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Facial nerve paralysis	Facial nerve paralysis is a common problem that involves the paralysis of any structures innervated by the facial nerve. The pathway of the facial nerve is long and relatively convoluted, so there are a number of causes that may result in facial nerve paralysis. The most common is Bells palsy, a disease of unknown cause that may only be diagnosed by exclusion of identifiable serious causes. Signs and symptoms Facial nerve paralysis is characterised by facial weakness, usually only in one side of the face, with other symptoms possibly including loss of taste, hyperacusis and decreased salivation and tear secretion. Other signs may be linked to the cause of the paralysis, such as vesicles in the ear, which may occur if the facial palsy is due to shingles. Symptoms may develop over several hours. : 1228 Acute facial pain radiating from the ear may precede the onset of other symptoms. : 2585 Causes Bells palsy Bells palsy is the most common cause of acute facial nerve paralysis. There is no known cause of Bells palsy, although it has been associated with herpes simplex infection. Bells palsy may develop over several days, and may last several months, in the majority of cases recovering spontaneously. It is typically diagnosed clinically, in patients with no risk factors for other causes, without vesicles in the ear, and with no other neurological signs. Recovery may be delayed in the elderly, or those with a complete paralysis. Bells palsy is often treated with corticosteroids. Infection Lyme disease, an infection caused by Borrelia burgdorferi bacteria and spread by ticks, can account for about 25% of cases of facial palsy in areas where Lyme disease is common. In the U.S., Lyme is most common in the New England and Mid-Atlantic states and parts of Wisconsin and Minnesota, but it is expanding into other areas. The first sign of about 80% of Lyme infections, typically one or two weeks after a tick bite, is usually an expanding rash that may be accompanied by headaches, body aches, fatigue, or fever. In up to 10-15% of Lyme infections, facial palsy appears several weeks later, and may be the first sign of infection that is noticed, as the Lyme rash typically does not itch and is not painful. Lyme disease is treated with antibiotics.Reactivation of herpes zoster virus, as well as being associated with Bells palsy, may also be a direct cause of facial nerve palsy. Reactivation of latent virus within the geniculate ganglion is associated with vesicles affecting the ear canal, and termed Ramsay Hunt syndrome type II. In addition to facial paralysis, symptoms may include ear pain and vesicles, sensorineural hearing loss, and vertigo. Management includes antiviral drugs and oral steroids. Otitis media is an infection in the middle ear, which can spread to the facial nerve and inflame it, causing compression of the nerve in its canal. Antibiotics are used to control the otitis media, and other options include a wide myringotomy (an incision in the tympanic membrane) or decompression if the patient does not improve. Chronic otitis media usually presents in an ear with chronic discharge (otorrhea), or hearing loss, with or without ear pain (otalgia). Once suspected, there should be immediate surgical exploration to determine if a cholesteatoma has formed as this must be removed if present. Inflammation from the middle ear can spread to the canalis facialis of the temporal bone - through this canal travels the facial nerve together with the statoacoustisus nerve. In the case of inflammation the nerve is exposed to edema and subsequent high pressure, resulting in a periferic type palsy. Trauma In blunt trauma, the facial nerve is the most commonly injured cranial nerve. Physical trauma, especially fractures of the temporal bone, may also cause acute facial nerve paralysis. Understandably, the likelihood of facial paralysis after trauma depends on the location of the trauma. Most commonly, facial paralysis follows temporal bone fractures, though the likelihood depends on the type of fracture. Transverse fractures in the horizontal plane present the highest likelihood of facial paralysis (40-50%). Patients may also present with blood behind the tympanic membrane, sensory deafness, and vertigo; the latter two symptoms due to damage to vestibulocochlear nerve and the inner ear. Longitudinal fracture in the vertical plane present a lower likelihood of paralysis (20%). Patients may present with blood coming out of the external auditory meatus), tympanic membrane tear, fracture of external auditory canal, and conductive hearing loss. In patients with mild injuries, management is the same as with Bells palsy – protect the eyes and wait. In patients with severe injury, progress is followed with nerve conduction studies. If nerve conduction studies show a large (>90%) change in nerve conduction, the nerve should be decompressed. The facial paralysis can follow immediately the trauma due to direct damage to the facial nerve, in such cases a surgical treatment may be attempted. In other cases the facial paralysis can occur a long time after the trauma due to oedema and inflammation. In those cases steroids can be a good help. Tumors A tumor compressing the facial nerve anywhere along its complex pathway can result in facial paralysis. Common culprits are facial neuromas, congenital cholesteatomas, hemangiomas, acoustic neuromas, parotid gland neoplasms, or metastases of other tumours.Often, since facial neoplasms have such an intimate relationship with the facial nerve, removing tumors in this region becomes perplexing as the physician is unsure how to manage the tumor without causing even more palsy. Typically, benign tumors should be removed in a fashion that preserves the facial nerve, while malignant tumors should always be resected along with large areas of tissue around them, including the facial nerve. While this will inevitably lead to heightened paralysis, safe removal of a malignant neoplasm is worth the often treatable palsy that follows. In the best case scenario, paralysis can be corrected with techniques including hypoglossal-facial nerve anastomosis, end-to-end nerve repair, cross facial nerve grafting, or muscle transfer/transposition techniques, such as the gracilis free muscle transfer. Patients with facial nerve paralysis resulting from tumours usually present with a progressive, twitching paralysis, other neurological signs, or a recurrent Bells palsy-type presentation. The latter should always be suspicious, as Bells palsy should not recur. A chronically discharging ear must be treated as a cholesteatoma until proven otherwise; hence, there must be immediate surgical exploration. Computed tomography (CT) or magnetic resonance (MR) imaging should be used to identify the location of the tumour, and it should be managed accordingly. Other neoplastic causes include leptomeningeal carcinomatosis. Stroke Central facial palsy can be caused by a lacunar infarct affecting fibers in the internal capsule going to the nucleus. The facial nucleus itself can be affected by infarcts of the pontine arteries. Unlike peripheral facial palsy, central facial palsy does not affect the forehead, because the forehead is served by nerves coming from both motor cortexes. Other Other causes may include: Diabetes mellitus Facial nerve paralysis, sometimes bilateral, is a common manifestation of sarcoidosis of the nervous system, neurosarcoidosis. Bilateral facial nerve paralysis may occur in Guillain–Barré syndrome, an autoimmune condition of the peripheral nervous system. Moebius syndrome is a bilateral facial paralysis resulting from the underdevelopment of the VII cranial nerve (facial nerve), which is present at birth. The VI cranial nerve, which controls lateral eye movement, is also affected, so people with Moebius syndrome cannot form facial expression or move their eyes from side to side. Moebius syndrome is extremely rare, and its cause or causes are not known. Facial piercings, namely eyebrow piercings or tongue piercings, can in very rare cases cause damage to the facial nerve. Diagnosis A medical history and physical examination, including a neurological examination, are needed for diagnosis. The first step is to observe what parts of the face do not move normally when the person tries to smile, blink, or raise the eyebrows. If the forehead wrinkles normally, a diagnosis of central facial palsy is made, and the person should be evaluated for stroke. Otherwise, the diagnosis is peripheral facial palsy, and its cause needs to be identified, if possible. Ramsey Hunts syndrome causes pain and small blisters in the ear on the same side as the palsy. Otitis media, trauma, or post-surgical complications may alternatively become apparent from history and physical examination. If there is a history of trauma, or a tumour is suspected, a CT scan or MRI may be used to clarify its impact. Blood tests or x-rays may be ordered depending on suspected causes. The likelihood that the facial palsy is caused by Lyme disease should be estimated, based on recent history of outdoor activities in likely tick habitats during warmer months, recent history of rash or symptoms such as headache and fever, and whether the palsy affects both sides of the face (much more common in Lyme than in Bells palsy). If that likelihood is more than negligible, a serological test for Lyme disease should be performed. If the test is positive, the diagnosis is Lyme disease. If no cause is found, the diagnosis is Bells Palsy. Classification Facial nerve paralysis may be divided into supranuclear and infranuclear lesions. In a clinical setting, other commonly used classifications include: intra-cranial and extra-cranial; acute, subacute and chronic duration. Supranuclear and nuclear lesions Central facial palsy can be caused by a lacunar infarct affecting fibers in the internal capsule going to the nucleus. The facial nucleus itself can be affected by infarcts of the pontine arteries. These are corticobulbar fibers travelling in internal capsule. Infranuclear lesions Infranuclear lesions refer to the majority of causes of facial palsy. Treatment If an underlying cause has been found for the facial palsy, it should be treated. If it is estimated that the likelihood that the facial palsy is caused by Lyme disease exceeds 10%, empiric therapy with antibiotics should be initiated, without corticosteroids, and reevaluated upon completion of laboratory tests for Lyme disease. All other patients should be treated with corticosteroids and, if the palsy is severe, antivirals. Facial palsy is considered severe if the person is unable to close the affected eye completely or the face is asymmetric even at rest. Corticosteroids initiated within three days of Bells palsy onset have been found to increase chances of recovery, reduce time to recovery, and reduce residual symptoms in case of incomplete recovery. However, for facial palsy caused by Lyme disease, corticosteroids have been found in some studies to harm outcomes. Other studies have found antivirals to possibly improve outcomes relative to corticosteroids alone for severe Bells palsy. In those whose blinking is disrupted by the facial palsy, frequent use of artificial tears while awake is recommended, along with ointment and a patch or taping the eye closed when sleeping. References == External links ==
Biliary sludge	Biliary sludge refers to a viscous mixture of small particles derived from bile. These sediments consist of cholesterol crystals, calcium salts, calcium bilirubinate, mucin, and other materials. Signs and symptoms Complications Biliary sludge may cause complications such as biliary colic, acute cholecystitis, acute cholangitis, and acute pancreatitis. Cause Biliary sludge has been associated with pregnancy, rapid weight loss, total parenteral nutrition, drugs such as ceftriaxone and octreotide, solid organ transplantation, and gastric surgery. In many of these conditions, it is thought that the impairment in the contractility of the gallbladder leads to the formation of the sludge. Pathophysiology The pathophysiology of biliary sludge formation is likely related to gallbladder dysmotility. It is presumed that because the gallbladder is unable to effectively empty, the biliary sludge can start to accumulate. Diagnosis Biliary sludge is typically diagnosed by CT scan or transabdominal ultrasonography. Endoscopic ultrasonography is another more sensitive option. However, the gold standard is considered to be direct microscopy of aspirated gallbladder bile. This method is much more sensitive, although it is less practical. Treatment For patients without symptoms, no treatment is recommended. If patients become symptomatic and/or develop complications, cholecystectomy is indicated. For those who are poor surgical candidates, endoscopic sphincterotomy may be performed to reduce the risk of developing pancreatitis. Prognosis The clinical course of biliary sludge can do one of three things: (1) it can resolve completely, (2) wax and wane, or (3) progress to gallstones. If the biliary sludge has a cause (e.g. pregnancy), it oftentimes is resolved when the underlying cause is removed. Epidemiology The prevalence of biliary sludge is low in the general population. It has been reported that the prevalence ranges from 0-0.20% in men and 0.18-0.27% in women. However, in patients with certain conditions, the prevalence may be higher. See also Biliary microlithiasis References == External links ==
Miscarriage	Miscarriage, also known in medical terms as a spontaneous abortion and pregnancy loss, is the death of an embryo or fetus before it is able to survive independently. Some use the cutoff of 20 weeks of gestation, after which fetal death is known as a stillbirth. The most common symptom of a miscarriage is vaginal bleeding with or without pain. Sadness, anxiety, and guilt may occur afterwards. Tissue and clot-like material may leave the uterus and pass through and out of the vagina. Recurrent miscarriage may also be considered a form of infertility.Risk factors for miscarriage include being an older parent, previous miscarriage, exposure to tobacco smoke, obesity, diabetes, thyroid problems, and drug or alcohol use. About 80% of miscarriages occur in the first 12 weeks of pregnancy (the first trimester). The underlying cause in about half of cases involves chromosomal abnormalities. Diagnosis of a miscarriage may involve checking to see if the cervix is open or closed, testing blood levels of human chorionic gonadotropin (hCG), and an ultrasound. Other conditions that can produce similar symptoms include an ectopic pregnancy and implantation bleeding.Prevention is occasionally possible with good prenatal care. Avoiding drugs, alcohol, infectious diseases, and radiation may decrease the risk of miscarriage. No specific treatment is usually needed during the first 7 to 14 days. Most miscarriages will complete without additional interventions. Occasionally the medication misoprostol or a procedure such as vacuum aspiration is used to remove the remaining tissue. Women who have a blood type of rhesus negative (Rh negative) may require Rho(D) immune globulin. Pain medication may be beneficial. Emotional support may help with processing the loss.Miscarriage is the most common complication of early pregnancy. Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilisation is around 30% to 50%. