both lay and expert life narratives before the 1930s". Physiological stress represents a wide range of physical responses that occur as a direct effect of a stressor causing an upset in the homeostasis of the body. Upon immediate disruption of either psychological or physical equilibrium the body responds by stimulating the nervous, endocrine, and immune systems. The reaction of these systems causes a number of physical changes that have both short- and long-term effects on the body.The Holmes and Rahe stress scale was developed as a method of assessing the risk of disease from life changes. The scale lists both positive and negative changes that elicit stress. These include things such as a major holiday or marriage, or death of a spouse and firing from a job. Biological need for equilibrium Homeostasis is a concept central to the idea of stress. In biology, most biochemical processes strive to maintain equilibrium (homeostasis), a steady state that exists more as an ideal and less as an achievable condition. Environmental factors, internal or external stimuli, continually disrupt homeostasis; an organisms present condition is a state of constant flux moving about a homeostatic point that is that organisms optimal condition for living. Factors causing an organisms condition to diverge too far from homeostasis can be experienced as stress. A life-threatening situation such as a major physical trauma or prolonged starvation can greatly disrupt homeostasis. On the other hand, an organisms attempt at restoring conditions back to or near homeostasis, often consuming energy and natural resources, can also be interpreted as stress.The ambiguity in defining this phenomenon was first recognized by Hans Selye (1907–1982) in 1926. In 1951 a commentator loosely summarized Selyes view of stress as something that "...in addition to being itself, was also the cause of itself, and the result of itself".First to use the term in a biological context, Selye continued to define stress as "the non-specific response of the body to any demand placed upon it". Neuroscientists such as Bruce McEwen and Jaap Koolhaas believe that stress, based on years of empirical research, "should be restricted to conditions where an environmental demand exceeds the natural regulatory capacity of an organism". Indeed, in 1995 Toates already defined stress as a "chronic state that arises only when defense mechanisms are either being chronically stretched or are actually failing," while according to Ursin (1988) stress results from an inconsistency between expected events ("set value") and perceived events ("actual value") that cannot be resolved satisfactorily, which also puts stress into the broader context of cognitive-consistency theory. Biological background Stress can have many profound effects on the human biological systems. Biology primarily attempts to explain major concepts of stress using a stimulus-response paradigm, broadly comparable to how a psychobiological sensory system operates. The central nervous system (brain and spinal cord) plays a crucial role in the bodys stress-related mechanisms. Whether one should interpret these mechanisms as the bodys response to a stressor or embody the act of stress itself is part of the ambiguity in defining what exactly stress is. The central nervous system works closely with the bodys endocrine system to regulate these mechanisms. The sympathetic nervous system becomes primarily active during a stress response, regulating many of the bodys physiological functions in ways that ought to make an organism more adaptive to its environment. Below there follows a brief biological background of neuroanatomy and neurochemistry and how they relate to stress.Stress, either severe, acute stress or chronic low-grade stress may induce abnormalities in three principal regulatory systems in the body: serotonin systems, catecholamine systems, and the hypothalamic-pituitary-adrenocortical axis. Aggressive behavior has also been associated with abnormalities in these systems. Biology of stress The brain endocrine interactions are relevant in the translation of stress into physiological and psychological changes. The autonomic nervous system (ANS), as mentioned above, plays an important role in translating stress into a response. The ANS responds reflexively to both physical stressors (for example baroreception), and to higher level inputs from the brain.The ANS is composed of the parasympathetic nervous system and sympathetic nervous system, two branches that are both tonically active with opposing activities. The ANS directly innervates tissue through the postganglionic nerves, which is controlled by preganglionic neurons originating in the intermediolateral cell column. The ANS receives inputs from the medulla, hypothalamus, limbic system, prefrontal cortex, midbrain and monoamine nuclei.The activity of the sympathetic nervous system drives what is called the "fight or flight" response. The fight or flight response to emergency or stress involves mydriasis, increased heart rate and force contraction, vasoconstriction, bronchodilation, glycogenolysis, gluconeogenesis, lipolysis, sweating, decreased motility of the digestive system, secretion of the epinephrine and cortisol from the adrenal medulla, and relaxation of the bladder wall. The parasympathetic nervous response, "rest and digest", involves return to maintaining homeostasis, and involves miosis, bronchoconstriction, increased activity of the digestive system, and contraction of the bladder walls. Complex relationships between protective and vulnerability factors on the effect of childhood home stress on psychological illness, cardiovascular illness and adaption have been observed. ANS related mechanisms are thought to contribute to increased risk of cardiovascular disease after major stressful events.The HPA axis is a neuroendocrine system that mediates a stress response. Neurons in the hypothalamus, particularly the paraventricular nucleus, release vasopressin and corticotropin releasing hormone, which travel through the hypophysial portal vessel where they travel to and bind to the corticotropin-releasing hormone receptor on the anterior pituitary gland. Multiple CRH peptides have been identified, and receptors have been identified on multiple areas of the brain, including the amygdala. CRH is the main regulatory molecule of the release of ACTH.The secretion of ACTH into systemic circulation allows it to bind to and activate Melanocortin receptor, where it stimulates the release of steroid hormones. Steroid hormones bind to glucocorticoid receptors in the brain, providing negative feedback by reducing ACTH release. Some evidence supports a second long term feedback that is non-sensitive to cortisol secretion. The PVN of the hypothalamus receives inputs from the nucleus of the solitary tract, and lamina terminalis. Through these inputs, it receives and can respond to changes in blood.The PVN innervation from the brain stem nuclei, particularly the noradrenergic nuclei stimulate CRH release. Other regions of the hypothalamus both directly and indirectly inhibit HPA axis activity. Hypothalamic neurons involved in regulating energy balance also influence HPA axis activity through the release of neurotransmitters such as neuropeptide Y, which stimulates HPA axis activity. Generally, the amygdala stimulates, and the prefrontal cortex and hippocampus attenuate, HPA axis activity; however, complex relationships do exist between the regions.The immune system may be heavily influenced by stress. The sympathetic nervous system innervates various immunological structures, such as bone marrow and the spleen, allowing for it to regulate immune function. The adrenergic substances released by the sympathetic nervous system can also bind to and influence various immunological cells, further providing a connection between the systems. The HPA axis ultimately results in the release of cortisol, which generally has immunosuppressive effects. However, the effect of stress on the immune system is disputed, and various models have been proposed in an attempt to account for both the supposedly "immunodeficiency" linked diseases and diseases involving hyper activation of the immune system. One model proposed to account for this suggests a push towards an imbalance of cellular immunity(Th1) and humoral immunity(Th2). The proposed imbalance involved hyperactivity of the Th2 system leading to some forms of immune hypersensitivity, while also increasing risk of some illnesses associated with decreased immune system function, such as infection and cancer. Effects of chronic stress Chronic stress is a term sometimes used to differentiate it from acute stress. Definitions differ, and may be along the lines of continual activation of the stress response, stress that causes an allostatic shift in bodily functions, or just as "prolonged stress". For example, results of one study demonstrated that individuals who reported relationship conflict lasting one month or longer have a greater risk of developing illness and show slower wound healing. Similarly, the effects that acute stressors have on the immune system may be increased when there is perceived stress and/or anxiety due to other events. For example, students who are taking exams show weaker immune responses if they also report stress due to daily hassles. While responses to acute stressors typically do not impose a health burden on young, healthy individuals, chronic stress in older or unhealthy individuals may have long-term effects that are detrimental to health. Immunological Acute time-limited stressors, or stressors that lasted less than two hours, results in an up regulation of natural immunity and down regulation of specific immunity. This type of stress saw in increase in granulocytes, natural killer cells, IgA, Interleukin 6, and an increase in cell cytotoxicity. Brief naturalistic stressors elicit a shift from Th1(cellular) to Th2(humoral) immunity, while decreased T-cell proliferation, and natural killer cell cytotoxicity. Stressful event sequences did not elicit a consistent immune response; however, some observations such as decreased T-Cell proliferation and cytotoxicity, increase or decrease in natural killer cell cytotoxicity, and an increase in mitogen PHA. Chronic stress elicited a shift toward Th2 immunity, as well as decreased interleukin 2, T cell proliferation, and antibody response to the influenza vaccine. Distant stressors did not consistently elicit a change in immune function. Infectious Some studies have observed increased risk of upper respiratory tract infection during chronic life stress. In patients with HIV, increased life stress and cortisol was associated with poorer progression of HIV. Chronic disease A link has been suggested between chronic stress and cardiovascular disease. Stress appears to play a role in hypertension, and may further predispose people to other conditions associated with hypertension. Stress may precipitate abuse of drugs and/or alcohol. Stress may also contribute to aging and chronic diseases in aging, such as depression and metabolic disorders.The immune system also plays a role in stress and the early stages of wound healing. It is responsible for preparing the tissue for repair and promoting recruitment of certain cells to the wound area. Consistent with the fact that stress alters the production of cytokines, Graham et al. found that chronic stress associated with care giving for a person with Alzheimers disease leads to delayed wound healing. Results indicated that biopsy wounds healed 25% more slowly in the chronically stressed group, or those caring for a person with Alzheimers disease. Development Chronic stress has also been shown to impair developmental growth in children by lowering the pituitary glands production of growth hormone, as in children associated with a home environment involving serious marital discord, alcoholism, or child abuse.More generally, prenatal life, infancy, childhood, and adolescence are critical periods in which the vulnerability to stressors is particularly high. Psychopathology Chronic stress is seen to affect the parts of the brain where memories are processed through and stored. When people feel stressed, stress hormones get over-secreted, which affects the brain. This secretion is made up of glucocorticoids, including cortisol, which are steroid hormones that the adrenal gland releases, although this can increase storage of flashbulb memories it decreases long-term potentiation (LTP). The hippocampus is important in the brain for storing certain kinds of memories and damage to the hippocampus can cause trouble in storing new memories but old memories, memories stored before the damage, are not lost. Also high cortisol levels can be tied to the deterioration of the hippocampus and decline of memory that many older adults start to experience with age. These mechanisms and processes may therefore contribute to age-related disease, or originate risk for earlier-onset disorders. For instance, extreme stress (e.g. trauma) is a requisite factor to produce stress-related disorders such as post-traumatic stress disorder.Chronic stress also shifts learning, forming a preference for habit based learning, and decreased task flexibility and spatial working memory, probably through alterations of the dopaminergic systems. Stress may also increase reward associated with food, leading to weight gain and further changes in eating habits. Stress may contribute to various disorders, such as fibromyalgia, chronic fatigue syndrome, depression, and functional somatic syndromes. Psychological concepts Eustress Selye published in year 1975 a model dividing stress into eustress and distress. Where stress enhances function (physical or mental, such as through strength training or challenging work), it may be considered eustress. Persistent stress that is not resolved through coping or adaptation, deemed distress, may lead to anxiety or withdrawal (depression) behavior. The difference between experiences that result in eustress and those that result in distress is determined by the disparity between an experience (real or imagined) and personal expectations, and resources to cope with the stress. Alarming experiences, either real or imagined, can trigger a stress response. Coping Responses to stress include adaptation, psychological coping such as stress management, anxiety, and depression. Over the long term, distress can lead to diminished health and/or increased propensity to illness; to avoid this, stress must be managed. Stress management encompasses techniques intended to equip a person with effective coping mechanisms for dealing with psychological stress, with stress defined as a persons physiological response to an internal or external stimulus that triggers the fight-or-flight response. Stress management is effective when a person uses strategies to cope with or alter stressful situations. There are several ways of coping with stress, such as controlling the source of stress or learning to set limits and to say "no" to some of the demands that bosses or family members may make. A persons capacity to tolerate the source of stress may be increased by thinking about another topic such as a hobby, listening to music, or spending time in a wilderness. A way to control stress is first dealing with what is causing the stress if it is something the individual has control over. Other methods to control stress and reduce it can be: to not procrastinate and leave tasks for the last minute, do things you like, exercise, do breathing routines, go out with friends, and take a break. Having support from a loved one also helps a lot in reducing stress.One study showed that the power of having support from a loved one, or just having social support, lowered stress in individual subjects. Painful shocks were applied to married womens ankles. In some trials women were able to hold their husbands hand, in other trials they held a strangers hand, and then held no ones hand. When the women were holding their husbands hand, the response was reduced in many brain areas. When holding the strangers hand the response was reduced a little, but not as much as when they were holding their husbands hand. Social support helps reduce stress and even more so if the support is from a loved one. Cognitive appraisal Lazarus argued that, in order for a psychosocial situation to be stressful, it must be appraised as such. He argued that cognitive processes of appraisal are central in determining whether a situation is potentially threatening, constitutes a harm/loss or a challenge, or is benign. Both personal and environmental factors influence this primary appraisal, which then triggers the selection of coping processes. Problem-focused coping is directed at managing the problem, whereas emotion-focused coping processes are directed at managing the negative emotions. Secondary appraisal refers to the evaluation of the resources available to cope with the problem, and may alter the primary appraisal. In other words, primary appraisal includes the perception of how stressful the problem is and the secondary appraisal of estimating whether one has more than or less than adequate resources to deal with the problem that affects the overall appraisal of stressfulness. Further, coping is flexible in that, in general, the individual examines the effectiveness of the coping on the situation; if it is not having the desired effect, s/he will, in general, try different strategies. Assessment Health risk factors Both negative and positive stressors can lead to stress. The intensity and duration of stress changes depending on the circumstances and emotional condition of the person with it (Arnold. E and Boggs. K. 2007). Some common categories and examples of stressors include: Sensory input such as pain, bright light, noise, temperatures, or environmental issues such as a lack of control over environmental circumstances, such as food, air and/or water quality, housing, health, freedom, or mobility. Social issues can also cause stress, such as struggles with conspecific or difficult individuals and social defeat, or relationship conflict, deception, or break ups, and major events such as birth and deaths, marriage, and divorce. Life experiences such as poverty, unemployment, clinical depression, obsessive compulsive disorder, heavy drinking, or insufficient sleep can also cause stress. Students and workers may face performance pressure stress from exams and project deadlines. Adverse experiences during development (e.g. prenatal exposure to maternal stress, poor attachment histories, sexual abuse) are thought to contribute to deficits in the maturity of an individuals stress response systems. One evaluation of the different stresses in peoples lives is the Holmes and Rahe stress scale. General adaptation syndrome Physiologists define stress as how the body reacts to a stressor - a stimulus, real or imagined. Acute stressors affect an organism in the short term; chronic stressors over the longer term. The general adaptation syndrome (GAS), developed by Hans Selye, is a profile of how organisms respond to stress; GAS is characterized by three phases: a nonspecific mobilization phase, which promotes sympathetic nervous system activity; a resistance phase, during which the organism makes efforts to cope with the threat; and an exhaustion phase, which occurs if the organism fails to overcome the threat and depletes its physiological resources. Stage 1 Alarm is the first stage, which is divided into two phases: the shock phase and the antishock phase. Shock phase: During this phase, the body can endure changes such as hypovolemia, hypoosmolarity, hyponatremia, hypochloremia, hypoglycemia—the stressor effect. This phase resembles Addisons disease. The organisms resistance to the stressor drops temporarily below the normal range and some level of shock (e.g. circulatory shock) may be experienced. Antishock phase: When the threat or stressor is identified or realized, the body starts to respond and is in a state of alarm. During this stage, the locus coeruleus and sympathetic nervous system activate the production of catecholamines including adrenaline, engaging the popularly-known fight-or-flight response. Adrenaline temporarily provides increased muscular tonus, increased blood pressure due to peripheral vasoconstriction and tachycardia, and increased glucose in blood. There is also some activation of the HPA axis, producing glucocorticoids (cortisol, aka the S-hormone or stress-hormone). Stage 2 Resistance is the second stage. During this stage, increased secretion of glucocorticoids intensifies the bodys systemic response. Glucocorticoids can increase the concentration of glucose, fat, and amino acid in blood. In high doses, one glucocorticoid, cortisol, begins to act similarly to a mineralocorticoid (aldosterone) and brings the body to a state similar to hyperaldosteronism. If the stressor persists, it becomes necessary to attempt some means of coping with the stress. The body attempts to respond to stressful stimuli, but after prolonged activation, the bodys chemical resources will be gradually depleted, leading to the final stage. Stage 3 The third stage could be either exhaustion or recovery: Recovery stage follows when the systems compensation mechanisms have successfully overcome the stressor effect (or have completely eliminated the factor which caused the stress). The high glucose, fat and amino acid levels in blood prove useful for anabolic reactions, restoration of homeostasis and regeneration of cells. Exhaustion is the alternative third stage in the GAS model. At this point, all of the bodys resources are eventually depleted and the body is unable to maintain normal function. The initial autonomic nervous system symptoms may reappear (sweating, raised heart rate, etc.). If stage three is extended, long-term damage may result (prolonged vasoconstriction results in ischemia which in turn leads to cell necrosis), as the bodys immune system becomes exhausted, and bodily functions become impaired, resulting in decompensation.The result can manifest itself in obvious illnesses, such as general trouble with the digestive system (e.g. occult bleeding, melena, constipation/obstipation), diabetes, or even cardiovascular problems (angina pectoris), along with clinical depression and other mental illnesses. History in research The current usage of the word stress arose out of Hans Selyes 1930s experiments. He started to use the term to refer not just to the agent but to the state of the organism as it responded and adapted to the environment. His theories of a universal non-specific stress response attracted great interest and contention in academic physiology and he undertook extensive research programs and publication efforts.While the work attracted continued support from advocates of psychosomatic medicine, many in experimental physiology concluded that his concepts were too vague and unmeasurable. During the 1950s, Selye turned away from the laboratory to promote his concept through popular books and lecture tours. He wrote for both non-academic physicians and, in an international bestseller entitled Stress of Life, for the general public. A broad biopsychosocial concept of stress and adaptation offered the promise of helping everyone achieve health and happiness by successfully responding to changing global challenges and the problems of modern civilization. Selye coined the term "eustress" for positive stress, by contrast to distress. He argued that all people have a natural urge and need to work for their own benefit, a message that found favor with industrialists and governments. He also coined the term stressor to refer to the causative event or stimulus, as opposed to the resulting state of stress. Selye was in contact with the tobacco industry from 1958 and they were undeclared allies in litigation and the promotion of the concept of stress, clouding the link between smoking and cancer, and portraying smoking as a "diversion", or in Selyes concept a "deviation", from environmental stress.From the late 1960s, academic psychologists started to adopt Selyes concept; they sought to quantify "life stress" by scoring "significant life events", and a large amount of research was undertaken to examine links between stress and disease of all kinds. By the late 1970s, stress had become the medical area of greatest concern to the general population, and more basic research was called for to better address the issue. There was also renewed laboratory research into the neuroendocrine, molecular, and immunological bases of stress, conceived as a useful heuristic not necessarily tied to Selyes original hypotheses. The US military became a key center of stress research, attempting to understand and reduce combat neurosis and psychiatric casualties.The psychiatric diagnosis post-traumatic stress disorder (PTSD) was coined in the mid-1970s, in part through the efforts of anti-Vietnam War activists and the Vietnam Veterans Against the War, and Chaim F. Shatan. The condition was added to the Diagnostic and Statistical Manual of Mental Disorders as posttraumatic stress disorder in 1980. PTSD was considered a severe and ongoing emotional reaction to an extreme psychological trauma, and
Stress (biology)	as such often associated with soldiers, police officers, and other emergency personnel. The stressor may involve threat to life (or viewing the actual death of someone else), serious physical injury, or threat to physical or psychological integrity. In some cases, it can also be from profound psychological and emotional trauma, apart from any actual physical harm or threat. Often, however, the two are combined. By the 1990s, "stress" had become an integral part of modern scientific understanding in all areas of physiology and human functioning, and one of the great metaphors of Western life. Focus grew on stress in certain settings, such as workplace stress, and stress management techniques were developed. The term also became a euphemism, a way of referring to problems and eliciting sympathy without being explicitly confessional, just "stressed out". It came to cover a huge range of phenomena from mild irritation to the kind of severe problems that might result in a real breakdown of health. In popular usage, almost any event or situation between these extremes could be described as stressful.The American Psychological Associations 2015 Stress In America Study found that nationwide stress is on the rise and that the three leading sources of stress were "money", "family responsibility", and "work". See also Autonomic nervous system Defense physiology HPA axis Trier social stress test Xenohormesis Stress in early childhood Weathering hypothesis References External links The American Institute of Stress "Research on Work-Related Stress", European Agency for Safety and Health at Work (EU-OSHA) Coping With Stress Stages of GAS & Evolving the Definition
Sulfhemoglobinemia	Sulfhemoglobinemia is a rare condition in which there is excess sulfhemoglobin (SulfHb) in the blood. The pigment is a greenish derivative of hemoglobin which cannot be converted back to normal, functional hemoglobin. It causes cyanosis even at low blood levels. It is a rare blood condition in which the β-pyrrole ring of the hemoglobin molecule has the ability to bind irreversibly to any substance containing a sulfur atom. When hydrogen sulfide (H2S) (or sulfide ions) and ferrous ions combine in the heme of hemoglobin, the blood is thus incapable of transport oxygen to the tissues. Presentation Symptoms include a blueish or greenish coloration of the blood (cyanosis), skin, and mucous membranes, even though a blood count test may not show any abnormalities in the blood. This discoloration is caused by greater than 5 grams per cent of deoxyhemoglobin, or 1.5 grams per cent of methemoglobin, or 0.5 grams per cent of sulfhemoglobin, all serious medical abnormalities. Causes Sulfhemoglobinemia is usually drug induced, with drugs associated with it including sulphonamides, such as sulfasalazine or sumatriptan. Another possible cause is occupational exposure to sulfur compounds.It can also be caused by phenazopyridine. Treatment The condition generally resolves itself with erythrocyte (red blood cell) turnover, although blood transfusions can be necessary in extreme cases. Notable cases On June 8, 2007, Canadian anesthesiologists Dr. Stephan Schwarz, Dr. Giuseppe Del Vicario, and Dr. Alana Flexman presented an unusual case in The Lancet. A 42-year-old male patient was brought into Vancouvers St. Pauls Hospital after falling asleep in a kneeling position, which caused compartment syndrome and a buildup of pressure in his legs. When doctors drew the mans blood prior to performing the surgery to relieve the pressure from the mans legs, they noted his blood was green. A sample of the blood was immediately sent to a lab. In this case, sulfhemoglobinemia was possibly caused by the patient taking higher-than-prescribed doses of sumatriptan. References External links Cancer Web Project Online Medical Dictionary
Localized pustular psoriasis	Localized pustular psoriasis presents as two distinct conditions that must be considered separate from generalized psoriasis, and without systemic symptoms, these two distinct varieties being pustulosis palmaris et plantaris and acrodermatitis continua.: 411 See also Psoriasis Skin lesion == References ==
Segmental arterial mediolysis	Segmental arterial mediolysis (SAM) is a rare disorder of the arteries characterized by the development of aneurysms, blood clots, narrowing of the arteries (stenoses), and blood collections (hematomas) in the affected distribution.SAM most commonly affects the arteries supplying the intestines and abdominal organs. Signs and Symptoms Varies depending on the location of the affected blood vessels. Gastrointestinal System: Acute abdominal pain (most common) Flank pain Nausea Vomiting Diarrhea Bloody stools Back painNervous System Headache StrokeThe most severe signs occur if an aneurysm ruptures potentially resulting in: Shock Loss of consciousness Bleeding into the abdominal cavity Bleeding into the brain Mechanism The middle layer of an artery, called the media, made of smooth muscle is damaged. Mediolysis occurs when the smooth muscle cells in the area of damage are destroyed. Small gaps are formed in the wall of the artery which then fill with blood. Gaps create weakness in the wall of the artery, allowing increasing pressure from blood to expand the gaps resulting in an aneurysm. Aneurysms have potential for rupture. Diagnosis Often Segmental Arterial Mediolysis is diagnosed after clinical presentation with symptoms as above followed by CT angiogram or MRI demonstrating aneurysm(s). The gold standard method for confirming the diagnosis is surgical resection of the affected area of blood vessel followed by histologic investigation under a microscope. Segmental Arterial Mediolysis must be differentiated from fibromuscular dysplasia, atherosclerosis, and other systemic vasculidites including polyarteritis nodosa, Takayasus arteritis, Behcets disease, cystic medial necrosis, and cystic adventitial artery disease. Treatment Patients presenting with bleeding into the abdominal cavity require possible blood transfusions and emergent intervention with coil embolization via catheter angiography. Patients without active bleeding, but diagnosed aneurysms should have strict blood pressure control with antihypertensive drugs to decrease the risk of aneurysm rupture. Epidemiology Since it was first reported in 1976 there have been 101 documented cases of Segmental Arterial Mediolysis. Although typically seen in older patients with an average age of 57 years old, it can affect patients of any age and does not favor one gender or the other. == References ==
Hydrosalpinx	A hydrosalpinx is a condition that occurs when a Fallopian tube is blocked and fills with serous or clear fluid near the ovary (distal to the uterus). The blocked tube may become substantially distended giving the tube a characteristic sausage-like or retort-like shape. The condition is often bilateral and the affected tubes may reach several centimeters in diameter. The blocked tubes cause infertility. A Fallopian tube filled with blood is a hematosalpinx, and with pus a pyosalpinx.Hydrosalpinx is a composite of the Greek words ὕδωρ (hydōr – "water") and σάλπιγξ (sálpinx – "trumpet"); its plural is hydrosalpinges. Signs and symptoms Symptoms can vary. Some patients have lower often recurring abdominal pain or pelvic pain, while others may be asymptomatic. As tubal function is impeded, infertility is a common symptom. Patients who are not trying to get pregnant and have no pain, may go undetected. Endometriosis, ruptured appendicitis, and abdominal surgery sometimes are associated with the problem. As a reaction to injury, the body rushes inflammatory cells into the area, and inflammation and later healing result in loss of the fimbria and closure of the tube. These infections usually affect both Fallopian tubes, and although a hydrosalpinx can be one-sided, the other tube on the opposite side is often abnormal. By the time it is detected, the tubal fluid usually is sterile, and does not contain an active infection. (Not symptoms) Cause The major cause for distal tubal occlusion is pelvic inflammatory disease, usually as a consequence of an ascending infection by chlamydia or gonorrhea. However, not all pelvic infections will cause distal tubal occlusion. Tubal tuberculosis is an uncommon cause of hydrosalpinx formation.While the cilia of the inner lining (endosalpinx) of the Fallopian tube beat towards the uterus, tubal fluid is normally discharged via the fimbriated end into the peritoneal cavity from where it is cleared. If the fimbriated end of the tube becomes agglutinated, the resulting obstruction does not allow the tubal fluid to pass; it accumulates and reverts its flow downstream, into the uterus, or production is curtailed by damage to the endosalpinx. This tube then is unable to participate in the reproductive process: sperm cannot pass, the egg is not picked up, and fertilization does not take place.Other causes of distal tubal occlusion include adhesion formation from surgery, endometriosis, and cancer of the tube, ovary or other surrounding organs. A hematosalpinx is most commonly associated with an ectopic pregnancy. A pyosalpinx is typically seen in a more acute stage of pelvic inflammatory disease and may be part of a tubo-ovarian abscess. Tubal phimosis refers to a situation where the tubal end is partially occluded, in this case fertility is impeded, and the risk of an ectopic pregnancy is increased. Diagnosis Hydrosalpinx may be diagnosed using ultrasonography as the fluid filled elongated and distended tubes display their typical echolucent pattern. However, a small hydrosalpinx may be missed by sonography. During an infertility work-up a hysterosalpingogram, an X-ray procedure that uses a contrast agent to image the Fallopian tubes, shows the retort-like shape of the distended tubes and the absence of spillage of the dye into the peritoneum. If, however, there is a tubal occlusion at the utero-tubal junction, a hydrosalpinx may go undetected. When a hydrosalpinx is detected by a hysterosalpingogram it is prudent to administer antibiotics to reduce the risk of reactivation of an inflammatory process. When laparoscopy is performed, the surgeon may note the distended tubes, identify the occlusion, and may also find associated adhesions affecting the pelvic organs. Laparoscopy not only allows for the diagnosis of hydrosalpinx, but also presents a platform for intervention (see management). Prevention As pelvic inflammatory disease is the major cause of hydrosalpinx formation, steps to reduce sexually transmitted disease will reduce incidence of hydrosalpinx. Also, as hydrosalpinx is a sequel to a pelvic infection, adequate and early antibiotic treatment of a pelvic infection is called for. Management For most of the past century patients with tubal infertility due to hydrosalpinx underwent tubal corrective surgery to open up the distally occluded end of the tubes (salpingostomy) and remove adhesions (adhesiolysis). Unfortunately, pregnancy rates tended to be low as the infection process often had permanently damaged the tubes, and in many cases hydrosalpinges and adhesions formed again. Further, ectopic pregnancy is a typical complication. Surgical interventions can be done by laparotomy or laparoscopy. Non-infertile patients who suffer from severe chronic pain due to hydrosalpinx formation that is not relieved by pain management may consider surgical removal of the affected tubes (salpingectomy) or even a hysterectomy with removal of the tubes, possibly ovaries. IVF Among the main causes for female infertility, tubal factors account for 25-35%. In particular, hydrosalpinx is found in 10-30% of couples with infertility; actually, this condition may impair fertility and IVF outcomes.With the advent of IVF which bypasses the need for tubal function a more successful treatment approach has become available for women who want to conceive. IVF has now become the major treatment for women with hydrosalpinx to achieve a pregnancy. Several studies have shown that IVF patients with untreated hydrosalpinx have lower conception rates than controls and it has been speculated that the tubal fluid that enters the endometrial cavity alters the local environment or affects the embryo in a detrimental way. Indeed, the presence of hydrosalpinx prior to IVF treatments, negatively affects pregnancy rates and increases the risk for spontaneous miscarriage. Even if the exact mechanism remains unclear, these effects could be ascribed to a combination of mechanical effects of hydrosalpinx fluid, toxic effects on the embryo and altered endometrial receptivity Thus, many specialists advocate that prior to an IVF attempt, the hydrosalpinx should be removed. However, the benefits seem to be higher when the hydrosalpinx is bilateral, visible on ultrasound, or both. Salpingectomy removes the chronically infected hydrosalpinx, decreasing the risk of infection after oocyte retrieval and increasing the accessibility to the ovary; anyway, it is a surgical procedure and it could also affect the ovarian blood flow. History Regnier de Graaf may have been the first to understand basic tubal function, describe hydrosalpinx, and link the development of hydrosalpinx with female infertility. The usually infectious cause of the process was well known to physicians by the end of the nineteenth century. With the introduction of hysterosalpingography (1914) and tubal insufflation (1920) its non-surgical diagnosis became possible. Surgery was gradually displaced by IVF as the main treatment for tubal infertility after the birth of Louise Brown in 1978. References External links fact sheet, ASRM Medpix pictures of hydrosalpinx
Hydrolethalus syndrome	Hydrolethalus syndrome (HLS) is a rare genetic disorder that causes improper fetal development, resulting in birth defects and, most commonly, stillbirth.HLS is associated with HYLS1 mutations. The gene encoding HYLS1 is responsible for proper cilial development within the human body. Cilia are microscopic projections that allow sensory input and signalling output within cells, as well as cell motility. Dysfunction results in a range of abnormalities that are often the result of improper cell signalling. A variant form, HLS2, with additional mutations to the KIF7 gene, is less common. KIF7 also ensures correct cilia formation and function, specifically cilia stability and length.Hydrolethalus syndrome (HLS) was first mistakenly identified in Finland, during a study on Meckel syndrome. Like HLS, Meckel syndrome presents with severe physiological abnormalities, namely disruptions to the central nervous system and the presence of extra fingers or toes (polydactyly). HLS can be distinguished from Meckel syndrome by analysing kidney function, which is dysfunctional in Meckel syndrome as a result of cyst formation. Signs and symptoms HLS presents itself as various, lethal developmental abnormalities, which often result in either premature stillbirth or death shortly after birth. Rare cases of children born with HLS surviving for several months have been noted. A characteristic abnormality of HLS is an absence of brain tissue and midline structures, with the presence of excess brain fluid (hydrocephalus) as a result of abnormal development of the central nervous system. Other common defects include incomplete lung development, heart defects, a cleft lip or palate, polydactyly, and an abnormally small jaw. Stillbirth and an excess of amniotic fluid (polyhydramnios) are common during pregnancy with a HLS-affected foetus, with cases of up to 8 litres cited compared to the normal 1 litre. Less common symptoms such as abnormally small eyes and a broad nose are also possible. Cause Genetic HLS is caused by a genetic missense mutation of the HYLS1 gene, encoding for Hydrolethalus syndrome protein 1, on chromosome 11; a single base change to the amino acid sequence for HYLS1 in exon 6 involves the replacement of aspartic acid 211 with glycine (D211G) in the polypeptide chain. Exon 6 is the only protein coding exon in HYLS1; proper functioning of exons 1-5 ensures regulation and expression of the entire protein. HLS is an autosomal recessive syndrome; development is only possible if both parents carry the defective gene, and in that instance, the risk of the foetus developing the syndrome is 25%. HLS is a member of the Finnish disease heritage, with incidences more common in Finland than the rest of the world; roughly 1 in 20,000 developing foetuses are affected in Finland. Rare cases in other regions have also been documented, often with less severe phenotypes as a result of allele variability across countries, allowing survival of affected offspring for up to several months. Individuals of Finnish descent are advised to undergo genetic testing before attempting to conceive.Prior to the discovery of HLS, the HYLS1 gene was unknown, and similar genes within humans have not been identified. Orthologs, genes in other species with common ancestral heritage, have been examined to explain the pathophysiology of HLS; a similar gene within the roundworm, Caenorhabditis elegans, is responsible for the formation of cilia. Current hypotheses place a dysfunction of cilia as the main cause of HLS defects arising from the HYLS1 mutation in humans. Differences between wild type and mutant HYLS1 have been clearly observed; the wild type form is localised to the cytoplasm, while the mutant form is localised to the nucleus and forms small clusters, suggesting that the mutant gene disrupts cellular localisation. The protein encoded by the HYLS1 mutant form is unable to carry out essential targeting of centrioles to the plasma membrane, disrupting ciliary function, which results in ciliopathy. As cilia are located in almost all cells throughout the body, cilial dysfunction causes developmental defects in a range of organs and thus the phenotype of HLS can vary greatly, though brain malformation and polydactyly are most commonly observed. Environmental Currently, no environmental factors are known to increase the likelihood of HLS development or progression; HLS is caused only by genetic abnormalities. Pathophysiology The pathophysiology of HLS is abnormal cilia development arising from the inability of the mutated HYLS1 gene to correctly target centrioles to the plasma membrane. Specifically, transition fibres within the transition zone, at the base of the axoneme and adjoining to the plasma membrane, lack proper development. As these structures form the cilial gate, improper development results in a loss of selectivity for protein entry into the ciliary compartment. Variations and related pathologies Mutations in KIF7 have also been noted in patients that present a similar phenotype to HLS and the characteristic HYLS1 A to G transformation; homozygous deletion of the KIF7 gene causes a variant form of HLS, HLS2. KIF7 encodes a structural factor vital to cilial transport, and is also implicated in other developmental disorders, such as Joubert syndrome (JS). Additionally, mutations in HYLS1 are no longer explicitly connected to HLS in humans. Homozygous mutations removing the stop codon in exon 4 of HYLS1 result in a different genomic sequence disruption to the missense mutation of HLS, and phenotypically present as JS. The ‘molar tooth sign’ of the brain, an anomaly in which cerebellar volume is reduced but cerebellar shape is retained, resembles the molar tooth and is used to identify JS. JS presents with mutations in more than 30 genes, whilst the HYLS1 mutation is the sole cause of HLS, but is also present in the HLS2 variant form with the mutated KIF7 gene. Diagnosis HLS can be readily diagnosed during pregnancy through the use of ultrasound, which will often reveal hydrocephaly and an abnormal structure of the brain. Precise examination via ultrasound or at birth is necessary to rule out Meckel syndrome, Trisomy 13, or Smith–Lemli–Opitz syndrome, which present with similar physiological defects. HLS can be detected at the end of the first trimester, approximately 13 weeks gestation. Treatment No cure or treatment option for individuals with HLS currently exist. Due to the severity of the foetal defects and the poor prognosis for those with HLS, the pregnancy is often terminated. Certain prevention can only be achieved by avoiding conception if genetic testing indicates both prospective parents as carriers of the defective HYLS1 gene. See also •HYLS1 References == External links ==
Urethral caruncle	A urethral caruncle is a benign cutaneous condition characterized by distal urethral lesions that are most commonly found in post-menopausal women. They appear red, and can be various sizes. They can have the appearance of a tumor. These epidermal growths are found around the posterior portion of the urethral meatus. They can bleed and occasionally cause dysuria and dyspareunia. The caruncles can be removed by surgery, electric cauterization and then with suture repair. Pathology studies are necessary to distinguish carcinoma of the urethra from urethral caruncles. Caruncles can grow back in some instances. Urethral caruncles can accompany the skin changes related to lowered estrogen levels. They can become a source of chronic hematuria, infection, and urethritis. See also Unilateral palmoplantar verrucous nevus References == External links ==
Respiratory failure	Respiratory failure results from inadequate gas exchange by the respiratory system, meaning that the arterial oxygen, carbon dioxide, or both cannot be kept at normal levels. A drop in the oxygen carried in the blood is known as hypoxemia; a rise in arterial carbon dioxide levels is called hypercapnia. Respiratory failure is classified as either Type 1 or Type 2, based on whether there is a high carbon dioxide level, and can be acute or chronic. In clinical trials, the definition of respiratory failure usually includes increased respiratory rate, abnormal blood gases (hypoxemia, hypercapnia, or both), and evidence of increased work of breathing. Respiratory failure causes an altered mental status due to ischemia in the brain. The typical partial pressure reference values are oxygen Pa O2 more than 80 mmHg (11 kPa) and carbon dioxide Pa CO2 less than 45 mmHg (6.0 kPa). Cause Several types of conditions can potentially result in respiratory failure: Conditions that reduce the flow of air into and out of the lungs, including physical obstruction by foreign bodies or masses and reduced breathing due to drugs or changes to the chest. Conditions that impair the lungs blood supply. These include thromboembolic conditions and conditions that reduce the output of the right heart, such as right heart failure and some myocardial infarctions. Conditions that limit the ability of the lung tissue to exchange oxygen and carbon dioxide between the blood and the air within the lungs. Any disease which can damage the lung tissue can fit into this category. The most common causes are (in no particular order) infections, interstitial lung disease, and pulmonary oedema. Diagnosis Type 1 Type 1 respiratory failure is defined as a low level of oxygen in the blood (hypoxemia) with either a standard (normocapnia) or low (hypocapnia) level of carbon dioxide (PaCO2) but not an increased level (hypercapnia). It is typically caused by a ventilation/perfusion (V/Q) mismatch; the volume of air flowing in and out of the lungs is not matched with the flow of blood to the lungs. The fundamental defect in type 1 respiratory failure is a failure of oxygenation characterized by: This type of respiratory failure is caused by conditions that affect oxygenation, such as: Low ambient oxygen (e.g. at high altitude) Ventilation-perfusion mismatch (parts of the lung receive oxygen but not enough blood to absorb it, e.g. pulmonary embolism) Alveolar hypoventilation (decreased minute volume due to reduced respiratory muscle activity, e.g. in acute neuromuscular disease); this form can also cause type 2 respiratory failure if severe. Diffusion problem (oxygen cannot enter the capillaries due to parenchymal disease, e.g. in pneumonia or ARDS) Shunt (oxygenated blood mixes with non-oxygenated blood from the venous system, e.g. right to left shunt) Type 2 Hypoxemia (PaO2 <8kPa or normal) with hypercapnia (PaCO2 >6.0kPa). The basic defect in type 2 respiratory failure is characterized by: Type 2 respiratory failure is caused by inadequate alveolar ventilation; both oxygen and carbon dioxide are affected. Defined as the buildup of carbon dioxide levels (PaCO2) that has been generated by the body but cannot be eliminated. The underlying causes include: Increased airways resistance (chronic obstructive pulmonary disease, asthma, suffocation) Reduced breathing effort (drug effects, brain stem lesion, extreme obesity) A decrease in the area of the lung available for gas exchange (such as in chronic bronchitis) Neuromuscular problems (Guillain–Barré syndrome, motor neuron disease) Deformed (kyphoscoliosis), rigid (ankylosing spondylitis), or flail chest. Type 3 Type 3 respiratory failure results from lung atelectasis. Because atelectasis occurs so commonly in the perioperative period, this form is also called perioperative respiratory failure. After general anesthesia, decreases in functional residual capacity leads to collapse of dependent lung units. Type 4 Type 4 respiratory failure results from hypoperfusion of respiratory muscles as in patients in shock. Patients in shock often experience respiratory distress due to pulmonary edema (e.g., in cardiogenic shock). Lactic acidosis and anemia can also result in type 4 respiratory failure. However, type 1 and 2 are the most widely accepted. Treatment Treatment of the underlying cause is required, if possible. The treatment of acute respiratory failure may involve medication such as bronchodilators (for airways disease), antibiotics (for infections), glucocorticoids (for numerous causes), diuretics (for pulmonary oedema), amongst others. Respiratory failure resulting from an overdose of opioids may be treated with the antidote naloxone. In contrast, most benzodiazepine overdose does not benefit from its antidote, flumazenil. Respiratory therapy/respiratory physiotherapy may be beneficial in some cases of respiratory failure.Type 1 respiratory failure may require oxygen therapy to achieve adequate oxygen saturation. Lack of oxygen response may indicate other modalities such as heated humidified high-flow therapy, continuous positive airway pressure or (if severe) endotracheal intubation and mechanical ventilation. .Type 2 respiratory failure often requires non-invasive ventilation (NIV) unless medical therapy can improve the situation. Mechanical ventilation is sometimes indicated immediately or otherwise if NIV fails. Respiratory stimulants such as doxapram are now rarely used.There is tentative evidence that in those with respiratory failure identified before arrival in hospital, continuous positive airway pressure can be helpful when started before conveying to hospital. See also Ventilation/perfusion ratio Pulmonary shunt References External links MedlinePlus: Respiratory Failure
Subepithelial mucinous corneal dystrophy	Subepithelial mucinous corneal dystrophy (SMCD) is a rare form of corneal dystrophy. It was first described in 1993 by Feder et al. Anterior to Bowman layer, deposits of glycosaminoglycan were detected and identified as chondroitin-4-sulfate and dermatan sulfate. References == External links ==
Crome syndrome	Crome syndrome is a rare disease defined by various symptoms, including epilepsy, intellectual disability, eye and kidney problems. It usually causes death in 4 to 8 months. History In 1963, a doctor studied two female infants who showed symptoms of intellectual disability, congenital cataracts, epileptic seizures and small stature. The two girls died at the age of 4 and 8 months. The autopsy revealed renal tubular necrosis and encephalopathy. References == External links ==