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. About 5% of women have two miscarriages in a row. Some recommend not using the term "abortion" in discussions with those experiencing a miscarriage in an effort to decrease distress. In Britain, the term "miscarriage" has replaced any use of the term "spontaneous abortion" in relation to pregnancy loss and in response to complaints of insensitivity towards women who had suffered such loss. An additional benefit of this change is reducing confusion among medical laymen, who may not realize that the term "spontaneous abortion" refers to a naturally-occurring medical phenomenon, and not the intentional termination of pregnancy. Signs and symptoms Signs of a miscarriage include vaginal spotting, abdominal pain, cramping, and fluid, blood clots, and tissue passing from the vagina. Bleeding can be a symptom of miscarriage, but many women also have bleeding in early pregnancy and do not miscarry. Bleeding during the first half of pregnancy may be referred to as a threatened miscarriage. Of those who seek treatment for bleeding during pregnancy, about half will miscarry. Miscarriage may be detected during an ultrasound exam, or through serial human chorionic gonadotropin (HCG) testing. Risk factors Miscarriage may occur for many reasons, not all of which can be identified. Risk factors are those things that increase the likelihood of having a miscarriage but do not necessarily cause a miscarriage. Up to 70 conditions, infections, medical procedures, lifestyle factors, occupational exposures, chemical exposure, and shift work are associated with increased risk for miscarriage. Some of these risks include endocrine, genetic, uterine, or hormonal abnormalities, reproductive tract infections, and tissue rejection caused by an autoimmune disorder. Trimesters First trimester Most clinically apparent miscarriages (two-thirds to three-quarters in various studies) occur during the first trimester. About 30% to 40% of all fertilized eggs miscarry, often before the pregnancy is known. The embryo typically dies before the pregnancy is expelled; bleeding into the decidua basalis and tissue necrosis causes uterine contractions to expel the pregnancy. Early miscarriages can be due to a developmental abnormality of the placenta or other embryonic tissues. In some instances an embryo does not form but other tissues do. This has been called a "blighted ovum".Successful implantation of the zygote into the uterus is most likely eight to ten days after fertilization. If the zygote has not implanted by day ten, implantation becomes increasingly unlikely in subsequent days.A chemical pregnancy is a pregnancy that was detected by testing but ends in miscarriage before or around the time of the next expected period.Chromosomal abnormalities are found in more than half of embryos miscarried in the first 13 weeks. Half of embryonic miscarriages (25% of all miscarriages) have an aneuploidy (abnormal number of chromosomes). Common chromosome abnormalities found in miscarriages include an autosomal trisomy (22–32%), monosomy X (5–20%), triploidy (6–8%), tetraploidy (2–4%), or other structural chromosomal abnormalities (2%). Genetic problems are more likely to occur with older parents; this may account for the higher rates observed in older women.Luteal phase progesterone deficiency may or may not be a contributing factor to miscarriage. Second and third trimesters Second trimester losses may be due to maternal factors such as uterine malformation, growths in the uterus (fibroids), or cervical problems. These conditions also may contribute to premature birth. Unlike first-trimester miscarriages, second-trimester miscarriages are less likely to be caused by a genetic abnormality; chromosomal aberrations are found in a third of cases. Infection during the third trimester can cause a miscarriage. Age The age of the pregnant woman is a significant risk factor. Miscarriage rates increase steadily with age, with more substantial increases after age 35. In those under the age of 35 the risk is about 10% while it is about 45% in those over the age of 40. Risk begins to increase around the age of 30. Paternal age is associated with increased risk. Obesity, eating disorders and caffeine Not only is obesity associated with miscarriage; it can result in sub-fertility and other adverse pregnancy outcomes. Recurrent miscarriage is also related to obesity. Women with bulimia nervosa and anorexia nervosa may have a greater risk for miscarriage. Nutrient deficiencies have not been found to impact miscarriage rates but hyperemesis gravidarum sometimes precedes a miscarriage.Caffeine consumption also has been correlated to miscarriage rates, at least at higher levels of intake. However, such higher rates are statistically significant only in certain circumstances. Vitamin supplementation has generally not shown to be effective in preventing miscarriage. Chinese traditional medicine has not been found to prevent miscarriage. Endocrine disorders Disorders of the thyroid may affect pregnancy outcomes. Related to this, iodine deficiency is strongly associated with an increased risk of miscarriage. The risk of miscarriage is increased in those with poorly controlled insulin-dependent diabetes mellitus. Women with well-controlled diabetes have the same risk of miscarriage as those without diabetes. Food poisoning Ingesting food that has been contaminated with listeriosis, toxoplasmosis, and salmonella is associated with an increased risk of miscarriage. Amniocentesis and chorionic villus sampling Amniocentesis and chorionic villus sampling (CVS) are procedures conducted to assess the fetus. A sample of amniotic fluid is obtained by the insertion of a needle through the abdomen and into the uterus. Chorionic villus sampling is a similar procedure with a sample of tissue removed rather than fluid. These procedures are not associated with pregnancy loss during the second trimester but they are associated with miscarriages and birth defects in the first trimester. Miscarriage caused by invasive prenatal diagnosis (chorionic villus sampling (CVS) and amniocentesis) is rare (about 1%). Surgery The effects of surgery on pregnancy are not well-known including the effects of bariatric surgery. Abdominal and pelvic surgery are not risk factors for miscarriage. Ovarian tumours and cysts that are removed have not been found to increase the risk of miscarriage. The exception to this is the removal of the corpus luteum from the ovary. This can cause fluctuations in the hormones necessary to maintain the pregnancy. Medications There is no significant association between antidepressant medication exposure and spontaneous abortion. The risk of miscarriage is not likely decreased by discontinuing SSRIs prior to pregnancy. Some available data suggest that there is a small increased risk of miscarriage for women taking any antidepressant, though this risk becomes less statistically significant when excluding studies of poor quality.Medicines that increase the risk of miscarriage include: retinoids nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen misoprostol methotrexate statins Immunizations Immunizations have not been found to cause miscarriage. Live vaccinations, like the MMR vaccine, can theoretically cause damage to the fetus as the live virus can cross the placenta and potentially increase the risk for miscarriage. Therefore, the Center for Disease Control (CDC) recommends against pregnant women receiving live vaccinations. However, there is no clear evidence that has shown live vaccinations to increase the risk for miscarriage or fetal abnormalities.Some live vaccinations include: MMR, varicella, certain types of the influenza vaccine, and rotavirus. Treatments for cancer Ionizing radiation levels given to a woman during cancer treatment cause miscarriage. Exposure can also impact fertility. The use of chemotherapeutic drugs used to treat childhood cancer increases the risk of future miscarriage. Pre-existing diseases Several pre-existing diseases in pregnancy can potentially increase the risk of miscarriage, including diabetes, polycystic ovary syndrome (PCOS), hypothyroidism, certain infectious diseases, and autoimmune diseases. PCOS may increase the risk of miscarriage. Two studies suggested treatment with the drug metformin significantly lowers the rate of miscarriage in women with PCOS, but the quality of these studies has been questioned. Metformin treatment in pregnancy has not been shown to be safe. In 2007 the Royal College of Obstetricians and Gynaecologists also recommended against use of the drug to prevent miscarriage. Thrombophilias or defects in coagulation and bleeding were once thought to be a risk in miscarriage but have been subsequently questioned. Severe cases of hypothyroidism increase the risk of miscarriage. The effect of milder cases of hypothyroidism on miscarriage rates has not been established. A condition called luteal phase defect (LPD) is a failure of the uterine lining to be fully prepared for pregnancy. This can keep a fertilized egg from implanting or result in miscarriage.Mycoplasma genitalium infection is associated with increased risk of preterm birth and miscarriage.Infections can increase the risk of a miscarriage: rubella (German measles), cytomegalovirus, bacterial vaginosis, HIV, chlamydia, gonorrhoea, syphilis, and malaria. Immune status Autoimmunity is a possible cause of recurrent or late-term miscarriages. In the case of an autoimmune-induced miscarriage, the womans body attacks the growing fetus or prevents normal pregnancy progression. Autoimmune disease may cause abnormalities in embryos, which in turn may lead to miscarriage. As an example, Celiac disease increases the risk of miscarriage by an odds ratio of approximately 1.4. A disruption in normal immune function can lead to the formation of antiphospholipid antibody syndrome. This will affect the ability to continue the pregnancy, and if a woman has repeated miscarriages, she can be tested for it. Approximately 15% of recurrent miscarriages are related to immunologic factors. The presence of anti-thyroid autoantibodies is associated with an increased risk with an odds ratio of 3.73 and 95% confidence interval 1.8–7.6. Having lupus also increases the risk for miscarriage. Immunohistochemical studies on decidual basalis and chorionic villi found that the imbalance of the immunological environment could be associated with recurrent pregnancy loss. Anatomical defects and trauma Fifteen per cent of women who have experienced three or more recurring miscarriages have some anatomical defect that prevents the pregnancy from being carried for the entire term. The structure of the uterus affects the ability to carry a child to term. Anatomical differences are common and can be congenital. In some women, cervical incompetence or cervical insufficiency occurs with the inability of the cervix to stay closed during the entire pregnancy. It does not cause first trimester miscarriages. In the second trimester, it is associated with an increased risk of miscarriage. It is identified after a premature birth has occurred at about 16–18 weeks into the pregnancy. During the second trimester, major trauma can result in a miscarriage. Smoking Tobacco (cigarette) smokers have an increased risk of miscarriage. There is an increased risk regardless of which parent smokes, though the risk is higher when the gestational mother smokes. Morning sickness Nausea and vomiting of pregnancy (NVP, or morning sickness) is associated with a decreased risk. Several possible causes have been suggested for morning sickness but there is still no agreement. NVP may represent a defense mechanism which discourages the mothers ingestion of foods that are harmful to the fetus; according to this model, a lower frequency of miscarriage would be an expected consequence of the different food choices made by women experiencing NVP. Chemicals and occupational exposure Chemical and occupational exposures may have some effect in pregnancy outcomes. A cause and effect relationship almost can never be established. Those chemicals that are implicated in increasing the risk for miscarriage are DDT, lead, formaldehyde, arsenic, benzene and ethylene oxide. Video display terminals and ultrasound have not been found to have an effect on the rates of miscarriage. In dental offices where nitrous oxide is used with the absence of anesthetic gas scavenging equipment, there is a greater risk of miscarriage. For women who work with cytotoxic antineoplastic chemotherapeutic agents there is a small increased risk of miscarriage. No increased risk for cosmetologists has been found. Other Alcohol increases the risk of miscarriage. Cocaine use increases the rate of miscarriage. Some infections have been associated with miscarriage. These include Ureaplasma urealyticum, Mycoplasma hominis, group B streptococci, HIV-1, and syphilis. Infections of Chlamydia trachomatis, Camphylobacter fetus, and Toxoplasma gondii have not been found to be linked to miscarriage. Subclinical infections of the lining of the womb, commonly known as chronic endometritis are also associated with poor pregnancy outcomes, compared to women with treated chronic endometritis or no chronic endometritis. Diagnosis In the case of blood loss, pain, or both, transvaginal ultrasound is performed. If a viable intrauterine pregnancy is not found with ultrasound, blood tests (serial βHCG tests) can be performed to rule out ectopic pregnancy, which is a life-threatening situation.If hypotension, tachycardia, and anemia are discovered, exclusion of an ectopic pregnancy is important.A miscarriage may be confirmed by an obstetric ultrasound and by the examination of the passed tissue. When looking for microscopic pathologic symptoms, one looks for the products of conception. Microscopically, these include villi, trophoblast, fetal parts, and background gestational changes in the endometrium. When chromosomal abnormalities are found in more than one miscarriage, genetic testing of both parents may be done. Ultrasound criteria A review article in The New England Journal of Medicine based on a consensus meeting of the Society of Radiologists in Ultrasound in America (SRU) has suggested that miscarriage should be diagnosed only if any of the following criteria are met upon ultrasonography visualization: Classification A threatened miscarriage is any bleeding during the first half of pregnancy. At investigation it may be found that the fetus remains viable and the pregnancy continues without further problems.An anembryonic pregnancy (also called an "empty sac" or "blighted ovum") is a condition where the gestational sac develops normally, while the embryonic part of the pregnancy is either absent or stops growing very early. This accounts for approximately half of miscarriages. All other miscarriages are classified as embryonic miscarriages, meaning that there is an embryo present in the gestational sac. Half of embryonic miscarriages have aneuploidy (an abnormal number of chromosomes).An inevitable miscarriage occurs when the cervix has already dilated, but the fetus has yet to be expelled. This usually will progress to a complete miscarriage. The fetus may or may not have cardiac activity. A complete miscarriage is when all products of conception have been expelled; these may include the trophoblast, chorionic villi, gestational sac, yolk sac, and fetal pole (embryo); or later in pregnancy the fetus, umbilical cord, placenta, amniotic fluid, and amniotic membrane. The presence of a pregnancy test that is still positive, as well as an empty uterus upon transvaginal ultrasonography, does, however, fulfil the definition of pregnancy of unknown location. Therefore, there may be a need for follow-up pregnancy tests to ensure that there is no remaining pregnancy, including ectopic pregnancy. An incomplete miscarriage occurs when some products of conception have been passed, but some remains inside the uterus. However, an increased distance between the uterine walls on transvaginal ultrasonography may also simply be an increased endometrial thickness and/or a polyp. The use of a Doppler ultrasound may be better in confirming the presence of significant retained products of conception in the uterine cavity. In cases of uncertainty, ectopic pregnancy must be excluded using techniques like serial beta-hCG measurements. A missed miscarriage is when the embryo or fetus has died, but a miscarriage has not yet occurred. It is also referred to as delayed miscarriage, silent miscarriage, or missed abortion.A septic miscarriage occurs when the tissue from a missed or incomplete miscarriage becomes infected, which carries the risk of spreading infection (septicaemia) and can be fatal.Recurrent miscarriage ("recurrent pregnancy loss" (RPL) or "habitual abortion") is the occurrence of multiple consecutive miscarriages; the exact number used to diagnose recurrent miscarriage varies. If the proportion of pregnancies ending in miscarriage is 15% and assuming that miscarriages are independent events, then the probability of two consecutive miscarriages is 2.25% and the probability of three consecutive miscarriages is 0.34%. The occurrence of recurrent pregnancy loss is 1%. A large majority (85%) of those who have had two miscarriages will conceive and carry normally afterward.The physical symptoms of a miscarriage vary according to the length of pregnancy, though most miscarriages cause pain or cramping. The size of blood clots and pregnancy tissue that are passed become larger with longer gestations. After 13 weeks gestation, there is a higher risk of placenta retention. Prevention Prevention of a miscarriage can sometimes be accomplished by decreasing risk factors. This may include good prenatal care, avoiding drugs and alcohol, preventing infectious diseases, and avoiding x-rays. Identifying the cause of the miscarriage may help prevent future pregnancy loss, especially in cases of recurrent miscarriage. Often there is little a person can do to prevent a miscarriage. Vitamin supplementation before or during pregnancy has not been found to affect the risk of miscarriage. Progesterone has been shown to prevent miscarriage in women with 1) vaginal bleeding early in their current pregnancy and 2) a previous history of miscarriage. Non-modifiable risk factors Preventing a miscarriage in subsequent pregnancies may be enhanced with assessments of: Modifiable risk factors Maintaining a healthy weight and good prenatal care can reduce the risk of miscarriage. Some risk factors can be minimized by avoiding the following: Smoking Cocaine use Alcohol Poor nutrition Occupational exposure to agents that can cause miscarriage Medications associated with miscarriage Drug abuse Management Women who miscarry early in their pregnancy usually do not require any subsequent medical treatment but they can benefit from support and counseling. Most early miscarriages will complete on their own; in other