Cerebral hypoxia	Cerebral hypoxia is a form of hypoxia (reduced supply of oxygen), specifically involving the brain; when the brain is completely deprived of oxygen, it is called cerebral anoxia. There are four categories of cerebral hypoxia; they are, in order of increasing severity: diffuse cerebral hypoxia (DCH), focal cerebral ischemia, cerebral infarction, and global cerebral ischemia. Prolonged hypoxia induces neuronal cell death via apoptosis, resulting in a hypoxic brain injury.Cases of total oxygen deprivation are termed "anoxia", which can be hypoxic in origin (reduced oxygen availability) or ischemic in origin (oxygen deprivation due to a disruption in blood flow). Brain injury as a result of oxygen deprivation either due to hypoxic or anoxic mechanisms are generally termed hypoxic/anoxic injuries (HAI). Hypoxic ischemic encephalopathy (HIE) is a condition that occurs when the entire brain is deprived of an adequate oxygen supply, but the deprivation is not total. While HIE is associated in most cases with oxygen deprivation in the neonate due to birth asphyxia, it can occur in all age groups, and is often a complication of cardiac arrest. Signs and symptoms The brain requires approximately 3.3 ml of oxygen per 100 g of brain tissue per minute. Initially the body responds to lowered blood oxygen by redirecting blood to the brain and increasing cerebral blood flow. Blood flow may increase up to twice the normal flow but no more. If the increased blood flow is sufficient to supply the brains oxygen needs then no symptoms will result.However, if blood flow cannot be increased or if doubled blood flow does not correct the problem, symptoms of cerebral hypoxia will begin to appear. Mild symptoms include difficulties with complex learning tasks and reductions in short-term memory. If oxygen deprivation continues, cognitive disturbances, and decreased motor control will result. The skin may also appear bluish (cyanosis) and heart rate increases. Continued oxygen deprivation results in fainting, long-term loss of consciousness, coma, seizures, cessation of brain stem reflexes, and brain death.Objective measurements of the severity of cerebral hypoxia depend on the cause. Blood oxygen saturation may be used for hypoxic hypoxia, but is generally meaningless in other forms of hypoxia. In hypoxic hypoxia 95–100% saturation is considered normal; 91–94% is considered mild and 86–90% moderate. Anything below 86% is considered severe.Cerebral hypoxia refers to oxygen levels in brain tissue, not blood. Blood oxygenation will usually appear normal in cases of hypemic, ischemic, and hystoxic cerebral hypoxia. Even in hypoxic hypoxia blood measures are only an approximate guide; the oxygen level in the brain tissue will depend on how the body deals with the reduced oxygen content of the blood. Causes Cerebral hypoxia can be caused by any event that severely interferes with the brains ability to receive or process oxygen. This event may be internal or external to the body. Mild and moderate forms of cerebral hypoxia may be caused by various diseases that interfere with breathing and blood oxygenation. Severe asthma and various sorts of anemia can cause some degree of diffuse cerebral hypoxia. Other causes include status epilepticus, work in nitrogen-rich environments, ascent from a deep-water dive, flying at high altitudes in an unpressurized cabin without supplemental oxygen, and intense exercise at high altitudes prior to acclimatization. Severe cerebral hypoxia and anoxia is usually caused by traumatic events such as choking, drowning, strangulation, smoke inhalation, drug overdoses, crushing of the trachea, status asthmaticus, and shock. It is also recreationally self-induced in the fainting game and in erotic asphyxiation. Transient ischemic attack (TIA), is often referred to as a "mini-stroke". The American Heart Association and American Stroke Association (AHA/ASA) refined the definition of transient ischemic attack. TIA is now defined as a transient episode of neurologic dysfunction caused by focal brain, spinal cord, or retinal ischemia, without acute infarction. The symptoms of a TIA can resolve within a few minutes, unlike a stroke. TIAs share the same underlying etiology as strokes; a disruption of cerebral blood flow. TIAs and strokes present with the same symptoms such as contralateral paralysis (opposite side of body from affected brain hemisphere), or sudden weakness or numbness. A TIA may cause sudden dimming or loss of vision, aphasia, slurred speech, and mental confusion. The symptoms of a TIA typically resolve within 24 hours, unlike a stroke. Brain injury may still occur in a TIA lasting only a few minutes. Having a TIA is a risk factor for eventually having a stroke. Silent stroke is a stroke which does not have any outward symptoms, and the patient is typically unaware they have had a stroke. Despite its lack of identifiable symptoms, a silent stroke still causes brain damage and places the patient at increased risk for a major stroke in the future. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or hemorrhages. Silent strokes typically cause lesions which are detected via the use of neuroimaging such as fMRI. The risk of silent stroke increases with age but may also affect younger adults. Women appear to be at increased risk for silent stroke, with hypertension and current cigarette smoking being predisposing factors. Pre- and postnatal Hypoxic-anoxic events may affect the fetus at various stages of fetal development, during labor and delivery and in the postnatal period. Sometimes, even an infant that is still in the womb may exhibit signs of HIE or other hypoxic ischemic injury. Fetal distress being one of the most common signs of HIE or other oxygen-depriving event. Other problems during pregnancy may include preeclampsia, maternal diabetes with vascular disease, congenital fetal infections, substance/alcohol use, severe fetal anemia, cardiac disease, lung malformations, or problems with blood flow to the placenta. Problems during labor and delivery can include umbilical cord occlusion, torsion or prolapse, rupture of the placenta or uterus, excessive bleeding from the placenta, abnormal fetal position such as the breech position, prolonged late stages of labor, or very low blood pressure in the mother. Problems after delivery can include severe prematurity, severe lung or heart disease, serious infections, trauma to the brain or skull, congenital malformations of the brain or very low blood pressure in the baby and due to suffocation in cases of Münchausen syndrome by proxy.The severity of a neonatal hypoxic-ischaemic brain injury may be assessed using Sarnat staging, which is based on clinical presentation and EEG findings, and also using MRI. Signs and symptoms of HIE may include: Low Apgar scores, <5 at 5 minutes and 10 minutes. Floppiness, or unreactive to sights or sounds, or more tense and agitated. Low heart rate. Low blood pressure. Poor muscle tone and absent reflexes. Weak breathing, no breathing at all, or rapid breathing. Need for resuscitation after delivery. Weak cry. Bluish or pale skin color. Excessive acid in the blood. Seizures or abnormal movements. Problems feeding Mechanism Details of the mechanism of damage from cerebral hypoxia, along with anoxic depolarization, can be found here: Mechanism of anoxic depolarization in the brain Diagnosis Classification Cerebral hypoxia is typically grouped into four categories depending on the severity and location of the brains oxygen deprivation: Diffuse cerebral hypoxia – A mild to moderate impairment of brain function due to low oxygen levels in the blood. Focal cerebral ischemia – A stroke occurring in a localized area that can either be acute or transient. This may be due to a variety of medical conditions such as an aneurysm that causes a hemorrhagic stroke, or an occlusion occurring in the affected blood vessels due to a thrombus (thrombotic stroke) or embolus (embolic stroke). Focal cerebral ischemia constitutes a large majority of the clinical cases in stroke pathology with the infarct usually occurring in the middle cerebral artery (MCA). Global cerebral ischemia – A complete stoppage of blood flow to the brain. Cerebral infarction – A "stroke", caused by complete oxygen deprivation due to an interference in cerebral blood flow which affects multiple areas of the brain.Cerebral hypoxia can also be classified by the cause of the reduced brain oxygen: Hypoxic hypoxia – Limited oxygen in the environment causes reduced brain function. Divers, aviators, mountain climbers, and fire fighters are all at risk for this kind of cerebral hypoxia. The term also includes oxygen deprivation due to obstructions in the lungs. Choking, strangulation, the crushing of the windpipe all cause this sort of hypoxia. Severe asthmatics may also experience symptoms of hypoxic hypoxia. Hypemic hypoxia – Reduced brain function is caused by inadequate oxygen in the blood despite adequate environmental oxygen. Anemia and carbon monoxide poisoning are common causes of hypemic hypoxia. Ischemic hypoxia ( or "stagnant hypoxia") – Reduced brain oxygen is caused by inadequate blood flow to the brain. Stroke, shock, cardiac arrest and heart attack may cause stagnant hypoxia. Ischemic hypoxia can also be created by pressure on the brain. Cerebral edema, brain hemorrhages and hydrocephalus exert pressure on brain tissue and impede their absorption of oxygen. Histotoxic hypoxia – Oxygen is present in brain tissue but cannot be metabolized by the brain tissue. Cyanide poisoning is a well-known example. Treatment For newborn infants starved of oxygen during birth there is now evidence that hypothermia therapy for neonatal encephalopathy applied within 6 hours of cerebral hypoxia effectively improves survival and neurological outcome. In adults, however, the evidence is less convincing and the first goal of treatment is to restore oxygen to the brain. The method of restoration depends on the cause of the hypoxia. For mild-to-moderate cases of hypoxia, removal of the cause of hypoxia may be sufficient. Inhaled oxygen may also be provided. In severe cases treatment may also involve life support and damage control measures. A deep coma will interfere with the bodys breathing reflexes even after the initial cause of hypoxia has been dealt with; mechanical ventilation may be required. Additionally, severe cerebral hypoxia causes an elevated heart rate, and in extreme cases the heart may tire and stop pumping. CPR, defibrilation, epinephrine, and atropine may all be tried in an effort to get the heart to resume pumping. Severe cerebral hypoxia can also cause seizures, which put the patient at risk of self-injury, and various anti-convulsant drugs may need to be administered before treatment. There has long been a debate over whether newborn infants with cerebral hypoxia should be resuscitated with 100% oxygen or normal air. It has been demonstrated that high concentrations of oxygen lead to generation of oxygen free radicals, which have a role in reperfusion injury after asphyxia. Research by Ola Didrik Saugstad and others led to new international guidelines on newborn resuscitation in 2010, recommending the use of normal air instead of 100% oxygen.Brain damage can occur both during and after oxygen deprivation. During oxygen deprivation, cells die due to an increasing acidity in the brain tissue (acidosis). Additionally, during the period of oxygen deprivation, materials that can easily create free radicals build up. When oxygen enters the tissue these materials interact with oxygen to create high levels of oxidants. Oxidants interfere with the normal brain chemistry and cause further damage (this is known as "reperfusion injury"). Techniques for preventing damage to brain cells are an area of ongoing research. Hypothermia therapy for neonatal encephalopathy is the only evidence-supported therapy, but antioxidant drugs, control of blood glucose levels, and hemodilution (thinning of the blood) coupled with drug-induced hypertension are some treatment techniques currently under investigation. Hyperbaric oxygen therapy is being evaluated with the reduction in total and myocardial creatine phosphokinase levels showing a possible reduction in the overall systemic inflammatory process.In severe cases it is extremely important to act quickly. Brain cells are very sensitive to reduced oxygen levels. Once deprived of oxygen they will begin to die off within five minutes. Prognosis Mild and moderate cerebral hypoxia generally has no impact beyond the episode of hypoxia; on the other hand, the outcome of severe cerebral hypoxia will depend on the success of damage control, amount of brain tissue deprived of oxygen, and the speed with which oxygen was restored. If cerebral hypoxia was localized to a specific part of the brain, brain damage will be localized to that region. A general consequence may be epilepsy. The long-term effects will depend on the purpose of that portion of the brain. Damage to the Brocas area and the Wernickes area of the brain (left side) typically causes problems with speech and language. Damage to the right side of the brain may interfere with the ability to express emotions or interpret what one sees. Damage on either side can cause paralysis of the opposite side of the body. The effects of certain kinds of severe generalized hypoxias may take time to develop. For example, the long-term effects of serious carbon monoxide poisoning usually may take several weeks to appear. Recent research suggests this may be due to an autoimmune response caused by carbon monoxide-induced changes in the myelin sheath surrounding neurons.If hypoxia results in coma, the length of unconsciousness is often indicative of long-term damage. In some cases coma can give the brain an opportunity to heal and regenerate, but, in general, the longer a coma, the greater the likelihood that the person will remain in a vegetative state until death. Even if the patient wakes up, brain damage is likely to be significant enough to prevent a return to normal functioning. Long-term comas can have a significant impact on a patients family. Families of coma patients often have idealized images of the outcome based on Hollywood movie depictions of coma. Adjusting to the realities of ventilators, feeding tubes, bedsores, and muscle wasting may be difficult. Treatment decisions often involve complex ethical choices and can strain family dynamics. See also Altitude sickness Choking game Hypothermia cap Space exposure Ulegyria References External links Hypoxia experiment
Pseudomelanoma	Pseudomelanoma (also known as a "recurrent melanocytic nevus", and "recurrent nevus") is a cutaneous condition in which melanotic skin lesions clinically resemble a superficial spreading melanoma at the site of a recent shave removal of a melanocytic nevus.: 689 Problem with the recurrent nevus The melanocytes left behind in the wound regrow in an abnormal pattern. Rather than the even and regular lace like network, the pigments tends to grow in streaks of varying width within the scar. This is often accompanied by scarring, inflammation, and blood vessel changes – giving both the clinical and histologic impression of a melanoma or a severe dysplastic nevus. When the patient is reexamined years later without the assistance of the original biopsy report, the physician will often require the removal of the scar with the recurrent nevus to assure that a melanoma is not missed. Saucerization biopsy Also known as "scoop", "scallop", or "shave" excisional biopsy, or "shave excision". A trend has occurred in dermatology over the last 10 years with the advocacy of a deep shave excision of a pigmented lesion An author published the result of this method and advocated it as better than standard excision and less time-consuming. The added economic benefit is that many surgeons bill the procedure as an excision, rather than a shave biopsy. This save the added time for hemostasis, instruments, and suture cost. The great disadvantage, seen years later is the numerous scallop scars, and a very difficult to deal with lesions called a "recurrent melanocytic nevus". What has happened is that many "shave" excisions does not adequately penetrate the dermis or subcutaneous fat enough to include the entire melanocytic lesion. Residual melanocytes regrow into the scar. The combination of scarring, inflammation, blood vessels, and atypical pigmented streaks seen in these recurrent nevus gives the perfect dermatoscopic picture of a melanoma. When a second physicians re-examine the patient, he or she has no choice but to recommend the reexcision of the scar. If one does not have access to the original pathology report, it is impossible to tell a recurring nevus from a severely dysplastic nevus or a melanoma. As the procedure is widely practiced, it is not unusual to see a patient with dozens of scallop scars, with as many as 20% of the scars showing residual pigmentation. The second issue with the shave excision is fat herniation, iatrogenic anetoderma, and hypertrophic scarring. As the deep shave excision either completely remove the full thickness of the dermis or greatly diminishing the dermal thickness, subcutaneous fat can herniate outward or pucker the skin out in an unattractive way. In areas prone to friction, this can result in pain, itching, or hypertrophic scarring. See also Balloon cell nevus Skin lesion List of cutaneous conditions References == External links ==
Radiation proctitis	Radiation proctitis or radiation proctopathy is condition characterized by damage to the rectum after exposure to x-rays or other ionizing radiation as a part of radiation therapy. Radiation proctopathy may occur as acute inflammation called "acute radiation proctitis" (and the related radiation colitis) or with chronic changes characterized by radiation associated vascular ectasiae (RAVE) and chronic radiation proctopathy. Radiation proctitis most commonly occurs after pelvic radiation treatment for cancers such as cervical cancer, prostate cancer, bladder cancer, and rectal cancer. RAVE and chronic radiation proctopathy involves the lower intestine, primarily the sigmoid colon and the rectum, and was previously called chronic radiation proctitis, pelvic radiation disease and radiation enteropathy. Signs and symptoms Acute radiation proctopathy often causes pelvic pain, diarrhea, urgency, and the urge to defecate despite having an empty colon (tenesmus). Hematochezia and fecal incontinence may occur, but are less common. Chronic radiation damage to the rectum (>3 months) may cause rectal bleeding, incontinence, or a change in bowel habits secondary. Severe cases may lead to with strictures or fistulae formation. Chronic radiation proctopathy can present at a median time of 8-12 months following radiation therapy. Histopathology Acute radiation proctopathy occurs due to direct damage of the lining (epithelium) of the colon. Rectal biopsies of acute radiation proctopathy show superficial depletion of epithelial cells and acute inflammatory cells located in the lamina propria. By contrast, rectal biopsies of RAVE and chronic radiation proctopathy demonstrates ischemic endarteritis of the submucosal arterioles, submucosal fibrosis, and neovascularization. Diagnosis Where chronic radiation proctopathy or RAVE is suspected, a thorough evaluation of symptoms is essential. Evaluation should include an assessment of risk factors for alternate causes of proctitis, such as C. difficile colitis, NSAID use, and travel history. Symptoms such as diarrhea and painful defecation need to be systematically investigated and the underlying causes each carefully treated. Testing for parasitic infections (amebiasis, giardiasis) and sexually transmitted infections (Neisseria gonorrhoeae and herpes simplex virus) should be considered. The location of radiation treatment is important, as radiation directed at regions of the body other than the pelvis (eg brain, chest, etc) should not prompt consideration of radiation proctopathy.Endoscopy is the mainstay of diagnosis for radiation damage to the rectum, with either colonoscopy or flexible sigmoidoscopy. RAVE is usually recognized by the macroscopic appearances on endoscopy characterized by vascular ectasias. Mucosal biopsy may aid in ruling out alternate causes of proctitis, but is not routinely necessary and may increase the risk of fistulae development. Telangiectasias are characteristic and prone to bleeding. Additional endoscopic findings may include pallor (pale appearance), edema, and friability of the mucosa. Classification Radiation proctitis can occur a few weeks after treatment, or after several months or years: Acute radiation proctitis — symptoms occur in the first 3 months after therapy. These symptoms include diarrhea and the urgent need to defecate. Radiation associated vascular ectasias (RAVE) and Chronic radiation proctopathy — previously known as "chronic radiation proctitis" occur 3-6 months after the initial exposure. RAVE is characterized by rectal bleeding, chronic blood loss and anemia. Chronic radiation proctopathy is characterized by urgency, change in stool caliber and consistency and increased mucus. Severe cases may present with fistulas and strictures which are rare. Treatment Several methods have been studied in attempts to lessen the effects of radiation proctitis. Acute radiation proctitis usually resolves without treatment after several months. When treatment is necessary, symptoms often improve with hydration, anti-diarrheal agents, and discontinuation of radiation. Butyrate enemas may also be effective.In contrast, RAVE and chronic radiation proctopathy usually is not self-limited and often requires additional therapies. These include sucralfate, hyperbaric oxygen therapy, corticosteroids, metronidazole, argon plasma coagulation, radiofrequency ablation and formalin irrigation. The average number of treatment sessions with argon plasma coagulation to achieve control of bleeding ranges from 1 to 2.7 sessions.In rare cases that do not respond to medical therapy and endoscopic treatment, surgery may be required. Overall, less than 10 percent of individuals with radiation proctopathy require surgery. In addition, complications such as obstruction and fistulae may require surgery. Epidemiology Up to 30 percent of individuals who receive pelvic radiation therapy for cancer may develop radiation proctopathy. See also Radiation enteropathy References == External links ==
Myelopathy	Myelopathy describes any neurologic deficit related to the spinal cord. When due to trauma, it is known as (acute) spinal cord injury. When inflammatory, it is known as myelitis. Disease that is vascular in nature is known as vascular myelopathy. The most common form of myelopathy in humans, cervical spondylotic myelopathy (CSM), also called degenerative cervical myelopathy is caused by arthritic changes (spondylosis) of the cervical spine, which result in narrowing of the spinal canal (spinal stenosis) ultimately causing compression of the spinal cord. In Asian populations, spinal cord compression often occurs due to a different, inflammatory process affecting the posterior longitudinal ligament. Presentation Clinical signs and symptoms depend on which spinal cord level (cervical, thoracic, or lumbar) is affected and the extent (anterior, posterior, or lateral) of the pathology, and may include: Upper motor neuron signs—weakness, spasticity, clumsiness, altered tonus, hyperreflexia and pathological reflexes, including Hoffmanns sign and inverted plantar reflex (positive Babinski sign) Lower motor neuron signs—weakness, clumsiness in the muscle group innervated at the level of spinal cord compromise, muscle atrophy, hyporeflexia, muscle hypotonicity or flaccidity, fasciculations Sensory deficits Bowel/bladder symptoms and sexual dysfunction Diagnosis Diagnosis of myelopathy Myelopathy is primarily diagnosed by clinical exam findings. Because the term myelopathy describes a clinical syndrome that can be caused by many pathologies the differential diagnosis of myelopathy is extensive. In some cases the onset of myelopathy is rapid, in others, such as CSM, the course may be insidious with symptoms developing slowly over a period of months. As a consequence, the diagnosis of CSM is often delayed. As the disease is thought to be progressive, this may impact negatively on outcome. Diagnosis of etiology Once the clinical diagnosis myelopathy is established, the underlying cause must be investigated. Most commonly this involves medical imaging. The best way to visualize the spinal cord is magnetic resonance imaging (MRI). Apart from T1 and T2 MRI images, which are commonly used for routine diagnosis, more recently researchers are exploring quantitative MRI signals. Further imaging modalities used for evaluating myelopathy include plain X-rays for detecting arthritic changes of the bones, and Computer Tomography, which is often used for pre-operative planning of surgical interventions for cervical spondylotic myelopathy. Angiography is used to examine blood vessels in suspected cases of vascular myelopathy.The presence and severity of myelopathy can also be evaluated by means of transcranial magnetic stimulation (TMS), a neurophysiological method that allows the measurement of the time required for a neural impulse to cross the pyramidal tracts, starting from the cerebral cortex and ending at the anterior horn cells of the cervical, thoracic or lumbar spinal cord. This measurement is called Central Conduction Time (CCT). TMS can aid physicians to: Determine whether myelopathy exists Identify the level of the spinal cord where myelopathy is located. This is especially useful in cases where more than two lesions may be responsible for the clinical symptoms and signs, such as in patients with two or more cervical disc hernias Follow-up the progression of myelopathy in time, for example before and after cervical spine surgeryTMS can also help in the differential diagnosis of different causes of pyramidal tract damage. Treatment The treatment and prognosis of myelopathy depends on the underlying cause: myelopathy caused by infection requires medical treatment with pathogen specific antibiotics. Similarly, specific treatments exist for multiple sclerosis, which may also present with myelopathy. As outlined above, the most common form of myelopathy is secondary to degeneration of the cervical spine. Newer findings have challenged the existing controversy with respect to surgery for cervical spondylotic myelopathy by demonstrating that patients benefit from surgery. See also Surfers myelopathy References == External links ==
Cystathioninuria	Cystathioninuria, also called cystathionase deficiency, is an autosomal recessive metabolic disorder. It is characterized by an abnormal accumulation of plasma cystathionine leading to excess cystathionine in the urine. Hereditary cystathioninuria is associated with the reduced activity of the enzyme cystathionine gamma-lyase. It is considered a biochemical anomaly. This is because it associated with a wide range of diseases and its inconsistency. Cystathionase catalyzes cystathionine to cysteine and α-ketobutyrate. Cysteine is an essential amino acid and its conversion from cystathionine occurs in the trans-sulfuration pathway. The availability of cysteine is necessary for the synthesis of an important anti-oxidant, glutathione. Cystathionase has a co-enzyme, pyridoxal phosphate, which is the active form the vitamin B6. This means that vitamin B6 is essential for the function of cystathionase. Cystathioninuria can be broken down into two main categories. Primary cystathioninuria is caused by the recessive inherited deficiency of cystathionase enzyme. Secondary cystathioninuria is described by non-genetic conditions of excess cystathionine. Secondary cystathioninuria includes temporary excess cystathionine of premature infants, severe generalized liver damage, thyrotoxicosis, hepatoblastoma, or neuroblastoma. Cases of secondary cystathioninuria are not responsive to vitamin B6 administration. Types Under primary cystathioninuria, the inherited mutation of CTH gene, there are two forms. There is vitamin B6 – unresponsive and vitamin B6 – responsive cystathioninuria. The vitamin B6 – unresponsive form is thought to be from a lack of the synthesis of cystathionase. This means that the mutation in CTH from this form of cystathioninuria, results in the absence of cystathionase. It could also result from the synthesis of a cystathionase that is so greatly mutated it cannot function at all. On the other hand, vitamin B6 – responsive form still has synthesis of cystathionase. However, the cystathionase has an altered ability to bind to vitamin B6, its coenzyme. This changed interaction lowers the efficiency of cystathionase, so it cannot convert cystathionine as well. Genetics Cystathioninuria is inherited in an autosomal recessive manner. This means the defective gene responsible for the disorder is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.Interestingly, homozygotes and heterozygotes were able to be distinguished in one study through both plasma and urinary levels of cystathionine. The homozygote individuals had cystathionine levels greater than 0.5 moles per milligram of creatinine. Each of the homozygote individuals had a significant amount of cystathionine in the plasma as well. In contrast, the heterozygote individuals excreted approximately one tenth the amount of cystathionine as the homozygote individuals. The heterozygote individuals also had no detectable amounts of cystathionine in their plasma.The gene for cystathionase, CTH, has been sequenced and multiple mutations have been shown to be associated with the development of cystathioninuria. Two nonsense mutations were found in exon 8 and exon 11 of CTH. Two missense mutations were also found, mainly in exon 2 and exon 7. In addition, a common non-synonymous single nucleotide polymorphism in exon 12 was also identified. The presence of various CTH mutations is consistent with the various categories associated with cystathioninuria. Diagnosis The main way to diagnosis cystathioninuria is simply through increased urinary excretion of cystathionine. In some cases, a genetic test is employed. Treatment The treatment, if any is available, varies depending on the category of cystathioninuria a patient has. The vitamin B6 – responsive form is best treated by an increased consumption of vitamin B6. This increased consumption helps with cystathionases altered ability to bind to the active form of vitamin B6. References == External links ==
Relapsing fever	Relapsing fever is a vector-borne disease caused by infection with certain bacteria in the genus Borrelia, which is transmitted through the bites of lice or soft-bodied ticks (genus Ornithodoros). Signs and symptoms Most people who are infected develop sickness between 5 and 15 days after they are bitten. The symptoms may include a sudden fever, chills, headaches, muscle or joint aches, and nausea. A rash may also occur. These symptoms usually continue for 2 to 9 days, then disappear. This cycle may continue for several weeks if the person is not treated. Causes Louse-borne relapsing fever Along with Rickettsia prowazekii and Bartonella quintana, Borrelia recurrentis is one of three pathogens of which the body louse (Pediculus humanus humanus) is a vector. Louse-borne relapsing fever is more severe than the tick-borne variety.Louse-borne relapsing fever occurs in epidemics amid poor living conditions, famine and war in the developing world. It is currently prevalent in Ethiopia and Sudan.Mortality rate is 1% with treatment and 30–70% without treatment. Poor prognostic signs include severe jaundice, severe change in mental status, severe bleeding and a prolonged QT interval on ECG.Lice that feed on infected humans acquire the Borrelia organisms that then multiply in the gut of the louse. When an infected louse feeds on an uninfected human, the organism gains access when the victim crushes the louse or scratches the area where the louse is feeding. B. recurrentis infects the person via mucous membranes and then invades the bloodstream. No non-human, animal reservoir exists. Tick-borne relapsing fever Tick-borne relapsing fever is found primarily in Africa, Spain, Saudi Arabia, Asia, and certain areas of Canada and the western United States. Other relapsing infections are acquired from other Borrelia species, which can be spread from rodents, and serve as a reservoir for the infection, by a tick vector. Borrelia crocidurae – occurs in Egypt, Mali, Senegal, Tunisia; vectors – Carios erraticus, Ornithodoros sonrai; animal host – shrew (Crocidura stampflii) Borrelia duttoni, transmitted by the soft-bodied African tick Ornithodoros moubata, is responsible for the relapsing fever found in central, eastern, and southern Africa. Borrelia hermsii Borrelia hispanica Borrelia miyamotoi Borrelia parkeri Borrelia turicatae Borrelia persicaB. hermsii and B. recurrentis cause very similar diseases. However, one or two relapses are common with the disease associated with B. hermsii, which is also the most common cause of relapsing disease in the United States. (Three or four relapses are common with the disease caused by B. recurrentis, which has longer febrile and afebrile intervals and a longer incubation period than B. hermsii.) Diagnosis The diagnosis of relapsing fever can be made on blood smear as evidenced by the presence of spirochetes. Other spirochete illnesses (Lyme disease, syphilis, leptospirosis) do not show spirochetes on blood smear. Although considered the gold standard, this method lacks sensitivity and has been replaced by PCR in many settings. Treatment Relapsing fever is easily treated with a one- to two-week-course of antibiotics, and most people improve within 24 hours. Complications and death due to relapsing fever are rare.Tetracycline-class antibiotics are most effective. These can, however, induce a Jarisch–Herxheimer reaction in over half those treated, producing anxiety, diaphoresis, fever, tachycardia and tachypnea with an initial pressor response followed rapidly by hypotension. Recent studies have shown tumor necrosis factor-alpha may be partly responsible for this reaction. Research Currently, no vaccine against relapsing fever is available, but research continues. Developing a vaccine is very difficult because the spirochetes avoid the immune response of the infected person (or animal) through antigenic variation. Essentially, the pathogen stays one step ahead of antibodies by changing its surface proteins. These surface proteins, lipoproteins called variable major proteins, have only 30–70% of their amino acid sequences in common, which is sufficient to create a new antigenic "identity" for the organism. Antibodies in the blood that are binding to and clearing spirochetes expressing the old proteins do not recognize spirochetes expressing the new ones. Antigenic variation is common among pathogenic organisms. These include the agents of malaria, gonorrhea, and sleeping sickness. Important questions about antigenic variation are also relevant for such research areas as developing a vaccine against HIV and predicting the next influenza pandemic. History Relapsing fever has been described since the days of the ancient Greeks. After an outbreak in Edinburgh in the 1840s, relapsing fever was given its name, but the etiology of the disease was not better understood for a decade. Physician David Livingstone is credited with the first account in 1857 of a malady associated with the bite of soft ticks in Angola and Mozambique. In 1873, Otto Obermeier first described the disease-causing ability and mechanisms of spirochetes, but was unable to reproduce the disease in inoculated test subjects and thereby unable to fulfill Kochs postulates. The disease was not successfully produced in an inoculated subject until 1874. In 1904 and 1905, a series of papers outlined the cause of relapsing fever and its relationship with ticks. Both Joseph Everett Dutton and John Lancelot Todd contracted relapsing fever by performing autopsies while working in the eastern region of the Congo Free State. Dutton died there on February 27, 1905. The cause of tick-borne relapsing fever across central Africa was named Spirillum duttoni. In 1984, it was renamed Borrelia duttoni. The first time relapsing fever was described in North America was in 1915 in Jefferson County, Colorado.Sir William MacArthur suggested that relapsing fever was the cause of the yellow plague, variously called pestis flava, pestis ictericia, buidhe chonaill, or cron chonnaill, which struck early Medieval Britain and Ireland, and of epidemics which struck modern Ireland in the famine. This is consistent with the description of the symptoms experienced by King Maelgwn of Gwynedd as recorded in words attributed to Taliesin and with the "great mortality in Britain" in 548 CE noted in the Annales Cambriae. See also Lyme disease Typhus Continuous fever Intermittent fever Remittent fever References External links CDC: Relapsing Fever
Thrombophilia	Thrombophilia (sometimes called hypercoagulability or a prothrombotic state) is an abnormality of blood coagulation that increases the risk of thrombosis (blood clots in blood vessels). Such abnormalities can be identified in 50% of people who have an episode of thrombosis (such as deep vein thrombosis in the leg) that was not provoked by other causes. A significant proportion of the population has a detectable thrombophilic abnormality, but most of these develop thrombosis only in the presence of an additional risk factor.There is no specific treatment for most thrombophilias, but recurrent episodes of thrombosis may be an indication for long-term preventive anticoagulation. The first major form of thrombophilia to be identified by medical science, antithrombin deficiency, was identified in 1965, while the most common abnormalities (including factor V Leiden) were described in the 1990s. Signs and symptoms The most common conditions associated with thrombophilia are deep vein thrombosis (DVT) and pulmonary embolism (PE), which are referred to collectively as venous thromboembolism (VTE). DVT usually occurs in the legs, and is characterized by pain, swelling and redness of the limb. It may lead to long-term swelling and heaviness due to damage to valves in the veins. The clot may also break off and migrate (embolize) to arteries in the lungs. Depending on the size and the location of the clot, this may lead to sudden-onset shortness of breath, chest pain, palpitations and may be complicated by collapse, shock and cardiac arrest.Venous thrombosis may also occur in more unusual places: in the veins of the brain, liver (portal vein thrombosis and hepatic vein thrombosis), mesenteric vein, kidney (renal vein thrombosis) and the veins of the arms. Whether thrombophilia also increases the risk of arterial thrombosis (which is the underlying cause of heart attacks and strokes) is less well established.Thrombophilia has been linked to recurrent miscarriage, and possibly various complications of pregnancy such as intrauterine growth restriction, stillbirth, severe pre-eclampsia and abruptio placentae.Protein C deficiency may cause purpura fulminans, a severe clotting disorder in the newborn that leads to both tissue death and bleeding into the skin and other organs. The condition has also been described in adults. Protein C and protein S deficiency have also been associated with an increased risk of skin necrosis on commencing anticoagulant treatment with warfarin or related drugs. Causes Thrombophilia can be congenital or acquired. Congenital thrombophilia refers to inborn conditions (and usually hereditary, in which case "hereditary thrombophilia" may be used) that increase the tendency to develop thrombosis, while, on the other hand, acquired thrombophilia refers to conditions that arise later in life. Congenital The most common types of congenital thrombophilia are those that arise as a result of overactivity of coagulation factors. They are relatively mild, and are therefore classified as "type II" defects. The most common ones are factor V Leiden (a mutation in the F5 gene at position 1691) and prothrombin G20210A, a mutation in prothrombin (at position 20210 in the 3 untranslated region of the gene).The rare forms of congenital thrombophilia are typically caused by a deficiency of natural anticoagulants. They are classified as "type I" and are more severe in their propensity to cause thrombosis. The main ones are antithrombin III deficiency, protein C deficiency and protein S deficiency. Milder rare congenital thrombophilias are factor XIII mutation and familial dysfibrinogenemia (an abnormal fibrinogen). It is unclear whether congenital disorders of fibrinolysis (the system that destroys clots) are major contributors to thrombosis risk. Congenital deficiency of plasminogen, for instance, mainly causes eye symptoms and sometimes problems in other organs, but the link with thrombosis has been more uncertain.Blood group determines thrombosis risk to a significant extent. Those with blood groups other than type O are at a 2- to 4-fold relative risk. O blood group is associated with reduced levels of von Willebrand factor – because of increased clearance – and factor VIII, which is related to thrombotic risk . Acquired A number of acquired conditions augment the risk of thrombosis. A prominent example is antiphospholipid syndrome, which is caused by antibodies against constituents of the cell membrane, particularly lupus anticoagulant (first found in people with the disease systemic lupus erythematosus but often detected in people without the disease), anti-cardiolipin antibodies, and anti-β2-glycoprotein 1 antibodies; it is therefore regarded as an autoimmune disease. In some cases, antiphospholipid syndrome can cause arterial as well as venous thrombosis. It is also more strongly associated with miscarriage, and can cause a number of other symptoms (such as livedo reticularis of the skin and migraine).Heparin-induced thrombocytopenia (HIT) is due to an immune system reaction against the anticoagulant drug heparin (or its derivatives). Though it is named for associated low platelet counts, HIT is strongly associated with risk of venous and arterial thrombosis. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare condition resulting from acquired alterations in the PIGA gene, which plays a role in the protection of blood cells from the complement system. PNH increases the risk of venous thrombosis but is also associated with hemolytic anemia (anemia resulting from destruction of red blood cells). Both HIT and PNH require particular treatment.Hematologic conditions associated with sluggish blood flow can increase risk for thrombosis. For example, sickle-cell disease (caused by mutations of hemoglobin) is regarded as a mild prothrombotic state induced by impaired flow. Similarly, myeloproliferative disorders, in which the bone marrow produces too many blood cells, predispose to thrombosis, particularly in polycythemia vera (excess red blood cells) and essential thrombocytosis (excess platelets). Again, these conditions usually warrant specific treatment when identified.Cancer, particularly when metastatic (spread to other places in the body), is a recognised risk factor for thrombosis. A number of mechanisms have been proposed, such as activation of the coagulation system by cancer cells or secretion of procoagulant substances. Furthermore, particular cancer treatments (such as the use of central venous catheters for chemotherapy) may increase the risk of thrombosis further.Nephrotic syndrome, in which protein from the bloodstream is released into the urine due to kidney diseases, can predispose to thrombosis; this is particularly the case in more severe cases (as indicated by blood levels of albumin below 25 g/L) and if the syndrome is caused by the condition membranous nephropathy. Inflammatory bowel disease (ulcerative colitis and Crohns disease) predispose to thrombosis, particularly when the disease is active. Various mechanisms have been proposed.Pregnancy is associated with an increased risk of thrombosis of 2- to 7-fold. This probably results from a physiological hypercoagulability in pregnancy that protects against postpartum hemorrhage. This hypercoagulability in turn is likely related to the high levels of estradiol and progesterone that occur during pregnancy.Estrogens, when used in combined hormonal birth control and in menopausal hormone therapy (in combination with progestogens), have been associated with a 2- to 6-fold increased risk of venous thrombosis. The risk depends on the types of hormones used, the dose of estrogen, and the presence of other thrombophilic risk factors. Various mechanisms, such as deficiency of protein S and tissue factor pathway inhibitor, are said to be responsible.Obesity has long been regarded as a risk factor for venous thrombosis. It more than doubles the risk in numerous studies, particularly in combination with the use of oral contraceptives or in the period after surgery. Various coagulation abnormalities have been described in the obese. Plasminogen activator inhibitor-1, an inhibitor of fibrinolysis, is present in higher levels in people with obesity. Obese people also have larger numbers of circulating microvesicles (fragments of damaged cells) that bear tissue factor. Platelet aggregation may be increased, and there are higher levels of coagulation proteins such as von Willebrand factor, fibrinogen, factor VII and factor VIII. Obesity also increases the risk of recurrence after an initial episode of thrombosis. Unclear A number of conditions that have been linked with venous thrombosis are possibly genetic and possibly acquired. These include: elevated levels of factor VIII, factor IX, factor XI, fibrinogen and thrombin-activatable fibrinolysis inhibitor, and decreased levels of tissue factor pathway inhibitor. Activated protein C resistance that is not attributable to factor V mutations is probably caused by other factors and remains a risk factor for thrombosis.There is an association between the blood levels of homocysteine and thrombosis, although this has not been reported consistently in all studies. Homocysteine levels are determined by mutations in the MTHFR and CBS genes, but also by levels of folic acid, vitamin B6 and vitamin B12, which depend on diet. Mechanism Thrombosis is a multifactorial problem because there are often multiple reasons why a person might develop thrombosis. These risk factors may include any combination of abnormalities in the blood vessel wall, abnormalities in the blood flow (as in immobilization), and abnormalities in the consistency of the blood. Thrombophilia is caused by abnormalities in blood consistency, which is determined by the levels of coagulation factors and other circulating blood proteins that participate in the "coagulation cascade".Normal coagulation is initiated by the release of tissue factor from damaged tissue. Tissue factor binds to circulating factor VIIa. The combination activates factor X to factor Xa and factor IX to factor IXa. Factor Xa (in the presence of factor V) activates prothrombin into thrombin. Thrombin is a central enzyme in the coagulation process: it generates fibrin from fibrinogen, and activates a number of other enzymes and cofactors (factor XIII, factor XI, factor V and factor VIII, TAFI) that enhance the fibrin clot. The process is inhibited by TFPI (which inactivates the first step catalyzed by factor VIIa/tissue factor), antithrombin (which inactivates thrombin, factor IXa, Xa and XIa), protein C (which inhibits factors Va and VIIIa in the presence of protein S), and protein Z (which inhibits factor Xa).In thrombophilia, the balance between "procoagulant" and "anticoagulant" activity is disturbed. The severity of the imbalance determines the likelihood that someone develops thrombosis. Even small perturbances of proteins, such as the reduction of antithrombin to only 70–80% of the normal level, can increase the thrombosis risk; this is in contrast with hemophilia, which only arises if levels of coagulation factors are markedly decreased.In addition to its effects on thrombosis, hypercoagulable states may accelerate the development of atherosclerosis, the arterial disease that underlies myocardial infarction and other forms of cardiovascular disease. Diagnosis Tests for thrombophilia include complete blood count (with examination of the blood film), prothrombin time, partial thromboplastin time, thrombodynamics test, thrombin time and reptilase time, lupus anticoagulant, anti-cardiolipin antibody, anti-β2 glycoprotein 1 antibody, activated protein C resistance, fibrinogen tests, factor V Leiden and prothrombin mutation, and basal homocysteine levels. Testing may be more or less extensive depending on clinical judgement and abnormalities detected on initial evaluation.For hereditary cases, the patient must have at least two abnormal tests plus family history. Screening There are divergent views as to whether everyone with an unprovoked episode of thrombosis should be investigated for thrombophilia. Even those with a form of thrombophilia may not necessarily be at risk of further thrombosis, while recurrent thrombosis is more likely in those who have had previous thrombosis even in those who have no detectable thrombophilic abnormalities. Recurrent thromboembolism, or thrombosis in unusual sites (e.g. the hepatic vein in Budd-Chiari syndrome), is a generally accepted indication for screening. It is more likely to be cost-effective in people with a strong personal or family history of thrombosis. In contrast, the combination of thrombophilia with other risk factors may provide an indication for preventive treatment, which is why thrombophilia testing may be performed even in those who would not meet the strict criteria for these tests. Searching for a coagulation abnormality is not normally undertaken in patients in whom thrombosis has an obvious trigger. For example, if the thrombosis is due to immobilization after recent orthopedic surgery, it is regarded as "provoked" by the immobilization and the surgery and it is less likely that investigations will yield clinically important results.When venous thromboembolism occurs when a patient is experiencing transient major risk factors such as prolonged immobility, surgery, or trauma, testing for thrombophilia is not appropriate because the outcome of the test would not change a patients indicated treatment. In 2013, the American Society of Hematology, as part of recommendations in the Choosing Wisely campaign, cautioned against overuse of thrombophilia screening; false positive results of testing would lead to people inappropriately being labeled as having thrombophilia, and being treated with anticoagulants without clinical needIn the United Kingdom, professional guidelines give specific indications for thrombophilia testing. It is recommended that testing be done only after appropriate counseling, and hence the investigations are usually not performed at the time when thrombosis is diagnosed but at a later time. In particular situations, such as retinal vein thrombosis, testing is discouraged altogether because thrombophilia is not regarded as a major risk factor. In other rare conditions generally linked with hypercoagulability, such as cerebral venous thrombosis and portal vein thrombosis, there is insufficient data to state for certain whether thrombophilia screening is helpful, and decisions on thrombophilia screening in these conditions are therefore not regarded as evidence-based. If cost-effectiveness (quality-adjusted life years in return for expenditure) is taken as a guide, it is generally unclear whether thrombophilia investigations justify the often high cost, unless the testing is restricted to selected situations.Recurrent miscarriage is an indication for thrombophilia screening, particularly antiphospholipid antibodies (anti-cardiolipin IgG and IgM, as well as lupus anticoagulant), factor V Leiden and prothrombin mutation, activated protein C resistance and a general assessment of coagulation through an investigation known as thromboelastography.Women who are planning to use oral contraceptives do not benefit from routine screening for thrombophilias, as the absolute risk of thrombotic events is low. If either the woman or a first-degree relative has had thrombosis, the risk of developing thrombosis is increased. Screening this selected group may be beneficial, but even when negative may still indicate residual risk. Professional guidelines therefore suggest that alternative forms of contraception be used rather than relying on screening.Thrombophilia screening in people with arterial thrombosis is generally regarded as unrewarding and is generally discouraged, except possibly for unusually young patients (especially when precipitated by smoking or use of estrogen-containing hormonal contraceptives) and those in whom revascularization, such as coronary arterial bypass, fails because of rapid occlusion of the graft. Treatment There is no specific treatment for thrombophilia, unless it is caused by an underlying medical illness (such as nephrotic syndrome), where the treatment of the underlying disease is needed. In those with unprovoked and/or recurrent thrombosis, or those with a high-risk form of thrombophilia, the most important decision is whether to use anticoagulation medications, such as warfarin, on a long-term basis to reduce the risk of further episodes. This risk needs to weighed against the risk that the treatment will cause significant bleeding, as the reported risk of major bleeding is over 3% per year, and 11% of those with major bleeding may die as a result.Apart from the abovementioned forms of thrombophilia, the risk of recurrence after an episode of thrombosis is determined by factors such as the extent and severity of the original thrombosis, whether it was provoked (such as by immobilization or pregnancy), the number of previous thrombotic events, male sex, the presence of an inferior vena cava filter, the presence of cancer, symptoms of post-thrombotic syndrome, and obesity. These factors tend to be more important in the decision than the presence or absence of a detectable thrombophilia.Those with antiphospholipid syndrome may be offered long-term anticoagulation after a first unprovoked episode of thrombosis. The risk is determined by the subtype of antibody detected, by the antibody titer (amount of antibodies), whether multiple antibodies are detected, and whether it is detected repeatedly or only on a single occasion.Women with a thrombophilia who are contemplating pregnancy or are pregnant usually require alternatives to warfarin during pregnancy, especially in the first 13 weeks, when it may produce abnormalities in the unborn child. Low molecular weight heparin (LMWH, such as enoxaparin) is generally used as an alternative. Warfarin and LMWH may safely be used in breastfeeding.When women experience recurrent pregnancy loss secondary to thrombophilia, some studies have suggested that low molecular weight heparin reduces the risk of miscarriage. When the results of all studies are analysed together, no statistically significant benefit could be demonstrated. Prognosis In people without a detectable thrombophilia, the cumulative risk of developing thrombosis by the age of 60 is about 12%. About 60% of people who are deficient in antithrombin will have experienced thrombosis at least once by age 60, as will about 50% of people with protein C deficiency and about a third of those with protein S deficiency. People with activated protein C resistance (usually resulting from factor V Leiden), in contrast, have a slightly raised absolute risk of thrombosis, with 15% having had at least one thrombotic event by the age of sixty. In general, men are more likely than women to experience repeated episodes of venous thrombosis.People with factor V Leiden are at a relatively low risk of thrombosis, but may develop thrombosis in the presence of an additional risk factor, such as immobilization. Most people with the prothrombin mutation (G20210A) never develop thrombosis. Epidemiology The major ("type 1") thrombophilias are rare. Antithrombin deficiency is present in 0.2% of the general population and 0.5–7.5% of people with venous thrombosis. Protein C deficiency, too, is present in 0.2% of the population, and can be found in 2.5–6% of people with thrombosis. The exact prevalence of protein S deficiency in the population is unknown; it is found 1.3–5% of people with thrombosis.The minor ("type 2") thrombophilias are much more common. Factor V Leiden is present in 5% of the population of Northern European descent, but much rarer in those of Asian or African extraction. In people with thrombosis, 10% have factor V Leiden. In those who are referred for thrombophilia testing, 30–50% have the defect. The prothrombin mutation occurs at rates of 1–4% in the general population, 5–10% of people with thrombosis, and 15% of people referred for thrombophilia testing. Like factor V Leiden, this abnormality is uncommon in Africans and Asians.The exact prevalence of antiphospholipid syndrome is not well known, as different studies employ different definitions of the condition. Antiphospholipid antibodies are detected in 24% of those referred to thrombophilia testing. History German physician Rudolf Virchow categorized abnormalities in the consistency of the blood as a factor in the development of thrombosis in 1856. The exact nature of these abnormalities remained elusive until the first form of thrombophilia, antithrombin deficiency, was recognized in 1965 by the Norwegian hematologist Olav Egeberg. Protein C deficiency followed in 1981, when described by researchers from the Scripps Research Institute and the U.S. Centers of Disease Control. Protein S deficiency followed in 1984, described by researchers at the University of Oklahoma.Antiphospholipid syndrome was described in full in the 1980s, after various previous reports of specific antibodies in people with systemic lupus erythematosus and thrombosis. The syndrome is often attributed to the British rheumatologist Graham R.V. Hughes, and is often referred to as Hughes syndrome for that reason.The more common genetic thrombophilias were described in the 1990s. Many studies had previously indicated that many people with thrombosis showed resistance activated protein C. In 1994 a group in Leiden, The Netherlands, identified the most common underlying defect—a mutation in factor V that made it resistant to the action of activated protein C. The defect was called factor V Leiden, as genetic abnormalities are typically named after the place where they are discovered. Two years later, the same group described a common mutation in the prothrombin gene that caused elevation of prothrombin levels and a mild increase in thrombosis risk.It is suspected that other genetic abnormalities underlying familial thrombosis will in future be discovered through studies of the entire genetic code, looking for small alternations in genes. References External links "Thrombophilia". Patient UK.
Monorchism	Monorchism (also monorchidism) is the state of having only one testicle within the scrotum. Terminology An individual having monorchism can be referred to as monorchid. Causes This can be due to: One testicle not descending into the scrotum during normal embryonic or fetal development (3–4% of normal live births), also known as undescended testis or cryptorchidism. In this case the testis is within the abdominal cavity, somewhere along the normal route of descent – most commonly, within the inguinal canal. Such a testis has an increased risk of malignancy. One testicle may disappear during development (the so-called vanishing testis) due to some intrauterine insult. This is thought to be most likely vascular, such as testicular torsion. One testicle may have been surgically removed through orchiectomy. One testicle may be injured. Notable cases Due to testicular cancer Lance Armstrong, American bicyclist. Ashley Gray, Ironman triathlete Frank Church, late U.S. Senator and a presidential aspirant in 1976. His monorchism was revealed publicly during the 1976 presidential campaign. Tom Green, Canadian comedian-actor. Richard Herring, English comedian and writer John Kruk, former baseball player Mark Latham, former Australian politician. Geoff Horsfield, English footballer. Nenê, Brazilian basketball player. Kevin Curtis, American football player. Nigel Farage, former leader of the UK Independence Party. Bobby Moore, English footballer and World Cup winner. Jimmy White, English snooker player. Due to injury Archibald Douglas, 4th Earl of Douglas, magnate of the Kingdom of Scotland, and Peer of France. Lost in 1403, while fighting at the Battle of Shrewsbury (The previous year he had lost an eye at the Battle of Homildon Hill). Troy Bayliss, world superbike champion in 2001, 2006 and 2008. In 2007 he lost a testicle during a race at Donington Park. Brian Foster, American mixed martial artist. John Starks, American basketball player. Paul Wood, English rugby league player who sustained a ruptured testicle during a match and subsequently had it removed. Thurgood Marshall, United States Supreme Court Justice who injured a testicle during a fraternity event in university. Tom Lamping, United Kingdom, injured a testicle during a dog fight gone wrong. Due to cryptorchidism Mao Zedong, founder of the Peoples Republic of China. Unknown Possible monorchism of Adolf Hitler Francisco Franco, caudillo of Spain. Monorchism in nonhuman animals Although extremely rare, monorchism has been observed to be characteristic of some animal species, notably in beetles. See also Anorchia Cryptorchidism Polyorchidism == References ==
Tophus	A tophus (Latin: "stone", plural tophi) is a deposit of monosodium urate crystals, in people with longstanding high levels of uric acid in the blood, a condition known as hyperuricemia. Tophi are pathognomonic for the disease gout. Most people with tophi have had previous attacks of acute arthritis, eventually leading to the formation of tophi. Chronic tophaceous gout is known as Harrison Syndrome.Tophi form in the joints, cartilage, bones, and other places throughout the body. Sometimes, tophi break through the skin and appear as white or yellowish-white, chalky nodules. Without treatment, tophi may develop on average about ten years after the onset of gout, although their first appearance can range from three to forty-two years. The development of gouty tophi can also limit joint function and cause bone destruction, leading to noticeable disabilities, especially when gout cannot successfully be treated. When uric acid levels and gout symptoms cannot be controlled with standard gout medicines that decrease the production of uric acid (e.g., allopurinol, febuxostat) or increase uric acid elimination from the body through the kidneys (e.g., probenecid), this can be referred to as refractory chronic gout (RCG). They are more apt to appear early in the course of the disease in people who are older. Although less common, tophi can also form in the kidneys and nasal cartilage. Pathophysiology It appears that monosodium urate crystals trigger a distinct physiological NETosis pathway that coats them in DNA. These coated crystals then persist in tissues as a foreign body granuloma constituting gouty tophus. Additional images See also Chondrocalcinosis (pseudogout) References == External links ==
Juvenile nephronophthisis	Juvenile nephronophthisis is the juvenile form of nephronophthisis that causes end stage kidney disease around the age of 13; infantile nephronophthisis and adolescent nephronophthisis cause ESKD around the ages of 1 and 19, respectively. Signs and symptoms Typically, the signs and symptoms of juvenile nephronophthisis are limited to the kidneys. They include polyuria, polydipsia, weakness, and fatigue.Anemia, growth retardation, no hypertension. Proteinuria and hematuria are usually absent. Polyuria is resistant to vasopressin. When other organ systems are affected, symptoms can include situs inversus, heart abnormalities, and liver fibrosis. Juvenile nephronophthisis can also be associated with other rare disorders, including Senior–Løken syndrome and Joubert syndrome. Pathophysiology Juvenile nephronophthisis causes fibrosis and scarring of the kidneys, which accounts for the symptoms observed. The kidneys also often have corticomedullary cysts. Inability to conserve sodium because of defect of tubules leading to polyuria and polydipsia. Anemia is attributed to a deficiency of erythropoietin production by failing kidneys. Growth retardation, malaise and pallor are secondary to anemia. No hypertension as nephronophthisis is a salt-losing enteropathy. Diagnosis Ultrasonography shows bilateral small kidneys with loss of corticomedullary junction and multiple cysts only in the medulla. Cysts may only be seen if they are large enough, they are rarely visible early in disease. Differential diagnosis Patients with medullary cystic disease present with similar features as juvenile nephronophthisis but they can be differentiated by: Absence of growth retardation. Age of presentation is third or fourth decade. Hypertension may occur (in JN, hypertension is not seen).In polycystic kidney disease, there is bilateral enlargement of kidneys (small kidneys in JN). Treatment The only option is renal transplant. Epidemiology It is the most common genetic cause of end stage kidney disease (kidney failure) in childhood and adolescence. References == External links ==
Antiphospholipid syndrome	Antiphospholipid syndrome, or antiphospholipid antibody syndrome (APS or APLS), is an autoimmune, hypercoagulable state caused by antiphospholipid antibodies. APS provokes blood clots (thrombosis) in both arteries and veins as well as pregnancy-related complications such as miscarriage, stillbirth, preterm delivery, and severe preeclampsia. Although the exact etiology of APS is still not clear, genetics is believed to play a key role in the development of the disease. The diagnostic criteria require one clinical event (i.e. thrombosis or pregnancy complication) and two positive blood test results spaced at least three months apart that detect lupus anticoagulant, anti-apolipoprotein antibodies, or anti-cardiolipin antibodies.Antiphospholipid syndrome can be primary or secondary. Primary antiphospholipid syndrome occurs in the absence of any other related disease. Secondary antiphospholipid syndrome occurs with other autoimmune diseases, such as systemic lupus erythematosus. In rare cases, APS leads to rapid organ failure due to generalised thrombosis; this is termed "catastrophic antiphospholipid syndrome" (CAPS or Asherson syndrome) and is associated with a high risk of death. Antiphospholipid syndrome often requires treatment with anticoagulant medication such as heparin to reduce the risk of further episodes of thrombosis and improve the prognosis of pregnancy. Warfarin (brand name Coumadin) is not used during pregnancy because it can cross the placenta, unlike heparin, and is teratogenic. Signs and symptoms The presence of antiphospholipid antibodies (aPL) in the absence of blood clots or pregnancy-related complications does not indicate APS (see below for the diagnosis of APS). Antiphospholipid syndrome can cause arterial or venous blood clots, in any organ system, or pregnancy-related complications. In APS patients, the most common venous event is deep vein thrombosis of the lower extremities, and the most common arterial event is stroke. In pregnant person affected by APS, there is an increased risk of recurrent miscarriage, intrauterine growth restriction, and preterm birth. A frequent cause of such complications is placental infarctions. In some cases, APS seems to be the leading cause of intellectual and/or developmental disabilities in the newborn, due to an aPL-induced inhibition of trophoblast differentiation. The antiphospholipid syndrome is responsible for most of the miscarriages in later trimesters seen in concomitant systemic lupus erythematosus and pregnancy.Other common findings, although not part of the APS classification criteria, are low platelet count, heart valve disease, and livedo reticularis. There are also associations between antiphospholipid antibodies and different neurologic manifestations including headache, migraine, epilepsy, and dementia. Some studies have shown the presence of antiphospholipid antibodies in the blood and spinal fluid of patients with psychological symptoms. Cancer is also observed to comorbid in patients with APS. Risk factors Risk factors for developing antiphospholipid syndrome include: Genetic Markers: HLA-DR4, HLA-DR7, and HLA-DRw53 Race: Blacks, Hispanics, Asians, and Native Americans Pathogenesis Antiphospholipid syndrome is an autoimmune disease, in which "antiphospholipid antibodies" (anticardiolipin antibodies and lupus anticoagulant) react against proteins that bind to anionic phospholipids on plasma membranes. Like many autoimmune diseases, it is more common in women than in men. The exact cause is not known, but activation of the system of coagulation is evident. Clinically important antiphospholipid antibodies (those that arise as a result of the autoimmune process) are associated with thrombosis and vascular disease. The syndrome can be divided into primary (no underlying disease state) and secondary (in association with an underlying disease state) forms.Anti-ApoH and a subset of anti-cardiolipin antibodies bind to ApoH. ApoH inhibits protein C, a glycoprotein with important regulatory function of coagulation (inactivates Factor Va and Factor VIIIa). Lupus anticoagulant antibodies bind to prothrombin, thus increasing its cleavage to thrombin, its active form.In APS there are also antibodies binding to protein S, which is a co-factor of protein C. Thus, anti-protein S antibodies decrease protein C efficiency.Annexin A5 forms a shield around negatively charged phospholipid molecules, thus reducing their availability for coagulation. Thus, anti-annexin A5 antibodies increase phospholipid-dependent coagulation steps.The lupus anticoagulant antibodies are those that show the closest association with thrombosis; those that target β2glycoprotein 1 have a greater association with thrombosis than those that target prothrombin. Anticardiolipin antibodies are associated with thrombosis at moderate to high titres (over 40 GPLU or MPLU). Patients with both lupus anticoagulant antibodies and moderate or high titre anticardiolipin antibodies show a greater risk of thrombosis than with one alone.The increased risks of recurrent miscarriage, intrauterine growth restriction and preterm birth by antiphospholipid antibodies, as supported by in vitro studies, include decreased trophoblast viability, syncytialization and invasion, deranged production of hormones and signalling molecules by trophoblasts, as well as activation of coagulation and complement pathways. Diagnosis Antiphospholipid syndrome is diagnosed using either liquid-phase coagulation assays to detect lupus anticoagulant or solid phase ELISA (enzyme-linked immunosorbent assay) to detect anti-cardiolipin antibodies or anti-apolipoprotein antibodies.Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some patients with APS. Presence of genetic thrombophilia may determine the need for anticoagulation therapy. Thus, genetic thrombophilia screening can consist of: Screening for factor V Leiden variant and the prothrombin G20210A and MTHFR mutations. Measuring serum levels of protein C, free and total protein S, factor VIII, antithrombin, plasminogen, tissue plasminogen activator and plasminogen activator inhibitor-1.Antiphospholipid antibodies do not recognize isolated cardiolipin, but bind to a cardiolipin-β2GPI (apolipoprotein H) complex. The use of testing for antibodies specific for individual targets of aPL such as β2 glycoprotein 1 and phosphatidylserine is currently under debate. Lupus anticoagulant This is tested for by using a minimum of two coagulation tests that are phospholipid-sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged partial thromboplastin time (PTT) that does not correct in an 80:20 mixture with normal human plasma (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The PTT (plus 80:20 mix), dilute Russells viper venom time, kaolin clotting time, dilute thromboplastin time, silica clotting time and prothrombin time (using a lupus-sensitive thromboplastin) are the principal tests used for the detection of lupus anticoagulant. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion, demonstrating persistent positivity, to allow a diagnosis of antiphospholipid syndrome. This is to prevent patients with transient positive tests (due to infection etc.) being diagnosed as positive.Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g.: factor VIII) is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. The lupus anticoagulant will inhibit all the contact activation pathway factors (factor VIII, factor IX, factor XI and factor XII). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iu/dl (35%) whereas a specific factor antibody will rarely give a result higher than 10 iu/dl (10%). Monitoring IV anticoagulant therapy by the PTT ratio is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of factor Xa by antithrombin in the presence of heparin. Anticardiolipin antibodies Anti-cardiolipin antibodies can be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test, which screens for the presence of β2glycoprotein 1 dependent anticardiolipin antibodies. A low platelet count and positivity for antibodies against β2-glycoprotein 1 or phosphatidylserine may also be observed in a positive diagnosis. Criteria Classification with APS requires evidence of both one or more specific, documented clinical events (either a vascular thrombosis and/or adverse obstetric event) and the confirmed presence of a repeated aPL. The Sapporo APS classification criteria (1998, published in 1999) were replaced by the Sydney criteria in 2006. Based on the most recent criteria, classification with APS requires one clinical and one laboratory manifestation: Clinical:A documented episode of arterial, venous, or small vessel thrombosis — other than superficial venous thrombosis — in any tissue or organ by objective validated criteria with no significant evidence of inflammation in the vessel wall 1 or more unexplained deaths of a morphologically normal fetus (documented by ultrasound or direct examination of the fetus) at or beyond the 10th week of gestation and/or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded or at least 1 premature birth of a morphologically normal neonate before the 34th week of gestation due to eclampsia or severe pre-eclampsia according to standard definitions, or recognized features of placental insufficiency Laboratory:Anti-cardiolipin IgG and/or IgM measured by standardized, non-cofactor dependent ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (i.e., > 40 GPL or MPL, or > the 99th percentile) Anti-β2 glycoprotein I IgG and/or IgM measured by standardized ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (> the 99th percentile) Lupus anticoagulant detected on 2 occasions not less than 12 weeks apart according to the guidelines of the International Society of Thrombosis and Hemostasis.There are 3 distinct APS disease entities: primary (the absence of any comorbidity), secondary (when there is a pre-existing autoimmune condition, most frequently systemic lupus erythematosus, SLE), and catastrophic (when there is simultaneous multi-organ failure with small vessel occlusion).According to a 2006 consensus statement, it is advisable to classify APS into one of the following categories for research purposes: I: more than one laboratory criterion present in any combination; IIa: lupus anticoagulant present alone IIb: anti-cardiolipin IgG and/or IgM present alone in medium or high titers IIc: anti-β2 glycoprotein I IgG and/or IgM present alone in a titer greater than 99th percentileThe International Consensus Statement is commonly used for Catastrophic APS diagnosis. Based on this statement, Definite CAPS diagnosis requires: a) Vascular thrombosis in three or more organs or tissues and b) Development of manifestations simultaneously or in less than a week and c) Evidence of small vessel thrombosis in at least one organ or tissue and d) Laboratory confirmation of the presence of aPL.VDRL, which detects antibodies against syphilis, may have a false positive result in aPL-positive patients (aPL bind to the lipids in the test and make it come out positive), although the more specific test for syphilis, FTA-Abs, that use recombinant antigens will not have a false-positive result. Treatment In people without symptoms, no treatment is required. In people with antiphospholipid antibody-associated thrombosis, anticoagulants such as warfarin are used to prevent further thrombosis. If warfarin is used, the INR is kept between 2.0 and 3.0. Direct-acting oral anticoagulants may be used as an alternative to warfarin, but not in people who are "triple positive" with all types of antiphospholipid antibody (lupus anticoagulant, anticardiolipin antibody and anti-β2 glycoprotein I antibody).Anticoagulation appears to prevent miscarriage in pregnant people. In pregnancy, low molecular weight heparin and low-dose aspirin are used instead of warfarin because of warfarins teratogenicity. People with recurrent miscarriages are often advised to take aspirin and to start low molecular weight heparin treatment after missing a menstrual cycle. In refractory cases plasmapheresis may be used. Prognosis The long-term prognosis for APS is determined mainly by recurrent thrombosis, which may occur in up to 29% of patients, sometimes despite antithrombotic therapy. History Antiphospholipid syndrome was described in full in the 1980s, by E. Nigel Harris and Aziz Gharavi. They published the first papers in 1983. The syndrome was referred to as "Hughes syndrome" among colleagues after the rheumatologist Graham R.V. Hughes (St. Thomas Hospital, London, UK), who brought together the team. Research APS ACTION (the AntiPhospholipid Syndrome Alliance for Clinical Trials and InternatiOnal Networking), is the first-ever international research network that has been created to design and conduct large-scale, multicenter clinical trials in persistently antiphospholipid antibody (aPL) positive patients. The network consists of a multidisciplinary group of physicians and investigators from around the world who are interested in antiphospholipid syndrome (APS) research. The primary mission of APS ACTION is to prevent, treat, and cure antiphospholipid antibody (aPL) associated clinical manifestations through high quality, multicenter, and multidisciplinary clinical research. References Bibliography Triona Holden (2003). Positive Options for Antiphospholipid Syndrome (APS): Self-Help and Treatment. Hunter House (CA). ISBN 978-0-89793-409-1. Kay Thackray (2003). Sticky Blood Explained. Braiswick. ISBN 978-1-898030-77-5. A personal account of dealing with the condition. Graham R V Hughes (2009). Understanding Hughes Syndrome: Case Studies for Patients. Springer. ISBN 978-1-84800-375-0. 50 case studies to help you work out whether you have it. External links Antiphospholipid Syndrome Explained - Genome.gov
Pyometra	Pyometra or pyometritis is a uterine infection. Though it is most commonly known as a disease of the unaltered female dog, it is also a notable human disease. It is also seen in female cattle, horses, goats, sheep, swine, cats, rabbits, hamsters, ferrets, rats and guinea pigs. Pyometra is an important disease to be aware of for any dog or cat owner because of the sudden nature of the disease and the deadly consequences if left untreated. It has been compared to acute appendicitis in humans, because both are essentially empyemas within an abdominal organ. Signs and symptoms The most obvious symptom of open pyometra is a discharge of pus from the vulva in a female that has recently been in heat. However, symptoms of closed pyometra are less obvious. Symptoms of both types include vomiting, loss of appetite, depression, and increased drinking and urinating. Fever is seen in less than a third of female dogs with pyometra. Closed pyometra is a more serious condition than open pyometra not only because there is no outlet for the infection, but also because a diagnosis of closed pyometra can easily be missed due to its insidious nature. Bloodwork may show dehydration and/or increased white blood cell count. X-rays will show an enlarged uterus, and ultrasound will confirm the presence of a fluid filled uterus. Cause The risk of developing pyometra differs between dog breeds. Pyometra is a result of hormonal and structural changes in the uterus lining. This can happen at any age, whether she has bred or not, and whether it is her 1st or 10th heat, although it becomes more common as the dog gets older. The main risk period for a female is for eight weeks after her peak standing heat has ended. Normally during this period, the cervix, which was open during her heat, begins to close, and the inner lining begins to adapt back to normal. However, cystic hyperplasia of the endometrium (inner lining of the uterus) – known as cystic endometrial hyperplasia (CEH) – may occur at this time for some animals, as an inappropriate response to progesterone. Under these circumstances, bacteria (especially E. coli) that have migrated from the vagina into the uterus find the environment favorable to growth, especially since progesterone also causes mucus secretion, closes the cervix (preventing uterine drainage), and decreases uterine contractility. The condition of the cervix is a major factor in the severity of the condition. If the cervix is open, the infected material can leave the body, and this is far easier and safer to treat. This is known as open pyometra. If the cervix is fully closed, there is no discharge from the vulva, and like in appendicitis, the uterus may rupture and pus escapes into the abdomen, causing peritonitis and possible rapid death. This is known as closed pyometra. Hormonal influences and mis-mating shots Females that have received estradiol as a mismating shot in diestrus are at risk for more severe disease because estrogen increases the number of progesterone receptors in the endometrium. 25 percent of females receiving estradiol in diestrus develop pyometra. Pyometra is less common in female cats because progesterone is only released by the ovaries after mating. Also in cats, the risk of developing the disease differs depending on breed. Treatment The most important aspect of treatment of pyometra is quick action to provide supportive care. Female dogs are often septic and in shock (see septic shock). Intravenous fluids and antibiotics should be given immediately. Once the female dog has been stabilized, then the treatment of choice is an emergency spay. In livestock the treatment of choice for minor cases is dinoprost tremethamine (lutalyse). Supportive antibiotic treatment may be recommended also. Severe cases require surgery. References External links Pyometra from The Pet Health Library Pyometra Surgery Photos and Description from The Pet Center
Distichia	A distichia is an eyelash that arises from an abnormal part of the eyelid. This abnormality, attributed to a genetic mutation, is known to affect dogs and humans. Distichiae usually exit from the duct of the meibomian gland at the eyelid margin. They are usually multiple, and sometimes more than one arises from a duct. They can affect either the upper or lower eyelid and are usually bilateral. The lower eyelids of dogs usually have no eyelashes.Distichiae usually cause no symptoms, because the lashes are soft, but they can irritate the eye and cause tearing, squinting, inflammation, corneal ulcers and scarring. Treatment options include manual removal, electrolysis, electrocautery, CO2 laser ablation, cryotherapy, and surgery. Commonly affected breeds In veterinary medicine, some canine breeds are affected by distichiasis more frequently than others: Cocker Spaniel Dachshund (especially the miniature longhaired Dachshund) Bulldog Pekingese Yorkshire Terrier Flat-Coated Retriever Shetland Sheepdog Boxer Poodle Ectopic cilia An ectopic cilia is a special type of distichia usually found in younger dogs. Commonly affected breeds include Poodles, Golden Retrievers, and Shih Tzus. The eyelash exits through the conjunctiva of the eyelid facing toward the eye, usually at the middle of the upper eyelid. It can cause intense pain and corneal ulcers. Treatment is surgery or cryotherapy. See also Trichiasis Lymphedema distichiasis References == External links ==
Smith–Magenis syndrome	Smith–Magenis Syndrome (SMS), also known as 17p- syndrome, is a microdeletion syndrome characterized by an abnormality in the short (p) arm of chromosome 17. It has features including intellectual disability, facial abnormalities, difficulty sleeping, and numerous behavioral problems such as self-harm. Smith–Magenis syndrome affects an estimated between 1 in 15,000 to 1 in 25,000 individuals. Signs and symptoms Facial features of children with Smith–Magenis syndrome include a broad and square face, deep-set eyes, large cheeks, and a prominent jaw, as well as a flat nose bridge (in the young child; as the child ages it becomes more ski-jump shaped). Eyes tend to be deep-set, close together and upwards-slanted. Eyebrows are heavy with lateral extension. The mouth is the most noticeable feature; both upper and lower lips are full, and the mouth is wide. The mouth curves downwards and the upper lip curves outwards, due to a fleshy philtrum. These facial features become more noticeable as the individual ages, as Mandible growth outstrips that of the maxilla leading to a clear midface hypoplasia. There is also a mild brachycephaly.Disrupted sleep patterns are characteristic of Smith–Magenis syndrome, typically beginning early in life. Affected individuals may be very sleepy during the day, but have trouble falling asleep and awaken several times each night, due to an inverted circadian rhythm of melatonin.People with Smith–Magenis syndrome have engaging personalities, but all also have a lot of behavioral problems. These behavioral problems include frequent temper tantrums, meltdowns and outbursts, aggression, anger, fidgeting, compulsive behavior, anxiety, impulsiveness, and difficulty paying attention. Self-harm, including biting, hitting, head banging, and skin picking, is very common. Behavioral complications in Smith-Magenis syndrome are thought to be worsened by issues with sleeping. Repetitive self-hugging is a behavioral trait that may be unique to Smith–Magenis syndrome. People with this condition may also compulsively lick their fingers and flip pages of books and magazines (a behavior known as "lick and flip"), as well as possessing an impressive ability to recall a wide range of small details about people or subject-specific trivia.Other symptoms can include short stature, abnormal curvature of the spine (scoliosis), reduced sensitivity to pain and temperature, and a hoarse voice. Some people with this disorder have ear abnormalities that lead to hearing loss. Affected individuals may have eye abnormalities that cause nearsightedness (myopia), strabismus, and other problems with vision. Heart and kidney defects also have been reported in people with Smith–Magenis syndrome, though they are less common. Genetics Smith–Magenis syndrome is a chromosomal condition related to low copy repeats of specific segments of chromosome 17. Most people with SMS have a deletion of genetic material from a specific region of chromosome 17 (17p11.2). Although this region contains multiple genes, recently researchers discovered that the loss of one particular gene the retinoic acid induced 1 or RAI1 is responsible for most of the characteristic features of this condition. Also, other genes within the chromosome 17 contribute to the variability and severity of the clinical features. The loss of other genes in the deleted region may help explain why the features of Smith–Magenis syndrome vary among affected individuals. A small percentage of people with Smith–Magenis syndrome have a mutation in the RAI1 gene instead of a chromosomal deletion. These deletions and mutations lead to the production of an abnormal or nonfunctional version of the RAI1 protein. RAI1 is a transcription factor that regulates the expression of multiple genes, including several that are involved in controlling circadian rhythm, such as CLOCK. The groups led by James Lupski (Baylor College of Medicine) and Sarah Elsea (Virginia Commonwealth University) are in the process of studying the exact function of this gene in relation to Smith Magenis Syndrome.SMS is typically not inherited. This condition usually results from a genetic change that occurs during the formation of reproductive cells (eggs or sperm) or in early fetal development. People with Smith–Magenis syndrome most often have no history of the condition in their family. Diagnosis SMS is usually confirmed by blood tests called chromosome (cytogenetic) analysis and utilize a technique called FISH (fluorescent in situ hybridization). The characteristic micro-deletion was sometimes overlooked in a standard FISH test, leading to a number of people with the symptoms of SMS with negative results. The recent development of the FISH for 17p11.2 deletion test has allowed more accurate detection of this deletion. However, further testing is required for variations of Smith–Magenis syndrome that are caused by a mutation of the RAI1 gene as opposed to a deletion. Children with SMS are often given psychiatric diagnoses such as autism, attention deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), attention deficit disorder (ADD) and/or mood disorders. Treatment Treatment for Smith–Magenis syndrome relies on managing its symptoms. Children with SMS often require several forms of support, including physical therapy, behaviour therapy, occupational therapy and speech therapy. Support is often required throughout an affected persons lifetime. Medication is often used to address some symptoms. Melatonin supplements and trazodone are commonly used to regulate sleep disturbances. In combination with exogenous melatonin, blockade of endogenous melatonin production during the day by the adrenergic antagonist acebutolol can increase concentration, improve sleep and sleep timing and aid in improvement of behaviour. Other medications (such as risperidone) are sometimes used to regulate violent behavior. Eponym The eponym Smith–Magenis refers to two scientists who described the condition in 1986, namely, Ann C. M. Smith, a genetic counselor at the National Institutes of Health, and R. Ellen Magenis, a pediatrician, medical geneticist and cytogeneticist at the Oregon Health Sciences University. See also Serine hydroxymethyltransferase Charcot-Marie-Tooth disease Potocki-Lupski syndrome Prader-Willi syndrome References This article incorporates public domain text from The U.S. National Library of Medicine == External links ==
Loose anagen syndrome	Loose anagen syndrome, also known as loose anagen hair syndrome, is a hair disorder related to dermatology. It is characterised by the easy and pain free detachment of anagen staged hairs from the scalp. This hair condition can be spontaneous or genetically inherited.Loose anagen syndrome is primarily described in fair-haired children who have easily dislodgeable hair.: 641 It is commonly present in younger children, generally between the ages of 2 to 8. It is especially observed in female children with light coloured hair. Females and males have differences in hair. There are knowledge gaps about loose anagen syndrome in males, and a 6 to 1 incidence ratio of females to males with loose anagen syndrome, respectively. Loose anagen syndrome may also be misdiagnosed in males, as males traditionally have short hair.Patients with loose anagen hair syndrome usually experience hair thinning around the whole scalp or at the occipital scalp, at the back of the head. Although this is a hair condition, there have only been reports of this condition also affecting the patients eyebrows. There are no noted impacts on any other hairs of the body such as eyebrows and eyelashes. It also does not have any impacts on nails, teeth or skin.Loose anagen syndrome is more predominantly seen in fairer skin and it is not as common in dark skin populations. Abdel-Raouf, El-Din, Awad, Ashraf, Mohammad, Hosan, Hasan, Moetaz, Tag and Mohammad have reported a population of dark skinned individuals with loose anagen syndrome. Each year there are approximately 2 to 2.5 cases per million people with loose anagen hair syndrome. Causes The main pathological cause of loose anagen syndrome is the absence or insufficient amount of the inner root sheath in the anagen staged hairs. This creates a gap in the linking between the inner root sheath and the hair cuticles. Both of these hair features stimulate hair growth but with this detachment in the linking, loose anagen hairs are not able to grow to a long length. The abnormalities caused by the inner root sheath creates disruption in the support and anchoring of the anagen hairs. Patients with loose anagen hair syndrome have mutations in the protein keratin K6HF, which is located in the middle of the hair shaft and inner root sheath, the companion layer. These mutations account for the phenotypical features of loose anagen syndrome. In the Huxley cells of the inner root sheath of abnormal anagen hairs, there is the formation of vacuoles and the build-up of fluid which is not usually seen. There are also dyskeratotic modifications in the Henle cells, as well as the cuticle cells in both the inner root sheath and hair shaft. The hair shaft has been reported as thin for some cases and normally structured for other loose anagen syndrome reports. The inner root sheath of normal anagen hairs usually do not have keratin in the Huxley cells, Henle cells and inner root sheath. They are usually organised in an orderly manner and densely compacted.Genetics is one of the causing factors of loose anagen syndrome. It has been studied that this hair condition is autosomal dominantly inherited. Diagnosis Patients with loose anagen syndrome do not report the same hair abnormalities. Loose anagen syndrome is usually diagnosed after taking into consideration the physical examination, clinical history and a microscopic examination of the hairs of the patient. Some patients visit a dermatologist for diagnosis and to distinguish between loose anagen hair syndrome and other conditions that it can be misdiagnosed for.A pull test is performed in order to diagnose a patient with loose anagen hair syndrome as one of the characteristics of this hair condition is hair that is easily removed from the scalp. A group of around 40-60 hairs, that are attached to the scalp, is pulled in a clement manner. The patient will be diagnosed with loose anagen syndrome if great amounts of hair is detached from the head. If at least 50% of the hairs removed is at the anagen hair stage, the outcome of the pull test is positive. The detachment of only 4-6 hairs is considered a normal outcome, as approximately 10% of the hairs on the scalp are at the telogen stage. The removed loose anagen hairs are not fragile and are of normal tensile strength.In an electron microscope image of a loose anagen hair, deformities such as grooves, curls and ridges are visible in the hair shaft, which is made from keratin. A cross-sectional examination of a loose anagen hair displays irregularity such as the shape of the hair being triangular rather than oval. The electron microscopy scanned image of the inner root sheath of a loose anagen hair would exhibit ultrastructural changes. These changes are visible in the Huxley layer, Henle layer and the cuticle of the loose anagen hair. An electron microscopy image of outer root sheath of an loose anagen hair would display malformations and weak linkage in the cells within the epithelium of the outer root sheath. This irregularity within the outer root sheath of a loose anagen hair is considered the most notable change when examining a loose anagen hair under an electron microscope.In a histopathological examination, the different layers of the loose anagen hair follicle will display a deficiency of clarity between the layers. This incoherence is also visible in a histological slide of the inner root sheath and of the outer root sheath.Biopsies are not necessary for the diagnosis of loose anagen hair syndrome. A biopsy will display non-inflammatory, non-scarring alopecia.The texture of the hair varies with some reports stating that patients with loose anagen syndrome have hairs that are rough, brittle and sticky. This may be the result of the deformations of the hair shaft. These changes in texture limits the ability for adjacent loose anagen hairs to rest flat on the scalp. The patient can have thinning and loss of hair around the whole scalp, at the occipital scalp or around the scalp in odd, irregular patches. Loose anagen syndrome hairs at the occipital scalp can be knotted easily when theres movement of those hairs against the pillow at night.There are 3 different types of loose anagen hair syndrome. Loose anagen syndrome type A is when the hair of the patient appears to be fine and thinly distributed. Patients with type A loose anagen syndrome experience a decrease in the density of their hairs. Patients diagnosed with type B loose anagen hair syndrome tend to have hair that is difficult to manage and has a disordered, unruly appearance. Type C loose anagen syndrome is when the hair sheds but the appearance of their hair appears to be normal. Loose anagen syndrome type A and B are more prevalent in children. Loose anagen hair syndrome type C is most frequently seen in adults. There is not specific treatment for each type of loose anagen syndrome. It is also unknown as to how each type is developed. Differential diagnosis Loose Anagen Syndrome can commonly be misdiagnosed for other skin and hair disorders such as short anagen syndrome, alopecia areata, telogen effluvium, trichotillomania and toxic ingestion. Similar symptoms and signs appear in these conditions, however there are different aspects that distinguish each one from another. Short anagen syndrome and loose anagen syndrome are similar as both conditions lead to the inability to grow long hair and patients rarely need to get their hair cut. A difference between these two hair disorders is that in loose anagen syndrome there are dystrophic hairs which are absent in patients with short anagen syndrome.Patients with loose anagen syndrome may experience the thinning of their hair which is also a factor of alopecia areata. In order to distinguish between these two conditions, if dots, hairs with tapered roots or vellus hairs are visible in a microscopic examination of the skin this will lead to the diagnosis of alopecia areta rather than loose anagen syndrome.Hair loss can lead to other symptoms and signs such as weight loss, behavioural changes, short temper, abdominal pain and problems with learning. These signs are also observed in children with toxic ingestion which is one of the differential diagnosis.A pull test is also used in the diagnosis of telogen effluvium. The hairs that are removed in a telogen effluvium pull test are telogen staged hairs instead of being at the anagen stage as seen in loose anagen hair syndrome. Associated conditions Loose anagen syndrome usually appears as an individual condition. Loose anagen syndrome can be present with other conditions related to genetics or developmental conditions. Examples of these conditions include; Coloboma, Noonan syndrome, Hypohidrotic ectodermal dysplasia, EEC (ectrodactyly- ectodermal dysplasia-clefting) syndrome, Neurofibromatosis, Trichorhinophalangeal syndrome, Trichotillomania, Nail-patella syndrome and Woolly hair. Loose anagen hair syndrome has also been associated with AIDS.Alopecia areata patients can also develop loose anagen syndrome. Treatment Loose anagen syndrome usually does not need treatment as this hair condition tends to improve with age and is self-limited. Many patients affected by loose anagen hair syndrome encounter spontaneous recovery by adulthood. The thickness and length of the hair of loose anagen syndrome patients have a tendency to improve and becomes more enhanced, especially post puberty. For some patients, improvement is observed from the ages of 8 or 9. There is still a defect in the connection of the hair shaft and inner root sheath, however it is not as severe and the hairs are not as easily detached as it was for these patients when they were young children. Patients can seek assistance and treatment can be pursued.The aims of treatment is to reduce the trauma being enacted on loose anagen hairs and to reassure loose anagen hair syndrome patients that over time there will be improvement in the cosmetics of their hair. Paediatricians, paediatric nurse practitioners and physician assistances are usually the first people to detect this hair condition in children. There are no surgical, physical or systemic medical treatment options for loose anagen syndrome.Patients with more severe cases of loose anagen hair syndrome can be treated with minoxidil, a topical medical treatment, as a first line treatment. Minoxidil can extend the duration of the hair in the anagen stage and restore the hair follicles for further growth or for the full period of the anagen phase. The hair of an individual without loose anagen hair syndrome is in the anagen hair phase for approximately 3 to 5 years. Minoxidil can be used as it enriches the cells of the hair by heightening the blood supply of local cutaneous. From this, there is intensified DNA synthesis occurring in both follicular keratinocytes and non-follicular, as well as an increase in cell multiplication. The degree of hair shedding is reduced with the use of minoxidil. 7 in 11 loose anagen hair syndrome patients find visible improvement after using minoxidil lotion. Treatment involving the maintenance of nutrients within the patient and biotin have not made any noted impacts to the improvement of loose anagen hair syndrome. Management For children, changes to their lifestyle and daily routine are altered and improved to reduce trauma to hair. This includes modifications in hair maintenance such as different washing, styling and combing techniques are adapted, as an attempt to minimise trauma to loose anagen syndrome hairs. Young girls are also recommended to avoid activities such as extreme braiding. Caring for hair gently will minimise the amount of loosely anchored hairs being removed from scalp. History The first published report on loose anagen syndrome was made in 1986 by Nodl and then by Zaun. Loose anagen syndrome was originally referred to as ‘syndrome of loosely attached hair in childhood’. The name ‘loose anagen syndrome’ was first adapted in 1989 by Price, Gummer, Hamm and Traupe in American literature. Early literature on loose anagen syndrome all reported identical findings. The genetic aspects and potential mechanisms for the cause of loose anagen syndrome was first discovered in 1992 by Baden, Kvedar and Magro. The ultrastructural changes in loose anagen hairs were examined by Mirmirani, Price and Uno. See also List of cutaneous conditions == References ==
Epileptic spasms	Epileptic spasms is an uncommon-to-rare epileptic disorder in infants, children and adults. One of the other names of the disorder, West syndrome, is in memory of the English physician, William James West (1793–1848), who first described it in an article published in The Lancet in 1841. The original case actually described his own son, James Edwin West (1840–1860). Other names for it are "generalized flexion epilepsy", "infantile epileptic encephalopathy", "infantile myoclonic encephalopathy", "jackknife convulsions", "massive myoclonia" and "Salaam spasms". The term "infantile spasms" can be used to describe the specific seizure manifestation in the syndrome, but is also used as a synonym for the syndrome itself. West syndrome in modern usage is the triad of infantile spasms, a pathognomonic EEG pattern (called hypsarrhythmia), and developmental regression – although the international definition requires only two out of these three elements. The syndrome is age-related, generally occurring between the third and the twelfth month, generally manifesting around the fifth month. There are various causes. The syndrome is often caused by an organic brain dysfunction whose origins may be prenatal, perinatal (caused during birth) or postnatal. Signs and symptoms The epileptic seizures observed in infants with West syndrome, fall into three categories, collectively known as infantile spasms. Typically, the following triad of attack types appears; while the three types usually appear simultaneously, they also can occur independently of each other: Lightning attacks: Sudden, severe myoclonic convulsions of the entire body or several parts of the body in split seconds, and the legs in particular are bent (flexor muscle convulsions here are generally more severe than extensor ones). Nodding attacks: Convulsions of the throat and neck flexor muscles, during which the chin is fitfully jerked towards the breast or the head is drawn inward. Salaam or jackknife attacks: a flexor spasm with rapid bending of the head and torso forward and simultaneous raising and bending of the arms while partially drawing the hands together in front of the chest and/or flailing. If one imagined this act in slow motion, it would appear similar to the Muslim ceremonial greeting (Salaam), from which this type of attack derives its name. Cause It is still unknown which bio-chemical mechanisms lead to the occurrence of West syndrome. It is known to be a malfunction of neurotransmitter function, or more precisely, a malfunction in the regulation of the GABA transmission process. Another possibility being researched is a hyper-production of the corticotropin-releasing hormone (CRH). It is possible that more than one factor is involved. Both hypotheses are supported by the effect of certain medications used to treat West syndrome.Cases of epilepsy have been historically divided into three different groups: symptomatic, cryptogenic, and unknown. The International League Against Epilepsy (ILAE) in 2011 recommended abandoning these terms for reasons of clarity and instead trying to place individual cases into one of the following three groups: genetic, structural/metabolic, and unknown. The new terms are more immediately clear in their meaning, except that the structural and metabolic group includes cases that have a genetic component that does not always directly lead to the condition. Only the genetic grouping has a known direct genetic cause. "Unknown" cases may be of unknown genetic, structural, metabolic, or other unknown cause.The old terminology was defined by the ILAE as follows: symptomatic: the epilepsy is the consequence of a known or suspected disorder of the central nervous system. cryptogenic: this refers to a disorder whose cause is hidden or occult. Cryptogenic epilepsies are presumed to be symptomatic. idiopathic: there is no underlying cause other than a possible hereditary predisposition.The remainder of this section will refer to the older terminology. Symptomatic If a cause presents itself, the syndrome is referred to as symptomatic West syndrome, as the attacks manifest as a symptom of another problem. Almost any cause of brain damage could be associated, and these are divided into prenatal, perinatal, and post-natal. The following is a partial list: In around one third of the children, there is evidence of a profound organic disorder of the brain. This includes:microcephaly cortical dysplasia cerebral atrophy lissencephaly bacterial meningitis phakomatoses (e.g. tuberous sclerosis) Aicardi syndrome cephalhematoma and vascular malformation. Furthermore, other causes increasingly being named in the literature are: Incontinentia pigmenti Foix–Chavany–Marie syndrome Patau syndrome (trisomy 13) Sturge–Weber syndrome neurometabolic diseases congential infections (e.g. Cytomegalovirus) hypoglycemia brain damage due to asphyxiation or hypoxia (lack of oxygen, e.g. during birth), periventricular leukomalacia, cephalhematoma, cerebrovascular accident or brain damage of various types as well as that caused by premature birth. Down syndrome West syndrome appears in 1% to 5% of infants with Down syndrome. This form of epilepsy is relatively difficult to treat in children who do not have the chromosomal abnormalities involved in Down syndrome. However, in children with Down syndrome, the syndrome is often far more mild, and the children often react better to medication. The German Down Syndrome Info Center noted in 2003 that what was normally a serious epilepsy was in such cases often a relatively benign one.EEG records for children with Down syndrome are often more symmetrical with fewer unusual findings. Although not all children can become entirely free from attacks with medication, children with Down syndrome are less likely to go on to develop Lennox-Gastaut syndrome or other forms of epilepsy than those without additional hereditary material on the 21st chromosome. The reason why it is easier to treat children with Down syndrome is not known.If, however, a child with Down syndrome has seizures that are difficult to control, the child should be assessed for autistic spectrum disorder. Cryptogenic When a direct cause cannot be determined but the child has other neurological disorder, the case is referred to as cryptogenic West syndrome. The cryptogenic group is often considered idiopathic while referred to as "cryptogenic".Sometimes multiple children within the same family develop West syndrome. In this case, it is also referred to as cryptogenic, in which genetic and sometimes hereditary influences play a role. There are known cases in which West syndrome appears in successive generations in boys; this has to do with X-chromosomal heredity. Genetic Mutations in several genes have been associated with West syndrome. These include the Aristaless related homeobox (ARX) and cyclin dependent kinase like 5 (CDKL5) genes. The ARX gene in particular seems to be responsible for at least some of the X linked cases. Variants in the KCNT1 gene can also in rare cases result in West syndrome. Idiopathic Occasionally the syndrome is referred to as idiopathic West syndrome, when a cause cannot be determined. Important diagnostic criteria are: Regular development until the onset of the attacks or before the beginning of the therapy no pathological findings in neurological or neuroradiological studies no evidence of a trigger for the spasmsThose are becoming rare due to modern medicine. Diagnosis Diagnosis can be made by EEG. In case of epileptic spasms, EEG shows typical hypsarrhythmia patterns. Treatment As of 2017, data on optimal treatment was limited. Therapies with hormones is the standard of care, namely adrenocorticotrophic hormone (ACTH), or oral corticosteroids such as prednisone. Vigabatrin is also a common consideration, though there is a risk of visual field loss with long term use. The high cost of ACTH leads doctors to avoid it in the US; higher dose prednisone appears to generate equivalent outcomes.As of 2017 data from clinical trials of the ketogenic diet for treating infantile spams was inconsistent; most trials were as a second-line therapy after failure of drug treatment, and as of 2017 it had not been explored as a first line treatment in an adequately designed clinical trial. Epilepsy surgery is recommended in patients with seizures arising from a restricted region. Prognosis It is not possible to make a generalised prognosis for development due to the variability of causes, as mentioned above, the differing types of symptoms and cause. Each case must be considered individually.The prognosis for children with idiopathic West syndrome are mostly more positive than for those with the cryptogenic or symptomatic forms. Idiopathic cases are less likely to show signs of developmental problems before the attacks begin, the attacks can often be treated more easily and effectively and there is a lower relapse rate. Children with this form of the syndrome are less likely to go on to develop other forms of epilepsy; around two in every five children develop at the same rate as healthy children.In other cases, however, treatment of West syndrome is relatively difficult and the results of therapy often dissatisfying; for children with symptomatic and cryptogenic West syndrome, the prognosis is generally not positive, especially when they prove resistant to therapy.Statistically, 5 out of every 100 children with West syndrome do not survive beyond five years of age, in some cases due to the cause of the syndrome, in others for reasons related to their medication. Only less than half of all children can become entirely free from attacks with the help of medication. Statistics show that treatment produces a satisfactory result in around three out of ten cases, with only one in every 25 childrens cognitive and motoric development developing more or less normally.A large proportion (up to 90%) of children experience severe physical and cognitive impairments, even when treatment for the seizures is successful. This is not usually because of the epileptic seizures, but rather because of the causes behind them (cerebral anomalies or their location or degree of severity). Severe, frequent attacks can (further) damage the brain.Permanent damage often associated with West syndrome in the literature include cognitive disabilities, learning difficulties and behavioural problems, cerebral palsy (up to 5 out of 10 children), psychological disorders and often autism (in around 3 out of 10 children). Once more, the cause of each individual case of West syndrome must be considered when debating cause and effect.As many as 6 out of 10 children with West syndrome have epilepsy later in life. Sometimes West syndrome turns into a focal or other generalised epilepsy. Around half of all children develop Lennox-Gastaut syndrome. Epidemiology Incidence is around 1:3200 to 1:3500 of live births. Statistically, boys are more likely to be affected than girls at a ratio of around 3:2. In 9 out of every 10 children affected, the spasms appear for the first time between the third and the twelfth month of age. In rarer cases, spasms may occur in the first two months or during the second to fourth year of age. History West syndrome was named after the English doctor and surgeon William James West (1793–1848), who lived in Tonbridge. In 1841 he observed this type of epilepsy in his own son, James E West, who was approximately four months old at the time. He published his observations from a scientific perspective in an article in The Lancet. He named the seizures "Salaam Tics" at the time. See also Epilepsy Phenome/Genome Project References External links Much of this article is translated from the German Wikipedia article
Steroid acne	Steroid acne is an adverse reaction to corticosteroids, and presents as small, firm follicular papules on the forehead, cheeks, and chest.: 137 Steroid acne presents with monomorphous pink paupules, as well as comedones, which may be indistinguishable from those of acne vulgaris. Steroid acne is commonly associated with endogenous or exogenous sources of androgen, drug therapy, or diabetes and is less commonly associated with HIV infection or Hodgkins disease. See also List of cutaneous conditions Steroid folliculitis References External links == External links ==