cases, medication treatment or aspiration of the products of conception can be used to remove remaining tissue. While bed rest has been advocated to prevent miscarriage, this has not been found to be of benefit. Those who are experiencing or who have experienced a miscarriage benefit from the use of careful medical language. Significant distress can often be managed by the ability of the clinician to clearly explain terms without suggesting that the woman or couple are somehow to blame.Evidence to support Rho(D) immune globulin after a spontaneous miscarriage is unclear. In the UK, Rho(D) immune globulin is recommended in Rh-negative women after 12 weeks gestational age and before 12 weeks gestational age in those who need surgery or medication to complete the miscarriage. Methods No treatment is necessary for a diagnosis of complete miscarriage (so long as ectopic pregnancy is ruled out). In cases of an incomplete miscarriage, empty sac, or missed abortion there are three treatment options: watchful waiting, medical management, and surgical treatment. With no treatment (watchful waiting), most miscarriages (65–80%) will pass naturally within two to six weeks. This treatment avoids the possible side effects and complications of medications and surgery, but increases the risk of mild bleeding, need for unplanned surgical treatment, and incomplete miscarriage. Medical treatment usually consists of using misoprostol (a prostaglandin) alone or in combination with mifepristone pre-treatment. These medications help the uterus to contract and expel the remaining tissue out of the body. This works within a few days in 95% of cases. Vacuum aspiration or sharp curettage can be used, with vacuum aspiration being lower-risk and more common. Delayed and incomplete miscarriage In delayed or incomplete miscarriage, treatment depends on the amount of tissue remaining in the uterus. Treatment can include surgical removal of the tissue with vacuum aspiration or misoprostol. Studies looking at the methods of anaesthesia for surgical management of incomplete miscarriage have not shown that any adaptation from normal practice is beneficial. Induced miscarriage An induced abortion may be performed by a qualified healthcare provider for women who cannot continue the pregnancy. Self-induced abortion performed by a woman or non-medical personnel can be dangerous and is still a cause of maternal mortality in some countries. In some locales it is illegal or carries heavy social stigma. However, in the United States, many choose to self-induce or self-manage their abortion and have done so safely. Sex Some organizations recommend delaying sex after a miscarriage until the bleeding has stopped to decrease the risk of infection. However, there is not sufficient evidence for the routine use of antibiotic to try to avoid infection in incomplete abortion. Others recommend delaying attempts at pregnancy until one period has occurred to make it easier to determine the dates of a subsequent pregnancy. There is no evidence that getting pregnant in that first cycle affects outcomes and an early subsequent pregnancy may actually improve outcomes. Support Organizations exist that provide information and counselling to help those who have had a miscarriage. Family and friends often conduct a memorial or burial service. Hospitals also can provide support and help memorialize the event. Depending on locale others desire to have a private ceremony. Providing appropriate support with frequent discussions and sympathetic counselling are part of evaluation and treatment. Those who experience unexplained miscarriage can be treated with emotional support. Miscarriage leave Miscarriage leave is leave of absence in relation to miscarriage. The following countries offer paid or unpaid leave to women who have had a miscarriage. The Philippines – 60 days fully paid leave for miscarriages (before 20 weeks of gestation) or emergency termination of the pregnancy (on the 20th week or after) The husband of the mother gets seven days fully paid leave up to the 4th pregnancy. India – six weeks leave New Zealand – three days bereavement leave for both parents Mauritius – two weeks leave Indonesia – six weeks leave Taiwan – five days, one week or four weeks, depending on how advanced the pregnancy was Outcomes Psychological and emotional effects Every womans personal experience of miscarriage is different, and women who have more than one miscarriage may react differently to each event.In Western cultures since the 1980s, medical providers assume that experiencing a miscarriage "is a major loss for all pregnant women". A miscarriage can result in anxiety, depression or stress for those involved. It can have an effect on the whole family. Many of those experiencing a miscarriage go through a grieving process. "Prenatal attachment" often exists that can be seen as parental sensitivity, love and preoccupation directed toward the unborn child. Serious emotional impact is usually experienced immediately after the miscarriage. Some may go through the same loss when an ectopic pregnancy is terminated. In some, the realization of the loss can take weeks. Providing family support to those experiencing the loss can be challenging because some find comfort in talking about the miscarriage while others may find the event painful to discuss. The father can have the same sense of loss. Expressing feelings of grief and loss can sometimes be harder for men. Some women are able to begin planning their next pregnancy after a few weeks of having the miscarriage. For others, planning another pregnancy can be difficult. Some facilities acknowledge the loss. Parents can name and hold their infant. They may be given mementos such as photos and footprints. Some conduct a funeral or memorial service. They may express the loss by planting a tree.Some health organizations recommend that sexual activity be delayed after the miscarriage. The menstrual cycle should resume after about three to four months. Women report that they were dissatisfied with the care they received from physicians and nurses. Subsequent pregnancies Some parents want to try to have a baby very soon after the miscarriage. The decision of trying to become pregnant again can be difficult. Reasons exist that may prompt parents to consider another pregnancy. For older mothers, there may be some sense of urgency. Other parents are optimistic that future pregnancies are likely to be successful. Many are hesitant and want to know about the risk of having another or more miscarriages. Some clinicians recommend that the women have one menstrual cycle before attempting another pregnancy. This is because the date of conception may be hard to determine. Also, the first menstrual cycle after a miscarriage can be much longer or shorter than expected. Parents may be advised to wait even longer if they have experienced late miscarriage or molar pregnancy, or are undergoing tests. Some parents wait for six months based upon recommendations from their health care provider.The risks of having another miscarriage vary according to the cause. The risk of having another miscarriage after a molar pregnancy is very low. The risk of another miscarriage is highest after the third miscarriage. Pre-conception care is available in some locales. Later cardiovascular disease There is a significant association between miscarriage and later development of coronary artery disease, but not of cerebrovascular disease. Epidemiology Among women who know they are pregnant, the miscarriage rate is roughly 10% to 20%, while rates among all fertilized zygotes are around 30% to 50%. A 2012 review found the risk of miscarriage between 5 and 20 weeks from 11% to 22%. Up to the 13th week of pregnancy, the risk of miscarriage each week was around 2%, dropping to 1% in week 14 and reducing slowly between 14 and 20 weeks.The precise rate is not known because a large number of miscarriages occur before pregnancies become established and before the woman is aware she is pregnant. Additionally, those with bleeding in early pregnancy may seek medical care more often than those not experiencing bleeding. Although some studies attempt to account for this by recruiting women who are planning pregnancies and testing for very early pregnancy, they still are not representative of the wider population.The prevalence of miscarriage increases with the age of both parents. In a Danish register-based study where the prevalence of miscarriage was 11%, the prevalence rose from
Miscarriage	9% at 22 years of age to 84% by 48 years of age. Another, later study in 2013 found that when either parent was over the age of 40, the rate of known miscarriages doubled.In 2010, 50,000 inpatient admissions for miscarriage occurred in the UK. Terminology Most affected women and family members refer to miscarriage as the loss of a baby, rather than an embryo or fetus, and healthcare providers are expected to respect and use the language that the person chooses. Clinical terms can suggest blame, increase distress, and even cause anger. Terms that are known to cause distress in those experiencing miscarriage include: abortion (including spontaneous abortion) rather than miscarriage, habitual aborter rather than a woman experiencing recurrent pregnancy loss, products of conception rather than baby, blighted ovum rather than early pregnancy loss or delayed miscarriage, cervical incompetence rather than cervical weakness, and evacuation of retained products of conception (ERPC) rather than surgical management of miscarriage.Pregnancy loss is a broad term that is used for miscarriage, ectopic and molar pregnancies. The term fetal death applies variably in different countries and contexts, sometimes incorporating weight, and gestational age from 16 weeks in Norway, 20 weeks in the US and Australia, 24 weeks in the UK to 26 weeks in Italy and Spain. A fetus that died before birth after this gestational age may be referred to as a stillbirth. Under UK law, all stillbirths should be registered, although this does not apply to miscarriages. History The medical terminology applied to experiences during early pregnancy has changed over time. Before the 1980s, health professionals used the phrase spontaneous abortion for a miscarriage and induced abortion for a termination of the pregnancy. In the late 1980s and 1990s, doctors became more conscious of their language in relation to early pregnancy loss. Some medical authors advocated change to use of miscarriage instead of spontaneous abortion because they argued this would be more respectful and help ease a distressing experience. The change was being recommended by some in the profession in Britain in the late 1990s. In 2005 the European Society for Human Reproduction and Embryology (ESHRE) published a paper aiming to facilitate a revision of nomenclature used to describe early pregnancy events. Society and culture Societys reactions to miscarriage have changed over time. In the early 20th century, the focus was on the mothers physical health and the difficulties and disabilities that miscarriage could produce. Other reactions, such as the expense of medical treatments and relief at ending an unwanted pregnancy, were also heard. In the 1940s and 1950s, people were more likely to express relief, not because the miscarriage ended an unwanted or mistimed pregnancy, but because people believed that miscarriages were primarily caused by birth defects, and miscarrying meant that the family would not raise a child with disabilities. The dominant attitude in the mid-century was that a miscarriage, although temporarily distressing, was a blessing in disguise for the family, and that another pregnancy and a healthier baby would soon follow, especially if women trusted physicians and reduced their anxieties. Media articles were illustrated with pictures of babies, and magazine articles about miscarriage ended by introducing the healthy baby—usually a boy—that had shortly followed it.Beginning in the 1980s, miscarriage in the US was primarily framed in terms of the individual womans personal emotional reaction, and especially her grief over a tragic outcome. The subject was portrayed in the media with images of an empty crib or an isolated, grieving woman, and stories about miscarriage were published in general-interest media outlets, not just womens magazines or health magazines. Family members were encouraged to grieve, to memorialize their losses through funerals and other rituals, and to think of themselves as being parents. This shift to recognizing these emotional responses was partly due to medical and political successes, which created an expectation that pregnancies are typically planned and safe, and to womens demands that their emotional reactions no longer be dismissed by the medical establishments. It also reinforces the anti-abortion movement’s belief that human life begins at conception or early in pregnancy, and that motherhood is a desirable life goal. The modern one-size-fits-all model of grief does not fit every womans experience, and an expectation to perform grief creates unnecessary burdens for some women. The reframing of miscarriage as a private emotional experience brought less awareness of miscarriage and a sense of silence around the subject, especially compared to the public discussion of miscarriage during campaigns for access to birth control during the early 20th century, or the public campaigns to prevent miscarriages, stillbirths, and infant deaths by reducing industrial pollution during the 1970s.In places where induced abortion is illegal or carries social stigma, suspicion may surround miscarriage, complicating an already sensitive issue. In the 1960s, the use of the word miscarriage in Britain (instead of spontaneous abortion) occurred after changes in legislation. Developments in ultrasound technology (in the early 1980s) allowed them to identify earlier miscarriages.According to French statutes, an infant born before the age of viability, determined to be 28 weeks, is not registered as a child. If birth occurs after this, the infant is granted a certificate that allows women who have given birth to a stillborn child, to have a symbolic record of that child. This certificate can include a registered and given name to allow a funeral and acknowledgement of the event. Other animals Miscarriage occurs in all animals that experience pregnancy, though in such contexts it is more commonly referred to as a spontaneous abortion (the two terms are synonymous). There are a variety of known risk factors in non-human animals. For example, in sheep, miscarriage may be caused by crowding through doors, or being chased by dogs. In cows, spontaneous abortion may be caused by contagious disease, such as brucellosis or Campylobacter, but often can be controlled by vaccination. In many species of sharks and rays, stress induced miscarriage occurs frequently on capture.Other diseases are also known to make animals susceptible to miscarriage. Spontaneous abortion occurs in pregnant prairie voles when their mate is removed and they are exposed to a new male, an example of the Bruce effect, although this effect is seen less in wild populations than in the laboratory. Female mice who had spontaneous abortions showed a sharp rise in the amount of time spent with unfamiliar males preceding the abortion than those who did not. See also Pregnancy and Infant Loss Remembrance Day Citations General and cited references Hoffman, Barbara; J. Whitridge Williams (2012). Williams Gynecology (2nd ed.). New York: McGraw-Hill Medical. ISBN 978-0071716727. == External links ==
Hyperpigmentation	Hyperpigmentation is the darkening of an area of skin or nails caused by increased melanin. Causes Hyperpigmentation can be caused by sun damage, inflammation, or other skin injuries, including those related to acne vulgaris.: 854 People with darker skin tones are more prone to hyperpigmentation, especially with excess sun exposure.Many forms of hyperpigmentation are caused by an excess production of melanin. Hyperpigmentation can be diffuse or focal, affecting such areas as the face and the back of the hands. Melanin is produced by melanocytes at the lower layer of the epidermis. Melanin is a class of pigment responsible for producing color in the body in places such as the eyes, skin, and hair. The process of melanin synthesis (melanogenesis) starts with the oxidation of L-tyrosine to L-DOPA by the enzyme tyrosine hydroxylase, then to L-Dopaquinone and Dopachrome, which forms melanin.As the body ages, melanocyte distribution becomes less diffuse and its regulation less controlled by the body. UV light stimulates melanocyte activity, and where concentration of the cells is greater, hyperpigmentation occurs. Another form of hyperpigmentation is post inflammatory hyperpigmentation. These are dark and discoloured spots that appear on the skin following acne that has healed. Diseases and conditions Hyperpigmentation is associated with a number of diseases or conditions, including the following: Addisons disease and other sources of adrenal insufficiency, in which hormones that stimulate melanin synthesis, such as melanocyte-stimulating hormone (MSH), are frequently elevated. Cushings disease or other excessive adrenocorticotropic hormone (ACTH) production, because MSH production is a byproduct of ACTH synthesis from proopiomelanocortin (POMC). Acanthosis nigricans—hyperpigmentation of intertriginous areas associated with insulin resistance. Melasma, also known as chloasma or the “mask of pregnancy,” when it occurs in pregnant women.— It is a common skin problem that causes dark discolored patchy hyperpigmentation. It typically occurs on the face and is symmetrical, with matching marks on both sides of the face. The condition is much more common in women than men, though men can get it too. According to the American Academy of Dermatology, 90 percent of people who develop melasma are women. Post-Acne marks from post-inflammatory hyperpigmentation. Linea nigra—a hyperpigmented line found on the abdomen during pregnancy. Peutz–Jeghers syndrome—an autosomal dominant disorder characterized by hyperpigmented macules on the lips and oral mucosa and gastrointestinal polyps. Exposure to certain chemicals such as salicylic acid, bleomycin, and cisplatin. Smokers melanosis Coeliac disease Cronkhite–Canada syndrome Porphyria Tinea fungal infections such as ringworm. Haemochromatosis—a common but debilitating genetic disorder characterized by the chronic accumulation of iron in the body. Mercury poisoning—particularly cases of cutaneous exposure resulting from the topical application of mercurial ointments or skin-whitening creams. Aromatase deficiency Nelsons syndrome Graves disease Schimke immunoosseous dysplasia (SOID). As a result of tinea cruris. Due to B12 deficiency. Atopic dermatitis as a result of inflammation.Hyperpigmentation can sometimes be induced by dermatological laser procedures. Diagnosis A physical examination including, Woods lamp examination and a detailed history, usually sufficient for diagnosis. Skin examination. Viewing medical history. Treatment There are a wide range of depigmenting treatments used for hyperpigmentation conditions, and responses to most are variable.Most often treatment of hyperpigmentation caused by melanin overproduction (such as melasma, acne scarring, liver spots) includes the use of topical depigmenting agents, which vary in their efficacy and safety, as well as in prescription rules. Topical treatments Many topical treatments disrupt the synthesis of melanin by inhibiting the enzyme tyrosine hydroxylase.Several are prescription only in the US, especially in high doses, such as hydroquinone, azelaic acid, and kojic acid. Some are available without prescription, such as niacinamide, l-ascorbic acid, retinoids such as tretinoin, or cysteamine hydrochloride. Hydroquinone was the most commonly prescribed hyperpigmentation treatment before the long-term safety concerns were raised, and the use of it became more regulated in several countries and discouraged in general by WHO. For the US only 2% is at present sold over-the-counter, and 4% needs prescription. In the EU hydroquinone was banned from cosmetic applications. Oral Oral medication with procyanidin plus vitamins A, C, and E also shows promise as safe and effective for epidermal melasma. In an 8-week randomized, double-blind, placebo-controlled trial in 56 Filipino women, treatment was associated with significant improvements in the left and right malar regions, and was safe and well tolerated. Other treatments that do not involve topical agents are also available, including fraction lasers and dermabrasion. Laser treatments Laser toning using YAG lasers and intense pulsed light have been used to treat hyperpigmentation such as melasma and post-inflammatory hyperpigmentation. See also Hypopigmentation List of skin conditions Drug-induced pigmentation References == External links ==
Fournier gangrene	Fournier gangrene is a type of necrotizing fasciitis or gangrene affecting the external genitalia or perineum. It commonly occurs in older men, but it can also occur in women and children. It is more likely to occur in diabetics, alcoholics, or those who are immunocompromised. About one per 62,500 males are affected per year. Males are affected about 40 times more often than females. It was first described by Baurienne in 1764 and is named after a French venereologist, Jean Alfred Fournier, following five cases he presented in clinical lectures in 1883. Signs and symptoms Initial symptoms of Fournier gangrene include swelling or sudden pain in the scrotum, fever, pallor, and generalized weakness. It is characterized by pain that extends beyond the border of the demarcated erythema. Most cases present mildly, but can progress in hours. Subcutaneous air is often one of the specific clinical signs, but is not seen in >50% of presenting clinical cases. More marked cases are characterized by a foul odor and necrotic infected tissue. Crepitus has been reported. It begins as a subcutaneous infection. However, necrotic patches soon appear in the overlying skin, which later develop into necrosis. Cause Most cases of Fournier gangrene are infected with both aerobic and anaerobic bacteria such as Clostridium perfringens. It can also result from infections caused by group A streptococcus (GAS), as well as other pathogens such as Staphylococcus aureus and Vibrio vulnificus. Lack of access to sanitation, medical care, and psychosocial resources has been linked to increased mortality.A 2006 Turkish study reported that blood sugar levels were elevated in 46 percent of patients diagnosed with Fourniers. Another study reported that about one third of patients were alcoholic, diabetic, and malnourished, while another ten percent had been immunosuppressed through chemotherapy, steroids, or malignancy.Fournier gangrene is a rare side effect of SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin), which increase the excretion of glucose in the urine. Diagnosis Fournier gangrene is usually diagnosed clinically, but laboratory tests and imaging studies are used to confirm diagnosis, determine severity, and predict outcomes. X-rays and ultrasounds may show the presence of gas below the surface of the skin. A CT scan can be useful in determining the site of origin and extent of spread. Treatment Fournier gangrene is a urological emergency requiring intravenous antibiotics and debridement (surgical removal) of dead tissue. In addition to surgery and antibiotics, hyperbaric oxygen therapy may be useful and acts to inhibit the growth of and kill the anaerobic bacteria. Multiple wound debridement may be required in cases with extensive tissue involvement. Simple reconstructive procedures following wound debridement yield satisfactory outcomes in majority of the cases. Prognosis While recent case series (n=980) studies have found a mortality rate of 20–40%, a large (n=1641) 2009 study reported a mortality rate of 7.5%. Epidemiology A 2009 epidemiological study found the incidence of Fournier gangrene to be 1.6 cases per 100,000 males, in the United States. Males 50 to 79 years old had the highest rate at 3.3 per 100,000. Of 1,680 cases identified in the study, 39 were women. References External links Fournier gangrene and Jean Alfred Fournier at Who Named It?
Cerebral vasculitis	Cerebral vasculitis (sometimes the word angiitis is used instead of "vasculitis") is vasculitis (inflammation of the blood vessel wall) involving the brain and occasionally the spinal cord. It affects all of the vessels: very small blood vessels (capillaries), medium-size blood vessels (arterioles and venules), or large blood vessels (arteries and veins). If blood flow in a vessel with vasculitis is reduced or stopped, the parts of the body that receive blood from that vessel begins to die. It may produce a wide range of neurological symptoms, such as headache, skin rashes, feeling very tired, joint pains, difficulty moving or coordinating part of the body, changes in sensation, and alterations in perception, thought or behavior, as well as the phenomena of a mass lesion in the brain leading to coma and herniation. Some of its signs and symptoms may resemble multiple sclerosis. 10% have associated bleeding in the brain. Causes "Primary" angiitis/vasculitis of the central nervous system (PACNS) is said to be present if there is no underlying cause. The exact mechanism of the primary disease is unknown, but the fundamental mechanism of all vasculitides is autoimmunity. Other possible secondary causes of cerebral vasculitis are infections, systemic auto-immune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis, medications and drugs (amphetamine, cocaine and heroin), some forms of cancer (lymphomas, leukemia and lung cancer) and other forms of systemic vasculitis such as granulomatosis with polyangiitis, polyarteritis nodosa or Behçets disease. It may imitate, and is in turn imitated by, a number of other diseases that affect the blood vessels of the brain diffusely such as fibromuscular dysplasia and thrombotic thrombocytopenic purpura. Diagnosis Cerebral angiography and magnetic resonance imaging, family medical history, symptoms, a complete physical examination, and ultimately biopsy of the brain, are often required for the diagnosis. Also, many lab tests must be done for the diagnosis; tests may reveal anemia (a shortage of red blood cells), a high white blood cell count, a high platelet count, allergic reactions, immune complexes, antibodies (tools the body uses to fight off threats) and elevation of inflammatory markers. Another crucial part in the diagnosis of cerebral vasculitis is the use of imaging techniques. Techniques such as conventional digital subtraction angiography (DSA) and magnetic resonance imaging (MRI) are used to find and monitor cerebral involvement. Treatment Treatment is first with many different high-dose steroids, namely glucocorticoids. Then, if symptoms do not improve additional immunosuppression such as cyclophosphamide are added to decrease the immune systems attack on the bodys own tissues. Cerebral vasculitis is a very rare condition that is difficult to diagnose, and as a result there are significant variations in the way it is diagnosed and treated. Specific Diseases Giant cell arteritis (GCA) (Also known as temporal arteritis) Symptoms Fever general uneasiness weight loss inflammation of the muscles causing stiffness in the shoulders; neck; and/or upper arms persisting headache pain in the jaw or ear while eating double vision partial loss of vision or blind spots (on rare occasions) stroke. Diagnostic criteria Three or more of the following five criteria must be met: Age 50 years or more New developed headache Tenderness of the superficial temporal artery Elevated sedimentation rate, at least 50 mm/hour (blood test that reveals inflammatory activity) Giant cell arteritis in a biopsy specimen from the temporal artery Takayasus arteritis Symptoms Starts with nonspecific symptoms such as: Localized joint pain Fever Fatigue Headaches Rashes Weight loss Diagnosis usually does not happen until the blockage causes deficient blood flow to the extremities or to a stroke. Classification criteria Three or more of the following six criteria must be met: Age when disease starts is under 50 Decreased brachial artery pulse Systolic blood pressure differs by more than 10mmHg between arms Cramping caused by exercise in the extremities Abnormal sounds (through stethoscope) over subclavian arteries or abdominal aorta A narrowing or blockage in the aorta, its primary branches, or large arteries as seen through a radiograph of the arteries. Treatment therapy 50% of patients respond to corticosteroid therapy alone in early phases Methotrexate or Azathioprine are an alternative to corticosteroid immunosuppressants There have been studies on Mycophenolate mofetil and anti-TNF therapies In Takayasu’s arteritis it is vital to combine drug treatments often with low-dose aspirin or statin Polyarteritis nodosa (PAN) Symptoms Systemic illness with fever General feeling of discomfort or uneasiness with cause difficult to identify Weight loss Arthritis Black discoloration of skin primarily on the extremities Severe inadequate blood supply to the extremities Ischemic stroke, hemorrhages and a progressive encephalopathy with or without seizures may occur Diagnostic Criteria Three or more of the following ten criteria are required: More than 4 kg (8.8 lb) weight loss Lace-like purplish discoloration of the skin (livedo reticularis) Testicular pain Pain in a muscle or group of muscles (myalgias) Damage to peripheral nerves Elevation of blood pressure by more than 90 mmHg Creatinine serum levels greater than 1,5 mg/dl Hepatitis B or C virus antibodies An aneurysm or occlusion as shown in a pathologic arteriography Histology findings typical of PAN Treatment therapy In PAN not associated with a hepatitis virus: prednisone and cyclophosphamide therapy. In case of emergency, plasmapheresis may be tried In PAN associated with a hepatitis virus: combination therapy of prednisone along with a virustatic, such as lamivudine (Hepatitis B) or interferon-alpha and ribavirin (Hepatitis C) Granulomatosis with polyangiitis (GPA) Symptoms Men are affected twice as often as women Compression of structures surrounding the nose and paranasal sinuses Diabetes insipidus Abnormal protrusion of the eyeball(s) Nonseptic meningitis Affection of the lung and kidney due to destruction of the arteries and veins Ischemic stroke, hemorrhages, or encephalopathy with possible seizures Diagnostic Criteria Two or more of the following four criteria are required: Necrotizing ulcerating inflammation of nose, sinuses, mouth or pharynx Irregular lung infiltrates Nephritis Granulomatous vascular and perivascular inflammation Treatment Therapy Corticosteroids (e.g., Prednisolone) Cyclophosphamide Azathioprine Mycophenolate mofetil References == External links ==
Human skin color	Human skin color ranges from the darkest brown to the lightest hues. Differences in skin color among individuals is caused by variation in pigmentation, which is the result of genetics (inherited from ones biological parents and or individual gene alleles), exposure to the sun, natural and sexual selection, or all of these. Differences across populations evolved through natural or sexual selection, because of social norms and differences in environment, as well as regulations of the biochemical effects of ultraviolet radiation penetrating the skin.The actual skin color of different humans is affected by many substances, although the single most important substance is the pigment melanin. Melanin is produced within the skin in cells called melanocytes and it is the main determinant of the skin color of darker-skin humans. The skin color of people with light skin is determined mainly by the bluish-white connective tissue under the dermis and by the hemoglobin circulating in the veins of the dermis. The red color underlying the skin becomes more visible, especially in the face, when, as consequence of physical exercise or sexual arousal, or the stimulation of the nervous system (anger, embarrassment), arterioles dilate. Color is not entirely uniform across an individuals skin; for example, the skin of the palm and the sole is lighter than most other skin, and this is especially noticeable in darker-skinned people.There is a direct correlation between the geographic distribution of ultraviolet radiation (UVR) and the distribution of indigenous skin pigmentation around the world. Areas that receive higher amounts of UVR, generally located closer to the equator, tend to have darker-skinned populations. Areas that are far from the tropics and closer to the poles have lower intensity of UVR, which is reflected in lighter-skinned populations. Some researchers suggest that human populations over the past 50,000 years have changed from dark-skinned to light-skinned and vice versa as they migrated to different UV zones, and that such major changes in pigmentation may have happened in as little as 100 generations (≈2,500 years) through selective sweeps. Natural skin color can also darken as a result of tanning due to exposure to sunlight. The leading theory is that skin color adapts to intense sunlight irradiation to provide partial protection against the ultraviolet fraction that produces damage and thus mutations in the DNA of the skin cells. In addition, it has been observed that females on average are significantly lighter in skin pigmentation than males. Females need more calcium during pregnancy and lactation. The body synthesizes vitamin D from sunlight, which helps it absorb calcium. Females evolved to have lighter skin so their bodies absorb more calcium.The social significance of differences in skin color has varied across cultures and over time, as demonstrated with regard to social status and discrimination. Melanin and genes Melanin is produced by cells called melanocytes in a process called melanogenesis. Melanin is made within small membrane–bound packages called melanosomes. As they become full of melanin, they move into the slender arms of melanocytes, from where they are transferred to the keratinocytes. Under normal conditions, melanosomes cover the upper part of the keratinocytes and protect them from genetic damage. One melanocyte supplies melanin to thirty-six keratinocytes according to