Glanzmanns thrombasthenia	Glanzmanns thrombasthenia is an abnormality of the platelets. It is an extremely rare coagulopathy (bleeding disorder due to a blood abnormality), in which the platelets contain defective or low levels of glycoprotein IIb/IIIa (GpIIb/IIIa), which is a receptor for fibrinogen. As a result, no fibrinogen bridging of platelets to other platelets can occur, and the bleeding time is significantly prolonged. Signs and symptoms Characteristically, there is increased mucosal bleeding: heavy menstrual bleeding easy bruising nosebleeds Bleeding from the gums gastrointestinal bleeding postpartum bleeding increased postoperative bleeding.The bleeding tendency is variable but may be severe. Bleeding into the joints, particularly spontaneous bleeds, are very rare, in contrast to the hemophilias. Platelet numbers and morphology are normal. Platelet aggregation is normal with ristocetin, but impaired with other agonists such as ADP, thrombin, collagen, or epinephrine. Cause Glanzmanns thrombasthenia can be inherited in an autosomal recessive manner or acquired as an autoimmune disorder.The bleeding tendency in Glanzmanns thrombasthenia is variable, some individuals having minimal bruising, while others have frequent, severe, potentially fatal hemorrhages. Moreover, platelet αIIbβ3 levels correlate poorly with hemorrhagic severity, as virtually undetectable αIIbβ3 levels can correlate with negligible bleeding symptoms, and 10%–15% levels can correlate with severe bleeding. Unidentified factors other than the platelet defect itself may have important roles. Pathophysiology Glanzmanns thrombasthenia is associated with abnormal integrin αIIbβ3, formerly known as glycoprotein IIb/IIIa (GpIIb/IIIa), which is an integrin aggregation receptor on platelets. This receptor is activated when the platelet is stimulated by ADP, epinephrine, collagen, or thrombin. GpIIb/IIIa is essential to blood coagulation since the activated receptor has the ability to bind fibrinogen (as well as von Willebrand factor, fibronectin, and vitronectin), which is required for fibrinogen-dependent platelet-platelet interaction (aggregation). Understanding of the role of GpIIb/IIIa in Glanzmanns thrombasthenia led to the development of GpIIb/IIIa inhibitors, a class of powerful antiplatelet agents. Diagnosis Light transmission aggregometry is widely accepted as the gold standard diagnostic tool for assessing platelet function, and a result of absent aggregation with any agonist except ristocetin is highly specific for Glanzmanns thrombasthenia. Following is a table comparing its result with other platelet aggregation disorders: Treatment Therapy involves both preventive measures and treatment of specific bleeding episodes. Dental hygiene lessens gingival bleeding Avoidance of antiplatelet agents such as aspirin and other anti-inflammatory drugs (NSAIDs) such as ibuprofen and naproxen, and anticoagulants Iron or folate supplementation may be necessary if excessive or prolonged bleeding has caused anemia Hepatitis B vaccine Antifibrinolytic drugs such as tranexamic acid or ε-aminocaproic acid (Amicar) Desmopressin (DDAVP) does not normalize the bleeding time in Glanzmanns thrombasthenia but anecdotally improves hemostasis Hormonal contraceptives to control excessive menstrual bleeding Topical agents such as gelfoam, fibrin sealants, polyethylene glycol polymers, custom dental splints Platelet transfusions (only if bleeding is severe; risk of platelet alloimmunization) Recombinant factor VIIa, AryoSeven or NovoSeven FDA approved this drug for the treatment of the disease in July 2014. Hematopoietic stem cell transplantation (HSCT) for severe recurrent hemorrhages Eponym It is named after Eduard Glanzmann (1887-1959), the Swiss pediatrician who originally described it. History The subsequent studies, following Eduard Glanzmanns description of hemorrhagic symptoms and "weak platelets" demonstrated that these patients have prolonged bleeding times and their platelets failed to aggregate in response to activation. In the mid-1970s, Nurden and Caen and Phillips and colleagues discovered that thrombasthenic platelets are deficient in integrins αIIbβ3. See also Platelet Coagulation Bernard-Soulier syndrome References == External links ==
Macrotia	Macrotia refers to an ear that is larger than would be expected. The normal auricular axis length is 58–62 mm (2.3–2.4 in) among females and 62–66 mm (2.4–2.6 in) among males. The average width of an adult ear, specifically the distance between the helix root (inner front edge) and the posterior auricle (outer front edge), is between 30 and 40 mm (1.2 and 1.6 in). Treatment for Macrotia Macrotia is an external ear malformation and is not known to cause any hearing impairment on its own, although it may occasionally occur simultaneously with other developmental disorders that do affect hearing. Treatment is typically not necessary, although patients may seek cosmetic treatment. In some cases, surgery (otoplasty) is performed to reduce the ear size. While generally considered a cosmetic procedure, otoplasty for macrotia can improve overall quality of life, especially for young patients who may be able to avoid reduced self-esteem and social avoidance behavior due to large ears. Otoplasty for macrotia typically focuses on reducing the size of the scapha, which is the concave region of the ear between the helix and antihelix ridge, while preserving ear shape and contour. References == External links ==
Ankyloblepharon	Ankyloblepharon is defined as the adhesion of the edges of the upper eyelid with the lower eyelid. Ankyloblepharon must be differentiated from blepharophimosis, in which palpebral aperture is reduced and there is telecanthus, but the eyelid margins are normal. Another condition similar to ankyloblepharon is symblepharon, in which the palpebral conjunctiva is attached to the bulbar conjunctiva. Recognition of ankyloblepharon necessitates systemic examination to detect associated abnormalities such as genitourinary and cardiac abnormalities and syndactyly. Presentation Complication The main complication of congenital ankyloblepharon is amblyopia. Timely separation of the eyelids is very important to avoid the development of occlusion amblyopia. Etiology Ankyloblepharon may be congenital or acquired. The most common type is congenital.Clinically, ankyloblepharon may be complete, partial, or interrupted. Complete ankyloblepharon is when the eyelids are fused throughout the lid margins. In the partial form, they are joined at one or more points. The interrupted form is also known as ankyloblepharon filiforme adnatum (AFA). Congenital ankyloblepharon During fetal development, eyelid margins remain fused until the fifth gestational month, and may not be completely separated until the seventh month of gestation. Congenital ankyloblepharon occurs when the lid margins fail to separate at birth. The exact etiology of this condition is unknown. The currently accepted theory is that this condition is due to temporary epithelial arrest and rapid mesenchymal proliferation, allowing union of eyelids at abnormal positions. Systemic associations Congenital ankyloblepharon is seen in association with: Hay–Wells syndrome: Ankyloblepharon-Ectodermal dysplasia-Clefting (AEC) syndrome also known as Hay-Wells syndrome is a rare autosomal dominant disorder characterized by ankyloblepharon, ectodermal dysplasia, and cleft palate and/or cleft lip. Curly hair–ankyloblepharon–nail disease (CHAND) syndrome: it is a clinical variant of AEC syndrome. It is also known as Baughman syndrome. Trisomy 18 (Edwards syndrome): AFA may be seen in association with trisomy 18. Popliteal pterygium syndrome (PPS): Popliteal pterygium syndrome (PPS) is a rare autosomal dominant disorder, first described by Trelat in 1869. The clinical features of the syndrome are highly variable and show different combinations of anomalies like cleft palate, cleft lip, lower lip pits or sinuses, popliteal webbing, syndactyly, genitourinary anomalies, nail anomalies, syngnathia, ankyloblepharon, talipes, and digital reduction defects. Acquired ankyloblepharon Acquired ankyloblepharon may occur due to trauma or inflammatory conditions. It may be associated with symblepharon also. The following conditions cause ankyloblepharon: Chemical burns, thermal burns, or trauma to the eyes Cicatrising diseases such as Stevens–Johnson syndrome or cicatricial ocular pemphigoid Inflammatory diseases such as herpes simplex infection or ulcerative blepharitis Trachoma Cicatricial conjunctivitis Mucous membrane pemphigoid: ocular form of mucous membrane pemphigoid may cause ankyloblepharon (4th stage of foster grading system). Treatment Lids should be separated by excision of adhesions between the lid margins and kept apart during the healing process. When adhesions extend to the angles, epithelial grafts should be given to prevent recurrences. History Ankyloblepharon was first described by von Anmmon in 1841. Ankyloblepharon filiforme adnatum (AFA), the interrupted form of Ankyloblepharon, was first described by Von Hasner in 1881. Etymology The word ankyloblepharon is derived from Greek ankylos (ἀγκύλος) bent, crooked, closed and blepharon (βλέφαρον) eyelid. See also Symblepharon Blepharophimosis == References ==
Neonatal hypocalcemia	Neonatal hypocalcemia is an abnormal clinical and laboratory hypocalcemia condition that is frequently observed in infants. It is commonly presented within the first 72 hours of a newborns life.Healthy term infants go through a physiological nadir of serum calcium levels at 7.5 - 8.5 mg/dL by day 2 of life. Hypocalcemia is a low blood calcium level. A total serum calcium of less than 8 mg/dL (2mmol/L) or ionized calcium less than 1.2 mmol/L in term neonates is defined as hypocalcemia. In preterm infants, it is defined as less than 7mg/dL (1.75 mmol/L) total serum calcium or less than 4mg/dL (1 mmol/L) ionized calcium. Both early onset hypocalcemia (presents within 72h of birth) and late onset hypocalcemia (presents in 3-7 days after birth) require calcium supplementation treatment. Infants with intrauterine growth retardation, perinatal asphyxia, preterm, and diabetic mothers are most likely to develop neonatal hypocalcemia. It is not understood why premature infants have hypocalcemia, but a proposed idea is that a large increase of calcitonin may lead to hypocalcemia. Another hypothesis includes impaired secretion of PTH or Parathyroid hormone. Cause Risk factors of early neonatal hypocalcemia Prematurity Perinatal asphyxia Diabetes mellitus in the mother Maternal hyperparathyroidism Intrauterine growth retardation (IUGR) Iatrogenic Risk factors Risk factors of late neonatal hypocalcemia Exogenous phosphate load Use of gentamicin Gender and ethnic: late neonatal hypocalcemia occurred more often in male infants and Hispanic infants OthersMagnesium deficiency Transient hypoparathyroidism of newborn Hypoparathyroidism due to other causes (DiGeorge Syndrome) References Jain, A., Agarwal, R., Sankar, M. J., Deorari, A., & Paul, V. K. (2010). Hypocalcemia in the newborn. Indian Journal of Pediatrics, 77, 1123-1128. Oden, J., Bourgeois, M. (2000). Neonatal endocrinology. Indian Journal of Pediatrics, 77, 21
Bowenoid papulosis	Bowenoid papulosis is a cutaneous condition characterized by the presence of pigmented verrucous papules on the body of the penis.: 730 : 408 They are associated with human papillomavirus, the causative agent of genital warts. The lesions have a typical dysplastic histology and are generally considered benign, although a small percentage will develop malignant characteristics.It is considered as a pre-malignant condition. Other terms used to describe the condition are: Erythroplasia of Queyrat, Squamous cell carcinoma in situ and Bowens disease. The term bowenoid papulosis was coined in 1977 by Kopf and Bart and is named after dermatologist John Templeton Bowen. The term "intraepithelial neoplasia" defines a premalignant intraepithelial change.On the vulva it is termed VIN (vulvar or vulval intraepithelial neoplasia); on the penis, PIN (penile intraepithelial neoplasia); and on or around the anus, AIN (anal intraepithelial neoplasia). The terminology has been very confusing and it is now recommended that the terms Bowens disease, erythroplasia of Queyrat, and bowenoid papulosis should not be used for lesions in the anogenital area. However, dermatologists still recognize a distinct clinical variant, bowenoid papulosis, characterized by discrete papules in a younger age group and a tendency for spontaneous regression. Additionally, some authorities believe that erythroplasia of Queyrat and Bowens disease remain useful terms in men. See also Skin lesion Sexually transmitted infection References == External links ==
Pubic symphysis	The pubic symphysis is a secondary cartilaginous joint between the left and right superior rami of the pubis of the hip bones. It is in front of and below the urinary bladder. In males, the suspensory ligament of the penis attaches to the pubic symphysis. In females, the pubic symphysis is close to the clitoris. In most adults it can be moved roughly 2 mm and with 1 degree rotation. This increases for women at the time of childbirth.The name comes from the Greek word symphysis, meaning growing together. Structure The pubic symphysis is a nonsynovial amphiarthrodial joint. The width of the pubic symphysis at the front is 3–5 mm greater than its width at the back. This joint is connected by fibrocartilage and may contain a fluid-filled cavity; the center is avascular, possibly due to the nature of the compressive forces passing through this joint, which may lead to harmful vascular disease. The ends of both pubic bones are covered by a thin layer of hyaline cartilage attached to the fibrocartilage. The fibrocartilaginous disk is reinforced by a series of ligaments. These ligaments cling to the fibrocartilaginous disk to the point that fibers intermix with it. Two such ligaments are the superior pubic ligament and the inferior pubic ligament, which provide the most stability; the anterior and posterior ligaments are weaker. The strong and thicker superior ligament is reinforced by the tendons of the rectus abdominis muscle, the abdominal external oblique muscle, the gracilis muscle, and by muscles of the hip. The superior pubic ligament connects together the two pubic bones superiorly, extending laterally as far as the pubic tubercles. The inferior ligament in the pubic arch is also known as the arcuate pubic ligament or subpubic ligament; it is a thick, triangular arch of ligamentous fibers, connecting together the two pubic bones below, and forming the upper boundary of the pubic arch. Above, it is blended with the interpubic fibrocartilaginous lamina; laterally, it is attached to the inferior rami of the pubic bones; below, it is free, and is separated from the fascia of the urogenital diaphragm by an opening through which the deep dorsal vein of the penis passes into the pelvis. Fibrocartilage Fibrocartilage is composed of small, chained bundles of thick, clearly defined, type I collagen fibers. This fibrous connective tissue bundles have cartilage cells between them; these cells to a certain extent resemble tendon cells. The collagenous fibers are usually placed in an orderly arrangement parallel to tension on the tissue. It has a low content of glycosaminoglycans (2% of dry weight). Glycosaminoglycans are long, unbranched polysaccharides (relatively complex carbohydrates) consisting of repeating disaccharide units. Fibrocartilage does not have a surrounding perichondrium. Perichondrium surrounds the cartilage of developing bone; it has a layer of dense, irregular connective tissue and functions in the growth and repair of cartilage. Hyaline cartilage Hyaline cartilage is the white, shiny gristle at the end of long bones. This cartilage has poor healing potential, and efforts to induce it to repair itself frequently end up with a similar, but poorer fibrocartilage. Development In the newborn, the symphysis pubis is 9–10 mm in width, with thick cartilaginous end-plates. By mid-adolescence the adult size is achieved. During adulthood the end-plates decrease in width to a thinner layer. Degeneration of the symphysis pubis accompanies aging and postpartum. Women have a greater thickness of this pubic disc which allows more mobility of the pelvic bones, hence providing a greater diameter of pelvic cavity during childbirth. Function Analysis of the pelvis shows the skinny regions function as arches, transferring the weight of the upright trunk from the sacrum to the hips. The symphysis pubis connects these two weight-bearing arches, and the ligaments that surround this pelvic region maintain the mechanical integrity. The main motions of the symphysis pubis are superior/inferior glide and separation/compression. The functions of the joint are to absorb shock during walking and allow delivery of a baby. Clinical significance Injury The pubic symphysis widens slightly when the legs are stretched far apart. In sports where these movements are often performed, the risk of a pubic symphysis blockage is high, in which case, after completion of the movement, the bones at the symphysis do not realign correctly and can get jammed in a dislocated position. The resulting pain can be severe, especially when further strain is put upon the affected joint. In most cases, the joint can only be successfully reduced into its normal position by a trained medical professional. Disease Metabolic diseases, such as renal osteodystrophy, produce widening, while ochronosis results in calcific deposits in the symphysis. Inflammatory diseases, such as ankylosing spondylitis, result in bony fusion of the symphysis. Osteitis pubis, the most common inflammatory disease in this area, is treated with anti-inflammatory medication and rest. Degenerative joint disease of the symphysis, which can cause groin pain, results from instability or from abnormal pelvic mechanics. Symphysiolysis is separation or slipping of the symphysis. It has been estimated to occur in 0.2% of pregnancies. Pregnancy During pregnancy in the human, hormones such as relaxin remodel this ligamentous capsule allowing the pelvic bones to be more flexible for delivery. The gap of the symphysis pubis, normally is 4–5 mm but during pregnancy there will be an increase of at least 2–3 mm, therefore, it is considered that a total width of up to 9 mm between the two bones is normal for a pregnant woman. The symphysis pubis separates to some degree during childbirth. In some women this separation can become a diastasis of the symphysis pubis. The diastasis could be the result of a rapid birth, or a forceps delivery, or may be a prenatal condition. A diastasis of the symphysis pubis is a cause of pelvic girdle pain (PGP). Overall, about 45% of all pregnant women and 25% of all women postpartum suffer from PGP. Symphysiotomy Symphysiotomy is a surgical procedure in which the cartilage of the pubic symphysis is divided to widen the pelvis allowing childbirth when there is a mechanical problem. It allows the safe delivery of the fetus where Caesarean section is not an option. Symphysiotomy is suggested for woman in isolated areas experiencing obstructed labor where other medical intervention is unavailable.This practice was carried out in Europe before the introduction of the Caesarean section. Historically, during obstructed labor, the skull of the fetus was also, at least occasionally, crushed in order to further facilitate the delivery. Society and culture Use in forensic anthropology Pubic symphyses have importance in the field of forensic anthropology, as they can be used to estimate the age of adult skeletons. Throughout life, the surfaces are worn at a fairly predictable rate. By examining the wear of the pubic symphysis, it is possible to estimate the age of the person at death. Additional images See also References External links Pelvic Instability Network Support (PINS) Anatomy photo:17:st-0206 at the SUNY Downstate Medical Center – "Major Joints of the Lower Extremity – hip and sacrum (anterior view)" Anatomy photo:44:03-0104 at the SUNY Downstate Medical Center – "The Male Pelvis: Hemisection of the Male Pelvis" Cross section image: pelvis/pelvis-e12-15—Plastination Laboratory at the Medical University of Vienna
Balkan endemic nephropathy	Balkan endemic nephropathy (BEN) is a form of interstitial nephritis causing kidney failure. It was first identified in the 1920s among several small, discrete communities along the Danube River and its major tributaries, in the modern countries of Croatia, Bosnia and Herzegovina, Serbia, Romania, and Bulgaria. It is caused by small long-term doses of aristolochic acid in the diet. The disease primarily affects people 30 to 60 years of age. Doses of the toxin are usually low and people moving to endemic areas typically develop the condition only when they have lived there for 10–20 years. People taking higher doses of aristolochic acid (as Chinese herbal supplements) have developed kidney failure after shorter durations of exposure. Signs and symptoms The patients are distinguished from those suffering from other causes of end-stage renal disease by showing an absence of high blood pressure, xanthochromia of palms and soles (Tanchevs sign), early hypochromic anemia, absence of proteinuria, and slow progression of kidney failure. There is no specific therapy; BEN causes end-stage renal disease, for which the only effective treatments are dialysis or a kidney transplant. In endemic areas BEN is responsible for up to 70% of end-stage renal disease. At least 25,000 individuals are known to have this form of the disease.Patients with BEN have a greatly increased rate of transitional cell carcinoma of the upper urothelial tract, (the renal pelvis and ureters). (In populations without BEN, most urothelial cancer occurs in the bladder. ) Causes Dietary exposure to aristolochic acid is the cause of BEN and its attendant transitional cell cancers. Former hypotheses that included roles for ochratoxin, poisoning by organic compounds leached from lignite or by heavy metals, viruses, and trace-element deficiencies, are not supported by current evidence. Genetic factors may be involved in determining which persons exposed to aristolochic acid suffer from BEN and which do not.In the Balkan region, dietary aristolochic acid exposure may come from the consumption of the seeds of Aristolochia clematitis (European birthwort), a plant native to the endemic region, which grows among wheat plants and whose seeds mingle with the wheat used for bread. Aristolochic-acid-containing herbal remedies used in traditional Chinese medicine are associated with a related—possibly identical—condition known as "Chinese herbs nephropathy".Exposure to aristolochic acid is associated with a high incidence of uroepithelial tumorigenesis. Diagnosis History The first official published description of the disease was made by the Bulgarian nephrologist Dr.Yoto Tanchev (1917–2000) and his team in 1956 in the Bulgarian Journal Savremenna Medizina, a priority generally acknowledged by the international nephrological community. Their study was based on a wide screening of inhabitants of the villages around the town of Vratsa, Bulgaria. Their contribution to the understanding of this unusual endemic disease of the kidneys was their description of symptoms which were not typical of common chronic nephritis, i.e., incidence only in adults (no children affected), absence of high blood pressure, xanthochromia of palms and soles (Tanchevs sign), early hypochromic anemia, absence of proteinuria, and slow progression of kidney failure.A striking feature of the disease is its very localized occurrence. There are approximately ten small areas where it occurs, all of them more or less rural, but nothing seems to connect those areas other than the occurrence of this illness. Tanchev and colleagues suggested that the condition was sui generis. Their initial tentative hypothesis for its cause was intoxication with heavy metals, because the affected villages were supplied with water coming from nearby Vratsa Mountain, a karst-type mountain.The disease was originally called "Vratsa nephritis," and became known as "Balkan endemic nephropathy" later, after people living in Yugoslavia and Romania were found to be suffering from it as well. But in Bulgaria and in neighbouring countries, the condition is known as "Tanchevs Nephropathy", in homage to Dr. Tanchevs work. See also Nephropathy Citrinin Ochratoxin A References == External links ==
Anorgasmia	Anorgasmia is a type of sexual dysfunction in which a person cannot achieve orgasm despite adequate stimulation. Anorgasmia is far more common in females (4.6 percent) than in males and is especially rare in younger men. The problem is greater in women who are post-menopausal. In males, it is most closely associated with delayed ejaculation. Anorgasmia can often cause sexual frustration. Causes The condition is sometimes classified as a psychiatric disorder. However, it can also be caused by physiological problems such as diabetic neuropathy, multiple sclerosis, Parkinsons disease, genital mutilation on any gender, complications from genital surgery, pelvic trauma (such as from a straddle injury caused by falling on the bars of a climbing frame, bicycle or gymnastics beam), hormonal imbalances, total hysterectomy, spinal cord injury, cauda equina syndrome, uterine embolisation, childbirth trauma (vaginal tearing through the use of forceps or suction or a large or unclosed episiotomy), vulvodynia and cardiovascular disease. Drugs-induced A common cause of anorgasmia, in both women and men, is the use of anti-depressants, particularly selective serotonin reuptake inhibitors (SSRIs). Though reporting of anorgasmia as a side effect of SSRIs is not precise, studies have found that 17–41% of users of such medications are affected by some form of sexual dysfunction.Another cause of anorgasmia is cocaine use and opiate addiction, particularly to heroin. Primary anorgasmia Primary anorgasmia is a condition where one has never experienced an orgasm. This is significantly more common in women, although it can occur in men who lack the gladipudendal (bulbocavernosus) reflex. Women with this condition can sometimes achieve a relatively low level of sexual excitement. Frustration, restlessness, and pelvic pain or a heavy pelvic sensation may occur because of vascular engorgement. On occasion, there may be no obvious reason why orgasm is unobtainable. In such cases, women report that they are unable to orgasm even if they have a caring, skilled partner, adequate time and privacy, and an absence of medical issues which would affect sexual satisfaction. About 15% of women report difficulties with orgasm, and 10% of women in the United States have never climaxed. 29% of women always have orgasms with their partner.Some social theorists believe that inability to orgasm may be related to residual psychosocial perceptions that female sexual desire is somehow wrong, and that this stems from the age of Victorian repression. It is thought that this view may impede some women – perhaps those raised in a more repressed environment – from being able to experience natural and healthy sexual feeling. Secondary anorgasmia Secondary anorgasmia is the loss of the ability to have orgasms (as opposed to primary anorgasmia which indicates a person who has never had an orgasm) or loss of the ability to reach orgasm of past intensity. The cause may be alcoholism, depression, grief, pelvic surgery (such as total hysterectomy) or injuries, certain medications, death-grip, illness, estrogen deprivation associated with menopause, or rape. Prostatectomy Secondary anorgasmia is close to 50% among males undergoing prostatectomy; 80% among radical prostatectomies. This is generally caused by damage to the primary nerves serving the penile area, which pass near the prostate gland. Removal of the prostate frequently damages or even completely removes these nerves, making sexual response unreasonably difficult. Radical prostatectomies are usually given to younger males who are expected to live more than 10 years. At more advanced ages, the prostate is less likely to grow during that persons remaining lifetime. Situational anorgasmia People who are orgasmic in some situations may not be in others. A person may have an orgasm from one type of stimulation but not from another, achieve orgasm with one partner but not another, or have an orgasm only under certain conditions or only with a certain type or amount of foreplay. These common variations are within the range of normal sexual expression and should not be considered problematic. A person who is troubled by experiencing situational anorgasmia should be encouraged to explore alone and with their partner those factors that may affect whether or not they are orgasmic, such as fatigue, emotional concerns, feeling pressured to have sex when they are not interested, or a partners sexual dysfunction. In the relatively common case of female situational anorgasmia during penile-vaginal intercourse, some sex therapists recommend that couples incorporate manual or vibrator stimulation during intercourse, or using the female-above position as it may allow for greater stimulation of the clitoris by the penis or pubic symphysis or both, and it allows the woman better control of movement. Diagnosis Effective treatment for anorgasmia depends on the cause. In the case of women with psychological sexual trauma or inhibition, psychosexual counselling might be advisable and could be obtained through general practitioner (GP) referral.Women with anorgasmia with no obvious psychological cause would need to be examined by their GP to check for absence of disease. Blood tests would also need to be done (full blood count, liver function, oestradiol/estradiol, total testosterone, SHBG, FSH/LH, prolactin, thyroid function, lipids and fasting blood sugar) to check for other conditions such as diabetes, lack of ovulation, low thyroid function or hormone imbalances. The normal thresholds for these tests and timing in a womans menstrual cycle is detailed in Berman et al., 2005. They would then need to be referred to a specialist in sexual medicine. The specialist would check the patients blood results for hormonal levels, thyroid function and diabetes, evaluate genital blood flow and genital sensation, as well as giving a neurological work-up to determine the degree (if any) of nerve damage. Recently, it has been proposed to add a subtype of FOD, called reduced orgasmic intensity, and field trials are underway to assess the suitability of this proposal. Treatment Just as with erectile dysfunction in men, lack of sexual function in women may be treated with hormonal patches or tablets to correct hormonal imbalances, clitoral vacuum pump devices and medication to improve blood flow, sexual sensation and arousal.Many practitioners today treat both men and women who have SSRI-induced anorgasmia with sildenafil, more commonly known as Viagra. While this approach is known to work well in men with sexual dysfunction, it is only recently that the effectiveness of sildenafil in women with sexual dysfunction is coming to light. A recent study by H. G. Nurnberg et al. showed a complete or very significant reversal of their sexual dysfunction upon taking sildenafil one hour prior to sexual activity. In this study, eight out of the nine women required 50 mg of sildenafil while the 9th woman required 100 mg of sildenafil. Another option for women who have SSRI-induced anorgasmia is the use of vardenafil. Vardenafil is a type 5 phosphodiesterase (PDE5) inhibitor that facilitates muscle relaxation and improves penile erection in men. However, there is much controversy about the efficiency of the drug used in the reversal of female sexual dysfunction. Vardenafil is similar to sildenafil, but vardenafil is less expensive and may be covered under some insurance plans. A study by A.K. Ashton M.D. has shown that in the case of one particular woman, the effects of vardenafil as opposed to sildenafil have not only been comparable in the effectiveness, but that vardenafil is cheaper and reversal of sexual dysfunction requires a smaller dose. So far, vardenafil has been approved by the Food and Drug administration only for use in men. The NIH states that yohimbine hydrochloride has been shown in human studies to be possibly effective in the treatment of male impotence resulting from erectile dysfunction or SSRI usage (e.g., anorgasmia). Published reports have shown it to be effective in the treatment of orgasmic dysfunction in men.Cabergoline, an agonist of dopamine D2 receptors which inhibits prolactin production, was found in a small study to fully restore orgasm in one third of anorgasmic subjects, and partially restore orgasm in another third. Limited data has shown that the drug amantadine may help to relieve SSRI-induced sexual dysfunction. Cyproheptadine, buspirone, stimulants such as amphetamines (including the antidepressant bupropion), nefazodone and yohimbine have been used to treat SSRI-induced anorgasmia. Reducing the SSRI dosage may also resolve anorgasmia problems. See also Dysorgasmia Sexual anhedonia References The original text for this article is taken from public domain CDC text. Berman, J. Bumiller, E. and Berman L. (2005) For Women Only, Revised Edition: A Revolutionary Guide to Reclaiming Your Sex Life, Owl Books, NY External links Anorgasmia.net Anorgasmia: definition, causes, diagnosis and treatment University of California, Santa Barbaras SexInfo includes statistics, causes, and treatments for anorgasmia Definition of Anorgasmia, Mayo Clinic
Progressive myoclonus epilepsy	Progressive Myoclonic Epilepsies (PME) are a rare group of inherited neurodegenerative diseases characterized by myoclonus, resistance to treatment, and neurological deterioration. The cause of PME depends largely on the type of PME. Most PMEs are caused by autosomal dominant or recessive and mitochondrial mutations. The location of the mutation also affects the inheritance and treatment of PME. Diagnosing PME is difficult due to their genetic heterogeneity and the lack of a genetic mutation identified in some patients. The prognosis depends largely on the worsening symptoms and failure to respond to treatment. There is no current cure for PME and treatment focuses on managing myoclonus and seizures through antiepileptic medication (AED).The age of onset depends on the specific PME but PME can affect people of all ages. In Unverricht-Lundborg disease (ULD) the age of onset is between 6–15 years, while in Adult Neuronal ceroid lipofuscinoses (Adult NCL) the age of onset can be as late as 30.Symptoms often include action or stimuli induced myoclonus, seizures, neuropathy, cognitive decline, and spike and wave or no cerebral discharges. The prognosis of those diagnosed with PME is poor. The person often becomes reliant on a wheelchair, enters a vegetative state due to myoclonus, and has a shortened life expectancy. Signs and symptoms The most common symptom of PME is myoclonus. The myoclonus can be fragmented or multifocal and can be triggered by posture, actions, and external stimuli such as light, sound, and touch. The type of myoclonus differs between the types of PME. Other symptoms of PME include generalized, tonic clonic, tonic, and atypical absence seizures. In Laforas disease the seizures are occipital and the person experiences transient blindness as well as visual hallucinations. The person may also have atypical absences and atonic and complex partial seizures. In Myoclonus epilepsy with ragged-red fibers (MERRF) the person experiences generalized epilepsy along with myoclonus, weakness, and dementia.As PME progresses neurological ability decreases and can lead to myopathy, neuropathy, cognitive decline, cerebellar ataxia, and dementia. The different symptoms in each of the PME and between individuals makes diagnosis difficult. Therefore, diagnosis of PME is dependent on failure to respond to antiepileptic drugs and therapy but diagnosis of specific PME depends on genetic testing, EEG (electroencephalography), enzyme measurements and more. Diagnosis Diagnosis of PME is based on the individuals signs and symptoms as well as failure to respond to antiepileptic drugs and therapy. Further diagnosis support includes EEG results, genetic testing, enzyme testing, and skin and muscle biopsies. Gauchers disease can be diagnosed through enzyme testing as it is a metabolic disease. Laforas disease can be diagnosed using skin biopsies. While Action myoclonus renal failure (AMRF) syndrome can only be diagnosed using genetic test. Using EEGs as a form of diagnosis can prove difficult as patients differ in their neurophysiology. In Laforas disease EEGs can show slowing background activity or focal discharges as well as epileptiform discharges. In ULD EEGs show generalized epileptiform discharges and in MERRF patients show background slowing. Therefore, diagnosis is best made using a combination of different tools like signs and symptoms, age of onset, EEG, gene testing, enzyme measurements, and biopsy of skin and muscle. Differential diagnosis The main component setting PME apart from other forms of epilepsy is progressive deterioration and resistance to treatment. Therefore, in the early stages of PME the symptoms and EEG may appear like Generalized epilepsy, Juvenile myoclonic epilepsy, benign childhood myoclonic epilepsy, and Huntingtons disease. It is crucial for ensure initial treatment is appropriate to measure how the condition progresses. Incorrect treatment can also result in wrong PME diagnosis. Management The is no cure for PME. Efforts are instead placed in managing the symptoms, specifically the myoclonus and seizures as these can cause major harm to the individual. However, treating the symptoms with antiepileptic drugs can be difficult because PME individuals can become resistant. Some antiepileptic drugs used in treatment are valproic acid, benzodiazepines, phehobarbital, piracetam, zonisamide, clonazepam, and levetiracetam. It is important to note that some antiepileptic drugs can worsen the symptoms, like vigabatrin, carbamazepine, phenytoin, and gabapentin. Clonazepam is currently the only drug approved by the FDA for monotherapy treatment of myoclonic seizures. Other treatments that have been used in PME patients are deep brain stimulation, vagus nerve stimulation , and diet but they have not been shown to improve seizures. Prognosis The prognosis of PME is ultimately dependent on the type of PME. In Lafora body disease the neurological deterioration progresses until resulting in a vegetative state and death within 10 years of diagnosis. Due to research and advances in antiepileptic medication, individuals with ULD can live up to 60 years of age. Nevertheless, severe myoclonus can lead to injury by falling and becoming reliant on a wheelchair. Research Because PME is so rare it is hard to do studies specifically double blind studies used to test different antiepileptic drugs. The wide range of symptoms including the differing EEG makes studying the effects of the AEDs difficult. In ULD, oligonucleotide therapeutic strategies have been used to replace gene effects while in Sialidosis enzyme replacement therapy has been studied in mouse models. In Laforas disease metformin has been approved for treatment by the European commission. In MERRF bacterial proteins have been identified in treatment in mitochondrial diseases but further studies are needed. History The first instance where myoclonus and its relationship to epilepsy was in 1822 by Prichard. Lundborg was the first to name progressive myoclonus epilepsy in 1903 due to his study of several Swedish families as well as research done by Heinrich Unverricht in 1891. However, ULD was not recognized as a disease until a century later due to the rarity of the disease. In 1911, Lafora identified Lafora bodies but believed to be part of ULD. Laforas genetics was not described until 1995. Specific disorders Several conditions can cause progressive myoclonic epilepsy. Unverricht-Lundborg disease (Baltic myoclonus) Myoclonus epilepsy and ragged red fibres (MERRF syndrome) Lafora disease Neuronal ceroid lipofuscinoses Sialidosis Dentatorubropallidoluysian atrophy (DRPLA) Noninfantile neuronopathic form of Gaucher disease Tetrahydrobiopterin deficiencies Alpers disease Juvenile Huntington disease Niemann-Pick disease type C North Sea progressive myoclonus epilepsy (NSPME) Unverricht-Lundborg disease This disease manifests between six and sixteen years and is most prevalent in Scandinavia and the Baltic countries. Myoclonus gradually becomes worse and less susceptible to medication. Cognitive decline is slow and sometimes mild. Patients typically do not live beyond middle-age, but there are exceptions. Phenytoin, an old and commonly used anticonvulsant, is known to seriously exacerbate the condition. It has autosomal recessive inheritance, and is caused by a mutation in the cystatin B (EPM1) gene on chromosome 21q22.3, which was discovered in 1996. It has been described as the least severe type of PME. Myoclonus epilepsy and ragged red fibres (MERRF syndrome) Onset of this disease may be at any time and the severity and progression are varied. Tonic-clonic seizures and dementia are less apparent than with other forms of PME. The cause is a mitochondrial DNA mutation, so most familial cases are transmitted from the mother. A skeletal muscle biopsy will show ragged red fibres, hence the name. Lafora body disease This disease typically begins between six and nineteen years after apparently normal development and generally results in death within ten years. It is characterised by the presence of Lafora bodies (polyglucosan inclusions) in neurons and other body tissue. The generalized seizures are usually well controlled by anticonvulsants, but the myoclonus soon proves refractory to treatment. Within a couple of years, a wheelchair is required for locomotion and within five to ten years, the person is confined to bed and is often tube fed. Valproic acid and zonisamide are first choice anticonvulsants, and the ketogenic diet may be helpful. An autosomal-recessive genetic defect is responsible, which has been tracked down to two genes. The EPM2A gene on chromosome 6q24 was discovered in 1998 and encodes for the protein laforin. It is responsible for 80% of cases. The EPM2B gene on chromosome 6p22.3 was discovered in 2003 and encodes for the protein malin. There may be a third gene of unknown locus. Neuronal ceroid lipofuscinoses There are various forms of these disorders, each with their own genetic cause and geographical variation, which lead to accumulation of lipopigments (lipofuscin) in the bodys tissues and are inherited in an autosomal-recessive fashion. Onset and symptoms vary with the particular form, but death usually occurs within five to fifteen years. Type I sialidosis This is an autosomal recessive disorder in which the body is deficient in α-neuraminidase. Myoclonic epilepsy and ataxia due to potassium (K+) channel mutation (MEAK) MEAK is a form of progressive myoclonus epilepsy that typically begins between the ages of 3 and 15 years (the average of onset is 10 years). The first symptoms may include ataxia and myoclonus (unsteadiness and difficulty coordinating movements), along with generalized tonic-clonic ("grand mal") seizures. Individuals with MEAK typically do not experience developmental delays. The symptoms are progressive, and individuals with MEAK often need to use a wheelchair by their late teenage years because of movement difficulties and myoclonus. Many individuals with MEAK report temporary improvement of symptoms when they have a high fever. Seizures may become less frequent in adulthood, but other neurological complications, including myoclonus, ataxia and tremor, may worsen. Myoclonic epilepsy and ataxia due to potassium (K+) channel mutation (MEAK) is caused by a specific pathogenic variant ("mutation") in KCNC1 (c. 959G>A; p.Arg320His). KCNC1-related developmental and epileptic encephalopathy is associated with other pathogenic variants in KCNC1. In most individuals with KCNC1-related disorders, the pathogenic KCNC1 variant occurred spontaneously (de novo) and was not inherited from either parent. Epidemiology PME accounts for less than 1% of epilepsy cases at specialist centres. The incidence and prevalence of PME is unknown, but there are considerable geography and ethnic variations amongst the specific genetic disorders. One cause, Unverricht Lundborg Disease, has an incidence of at least 1:20,000 in Finland. See also Juvenile myoclonic epilepsy Spinal muscular atrophy with progressive myoclonic epilepsy References External links GeneReview/NCBI/NIH/UW entry on Progressive Myoclonus Epilepsy with Ataxia
Goitre	A goitre, or goiter, is a swelling in the neck resulting from an enlarged thyroid gland. A goitre can be associated with a thyroid that is not functioning properly. Worldwide, over 90% of goitre cases are caused by iodine deficiency. The term is from the Latin gutturia, meaning throat. Most goitres are not cancerous (benign), though they may be potentially harmful. Signs and symptoms A goitre can present as a palpable or visible enlargement of the thyroid gland at the base of the neck. A goitre, if associated with hypothyroidism or hyperthyroidism, may be present with symptoms of the underlying disorder. For hyperthyroidism, the most common symptoms are associated with adrenergic stimulation: tachycardia (increased heart rate), palpitations, nervousness, tremor, increased blood pressure and heat intolerance. Clinical manifestations are often related to hypermetabolism, (increased metabolism), excessive thyroid hormone, an increase in oxygen consumption, metabolic changes in protein metabolism, immunologic stimulation of diffuse goitre, and ocular changes (exophthalmos). Hypothyroid people commonly have poor appetite, cold intolerance, constipation, lethargy and may undergo weight gain. However, these symptoms are often non-specific and make diagnosis difficult.According to the WHO classification of goitre by palpation, the severity of goitre is currently graded as grade 0, grade 1, grade 2. Causes Worldwide, the most common cause for goitre is iodine deficiency, commonly seen in countries that scarcely use iodized salt. Selenium deficiency is also considered a contributing factor. In countries that use iodized salt, Hashimotos thyroiditis is the most common cause. Goitre can also result from cyanide poisoning, which is particularly common in tropical countries where people eat the cyanide-rich cassava root as the staple food. Sarcoidosis Amyloidosis Hydatidiform mole Cysts Acromegaly Pendred syndrome Diagnosis Goitre may be diagnosed via a thyroid function test in an individual suspected of having it. Types A goitre may be classified either as nodular or diffuse. Nodular goitres are either of one nodule (uninodular) or of multiple nodules (multinodular). Growth pattern Uninodular goitre: one thyroid nodule; can be either inactive, or active (toxic) – autonomously producing thyroid hormone. Multinodular goitre: multiple nodules; can likewise be inactive or toxic, the latter is called toxic multinodular goitre and associated with hyperthyroidism. These nodules grow up at varying rates and secrete thyroid hormone autonomously, thereby suppressing TSH-dependent growth and function in the rest of gland. Inactive nodules in the same goitre can be malignant. Thyroid cancer is identified in 13.7% of the patients operated for multinodular goitre. Diffuse goitre: the whole thyroid appearing to be enlarged due to hyperplasia.Size Class I: the goitre in normal posture of the head cannot be seen; it is only found by palpation. Class II: the goitre is palpable and can be easily seen. Class III: the goitre is very large and is retrosternal (partially or totally lying below the sternum), pressure results in compression marks. Treatment Goitre is treated according to the cause. If the thyroid gland is producing an excess of thyroid hormones (T3 and T4), radioactive iodine is given to the patient to shrink the gland. If goitre is caused by iodine deficiency, small doses of iodide in the form of Lugols iodine or KI solution are given. If the goitre is associated with an underactive thyroid, thyroid supplements are used as treatment. Sometimes a partial or complete thyroidectomy is required. Epidemiology Goitre is more common among women, but this includes the many types of goitre caused by autoimmune problems, and not only those caused by simple lack of iodine. History Chinese physicians of the Tang Dynasty (618–907) were the first to successfully treat patients with goitre by using the iodine-rich thyroid gland of animals such as sheep and pigs—in raw, pill, or powdered form. This was outlined in Zhen Quans (d. 643 AD) book, as well as several others. One Chinese book, The Pharmacopoeia of the Heavenly Husbandman, asserted that iodine-rich sargassum was used to treat goitre patients by the 1st century BC, but this book was written much later.In the 12th century, Zayn al-Din al-Jurjani, a Persian physician, provided the first description of Graves disease after noting the association of goitre and a displacement of the eye known as exophthalmos in his Thesaurus of the Shah of Khwarazm, the major medical dictionary of its time. The disease was later named after Irish doctor Robert James Graves, who described a case of goitre with exophthalmos in 1835. The German Karl Adolph von Basedow also independently reported the same constellation of symptoms in 1840, while earlier reports of the disease were also published by the Italians Giuseppe Flajani and Antonio Giuseppe Testa, in 1802 and 1810 respectively, and by the English physician Caleb Hillier Parry (a friend of Edward Jenner) in the late 18th century.Paracelsus (1493–1541) was the first person to propose a relationship between goitre and minerals (particularly lead) in drinking water. Iodine was later discovered by Bernard Courtois in 1811 from seaweed ash.Goitre was previously common in many areas that were deficient in iodine in the soil. For example, in the English Midlands, the condition was known as Derbyshire Neck. In the United States, goitre was found in the Appalachian, Great Lakes, Midwest, and Intermountain regions. The condition is now practically absent in affluent nations, where table salt is supplemented with iodine. However, it is still prevalent in India, China, Central Asia, and Central Africa. Goitre had been prevalent in the alpine countries for a long time. Switzerland reduced the condition by introducing iodised salt in 1922. The Bavarian tracht in the Miesbach and Salzburg regions, which appeared in the 19th century, includes a choker, dubbed Kropfband (struma band) which was used to hide either the goitre or the remnants of goitre surgery. Society and culture In the 1920s wearing bottles of iodine around the neck was believed to prevent goitre. Notable cases Former U.S. President George H. W. Bush and his wife Barbara Bush were both diagnosed with Graves disease and goitres, within two years of each other. The disease caused hyperthyroidism and cardiac dysrhythmia. Scientists said that, absent an environmental cause, the odds of both a husband and wife having Graves disease might be 1 in 100,000 or as low as 1 in 3,000,000. Heraldry The coat of arms and crest of Die Kröpfner, of Tyrol showed a man "afflicted with a large goitre", an apparent pun on the German for the word ("Kropf"). See also David Marine conducted substantial research on the treatment of goitre with iodine. Endemic goitre Struma ovarii—a kind of teratoma Thyroid hormone receptor References == External links ==
Postterm pregnancy	Postterm pregnancy is when a woman has not yet delivered her baby after 42 weeks of gestation, two weeks beyond the typical 40-week duration of pregnancy. Postmature births carry risks for both the mother and the baby, including fetal malnutrition, meconium aspiration syndrome, and stillbirths. After the 42nd week of gestation, the placenta, which supplies the baby with nutrients and oxygen from the mother, starts aging and will eventually fail. Postterm pregnancy is a reason to induce labor. Definitions The management of labor and delivery may vary depending on the gestational age. It is common to encounter the following terms when describing different time periods of pregnancy. Postterm – ≥ 42 weeks + 0 days of gestation (> 293 days from the first day of last menstrual period, or > 13 days from the estimated due date) Late term – 41 weeks + 0 days to 41 weeks + 6 days of gestation Full term – 39 weeks + 0 days to 40 weeks + 6 days of gestation Early term – 37 weeks + 0 days to 38 weeks + 6 days of gestation Preterm – ≤ 36 weeks + 6 days of gestationBesides postterm pregnancy, other terminologies have been used to describe the same condition (≥ 42w+0d), such as prolonged pregnancy, postdates, and postdatism. However, these terminologies are less commonly used to avoid confusion.Postterm pregnancy should not be confused with postmaturity, postmaturity syndrome, or dysmaturity. These terms describe the neonatal condition that may be caused by postterm pregnancy instead of the duration of pregnancy. Signs and symptoms Because postterm pregnancy is a condition solely based on gestational age, there are no confirming physical signs or symptoms. While it is difficult to determine gestational age physically, infants that are born postterm may be associated with a physical condition called postmaturity. The most common symptoms for this condition are dry skin, overgrown nails, creases on the babys palms and soles of their feet, minimal fat, abundant hair on their head, and either a brown, green, or yellow discoloration of their skin. Doctors diagnose postmature birth based on the babys physical appearance and the length of the mothers pregnancy. However, some postmature babies may show no or few signs of postmaturity. Baby Reduced placental perfusion – Once a pregnancy has surpassed the 40-week gestation period, doctors closely monitor the mother for signs of placental deterioration. Toward the end of pregnancy, calcium is deposited on the walls of blood vessels, and proteins are deposited on the surface of the placenta, which changes the placenta. This limits the blood flow through the placenta and ultimately leads to placental insufficiency, and the baby is no longer properly nourished. Induced labor is strongly encouraged if this happens. Oligohydramnios – Low volume of amniotic fluid surrounding the fetus. It is associated with complications such as cord compression, abnormal heart rate, fetal acidosis, and meconium amniotic fluid. Meconium aspiration syndrome – Respiratory compromise secondary to meconium present in infants lungs. Macrosomia – Estimated fetal weight of ≥ 4.5 kg. It can further increase the risk of prolonged labor and shoulder dystocia. Shoulder dystocia – Difficulty in delivering the shoulders due to increased body size. Increased forceps-assisted or vacuum-assisted birth – When postterm babies are larger than average, forceps or vacuum delivery may be used to resolve the difficulties at the delivery time, such as shoulder dystocia. Complications include lacerations, skin markings, external eye trauma, intracranial injury, facial nerve injury, skull fracture, and rarely death. Mother Increased labor induction – Induction may be needed if labor progression is abnormal. Oxytocin, a medication used in induction, may have side effects such as low blood pressure. Increased forceps assisted or vacuum assisted birth – operative vaginal deliveries increase maternal risks of genital trauma. Increased Caesarean birth – Postterm babies may be larger than an average baby, thus increasing the length of labor. The labor is increased because the babys head is too big to pass through the mothers pelvis. This is called cephalopelvic disproportion. Caesarean sections are encouraged if this happens. Complications include bleeding, infection, abnormal wound healing, abnormal placenta in future pregnancies, and rarely death.A 2019 randomized control trial of induced labor at 42 or 43 weeks was terminated early due to statistical evidence of "significantly increased risk for women induced at the start of week 43". The study implies clinical guidelines for induction of labor no later than at 41 gestational weeks. Causes The causes of post-term births are unknown, but postmature births are more likely when the mother has experienced a previous postmature birth. Due dates are easily miscalculated when the mother is unsure of her last menstrual period. When there is a miscalculation, the baby could be delivered before or after the expected due date. Postmature births can also be attributed to irregular menstrual cycles. When the menstrual period is irregular it is difficult to judge the moment of ovulation and subsequent fertilization and pregnancy. Some postmature pregnancies may not be postmature in reality due to the uncertainty of mothers last menstrual period. However, in most countries where gestation is measured by ultrasound scan technology, this is less likely. Monitoring Once a pregnancy is diagnosed postterm, usually at or greater than 42 weeks of gestational age, the mother should be offered additional monitoring as this can provide valuable clues that the fetal health is being maintained. Fetal movement recording Regular movements of the fetus is the best sign indicating that it is still in good health. The mother should keep a "kick-chart" to record the movements of her fetus. If there is a reduction in the number of movements it could indicate placental deterioration. Doppler fetal monitor Doppler fetal monitor is a hand-held device that is routinely used in prenatal care. When it is used correctly, it can quickly measure the fetal heart rate. The baseline of fetal heart rate is typically between 110 and 160 beats per minute. Doppler flow study Doppler flow study is a type of ultrasound that measures the amount of blood flowing in and out of the placenta. The ultrasound machine can also detect the direction of blood flow and display it in red or blue. Usually, a red color indicates a flow toward the ultrasound transducer, while blue indicates a flow away from the transducer. Based on the display, doctors can evaluate blood flow to the umbilical arteries, umbilical veins, or other organs such as heart and brain. Nonstress test Nonstress test (NST) is a type of electronic fetal monitoring that uses a cardiotocograph to monitor fetal heartbeat, fetal movement and mothers contraction. NST is typically monitored for at least 20 minutes. Signs of a reactive (normal) NST include a baseline fetal heart rate (FHR) between 110 and 160 beats per minute (bpm) and 2 accelerations of FHR of at least 15 bpm above baseline for over 15 seconds. Vibroacoustic stimulation and longer monitoring may be needed if NST is non-reactive. Biophysical profile A biophysical profile is a noninvasive procedure that uses the ultrasound to evaluate the fetal health based on NST and four ultrasound parameters: fetal movement, fetal breathing, fetal muscle tone, and the amount of amniotic fluid surrounding the fetus. A score of 2 points is given for each category that meets the criteria or 0 points if the criteria are not met (no 1 point). Sometimes, the NST is omitted, making the highest score 8/8 instead of 10/10. Generally, a score of 8/10 or 10/10 is considered a normal test result, unless 0 points is given for amniotic fluid. A score of 6/10 with normal amniotic fluid is considered equivocal, and a repeated test within 24 hours may be needed. A score of 4/10 or less is considered abnormal, and delivery may be indicated. Low amniotic fluid can cause pinching umbilical cord, decreasing blood flow to the fetus. Therefore, a score of 0 points for amniotic fluid may indicate the fetus is at risk. Management Expectant A woman who has reached 42 weeks of pregnancy is likely to be offered induction of labour. Alternatively, she can choose expectant management, that is, she waits for the natural onset of labour. Women opting for expectant management may also choose to carry on with additional monitoring of their baby, with regular CTG, ultrasound, and biophysical profile. Risks of expectant management vary between studies.In many places in the World, according to the World Health Organization and others, such services are rudimentary or not available, and deserve improvement. Inducing labor Inducing labor artificially starts the labor process by using medication and other techniques. Labor is usually only induced if there is potential danger on the mother or child. There are several reasons for labor induction; the mothers water breaks, and contractions have not started, the child is postmature, the mother has diabetes or high blood pressure, or there is not enough amniotic fluid around the baby. Labor induction is not always the best choice because it has its own risks. Sometimes mothers will request to be induced for reasons that are not medical. This is called an elective induction. Doctors try to avoid inducing labor unless it is completely necessary. Procedure There are four common methods of starting contractions. The four most common are stripping the membranes, breaking the mothers water, giving the hormone prostaglandin, and giving the synthetic hormone pitocin. Stripping the membranes does not work for all women, but can for most. A doctor inserts a finger into the mothers cervix and moves it around to separate the membrane connecting the amniotic sac, which houses the baby, from the walls of the uterus. Once this membrane is stripped, the hormone prostaglandin is naturally released into the mothers body and initiates contractions. Most of the time doing this only once will not immediately start labor. It may have to be done several times before the stimulant hormone is released, and contractions start. The next method is breaking the mothers water, which is also referred to as an amniotomy. The doctor uses a plastic hook to break the membrane and rupture the amniotic sac. Within a few hours labor usually begins. Giving the hormone prostaglandin ripens the cervix, meaning the cervix softens, thins out, or dilates. The drug Cervidil is administered by mouth in tablet form or in gel form as an insert. This is most often done in the hospital overnight. The hormone oxytocin is usually given in the synthetic form of Pitocin. It is administered through an IV throughout the labor process. This hormone stimulates contractions. Pitocin is also used to "restart" labor when it is lagging.The use of misoprostol is also allowed, but close monitoring of the mother is required. Feelings Stripping the membranes: Stripping the membranes only takes a few minutes and causes a few intense cramps. Many women report a feeling similar to urination, others report it to be quite painful. Breaking the water: Having ones water broken feels like a slight tug and then a warm flow of liquid. Pitocin: When the synthetic hormone, pitocin, is used, contractions occur more frequently than a natural occurring birth; they are also more intense. Epidemiology Prevalence of postterm pregnancy may vary between countries due to different population characteristics or medical management. Factors include number of first-time pregnancies, genetic predisposition, timing of ultrasound assessment, and Caesarean section rates, etc. The incidence is approximately 7%. Postterm pregnancy occurs in 0.4% of pregnancies approximately in the United States according to birth certificate data. Notes == External links ==
Rhombencephalosynapsis	Rhombencephalosynapsis is a rare genetic brain abnormality of malformation of the cerebellum. The cerebellar vermis is either absent or only partially formed, and fusion is seen in varying degree between the cerebellar hemispheres, fusion of the middle cerebellar peduncles, and fusion of the dentate nuclei. Findings range from mild truncal ataxia, to severe cerebral palsy.Rhombencephalosynapsis is a constantly found feature of Gomez-Lopez-Hernandez syndrome. One case of which has shown a co-occurrence with autism-spectrum disorder. Presentation Clinical indications range from mild truncal ataxia with unaffected cognitive abilities, to severe cerebral palsy and intellectual disability. Genetics An association with mutations in the MN1 gene has been reported in cases of atypical rhomboencephalosynapsis. Pathology Rhombencephalosynapsis is a rare brain disorder of malformation of the cerebellum that may be detected on ultrasound of the fetus. The vermis is either absent or partially formed. There is dorsal fusion of the cerebellar hemispheres, fusion of the dentate nuclei, and fusion of the middle cerebellar peduncles. The degree of severity of this disorder is associated with the degree of maldevelopment of the cerebellar vermis.Aqueductal stenosis commonly exists with the disorder, as does its often resulting hydrocephalus. In some cases additional abnormalities may be present, such as ventriculomegaly (enlarged ventricles), and supratentorial abnormalities. Diagnosis Rhombencephalosynapsis can be detected on imaging of the fetus. It is one of the triad of features characteristic of Gomez-Lopez-Hernandez syndrome (GLHS). When detected, signs of GLHS ought to be looked for on post-natal review. Signs include partial alopecia and some facial peculiarities. It is thought that due to the co-occurrence of these two disorders they may have a common etiology.As a feature of GLHS one case study has shown GLHS to co-occur with autism spectrum disorder. Epidemiology As of 2018 only 36 cases have been reported. History The first case was reported by Heinrich Obersteiner in 1914. == References ==
Reflex seizure	Reflex seizures are epileptic seizures that are consistently induced by a specific stimulus or trigger making them distinct from other epileptic seizures, which are usually unprovoked. Reflex seizures are otherwise similar to unprovoked seizures and may be focal (simple or complex), generalized, myoclonic, or absence seizures. Epilepsy syndromes characterized by repeated reflex seizures are known as reflex epilepsies. Photosensitive seizures are often myoclonic, absence, or focal seizures in the occipital lobe, while musicogenic seizures are associated with focal seizures in the temporal lobe.Triggers may include various stimuli with the most common (75 to 80%) being flickering lights resulting in photosensitive seizures. Reflex epilepsies are generally thought to be genetic in origin. The inheritance pattern is dependent on the type of reflex epilepsy with some types lacking a specific genetic inheritance patterns. For example, photogenic epilepsy is thought to follow an autosomal dominant pattern with incomplete penetrance, while seizures triggered by proprioceptive stimuli do not follow an observable inheritance pattern. The underlying mechanism involves the stimulation of existing network of neurons by the specific trigger.The treatment of reflex epilepsy generally involves decreasing exposure to a persons triggers as well as anti-epileptic medications. Reflex epilepsy is relatively rare, making up approximately 5% of epilepsy syndromes. Signs and symptoms Reflex seizures can be either generalized or focal seizures or both. However, for any given stimulus there may be a large variation in the kind of elicited seizure. For example, reading epilepsy may cause myoclonic jerks in the jaw or may cause focal seizures in the regions of the brain responsible for reading. In reflex epilepsy generalized seizures are more common than focal seizures. Generalized seizures Generalized seizures are seizures that arise in large areas of the brain including both hemispheres. Generalized seizures can take the form of myoclonic jerks, absences, or generalized tonic-clonic seizures. Myoclonic jerks are the most common generalized seizures seen among reflex seizures and can be the located in the limbs, trunk, or in specific regions of the body (Ex. in the muscles of the jaw or the eyelids). Reflex absence seizures are also common especially in response to certain kinds of triggering stimuli such as light, proprioseptive, cognitive, emotional, or linguistic. Generalized tonic-clonic seizures are less common and can occur independently or more commonly after a cluster of myoclonic jerks or absence seizures. Focal seizures Focal seizures are seizures that arise from a small area of the brain in one hemisphere. Focal seizures are divided into simple or complex focal seizures. Simple focal seizures do not involve the impairment of consciousness but instead may have motor, sensory, or autonomic manifestations. Complex focal seizures do involve impairment or loss of consciousness. Focal seizures are usually only seen in certain types of reflex epilepsies such as occipital lobe seizures in photosensitive occipital lobe epilepsies or temporal lobe seizures in musicogenic epilepsies. Focal seizures can be located only in the area of the brain responsible for the stimulus, spread to other areas of the brain, or even develop into a generalized seizure. Triggers Stimuli that cause reflex seizures can be categorized as either intrinsic or extrinsic. For a given person, the stimulus that triggers may be intrinsic, extrinsic, or a combination of both. Extrinsic stimuli Extrinsic stimuli are sensory stimuli that originate from the persons environment. Similar to intrinsic stimuli, extrinsic stimuli can be divided into two categories, either simple or complex. Examples of simple extrinsic stimuli include flashing lights or touch while complex extrinsic stimuli can include music, language, reading, or stimulation from eating. Some of the more common types of reflex epilepsy include light and music.Photosensitive epilepsy is an abnormal sensitivity of the brain to visual stimuli and is the most common trigger in reflex seizures. Reflex seizures can be induced by both flickering or non-flicking light, television, video games, or other visual patterns. Most people who have photosensitive epilepsy are sensitive to specific patterns for visual stimuli. Visual stimuli of a particular frequency (15-25 flashes/second), wavelength (red light at 660-720 nm), and at high contrast have been shown to have a higher risk of inducing seizures in people who are photosensitive. In addition, emotional excitement, fatigue, or length of exposure can all effect the risk of seizures.Musicogenic epilepsy is a rare reflex epilepsy that is thought to be an abnormal sensitivity of the brain to musical stimuli, however, the exact mechanism of these seizures is unknown. People with musicogenic epilepsy may have seizures triggered not just by musical stimuli but also by the emotional content or memory associated with that melody or rhythm. Seizures can also be triggered when people with the condition think about certain kinds of music without actually hearing the music. In addition, musicogenic epilepsy may occur with sounds that one would not usually associate with music, the sounds of machinery for example. While certain types of music may induce a seizure in a certain person, listening to other kinds of music may prevent or terminate the epileptic activity. Intrinsic stimuli Intrinsic stimuli are specific actions or activities performed by the person that result in a reflex seizure. Intrinsic stimuli can be divided into two categories, either elementary or elaborate. Elementary intrinsic stimuli are usually simple motor movements while elaborate intrinsic stimuli can include emotions, thoughts, calculations or decision making.Thinking epilepsy is a rare form of reflex epilepsy that is triggered by a specific cognitive task. This can include thinking, calculations, solving problems, abstract reasoning, or making decisions. Thinking epilepsy does not occur in response to reading, writing, or verbal communication. Reading epilepsy is recognized as another distinct kind of reflex epilepsy. Thinking epilepsy usually results in generalized seizures which manifest as bilateral monoclonus, absence seizures, or generalized tonic-clonic seizure that are preceded by myoclonic jerks. Cause Although reflex seizures are thought to have a genetic component, the exact genes involved are unclear. As of 2016, some genes of interest include: Pathophysiology Epileptic seizures occur due to changes in the brain that result in the lowering of the seizure threshold in a particular individual making that person vulnerable to recurring seizures. These changes can be a result of a structural abnormality, brain lesions, or simply a genetic disposition to seizures. In reflex epilepsy, these changes in the brain result in a small area that is capable of interrupting normal firing patterns and more likely to produce the synchronous firing patterns that characterize a seizure. These hyper-excitable areas may then be activated by certain stimuli resulting in a reflex seizure. Reflex seizures are thus notable because the presentation of a particular stimulus, that activates the hyper-excitable areas of the brain, directly overcomes the seizure threshold, and results in a reflex seizure.The activation of the hyper-excitable areas of the brain are additionally regulated by facilitating factors that may increase the likelihood of eliciting a seizure. Most commonly these include fatigue, sleep deprivation, or stress. Facilitating factors are different for each individual. Due to the large variance between the different kinds of reflex epilepsies, the specific mechanism causing reflex seizures may vary. Diagnosis The diagnosis of reflex epilepsy usually includes a comprehensive medical and family history as well as a variety of tests. These tests may include a electroencephalography (EEG), magnetic resonance imaging (MRI), as well as genetic testing.The procedure for diagnosing epilepsy generally follows three steps: Determining if the seizure or seizure like event is truly an epileptic seizure. Determining what kind of seizure that someone has had. Determining if this seizure or seizures are a part of a specific epilepsy syndrome or disease. Treatment The treatment of reflex epilepsy generally involves decreasing exposure to a persons triggers as well as anti-epileptic medications. Specific treatment depends both on the person as well on the kind of reflex triggers. For example, in photosensitive epilepsy, some people may rely only on managing exposure to their triggers, while others, may benefit greatly from anti-epileptic drugs. In addition, different anti-epileptic medications may be used in order to treat a given persons reflex epilepsy depending on the kind of seizures that they experience. Photosensitive epilepsy Photosensitive reflex epilepsy is usually treated with both lifestyle changes and anti-epileptic medications. Some lifestyle modifications that may be recommended are limiting the amount of time one is exposed to television or screens, watching television in a bright well-lit room at a distance of at least 2 meters, and avoiding television or video games when tired. LCD TV screens or Televisions with higher refresh rates (100 Hz) cause less flickering and thus lower the likelihood of a seizure. In addition, special blue lens Z1 glasses have been shown to reduce seizures in many people with photosensitive reflex epilepsy.If the above lifestyle modifications do not manage the condition, anti-epileptic medications may also be used. Valproate is usually the first line medication of choice in people with photosensitive reflex epilepsy with many people becoming seizure free. Second line anti-epileptic medications include levetiracetam, benzodiazepines (such as clonazepam), lamotrigine, carbamazepine, brivaracetam, ethosuximide, and topiramate.Photosensitive reflex epilepsy tends to decrease with age, especially in ones thirties. In 25-50% of people, seizures may spontaneously subside or disappear. Epidemiology In 2015 epilepsy was present in about 1.3% of the population of the United States, approximately 3 million adults and 470,000 children. Reflex epilepsy is found in approximately 5% of people who have epilepsy. Photosensitive epilepsy is the most common type of reflex epilepsy, accounting for 75-80% of cases. In addition, reflex epilepsies may show preferential distribution between the two sexes or certain age groups. Photosensitive epilepsy, for example, is more common in females (60% of cases) and is also more common in younger people (7–19 years old). History Triggering seizures in epilepsy has been a phenomenon that has been observed since ancient times. The Apologia records instances of a spinning potters wheel causing seizures in epileptic slaves. In 1850 Marshal Hall described the role of specific stimuli on causing seizures. Since then, many types of stimuli that can trigger seizures have been identified. The International League Against Epilepsy (ILAE) identified epilepsy caused by a specific stimuli in 1989 in their official definition of epilepsy and more recently, has updated this definition to recognize new types of focal and generalized seizures. Currently reflex epilepsies are classified as miscellaneous types of epilepsy and are identified by the type of triggering stimulus. References External links Reflex Epilepsy Overview Medscape Reference
Female genital mutilation	Female genital mutilation (FGM), also known as female genital cutting, female genital mutilation/cutting (FGM/C) and female circumcision, is the ritual cutting or removal of some or all of the external female genitalia. The practice is found in some countries of Africa, Asia and the Middle East, and within communities abroad from countries in which FGM is common. UNICEF estimated, in 2016, that 200 million women in 30 countries—Indonesia, Iraqi Kurdistan, Yemen, and 27 African countries—had been subjected to one or more types of FGM.Typically carried out by a traditional circumciser using a blade, FGM is conducted from days after birth to puberty and beyond. In half of the countries for which national figures are available, most girls are cut before the age of five. Procedures differ according to the country or ethnic group. They include removal of the clitoral hood (type 1-a) and clitoral glans (1-b); removal of the inner labia; and removal of the inner and outer labia and closure of the vulva. In this last procedure, known as infibulation, a small hole is left for the passage of urine and menstrual fluid; the vagina is opened for intercourse and opened further for childbirth.The practice is rooted in gender inequality, attempts to control womens sexuality, and ideas about purity, modesty, and beauty. It is usually initiated and carried out by women, who see it as a source of honour, and who fear that failing to have their daughters and granddaughters cut will expose the girls to social exclusion. Adverse health effects depend on the type of procedure; they can include recurrent infections, difficulty urinating and passing menstrual flow, chronic pain, the development of cysts, an inability to get pregnant, complications during childbirth, and fatal bleeding. There are no known health benefits.There have been international efforts since the 1970s to persuade practitioners to abandon FGM, and it has been outlawed or restricted in most of the countries in which it occurs, although the laws are often poorly enforced. Since 2010, the United Nations has called upon healthcare providers to stop performing all forms of the procedure, including reinfibulation after childbirth and symbolic "nicking" of the clitoral hood. The opposition to the practice is not without its critics, particularly among anthropologists, who have raised difficult questions about cultural relativism and the universality of human rights. Terminology Until the 1980s, FGM was widely known in English as "female circumcision", implying an equivalence in severity with male circumcision. From 1929 the Kenya Missionary Council referred to it as the sexual mutilation of women, following the lead of Marion Scott Stevenson, a Church of Scotland missionary. References to the practice as mutilation increased throughout the 1970s. In 1975 Rose Oldfield Hayes, an American anthropologist, used the term female genital mutilation in the title of a paper in American Ethnologist, and four years later Fran Hosken called it mutilation in her influential The Hosken Report: Genital and Sexual Mutilation of Females. The Inter-African Committee on Traditional Practices Affecting the Health of Women and Children began referring to it as female genital mutilation in 1990, and the World Health Organization (WHO) followed suit in 1991. Other English terms include female genital cutting (FGC) and female genital mutilation/cutting (FGM/C), preferred by those who work with practitioners.In countries where FGM is common, the practices many variants are reflected in dozens of terms, often alluding to purification. In the Bambara language, spoken mostly in Mali, it is known as bolokoli ("washing your hands") and in the Igbo language in eastern Nigeria as isa aru or iwu aru ("having your bath"). A common Arabic term for purification has the root t-h-r, used for male and female circumcision (tahur and tahara). It is also known in Arabic as khafḍ or khifaḍ. Communities may refer to FGM as "pharaonic" for infibulation and "sunna" circumcision for everything else; sunna means "path or way" in Arabic and refers to the tradition of Muhammad, although none of the procedures are required within Islam. The term infibulation derives from fibula, Latin for clasp; the Ancient Romans reportedly fastened clasps through the foreskins or labia of slaves to prevent sexual intercourse. The surgical infibulation of women came to be known as pharaonic circumcision in Sudan and as Sudanese circumcision in Egypt. In Somalia, it is known simply as qodob ("to sew up"). Methods The procedures are generally performed by a traditional circumciser (cutter or exciseuse) in the girls homes, with or without anaesthesia. The cutter is usually an older woman, but in communities where the male barber has assumed the role of health worker, he will also perform FGM. When traditional cutters are involved, non-sterile devices are likely to be used, including knives, razors, scissors, glass, sharpened rocks, and fingernails. According to a nurse in Uganda, quoted in 2007 in The Lancet, a cutter would use one knife on up to 30 girls at a time. In several countries, health professionals are involved; in Egypt, 77 percent of FGM procedures, and in Indonesia over 50 percent, were performed by medical professionals as of 2008 and 2016. Classification Variation The WHO, UNICEF, and UNFPA issued a joint statement in 1997 defining FGM as "all procedures involving partial or total removal of the external female genitalia or other injury to the female genital organs whether for cultural or other non-therapeutic reasons". The procedures vary according to ethnicity and individual practitioners; during a 1998 survey in Niger, women responded with over 50 terms when asked what was done to them. Translation problems are compounded by the womens confusion over which type of FGM they experienced, or even whether they experienced it. Studies have suggested that survey responses are unreliable. A 2003 study in Ghana found that in 1995 four percent said they had not undergone FGM, but in 2000 said they had, while 11 percent switched in the other direction. In Tanzania in 2005, 66 percent reported FGM, but a medical exam found that 73 percent had undergone it. In Sudan in 2006, a significant percentage of infibulated women and girls reported a less severe type. Types Standard questionnaires from United Nations bodies ask women whether they or their daughters have undergone the following: (1) cut, no flesh removed (symbolic nicking); (2) cut, some flesh removed; (3) sewn closed; or (4) type not determined/unsure/doesnt know. The most common procedures fall within the "cut, some flesh removed" category and involve complete or partial removal of the clitoral glans. The World Health Organization (a UN agency) created a more detailed typology in 1997: Types I–II vary in how much tissue is removed; Type III is equivalent to the UNICEF category "sewn closed"; and Type IV describes miscellaneous procedures, including symbolic nicking. Type I Type I is "partial or total removal of the clitoral glans (the external and visible part of the clitoris, which is a sensitive part of the female genitals), and/or the prepuce/clitoral hood (the fold of skin surrounding the clitoral glans)". Type Ia involves removal of the clitoral hood only. This is rarely performed alone. The more common procedure is Type Ib (clitoridectomy), the complete or partial removal of the clitoral glans (the visible tip of the clitoris) and clitoral hood. The circumciser pulls the clitoral glans with her thumb and index finger and cuts it off. Type II Type II (excision) is the complete or partial removal of the inner labia, with or without removal of the clitoral glans and outer labia. Type IIa is removal of the inner labia; Type IIb, removal of the clitoral glans and inner labia; and Type IIc, removal of the clitoral glans, inner and outer labia. Excision in French can refer to any form of FGM. Type III Type III (infibulation or pharaonic circumcision), the "sewn closed" category, is the removal of the external genitalia and fusion of the wound. The inner and/or outer labia are cut away, with or without removal of the clitoral glans. Type III is found largely in northeast Africa, particularly Djibouti, Eritrea, Ethiopia, Somalia, and Sudan (although not in South Sudan). According to one 2008 estimate, over eight million women in Africa are living with Type III FGM. According to UNFPA in 2010, 20 percent of women with FGM have been infibulated. In Somalia, according to Edna Adan Ismail, the child squats on a stool or mat while adults pull her legs open; a local anaesthetic is applied if available: The element of speed and surprise is vital and the circumciser immediately grabs the clitoris by pinching it between her nails aiming to amputate it with a slash. The organ is then shown to the senior female relatives of the child who will decide whether the amount that has been removed is satisfactory or whether more is to be cut off. After the clitoris has been satisfactorily amputated... the circumciser can proceed with the total removal of the labia minora and the paring of the inner walls of the labia majora. Since the entire skin on the inner walls of the labia majora has to be removed all the way down to the perineum, this becomes a messy business. By now, the child is screaming, struggling, and bleeding profusely, which makes it difficult for the circumciser to hold with bare fingers and nails the slippery skin and parts that are to be cut or sutured together.... Having ensured that sufficient tissue has been removed to allow the desired fusion of the skin, the circumciser pulls together the opposite sides of the labia majora, ensuring that the raw edges where the skin has been removed are well approximated. The wound is now ready to be stitched or for thorns to be applied. If a needle and thread are being used, close tight sutures will be placed to ensure that a flap of skin covers the vulva and extends from the mons veneris to the perineum, and which, after the wound heals, will form a bridge of scar tissue that will totally occlude the vaginal introitus. The amputated parts might be placed in a pouch for the girl to wear. A single hole of 2–3 mm is left for the passage of urine and menstrual fluid. The vulva is closed with surgical thread, or agave or acacia thorns, and might be covered with a poultice of raw egg, herbs, and sugar. To help the tissue bond, the girls legs are tied together, often from hip to ankle; the bindings are usually loosened after a week and removed after two to six weeks. If the remaining hole is too large in the view of the girls family, the procedure is repeated.The vagina is opened for sexual intercourse, for the first time either by a midwife with a knife or by the womans husband with his penis. In some areas, including Somaliland, female relatives of the bride and groom might watch the opening of the vagina to check that the girl is a virgin. The woman is opened further for childbirth (defibulation or deinfibulation), and closed again afterwards (reinfibulation). Reinfibulation can involve cutting the vagina again to restore the pinhole size of the first infibulation. This might be performed before marriage, and after childbirth, divorce and widowhood. Hanny Lightfoot-Klein interviewed hundreds of women and men in Sudan in the 1980s about sexual intercourse with Type III: The penetration of the brides infibulation takes anywhere from 3 or 4 days to several months. Some men are unable to penetrate their wives at all (in my study over 15%), and the task is often accomplished by a midwife under conditions of great secrecy, since this reflects negatively on the mans potency. Some who are unable to penetrate their wives manage to get them pregnant in spite of the infibulation, and the womans vaginal passage is then cut open to allow birth to take place.... Those men who do manage to penetrate their wives do so often, or perhaps always, with the help of the "little knife". This creates a tear which they gradually rip more and more until the opening is sufficient to admit the penis. Type IV Type IV is "[a]ll other harmful procedures to the female genitalia for non-medical purposes", including pricking, piercing, incising, scraping and cauterization. It includes nicking of the clitoris (symbolic circumcision), burning or scarring the genitals, and introducing substances into the vagina to tighten it. Labia stretching is also categorized as Type IV. Common in southern and eastern Africa, the practice is supposed to enhance sexual pleasure for the man and add to the sense of a woman as a closed space. From the age of eight, girls are encouraged to stretch their inner labia using sticks and massage. Girls in Uganda are told they may have difficulty giving birth without stretched labia.A definition of FGM from the WHO in 1995 included gishiri cutting and angurya cutting, found in Nigeria and Niger. These were removed from the WHOs 2008 definition because of insufficient information about prevalence and consequences. Angurya cutting is excision of the hymen, usually performed seven days after birth. Gishiri cutting involves cutting the vaginas front or back wall with a blade or penknife, performed in response to infertility, obstructed labour, and other conditions. In a study by Nigerian physician Mairo Usman Mandara, over 30 percent of women with gishiri cuts were found to have vesicovaginal fistulae (holes that allow urine to seep into the vagina). Complications Short term FGM harms womens physical and emotional health throughout their lives. It has no known health benefits. The short-term and late complications depend on the type of FGM, whether the practitioner has had medical training, and whether they used antibiotics and sterilized or single-use surgical instruments. In the case of Type III, other factors include how small a hole was left for the passage of urine and menstrual blood, whether surgical thread was used instead of agave or acacia thorns, and whether the procedure was performed more than once (for example, to close an opening regarded as too wide or re-open one too small).Common short-term complications include swelling, excessive bleeding, pain, urine retention, and healing problems/wound infection. A 2014 systematic review of 56 studies suggested that over one in ten girls and women undergoing any form of FGM, including symbolic nicking of the clitoris (Type IV), experience immediate complications, although the risks increased with Type III. The review also suggested that there was under-reporting. Other short-term complications include fatal bleeding, anaemia, urinary infection, septicaemia, tetanus, gangrene, necrotizing fasciitis (flesh-eating disease), and endometritis. It is not known how many girls and women die as a result of the practice, because complications may not be recognized or reported. The practitioners use of shared instruments is thought to aid the transmission of hepatitis B, hepatitis C and HIV, although no epidemiological studies have shown this. Long term Late complications vary depending on the type of FGM. They include the formation of scars and keloids that lead to strictures and obstruction, epidermoid cysts that may become infected, and neuroma formation (growth of nerve tissue) involving nerves that supplied the clitoris. An infibulated girl may be left with an opening as small as 2–3 mm, which can cause prolonged, drop-by-drop urination, pain while urinating, and a feeling of needing to urinate all the time. Urine may collect underneath the scar, leaving the area under the skin constantly wet, which can lead to infection and the formation of small stones. The opening is larger in women who are sexually active or have given birth by vaginal delivery, but the urethra opening may still be obstructed by scar tissue. Vesicovaginal or rectovaginal fistulae can develop (holes that allow urine or faeces to seep into the vagina). This and other damage to the urethra and bladder can lead to infections and incontinence, pain during sexual intercourse and infertility.Painful periods are common because of the obstruction to the menstrual flow, and blood can stagnate in the vagina and uterus. Complete obstruction of the vagina can result in hematocolpos and hematometra (where the vagina and uterus fill with menstrual blood). The swelling of the abdomen and lack of menstruation can resemble pregnancy. Asma El Dareer, a Sudanese physician, reported in 1979 that a girl in Sudan with this condition was killed by her family. Pregnancy, childbirth FGM may place women at higher risk of problems during pregnancy and childbirth, which are more common with the more extensive FGM procedures. Infibulated women may try to make childbirth easier by eating less during pregnancy to reduce the babys size.: 99 In women with vesicovaginal or rectovaginal fistulae, it is difficult to obtain clear urine samples as part of prenatal care, making the diagnosis of conditions such as pre-eclampsia harder. Cervical evaluation during labour may be impeded and labour prolonged or obstructed. Third-degree laceration (tears), anal-sphincter damage and emergency caesarean section are more common in infibulated women.Neonatal mortality is increased. The WHO estimated in 2006 that an additional 10–20 babies die per 1,000 deliveries as a result of FGM. The estimate was based on a study conducted on 28,393 women attending delivery wards at 28 obstetric centres in Burkina Faso, Ghana, Kenya, Nigeria, Senegal, and Sudan. In those settings all types of FGM were found to pose an increased risk of death to the baby: 15 percent higher for Type I, 32 percent for Type II, and 55 percent for Type III. The reasons for this were unclear, but may be connected to genital and urinary tract infections and the presence of scar tissue. According to the study, FGM was associated with an increased risk to the mother of damage to the perineum and excessive blood loss, as well as a need to resuscitate the baby, and stillbirth, perhaps because of a long second stage of labour. Psychological effects, sexual function According to a 2015 systematic review there is little high-quality information available on the psychological effects of FGM. Several small studies have concluded that women with FGM develop anxiety, depression, and post-traumatic stress disorder. Feelings of shame and betrayal can develop when women leave the culture that practices FGM and learn that their condition is not the norm, but within the practicing culture, they may view their FGM with pride because for them it signifies beauty, respect for tradition, chastity and hygiene. Studies on sexual function have also been small. A 2013 meta-analysis of 15 studies involving 12,671 women from seven countries concluded that women with FGM were twice as likely to report no sexual desire and 52 percent more likely to report dyspareunia (painful sexual intercourse). One-third reported reduced sexual feelings. Distribution Household surveys Aid agencies define the prevalence of FGM as the percentage of the 15–49 age group that has experienced it. These figures are based on nationally representative household surveys known as Demographic and Health Surveys (DHS), developed by Macro International and funded mainly by the United States Agency for International Development (USAID); and Multiple Indicator Cluster Surveys (MICS) conducted with financial and technical help from UNICEF. These surveys have been carried out in Africa, Asia, Latin America, and elsewhere roughly every five years since 1984 and 1995 respectively. The first to ask about FGM was the 1989–1990 DHS in northern Sudan. The first publication to estimate FGM prevalence based on DHS data (in seven countries) was written by Dara Carr of Macro International in 1997. Type of FGM Questions the women are asked during the surveys include: "Was the genital area just nicked/cut without removing any flesh? Was any flesh (or something) removed from the genital area? Was your genital area sewn?" Most women report "cut, some flesh removed" (Types I and II).Type I is the most common form in Egypt, and in the southern parts of Nigeria. Type III (infibulation) is concentrated in northeastern Africa, particularly Djibouti, Eritrea, Somalia, and Sudan. In surveys in 2002–2006, 30 percent of cut girls in Djibouti, 38 percent in Eritrea, and 63 percent in Somalia had experienced Type III. There is also a high prevalence of infibulation among girls in Niger and Senegal, and in 2013 it was estimated that in Nigeria three percent of the 0–14 age group had been infibulated. The type of procedure is often linked to ethnicity. In Eritrea, for example, a survey in 2002 found that all Hedareb girls had been infibulated, compared with two percent of the Tigrinya, most of whom fell into the "cut, no flesh removed" category. Prevalence FGM is mostly found in what Gerry Mackie called an "intriguingly contiguous" zone in Africa—east to west from Somalia to Senegal, and north to south from Egypt to Tanzania. Nationally representative figures are available for 27 countries in Africa, as well as Indonesia, Iraqi Kurdistan and Yemen. Over 200 million women and girls are thought to be living with FGM in those 30 countries.The highest concentrations among the 15–49 age group are in Somalia (98 percent), Guinea (97 percent), Djibouti (93 percent), Egypt (91 percent), and Sierra Leone (90 percent). As of 2013, 27.2 million women had undergone FGM in Egypt, 23.8 million in Ethiopia, and 19.9 million in Nigeria. There is a high concentration in Indonesia, where according to UNICEF Type I (clitoridectomy) and Type IV (symbolic nicking) are practised; the Indonesian Ministry of Health and Indonesian Ulema Council both say the clitoris should not be cut. The prevalence rate for the 0–11 group in Indonesia is 49 percent (13.4 million).: 2 Smaller studies or anecdotal reports suggest that various types of FGM are also practised in various circumstances in Colombia, Jordan, Oman, Saudi Arabia, Malaysia, the United Arab Emirates, and India, but there are no representative data on the prevalence in these countries.Prevalence figures for the 15–19 age group and younger show a downward trend. For example, Burkina Faso fell from 89 percent (1980) to 58 percent (2010); Egypt from 97 percent (1985) to 70 percent (2015); and Kenya from 41 percent (1984) to 11 percent (2014). Beginning in 2010, household surveys asked women about the FGM status of all their living daughters. The highest concentrations among girls aged 0–14 were in Gambia (56 percent), Mauritania (54 percent), Indonesia (49 percent for 0–11) and Guinea (46 percent). The figures suggest that a girl was one third less likely in 2014 to undergo FGM than she was 30 years ago. According to a 2018 study published in BMJ Global Health, the prevalence within the 0–14 year old group fell in East Africa from 71.4 percent in 1995 to 8 percent in 2016; in North Africa from 57.7 percent in 1990 to 14.1 percent in 2015; and in West Africa from 73.6 percent in 1996 to 25.4 percent in 2017. If the current rate of decline continues, the number of girls cut will nevertheless continue to rise because of population growth, according to UNICEF in 2014; they estimate that the figure will increase from 3.6 million a year in 2013 to 4.1 million in 2050. Rural areas, wealth, education Surveys have found FGM to be more common in rural areas, less common in most countries among girls from the wealthiest homes, and (except in Sudan and Somalia) less common in girls whose mothers had access to primary or secondary/higher education. In Somalia and Sudan the situation was reversed: in Somalia, the mothers access to secondary/higher education was accompanied by a rise in prevalence of FGM in their daughters, and in Sudan, access to any education was accompanied by a rise. Age, ethnicity FGM is not invariably a rite of passage between childhood and adulthood but is often performed on much younger children. Girls are most commonly cut shortly after birth to age 15. In half the countries for which national figures were available in 2000–2010, most girls had been cut by age five. Over 80 percent (of those cut) are cut before the age of five in Nigeria, Mali, Eritrea, Ghana and Mauritania. The 1997 Demographic and Health Survey in Yemen found that 76 percent of girls had been cut within two weeks of birth. The percentage is reversed in Somalia, Egypt, Chad, and the Central African Republic, where over 80 percent (of those cut) are cut between five and 14. Just as the type of FGM is often linked to ethnicity, so is the mean age. In Kenya, for example, the Kisi cut around age 10 and the Kamba at 16.A countrys national prevalence often reflects a high sub-national prevalence among certain ethnicities, rather than a widespread practice. In Iraq, for example, FGM is found mostly among the Kurds in Erbil (58 percent prevalence within age group 15–49, as of 2011), Sulaymaniyah (54 percent) and Kirkuk (20 percent), giving the country a national prevalence of eight percent. The practice is sometimes an ethnic marker, but it may differ along national lines. For example, in the northeastern regions of Ethiopia and Kenya, which share a border with Somalia, the Somali people practise FGM at around the same rate as they do in Somalia. But in Guinea all Fulani women responding to a survey in 2012 said they had experienced FGM, against 12 percent of the Fulani in Chad, while in Nigeria the Fulani are the only large ethnic group in the country not to practise it. Reasons Support from women Dahabo Musa, a Somali woman, described infibulation in a 1988 poem as the "three feminine sorrows": the procedure itself, the wedding night when the woman is cut open, then childbirth when she is cut again. Despite the evident suffering, it is women who organize all forms of FGM. Anthropologist Rose Oldfield Hayes wrote in 1975 that educated Sudanese men who did not want their daughters to be infibulated (preferring clitoridectomy) would find the girls had been sewn up after the grandmothers arranged a visit to relatives. Gerry Mackie has compared the practice to footbinding. Like FGM, footbinding was carried out on young girls, nearly universal where practised, tied to ideas about honour, chastity, and appropriate marriage, and "supported and transmitted" by women. FGM practitioners see the procedures as marking not only ethnic boundaries but also gender differences. According to this view, male circumcision defeminizes men while FGM demasculinizes women. Fuambai Ahmadu, an anthropologist and member of the Kono people of Sierra Leone, who in 1992 underwent clitoridectomy as an adult during a Sande society initiation, argued in 2000 that it is a male-centred assumption that the clitoris is important to female sexuality. African female symbolism revolves instead around the concept of the womb. Inf
Female genital mutilation	ibulation draws on that idea of enclosure and fertility. "[G]enital cutting completes the social definition of a childs sex by eliminating external traces of androgyny," Janice Boddy wrote in 2007. "The female body is then covered, closed, and its productive blood bound within; the male body is unveiled, opened, and exposed."In communities where infibulation is common, there is a preference for womens genitals to be smooth, dry and without odour, and both women and men may find the natural vulva repulsive. Some men seem to enjoy the effort of penetrating an infibulation. The local preference for dry sex causes women to introduce substances into the vagina to reduce lubrication, including leaves, tree bark, toothpaste and Vicks menthol rub. The WHO includes this practice within Type IV FGM, because the added friction during intercourse can cause lacerations and increase the risk of infection. Because of the smooth appearance of an infibulated vulva, there is also a belief that infibulation increases hygiene.Common reasons for FGM cited by women in surveys are social acceptance, religion, hygiene, preservation of virginity, marriageability and enhancement of male sexual pleasure. In a study in northern Sudan, published in 1983, only 17.4 percent of women opposed FGM (558 out of 3,210), and most preferred excision and infibulation over clitoridectomy. Attitudes are changing slowly. In Sudan in 2010, 42 percent of women who had heard of FGM said the practice should continue. In several surveys since 2006, over 50 percent of women in Mali, Guinea, Sierra Leone, Somalia, Gambia, and Egypt supported FGMs continuance, while elsewhere in Africa, Iraq, and Yemen most said it should end, although in several countries only by a narrow margin. Social obligation, poor access to information Against the argument that women willingly choose FGM for their daughters, UNICEF calls the practice a "self-enforcing social convention" to which families feel they must conform to avoid uncut daughters facing social exclusion. Ellen Gruenbaum reported that, in Sudan in the 1970s, cut girls from an Arab ethnic group would mock uncut Zabarma girls with Ya, Ghalfa! ("Hey, unclean!"). The Zabarma girls would respond Ya, mutmura! (A mutmara was a storage pit for grain that was continually opened and closed, like an infibulated woman.) But despite throwing the insult back, the Zabarma girls would ask their mothers, "Whats the matter? Dont we have razor blades like the Arabs?"Because of poor access to information, and because circumcisers downplay the causal connection, women may not associate the health consequences with the procedure. Lala Baldé, president of a womens association in Medina Cherif, a village in Senegal, told Mackie in 1998 that when girls fell ill or died, it was attributed to evil spirits. When informed of the causal relationship between FGM and ill health, Mackie wrote, the women broke down and wept. He argued that surveys taken before and after this sharing of information would show very different levels of support for FGM. The American non-profit group Tostan, founded by Molly Melching in 1991, introduced community-empowerment programs in several countries that focus on local democracy, literacy, and education about healthcare, giving women the tools to make their own decisions. In 1997, using the Tostan program, Malicounda Bambara in Senegal became the first village to abandon FGM. By August 2019, 8,800 communities in eight countries had pledged to abandon FGM and child marriage. Religion Surveys have shown a widespread belief, particularly in Mali, Mauritania, Guinea, and Egypt, that FGM is a religious requirement. Gruenbaum has argued that practitioners may not distinguish between religion, tradition, and chastity, making it difficult to interpret the data. FGMs origins in northeastern Africa are pre-Islamic, but the practice became associated with Islam because of that religions focus on female chastity and seclusion. According to a 2013 UNICEF report, in 18 African countries at least 10 percent of Muslim females had experienced FGM, and in 13 of those countries, the figure rose to 50–99 percent. There is no mention of the practice in the Quran. It is praised in a few daʻīf (weak) hadith (sayings attributed to Muhammad) as noble but not required, although it is regarded as obligatory by the Shafii version of Sunni Islam. In 2007 the Al-Azhar Supreme Council of Islamic Research in Cairo ruled that FGM had "no basis in core Islamic law or any of its partial provisions".There is no mention of FGM in the Bible. Christian missionaries in Africa were among the first to object to FGM, but Christian communities in Africa do practise it. In 2013 UNICEF identified 19 African countries in which at least 10 percent of Christian women and girls aged 15 to 49 had undergone FGM; in Niger, 55 percent of Christian women and girls had experienced it, compared with two percent of their Muslim counterparts. The only Jewish group known to have practised it is the Beta Israel of Ethiopia. Judaism requires male circumcision but does not allow FGM. FGM is also practised by animist groups, particularly in Guinea and Mali. History Antiquity The practices origins are unknown. Gerry Mackie has suggested that, because FGMs east–west, north–south distribution in Africa meets in Sudan, infibulation may have begun there with the Meroite civilization (c. 800 BCE – c. 350 CE), before the rise of Islam, to increase confidence in paternity. According to historian Mary Knight, Spell 1117 (c. 1991–1786 BCE) of the Ancient Egyptian Coffin Texts may refer in hieroglyphs to an uncircumcised girl (mt): The spell was found on the sarcophagus of Sit-hedjhotep, now in the Egyptian Museum, and dates to Egypts Middle Kingdom. (Paul F. ORourke argues that mt probably refers instead to a menstruating woman.) The proposed circumcision of an Egyptian girl, Tathemis, is also mentioned on a Greek papyrus, from 163 BCE, in the British Museum: "Sometime after this, Nephoris [Tathemiss mother] defrauded me, being anxious that it was time for Tathemis to be circumcised, as is the custom among the Egyptians."The examination of mummies has shown no evidence of FGM. Citing the Australian pathologist Grafton Elliot Smith, who examined hundreds of mummies in the early 20th century, Knight writes that the genital area may resemble Type III because during mummification the skin of the outer labia was pulled toward the anus to cover the pudendal cleft, possibly to prevent a sexual violation. It was similarly not possible to determine whether Types I or II had been performed, because soft tissues had deteriorated or been removed by the embalmers.The Greek geographer Strabo (c. 64 BCE – c. 23 CE) wrote about FGM after visiting Egypt around 25 BCE: "This is one of the customs most zealously pursued by them [the Egyptians]: to raise every child that is born and to circumcise [peritemnein] the males and excise [ektemnein] the females..." Philo of Alexandria (c. 20 BCE – 50 CE) also made reference to it: "the Egyptians by the custom of their country circumcise the marriageable youth and maid in the fourteenth (year) of their age when the male begins to get seed, and the female to have a menstrual flow." It is mentioned briefly in a work attributed to the Greek physician Galen (129 – c. 200 CE): "When [the clitoris] sticks out to a great extent in their young women, Egyptians consider it appropriate to cut it out." Another Greek physician, Aëtius of Amida (mid-5th to mid-6th century CE), offered more detail in book 16 of his Sixteen Books on Medicine, citing the physician Philomenes. The procedure was performed in case the clitoris, or nymphê, grew too large or triggered sexual desire when rubbing against clothing. "On this account, it seemed proper to the Egyptians to remove it before it became greatly enlarged," Aëtius wrote, "especially at that time when the girls were about to be married": The surgery is performed in this way: Have the girl sit on a chair while a muscled young man standing behind her places his arms below the girls thighs. Have him separate and steady her legs and whole body. Standing in front and taking hold of the clitoris with a broad-mouthed forceps in his left hand, the surgeon stretches it outward, while with the right hand, he cuts it off at the point next to the pincers of the forceps. It is proper to let a length remain from that cut off, about the size of the membrane thats between the nostrils, so as to take away the excess material only; as I have said, the part to be removed is at that point just above the pincers of the forceps. Because the clitoris is a skinlike structure and stretches out excessively, do not cut off too much, as a urinary fistula may result from cutting such large growths too deeply. The genital area was then cleaned with a sponge, frankincense powder and wine or cold water, and wrapped in linen bandages dipped in vinegar, until the seventh day when calamine, rose petals, date pits, or a "genital powder made from baked clay" might be applied.Whatever the practices origins, infibulation became linked to slavery. Mackie cites the Portuguese missionary João dos Santos, who in 1609 wrote of a group near Mogadishu who had a "custome to sew up their Females, especially their slaves being young to make them unable for conception, which makes these slaves sell dearer, both for their chastitie, and for better confidence which their Masters put in them". Thus, Mackie argues, a "practice associated with shameful female slavery came to stand for honor". Europe and the United States Gynaecologists in 19th-century Europe and the United States removed the clitoris to treat insanity and masturbation. A British doctor, Robert Thomas, suggested clitoridectomy as a cure for nymphomania in 1813. In 1825 The Lancet described a clitoridectomy performed in 1822 in Berlin by Karl Ferdinand von Graefe on a 15-year-old girl who was masturbating excessively.Isaac Baker Brown, an English gynaecologist, president of the Medical Society of London and co-founder in 1845 of St. Marys Hospital, believed that masturbation, or "unnatural irritation" of the clitoris, caused hysteria, spinal irritation, fits, idiocy, mania, and death. He, therefore "set to work to remove the clitoris whenever he had the opportunity of doing so", according to his obituary. Brown performed several clitoridectomies between 1859 and 1866. In the United States, J. Marion Sims followed Browns work and in 1862 slit the neck of a womans uterus and amputated her clitoris, "for the relief of the nervous or hysterical condition as recommended by Baker Brown". When Brown published his views in On the Curability of Certain Forms of Insanity, Epilepsy, Catalepsy, and Hysteria in Females (1866), doctors in London accused him of quackery and expelled him from the Obstetrical Society.Later in the 19th century, A. J. Bloch, a surgeon in New Orleans, removed the clitoris of a two-year-old girl who was reportedly masturbating. According to a 1985 paper in the Obstetrical & Gynecological Survey, clitoridectomy was performed in the United States into the 1960s to treat hysteria, erotomania and lesbianism. From the mid-1950s, James C. Burt, a gynaecologist in Dayton, Ohio, performed non-standard repairs of episiotomies after childbirth, adding more stitches to make the vaginal opening smaller. From 1966 until 1989, he performed "love surgery" by cutting womens pubococcygeus muscle, repositioning the vagina and urethra, and removing the clitoral hood, thereby making their genital area more appropriate, in his view, for intercourse in the missionary position. "Women are structurally inadequate for intercourse," he wrote; he said he would turn them into "horny little mice". In the 1960s and 1970s he performed these procedures without consent while repairing episiotomies and performing hysterectomies and other surgery; he said he had performed a variation of them on 4,000 women by 1975. Following complaints, he was required in 1989 to stop practicing medicine in the United States. Opposition and legal status Colonial opposition in Kenya Protestant missionaries in British East Africa (present-day Kenya) began campaigning against