signals from the keratinocytes. They also regulate melanin production and replication of melanocytes. People have different skin colors mainly because their melanocytes produce different amount and kinds of melanin. The genetic mechanism behind human skin color is mainly regulated by the enzyme tyrosinase, which creates the color of the skin, eyes, and hair shades. Differences in skin color are also attributed to differences in size and distribution of melanosomes in the skin. Melanocytes produce two types of melanin. The most common form of biological melanin is eumelanin, a brown-black polymer of dihydroxyindole carboxylic acids, and their reduced forms. Most are derived from the amino acid tyrosine. Eumelanin is found in hair, areola, and skin, and the hair colors gray, black, blond, and brown. In humans, it is more abundant in people with dark skin. Pheomelanin, a pink to red hue is found in particularly large quantities in red hair, the lips, nipples, glans of the penis, and vagina.Both the amount and type of melanin produced is controlled by a number of genes that operate under incomplete dominance. One copy of each of the various genes is inherited from each parent. Each gene can come in several alleles, resulting in the great variety of human skin tones. Melanin controls the amount of ultraviolet (UV) radiation from the sun that penetrates the skin by absorption. While UV radiation can assist in the production of vitamin D, excessive exposure to UV can damage health. Evolution of skin color Loss of body hair in Hominini species is assumed to be related to the emergence of bipedalism some 5 to 7 million years ago. Bipedal hominin body hair may have disappeared gradually to allow better heat dissipation through sweating. The emergence of skin pigmentation dates to about 1.2 million years ago, under conditions of a megadrought that drove early humans into arid, open landscapes. Such conditions likely caused excess UV-B radiation. This favored the emergence of skin pigmentation in order to protect from folate depletion due to the increased exposure to sunlight. A theory that the pigmentation helped counter xeric stress by increasing the epidermal permeability barrier has been disproved.With the evolution of hairless skin, abundant sweat glands, and skin rich in melanin, early humans could walk, run, and forage for food for long periods of time under the hot sun without brain damage due to overheating, giving them an evolutionary advantage over other species. By 1.2 million years ago, around the time of Homo ergaster, archaic humans (including the ancestors of Homo sapiens) had exactly the same receptor protein as modern sub-Saharan Africans.This was the genotype inherited by anatomically modern humans, but retained only by part of the extant populations, thus forming an aspect of human genetic variation. About 100,000–70,000 years ago, some anatomically modern humans (Homo sapiens) began to migrate away from the tropics to the north where they were exposed to less intense sunlight. This was possibly in part due to the need for greater use of clothing to protect against the colder climate. Under these conditions there was less photodestruction of folate and so the evolutionary pressure working against the survival of lighter-skinned gene variants was reduced. In addition, lighter skin is able to generate more vitamin D (cholecalciferol) than darker skin, so it would have represented a health benefit in reduced sunlight if there were limited sources of vitamin D. Hence the leading hypothesis for the evolution of human skin color proposes that: From about 1.2 million years ago to less than 100,000 years ago, archaic humans, including archaic Homo sapiens, were dark-skinned. As Homo sapiens populations began to migrate, the evolutionary constraint keeping skin dark decreased proportionally to the distance north a population migrated, resulting in a range of skin tones within northern populations. At some point, some northern populations experienced positive selection for lighter skin due to the increased production of vitamin D from sunlight and the genes for darker skin disappeared from these populations. Subsequent migrations into different UV environments and admixture between populations have resulted in the varied range of skin pigmentations we see today.The genetic mutations leading to light skin, though partially different among East Asians and Western Europeans, suggest the two groups experienced a similar selective pressure after settlement in northern latitudes.The theory is partially supported by a study into the SLC24A5 gene which found that the allele associated with light skin in Europe "determined […] that 18,000 years had passed since the light-skin allele was fixed in Europeans" but may have originated as recently as 12,000–6,000 years ago "given the imprecision of method", which is in line with the earliest evidence of farming.Research by Nina Jablonski suggests that an estimated time of about 10,000 to 20,000 years is enough for human populations to achieve optimal skin pigmentation in a particular geographic area but that development of ideal skin coloration may happen faster if the evolutionary pressure is stronger, even in as little as 100 generations. The length of time is also affected by cultural practices such as food intake, clothing, body coverings, and shelter usage which can alter the ways in which the environment affects populations.One of the most recently proposed drivers of the evolution of skin pigmentation in humans is based on research that shows a superior barrier function in darkly pigmented skin. Most protective functions of the skin, including the permeability barrier and the antimicrobial barrier, reside in the stratum corneum (SC) and the researchers surmise that the SC has undergone the most genetic change since the loss of human body hair. Natural selection would have favored mutations that protect this essential barrier; one such protective adaptation is the pigmentation of interfollicular epidermis, because it improves barrier function as compared to non-pigmented skin. In lush rainforests, however, where UV-B radiation and xeric stress were not in excess, light pigmentation would not have been nearly as detrimental. This explains the side-by-side residence of lightly pigmented and darkly pigmented peoples.Population and admixture studies suggest a three-way model for the evolution of human skin color, with dark skin evolving in early hominids in Africa and light skin evolving partly separately at least two times after modern humans had expanded out of Africa.For the most part, the evolution of light skin has followed different genetic paths in Western and Eastern Eurasian populations. Two genes however, KITLG and ASIP, have mutations associated with lighter skin that have high frequencies in Eurasian populations and have estimated origin dates after humans spread out of Africa but before the divergence of the two lineages. Genetics The understanding of the genetic mechanisms underlying human skin color variation is still incomplete; however, genetic studies have discovered a number of genes that affect human skin color in specific populations, and have shown that this happens independently of other physical features such as eye and hair color. Different populations have different allele frequencies of these genes, and it is the combination of these allele variations that bring about the complex, continuous variation in skin coloration we can observe today in modern humans. Population and admixture studies suggest a 3-way model for the evolution of human skin color, with dark skin evolving in early hominids in sub-Saharan Africa and light skin evolving independently in Europe and East Asia after modern humans had expanded out of Africa.For skin color, the broad sense heritability (defined as the overall effect of genetic vs. nongenetic factors) is very high, provided one is able to control for the most important nongenetic factor, exposure to sunlight. Many aspects of the evolution of human skin and skin color can be reconstructed using comparative anatomy, physiology, and genomics. Enhancement of thermal sweating was a key innovation in human evolution that allowed maintenance of homeostasis (including constant brain temperature) during sustained physical activity in hot environments. Dark skin evolved pari passu with the loss of body hair and was the original state for the genus Homo. Melanin pigmentation is adaptive and has been maintained by natural selection. In recent prehistory, humans became adept at protecting themselves from the environment through clothing and shelter, thus reducing the scope for the action of natural selection on human skin. Credit for describing the relationship between latitude and skin color in modern humans is usually ascribed to an Italian geographer, Renato Basutti, whose widely reproduced "skin color maps" illustrate the correlation of darker skin with equatorial proximity. More recent studies by physical anthropologists have substantiated and extended these observations; a recent review and analysis of data from more than 100 populations (Relethford 1997) found that skin reflectance is lowest at the equator, then gradually increases, about 8% per 10° of latitude in the Northern Hemisphere and about 4% per 10° of latitude in the Southern Hemisphere. This pattern is inversely correlated with levels of UV irradiation, which are greater in the Southern than in the Northern Hemisphere. An important caveat is that we do not know how patterns of UV irradiation have changed over time; more importantly, we do not know when skin color is likely to have evolved, with multiple migrations out of Africa and extensive genetic interchange over the last 500,000 years (Templeton 2002).Regardless, most anthropologists accept the notion that differences in UV irradiation have driven selection for dark human skin at the equator and for light human skin at greater latitudes. What remains controversial are the exact mechanisms of selection. The most popular theory posits that protection offered by dark skin from UV irradiation becomes a liability in more polar latitudes due to vitamin D deficiency (Murray 1934). UVB (short-wavelength UV) converts 7-dehydrocholesterol into an essential precursor of cholecaliferol (vitamin D3); when not otherwise provided by dietary supplements, deficiency for vitamin D causes rickets, a characteristic pattern of growth abnormalities and bony deformities. An oft-cited anecdote in support of the vitamin D hypothesis is that Arctic populations whose skin is relatively dark given their latitude, such as the Inuit and the Lapp, have had a diet that is historically rich in vitamin D. Sensitivity of modern humans to vitamin D deficiency is evident from the widespread occurrence of rickets in 19th-century industrial Europe, but whether dark-skinned humans migrating to polar latitudes tens or hundreds of thousands of years ago experienced similar problems is open to question. In any case, a risk for vitamin D deficiency can only explain selection for light skin. Among several mechanisms suggested to provide a selective advantage for dark skin in conditions of high UV irradiation (Loomis 1967; Robins 1991; Jablonski and Chaplin 2000), the most tenable are protection from sunburn and skin cancer due to the physical barrier imposed by epidermal melanin. Dark skin All modern humans share a common ancestor who lived around 200,000 years ago in Africa. Comparisons between known skin pigmentation genes in chimpanzees and modern Africans show that dark skin evolved along with the loss of body hair about 1.2 million years ago and that this common ancestor had dark skin. Investigations into dark-skinned populations in South Asia and Melanesia indicate that skin pigmentation in these populations is due to the preservation of this ancestral state and not due to new variations on a previously lightened population. MC1R The melanocortin 1 receptor (MC1R) gene is primarily responsible for determining whether pheomelanin and eumelanin are produced in the human body. Research shows at least 10 differences in MC1R between African and chimpanzee samples and that the gene has probably undergone a strong positive selection (a selective sweep) in early Hominins around 1.2 million years ago. This is consistent with positive selection for the high-eumelanin phenotype seen in Africa and other environments with high UV exposure. Light skin For the most part, the evolution of light skin has followed different genetic paths in European and East Asian populations. Two genes, however, KITLG and ASIP, have mutations associated with lighter skin that have high frequencies in both European and East Asian populations. They are thought to have originated after humans spread out of Africa but before the divergence of the European and Asian lineages around 30,000 years ago. Two subsequent genome-wide association studies found no significant correlation between these genes and skin color, and suggest that the earlier findings may have been the result of incorrect correction methods and small panel sizes, or that the genes have an effect too small to be detected by the larger studies. KITLG The KIT ligand (KITLG) gene is involved in the permanent survival, proliferation and migration of melanocytes. A mutation in this gene, A326G (rs642742), has been positively associated with variations of skin color in African-Americans of mixed West African and European descent and is estimated to account for 15–20% of the melanin difference between African and European populations. This allele shows signs of strong positive selection outside Africa and occurs in over 80% of European and Asian samples, compared with less than 10% in African samples. ASIP Agouti signalling peptide (ASIP) acts as an inverse agonist, binding in place of alpha-MSH and thus inhibiting eumelanin production. Studies have found two alleles in the vicinity of ASIP are associated with skin color variation in humans. One, rs2424984, has been identified as an indicator of skin reflectance in a forensics analysis of human phenotypes across Caucasian, African-American, South Asian, East Asian, Hispanic and Native American populations and is about three times more common in non-African populations than in Africa. The other allele, 8188G (rs6058017) is significantly associated with skin color variation in African-Americans and the ancestral version occurs in only 12% of European and 28% of East Asian samples compared with 80% of West African samples. Europe A number of genes have been positively associated with the skin pigmentation difference between European and non-European populations. Mutations in SLC24A5 and SLC45A2 are believed to account for the bulk of this variation and show very strong signs of selection. A variation in TYR has also been identified as a contributor. Research indicates the selection for the light-skin alleles of these genes in Europeans is comparatively recent, having occurred later than 20,000 years ago and perhaps as recently as 12,000 to 6,000 years ago. In the 1970s, Luca Cavalli-Sforza suggested that the selective sweep that rendered light skin ubiquitous in Europe might be correlated with the advent of farming and thus have taken place only around 6,000 years ago; This scenario found support in a 2014 analysis of mesolithic (7,000 years old) hunter-gatherer DNA from La Braña, Spain, which showed a version of these genes not corresponding with light skin color. In 2015 researchers analysed for light skin genes in the DNA of 94 ancient skeletons ranging from 8,000 to 3,000 years old from Europe and Russia. They found c. 8,000-year-old hunter-gatherers in Spain, Luxembourg, and Hungary were dark skinned while similarly aged hunter gatherers in Sweden were light skinned (having predominately derived alleles of SLC24A5, SLC45A2 and also HERC2/OCA2). Neolithic farmers entering Europe at around the same time were intermediate, being nearly fixed for the derived SLC24A5 variant but only having the derived SLC45A2 allele in low frequencies. The SLC24A5 variant spread very rapidly throughout central and southern Europe from about 8,000 years ago, whereas the light skin variant of SLC45A2 spread throughout Europe after 5,800 years ago. SLC24A5 Solute carrier family 24 member 5 (SLC24A5) regulates calcium in melanocytes and is important in the process of melanogenesis. The SLC24A5 genes derived Ala111Thr allele (rs1426654) has been shown to be a major factor in light skin pigmentation and is common in Western Eurasia. Recent studies have found that the variant represents as much as 25–40% of the average skin tone difference between Europeans and West Africans. This derived allele is a reliable predictor of phenotype across a range of populations. It has been the subject of recent selection in Western Eurasia, and is fixed in European populations. SLC45A2 Solute carrier family 45 member 2 (SLC45A2 or MATP) aids in the transport and processing of tyrosine, a precursor to melanin. It has also been shown to be one of the significant components of the skin color of modern Europeans through its Phe374Leu (rs16891982) allele that has been directly correlated with skin color