FGM in the early 20th century, when Dr. John Arthur joined the Church of Scotland Mission (CSM) in Kikuyu. An important ethnic marker, the practice was known by the Kikuyu, the countrys main ethnic group, as irua for both girls and boys. It involved excision (Type II) for girls and removal of the foreskin for boys. Unexcised Kikuyu women (irugu) were outcasts.Jomo Kenyatta, general secretary of the Kikuyu Central Association and later Kenyas first prime minister, wrote in 1938 that, for the Kikuyu, the institution of FGM was the "conditio sine qua non of the whole teaching of tribal law, religion and morality". No proper Kikuyu man or woman would marry or have sexual relations with someone who was not circumcised, he wrote. A womans responsibilities toward the tribe began with her initiation. Her age and place within tribal history were traced to that day, and the group of girls with whom she was cut was named according to current events, an oral tradition that allowed the Kikuyu to track people and events going back hundreds of years. Beginning with the CSM in 1925, several missionary churches declared that FGM was prohibited for African Christians; the CSM announced that Africans practising it would be excommunicated, which resulted in hundreds leaving or being expelled. In 1929 the Kenya Missionary Council began referring to FGM as the "sexual mutilation of women", and a persons stance toward the practice became a test of loyalty, either to the Christian churches or to the Kikuyu Central Association. The stand-off turned FGM into a focal point of the Kenyan independence movement; the 1929–1931 period is known in the countrys historiography as the female circumcision controversy. When Hulda Stumpf, an American missionary who opposed FGM in the girls school she helped to run, was murdered in 1930, Edward Grigg, the governor of Kenya, told the British Colonial Office that the killer had tried to circumcise her.There was some opposition from Kenyan women themselves. At the mission in Tumutumu, Karatina, where Marion Scott Stevenson worked, a group calling themselves Ngo ya Tuiritu ("Shield of Young Girls"), the membership of which included Raheli Warigia (mother of Gakaara wa Wanjaũ), wrote to the Local Native Council of South Nyeri on 25 December 1931: "[W]e of the Ngo ya Tuiritu heard that there are men who talk of female circumcision, and we get astonished because they (men) do not give birth and feel the pain and even some die and even others become infertile, and the main cause is circumcision. Because of that, the issue of circumcision should not be forced. People are caught like sheep; one should be allowed to cut her own way of either agreeing to be circumcised or not without being dictated on ones own body."Elsewhere, support for the practice from women was strong. In 1956 in Meru, eastern Kenya, when the council of male elders (the Njuri Nchecke) announced a ban on FGM in 1956, thousands of girls cut each others genitals with razor blades over the next three years as a symbol of defiance. The movement came to be known as Ngaitana ("I will circumcise myself"), because to avoid naming their friends the girls said they had cut themselves. Historian Lynn Thomas described the episode as significant in the history of FGM because it made clear that its victims were also its perpetrators. FGM was eventually outlawed in Kenya in 2001, although the practice continued, reportedly driven by older women. Growth of opposition One of the earliest campaigns against FGM began in Egypt in the 1920s, when the Egyptian Doctors Society called for a ban. There was a parallel campaign in Sudan, run by religious leaders and British women. Infibulation was banned there in 1946, but the law was unpopular and barely enforced. The Egyptian government banned infibulation in state-run hospitals in 1959, but allowed partial clitoridectomy if parents requested it. (Egypt banned FGM entirely in 2007.) In 1959, the UN asked the WHO to investigate FGM, but the latter responded that it was not a medical matter. Feminists took up the issue throughout the 1970s. The Egyptian physician and feminist Nawal El Saadawi criticized FGM in her book Women and Sex (1972); the book was banned in Egypt and El Saadawi lost her job as director-general of public health. She followed up with a chapter, "The Circumcision of Girls", in her book The Hidden Face of Eve: Women in the Arab World (1980), which described her own clitoridectomy when she was six years old: I did not know what they had cut off from my body, and I did not try to find out. I just wept, and called out to my mother for help. But the worst shock of all was when I looked around and found her standing by my side. Yes, it was her, I could not be mistaken, in flesh and blood, right in the midst of these strangers, talking to them and smiling at them, as though they had not participated in slaughtering her daughter just a few moments ago. In 1975, Rose Oldfield Hayes, an American social scientist, became the first female academic to publish a detailed account of FGM, aided by her ability to discuss it directly with women in Sudan. Her article in American Ethnologist called it "female genital mutilation", rather than female circumcision, and brought it to wider academic attention. Edna Adan Ismail, who worked at the time for the Somalia Ministry of Health, discussed the health consequences of FGM in 1977 with the Somali Womens Democratic Organization. Two years later Fran Hosken, an Austrian-American feminist, published The Hosken Report: Genital and Sexual Mutilation of Females (1979), the first to offer global figures. She estimated that 110,529,000 women in 20 African countries had experienced FGM. The figures were speculative but consistent with later surveys. Describing FGM as a "training ground for male violence", Hosken accused female practitioners of "participating in the destruction of their own kind". The language caused a rift between Western and African feminists; African women boycotted a session featuring Hosken during the UNs Mid-Decade Conference on Women in Copenhagen in July 1980.In 1979, the WHO held a seminar, "Traditional Practices Affecting the Health of Women and Children", in Khartoum, Sudan, and in 1981, also in Khartoum, 150 academics and activists signed a pledge to fight FGM after a workshop held by the Babiker Badri Scientific Association for Womens Studies (BBSAWS), "Female Circumcision Mutilates and Endangers Women – Combat it!" Another BBSAWS workshop in 1984 invited the international community to write a joint statement for the United Nations. It recommended that the "goal of all African women" should be the eradication of FGM and that, to sever the link between FGM and religion, clitoridectomy should no longer be referred to as sunna.The Inter-African Committee on Traditional Practices Affecting the Health of Women and Children, founded in 1984 in Dakar, Senegal, called for an end to the practice, as did the UNs World Conference on Human Rights in Vienna in 1993. The conference listed FGM as a form of violence against women, marking it as a human-rights violation, rather than a medical issue. Throughout the 1990s and 2000s governments in Africa and the Middle East passed legislation banning or restricting FGM. In 2003 the African Union ratified the Maputo Protocol on the rights of women, which supported the elimination of FGM. By 2015 laws restricting FGM had been passed in at least 23 of the 27 African countries in which it is concentrated, although several fell short of a ban. United Nations In December 1993, the United Nations General Assembly included FGM in resolution 48/104, the Declaration on the Elimination of Violence Against Women, and from 2003 sponsored International Day of Zero Tolerance for Female Genital Mutilation, held every 6 February. UNICEF began in 2003 to promote an evidence-based social norms approach, using ideas from game theory about how communities reach decisions about FGM, and building on the work of Gerry Mackie on the demise of footbinding in China. In 2005 the UNICEF Innocenti Research Centre in Florence published its first report on FGM. UNFPA and UNICEF launched a joint program in Africa in 2007 to reduce FGM by 40 percent within the 0–15 age group and eliminate it from at least one country by 2012, goals that were not met and which they later described as unrealistic. In 2008 several UN bodies recognized FGM as a human-rights violation, and in 2010 the UN called upon healthcare providers to stop carrying out the procedures, including reinfibulation after childbirth and symbolic nicking. In 2012 the General Assembly passed resolution 67/146, "Intensifying global efforts for the elimination of female genital mutilations". Non-practising countries Overview Immigration spread the practice to Australia, New Zealand, Europe, and North America, all of which outlawed it entirely or restricted it to consenting adults. Sweden outlawed FGM in 1982 with the Act Prohibiting the Genital Mutilation of Women, the first Western country to do so. Several former colonial powers, including Belgium, Britain, France, and the Netherlands, introduced new laws or made clear that it was covered by existing legislation. As of 2013, legislation banning FGM had been passed in 33 countries outside Africa and the Middle East. North America In the United States, an estimated 513,000 women and girls had experienced FGM or were at risk as of 2012. A Nigerian woman successfully contested deportation in March 1994, asking for "cultural asylum" on the grounds that her young daughters (who were American citizens) might be cut if she took them to Nigeria, and in 1996 Fauziya Kasinga from Togo became the first to be officially granted asylum to escape FGM. In 1996 the Federal Prohibition of Female Genital Mutilation Act made it illegal to perform FGM on minors for non-medical reasons, and in 2013 the Transport for Female Genital Mutilation Act prohibited transporting a minor out of the country for the purpose of FGM.: 2 The first FGM conviction in the US was in 2006, when Khalid Adem, who had emigrated from Ethiopia, was sentenced to ten years for aggravated battery and cruelty to children after severing his two-year-old daughters clitoris with a pair of scissors. A federal judge ruled in 2018 that the 1996 Act was unconstitutional, arguing that FGM is a "local criminal activity" that should be regulated by states. Twenty-four states had legislation banning FGM as of 2016,: 2 and in 2021 the STOP FGM Act of 2020 was signed into federal law. The American Academy of Pediatrics opposes all forms of the practice, including pricking the clitoral skin.Canada recognized FGM as a form of persecution in July 1994, when it granted refugee status to Khadra Hassan Farah, who had fled Somalia to avoid her daughter being cut. In 1997 section 268 of its Criminal Code was amended to ban FGM, except where "the person is at least eighteen years of age and there is no resulting bodily harm". As of February 2019, there had been no prosecutions. Officials have expressed concern that thousands of Canadian girls are at risk of being taken overseas to undergo the procedure, so-called "vacation cutting". Europe According to the European Parliament, 500,000 women in Europe had undergone FGM as of March 2009. In France up to 30,000 women were thought to have experienced it as of 1995. According to Colette Gallard, a family-planning counsellor, when FGM was first encountered in France, the reaction was that Westerners ought not to intervene. It took the deaths of two girls in 1982, one of them three months old, for that attitude to change. In 1991 a French court ruled that the Convention Relating to the Status of Refugees offered protection to FGM victims; the decision followed an asylum application from Aminata Diop, who fled an FGM procedure in Mali. The practice is outlawed by several provisions of Frances penal code that address bodily harm causing permanent mutilation or torture. The first civil suit was in 1982, and the first criminal prosecution in 1993. In 1999 a woman was given an eight-year sentence for having performed FGM on 48 girls. By 2014 over 100 parents and two practitioners had been prosecuted in over 40 criminal cases.Around 137,000 women and girls living in England and Wales were born in countries where FGM is practised, as of 2011. Performing FGM on children or adults was outlawed under the Prohibition of Female Circumcision Act 1985. This was replaced by the Female Genital Mutilation Act 2003 and Prohibition of Female Genital Mutilation (Scotland) Act 2005, which added a prohibition on arranging FGM outside the country for British citizens or permanent residents. The United Nations Committee on the Elimination of Discrimination against Women (CEDAW) asked the government in July 2013 to "ensure the full implementation of its legislation on FGM". The first charges were brought in 2014 against a physician and another man; the physician had stitched an infibulated woman after opening her for childbirth. Both men were acquitted in 2015. Criticism of opposition Tolerance versus human rights Anthropologists have accused FGM eradicationists of cultural colonialism, and have been criticized in turn for their moral relativism and failure to defend the idea of universal human rights. According to critics of the eradicationist position, the biological reductionism of the opposition to FGM, and the failure to appreciate FGMs cultural context, serves to "other" practitioners and undermine their agency—in particular when parents are referred to as "mutilators".Africans who object to the tone of FGM opposition risk appearing to defend the practice. The feminist theorist Obioma Nnaemeka, herself strongly opposed to FGM, argued in 2005 that renaming the practice female genital mutilation had introduced "a subtext of barbaric African and Muslim cultures and the Wests relevance (even indispensability) in purging [it]". According to Ugandan law professor Sylvia Tamale, the early Western opposition to FGM stemmed from a Judeo-Christian judgment that African sexual and family practices, including not only FGM but also dry sex, polygyny, bride price and levirate marriage, required correction. African feminists "take strong exception to the imperialist, racist and dehumanising infantil
Female genital mutilation	ization of African women", she wrote in 2011. Commentators highlight the voyeurism in the treatment of womens bodies as exhibits. Examples include images of womens vulvas after FGM or girls undergoing the procedure. The 1996 Pulitzer-prize-winning photographs of a 16-year-old Kenyan girl experiencing FGM were published by 12 American newspapers, without her consent either to be photographed or to have the images published.The debate has highlighted a tension between anthropology and feminism, with the formers focus on tolerance and the latters on equal rights for women. According to the anthropologist Christine Walley, a common position in anti-FGM literature has been to present African women as victims of false consciousness participating in their own oppression, a position promoted by feminists in the 1970s and 1980s, including Fran Hosken, Mary Daly and Hanny Lightfoot-Klein. It prompted the French Association of Anthropologists to issue a statement in 1981, at the height of the early debates, that "a certain feminism resuscitates (today) the moralistic arrogance of yesterdays colonialism". Comparison with other procedures Cosmetic procedures Nnaemeka argues that the crucial question, broader than FGM, is why the female body is subjected to so much "abuse and indignity", including in the West. Several authors have drawn a parallel between FGM and cosmetic procedures. Ronán Conroy of the Royal College of Surgeons in Ireland wrote in 2006 that cosmetic genital procedures were "driving the advance" of FGM by encouraging women to see natural variations as defects. Anthropologist Fadwa El Guindi compared FGM to breast enhancement, in which the maternal function of the breast becomes secondary to mens sexual pleasure. Benoîte Groult, the French feminist, made a similar point in 1975, citing FGM and cosmetic surgery as sexist and patriarchal. Against this, the medical anthropologist Carla Obermeyer argued in 1999 that FGM may be conducive to a subjects social well-being in the same way that rhinoplasty and male circumcision are. Despite the 2007 ban in Egypt, Egyptian women wanting FGM for their daughters seek amalyet tajmeel (cosmetic surgery) to remove what they see as excess genital tissue. Cosmetic procedures such as labiaplasty and clitoral hood reduction do fall within the WHOs definition of FGM, which aims to avoid loopholes, but the WHO notes that these elective practices are generally not regarded as FGM. Some legislation banning FGM, such as in Canada and the US, covers minors only, but several countries, including Sweden and the UK, have banned it regardless of consent. Sweden, for example, has banned operations "on the outer female sexual organs with a view to mutilating them or bringing about some other permanent change in them, regardless of whether or not consent has been given for the operation". Gynaecologist Birgitta Essén and anthropologist Sara Johnsdotter argue that the law seems to distinguish between Western and African genitals, and deems only African women (such as those seeking reinfibulation after childbirth) unfit to make their own decisions.The philosopher Martha Nussbaum argues that a key concern with FGM is that it is mostly conducted on children using physical force. The distinction between social pressure and physical force is morally and legally salient, comparable to the distinction between seduction and rape. She argues further that the literacy of women in practising countries is generally poorer than in developed nations, which reduces their ability to make informed choices. Intersex children, male circumcision Several commentators maintain that childrens rights are violated not only by FGM, but also by the genital alteration of intersex children, who are born with anomalies that physicians choose to correct. Arguments have been made that non-therapeutic circumcision of boys, also violates childrens rights. Religious male circumcision is practised by Muslims, Jews, and some Christian groups. Globally, about 30 percent of males over 15 are circumcised; of these, about two-thirds are Muslim. At least half the male population of the United States is circumcised, while most men in Europe are not. The positions of the worlds major medical organizations range from the view that elective circumcision of male babies and children carries significant risks and offers no medical benefits, to a belief that the procedure has a modest health benefit that outweighs small risks. See also No FGM Australia Sources Notes References Works cited Books and book chapters Journal articles United Nations reports Further reading "Circumcision, female", The Kinsey Institute (bibliography 1960s–1980s). FGM archive, The Guardian. Haworth, Abigail (18 November 2012). "The day I saw 248 girls suffering genital mutilation", The Observer. Lightfoot-Klein, Hanny (1989). Prisoners of Ritual: An Odyssey Into Female Genital Circumcision in Africa. New York: Routledge. Westley, David M. (1999). "Female circumcision and infibulation in Africa", Electronic Journal of Africana Bibliography, 4 (bibliography up to 1997).Personal stories El Saadawi, Nawal (1975). Woman at Point Zero. London: Zed Books. Dirie, Waris and Miller, Cathleen (1998). Desert Flower. New York: William Morrow. Kassindja, Fauziya and Miller-Muro, Layli (1998). Do They Hear You When You Cry. New York: Delacorte Press. Ali, Ayaan Hirsi (2007). Infidel: My Life. New York: Simon & Schuster. External links Media related to Female genital mutilation at Wikimedia Commons Quotations related to Female genital mutilation at Wikiquote
Melanoderma	Melanoderma is a genus of two species of white rot poroid fungi in the family Polyporaceae. The genus was circumscribed in 2011 to accommodate the type species Melanoderma microcarpum, found in China. Melanoderma disciforme, found in Yunnan, was added to the genus in 2015. The generic name Melanoderma refers to the dark-coloured crust of the cap. Phylogenetic analyses shows that Melanoderma is closely related to the genus Vanderbylia. == References ==
Hairy leukoplakia	Hairy leukoplakia is a white patch on the side of the tongue with a corrugated or hairy appearance. It is caused by Epstein-Barr virus (EBV) and occurs usually in persons who are immunocompromised, especially those with human immunodeficiency virus infection/acquired immunodeficiency syndrome (HIV/AIDS). The white lesion, which cannot be scraped off, is benign and does not require any treatment, although its appearance may have diagnostic and prognostic implications for the underlying condition. Depending upon what definition of leukoplakia is used, hairy leukoplakia is sometimes considered a subtype of leukoplakia, or a distinct diagnosis. Signs and symptoms There are no symptoms associated with the lesion itself, although many and varied symptoms and signs may be associated with the underlying cause of immunosuppression. The lesion is a white patch, which almost exclusively occurs on the lateral surfaces of the tongue, although rarely it may occur on the buccal mucosa, soft palate, pharynx or esophagus. The lesion may grow to involve the dorsal surface of the tongue. The texture is vertically corrugated ("hairy") or thickly furrowed and shaggy in appearance. Causes The white appearance is created by hyperkeratosis (overproduction of keratin) and epithelial hyperplasia. The causative agent implicated is Epstein-Barr virus, the same virus that causes infectious mononucleosis (glandular fever). After the primary EBV infection has been overcome, the virus will persist for the rest of the hosts life and "hides" from the immune system by latent infection of B lymphocytes. The virus also causes lytic infection in the oropharynx, but is kept in check by a normal, functioning immune system. Uncontrolled lytic infection is manifested as oral hairy leukoplakia in immunocompromised hosts. OHL usually arises where the immunocompromise is secondary to HIV/AIDS. Rarely are other causes of immunocompromise associated with OHL, but it has been reported in people who have received transplants and are taking immunosuppressive medication. OHL may also accompany chronic graft versus host disease. Even more rare are reports of OHL in persons with competent immune systems. Diagnosis The white lesion cannot be wiped away, unlike some other common oral white lesions, e.g. pseudomembranous candidiasis, and this may aid in the diagnosis. Diagnosis of OHL is mainly clinical, but can be supported by proof of EBV in the lesion (achieved by in situ hybridization, polymerase chain reaction, immunohistochemistry, Southern blotting, or electron microscopy) and HIV serotesting. When clinical appearance alone is used to diagnose OHL, there is a false positive rate of 17% compared to more objective methods. The appearance of OHL in a person who is known to be infected with HIV does not usually require further diagnostic tests as the association is well known. OHL in persons with no known cause of immunocompromise usually triggers investigations to look for an underlying cause. If tissue biopsy is carried out, the histopathologic appearance is of hyperplastic and parakeratinized epithelium, with "balloon cells" (lightly staining cells) in the upper stratum spinosum and "nuclear beading" in the superficial layers (scattered cells with peripheral margination of chromatin and clear nuclei, created by displacement of chromatin to the peripheral nucleus by EBV replication). Candida usually is seen growing in the parakeratin layer, but there are no normal inflammatory reactions to this in the tissues. There is no dysplasia (OHL is not a premalignant lesion). Classification In a classification of the oral lesions in HIV disease, OHL is grouped as "lesions strongly associated with HIV infection" (group I). It could also be classed as an opportunistic, viral disease. Hairy leukoplakia occurs on the tongue and has a similar name to hairy tongue, but these are separate conditions with different causes. Treatment Treatment is not necessary since the lesion is benign, however, the person may have aesthetic concerns about the appearance. The condition often resolves rapidly with high dose acyclovir or desiclovir but recurs once this therapy is stopped, or as the underlying immunocompromise worsens. Topical use of podophyllum resin or retinoids has also been reported to produce temporary remission.Antiretroviral drugs such as zidovudine may be effective in producing a significant regression of OHL. Recurrence of the lesion may also signify that highly active antiretroviral therapy (HAART) is becoming ineffective. Prognosis The oral lesion itself is benign and self-limiting, however this may not necessarily be the case for the underlying cause of immunocompromise. For instance, OHL with HIV/AIDS is a predictor of bad prognosis, (i.e. severe immunosuppression and advanced disease). Epidemiology Hairy leukoplakia is one of the most common oral manifestations of HIV/AIDS, along with oral candidiasis. It is the most common HIV/AIDS related condition caused by EBV, although EBV associated lymphomas may also occur. OHL mainly occurs in adult males, less commonly in adult females and rarely in children. The incidence rises as the CD4 count falls, and the appearance of OHL may signify progression of HIV to AIDS. A study from 2001 reported a significant decrease in the incidence of some oral manifestations of AIDS (including OHL and necrotizing ulcerative periodontitis), which was attributed to the use of HAART, whilst the incidence of other HIV-associated oral lesions did not alter significantly. History Oral hairy leukoplakia was discovered by Deborah Greenspan and John S. Greenspan, and in 1985 they identified a connection between it and Epstein-Barr virus (EBV). Oral hairy leukoplakia was first described by Greenspan et al. in 1984, a few years after the start of the AIDS epidemic. A link with OHL was not initially reported as scientific understanding of HIV/AIDS was just beginning to develop at that time. It was subsequently thought to occur only in HIV-infected, homosexual males, however, this is now known to not always be the case. Research directions It has been suggested that OHL be renamed according to its causative factor as “EBV leucoplakia”. References == External links ==
Steatocystoma multiplex	Steatocystoma multiplex, is a benign, autosomal dominant congenital condition resulting in multiple cysts on a persons body. Steatocystoma simplex is the solitary counterpart to steatocystoma multiplex.In steatocystoma multiplex, the tendency to develop cysts is inherited in an autosomal dominant fashion, so one parent can be expected to also have steatocystoma multiplex. It may also occur sporadically. Both males and females may be affected. The onset at puberty is presumably due to hormonal stimulus of the pilosebaceous unit. They most often arise on the chest and may also occur on the abdomen, upper arms, armpits and face. In some cases cysts may develop all over the body. The cysts are mostly small (2–20 mm) but they may be several centimetres in diameter. They tend to be soft to firm semi-translucent bumps, and contain an oily, yellow liquid. Sometimes a small central punctum can be identified and they may contain one or more hairs (eruptive vellus hair cysts). They may become inflamed and heal with scarring, like acne nodules (see nodulocystic acne and hidradenitis suppurativa). On inflammation they can become incredibly painful and reach sizes between 4-6cm in diameter. The area around the cyst can become red and painful to the touch; making mobility, sitting, strenuous movement or everyday activities very difficult and painful. Steatocystomas are thought to come from an abnormal lining of the passageway to the oil glands (sebaceous duct). Localised, generalised, facial, acral, and suppurative types of steatocystoma multiplex have been described. Causes It is associated with defects in Keratin 17. The condition is inherited in an autosomal dominant manner. This indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. However, a solitary case can also emerge in a family with no prior history of the disorder due to the occurrence of a mutation (often referred to as a sporadic or spontaneous mutation). Diagnosis It is difficult to diagnose genetic and rare diseases. Healthcare professionals would look at a combination of a patients medical history, symptoms, physical exam and other laboratory tests to inform their diagnosis. Treatment The cysts can be removed via excision, though conventional cyst excision techniques have proven impractical, and a specialized regimen is required.Cryotherapy and electrosessication may also be tried, but since it is genetic disorder all the modalities have very little effect. Individual cysts can be removed surgically. In most cases, small incisions (cuts into the skin) allow the cyst and its contents to be extracted through the opening. If it is tethered to the underlying skin, excision biopsy may be necessary. Cysts can also be removed by laser, electrosurgery or cryotherapy. Inflammation can be reduced with oral antibiotics. Oral isotretinoin is not curative but may temporarily shrink the cysts and reduce inflammation. See also Keratin disease Steatocystoma simplex List of cutaneous conditions List of cutaneous conditions caused by mutations in keratins References == External links ==
Acute eosinophilic leukemia	Acute eosinophilic leukemia (AEL) is a rare subtype of acute myeloid leukemia with 50 to 80 percent of eosinophilic cells in the blood and marrow. It can arise de novo or may develop in patients having the chronic form of a hypereosinophilic syndrome. Patients with acute eosinophilic leukemia have a propensity for developing bronchospasm as well as symptoms of the acute coronary syndrome and/or heart failure due to eosinophilic myocarditis and eosinophil-based endomyocardial fibrosis. Hepatomegaly and splenomegaly are more common than in other variants of AML. Diagnosis A specific histochemical reaction, cyanide-resistant peroxidase, permits identification of leukemic blast cells with eosinophilic differentiation and diagnosis of acute eosinoblastic leukemia in some cases of AML with few identifiable eosinophils in blood or marrow. Treatment and prognosis when there is eosinophilia with increased immature precursors along with blasts; one need to identify lineage of blasts. As per old FAB classification most of the time blast lineage will be myeloid and may fall in M4EO of FAB classification. This entity need treatment like acute myeloid leukemia. However more rarely Eosinophilic leukemia may have underlying lymphoid blasts with t(5;14) (IL3;IGH). with this gene fusion and eosinophilic cytokine comes under control of immunoglobulin heavy chain (IgH) locus. This entity need treatment as ALL. Overall prognosis is not dependent on eosinophilia but underlying lineage and genetic abnormalities. References == External links ==
Acephalgic migraine	Acephalgic migraine (also called migraine aura without headache, amigrainous migraine, isolated visual migraine, and optical migraine) is a neurological syndrome. It is a relatively uncommon variant of migraine in which the patient may experience some migraine symptoms such as aura, nausea, photophobia, and hemiparesis, but does not experience headache. It is generally classified as an event fulfilling the conditions of migraine with aura with no (or minimal) headache. It is sometimes distinguished from visual-only migraine aura without headache, also called ocular migraine. Symptoms and misdiagnosis Acephalgic migraines can occur in individuals of any age. Some individuals, more commonly male, only experience acephalgic migraine, but frequently patients also experience migraine with headache. Generally, the condition is more than twice as likely to occur in females than males. Pediatric acephalgic migraines are listed along with other childhood periodic syndromes by W.A. Al-Twaijri and M.I. Shevell as "migraine equivalents" (although not listed as such in the International Classification of Headache Disorders), which can be good predictors of the future development of typical migraines. Individuals who experience acephalgic migraines in childhood are highly likely to develop typical migraines as they grow older. Among women, incidents of acephalgic migraine increase during perimenopause.Scintillating scotoma is the most common symptom which usually happens concurrently with Expanding Fortification Spectra. Also frequently reported is monocular blindness. Acephalgic migraines typically do not persist more than a few hours and may last for as little as 15 seconds. On rare occasions, they may continue for up to two days.Acephalgic migraines may resemble transient ischemic attacks or, when longer in duration, stroke. The concurrence of other symptoms such as photophobia and nausea can help in determining the proper diagnosis. Occasionally, patients with acephalgic migraine are misdiagnosed as having epilepsy with visual seizures, but the reverse misdiagnosis is more common. Treatment The prevention and treatment of acephalgic migraine is broadly the same as for classical migraine, but the symptoms are usually less severe than those of classic migraine, so treatment is less likely to be required. See also ICHD classification and diagnosis of migraine == References ==
Loa loa filariasis	Loa loa filariasis is a skin and eye disease caused by the nematode worm Loa loa. Humans contract this disease through the bite of a deer fly or mango fly (Chrysops spp.), the vectors for Loa loa. The adult Loa loa filarial worm migrates throughout the subcutaneous tissues of humans, occasionally crossing into subconjunctival tissues of the eye where it can be easily observed. Loa loa does not normally affect ones vision but can be painful when moving about the eyeball or across the bridge of the nose. The disease can cause red itchy swellings below the skin called "Calabar swellings". The disease is treated with the drug diethylcarbamazine (DEC), and when appropriate, surgical methods may be employed to remove adult worms from the conjunctiva. Loiasis belongs to the so-called neglected diseases. Signs and symptoms A filariasis such as loiasis most often consists of asymptomatic microfilaremia. Some patients can develop lymphatic dysfunction causing lymphedema. Episodic angioedema (Calabar swellings) in the arms and legs, caused by immune reactions, are common. Calabar swellings are 3–10 cm in surface area, sometimes erythematous, and not pitting. When chronic, they can form cyst-like enlargements of the connective tissue around the sheaths of muscle tendons, becoming very painful when moved. The swellings may last for one to three days and may be accompanied by localized urticaria (skin eruptions) and pruritus (itching). They reappear at referent locations at irregular time intervals. Subconjunctival migration of an adult worm to the eyes can also occur frequently, and this is the reason Loa loa is also called the "African eye worm." The passage over the eyeball can be sensed, but it usually takes less than 15 minutes. Eyeworms affect men and women equally, but advanced age is a risk factor. Eosinophilia is often prominent in filarial infections. Dead worms may cause chronic abscesses, which may lead to the formation of granulomatous reactions and fibrosis.In the human host, Loa loa larvae migrate to the subcutaneous tissue, where they mature to adult worms in approximately one year, but sometimes up to four years. Adult worms migrate in the subcutaneous tissues at a speed less than 1 cm/min, mating and producing more microfilariae. The adult worms can live up to 17 years in the human host. Cause Transmission Loa loa infective larvae (L3) are transmitted to humans by the deer fly vectors Chrysops silica and C. dimidiata. These carriers are blood-sucking and day-biting, and they are found in rainforest-like environments in western and central Africa. Infective larvae (L3) mature to adults (L5) in the subcutaneous tissues of the human host, after which the adult worms—assuming presence of a male and female worm—mate and produce microfilariae. The cycle of infection continues when a non-infected mango or deer fly takes a blood meal from a microfilaremic human host, and this stage of the transmission is possible because of the combination of the diurnal periodicity of microfilariae and the day-biting tendencies of the Chrysops spp. Reservoir Humans are the primary reservoir for Loa loa. Other minor potential reservoirs have been indicated in various fly-biting habit studies, such as hippopotamus, wild ruminants (e.g. buffalo), rodents and lizards. A simian type of loiasis exists in monkeys and apes but it is transmitted by Chrysops langi. There is no crossover between the human and simian types of the disease. A related fly, Chrysops langi, has been isolated as a vector of simian loiasis, but this variant hunts within the forest and has not as yet been associated with human infection. Vector Loa loa is transmitted by several species of tabanid flies (Order: Diptera; Family: Tabanidae). Although horseflies of the genus Tabanus are often mentioned as vectors, the two most prominent vectors are from the tabanid genus Chrysops—C. silacea and C. dimidiata. These species exist only in Africa and are popularly known as deer flies and mango, or mangrove, flies.Chrysops spp. are small (5–20 mm long) with a large head and downward-pointing mouthparts. Their wings are clear or speckled brown. They are hematophagous and typically live in forested and muddy habitats like swamps, streams and reservoirs, and in rotting vegetation. Female mango and deer flies require a blood meal for production of a second batch of eggs. This batch is deposited near water, where the eggs hatch in 5–7 days. The larvae mature in water or soil, where they feed on organic material such as decaying animal and vegetable products. Fly larvae are 1–6 cm long and take 1–3 years to mature from egg to adult. When fully mature, C. silacea and C. dimidiata assume the day-biting tendencies of all tabanids.The bite of the mango fly can be very painful, possibly because of the laceration style employed; rather than puncturing the skin as a mosquito does, the mango fly (and deer fly) makes a laceration in the skin and subsequently laps up the blood. Female flies require a fair amount of blood for their aforementioned reproductive purposes and thus may take multiple blood meals from the same host if disturbed during the first one.Although Chrysops silacea and C. dimidiata are attracted to canopied rainforests, they do not do their biting there. Instead, they leave the forest and take most blood meals in open areas. The flies are attracted to smoke from wood fires and they use visual cues and sensation of carbon dioxide plumes to find their preferred host, humans.A study of Chrysops spp. biting habits showed that C. silacea and C. dimidiata take human blood meals approximately 90% of the time, with hippopotamus, wild ruminant, rodent and lizard blood meals making up the other 10%. Morphology Adult Loa worms are sexually dimorphic, with males considerably smaller than females at 30–34 mm long and 0.35–0.42 mm wide compared to 40–70 mm long and 0.5 mm wide. Adults live in the subcutaneous tissues of humans, where they mate and produce wormlike eggs called microfilariae. These microfilariae are 250–300 μm long, 6–8 μm wide and can be distinguished morphologically from other filariae, as they are sheathed and contain body nuclei that extend to the tip of the tail. Lifecycle The vector for Loa loa filariasis originates with flies from two hematophagous species of the genus Chrysops (deer flies), C. silacea and C. dimidiata. During a blood meal, an infected fly (genus Chrysops, day-biting flies) introduces third-stage filarial larvae onto the skin of the human host, where they penetrate into the bite wound. The larvae develop into adults that commonly reside in subcutaneous tissue. The female worms measure 40 to 70 mm in length and 0.5 mm in diameter, while the males measure 30 to 34 mm in length and 0.35 to 0.43 mm in diameter. Adults produce microfilariae measuring 250 to 300 μm by 6 to 8 μm, which are sheathed and have diurnal periodicity. Microfilariae have been recovered from spinal fluids, urine and sputum. During the day, they are found in peripheral blood, but during the noncirculation phase, they are found in the lungs. The fly ingests microfilariae during a blood meal. After ingestion, the microfilariae lose their sheaths and migrate from the flys midgut through the hemocoel to the thoracic muscles of the arthropod. There the microfilariae develop into first-stage larvae and subsequently into third-stage infective larvae. The third-stage infective larvae migrate to the flys proboscis and can infect another human when the fly takes a blood meal. Diagnosis Microscopic examination of microfilariae is a practical diagnostic procedure to find Loa loa. It is important to time the blood collection with the known periodicity of the microfilariae (between 10:00 a.m. and 2:00 p.m.). The blood sample can be a thick smear, stained with Giemsa or haematoxylin and eosin (see staining). For increased sensitivity, concentration techniques can be used. These include centrifugation of the blood sample lyzed in 2% formalin (Knotts technique), or filtration through a nucleopore membrane.Antigen detection using an immunoassay for circulating filarial antigens constitutes a useful diagnostic approach, because microfilaremia can be low and variable. Though the Institute for Tropical Medicine reports that no serologic diagnostics are available, tests that are highly specific to Loa loa have been developed in recent years. This is despite the fact that many recently developed methods of antibody detection are of limited value because substantial antigenic cross-reactivity exists between filaria and other parasitic worms (helminths), and that a positive serologic test does not necessarily distinguish among infections. The new tests have not reached the point-of-care level yet, but show promise for highlighting high-risk areas and individuals with co-endemic loiasis and onchocerciasis. Specifically, Thomas Nutman and colleagues at the National Institutes of Health have described the a luciferase immunoprecipitation assay (LIPS) and the related QLIPS (quick version). Whereas a previously described LISXP-1 ELISA test had a poor sensitivity (55%), the QLIPS test is practical, as it requires only a 15 minutes incubation, while delivering high sensitivity (97%) and specificity (100%). No report on the distribution status of LIPS or QLIPS testing is available, but these tests would help to limit complications derived from mass ivermectin treatment for onchocerciasis or dangerous strong doses of diethylcarbamazine for loiasis alone (as pertains to individual with high Loa loa microfilarial loads).Calabar swellings are the primary tool for visual diagnosis. Identification of adult worms is possible from tissue samples collected during subcutaneous biopsies. Adult worms migrating across the eye are another potential diagnostic, but the short timeframe for the worms passage through the conjunctiva makes this observation less common.In the past, healthcare providers used a provocative injection of Dirofilaria immitis as a skin-test antigen for filariasis diagnosis. If the patient was infected, the extract would cause an artificial allergic reaction and associated Calabar swelling similar to that caused, in theory, by metabolic products of the worm or dead worms.Blood tests to reveal microfilaremia are useful in many, but not all cases, as one-third of loiasis patients are amicrofilaremic. By contrast, eosinophilia is almost guaranteed in cases of loiasis, and blood testing for eosinophil fraction may be useful. Prevention Diethylcarbamazine has been shown as an effective prophylaxis for Loa loa infection. A study of Peace Corps volunteers in the highly Loa—endemic Gabon, for example, had the following results: 6 of 20 individuals in a placebo group contracted the disease, compared to 0 of 16 in the DEC-treated group. Seropositivity for antifilarial IgG antibody was also much higher in the placebo group. The recommended prophylactic dose is 300 mg DEC given orally once weekly. The only associated symptom in the Peace Corps study was nausea.Researchers believe that geo-mapping of appropriate habitat and human settlement patterns may, with the use of predictor variables such as forest, land cover, rainfall, temperature, and soil type, allow for estimation of Loa loa transmission in the absence of point-of-care diagnostic tests. In addition to geo-mapping and chemoprophylaxis, the same preventative strategies used for malaria should be undertaken to avoid contraction of loiasis. Specifically, DEET-containing insect repellent, permethrin-soaked clothing, and thick, long-sleeved and long-legged clothing ought to be worn to decrease susceptibility to the bite of the mango or deer fly vector. Because the vector is day-biting, mosquito (bed) nets do not increase protection against loiasis.Vector elimination strategies are an interesting consideration. It has been shown that the Chrysops vector has a limited flying range, but vector elimination efforts are not common, likely because the insects bite outdoors and have a diverse, if not long, range, living in the forest and biting in the open, as mentioned in the vector section. No vaccine has been developed for loiasis and there is little report on this possibility. Treatment Treatment of loiasis involves chemotherapy or, in some cases, surgical removal of adult worms followed by systemic treatment. The current drug of choice for therapy is diethylcarbamazine (DEC), though ivermectin use while not curative (i.e., it will not kill the adult worms) can substantially reduce the microfilarial load. The recommended dosage of DEC is 8–10 mg/kg/d taken three times daily for 21 days per CDC. The pediatric dose is the same. DEC is effective against microfilariae and somewhat effective against macrofilariae (adult worms). The recommended dosage of ivermectin is 150 µg/kg in patients with a low microfilaria load (with densities less than 8000 mf/mL).In patients with high microfilaria load and/or the possibility of an onchocerciasis coinfection, treatment with DEC and/or ivermectin may be contraindicated or require a substantially lower initial dose, as the rapid microfilaricidal actions of the drugs can provoke encephalopathy. In these cases, initial albendazole administration has proved helpful (and is superior to ivermectin, which can also be risky despite its slower-acting microfilaricidal effects over DEC). The CDC recommended dosage for albendazole is 200 mg taken twice a day for 21 days. Also, in cases where two or more DEC treatments have failed to provide a cure, subsequent albendazole treatment can be administered.Management of Loa loa infection in some instances can involve surgery, though the timeframe during which surgical removal of the worm must be carried out is very short. A detailed surgical strategy to remove an adult worm is as follows (from a real case in New York City). The 2007 procedure to remove an adult worm from a male Gabonian immigrant employed proparacaine and povidone-iodine drops, a wire eyelid speculum, and 0.5 ml 2% lidocaine with epinephrine 1:100,000, injected superiorly. A 2-mm incision was made and the immobile worm was removed with forceps. Gatifloxacin drops and an eye-patch over ointment were utilized post surgery and there were no complications (unfortunately, the patient did not return for DEC therapy to manage the additional worm—and microfilariae—present in his body). Epidemiology As of 2009, loiasis is endemic to 11 countries, all in western or central Africa, and an estimated 12–13 million people have the disease. The highest incidence is seen in Cameroon, Republic of the Congo, Democratic Republic of Congo, Central African Republic, Nigeria, Gabon, and Equatorial Guinea. The rates of Loa loa infection are lower but it is still present in and Angola, Benin, Chad and Uganda. The disease was once endemic to the western African countries of Ghana, Guinea, Guinea Bissau, Ivory Coast and Mali but has since disappeared.Throughout Loa loa-endemic regions, infection rates vary from 9 to 70 percent of the population. Areas at high risk of severe adverse reactions to mass treatment (with Ivermectin) are at present determined by the prevalence in a population of >20% microfilaremia, which has been recently shown in eastern Cameroon (2007 study), for example, among other locales in the region.Endemicity is closely linked to the habitats of the two known human loiasis vectors, Chrysops dimidiata and C. silicea.Cases have been reported on occasion in the United States but are restricted to travelers who have returned from endemic regions.In the 1990s, the only method of determining Loa loa intensity was with microscopic examination of standardized blood smears, which is not practical in endemic regions. Because mass diagnostic methods were not available, complications started to surface once mass ivermectin treatment programs started being carried out for onchocerciasis, another filariasis. Ivermectin, a microfilaricidal drug, may be contraindicated in patients who are co-infected with loiasis and have associated high microfilarial loads. The theory is that the killing of massive numbers of microfilaria, some of which may be near the ocular and brain region, can lead to encephalopathy. Indeed, cases of this have been documented so frequently over the last decade that a term has been given for this set of complication: neurologic serious adverse events (SAEs).Advanced diagnostic methods have been developed since the appearance the SAEs, but more specific diagnostic tests that have been or are currently being development (see: Diagnostics) must to be supported and distributed if adequate loiasis surveillance is to be achieved.There is much overlap between the endemicity of the two distinct filariases, which complicates mass treatment programs for onchocerciasis and necessitates the development of greater diagnostics for loiasis.In Central and West Africa, initiatives to control onchocerciasis involve mass treatment with Ivermectin. However, these regions typically have high rates of co-infection with both L. loa and O. volvulus, and mass treatment with Ivermectin can have severe adverse effects (SAE). These include hemorrhage of the conjunctiva and retina, heamaturia, and other encephalopathies that are all attributed to the initial L. loa microfilarial load in the patient prior to treatment. Studies have sought to delineate the sequence of events following Ivermectin treatment that lead to neurologic SAE and sometimes death, while also trying to understand the mechanisms of adverse reactions to develop more appropriate treatments.In a study looking at mass Ivermectin treatment in Cameroon, one of the greatest endemic regions for both onchocerciasis and loiasis, a sequence of events in the clinical manifestation of adverse effects was outlined.It was noted that the patients used in this study had a L. loa microfilarial load of greater than 3,000 per ml of blood.Within 12–24 hours post-Ivermectin treatment (D1), individuals complained of fatigue, anorexia, and headache, joint and lumbar pain—a bent forward walk was characteristic during this initial stage accompanied by fever. Stomach pain and diarrhea were also reported in several individuals.By day 2 (D2), many patients experienced confusion, agitation, dysarthria, mutism and incontinence. Some cases of coma were reported as early as D2. The severity of adverse effects increased with higher microfilarial loads. Hemorrhaging of the eye, particularly the retinal and conjunctiva regions, is another common sign associated with SAE of Ivermectin treatment in patients with L. loa infections and is observed between D2 and D5 post-treatment. This can be visible for up to 5 weeks following treatment and has increased severity with higher microfilarial loads.Haematuria and proteinuria have also been observed following Ivermectin treatment, but this is common when using Ivermectin to treat onchocerciasis. The effect is exacerbated when there are high L. loa microfilarial loads however, and microfilariae can be observed in the urine occasionally. Generally, patients recovered from SAE within 6–7 months post-Ivermectin treatment; however, when their complications were unmanaged and patients were left bed-ridden, death resulted due to gastrointestinal bleeding, septic shock, and large abscesses.Mechanisms for SAE have been proposed. Though microfilarial load is a major risk factor to post-Ivermectin SAE, three main hypotheses have been proposed for the mechanisms.The first mechanism suggests that Ivermectin causes immobility in microfilariae, which then obstructs microcirculation in cerebral regions. This is supported by the retinal hemorrhaging seen in some patients, and is possibly responsible for the neurologic SAE reported.The second hypothesis suggests that microfilariae may try to escape drug treatment by migrating to brain capillaries and further into brain tissue; this is supported by pathology reports demonstrating a microfilarial presence in brain tissue post-Ivermectin treatment.Lastly, the third hypothesis attributes hypersensitivity and inflammation at the cerebral level to post-Ivermectin treatment complications, and perhaps the release of bacteria from L. loa after treatment to SAE. This has been observed with the bacteria Wolbachia that live with O. volvulus.More research into the mechanisms of post-Ivermectin treatment SAE is needed to develop drugs that are appropriate for individuals with multiple parasitic infections.One drug that has been proposed for the treatment of onchocerciasis is doxycycline. This drug has been shown to be effective in killing both the adult worm of O. volvulus and Wolbachia, the bacteria believed to play a major role in the onset of onchocerciasis, while having no effect on the microfilariae of L. loa. In a study done at 5 different co-endemic regions for onchocerciasis and loiasis, doxycycline was shown to be effective in treating over 12,000 individuals infected with both parasites with minimal complications. Drawbacks to using Doxycycline include bacterial resistance and patient compliance because of a longer treatment regimen and emergence of doxycycline-resistant Wolbachia. However, in the study over 97% of the patients complied with treatment, so it does pose as a promising treatment for onchocerciasis, while avoiding complications associated with L. loa co-infections.Human loiasis geographical distribution is restricted to the rain forest and swamp forest areas of West Africa, being especially common in Cameroon and on the Ogooué River. Humans are the only known natural reservoir. It is estimated that over 10 million humans are infected with Loa loa larvae.An area of tremendous concern regarding loiasis is its co-endemicity with onchocerciasis in certain areas of west and central Africa, as mass ivermectin treatment of onchocerciasis can lead to serious adverse events (SAEs) in patients who have high Loa loa microfilarial densities, or loads. This fact necessitates the development of more specific diagnostics tests for Loa loa so that areas and individuals at a higher risk for neurologic consequences can be identified prior to microfilaricidal treatment. Additionally, the treatment of choice for loiasis, diethylcarbamazine, can lead to serious complications in and of itself when administered in standard doses to patients with high Loa loa microfilarial loads. History The first case of Loa loa infection was noted in the Caribbean (Santo Domingo) in 1770. A French surgeon named Mongin tried but failed to remove a worm passing across a womans eye. A few years later, in 1778, the surgeon François Guyot noted worms in the eyes of West African slaves on a French ship to America; he successfully removed a worm from one mans eye.The identification of microfilariae was made in 1890 by the ophthalmologist Stephen McKenzie. Localized angioedema, a common clinical presentation of loiasis, was observed in 1895 in the coastal Nigerian town of Calabar—hence the name "Calabar" swellings. This observation was made by a Scottish ophthalmologist named Douglas Argyll-Robertson, but the association between Loa loa and Calabar swellings was not realized until 1910 (by Patrick Manson). The determination of vector—Chrysops spp.—was made in 1912 by the British parasitologist Robert Thomson Leiper. Synonyms Synonyms for the disease include African eye worm, loaiasis, loaina, Loa loa filariasis, filaria loa, filaria lacrimalis, filaria subconjunctivalis, Calabar swellings, Fugitive swellings, and microfilaria diurnal. Loa loa, the scientific name for the infectious agent, is an indigenous term itself and it is likely that there are many other terms used from region to region. References == External links ==