variation across a range of populations. This variation is ubiquitous in European populations but extremely rare elsewhere and shows strong signs of selection. TYR The TYR gene encodes the enzyme tyrosinase, which is involved in the production of melanin from tyrosine. It has an allele, Ser192Tyr (rs1042602), found solely in 40–50% of Europeans and linked to light-colored skin in studies of South Asian and African-American populations. East Asia A number of genes known to affect skin color have alleles that show signs of positive selection in East Asian populations. Of these, only OCA2 has been directly related to skin color measurements, while DCT, MC1R and ATRN are marked as candidate genes for future study. OCA2 Oculocutaneous albinism II (OCA2) assists in the regulation of pH in melanocytes. The OCA2 genes derived His615Arg (rs1800414) allele has been shown to account for about 8% of the skin tone difference between African and East Asian populations in studies of an East Asian population living in Toronto and a Chinese Han population. This variant is essentially restricted to East Asia, with highest frequencies in Eastern East Asia (49–63%), midrange frequencies in Southeast Asia, and the lowest frequencies in Western China and some Eastern European populations. Candidate genes A number of studies have found genes linked to human skin pigmentation that have alleles with statistically significant frequencies in Chinese and East Asian populations. While not linked to measurements of skin tone variation directly, dopachrome tautomerase (DCT or TYRP2 rs2031526), melanocortin 1 receptor (MC1R) Arg163Gln (rs885479) and attractin (ATRN) have been indicated as potential contributors to the evolution of light skin in East Asian populations. Tanning response Tanning response in humans is controlled by a variety of genes. MC1R variants Arg151Sys (rs1805007), Arg160Trp (rs1805008), Asp294Sys (rs1805009), Val60Leu (rs1805005) and Val92Met (rs2228479) have been associated with reduced tanning response in European and/or East Asian populations. These alleles show no signs of positive selection and only occur in relatively small numbers, reaching a peak in Europe with around 28% of the population having at least one allele of one of the variations. A study of self-reported tanning ability and skin type in American non-Hispanic Caucasians found that SLC24A5 Phe374Leu is significantly associated with reduced tanning ability and also associated TYR Arg402Gln (rs1126809), OCA2 Arg305Trp (rs1800401) and a 2-SNP haplotype in ASIP (rs4911414 and rs1015362) to skin type variation within a "fair/medium/olive" context. Albinism Oculocutaneous albinism (OCA) is a lack of pigment in the eyes, skin and sometimes hair that occurs in a very small fraction of the population. The four known types of OCA are caused by mutations in the TYR, OCA2, TYRP1, and SLC45A2 genes. Age In hominids, the parts of the body not covered with hair, like the face and the back of the hands, start out pale in infants and turn darker as the skin is exposed to more sun. All human babies are born pale, regardless of what their adult color will be. In humans, melanin production does not peak until after puberty.The skin of children becomes darker as they go through puberty and experience the effects of sex hormones. This darkening is especially noticeable in the skin of the nipples, the areola of the nipples, the labia majora in females, and the scrotum in males. In some people, the armpits become slightly darker during puberty. The interaction of genetic, hormonal, and environmental factors on skin coloration with age is still not adequately understood, but it is known that men are at their darkest baseline skin color around the age of 30, without considering the effects of tanning. Around the same age, women experience darkening of some areas of their skin.Human skin color fades with age. Humans over the age of thirty experience a decrease in melanin-producing cells by about 10% to 20% per decade as melanocyte stem cells gradually die. The skin of face and hands has about twice the amount of pigment cells as unexposed areas of the body, as chronic exposure to the sun continues to stimulate melanocytes. The blotchy appearance of skin color in the face and hands of older people is due to the uneven distribution of pigment cells and to changes in the interaction between melanocytes and keratinocytes. Sexual dimorphism It has been observed that females are found to have lighter skin pigmentation than males in some studied populations. This may be a form of sexual dimorphism due to the requirement in women for high amounts of calcium during pregnancy and lactation. Breastfeeding newborns, whose skeletons are growing, require high amounts of calcium intake from the mothers milk (about 4 times more than during prenatal development), part of which comes from reserves in the mothers skeleton. Adequate vitamin D resources are needed to absorb calcium from the diet, and it has been shown that deficiencies of vitamin D and calcium increase the likelihood of various birth defects such as spina bifida and rickets. Natural selection may have led to females with lighter skin than males in some indigenous populations because women must get enough vitamin D and calcium to support the development of fetus and nursing infants and to maintain their own health. However, in some populations such as in Italy, Poland, Ireland, Spain and Portugal men are found to have fairer complexions, and this has been ascribed as a cause to increased melanoma risk in men. Similarly, studies done in the late 19th Century/early 20th Century in Europe also conflicted with the notion at least in regards to Northern Europeans. The studies found that in England women tend to have darker hair, eyes, and skin complexation than men, and in particular women darken in relation to men during puberty. A study in Germany during this period showed that German men were more likely to have lighter skin, blond hair, and lighter eyes, while German women had darker hair, eyes and skin tone on average.The sexes also differ in how they change their skin color with age. Men and women are not born with different skin color, they begin to diverge during puberty with the influence of sex hormones. Women can also change pigmentation in certain parts of their body, such as the areola, during the menstrual cycle and pregnancy and between 50 and 70% of pregnant women will develop the "mask of pregnancy" (melasma or chloasma) in the cheeks, upper lips, forehead, and chin. This is caused by increases in the female hormones estrogen and progesterone and it can develop in women who take birth control pills or participate in hormone replacement therapy. Disorders of pigmentation Uneven pigmentation of some sort affects most people, regardless of bioethnic background or skin color. Skin may either appear lighter, or darker than normal, or lack pigmentation at all; there may be blotchy, uneven areas, patches of brown to gray discoloration or freckling. Apart from blood-related conditions such as jaundice, carotenosis, or argyria, skin pigmentation disorders generally occur because the body produces either too much or too little melanin. Depigmentation Albinism Some types of albinism affect only the skin and hair, while other types affect the skin, hair and eyes, and in rare cases only the eyes. All of them are caused by different genetic mutations. Albinism is a recessively inherited trait in humans where both pigmented parents may be carriers of the gene and pass it down to their children. Each child has a 25% chance of being albino and a 75% chance of having normally pigmented skin. One common type of albinism is oculocutaneous albinism or OCA, which has many subtypes caused by different genetic mutations. Albinism is a serious problem in areas of high sunlight intensity, leading to extreme sun sensitivity, skin cancer, and eye damage.Albinism is more common in some parts of the world than in others, but it is estimated that 1 in 70 humans carry the gene for OCA. The most severe type of albinism is OCA1A, which is characterized by complete, lifelong loss of melanin production, other forms of OCA1B, OCA2,
Human skin color	OCA3, OCA4, show some form of melanin accumulation and are less severe. The four known types of OCA are caused by mutations in the TYR, OCA2, TYRP1, and SLC45A2 genes. Albinos often face social and cultural challenges (even threats), as the condition is often a source of ridicule, racism, fear, and violence. Many cultures around the world have developed beliefs regarding people with albinism. Albinos are persecuted in Tanzania by witchdoctors, who use the body parts of albinos as ingredients in rituals and potions, as they are thought to possess magical power. Vitiligo Vitiligo is a condition that causes depigmentation of sections of skin. It occurs when melanocytes die or are unable to function. The cause of vitiligo is unknown, but research suggests that it may arise from autoimmune, genetic, oxidative stress, neural, or viral causes. The incidence worldwide is less than 1%. Individuals affected by vitiligo sometimes suffer psychological discomfort because of their appearance. Hyperpigmentation Increased melanin production, also known as hyperpigmentation, can be a few different phenomena: Melasma describes the darkening of the skin. Chloasma describes skin discolorations caused by hormones. These hormonal changes are usually the result of pregnancy, birth control pills or estrogen replacement therapy. Solar lentigo, also known as "liver spots" or "senile freckles", refers to darkened spots on the skin caused by aging and the sun. These spots are quite common in adults with a long history of unprotected sun exposure.Aside from sun exposure and hormones, hyperpigmentation can be caused by skin damage, such as remnants of blemishes, wounds or rashes. This is especially true for those with darker skin tones. The most typical cause of darkened areas of skin, brown spots or areas of discoloration is unprotected sun exposure. Once incorrectly referred to as liver spots, these pigment problems are not connected with the liver. On lighter to medium skin tones, solar lentigenes emerge as small- to medium-sized brown patches of freckling that can grow and accumulate over time on areas of the body that receive the most unprotected sun exposure, such as the back of the hands, forearms, chest, and face. For those with darker skin colors, these discolorations can appear as patches or areas of ashen-gray skin. Exposure to the Sun Melanin in the skin protects the body by absorbing solar radiation. In general, the more melanin there is in the skin the more solar radiation can be absorbed. Excessive solar radiation causes direct and indirect DNA damage to the skin and the body naturally combats and seeks to repair the damage and protect the skin by creating and releasing further melanin into the skins cells. With the production of the melanin, the skin color darkens, but can also cause sunburn. The tanning process can also be created by artificial UV radiation. There are two different mechanisms involved. Firstly, the UVA-radiation creates oxidative stress, which in turn oxidizes existing melanin and leads to rapid darkening of the melanin, also known as IPD (immediate pigment darkening). Secondly, there is an increase in production of melanin known as melanogenesis. Melanogenesis leads to delayed tanning and first becomes visible about 72 hours after exposure. The tan that is created by an increased melanogenesis lasts much longer than the one that is caused by oxidation of existing melanin. Tanning involves not just the increased melanin production in response to UV radiation but the thickening of the top layer of the epidermis, the stratum corneum.A persons natural skin color affects their reaction to exposure to the sun. Generally, those who start out with darker skin color and more melanin have better abilities to tan. Individuals with very light skin and albinos have no ability to tan. The biggest differences resulting from sun exposure are visible in individuals who start out with moderately pigmented brown skin: the change is dramatically visible as tan lines, where parts of the skin which tanned are delineated from unexposed skin.Modern lifestyles and mobility have created mismatch between skin color and environment for many individuals. Vitamin D deficiencies and UVR overexposure are concerns for many. It is important for these people individually to adjust their diet and lifestyle according to their skin color, the environment they live in, and the time of year. For practical purposes, such as exposure time for sun tanning, six skin types are distinguished following Fitzpatrick (1975), listed in order of decreasing lightness: Fitzpatrick scale The following list shows the six categories of the Fitzpatrick scale in relation to the 36 categories of the older von Luschan scale: Dark skin with large concentrations of melanin protects against ultraviolet light and skin cancers; light-skinned people have about a tenfold greater risk of dying from skin cancer, compared with dark-skinned persons, under equal sunlight exposure. Furthermore, UV-A rays from sunlight are believed to interact with folic acid in ways that may damage health. In a number of traditional societies the sun was avoided as much as possible, especially around noon when the ultraviolet radiation in sunlight is at its most intense. Midday was a time when people stayed in the shade and had the main meal followed by a nap, a practice similar to the modern siesta. Geographic variation Approximately 10% of the variance in skin color occurs within regions, and approximately 90% occurs between regions. Because skin color has been under strong selective pressure, similar skin colors can result from convergent adaptation rather than from genetic relatedness; populations with similar pigmentation may be genetically no more similar than other widely separated groups. Furthermore, in some parts of the world where people from different regions have mixed extensively, the connection between skin color and ancestry has substantially weakened. In Brazil, for example, skin color is not closely associated with the percentage of recent African ancestors a person has, as estimated from an analysis of genetic variants differing in frequency among continent groups.In general, people living close to the equator are highly darkly pigmented, and those living near the poles are generally very lightly pigmented. The rest of humanity shows a high degree of skin color variation between these two extremes, generally correlating with UV exposure. The main exception to this rule is in the New World, where people have only lived for about 10,000 to 15,000 years and show a less pronounced degree of skin pigmentation.In recent times, humans have become increasingly mobile as a consequence of improved technology, domestication, environmental change, strong curiosity, and risk-taking. Migrations over the last 4000 years, and especially the last 400 years, have been the fastest in human history and have led to many people settling in places far away from their ancestral homelands. This means that skin colors today are not as confined to geographical location as they were previously. Social status, colorism and racism According to classical scholar Frank Snowden, skin color did not determine social status in ancient Egypt, Greece or Rome. These ancient civilizations viewed relations between the major power and the subordinate state as more significant in a persons status than their skin colors.Nevertheless, some social groups favor specific skin coloring. The preferred skin tone varies by culture and has varied over time. A number of indigenous African groups, such as the Maasai, associated pale skin with being cursed or caused by evil spirits associated with witchcraft. They would abandon their children born with conditions such as albinism and showed a sexual preference for darker skin.Many cultures have historically favored lighter skin for women. Before the Industrial Revolution, inhabitants of the continent of Europe preferred pale skin, which they interpreted as a sign of high social status. The poorer classes worked outdoors and got darker skin from exposure to the sun, while the upper class stayed indoors and had light skin. Hence light skin became associated with wealth and high position. Women would put lead-based cosmetics on their skin to whiten their skin tone artificially. However, when not strictly monitored, these cosmetics caused lead poisoning. Other methods also aimed at achieving a light-skinned appearance, including the use of arsenic to whiten skin, and powders. Women would wear full-length clothes when outdoors, and would use gloves and parasols to provide shade from the sun. Colonization and enslavement as carried out by European countries became involved with colorism and racism, associated with the belief that people with dark skin were uncivilized, inferior, and should be subordinate to lighter-skinned invaders. This belief exists to an extent in modern times as well. Institutionalized slavery in North America led people to perceive lighter-skinned African-Americans as more intelligent, cooperative, and beautiful. Such lighter-skinned individuals had a greater likelihood of working as house slaves and of receiving preferential treatment from plantation owners and from overseers. For example, they had a chance to get an education. The preference for fair skin remained prominent until the end of the Gilded Age, but racial stereotypes about worth and beauty persisted in the last half of the 20th century and continue in the present day. African-American journalist Jill Nelson wrote that, "To be both prettiest and black was impossible," and elaborated: We learn as girls that in ways both subtle and obvious, personal and political, our value as females is largely determined by how we look.... For black women, the domination of physical aspects of beauty in womens definition and value render us invisible, partially erased, or obsessed, sometimes for a lifetime, since most of us lack the major talismans of Western beauty. Black women find themselves involved in a lifelong effort to self-define in a culture that provides them no positive reflection. A preference for fair or lighter skin continues in some countries, including Latin American countries where whites form a minority. In Brazil, a dark-skinned person is more likely to experience discrimination. Many actors and actresses in Latin America have European features—blond hair, blue eyes, and pale skin. A light-skinned person is more privileged and has a higher social status; a person with light skin is considered more beautiful and lighter skin suggests that the person has more wealth. Skin color is such an obsession in some countries that specific words describe distinct skin tones - from (for example) "jincha", Puerto Rican slang for "glass of milk" to "morena", literally "brown".In South Asia, society regards pale skin as more attractive and associates dark skin with lower class status; this results in a massive market for skin-whitening creams. Fairer skin-tones also correlate to higher caste-status in the Hindu social order—although the system is not based on skin tone. Actors and actresses in Indian cinema tend to have light skin tones, and Indian cinematographers have used graphics and intense lighting to achieve more "desirable" skin tones. Fair skin tones are advertised as an asset in Indian marketing.Skin-whitening products have remained popular over time, often due to historical beliefs and perceptions about fair skin. Sales of skin-whitening products across the world grew from $40 billion to $43 billion in 2008. In South and East Asian countries, people have traditionally seen light skin as more attractive, and a preference for lighter skin remains prevalent. In ancient China and Japan, for example, pale skin can be traced back to ancient drawings depicting women and goddesses with fair skin tones. In ancient China, Japan, and Southeast Asia, pale skin was seen as a sign of wealth. Thus skin-whitening cosmetic products are popular in East Asia. Four out of ten women surveyed in Hong Kong, Malaysia, the Philippines and South Korea used a skin-whitening cream, and more than 60 companies globally compete for Asias estimated $18 billion market. Changes in regulations in the cosmetic industry led to skin-care companies introducing harm-free skin lighteners. In Japan, the geisha have a reputation for their white-painted faces, and the appeal of the bihaku (美白), or "beautiful white", ideal leads many Japanese women to avoid any form of tanning. There are exceptions to this, with Japanese fashion trends such as ganguro emphasizing tanned skin. Skin whitening is also not uncommon in Africa, and several research projects have suggested a general preference for lighter skin in the African-American community. In contrast, one study on men of the Bikosso tribe in Cameroon found no preference for attractiveness of females based on lighter skin color, bringing into question the universality of earlier studies that had exclusively focused on skin-color preferences among non-African populations.Significant exceptions to a preference for lighter skin started to appear in Western culture in the mid-20th century. However a 2010 study found a preference for lighter-skinned women in New Zealand and California. Though sun-tanned skin was once associated with the sun-exposed manual labor of the lower class, the associations became dramatically reversed during this time—a change usually credited to the trendsetting Frenchwoman Coco Chanel (1883–1971) presenting tanned skin as fashionable, healthy, and luxurious. As of 2017, though an overall preference for lighter skin remains prevalent in the United States, many within the country regard tanned skin as both more attractive and healthier than pale or very dark skin. Western mass media and popular culture continued to reinforce negative stereotypes about dark skin, but in some circles pale skin has become associated with indoor office-work while tanned skin has become associated with increased leisure time, sportiness and good health that comes with wealth and higher social status. Studies have also emerged indicating that the degree of tanning is directly related to how attractive a young woman is. See also References Further reading External links "Key gene controls skin colour", BBC News. SLC24A5 gene controls up to 38% of the tonal range in people with mixed European and West African ancestry "The Biology of Skin Color: Black and White"—PBS "The Biology of Skin Color — HHMI BioInteractive Video"—YouTube
Flushing (physiology)	Flushing is to become markedly red in the face and often other areas of the skin, from various physiological conditions. Flushing is generally distinguished, despite a close physiological relation between them, from blushing, which is milder, generally restricted to the face, cheeks or ears, and generally assumed to reflect emotional stress, such as embarrassment, anger, or romantic stimulation. Flushing is also a cardinal symptom of carcinoid syndrome—the syndrome that results from hormones (often serotonin or histamine) being secreted into systemic circulation. Causes Sex flush Commonly referred to as the sex flush, vasocongestion (increased blood flow) of the skin can occur during all four phases of the human sexual response cycle. Studies show that the sex flush occurs in approximately 50–75% of females and 25% of males, yet not consistently. The sex flush tends to occur more often under warmer conditions and may not appear at all under lower temperatures.During the female sex flush, pinkish spots develop under the breasts, then spread to the breasts, torso, face, hands, soles of the feet, and possibly over the entire body. Vasocongestion is also responsible for the darkening of the clitoris and the walls of the vagina during sexual arousal. During the male sex flush, the coloration of the skin develops less consistently than in the female, but typically starts with the epigastrium (upper abdomen), spreads across the chest, then continues to the neck, face, forehead, back, and sometimes, shoulders and forearms.The sex flush typically disappears soon after reaching orgasm, but in other cases, may take up to two hours or more, and sometimes intense sweating occurs simultaneously. See also Cholinergic urticaria Erythema Pallor Rash == References ==
Diabetic neuropathy	Diabetic neuropathy refers to various types of nerve damage associated with diabetes mellitus. Symptoms depend on the site of nerve damage and can include motor changes such as weakness; sensory symptoms such as numbness, tingling, or pain; or autonomic changes such as urinary symptoms. These changes are thought to result from microvascular injury involving small blood vessels that supply nerves (vasa nervorum). Relatively common conditions which may be associated with diabetic neuropathy include distal symmetric polyneuropathy; third, fourth, or sixth cranial nerve palsy; mononeuropathy; mononeuropathy multiplex; diabetic amyotrophy; and autonomic neuropathy. Signs and symptoms Diabetic neuropathy can affect any peripheral nerves including sensory neurons, motor neurons, and the autonomic nervous system. Therefore, diabetic neuropathy has the potential to affect essentially any organ system and can cause a range of symptoms. There are several distinct syndromes based on the organ systems affected. Sensorimotor polyneuropathy Longer nerve fibers are affected to a greater degree than shorter ones because nerve conduction velocity is slowed in proportion to a nerves length. In this syndrome, decreased sensation and loss of reflexes occurs first in the toes on each foot, then extends upward. It is usually described as a glove-stocking distribution of numbness, sensory loss, dysesthesia and night time pain. The pain can feel like burning, pricking sensation, achy or dull. A pins and needles sensation is common. Loss of proprioception, the sense of where a limb is in space, is affected early. These patients cannot feel when they are stepping on a foreign body, like a splinter, or when they are developing a callus from an ill-fitting shoe. Consequently, they are at risk of developing ulcers and infections on the feet and legs, which can lead to amputation. Similarly, these patients can get multiple fractures of the knee, ankle or foot, and develop a Charcot joint. Loss of motor function results in dorsiflexion, contractures of the toes, loss of the interosseous muscle function that leads to contraction of the digits, so-called hammer toes. These contractures occur not only in the foot but also in the hand where the loss of the musculature makes the hand appear gaunt and skeletal. The loss of muscular function is progressive. Autonomic neuropathy The autonomic nervous system is composed of nerves serving the heart, lungs, blood vessels, bone, adipose tissue, sweat glands, gastrointestinal system and genitourinary system. Autonomic neuropathy can affect any of these organ systems. One commonly recognized autonomic dysfunction in diabetics is orthostatic hypotension, or becoming dizzy and possibly fainting when standing up due to a sudden drop in blood pressure. In the case of diabetic autonomic neuropathy, it is due to the failure of the heart and arteries to appropriately adjust heart rate and vascular tone to keep blood continually and fully flowing to the brain. This symptom is usually accompanied by a loss of respiratory sinus arrhythmia – the usual change in heart rate seen with normal breathing. These two findings suggest autonomic neuropathy.Gastrointestinal manifestations include gastroparesis, nausea, bloating, and diarrhea. Because many diabetics take oral medication for their diabetes, absorption of these medicines is greatly affected by the delayed gastric emptying. This can lead to hypoglycemia when an oral diabetic agent is taken before a meal and does not get absorbed until hours, or sometimes days later when there is normal or low blood sugar already. Sluggish movement of the small intestine can cause bacterial overgrowth, made worse by the presence of hyperglycemia. This leads to bloating, gas and diarrhea.Urinary symptoms include urinary frequency, urgency, incontinence and retention. Again, because of the retention of urine, urinary tract infections are frequent. Urinary retention can lead to bladder diverticula, kidney stones, and reflux nephropathy. Cranial neuropathy When cranial nerves are affected, neuropathies of the oculomotor nerve (cranial nerve #3 or CNIII) are most common. The oculomotor nerve controls all the muscles that move the eye except for the lateral rectus and superior oblique muscles. It also serves to constrict the pupil and open the eyelid. The onset of a diabetic third nerve palsy is usually abrupt, beginning with frontal or pain around the eye and then double vision. All the oculomotor muscles innervated by the third nerve may be affected, but those that control pupil size are usually well-preserved early on. This is because the parasympathetic nerve fibers within CNIII that influence pupillary size are found on the periphery of the nerve (in terms of a cross-sectional view), which makes them less susceptible to ischemic damage (as they are closer to the vascular supply). The sixth nerve, the abducens nerve, which innervates the lateral rectus muscle of the eye (moves the eye laterally), is also commonly affected but fourth nerve, the trochlear nerve, (innervates the superior oblique muscle, which moves the eye downward) involvement is unusual. Damage to a specific nerve of the thoracic or lumbar spinal nerves can occur and may lead to painful syndromes that mimic a heart attack, gallbladder inflammation, or appendicitis. Diabetics have a higher incidence of entrapment neuropathies, such as carpal tunnel syndrome. Pathogenesis The following processes are thought to be involved in the development of diabetic neuropathy: Microvascular disease Vascular and neural diseases are closely related. Blood vessels depend on normal nerve function, and nerves depend on adequate blood flow. The first pathological change in the small blood vessels is narrowing of the blood vessels. As the disease progresses, neuronal dysfunction correlates closely with the development of blood vessel abnormalities, such as capillary basement membrane thickening and endothelial hyperplasia, which contribute to diminished oxygen tension and hypoxia. Neuronal ischemia is a well-established characteristic of diabetic neuropathy. Blood vessel opening agents (e.g., ACE inhibitors, α1-antagonists) can lead to substantial improvements in neuronal blood flow, with corresponding improvements in nerve conduction velocities. Thus, small blood vessel dysfunction occurs early in diabetes, parallels the progression of neural dysfunction, and may be sufficient to support the severity of structural, functional, and clinical changes observed in diabetic neuropathy. Advanced glycated end products Elevated levels of glucose within cells cause a non-enzymatic covalent bonding with proteins, which alters their structure and inhibits their function. Some of these glycated proteins have been implicated in the pathology of diabetic neuropathy and other long-term complications of diabetes. Polyol pathway Also called the sorbitol/aldose reductase pathway, the polyol pathway appears to be implicated in diabetic complications, especially in microvascular damage to the retina, kidney, and nerves. Diagnosis Diabetic peripheral neuropathy can be diagnosed with a history and physical examination. The diagnosis is considered in people who develop pain or numbness in a leg or foot with a history of diabetes. Muscle weakness, pain, balance loss, and lower limb dysfunction are the most common clinical manifestations. Physical exam findings may include changes in appearance of the feet, presence of ulceration, and diminished ankle reflexes. The most useful physical examination finding for large fiber neuropathy is an abnormally decreased vibration perception to a 128-Hz tuning fork (likelihood ratio (LR) range, 16–35) or pressure sensation with a 5.07 Semmes-Weinstein monofilament (LR range, 11–16). Normal results on vibration testing (LR range, 0.33–0.51) or monofilament (LR range, 0.09–0.54) make large fiber peripheral neuropathy from diabetes less likely. Nerve conduction tests may show reduced functioning of the peripheral nerves, but seldom correlate with the severity of diabetic peripheral neuropathy and are not appropriate as routine tests for the condition. Small fiber neuropathy measured by QST and Sudomotor function tests, through electrochemical skin conductance, is more and more indicated to assess early signs of diabetic neuropathy and autonomic neuropathy. Classification Diabetic neuropathy encompasses a series of different neuropathic syndromes which can be categorized as follows: Focal and multifocal neuropathies: Mononeuropathy which affects one nerve Amyotrophy or radiculopathy such as proximal diabetic neuropathy, affecting a specific pattern of nerves Multiple lesions, affecting nerves that dont follow a specific pattern, also called "mononeuritis multiplex" Nerve damage from entrapment (e.g. median, ulnar, peroneal) Symmetrical neuropathies: Sensory Autonomic Distal symmetrical polyneuropathy (DSPN), the diabetic type of which is also known as diabetic peripheral neuropathy (DPN) (most common presentation) Prevention Diabetic neuropathy can be largely prevented by maintaining blood glucose levels and lifestyle modifications. Enhanced glucose control methods include more frequent subcutaneous insulin administration, continuous insulin infusion, oral antidiabetic agents, while lifestyle modifications may include exercise alone, or in combination with dietary modifications. Enhanced glucose control prevents the development of clinical neuropathy and reduces nerve abnormalities in type 1 diabetes, and delays the onset of neuropathy in both types of diabetes. However, such methods may increase the likelihood of experiencing a hypoglycemic event, and many of these more aggressive methods require more frequent insulin use which has been associated with excessive risk of falls. Treatment Blood glucose management Treatment of early manifestations of sensorimotor polyneuropathy involves