Squamous cell carcinoma	Squamous-cell carcinomas (SCCs), also known as epidermoid carcinomas, comprise a number of different types of cancer that begin in squamous cells. These cells form on the surface of the skin, on the lining of hollow organs in the body, and on the lining of the respiratory and digestive tracts.Common types include: Squamous-cell skin cancer: A type of skin cancer Squamous-cell carcinoma of the lung: A type of lung cancer Squamous-cell thyroid carcinoma: A type of thyroid cancer Esophageal squamous-cell carcinoma: A type of esophageal cancer Squamous-cell carcinoma of the vagina: A type of vaginal cancerDespite sharing the name "squamous-cell carcinoma", the SCCs of different body sites can show differences in their presented symptoms, natural history, prognosis, and response to treatment. By body location Human papillomavirus infection has been associated with SCCs of the oropharynx, lung, fingers, and anogenital region. Head and neck cancer About 90% of cases of head and neck cancer (cancer of the mouth, nasal cavity, nasopharynx, throat and associated structures) are due to SCC. Skin Squamous cell carcinoma of the skin is the second most common skin cancer, accounting for over 1 million cases in the United States each year. Thyroid Primary squamous-cell thyroid carcinoma shows an aggressive biological phenotype resulting in poor prognosis for patients. Esophagus Esophageal cancer may be due to either esophageal squamous cell carcinoma (ESCC) or adenocarcinoma (EAC). SCCs tend to occur closer to the mouth, while adenocarcinomas occur closer to the stomach. Dysphagia (difficulty swallowing, solids worse than liquids) and painful swallowing are common initial symptoms. If the disease is localized, surgical removal of the affected esophagus may offer the possibility of a cure. If the disease has spread, chemotherapy and radiotherapy are commonly used. Lung When associated with the lung, it is typically a centrally located large-cell cancer (nonsmall-cell lung cancer). It often has a paraneoplastic syndrome causing ectopic production of parathyroid hormone-related protein, resulting in hypercalcemia, but paraneoplastic syndrome is more commonly associated with small-cell lung cancer. It is primarily due to smoking. Penis Human papillomavirus (HPV), primarily HPV 16 and 18, are strongly implicated in the development of SCC of the penis. Three carcinomas in situ are associated with SCCs of the penis: Bowens disease presents as leukoplakia on the shaft. Around a third of cases progress to SCC. Erythroplasia of Queyrat, a variation of Bowens disease, presents as erythroplakia on the glans. Bowenoid papulosis, which histologically resembles Bowen disease, presents as reddish papules. Prostate When associated with the prostate, squamous-cell carcinoma is very aggressive in nature. It is difficult to detect as no increase in prostate-specific antigen levels is seen, meaning that the cancer is often diagnosed at an advanced stage. Vagina and cervix Vaginal SCC spreads slowly and usually stays near the vagina, but may spread to the lungs and liver. This is the most common type of vaginal cancer. Bladder Most bladder cancer is transitional cell, but bladder cancer associated with schistosomiasis is often SCC. Diagnosis Medical history, physical examination and medical imaging may suggest a squamous cell carcinoma, but a biopsy for histopathology generally establishes the diagnosis. TP63 staining is the main histological marker for Squamous cell carcinoma. In addition, TP63 is an essential transcription factor to establish squamous cell identity. Classification Cancer can be considered a very large and exceptionally heterogeneous family of malignant diseases, with squamous cell carcinomas comprising one of the largest subsets. All SCC lesions are thought to begin via the repeated, uncontrolled division of cancer stem cells of epithelial lineage or characteristics. SCCs arise from squamous cells, which are flat cells that line many areas of the body. Some of which are keratinocytes. Accumulation of these cancer cells causes a microscopic focus of abnormal cells that are, at least initially, locally confined within the specific tissue in which the progenitor cell resided. This condition is called squamous cell carcinoma in situ, and it is diagnosed when the tumor has not yet penetrated the basement membrane or other delimiting structure to invade adjacent tissues. Once the lesion has grown and progressed to the point where it has breached, penetrated, and infiltrated adjacent structures, it is referred to as "invasive" squamous cell carcinoma. Once a carcinoma becomes invasive, it is able to spread to other organs and cause the formation of a metastasis, or "secondary tumor". Tissue of origin The International Classification of Diseases for Oncology (ICD-O) system lists a number of morphological subtypes and variants of malignant squamous cell neoplasms, including: Papillary thyroid carcinoma (code 8050/3) Verrucous squamous cell carcinoma (code 8051/3) Papillary squamous cell carcinoma (code 8052/3) Squamous cell carcinoma (code 8070/3) Large-cell keratinizing squamous cell carcinoma (code 8071/3) Large-cell nonkeratinizing squamous cell carcinoma (code 8072/3) Small-cell keratinizing squamous cell carcinoma (code 8073/3) Spindle-cell squamous cell carcinoma (code 8074/3) It is also known as spindle-cell carcinoma, and is a subtype characterized by spindle-shaped atypical cells. Adenoid/pseudoglandular squamous cell carcinoma (code 8075/3) Intraepidermal squamous cell carcinoma (code 8081/3) Lymphoepithelial carcinoma (code 8082/3)Other variants of SCCs are recognized under other systems, such as keratoacanthoma. Other histopathologic subtypes Erythroplasia of Queyrat Marjolins ulcer is a type of SCC that arises from a nonhealing ulcer or burn wound. More recent evidence, however, suggests that genetic differences exist between SCC and Marjolins ulcer, which were previously underappreciated.One method of classifying squamous cell carcinomas is by their appearance under microscope. Subtypes may include: Adenoid squamous cell carcinoma (also known as pseudoglandular squamous cell carcinoma) is characterized by a tubular microscopic pattern and keratinocyte acantholysis. Basaloid squamous cell carcinoma is characterized by a predilection for the tongue base. Clear-cell squamous cell carcinoma (also known as clear-cell carcinoma of the skin) is characterized by keratinocytes that appear clear as a result of hydropic swelling. Signet ring-cell squamous cell carcinoma (occasionally rendered as signet ring-cell squamous cell carcinoma) is a histological variant characterized by concentric rings composed of keratin and large vacuoles corresponding to markedly dilated endoplasmic reticulum. These vacuoles grow to such an extent that they radically displace the cell nucleus toward the cell membrane, giving the cell a distinctive superficial resemblance to a "signet ring" when viewed under a microscope. Prevention Studies have found evidences for an association between diet and skin cancers, including SCC. The consumption of high-fat dairy foods increases SCC tumor risk in people with previous skin cancer. Green leafy vegetables may help prevent development of subsequent SCC and multiple studies found that raw vegetables and fruits are significantly protective against SCC risk. On the other hand, consumption of whole milk, yogurt, and cheese may increase SCC risk in susceptible people. In addition, meat and fat dietary pattern can increase the risk of SCC in people without a history of SCC, but the association is again more prominent in people with a history of skin cancer. Tobacco smoking and a dietary pattern characterized by high beer and liquor intake also increase the risk of SCC significantly. == References ==
Page kidney	Page kidney or Page phenomena is a potentially reversible form of secondary arterial hypertension caused by external compression of the renal parenchyma by some perirenal process. Any process that causes mass effect can be a potential cause of Page kidney. Hematomas, urinomas, tumors, cysts, lymphoceles, and aneurysms have all been reported in the literature. The compression is believed to cause activation of the renin–angiotensin–aldosterone system (RAAS) via microvascular ischemia.Initially, the majority of cases that were described had a traumatic etiology but this has since shifted to iatrogenic causes. Since Page kidney is primarily a unilateral process, symptoms will differ depending on if the patient has native kidneys or not. In patients with only one solitary functioning kidney, the acute hypertension will also be accompanied by an acute decrease in renal function. In patients with one functioning kidney, prompt diagnosis and surgical treatment are needed to prevent irreversible kidney damage and restoration of kidney function. Medical treatment involves use of an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB) to control the hypertension. Signs & Symptoms Since Page kidney is a unilateral process, symptom presentation differs significantly depending on if patients have native kidneys or only one functioning kidney, such as renal transplant recipients. In those with a normally functioning second kidney, the only symptom may be new-onset hypertension. However, this is in contrast to patients with just one functioning kidney. These patients will show signs of worsening renal function and decreased urine output in addition to hypertension. Causes Causes of Page kidney have appeared to change over time. Initially, the phenomena were most often caused by traumatic injuries, such as contact sports or motor vehicle collisions. More recently, the majority of cases are postprocedural or secondary to mass lesions. Several factors have been implicated as contributory to this change, namely: the more liberal use of high-quality imaging and the increased utilization of invasive procedures. Documented iatrogenic causes include: intra-abdominal surgery, lithotripsy, renal biopsy, and percutaneous endopyelotomy. The biggest shift in cause comes from kidney allograft biopsy, which now accounts for the majority of Page kidney cases. Pathophysiology Although to date there have not been any studies specific to Page kidney in humans, two studies in animals and known renal physiology provide a likely mechanism. The elevated blood pressure seen in Page kidney is thought to be caused by the activation of the renin–angiotensin–aldosterone system (RAAS). Compression of the renal parenchyma alters intrarenal blood flow, resulting in a localized decrease in blood flow to the affected nephrons. This decrease in blood flow is recognized by the juxtaglomerular (JG) cells and promotes the cleavage of prorenin into renin. Each kidney is surrounded by two layers of connective tissue, the inner renal capsule and outer renal (Gerotas) fascia. These layers thus form two potential spaces where fluid can form, the small subcapsular space and the large perinephric space. The renal capsule is fibrous and does not easily expand. Thus, even a small collection of blood in the subcapsular space can cause mass effect on the renal parenchyma. Diagnosis Techniques for the diagnosis of Page kidney are all imaging based, including abdominal x-ray, intravenous pyelography, angiography, renal doppler ultrasound, CT scan, and Magnetic resonance imaging (MRI). X-ray and pyelography may add in diagnosis, but are non-diagnostic when used alone. Additionally, pyelograms use potentially nephrotoxic contrast agents, further limiting their utility. Diagnosis is primarily made using ultrasound and CT. CT and MRI imaging can show the space occupying lesions but doppler ultrasound is needed to display the hemodynamic changes occurring in the kidney. Ultrasound is often the initial diagnostic test of choice but due to its low resolution further imaging may be necessary. Treatment Surgical Surgical treatment of Page kidney has evolved over time as newer techniques have become more popular. Open surgical procedures such as nephrectomy, which was once the treatment of choice have been replaced by less invasive options such as percutaneous drainage or endoscopic capsulotomy. Medical Some cases of Page kidney will resolve spontaneously without need for surgical treatment. In this case, medical treatment focuses on symptomatic treatment of the hypertension with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB). Adding a calcium channel blocker (CCB) or beta blocker to the ACEi or ARB has also been described. History Irvine H. Page first demonstrated the Page kidney phenomena experimentally in animals in 1939. He found that wrapping one of the animals kidneys in cellophane produced hypertension that could be reversed after removal of the kidney. Although he postulated that a similar scenario could be produced clinically in humans due to a hematoma, it was not until 1955 that Page and his colleague William J. Engel published the first case report on Page kidney. == References ==
Marchiafava–Bignami disease	Marchiafava–Bignami disease is a progressive neurological disease of alcohol use disorder, characterized by corpus callosum demyelination and necrosis and subsequent atrophy. The disease was first described in 1903 by the Italian pathologists Amico Bignami and Ettore Marchiafava in an Italian Chianti drinker. In this autopsy, Marchiafava and Bignami noticed that the middle two-thirds of the corpus callosum were necrotic. It is very difficult to diagnose and there is no specific treatment. Until 2008 only around 300 cases had been reported. If caught early enough, most patients survive. Symptoms and signs Symptoms can include, but are not limited to lack of consciousness, aggression, seizures, depression, hemiparesis, ataxia, apraxia, coma, etc. There will also be lesions in the corpus callosum. Causes It is classically associated with chronic alcoholism especially with red wine consumption and sometimes associated nutritional deficiencies. Alcohol use disorder can also cause thiamine deficiency, which is also observed to cause MBD. Mechanism Individuals with MBD usually have a history of excessive alcohol consumption, but this is not always the case. The mechanism of the disease is not completely understood, but it is believed to be caused by a Vitamin B deficiency, malnutrition, or alcohol use disorder. The damage to the brain can extend into neighboring white matter and sometimes go out as far as subcortical regions. Diagnosis Marchiafava–Bignami disease is routinely diagnosed with the use of an MRI because the majority of clinical symptoms are non-specific. Before the use of such imaging equipment, it was unable to be diagnosed until autopsy. The patient usually has a history of alcohol use disorder or malnutrition and neurological symptoms are sometimes present and can help lead to a diagnosis. MBD can be told apart from other neural diseases due to the symmetry of the lesions in the corpus callosum as well as the fact that these lesions dont affect the upper and lower edges.There are two clinical subtypes of MBD Type A- Stupor and coma predominate. Radiological imaging shows involvement of the entire corpus callosum. This type is also associated with symptoms of the upper motor neurons.Type B- This type has normal or only mildly impaired mental status and radiologic imaging shows partial lesions in the corpus callosum. Treatment Treatment is variable depending on individuals. Some treatments work extremely well with some patients and not at all with others. Some treatments include therapy with thiamine and vitamin B complex. Alcohol consumption should be stopped. Some patients survive, but with residual brain damage and dementia. Others remain in comas that eventually lead to death. Nutritional counseling is also recommended. Treatment is often similar to those administered for Wenicke-Korsakoff syndrome or for alcohol use disorder.Type A has 21% mortality rate and an 81% long-term disability rate. Type B has a 0% mortality rate and a 19% long-term disability rate. Recent Research In a study published in 2015, a patient was observed to have MBD, but no history of excessive alcohol use. It is believed that he had protein, folic acid, and thiamine deficiencies, which are what caused the demyelination of the corpus callosum. The patient was diagnosed through MRI, but countless other neurological diseases needed to be ruled out initially.In a study published in 2016, a 45-year-old patient was observed to have taken high amounts of alcohol intake over 20 years and was malnourished. He was diagnosed with liver cirrhosis. He was confused and had a lack of motor coordination. He also had altered sensorium and seizures. An MRI was performed and the patient was diagnosed with MBD. See also Central pontine myelinolysis References External links MedPix eMedicine overview
Pyostomatitis vegetans	Pyostomatitis vegetans is an inflammatory stomatitis and most often seen in association with inflammatory bowel disease, namely ulcerative colitis and Crohns disease. Uncommonly, it may be one of the features of orofacial granulomatosis. See also Cheilitis Skin lesion List of cutaneous References External links Pyostomatitis vegetans associated with inflammatory bowel disease
Syringocystadenoma papilliferum	Syringocystadenoma papilliferum is a benign apocrine tumor.It can arise with nevus sebaceus. Additional images See also List of cutaneous conditions Hidradenoma papilliferum Papillary eccrine adenoma List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer References == External links ==
Meibomian gland dysfunction	Meibomian gland dysfunction (also known as MGD) is a chronic disease of the meibomian glands, which is commonly characterized by obstruction of the end of the duct that delivers the secretion produced by the glands (called meibum) to the eye surface, which prevents the glandular secretion to reach the ocular surface. The dysfunction could be that the amount of secretion produced may be abnormal (either too little or too much meibum produced). Dysfunction could also be related to the quality of the meibum produced. MGD may result in evaporative dry eye, blepharitis, chalazion, unsealed lid during sleep, and meibomian gland atrophy.MGD causes the glands to be obstructed by thick, cloudy-to-yellow, more opaque and viscous-like, oily and waxy secretions, a change from the glands normal clear secretions. Besides leading to dry eyes, the obstructions can be degraded by bacterial lipases, resulting in the formation of free fatty acids, which irritate the eyes and sometimes cause punctate keratopathy. MGD has been described as "the most underrecognized, underappreciated and undertreated disease in ophthalmic care [...] so common as to be taken as ‘normal’ in many clinical practices".The dysfunction is more often seen in women, and is regarded as the main cause of dry eye syndrome. Factors that contribute to the dysfunction can include things such as a persons age and/or hormones, or severe infestation of Demodex brevis mites. Treatment can include warm compresses to thin the secretions and eyelid scrubs with baby shampoo or eyelid cleanser, or emptying ("expression") of the gland by a professional. Lifitegrast and Restasis are topical medication commonly used to control the inflammation and improve the oil quality. In some cases topical steroids and topical (drops or ointment)/oral antibiotics (to reduce bacteria on the lid margin) are also prescribed to reduce inflammation. Intense pulsed light (IPL) treatments have also been shown to reduce inflammation and improve gland function. Meibomian gland probing is also used on patients who experience deep clogging of the glands. The dysfunction may be caused by some prescription medications, notably isotretinoin. A blocked meibomian gland can cause a meibomian cyst known as a chalazion to form in the eyelid. Untreated blepharitis or MGD makes the eyes look red and puffy as if the person have been drinking or have a substance abuse problem. Classification MGD can be classified based on gland secretion. MGD can be low delivery and high delivery. Low delivery is the most common form and is classified in hyposecretory and obstructive. Hyposecretory implies low meibum secretion without terminal duct obstruction. This is associated with gland atrophy. Contact lens wear can lead to a decreased number of functional meibomian glands. Obstructive MGD, where the terminal duct is obstructed, is the most common type of MGD. Obstructive MGD has been associated with age and acne treatment products with retinoids. Obstructive MGD can be classified into noncicatricial and cicatricial. In noncicatricial, the terminal duct of meibomian glands are in their normal anatomic position. In cicatricial, they are dragged posteriorly into the mucosa.High delivery implies an increased release of meibum into the tear surface. This has been associated with seborrheic dermatitis. See also Meibography == References ==
Lymphangiomatosis	Lymphangiomatosis is a condition where a lymphangioma is not present in a single localised mass, but in a widespread or multifocal manner. It is a rare type of tumor which results from an abnormal development of the lymphatic system.It is thought to be the result of congenital errors of lymphatic development occurring prior to the 20th week of gestation. Lymphangiomatosis is a condition marked by the presence of cysts that result from an increase both in the size and number of thin-walled lymphatic channels that are abnormally interconnected and dilated. 75% of cases involve multiple organs. It typically presents by age 20 and, although it is technically benign, these deranged lymphatics tend to invade surrounding tissues and cause problems due to invasion and/or compression of adjacent structures. The condition is most common in the bones and lungs and shares some characteristics with Gorham’s disease. Up to 75% of patients with lymphangiomatosis have bone involvement, leading some to conclude that lymphangiomatosis and Gorham’s disease should be considered as a spectrum of disease rather than separate diseases. When it occurs in the lungs, lymphangiomatosis has serious consequences and is most aggressive in the youngest children. When the condition extends into the chest it commonly results in the accumulation of chyle in the linings of the heart and/or lungs.Chyle is composed of lymph fluid and fats that are absorbed from the small intestine by specialized lymphatic vessels called lacteals during digestion. The accumulations are described based on location: chylothorax is chyle in the chest; chylopericardium is chyle trapped inside the sack surrounding the heart; chyloascites is chyle trapped in the linings of the abdomen and abdominal organs. The presence of chyle in these places accounts for many of the symptoms and complications associated with both lymphangiomatosis and Gorham’s disease. The incidence of lymphangiomatosis is unknown and it is often misdiagnosed. It is separate and distinct from lymphangiectasis, lymphangioleiomyomatosis (LAM), pulmonary capillary hemangiomatosis, Kaposi’s sarcoma, and kaposiform hemangioendothelioma. Its unusual nature makes lymphangiomatosis (and Gorham’s disease) a diagnostic and therapeutic challenge. A multidisciplinary approach is generally necessary for optimal diagnosis and symptom management. The term literally means lymphatic system (lymph) vessel (angi) tumor or cyst (oma) condition (tosis). Signs and symptoms Lymphangiomatosis is a multi-system disorder. Symptoms depend on the organ system involved and, to varying degrees, the extent of the disease. Early in the course of the disease patients are usually asymptomatic, but over time the abnormally proliferating lymphatic channels that constitute lymphangiomatosis are capable of massive expansion and infiltration into surrounding tissues, bone, and organs. Because of its slow course and often vague symptoms, the condition is frequently under-recognized or misdiagnosed.Early signs of disease in the chest include wheezing, cough, and feeling short of breath, which is often misdiagnosed as asthma. The pain that accompanies bone involvement may be attributed to "growing pains" in younger children. With bone involvement the first indication for disease may be a pathological fracture. Symptoms may not raise concern, or even be noted, until the disease process has advanced to a point where it causes restrictive compression of vital structures. Further, the occurrence of chylous effusions seems to be unrelated to the pathologic "burden" of the disease, the extent of involvement in any particular tissue or organ, or the age of the patient. This offers one explanation as to why, unfortunately, the appearance of chylous effusions in the chest or abdomen may be the first evidence of the disease.Following are some of the commonly reported symptoms of lymphangiomatosis, divided into the regions/systems in which the disease occurs: Heart and chest Symptoms that arise from disease of the cardiothoracic region include a chronic cough, wheezing, dyspnea (shortness of breath)—especially serious when occurring at rest or when lying down—fever, chest pain, rapid heartbeat, dizziness, anxiety, and coughing up blood or chyle. As the deranged lymphatic vessels invade the organs and tissues in the chest they put stress on the heart and lungs, interfering with their ability to function normally. Additionally, these lymphatic vessels may leak, allowing fluid to accumulate in the chest, which puts further pressure on the vital organs, thus increasing their inability to function properly. Accumulations of fluid and chyle are named based on their contents and location: pulmonary edema (the presence of fluid and/or chyle in the lung), pleural effusions (fluid in the lung lining), pericardial effusions (fluid in the heart sack), chylothorax (chyle in the pleural cavity); and chylopericardium (chyle in the heart sack). Abdominal Lymphangiomatosis has been reported in every region of the abdomen, though the most reported sites involve the intestines and peritoneum; spleen, kidneys, and liver. Often there are no symptoms until late in the progression of the disease. When they do occur, symptoms include abdominal pain and/or distension; nausea, vomiting, diarrhea; decreased appetite and malnourishment. When the disease affects the kidneys the symptoms include flank pain, abdominal distension, blood in the urine, and, possibly, elevated blood pressure, which may result in it being confused with other cystic renal disease. When lymphangiomatosis occurs in the liver and/or spleen it may be confused with polycystic liver disease. Symptoms may include abdominal fullness and distension; anemia, disseminated intravascular coagulopathy (DIC), fluid accumulation in the abdomen(ascites), decreased appetite, weight loss, fatigue; late findings include liver failure. Bones Symptoms of lymphangiomatosis in the skeletal system are the same as those of Gorham’s disease. Frequently asymptomatic, skeletal lymphangiomatosis may be discovered incidentally or when a pathological fracture occurs. Patients may experience pain of varying severity in areas around the effected bone. When the disease occurs in the bones of the spine, neurological symptoms such as numbness and tingling may occur due to spinal nerve compression. Progression of disease in the spine may lead to paralysis. Lymphangiomatosis in conjunction with Chiari I malformation also has been reported. Causes The cause of lymphangiomatosis is not yet known. As stated earlier, it is generally considered to be the result of congenital errors of lymphatic development occurring prior to the 20th week of gestation. However, the root causes of these conditions remains unknown and further research is necessary. Diagnosis Because it is rare and has a wide spectrum of clinical, histological, and imaging features, diagnosing lymphangiomatosis can be challenging. Plain x-rays reveal the presence of lytic lesions in bones, pathological fractures, interstitial infiltrates in the lungs, and chylous effusions that may be present even when there are no outward symptoms.The most common locations of lymphangiomatosis are the lungs and bones and one important diagnostic clue is the coexistence of lytic bone lesions and chylous effusion. An isolated presentation usually carries a better prognosis than does multi-organ involvement; the combination of pleural and peritoneal involvement with chylous effusions and lytic bone lesions carries the least favorable prognosis.When lung involvement is suspected, high resolution computed tomography (HRCT) scans may reveal a diffuse liquid-like infiltration in the mediastinal and hilar soft tissue, resulting from diffuse proliferation of lymphatic channels and accumulation of lymphatic fluid; diffuse peribronchovascular and interlobular septal thickening; ground-glass opacities; and pleural effusion. Pulmonary function testing reveals either restrictive pattern or a mixed obstructive/restrictive pattern. While x-rays, HRCT scan, MRI, ultrasound, lymphangiography, bone scan, and bronchoscopy all can have a role in identifying lymphangiomatosis, biopsy remains the definitive diagnostic tool.Microscopic examination of biopsy specimens reveals an increase in both the size and number of thin walled lymphatic channels along with lymphatic spaces that are interconnecting and dilated, lined by a single attenuated layer of endothelial cells involving the dermis, subcutis, and possibly underlying fascia and skeletal muscle. Additionally, Tazelaar, et al., described a pattern of histological features of lung specimens from nine patients in whom no extrathoracic lesions were identified, which they termed "diffuse pulmonary lymphangiomatosis" (DPL).Recognition of the disease requires a high index of suspicion and an extensive workup. Because of its serious morbidity, lymphangiomatosis must always be considered in the differential diagnosis of lytic bone lesions accompanied by chylous effusions, in cases of primary chylopericardium, and as part of the differential diagnosis in pediatric patients presenting with signs of interstitial lung disease. Treatment There is no standard approach to the treatment of lymphangiomatosis and treatment often is aimed at reducing symptoms. Surgical intervention may be indicated when complications arise and a number of reports of response to surgical interventions, medications, and dietary approaches can be found in the medical literature.Unfortunately, there is no standardized treatment for lymphangiomatosis and no cure. Treatment modalities that have been reported in the medical literature, by system, include: Heart and chest Thoracocentesis, pericardiocentesis, pleurodesis, ligation of thoracic duct, pleuroperitoneal shunt, radiation therapy, pleurectomy, pericardial window, pericardiectomy, thalidomide, interferon alpha 2b, Total Parenteral Nutrition (TPN), medium chain triglyceride (MCT) and high protein diet, chemotherapy, sclerotherapy, transplant; Abdominal interferon alpha 2b, sclerotherapy, resection, percutaneous drainage, Denver shunt, Total Parenteral Nutrition (TPN), medium chain triglyceride (MCT) and high protein diet, transplant, splenectomy; Bone Interferon alpha 2b, bisphosphonates (i.e. pamidronate), surgical resection, radiation therapy, sclerotherapy, percutaneous bone cement, bone grafts, prosthesis, surgical stabilization. Epidemiology Lymphangiomatosis can occur at any age, but the incidence is highest in children and teenagers. Signs and symptoms are typically present before the age of 20 and the condition is often under-recognized in adults.It affects males and females of all races and exhibits no inheritance pattern. The medical literature contains case reports from every continent.Because it is so rare, and commonly misdiagnosed, it is not known exactly how many people are affected by this disease. References Further reading Dellinger M. T., Garg N, Olsen B.R. (2014). "Viewpoints on vessels and vanishing bones in Gorham-Stout disease". Bone. 63C: 47–52. doi:10.1016/j.bone.2014.02.011. PMID 24583233.{{cite journal}}: CS1 maint: multiple names: authors list (link) Trenor C, Chaudry G (Aug 2014). "Complex lymphatic anomalies". Semin Pediatr Surg. 23 (4): 186–90. doi:10.1053/j.sempedsurg.2014.07.006. PMID 25241096. Lala S, Mulliken JB, Alomari AI, Fishman SJ, Kozakewich HP, Chaudry G (Jul 2013). "Gorham-Stout disease and generalized lymphatic anomaly—clinical, radiologic, and histologic differentiation". Skeletal Radiol. 42 (7): 917–24. doi:10.1007/s00256-012-1565-4. PMID 23371338. S2CID 22640055.{{cite journal}}: CS1 maint: multiple names: authors list (link)
Phthisis bulbi	Phthisis bulbi is a shrunken, non-functional eye. It may result from severe eye disease, inflammation or injury, or it may represent a complication of eye surgery. Treatment options include insertion of a prosthesis, which may be preceded by enucleation of the eye. Symptoms The affected eye is shrunken, and has little to no vision. The intraocular pressure in the affected eye is very low or nonexistent. The layers in the eye may be fused together, thickened, or edematous. The eyelids may be glued shut. The eye may be soft when palpated. Under a microscope there may be deposits of calcium or bone, and the cornea is often affected by cataracts. Causes It can be caused by injury, including burns to the eye, or long-term eye disease or inflammation. End-stage glaucoma can cause it. It can often complicate eye surgery. Other common causes include cancer, retinal detachment, vascular lesions, infection, and inflammation. Treatment Treatment for the affected eye is often futile. Usually, treatment is to end the pain in the affected eye and for cosmetic purposes, not to restore vision. It can be removed, a procedure called enucleation of the eye. Sometimes, though, it is possible to transplant only parts of the eye, and some vision can be restored. References == External links ==
Paraneoplastic cerebellar degeneration	Paraneoplastic cerebellar degeneration (PCD) is a paraneoplastic syndrome associated with a broad variety of tumors including lung cancer, ovarian cancer, breast cancer, Hodgkin’s lymphoma and others. PCD is a rare condition that occurs in less than 1% of cancer patients. As is the case with other paraneoplastic syndromes, PCD is believed to be due to an autoimmune reaction targeted against components of the central nervous system, mostly to Purkinje cells.It is thought to be triggered when tumor cells (in PCD, most commonly ovarian or breast cancer) ectopically express proteins normally expressed in the cerebellum. This is believed to trigger an anti-tumor immune response that may be clinically significant, but also an anti-neural immune response. A broad spectrum of neuronal and glial proteins has been identified as target antigens in PCD. Presentation Neurological symptoms may include, among others, dysarthria, truncal, limb and gait ataxia and nystagmus. Symptoms often develop subacutely and progress rapidly over a period of weeks or months to a plateau period that can last for months to years and which often reflects complete loss of Purkinje cells. Pathophysiology The anti-Purkinje cell antibodies originally described in PCD led to the hypothesis that the antibody might be pathogenic, much as earlier studies had demonstrated pathogenicity of anti-acetylcholine receptor antibodies in myasthenia gravis. However, when the antibody was used to clone the cDNA encoding the cdr2 antigen, it was found to be an intracellular protein. This led to the suggestion that there might be a cell-mediated component (T cell) in disease pathogenesis. cdr2 antigen-specific CD8+ T cells were subsequently described in more anti-Yo-positive PCD patients,. These T cells are likely components in both the anti-tumor immune response and in the neuronal degeneration. Diagnosis Of particular note, PCD symptoms precede the diagnosis of the underlying cancer in the majority of cases, and often present insidiously and progress rapidly for weeks to months to a severely disabled state followed by a variable plateau period that can last for months to years. Therefore, newly developing cerebellar ataxia should always prompt proper diagnostic measures to exclude PCD. Treatment Tumor removal is still the therapeutic mainstay with very early treatment being essential to prevent irreversible neuronal loss. Immunosuppressive or immunomodulatory treatments are often ineffective. There may be a role for high-dose gammaglobulin therapy in the treatment PCD, but due to the rare occurrence of this disease, controlled trials of this therapy may be difficult. References == External links ==
Sigmoid colon volvulus	Sigmoid colon volvulus, also known as sigmoid volvulus, is volvulus affecting the sigmoid colon. It is a common cause of bowel obstruction and constipation. It is common in Asia, India (7% of intestinal obstruction) and especially South India because of the high fibre diet. It is a very common cause of large bowel obstruction in Peru and Bolivia due to high altitude. Signs and symptoms Pain in abdomen – initially left-sided, eventually all over Absolute constipation Enormous distension of abdomen Late vomiting and eventually dehydration Features of peritonitis Hiccup and retching may occur Tyre-like feel of the abdomen is diagnostic Cause The condition is more common in males and with old age. It is also common in people with chronic constipation and laxative abuse. It is common in: Ogilvie syndrome Individuals with learning difficulties Chagas disease Hypothyroidism Anticholinergic drugs Multiple sclerosis Scleroderma Parkinsons diseaseIn sigmoid, volvulus rotation is always anticlockwise. It requires one and a half rotation to cause vascular obstruction and gangrene which eventually leads to perforation either at the root or at the summit of the sigmoid loop. Diagnosis Plain X-ray (diagnostic in 70–80%): coffee bean sign is seen Contrast enema: bird beak sign CT scan: shows characteristic whirl pattern Blood: haematocrit, renal functions, serum electrolytes Treatment RT aspiration IV fluids Catheterisation Antibiotics By flatus tube or sigmoidoscope, derotation is done If derotation does not occur, then laparotomy through midline incision should be done. It is derotated manually. If viable, it can be fixed to lateral wall of abdomen or pelvis If sigmoid colon is gangrenous, then Hartmanns operation or Paul Mikulicz operation is done References == External links ==
Autoimmune retinopathy	Autoimmune retinopathy (AIR) is a rare disease in which the patients immune system attacks proteins in the retina, leading to loss of eyesight. The disease is poorly understood, but may be the result of cancer or cancer chemotherapy. The disease is an autoimmune condition characterized by vision loss, blind spots, and visual field abnormalities. It can be divided into cancer-associated retinopathy (CAR) and melanoma-associated retinopathy (MAR). The condition is associated with retinal degeneration caused by autoimmune antibodies recognizing retinal proteins as antigens and targeting them. AIRs prevalence is extremely rare, with CAR being more common than MAR. It is more commonly diagnosed in females (approximately 60% of diagnosed patients are females) in the age range of 50–60. Types Cancer-associated retinopathy A division of AIR, cancer-associated retinopathy is a paraneoplastic syndrome, which is a disorder caused by an immune system response to an abnormality. Autoimmune antibodies target proteins in retinal photoreceptor cells. The proteins targeted as antigenic are recoverin, α‐enolase and transducin. This autoimmune response leads to photoreceptor cell death. It causes progressive vision loss that can lead to blindness. CAR is typically associated with the anti-recoverin antibody. Melanoma-associated retinopathy Retinal bipolar cells (cells in retina that transmit signals) react with the antibodies, leading to cell death. Although it is less prevalent than CAR, diagnosed cases of MAR continue to increase while CAR numbers decrease. Signs and symptoms Both CAR and MAR share the same symptoms. This is because they are both paraneoplastic syndromes. AIR symptoms are numerous and shared by many other diseases. Diagnosis Diagnosis of AIR can be difficult due to the overlap of symptoms with other disorders. Examination of the fundus (inner surface of eye) can show no results or it can show narrowing of the blood vessels, abnormal colouration of the optic disc, and retinal atrophy. Fundus examination results are not indicative of autoimmune retinopathy but they are used to initiate the diagnostic process. An electroretinogram (eye test used to see abnormalities in the retina) is used to detect AIR. An abnormal electroretinogram (ERG) with respect to light and dark adaptations indicates AIR. The ERG also allows differentiation between cancer-associated retinopathy and melanoma-associated retinopathy. If the ERG shows cone responses, CAR can be prematurely diagnosed. If the ERG shows a significant decrease in b-wave amplitude, MAR can be prematurely diagnosed. To confirm, analysis for anti-retinal antibodies through Western blotting of serum collected from the patient is done. Treatment Due to the difficulty of diagnosis, managing this disease is a challenge. For this reason, there is no established treatment for AIR. Clinicians try to reduce and control the autoimmune system attack to prevent any irreversible retinal damage. Methods of treatment include intravenous immunoglobulin (IVIG), plasmapheresis, and corticosteroids. Immunoglobulin Immunoglobulin samples are obtained from a large pool of healthy, matched donors (10000 - 20000). The immunoglobulin mixture is then administered through IV at a rate of 0.4g/kg/day for 5 days. Antibodies in the IVIG mixture interact with binding sites of the disease-associated antibodies (such as anti-recoverin antibodies). This prevents binding to proteins targeted as antigenic and reduces disease activity. Responses to this treatment can vary and are impacted if the patient is diagnosed with any type of cancer. Patients who respond positively show improvement in the clarity of their vision and their visual field. Plasmapheresis Plasmapheresis involves separating blood into two parts - blood cells and plasma. The blood plasma components, such as the antibodies, are treated outside of the body. After removal of the disease-associated antibodies, the blood cells and plasma are transfused back into the body. Response to this treatment depends on how much retinal damage has been done. Patients who respond positively show significant visual gains. Corticosteroids Corticosteroids are administered through IV or orally. They cause lymphocytopenia, a condition where white blood cell levels are abnormally low. Corticosteroids cause white blood cell death, lowering their numbers throughout the body. They also cause white blood cells to recirculate away from the area of damage (the retina). This minimizes damage caused by the antibodies produced by the white blood cells. Often, this is treatment is combined with plasmapheresis. Instead of treating the plasma and blood cells, they are replaced with a healthy donor mixture. Patients who respond positively show improved visual fields and an almost complete disappearance of anti-retinal antibodies. == References ==
Boomerang dysplasia	Boomerang dysplasia is a lethal form of osteochondrodysplasia known for a characteristic congenital feature in which bones of the arms and legs are malformed into the shape of a boomerang. Death usually occurs in early infancy due to complications arising from overwhelming systemic bone malformations.Osteochondrodysplasias are skeletal disorders that cause malformations of both bone and cartilage. Presentation Prenatal and neonatal diagnosis of boomerang dysplasia includes several prominent features found in other osteochondrodysplasias, though the "boomerang" malformation seen in the long bones is the delineating factor.Featured symptoms of boomerang dysplasia include: dwarfism (a lethal type of infantile dwarfism caused by systemic bone deformities), underossification (lack of bone formation) in the limbs, spine and ilium (pelvis); proliferation of multinucleated giant-cell chondrocytes (cells that produce cartilage and play a role in skeletal development - chondrocytes of this type are rarely found in osteochondrodysplasias), brachydactyly (shortened fingers) and micromelia (undersized, shortened bones).The characteristic "boomerang" malformation presents intermittently among random absences of long bones throughout the skeleton, in affected individuals. For example, one individual may have an absent radius and fibula, with the "boomerang" formation found in both ulnas and tibias. Another patient may present "boomerang" femora, and an absent tibia. Cause Mutations in the Filamin B (FLNB) gene cause boomerang dysplasia. FLNB is a cytoplasmic protein that regulates intracellular communication and signalling by cross-linking the protein actin to allow direct communication between the cell membrane and cytoskeletal network, to control and guide proper skeletal development. Disruptions in this pathway, caused by FLNB mutations, result in the bone and cartilage abnormalities associated with boomerang dysplasia.Chondrocytes, which also have a role in bone development, are susceptible to these disruptions and either fail to undergo ossification, or ossify incorrectly.FLNB mutations are involved in a spectrum of lethal bone dysplasias. One such disorder, atelosteogenesis type I, is very similar to boomerang dysplasia, and several symptoms of both often overlap. Genetics Early journal reports of boomerang dysplasia suggested X-linked recessive inheritance, based on observation and family history. It was later discovered, however, that the disorder is actually caused by a sporadic genetic mutation fitting an autosomal dominant genetic profile.Autosomal dominant inheritance indicates that the defective gene responsible for a disorder is located on an autosome, and only one copy of the gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.Boomerang dysplasia, although an autosomal dominant disorder, is not inherited because those afflicted do not live beyond infancy. They cannot pass the gene to the next generation. Diagnosis Treatment See also Larsen syndrome References == External links ==
Atherosclerosis	Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no symptoms, but if they develop, symptoms generally begin around middle age. When severe, it can result in coronary artery disease, stroke, peripheral artery disease, or kidney problems, depending on which arteries are affected.The exact cause is not known and is proposed to be multifactorial. Risk factors include abnormal cholesterol levels, elevated levels of inflammatory markers, high blood pressure, diabetes, smoking, obesity, family history, genetic, and an unhealthy diet. Plaque is made up of fat, cholesterol, calcium, and other substances found in the blood. The narrowing of arteries limits the flow of oxygen-rich blood to parts of the body. Diagnosis is based upon a physical exam, electrocardiogram, and exercise stress test, among others.Prevention is generally by eating a healthy diet, exercising, not smoking, and maintaining a normal weight. Treatment of established disease may include medications to lower cholesterol such as statins, blood pressure medication, or medications that decrease clotting, such as aspirin. A number of procedures may also be carried out such as percutaneous coronary intervention, coronary artery bypass graft, or carotid endarterectomy.Atherosclerosis generally starts when a person is young and worsens with age. Almost all people are affected to some degree by the age of 65. It is the number one cause of death and disability in the developed world. Though it was first described in 1575, there is evidence that the condition occurred in people more than 5,000 years ago. Signs and symptoms Atherosclerosis is asymptomatic for decades because the arteries enlarge at all plaque locations, thus there is no effect on blood flow. Even most plaque ruptures do not produce symptoms until enough narrowing or closure of an artery, due to clots, occurs. Signs and symptoms only occur after severe narrowing or closure impedes blood flow to different organs enough to induce symptoms. Most of the time, patients realize that they have the disease only when they experience other cardiovascular disorders such as stroke or heart attack. These symptoms, however, still vary depending on which artery or organ is affected.Abnormalities associated with atherosclerosis begin in childhood. Fibrous and gelatinous lesions have been observed in the coronary arteries of children aged 6–10. Fatty streaks have been observed in the coronary arteries of juveniles aged 11–15, though they appear at a much younger age within the aorta.Clinically, given enlargement of the arteries for decades, symptomatic atherosclerosis is typically associated with men in their 40s and women in their 50s to 60s. Sub-clinically, the disease begins to appear in childhood and rarely is already present at birth. Noticeable signs can begin developing at puberty. Though symptoms are rarely exhibited in children, early screening of children for cardiovascular diseases could be beneficial to both the child and his/her relatives. While coronary artery disease is more prevalent in men than women, atherosclerosis of the cerebral arteries and strokes equally affect both sexes.Marked narrowing in the coronary arteries, which are responsible for bringing oxygenated blood to the heart, can produce symptoms such as chest pain of angina and shortness of breath, sweating, nausea, dizziness or light-headedness, breathlessness or palpitations. Abnormal heart rhythms called arrhythmias—the heart beating either too slowly or too quickly—are another consequence of ischemia.Carotid arteries supply blood to the brain and neck. Marked narrowing of the carotid arteries can present with symptoms such as: a feeling of weakness; being unable to think straight; difficulty speaking; dizziness; difficulty in walking or standing up straight; blurred vision; numbness of the face, arms and legs; severe headache; and loss of consciousness. These symptoms are also related to stroke (death of brain cells). Stroke is caused by marked narrowing or closure of arteries going to the brain; lack of adequate blood supply leads to the death of the cells of the affected tissue.Peripheral arteries, which supply blood to the legs, arms and pelvis, also experience marked narrowing due to plaque rupture and clots. Symptoms of the narrowing are numbness within the arms or legs, as well as pain. Another significant location for plaque formation is the renal arteries, which supply blood to the kidneys. Plaque occurrence and accumulation lead to decreased kidney blood flow and chronic kidney disease, which, like in all other areas, is typically asymptomatic until late stages.According to United States data for 2004, in about 66% of men and 47% of women, the first symptom of atherosclerotic cardiovascular disease is a heart attack or sudden cardiac death (death within one hour of onset of the symptom). Cardiac stress testing, traditionally the most commonly performed non-invasive testing method for blood flow limitations, in general, detects only lumen narrowing of ≈75% or greater, although some physicians claim that nuclear stress methods can detect as little as 50%.Case studies have included autopsies of U.S. soldiers killed in World War II and the Korean War. A much-cited report involved the autopsies of 300 U.S. soldiers killed in Korea. Although the average age of the men was 22.1 years, 77.3 percent had "gross evidence of coronary arteriosclerosis". Other studies done of soldiers in the Vietnam War showed similar results, although often worse than the ones from the earlier wars. Theories include high rates of tobacco use and (in the case of the Vietnam soldiers) the advent of processed foods after World War II. Risk factors The atherosclerotic process is not well understood. Atherosclerosis is associated with inflammatory processes in the endothelial cells of the vessel wall associated with retained low-density lipoprotein (LDL) particles. This retention may be a cause, an effect, or both, of the underlying inflammatory process.The presence of the plaque induces the muscle cells of the blood vessel to stretch, compensating for the additional bulk. The endothelial lining then thickens, increasing the separation between the plaque and lumen. The thickening somewhat offsets the narrowing caused by the growth of the plaque, but moreover, it causes the wall to stiffen and become less compliant to stretching with each heartbeat. Modifiable Western pattern diet Abdominal obesity Insulin resistance Diabetes Dyslipidemia Hypertension Trans fat Tobacco smoking Bacterial infections HIV/AIDS Nonmodifiable South Asian descent Advanced age Genetic abnormalities Family history Coronary anatomy and branch pattern Lesser or uncertain Thrombophilia Saturated fat Excessive carbohydrates Elevated triglycerides Systemic inflammation Hyperinsulinemia Sleep deprivation Air pollution Sedentary lifestyle Arsenic poisoning Alcohol Chronic stress Hypothyroidism Periodontal disease Dietary The relation between dietary fat and atherosclerosis is controversial. The USDA, in its food pyramid, promotes a diet of about 64% carbohydrates from total calories. The American Heart Association, the American Diabetes Association and the National Cholesterol Education Program make similar recommendations. In contrast, Prof Walter Willett (Harvard School of Public Health, PI of the second Nurses Health Study) recommends much higher levels of fat, especially of monounsaturated and polyunsaturated fat. These dietary recommendations reach a consensus, though, against consumption of trans fats.The role of eating oxidized fats (rancid fats) in humans is not clear. Rabbits fed rancid fats develop atherosclerosis faster. Rats fed DHA-containing oils experienced marked disruptions to their antioxidant systems, and accumulated significant amounts of phospholipid hydroperoxide in their blood, livers and kidneys.Rabbits fed atherogenic diets containing various oils were found to undergo the most oxidative susceptibility of LDL via polyunsaturated oils. In another study, rabbits fed heated soybean oil "grossly induced atherosclerosis and marked liver damage were histologically and clinically demonstrated." However, Fred Kummerow claims that it is not dietary cholesterol, but oxysterols, or oxidized cholesterols, from fried foods and smoking, that are the culprit.Rancid fats and oils taste very unpleasant in even small amounts, so people avoid eating them. It is very difficult to measure or estimate the actual human consumption of these substances. Highly unsaturated omega-3 rich oils such as fish oil, when being sold in pill form, can hide the taste of oxidized or rancid fat that might be present. In the US, the health food industrys dietary supplements are self-regulated and outside of FDA regulations. To properly protect unsaturated fats from oxidation, it is best to keep them cool and in oxygen-free environments. Pathophysiology Atherogenesis is the developmental process of atheromatous plaques. It is characterized by a remodeling of arteries leading to subendothelial accumulation of fatty substances called plaques. The buildup of an atheromatous plaque is a slow process, developed over a period of several years through a complex series of cellular events occurring within the arterial wall and in response to a variety of local vascular circulating factors. One recent hypothesis suggests that, for unknown reasons, leukocytes, such as monocytes or basophils, begin to attack the endothelium of the artery lumen in cardiac muscle. The ensuing inflammation leads to the formation of atheromatous plaques in the arterial tunica intima, a region of the vessel wall located between the endothelium and the tunica media. The bulk of these lesions is made of excess fat, collagen, and elastin. At first, as the plaques grow, only wall thickening occurs without any narrowing. Stenosis is a late event, which may never occur and is often the result of repeated plaque rupture and healing responses, not just the atherosclerotic process by itself. Cellular Early atherogenesis is characterized by the adherence of blood circulating monocytes (a type of white blood cell) to the vascular bed lining, the endothelium, then by their migration to the sub-endothelial space, and further activation into monocyte-derived macrophages. The primary documented driver of this process is oxidized lipoprotein particles within the wall, beneath the endothelial cells, though upper normal or elevated concentrations of blood glucose also plays a major role and not all factors are fully understood. Fatty streaks may appear and disappear.Low-density lipoprotein (LDL) particles in blood plasma invade the endothelium and become oxidized, creating risk of cardiovascular disease. A complex set of biochemical reactions regulates the oxidation of LDL, involving enzymes (such as Lp-LpA2) and free radicals in the endothelium.Initial damage to the endothelium results in an inflammatory response. Monocytes enter the artery wall from the bloodstream, with platelets adhering to the area of insult. This may be promoted by redox signaling induction of factors such as VCAM-1, which recruit circulating monocytes, and M-CSF, which is selectively required for the differentiation of monocytes to macrophages. The monocytes differentiate into macrophages, which proliferate locally, ingest oxidized LDL, slowly turning into large "foam cells" – so-called because of their changed appearance resulting from the numerous internal cytoplasmic vesicles and resulting high lipid content. Under the microscope, the lesion now appears as a fatty streak. Foam cells eventually die and further propagate the inflammatory process.In addition to these cellular activities, there is also smooth muscle proliferation and migration from the tunica media into the intima in response to cytokines secreted by damaged endothelial cells. This causes the formation of a fibrous capsule covering the fatty streak. Intact endothelium can prevent this smooth muscle proliferation by releasing nitric oxide. Calcification and lipids Calcification forms among vascular smooth muscle cells of the surrounding muscular layer, specifically in the muscle cells adjacent to atheromas and on the surface of atheroma plaques and tissue. In time, as cells die, this leads to extracellular calcium deposits between the muscular wall and outer portion of the atheromatous plaques. With the atheromatous plaque interfering with the regulation of the calcium deposition, it accumulates and crystallizes. A similar form of intramural calcification, presenting the picture of an early phase of arteriosclerosis, appears to be induced by many drugs that have an antiproliferative mechanism of action (Rainer Liedtke 2008).Cholesterol is delivered into the vessel wall by cholesterol-containing low-density lipoprotein (LDL) particles. To attract and stimulate macrophages, the cholesterol must be released from the LDL particles and oxidized, a key step in the ongoing inflammatory process. The process is worsened if it is insufficient high-density lipoprotein (HDL), the lipoprotein particle that removes cholesterol from tissues and carries it back to the liver.The foam cells and platelets encourage the migration and proliferation of smooth muscle cells, which in turn ingest lipids, become replaced by collagen, and transform into foam cells themselves. A protective fibrous cap normally forms between the fatty deposits and the artery lining (the intima).These capped fatty deposits (now called atheromas) produce enzymes that cause the artery to enlarge over time. As long as the artery enlarges sufficiently to compensate for the extra thickness of the atheroma, then no narrowing ("stenosis") of the opening ("lumen") occurs. The artery becomes expanded with an egg-shaped cross-section, still with a circular opening. If the enlargement is beyond proportion to the atheroma thickness, then an aneurysm is created. Visible features Although arteries are not typically studied microscopically, two plaque types can be distinguished: The fibro-lipid (fibro-fatty) plaque is characterized by an accumulation of lipid-laden cells underneath the intima of the arteries, typically without narrowing the lumen due to compensatory expansion of the bounding muscular layer of the artery wall. Beneath the endothelium, there is a "fibrous cap" covering the atheromatous "core" of the plaque. The core consists of lipid-laden cells (macrophages and smooth muscle cells) with elevated tissue cholesterol and cholesterol ester content, fibrin, proteoglycans, collagen, elastin, and cellular debris. In advanced plaques, the central core of the plaque usually contains extracellular cholesterol deposits (released from dead cells), which form areas of cholesterol crystals with empty, needle-like clefts. At the periphery of the plaque are younger "foamy" cells and capillaries. These plaques usually produce the most damage to the individual when they rupture. Cholesterol crystals may also play a role. The fibrous plaque is also localized under the intima, within the wall of the artery resulting in thickening and expansion of the wall and, sometimes, spotty localized narrowing of the lumen with some atrophy of the muscular layer. The fibrous plaque contains collagen fibers (eosinophilic), precipitates of calcium (hematoxylinophilic), and rarely, lipid-laden cells.In effect, the muscular portion of the artery wall forms small aneurysms just large enough to hold the atheroma that are present. The muscular portion of artery walls usually remains strong, even after they have remodeled to compensate for the atheromatous plaques.However, atheromas within the vessel wall are soft and fragile with little elasticity. Arteries constantly expand and contract with each heartbeat, i.e., the pulse. In addition, the calcification deposits between the outer portion of the atheroma and the muscular wall, as they progress, lead to a loss of elasticity and stiffening of the artery as a whole.The calcification deposits, after they have become sufficiently advanced, are partially visible on coronary artery computed tomography or electron beam tomography (EBT) as rings of increased radiographic density, forming halos around the outer edges of the atheromatous plaques, within the artery wall. On CT, >130 units on the Hounsfield scale (some argue for 90 units) has been the radiographic density usually accepted as clearly representing tissue calcification within arteries. These deposits demonstrate unequivocal evidence of the disease, relatively advanced, even though the lumen of the artery is often still normal by angiography. Rupture and stenosis Although the disease process tends to be slowly progressive over decades, it usually remains asymptomatic until an atheroma ulcerates, which leads to immediate blood clotting at the site of the atheroma ulcer. This triggers a cascade of events that leads to clot enlargement, which may quickly obstruct the flow of blood. A complete blockage leads to ischemia of the myocardial (heart) muscle and damage. This process is the myocardial infarction or "heart attack".If the heart attack is not fatal, fibrous organization of the clot within the lumen ensues, covering the rupture but also producing stenosis or closure of the lumen, or over time and after repeated ruptures, resulting in a persistent, usually localized stenosis or blockage of the artery lumen. Stenoses can be slowly progressive, whereas plaque ulceration is a sudden event that occurs specifically in atheromas with thinner/weaker fibrous caps that have become "unstable".Repeated plaque ruptures, ones not resulting in total lumen closure, combined with the clot patch over the rupture and healing response to stabilize the clot is the process that produces most stenoses over time. The stenotic areas tend to become more stable despite increased flow velocities at these narrowings. Most major blood-flow-stopping events occur at large plaques, which, before their rupture, produced very little if any stenosis.From clinical trials, 20% is the average stenosis at plaques that subsequently rupture with resulting complete artery closure. Most severe clinical events do not occur at plaques that produce high-grade stenosis. From clinical trials, only 14% of heart attacks occur from artery closure at plaques producing a 75% or greater stenosis before the vessel closing.If the fibrous cap separating a soft atheroma from the bloodstream within the artery ruptures, tissue fragments are exposed and released. These tissue fragments are very clot-promoting, containing collagen and tissue factor; they activate platelets and activate the system of coagulation. The result is the formation of a thrombus (blood clot) overlying the atheroma, which obstructs blood flow acutely. With the obstruction of blood flow, downstream tissues are starved of oxygen and nutrients. If this is the myocardium (heart muscle) angina (cardiac chest pain) or myocardial infarction (heart attack) develops. Accelerated growth of plaques The distribution of atherosclerotic plaques in a part of arterial endothelium is inhomogeneous. The multiple and focal development of atherosclerotic changes is similar to that in the development of amyloid plaques in the brain and that of age spots on the skin. Misrepair-accumulation aging theory suggests that misrepair mechanisms play an important role in the focal development of atherosclerosis. Development of a plaque is a result of repair of injured endothelium. Because of the infusion of lipids into sub-endothelium, the repair has to end up with altered remodeling of local endothelium. This is the manifestation of a misrepair. Important is this altered remodeling makes the local endothelium have increased fragility to damage and have reduced repair efficiency. As a consequence, this part of endothelium has an increased risk factor of being injured and improperly repaired. Thus, the accumulation of misrepairs of endothelium is focalized and self-accelerating. In this way, the growing of a plaque is also self-accelerating. Within a part of the arterial wall, the oldest plaque is always the biggest, and is the most dangerous one to cause blockage of a local artery. Components The plaque is divided into three distinct components: The atheroma ("lump of gruel", from Greek ἀθήρα (athera) gruel), which is the nodular accumulation of a soft, flaky, yellowish material at the center of large plaques, composed of macrophages nearest the lumen of the artery Underlying areas of cholesterol crystals Calcification at the outer base of older or more advanced lesions. Atherosclerotic lesions, or atherosclerotic plaques, are separated into two broad categories: Stable and unstable (also called vulnerable). The pathobiology of atherosclerotic lesions is very complicated, but generally, stable atherosclerotic plaques, which tend to be asymptomatic, are rich in extracellular matrix and smooth muscle cells. On the other hand, unstable plaques are rich in macrophages and foam cells, and the extracellular matrix separating the lesion from the arterial lumen (also known as the fibrous cap) is usually weak and prone to rupture. Ruptures of the fibrous cap expose thrombogenic material, such as collagen, to the circulation and eventually induce thrombus formation in the lumen. Upon formation, intraluminal thrombi can occlude arteries outright (e.g., coronary occlusion), but more often they detach, move into the circulation, and eventually occlude smaller downstream branches causing thromboembolism.Apart from thromboembolism, chronically expanding atherosclerotic lesions can cause complete closure of the lumen. Chronically expanding lesions are often asymptomatic until lumen stenosis is so severe (usually over 80%) that blood supply to downstream tissue(s) is insufficient, resulting in ischemia. These complications of advanced atherosclerosis are chronic, slowly progressive, and cumulative. Most commonly, soft plaque suddenly ruptures (see vulnerable plaque), causing the formation of a thrombus that will rapidly slow or stop blood flow, leading to the death of the tissues fed by the artery in approximately five minutes. This event is called an infarction. Diagnosis Areas of severe narrowing, stenosis, detectable by angiography, and to a lesser extent "stress testing" have long been the focus of human diagnostic techniques for cardiovascular disease, in general. However, these methods focus on detecting only severe narrowing, not the underlying atherosclerosis disease. As demonstrated by human clinical studies, most severe events occur in locations with heavy plaque, yet little or no lumen narrowing present before debilitating events suddenly occur. Plaque rupture can lead to artery lumen occlusion within seconds to minutes, and potential permanent debility, and sometimes sudden death.Plaques that have ruptured are called complicated lesions. The extracellular matrix of the lesion breaks, usually at the shoulder of the fibrous cap that separates the lesion from the arterial lumen, where the exposed thrombogenic components of the plaque, mainly collagen, will trigger thrombus formation. The thrombus then travels downstream to other blood vessels, where the blood clot may partially or completely block blood flow. If the blood flow is completely blocked, cell deaths occur due to the lack of oxygen supply to nearby cells, resulting in necrosis. The narrowing or obstruction of blood flow can occur in any artery within the body. Obstruction of arteries supplying the heart muscle results in a heart attack, while the obstruction of arteries supplying the brain results in an ischaemic stroke. Lumen stenosis that is greater than 75% was considered the hallmark of clinically significant disease in the past because recurring episodes of angina and abnormalities in stress tests are only detectable at that particular severity of stenosis. However, clinical trials have shown that only about 14% of clinically debilitating events occur at sites with more than 75% stenosis. The majority of cardiovascular events that involve sudden rupture of the atheroma plaque do not display any evident narrowing of the lumen. Thus, greater attention has been focused on "vulnerable plaque" from the late 1990s onwards.Besides the traditional diagnostic methods such as angiography and stress-testing, other detection techniques have been developed in the past decades for earlier detection of atherosclerotic disease. Some of the detection approaches include anatomical detection and physiologic measurement.Examples of anatomical detection methods include coronary calcium scoring by CT, carotid IMT (intimal media thickness) measurement by ultrasound, and intravascular ultrasound (IVUS). Examples of physiologic measurement methods include lipoprotein subclass analysis, HbA1c, hs-CRP, and homocysteine. Both anatomic and physiologic methods allow early detection before symptoms show up, disease staging, and tracking of disease progression. Anatomic methods are more expensive and some of them are invasive in nature, such as IVUS. On the other hand, physiologic methods are often less expensive and safer. But they do not quantify the current state of the disease or directly track progression. In recent years, developments in nuclear imaging techniques such as PET and SPECT have provided ways of estimating the severity of atherosclerotic plaques. Prevention Up to 90% of cardiovascular disease may be preventable if established risk factors are avoided. Medical management of atherosclerosis first involves modification to risk factors–for example, via smoking cessation and diet restrictions. Prevention then is generally by eating a healthy diet, exercising, not smoking, and maintaining a normal weight. Diet Changes in diet may help prevent the development of atherosclerosis. Tentative evidence suggests that a diet containing dairy products has no effect on or decreases the risk of cardiovascular disease.A diet high in fruits and vegetables decreases the risk of cardiovascular disease and death. Evidence suggests that the Mediterranean diet may improve cardiovascular results. There is also evidence that a Mediterranean diet may be better than a low-fat diet in bringing about long-term changes to cardiovascular risk factors (e.g., lower cholesterol level and blood pressure). Exercise A controlled exercise program combats atherosclerosis by improving circulation and functionality of the vessels. Exercise is also used to manage weight in patients who are obese, lower blood pressure, and decrease cholesterol. Often lifestyle modification is combined with medication therapy. For example, statins help to lower cholesterol. Antiplatelet medications like aspirin help to prevent clots, and a variety of antihypertensive medications are routinely used to control blood pressure. If the combined efforts of risk factor modification and medication therapy are not sufficient to control symptoms or fight imminent threats of ischemic events, a physician may resort to interventional or surgical procedures to correct the obstruction. Treatment Treatment of established disease may include medications to lower cholesterol such as statins, blood pressure medication, or medications that decrease clotting, such as aspirin. A number of procedures may also be carried out such as percutaneous coronary intervention, coronary artery bypass graft, or carotid endarterectomy.Medical treatments often focus on alleviating symptoms. However measures which focus on decreasing underlying atherosclerosis—as opposed to simply treating symptoms—are more effective. Non-pharmaceutical means are usually the first method of treatment, such as stopping smoking and practicing regular exercise. If these methods do not work, medicines are usually the next step in treating cardiovascular diseases and, with improvements, have increasingly become the most effective method over the long term.The key to the more effective approaches is to combine multiple different treatment strategies. In addition, for those approaches, such as lipoprotein transport behaviors, which have been shown to produce the most success, adopting more aggressive combination treatment strategies taken on a daily basis and indefinitely has generally produced better results, both before and especially after people are symptomatic. Statins The group of medications referred to as statins are widely prescribed for treating atherosclerosis. They have shown benefit in reducing cardiovascular disease and mortality in those with high cholesterol with few side effects. Secondary prevention therapy, which includes high-intensity statins and aspirin, is recommended by multi-society guidelines for all patients with history of ASCVD (atherosclerotic cardiovascular disease) to prevent recurrence of coronary artery disease, ischemic stroke, or peripheral arterial disease. However, prescription of and adherence to these guideline-concordant therapies is lacking, particularly among young patients and women.Statins work by inhibiting HMG-CoA (hydroxymethylglutaryl-coenzyme A) reductase, a hepatic rate-limiting enzyme in cholesterols biochemical production pathway. By inhibiting this rate-limiting enzyme, the body is unable to produce cholesterol endogenously, therefore reducing serum LDL-cholesterol. This reduced endogenous cholesterol production triggers the body to then pull cholesterol from other cellular sources, enhancing serum HDL-cholesterol. These data are primarily in middle-age men and the conclusions are less clear for women and people over the age of
Atherosclerosis	70. Surgery When atherosclerosis has become severe and caused irreversible ischemia, such as tissue loss in the case of peripheral artery disease, surgery may be indicated. Vascular bypass surgery can re-establish flow around the diseased segment of artery, and angioplasty with or without stenting can reopen narrowed arteries and improve blood flow. Coronary artery bypass grafting without manipulation of the ascending aorta has demonstrated reduced rates of postoperative stroke and mortality compared to traditional on-pump coronary revascularization. Other There is evidence that some anticoagulants, particularly warfarin, which inhibit clot formation by interfering with Vitamin K metabolism, may actually promote arterial calcification in the long term despite reducing clot formation in the short term. Also, single peptides such as 3-hydroxybenzaldehyde and protocatechuic aldehyde have shown vasculoprotective effects to reduce risk of atherosclerosis. Epidemiology Cardiovascular disease, which is predominantly the clinical manifestation of atherosclerosis, is one of the leading causes of death worldwide. Etymology The following terms are similar, yet distinct, in both spelling and meaning, and can be easily confused: arteriosclerosis, arteriolosclerosis, and atherosclerosis. Arteriosclerosis is a general term describing any hardening (and loss of elasticity) of medium or large arteries (from Greek ἀρτηρία (artēria) artery, and σκλήρωσις (sklerosis) hardening); arteriolosclerosis is any hardening (and loss of elasticity) of arterioles (small arteries); atherosclerosis is a hardening of an artery specifically due to an atheromatous plaque (from Ancient Greek ἀθήρα (athḗra) gruel). The term atherogenic is used for substances or processes that cause formation of atheroma. Economics In 2011, coronary atherosclerosis was one of the top ten most expensive conditions seen during inpatient hospitalizations in the US, with aggregate inpatient hospital costs of $10.4 billion. Research Lipids An indication of the role of high-density lipoprotein (HDL) on atherosclerosis has been with the rare Apo-A1 Milano human genetic variant of this HDL protein. A small short-term trial using bacterial synthesized human Apo-A1 Milano HDL in people with unstable angina produced a fairly dramatic reduction in measured coronary plaque volume in only six weeks vs. the usual increase in plaque volume in those randomized to placebo. The trial was published in JAMA in early 2006. Ongoing work starting in the 1990s may lead to human clinical trials—probably by about 2008. These may use synthesized Apo-A1 Milano HDL directly, or they may use gene-transfer methods to pass the ability to synthesize the Apo-A1 Milano HDLipoprotein.Methods to increase HDL particle concentrations, which in some animal studies largely reverses and removes atheromas, are being developed and researched. However, increasing HDL by any means is not necessarily helpful. For example, the drug torcetrapib is the most effective agent currently known for raising HDL (by up to 60%). However, in clinical trials, it also raised deaths by 60%. All studies regarding this drug were halted in December 2006.The actions of macrophages drive atherosclerotic plaque progression. Immunomodulation of atherosclerosis is the term for techniques that modulate immune system function to suppress this macrophage action.Involvement of lipid peroxidation chain reaction in atherogenesis triggered research on the protective role of the heavy isotope (deuterated) polyunsaturated fatty acids (D-PUFAs) that are less prone to oxidation than ordinary PUFAs (H-PUFAs). PUFAs are essential nutrients – they are involved in metabolism in that very form as they are consumed with food. In transgenic mice, that are a model for human-like lipoprotein metabolism, adding D-PUFAs to diet indeed reduced body weight gain, improved cholesterol handling and reduced atherosclerotic damage to the aorta. miRNA MicroRNAs (miRNAs) have complementary sequences in the 3 UTR and 5 UTR of target mRNAs of protein-coding genes, and cause mRNA cleavage or repression of translational machinery. In diseased vascular vessels, miRNAs are dysregulated and highly expressed. miR-33 is found in cardiovascular diseases. It is involved in atherosclerotic initiation and progression including lipid metabolism, insulin signaling and glucose homeostatis, cell type progression and proliferation, and myeloid cell differentiation. It was found in rodents that the inhibition of miR-33 will raise HDL level and the expression of miR-33 is down-regulated in humans with atherosclerotic plaques.miR-33a and miR-33b are located on intron 16 of human sterol regulatory element-binding protein 2 (SREBP2) gene on chromosome 22 and intron 17 of SREBP1 gene on chromosome 17. miR-33a/b regulates cholesterol/lipid homeostatis by binding in the 3UTRs of genes involved in cholesterol transport such as ATP binding cassette (ABC) transporters and enhance or represses its expression. Study have shown that ABCA1 mediates transport of cholesterol from peripheral tissues to Apolipoprotein-1 and it is also important in the reverse cholesterol transport pathway, where cholesterol is delivered from peripheral tissue to the liver, where it can be excreted into bile or converted to bile acids prior to excretion. Therefore, we know that ABCA1 plays an important role in preventing cholesterol accumulation in macrophages. By enhancing miR-33 function, the level of ABCA1 is decreased, leading to decrease cellular cholesterol efflux to apoA-1. On the other hand, by inhibiting miR-33 function, the level of ABCA1 is increased and increases the cholesterol efflux to apoA-1. Suppression of miR-33 will lead to less cellular cholesterol and higher plasma HDL level through the regulation of ABCA1 expression.The sugar, cyclodextrin, removed cholesterol that had built up in the arteries of mice fed a high-fat diet. DNA damage Aging is the most important risk factor for cardiovascular problems. The causative basis by which aging mediates its impact, independently of other recognized risk factors, remains to be determined. Evidence has been reviewed for a key role of DNA damage in vascular aging.8-oxoG, a common type of oxidative damage in DNA, is found to accumulate in plaque vascular smooth muscle cells, macrophages and endothelial cells, thus linking DNA damage to plaque formation. DNA strand breaks also increased in atherosclerotic plaques. Werner syndrome (WS) is a premature aging condition in humans. WS is caused by a genetic defect in a RecQ helicase that is employed in several repair processes that remove damages from DNA. WS patients develop a considerable burden of atherosclerotic plaques in their coronary arteries and aorta: calcification of the aortic valve is also frequently observed. These findings link excessive unrepaired DNA damage to premature aging and early atherosclerotic plaque development (see DNA damage theory of aging). Microorganisms The microbiota – all the microorganisms in the body, can contribute to atherosclerosis in many ways: modulation of the immune system, changes in metabolism, processing of nutrients and production of certain metabolites that can get into blood circulation. One such metabolite, produced by gut bacteria, is trimethylamine N-oxide (TMAO). Its levels have been associated with atherosclerosis in human studies and animal research suggest that there can be a causal relation. An association between the bacterial genes encoding trimethylamine lyases — the enzymes involved in TMAO generation — and atherosclerosis has been noted. Vascular smooth muscle cells Vascular smooth muscle cells play a key role in atherogenesis and were historically considered to be beneficial for plaque stability by forming a protective fibrous cap and synthesising strength-giving extracellular matrix components. However, in addition to the fibrous cap, vascular smooth muscle cells also give rise to many of the cell types found within the plaque core and can modulate their phenotype to both promote and reduce plaque stability. Vascular smooth muscle cells exhibit pronounced plasticity within atherosclerotic plaque and can modify their gene expression profile to resemble various other cell types, including macrophages, myofibroblasts, mesenchymal stem cells and osteochondrocytes. Importantly, genetic lineage‐tracing experiments have unequivocally shown that 40-90% of plaque-resident cells are vascular smooth muscle cell derived. Therefore, it is important to research the role of vascular smooth muscle cells in atherosclerosis to identify new therapeutic targets. References External links Quotations related to Atherosclerosis at Wikiquote Atherosclerosis at Curlie Atherosclerosis pathophysiology-stages and types
Supraclavicular lymph nodes	Supraclavicular lymph nodes are lymph nodes found above the clavicle, that can be felt in the supraclavicular fossa. The supraclavicular lymph nodes on the left side are called Virchows nodes. It leads to an appreciable mass that can be recognized clinically, called Troisier sign. Structure A Virchows node is a left-sided supraclavicular lymph node. Clinical significance Malignancies of the internal organs can reach an advanced stage before giving symptoms. Stomach cancer, for example, can remain asymptomatic while metastasizing. One of the first visible spots where these tumors metastasize is one of the left supraclavicular lymph node. Virchows nodes take their supply from lymph vessels in the abdominal cavity, and are therefore sentinel lymph nodes of cancer in the abdomen, particularly gastric cancer, ovarian cancer, testicular cancer and kidney cancer, that has spread through the lymph vessels, and Hodgkins lymphoma. Such spread typically results in Troisiers sign, which is the finding of an enlarged, hard Virchows node.The left supraclavicular nodes are the classical Virchows node because they receive lymphatic drainage of most of the body (from the thoracic duct) and enters the venous circulation via the left subclavian vein. The metastasis may block the thoracic duct leading to regurgitation into the surrounding Virchows nodes. Another concept is that one of the supraclavicular nodes corresponds to the end node along the thoracic duct and hence the enlargement.Differential diagnosis of an enlarged Virchows node includes lymphoma, various intra-abdominal malignancies, breast cancer, and infection (e.g. of the arm). Similarly, an enlarged right supraclavicular lymph node tends to drain thoracic malignancies such as lung and esophageal cancer, as well as Hodgkins lymphoma. History Virchows nodes are named after Rudolf Virchow (1821–1902), the German pathologist who first described the nodes and their association with gastric cancer in 1848. The French pathologist Charles Emile Troisier noted in 1889 that other abdominal cancers, too, could spread to the nodes. Additional images References This article incorporates text in the public domain from page 697 of the 20th edition of Grays Anatomy (1918) Further reading Cervin, J. R.; Silverman, J. F.; Loggie, B. W.; Geisinger, K. R. (1995). "Virchows node revisited. Analysis with clinicopathologic correlation of 152 fine-needle aspiration biopsies of supraclavicular lymph nodes". Archives of Pathology & Laboratory Medicine. 119 (8): 727–30. PMID 7646330. INIST:3670181 NAID 10026546830. Negus, D; Edwards, J M; Kinmonth, J B (7 December 2005). "Filling of cervical and mediastinal nodes from the thoracic duct and the physiology of virchows node—studies by lymphography". British Journal of Surgery. 57 (4): 267–271. doi:10.1002/bjs.1800570407. PMID 5437920. S2CID 19698597. Mizutani, Masaomi; Nawata, Shin-ichi; Hirai, Ichiro; Murakami, Gen; Kimura, Wataru (December 2005). "Anatomy and histology of Virchows node". Anatomical Science International. 80 (4): 193–198. doi:10.1111/j.1447-073x.2005.00114.x. PMID 16333915. S2CID 40130186. External links synd/1222 at Who Named It? Image at umich.edu - must rollover https://web.archive.org/web/20080216031919/http://www.med.mun.ca/anatomyts/head/hnl3a.htm http://www.aafp.org/afp/20021201/2103.html
Volkmanns contracture	Volkmanns contracture is a permanent flexion contracture of the hand at the wrist, resulting in a claw-like deformity of the hand and fingers. Passive extension of fingers is restricted and painful. Causes Any fracture in the elbow region or upper arm may lead to Volkmanns ischemic contracture, but it is especially associated with supracondylar fracture of the humerus. It is also caused by fractures of the forearm bones if they cause bleeding from the major blood vessels of the forearm.The condition may be caused by obstruction on the brachial artery near the elbow, possibly from improper use of a tourniquet, improper use of a plaster cast, or compartment syndrome. Pathophysiology Volkmanns contracture results from acute ischaemia and necrosis of the muscle fibres of the flexor group of muscles of the forearm, especially the flexor digitorum profundus and flexor pollicis longus. The muscles become fibrotic and shortened. Prevention Prevention of the condition requires restoration of blood flow after injury and reduction of compartmental pressure on the muscles. Any splints, bandages, or other devices that might be obstructing circulation must be removed.A fasciotomy may be required to reduce pressure in the muscle compartment. Treatment If contracture occurs, surgery to release the fixed tissues may help with the deformity and function of the hand. History It is named after Richard von Volkmann (1830–1889), the 19th century German doctor who first described it, in a paper on "non-Infective Ischemic conditions of various fascial compartments in the extremities". Because the contracture occurred at the same time as the paralysis, he considered a nerve cause to be unlikely. References External links Volkmanns contracture at the Duke University Health Systems Orthopedics program
Chimera	Chimera, chimaera, or chimaira may refer to: Chimera (mythology), a monstrous creature with parts from multiple animals Mount Chimaera, the region in Lycia that some believe was an inspiration for the myth Biology Chimaera, any of various cartilaginous fishes of the order Chimaeriformes Chimaera (genus), the eponymous genus of the order Chimaeriformes Chimera (EST), a single cDNA sequence originating from two transcripts Chimera (genetics), a single animal or plant with genetically distinct cells from two different zygotes Chimera (virus), a virus containing genetic material from other organisms Chimera, or fusion protein, a hybrid protein made by the splicing of two genes Chimera (paleontology), a fossil which was reconstructed with parts from different animals Chimera Project, a Soviet biological weapons program Media Fictional entities Chimera (Fullmetal Alchemist), characters in Fullmetal Alchemist Chimera (Marvel Comics), a Marvel Comics character Chimera (Dungeons & Dragons), a magical beast in Dungeons & Dragons Chimera Anima, a name grouping of animals in the anime Tokyo Mew Mew The Chimera, an alien race in Resistance Films Chimera (1968 film), an Italian musicarello film Chimera (2001 film), an Italian romance film Chimère (film), a 1989 French film Chimères (film), a 2013 French-language film Chimera Strain, a 2018 Indian-American sci-fi film Gaming Chimera (video game), a 1985 isometric maze arcade adventure Chimera (larp convention), a convention in Auckland, New Zealand Chimera Entertainment, a game development studio in Munich, Germany Literature The Chimeras, an 1854 sequence of sonnets by Gérard de Nerval Chimaira, a 2001 novel by Valerio Massimo Manfredi Chimera (Barth novel) (1972) Chimera (CrossGen), a 2003 comic book mini series Chimaera (novel), a 2004 novel by Ian Irvine Chimera (novel series), a Japanese novel series by Baku Yumemakura Chimera (short story), a short story by Lee Youngdo Chimera (2015), the third novel in Mira Grants Parasitology trilogy Music Groups or artists Chimaira, an American heavy metal band from Cleveland, Ohio Chimera (Irish band), a musical group Chimera (Russian band), an underground musical band Mike Dred or Chimera (born 1967), techno musician Albums Chimaira (album), a 2005 album by Chimaira Chimera (Andromeda album) (2006) Chimera (Aria album) (2001) Chimera (Delerium album), a 2003 album by Delerium Chimera (EP), a 2014 EP by Marié Digby Chimera (Erik Friedlander album) (1995) Chimera (Mayhem album) (2004) Chimeras (album), a 2003 album by John Zorn Chimera, a 2002 album by The Cost Chimera, a 1974 album by Duncan Mackay Chimera, a 1983 album by Bill Nelson 鵺-chimera-, a 2016 EP by Girugamesh Songs "Chimeres I, II and III", 2007 compositions by Fred Momotenko "Chimera", a song by Duncan Sheik from a version of Daylight "Chimaera", a 1992 song by Bad Religion from Generator "Chimera", a 1999 song by the Tea Party from Triptych "Chimeras", a track by Tim Hecker from Harmony in Ultraviolet "Chimera", a song by Bonham from Mad Hatter "The Chimera", a 2012 song by the Smashing Pumpkins from Oceania Television Chimera (British TV series), a 1991 British science fiction serial "Chimera" (NCIS), an episode of NCIS "Chimera" Star Trek: Deep Space Nine), a 1999 episode of Star Trek: Deep Space Nine "Chimera" (Stargate SG-1), an episode of Stargate SG-1 "Chimera" (The X-Files), an episode of The X-Files Chimera (South Korean TV series), a 2021 South Korean television series People Jason Chimera (born 1979), NHL ice hockey forward for the Washington Capitals Ricardo Rodriguez (wrestler) or Chimaera (born 1986), professional wrestler Computing Chimera (software library), a peer-to-peer software research project Camino (web browser) or Chimera, a free Mac OS X web browser UCSF Chimera, a software program for visualizing molecules Other uses Chimaera (Epirus), a town of ancient Epirus, now in Albania Chimera (spacecraft), a proposed spacecraft mission Chimera (architecture), a fantastic, mythical or grotesque decorative feature TVR Chimaera, a model of sports car Chimera (roller coaster), in La Feria Chapultepec Mágico, Mexico City See also Quimera International Festival, an annual cultural festival in Metepec, Toluca, Mexico All pages with titles beginning with Chimera All pages with titles containing Chimera
Preureteric vena cava	A preureteric vena cava, also known as a retrocaval ureter, is a rare congenital malformation of the right human ureter, in which the ureter passes behind the inferior vena cava, causing compression possibly leading to hydronephrosis. The prevalence of this condition is approximately 1 per 1,000 persons, with males 2-3 times more likely than females to develop the condition. Symptoms often do not manifest until those with the condition are aged in their 20s or 30s. References "preureteric vena cava" (PDF). Retrieved 15 July 2019. Morganstern, S. L.; Seery, W. H.; Cole, A. T. (1977). "Preureteric vena cava". Urology. 9 (6): 664–666. doi:10.1016/0090-4295(77)90317-x. ISSN 0090-4295. PMID 883067.
Congenital blindness	Congenital blindness refers to a group of diseases and conditions occurring in childhood or early adolescence of below 16 years old, which, if left untreated, result in blindness or severe visual impairment that are likely to be permanent blindness later in life. Congenital blindness is a hereditary disease and can be cured by gene therapy. Visual loss in children or infant can occur either at the stage of prenatal (during the time of conception or intrauterine period) or postnatal stage (during birth). A variety of causes can promote congenital blindness but the most concern and highest cause of it is a genetic mutation. In general, 60% of congenital blindness cases are contributed from prenatal stage and 40% are contributed from inherited disease. However, most of the congenital blindness cases show that it can be avoidable or preventable with early treatment. Causes Prenatal stage Premature Birth Refractive error Congenital cataract Retinopathy of prematurity (ROP) Infection such as Ophtalmia neonatorum that happen during time of conception or intrauterine period Vitamin A deficiency MeaslesPostnatal stage Genetic mutationThe mutation can usually be an autosomal recessive condition and unusual condition of infant happened where it forms retinoblastoma result from autosomal dominant condition. The mutation of Retinal pigment epithelium-specific 65 kDa protein (RPE65) gene which function to produce retinoid isomerohydrolase which is an enzyme. RPE65 performs a key role in the trans-cis isomerization of retinol in the retinal pigment epithelium of the eye. The palmitoylation of RPE65 serves to switch off the visual cycle in darkness and to switch it on in the light. Mutation in this gene causing disorder of phototransduction pathway through brain which detect light fail to function. Diagnosis Paediatric nurses, medical officers and paediatricians trained in eye screening could detect small or large eyeballs, nystagmus, strabismus, “white pupils” and birth defects like coloboma and aniridia. For pregnant women from family with history of congenital blindness will be closely monitor and need to carry out genetic test in order to identify is there mutation occur or not. Gene therapy treatment Gene therapy treatment is done as an outpatient. Patients come to the hospital for the treatment, then return home. Patients do not need to be monitored strictly or stay in the hospital. The gene therapy treatment is in vivo which involves the use of a delivery vector to transmit the therapeutic gene into the targeted cells. The delivery vector uses a recombinant adeno-associated virus (AAV) carrying the RPE65 gene (AAV2-hRPE65v2). The procedure is a single injection of the AAV2-hRPE65v2 therapeutic gene into the unilateral subretinal of the eye. Gene therapy can only improve eye vision, but cannot cure the condition. The therapeutic gene, Voretigene neparvovec (Luxturna), was the first gene therapy approved by FDA for inherited diseases. == References ==
Sponastrime dysplasia	Sponastrime dysplasia is a rare condition characterised by facial and skeletal abnormalities. Signs and symptoms The main features of this condition are evident in skeleton and face.Facial features: Macrocephaly Frontal bossing Midface hypoplasia Depressed nasal root Small upturned nose PrognathismSkeletal features: Shortened limbs (more pronounced in lower limbs) Short stature Progressive coxa varaOn X ray: Abnormal vertebral bodies (particularly in the lumbar region) Avascular necrosis of the capital femoral epiphyses Striated metaphyses Generalized mild osteoporosis Delayed ossification of the carpal bonesOther associated conditions: These are variably present Cataracts Hypogammaglobulinemia Intellectual disability Short dental roots Subglottic stenosis Tracheobronchomalacia Genetics This condition has been associated with mutations in the Tonsoku-like, DNA repair protein (TONSL) gene. This gene is located on the long arm of chromosome 8 (8q24.3). This gene is also known as NFKBIL2. Pathopysiology This is not understood. It appears that the TONSL gene product is involved in genome repair. Diagnosis This can be suspected when the usual facial and skeletal features are present. It is confirmed by sequencing the TONSL gene. Differential diagnosis Short limbed dwarfism syndrome in association with immunodeficiency. Treatment There is no specific treatment for this condition. Management is supportive. Epidemiology This condition is considered to be rare with less than 100 cases reported in the literature. History This condition was first described in 1983. == References ==
Ostium primum atrial septal defect	The ostium primum atrial septal defect is a defect in the atrial septum at the level of the tricuspid and mitral valves. This is sometimes known as an endocardial cushion defect because it often involves the endocardial cushion, which is the portion of the heart where the atrial septum meets the ventricular septum and the mitral valve meets the tricuspid valve. Endocardial cushion defects are associated with abnormalities of the atrioventricular valves (the mitral valve and the tricuspid valve). These include the cleft mitral valve, and the single atrioventricular valve (a single large, deformed valve that flows into both the right ventricle and the left ventricle). Endocardial cushion defects are the most common congenital heart defect that is associated with Down syndrome. Signs and symptoms On ECG a left axis deviation is generally found in ostium primum ASD, but an RSR pattern (M pattern) in V1 is characteristic. Fixed splitting of the second heart sound (S2) occurs because of equal filling of the left and right atria during all phases of the respiratory cycle. Patients with atrial Septal Defects may have atrial fibrillation, atrial tachycardia, or atrial flutter, but these abnormal heart rhythms are not usually seen until the affected individual grows older. Features also seen on the ECG include right atrial enlargement and varying degrees of atrioventricular block. When a person is suspected of having an ASD based on the findings of an incomplete right bundle branch block with a rSr or rSR, the frontal plane QRS should be examined. The frontal plane QRS is the most helpful clue to distinguish between an ostium secundum ASD and an ostium primum ASD. In primum defects left axis deviation is seen in most patients with an axis of > -30 degrees and very few patients have right axis deviation. In contrast ostium secundum defects have an axis between 0 degrees and 180 degrees with most cases to the right of 100 degrees.In the ECG above, you can see an example of the rSR pattern in V1 with a R greater than S with T wave inversion which is commonly seen in volume overload right ventricular hypertrophy. Diagnosis Classification A defect in the ostium primum is occasionally classified as an atrial septal defect, but it is more commonly classified as an atrioventricular septal defect. Treatment Hemodynamically significant ASDs (flow ratio 1.5:1) are large enough to be closed surgically. The long term prognosis is excellent. Pulmonary hypertension with shunt reversal is a contraindication for surgery, however the pulmonary hypertension can frequently be treated with medicines. The hole can then be closed safely with a good long term prognosis. References Notes External links This article incorporates text available under the CC BY-SA 3.0 license.
Spinocerebellar tract	The spinocerebellar tract is a nerve tract originating in the spinal cord and terminating in the same side (ipsilateral) of the cerebellum. Origins of proprioceptive information Proprioceptive information is obtained by Golgi tendon organs and muscle spindles. Golgi tendon organs consist of a fibrous capsule enclosing tendon fascicles and bare nerve endings that respond to tension in the tendon by causing action potentials in type Ib afferents. These fibers are relatively large, myelinated, and quickly conducting. Muscle spindles monitor the length within muscles and send information via faster Ia afferents. These axons are larger and faster than type Ib (from both nuclear bag fibers and nuclear chain fibers) and type II afferents (solely from nuclear chain fibers).All of these neurons are sensory (first order, or primary) and have their cell bodies in the dorsal root ganglia. They pass through Rexed laminae layers I-VI of the posterior grey column (dorsal horn) to form synapses with second order or secondary neurons in layer VII just beneath the dorsal horn. Subdivisions of the tract The tract is divided into: Dorsal spinocerebellar tract The dorsal spinocerebellar tract (posterior spinocerebellar tract, Flechsigs fasciculus, Flechsigs tract) conveys proprioceptive information from proprioceptors in the skeletal muscles and joints to the cerebellum.It is part of the somatosensory system and runs in parallel with the ventral spinocerebellar tract. It carries proprioceptive information from muscle spindles and Golgi tendon organs of ipsilateral part of trunk and lower limb. Proprioceptive information is taken to the spinal cord via central processes of dorsal root ganglia (first order neurons). These central processes travel through the dorsal horn where they synapse with second order neurons of Clarkes nucleus. Axon fibers from Clarkes Nucleus convey this proprioceptive information in the spinal cord in the peripheral region of the funiculus posterior ipsilaterally. The fibers continue to course through the medulla oblongata of the brainstem, at which point they pass through the inferior cerebellar peduncle and into the cerebellum, where unconscious proprioceptive information is processed. This tract involves two neurons and ends up on the same side of the body. The terms Flechsigs fasciculus and Flechsigs tract are named after German neuroanatomist, psychiatrist and neuropathologist Paul Flechsig. Ventral spinocerebellar tract The ventral spinocerebellar tract (or anterior spinocerebellar tract) conveys proprioceptive information from the body to the cerebellum. Historically, it has also been known as Gowers column (or fasciculus or tract), after Sir William Richard Gowers. It is part of the somatosensory system and runs in parallel with the dorsal spinocerebellar tract. Both these tracts involve two neurons. The ventral spinocerebellar tract will cross to the opposite side of the body first in the spinal cord as part of the anterior white commissure and then cross again to end in the cerebellum (referred to as a "double cross"), as compared to the dorsal spinocerebellar tract, which does not decussate, or cross sides, at all through its path. The ventral tract (under L2/L3) gets its proprioceptive/fine touch/vibration information from a first order neuron, with its cell body in a dorsal ganglion. The axon runs via the fila radicularia to the dorsal horn of the grey matter. There it makes a synapse with the dendrites of two neurons: they send their axons bilaterally to the ventral border of the lateral funiculi. The fibers of the ventral spinocerebellar tract then enters the cerebellum via the superior cerebellar peduncle. This is in contrast with the dorsal spinocerebellar tract (C8 - L2/L3), which only has 1 unilateral axon that has its cell body in Clarkes column (only at the level of C8 - L2/L3). Originates from ventral horn at lumbosacral spinal levels. Axons first cross midline in the spinal cord and run in the ventral border of the lateral funiculi. These axons ascend to the pons where they join the superior cerebellar peduncle to enter the cerebellum. Once in the deep white matter of the cerebellum, the axons recross the midline, give off collaterals to the globose and emboliform nuclei, and terminate in the cortex of the anterior lobe and vermis of the posterior lobe. Comparison with dorsal spinocerebellar tract When the dorsal roots are cut in a cat performing a step cycle, peripheral excitation is lost, and the dorsal spinocerebellar tract has no activity; the ventral spinocerebellar tract continues to show activity. This suggests that the dorsal spinocerebellar tract carries sensory information to the spinocerebellum through the inferior cerebellar peduncle during movement (since the inferior peduncle is known to contain fibres from the dorsal tract), and that the ventral spinocerebellar tract carries internally generated motor information about the movement through the superior cerebellar peduncle. Posterior external arcuate fibers The posterior external arcuate fibers (dorsal external arcuate fibers or cuneocerebellar tract) take origin in the accessory cuneate nucleus; they pass to the inferior cerebellar peduncle of the same side. The term "cuneocerebellar tract" is also used to describe an exteroceptive and proprioceptive components that take origin in the gracile and cuneate nuclei; they pass to the inferior cerebellar peduncle of the same side.The posterior external arcuate fibers carry proprioceptive information from the upper limbs and neck. It is an analogue to the dorsal spinocerebellar tract for the upper limbs. In this context, the "cuneo-" derives from the accessory cuneate nucleus, not the cuneate nucleus. (The two nuclei are related in space, but not in function.) It is uncertain whether fibers are continued directly from the gracile and cuneate fasciculi into the inferior peduncle. Rostral spinocerebellar tract The rostral spinocerebellar tract is a tract which transmits information from the golgi tendon organs of the cranial half of the body to the cerebellum. It terminates bilaterally in the anterior lobe of the cerebellum (lower cerebellar peduncle) after travelling ipsilaterally from its origin in the cervical portion of the spinal cord. It reaches the cerebellum partly through the brachium conjunctivum (superior cerebellar peduncle) and partly through the restiform body (inferior cerebellar peduncle). Pathway for dorsal and spinocuneocerebellar tracts The sensory neurons synapse in an area known as Clarkes nucleus or "Clarkes column". This is a column of relay neuron cell bodies within the medial gray matter within the spinal cord in layer VII (just beneath the dorsal horn), specifically between T1-L3. These neurons then send axons up the spinal cord, and project ipsilaterally to medial zones of the cerebellum through the inferior cerebellar peduncle. Below L3, relevant neurons pass into the fasciculus gracilis (usually associated with the dorsal column-medial lemniscal system) until L3 where they synapse with Clarkes nucleus (leading to considerable caudal enlargement). The neurons in the accessory cuneate nucleus have axons leading to the ipsilateral cerebellum via the inferior cerebellar peduncle. Pathway for ventral and rostral spinocerebellar tracts Some neurons of the ventral spinocerebellar tract instead form synapses with neurons in layer VII of L4-S3. Most of these fibers cross over to the contralateral lateral funiculus via the anterior white commissure and through the superior cerebellar peduncle. The fibers then often cross over again within the cerebellum to end on the ipsilateral side. For this reason the tract is sometimes termed the "double-crosser." The Rostral Tract synapses at the dorsal horn lamina (intermediate gray zone) of the spinal cord and ascends ipsilaterally to the cerebellum through the inferior cerebellar peduncle Additional images References Further reading OSCARSSON, O.; UDDENBERG, N. (1 May 1965). "Properties of Afferent Connections to the Rostral Spinocerebellar Tract in the Cat". Acta Physiologica Scandinavica. 64 (1–2): 143–153. doi:10.1111/j.1748-1716.1965.tb04163.x. PMID 14347272. External links hier-804 at NeuroNames hier-805 at NeuroNames hier-793 at NeuroNames - dorsal external arcuate fibers hier-800 at NeuroNames - cuneocerebellar tract Anatomyatlases Plate17327 NIF Search - Anterior Spinocerebellar Tract via the Neuroscience Information Framework
Heat exhaustion	Heat exhaustion is a severe form of heat illness. It is a medical emergency. Heat exhaustion is caused by the loss of water and electrolytes through sweating. The United States Department of Labor makes the following recommendation, "Heat illness can be prevented. Remember these three things: water, rest, and shade." Causes Common causes of heat exhaustion include: Hot, sunny, humid weather Physical exertion, especially in hot, humid weather Due to impaired thermoregulation, elderly people and infants can get serious heat illness even at rest, if the weather outside is hot and humid, and they are not getting enough cool air. Some drugs, such as diuretics, antihistamines, beta-blockers, alcohol, MDMA (Ecstasy, Molly), and other amphetamines can cause an increase in the risk of heat exhaustion.Especially during physical exertion, risk factors for heat exhaustion include: Wearing dark, padded, or insulated clothing; hats; and/or helmets (for example, football pads, turnout gear, etc.) Having a higher percentage of body fat Dehydration Fever Some medications, like beta blockers and antipsychotic medicines Signs and symptoms Symptoms of heat exhaustion include skin tingling, nausea, dizziness, irritability, headache, thirst, weakness, vomiting, high body temperature, excessive sweating, pupil dilation, and decreased urine output. Treatment First aid First aid for heat exhaustion includes: Moving the person to a cool place Having the patient take off extra layers of clothes Cooling the patient down by fanning them and/or putting wet towels on their body Having them lie down and put their feet up if they are feeling dizzy Having them drink water or sports drinks unless they are unconscious, too disoriented to drink, or vomiting Turning the patient on their side if they are vomiting Emergency medical treatment If an individual with heat exhaustion receives medical treatment, Emergency Medical Technicians (EMTs), doctors, and/or nurses may also: Provide supplemental oxygen Administer intravenous fluids and electrolytes if they are too confused to drink and/or are vomiting Prognosis If left untreated, heat exhaustion may progress to heat stroke. See also Occupational heat stress Heat stroke == References ==
Aphakia	Aphakia is the absence of the lens of the eye, due to surgical removal, such as in cataract surgery, a perforating wound or ulcer, or congenital anomaly. It causes a loss of accommodation, high degree of farsightedness (hyperopia), and a deep anterior chamber. Complications include detachment of the vitreous or retina, and glaucoma. Babies are rarely born with aphakia. Occurrence most often results from surgery to remove congenital cataract. Congenital cataracts usually develop as a result of infection of the fetus or genetic reasons. It is often difficult to identify the exact cause of these cataracts, especially if only one eye is affected. People with aphakia have relatively small pupils and their pupils dilate to a lesser degree. Causes Surgical removal of a lens, mainly in cataract surgery, is the most common cause of aphakia. Spontaneous traumatic absorption or congenital absence of lens matter is rare. Traumatic subluxation or dislocation of a lens may cause it. Signs and symptoms Hypermetropia: Without the focusing power of the lens, the eye becomes very farsighted. Loss of accommodation: Since the lens and its zonules are responsible for adjusting the focus of vision to different lengths, patients with aphakia will have a total loss of accommodation. Defective vision: High degree hypermetropia and total loss of accommodation cause defective vision for both distance and near. Cyanopsia: Absence of lens cause cyanopsia or blue vision. Some individuals have said that they perceive ultraviolet light, invisible to those with a lens, as whitish blue or whitish-violet. Erythropsia: Sometimes, objects appear reddish. Deep anterior chamber: Since lens is absent, anterior chamber will be deep. Iridodonesis: Iridodonesis is the vibration or agitated motion of the iris with eye movement. Purkinje test shows only two images; the reflection from anterior and posterior corneal surfaces. Iridectomy mark may be seen in surgical aphakia. Astigmatism: With-the-rule astigmatism due to corneal wound healing may occur in surgical aphakia, mainly after ICCE or ECCE. Complications Main complications of surgical aphakia include: Spectacle intolerance: Due to image magnification (up to 30%), optical aberration, prismatic effect and roving ring scotoma, spectacles are not well tolerated by aphakic patients. Due to high anisometropia, spectacle correction in uniocular aphakia may cause diplopia. Glaucoma: Secondary angle closure glaucoma may occur due to vitreous prolapse. Retinal detachment Aphakic bullous keratopathy Treatment Aphakia can be corrected by wearing glasses, contact lenses, artificial lens implantation, or refractive corneal surgeries. Eye with artificial lenses are described as "pseudophakic". Etymology Gr. a- alfa priv + phakos, lens, anything shaped like a lens References == External links ==

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