improving glycemic control. Tight control of blood glucose can reverse the changes of diabetic neuropathy if the neuropathy and diabetes are recent in onset. This is the primary treatment of diabetic neuropathy that may change the course of the condition as the other treatments focus on reducing pain and other symptoms. Topical agents Capsaicin applied to the skin in a 0.075% concentration has not been found to be more effective than placebo for treating pain associated with diabetic neuropathy. There is insufficient evidence to draw conclusions for more concentrated forms of capsaicin, clonidine, or lidocaine applied to the skin. About 10% of people who use capsaicin cream have a large benefit. Medications Medication options for pain control include antiepileptic drugs (AEDs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs).A systematic review concluded that "tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants." A further analysis of previous studies showed that the agents carbamazepine, venlafaxine, duloxetine, and amitriptyline were more effective than placebo, but that comparative effectiveness between each agent is unclear.The only three medications approved by the United States Food and Drug Administration for diabetic peripheral neuropathy (DPN) are the antidepressant duloxetine, the anticonvulsant pregabalin, and the long-acting opioid tapentadol ER (extended release). Before trying a systemic medication, some doctors recommend treating localized diabetic peripheral neuropathy with lidocaine patches. Antiepileptic drugs Multiple guidelines from medical organizations such as the American Association of Clinical Endocrinologists, American Academy of Neurology, European Federation of Neurological Societies, and the National Institute of Clinical Excellence recommend AEDs, such as pregabalin, as first-line treatment for painful diabetic neuropathy. Pregabalin is supported by low-quality evidence as more effective than placebo for reducing diabetic neuropathic pain but its effect is small. Studies have reached differing conclusions about whether gabapentin relieves pain more effectively than placebo. Available evidence is insufficient to determine if zonisamide or carbamazepine are effective for diabetic neuropathy. The first metabolite of carbamazepine, known as oxcarbazepine, appears to have a small beneficial effect on pain. A 2014 systematic review and network meta-analysis concluded topiramate, valproic acid, lacosamide, and lamotrigine are ineffective for pain from diabetic peripheral neuropathy. The most common side effects associated with AED use include sleepiness, dizziness, and nausea. Serotonin-norepinephrine reuptake inhibitors As above, the serotonin-norepinephrine reuptake inhibitors (SNRIs) duloxetine and venlafaxine are recommended in multiple medical guidelines as first or second-line therapy for DPN. A 2017 systematic review and meta-analysis of randomized controlled trials concluded there is moderate quality evidence that duloxetine and venlafaxine each provide a large benefit in reducing diabetic neuropathic pain. Common side effects include dizziness, nausea, and sleepiness. Tricyclic antidepressants TCAs include imipramine, amitriptyline, desipramine, and nortriptyline. They are generally regarded as first or second-line treatment for DPN. Of the TCAs, imipramine has been the best studied. These medications are effective at decreasing painful symptoms but lead to multiple side effects that are dose-dependent. One notable side effect is cardiac toxicity, which can lead to fatal abnormal heart rhythms. Additional common side effects include dry mouth, difficulty sleeping, and sedation. At low dosages used for neuropathy, toxicity is rare, but if symptoms warrant higher doses, complications are more common. Among the TCAs, amitriptyline is most widely used for this condition, but desipramine and nortriptyline have fewer side effects. Opioids Typical opioid medications, such as oxycodone, appear to be no more effective than placebo. In contrast, low-quality evidence supports a moderate benefit from the use of atypical opioids (e.g., tramadol and tapentadol), which also have SNRI properties. Opioid medications are recommended as second or third-line treatment for DPN. Medical devices Monochromatic infrared photo energy treatment (MIRE) has been shown to be an effective therapy in reducing and often eliminating pain associated with diabetic neuropathy. The studied wavelength of 890 nm is able to penetrate into the subcutaneous tissue where it acts upon a specialized part of the cell called the cytochrome C. The infrared light energy prompts the cytochrome C to release nitric oxide into the cells. The nitric oxide in turn promotes vasodilation which results in increased blood flow that helps nourish damaged nerve cells. Once the nutrient rich blood is able to reach the affected areas (typically the feet, lower legs and hands) it promotes the regeneration of nerve tissues and helps reduce inflammation thereby reducing and/or eliminating pain in the area. Transcutaneous electrical nerve stimulation (TENS) and interferential current (IFC) use a painless electric current and the physiological effects from low frequency electrical stimulation to relieve stiffness, improve mobility, relieve neuropathic pain, reduce oedema, and heal resistant foot ulcers. Physical therapy Physical therapy may help reduce dependency on pain relieving drug therapies. Certain physiotherapy techniques can help alleviate symptoms brought on from diabetic neuropathy such as deep pain in the feet and legs, tingling or burning sensation in extremities, muscle cramps, muscle weakness, sexual dysfunction, and diabetic foot.Gait training, posture training, and teaching these patients the basic principles of off-loading can help prevent and/or stabilize foot complications such as foot ulcers. Off-loading techniques can include the use of mobility aids (e.g. crutches) or foot splints. Gait re-training would also be beneficial for individuals who have lost limbs, due to diabetic neuropathy, and now wear a prosthesis.Exercise programs, along with manual therapy, will help to prevent muscle contractures, spasms and atrophy. These programs may include general muscle stretching to maintain muscle length and a persons range of motion. General muscle strengthening exercises will help to maintain muscle strength and reduce muscle wasting. Aerobic exercise such as swimming and using a stationary bicycle can help peripheral neuropathy, but activities that place excessive pressure on the feet (e.g. walking long distances, running) may be contraindicated. Exercise therapy has been shown to increase the blood flow to the peripheral nerves, can improve gait function.Heat, therapeutic ultrasound, hot wax are also useful for treating diabetic neuropathy. Pelvic floor muscle exercises can improve sexual dysfunction caused by neuropathy. Electric stimulation of the plantar aspect of the foot showed improved balance and sensation when performed daily. Other Low-quality evidence supports a moderate-large beneficial effect of botulinum toxin injections. There is insufficient evidence to draw firm conclusions for the utility of the cannabinoids nabilone and nabiximols. Prognosis The mechanisms of diabetic neuropathy are poorly understood. At present, treatment alleviates pain and can control some associated symptoms, but the process is generally progressive. As a complication, there is an increased risk of injury to the feet because of loss of sensation (see diabetic foot). Small infections can progress to ulceration and this may require amputation. Epidemiology Globally diabetic neuropathy affects approximately 132 million people as of 2010 (1.9% of the population).Diabetes is the leading known cause of neuropathy in developed countries, and neuropathy is the most common complication and greatest source of morbidity and mortality in diabetes. It is estimated that neuropathy affects 25% of people with diabetes. Diabetic neuropathy is implicated in 50–75% of nontraumatic amputations. The main risk factor for diabetic neuropathy is hyperglycemia. In the DCCT (Diabetes Control and Complications Trial, 1995) study, the annual incidence of neuropathy was 2% per year but dropped to 0.56% with intensive treatment of Type 1 diabetics. The progression of neuropathy is dependent on the degree of glycemic control in both Type 1 and Type 2 diabetes. Duration of diabetes, age, cigarette smoking, hypertension, height, and hyperlipidemia are also risk factors for diabetic neuropathy. References Further reading External links Diabetic Neuropathy at WebMD Diabetic Polyneuropathy at Medscape Diabetic Nerve Problems. MedlinePlus extensive reference list of pertinent sites.
Necrotizing enterocolitis	Necrotizing enterocolitis (NEC) is a devastating intestinal disease that affects premature or very low birth weight infants. Symptoms may include poor feeding, bloating, decreased activity, blood in the stool, vomiting of bile, bowel death, multiorgan failure, and even death.The exact cause is unclear. However, several risk factors have been identified. Consistently described risk factors include formula feeding, intestinal dysbiosis, low birth weight, and prematurity. Maternal factors such as chorioamnionitis, cocaine abuse, in utero growth restriction, intrahepatic cholestasis during pregnancy, increased body mass index, lack of prenatal steroids, mode of delivery, placental abruption, preeclampsia, and smoking have not been consistently implicated with the development of NEC. Other risk factors potentially implicated include congenital heart disease, birth asphyxia, exchange transfusion, and prelabor rupture of membranes. The underlying mechanism is believed to involve a combination of poor blood flow and infection of the intestines. Diagnosis is based on symptoms and confirmed with medical imaging.Prevention includes the use of breast milk and probiotics. Treatment includes bowel rest, orogastric tube, intravenous fluids, and intravenous antibiotics. Surgery is required in those who have free air in the abdomen. A number of other supportive measures may also be required. Complications may include short-gut syndrome, intestinal strictures, or developmental delay.About 7% of those who are born prematurely develop NEC; however the odds of an infant developing this illness is directly related to the intensive care unit they are placed in. Onset is typically in the first four weeks of life. Among those affected, about 25% die. The sexes are affected with equal frequency. The condition was first described between 1888 and 1891. Signs and symptoms The condition is typically seen in premature infants, and the timing of its onset is generally inversely proportional to the gestational age of the baby at birth (i.e., the earlier a baby is born, the later signs of NEC are typically seen).Initial symptoms include feeding intolerance and failure to thrive, increased gastric residuals, abdominal distension, and bloody stools. Symptoms may progress rapidly to abdominal discoloration with intestinal perforation and peritonitis and systemic hypotension requiring intensive medical support. Cause The exact cause is unclear. Several risk factors have been implicated: Maternal factors Acid-suppressing medications Chorioamnionitis Cocaine abuse In utero growth restriction Increased body mass index Intrahepatic cholestasis during pregnancy Lack of prenatal steroids Mode of delivery Placental abruption Pre-eclampsia Smoking Main risk factors Low birth weight Prematurity Formula feeding (bovine based) Intestinal dysbiosis Other risk factors Acute hypoxia Antibiotic exposure Blood transfusions Cardiac anomalies Neonatal anemia Poor intestinal perfusion Prolonged use of indomethacin for patent ductus arteriosus closure Diagnosis Diagnosis is usually suspected clinically, but often requires the aid of diagnostic imaging, most commonly radiography, which can show the intestines and may show areas with death tissue or a bowel perforation. Specific radiographic signs of NEC are associated with specific Bells stages of the disease: Bells stage 1 (suspected disease): Mild systemic disease (apnea, lethargy, slowed heart rate, temperature instability) Mild intestinal signs (abdominal distention, increased gastric residuals, bloody stools) Nonspecific or normal radiological signs Bells stage 2 (definite disease): Mild to moderate systemic signs Additional intestinal signs (absent bowel sounds, abdominal tenderness) Specific radiologic signs (pneumatosis intestinalis or portal venous gas) Laboratory changes (metabolic acidosis, too few platelets in the bloodstream) Bells stage 3 (advanced disease): Severe systemic illness (low blood pressure) Additional intestinal signs (striking abdominal distention, peritonitis) Severe radiologic signs (pneumoperitoneum) Additional laboratory changes (metabolic and respiratory acidosis, disseminated intravascular coagulation)Ultrasonography has proven to be useful, as it may detect signs and complications of NEC before they are evident on radiographs, specifically in cases that involve a paucity of bowel gas, a gasless abdomen, or a sentinel loop. Diagnosis is ultimately made in 5–10% of very-low-birth-weight infants (<1,500g). Diagnosis of NEC is more challenging in premature infants, due to inexplicit symptoms and radiographic signs. The most preterm infant is at highest risk of developing NEC. Prevention Prevention includes the use of breast milk and probiotics. A 2012 policy by the American Academy of Pediatrics recommended feeding preterm infants human milk, finding "significant short- and long-term beneficial effects," including reducing the rate of NEC by a factor of one-half to three-quarters.Small amounts of oral feeds of human milk starting as soon as possible, while the infant is being primarily fed intravenously, primes the immature gut to mature and become ready to receive greater intake by mouth. Human milk from a milk bank or donor can be used if mothers milk is unavailable. The gut mucosal cells do not get enough nourishment from arterial blood supply to stay healthy, especially in very premature infants, where the blood supply is limited due to immature development of the capillaries, so nutrients from the lumen of the gut are needed.Towards understanding intervention with human milk, experts have noted cows and human milk differ in their immunoglobular and glycan compositions. Due to their relative ease of production, human milk oligosaccharides (HMO) are a subject of particular interest in supplementation and intervention.A Cochrane review in 2020 found low- to moderate-quality evidence that supplementation of probiotics enterally "prevents severe NEC, as well as all-cause mortality in preterm infants" and that further high-quality trials are needed to inform policy and practice.Advancing enteral feed volumes at lower rates does not appear to reduce the risk of NEC or death in very preterm infants and seems to increase the risk of invasive infection. Not beginning feeding an infant by mouth for more than 4 days does not appear to have protective benefits. Treatment If a baby is diagnosed with NEC, treatment should begin immediately. Treatment consists primarily of supportive care, including providing bowel rest by stopping enteral feeds, gastric decompression with intermittent suction, fluid repletion to correct electrolyte abnormalities and third-space losses, support for blood pressure, parenteral nutrition, and prompt antibiotic therapy. Monitoring is clinical, although serial supine and left lateral decubitus abdominal X-rays should be performed every six hours.As an infant recovers from NEC, feeds are gradually introduced. "Trophic feeds" or low-volume feeds (<20 ml/kg/day) are usually initiated first. How and what to feed are determined by the extent of bowel involved, the need for surgical intervention, and the infants clinical appearance.Where the disease is not halted through medical treatment alone, or when the bowel perforates, immediate emergency surgery to resect the dead bowel is generally required, although abdominal drains may be placed in very unstable infants as a temporizing measure. Surgery may require a colostomy, which may be able to be reversed at a later time. Some children may develop short bowel syndrome if extensive portions of the bowel must be removed.In the case of an infant whose bowel is left in discontinuity, the surgical creation of a mucous fistula or connection to the distal bowel may be helpful, as this allows for refeeding of ostomy output to the distal bowel. This refeeding process is believed to improve bowel adaptation and aid in advancement of feeds. Prognosis Typical recovery from NEC if medical, nonsurgical treatment succeeds, includes 10–14 days or more without oral intake, and then demonstrated ability to resume feedings and gain weight. Recovery from NEC alone may be compromised by co-morbid conditions that frequently accompany prematurity. Long-term complications of medical NEC include bowel obstruction and anemia.In the United States, NEC caused 355 deaths per 100,000 live births in 2013, down from 484 per 100,000 live births in 2009. Rates of death were almost three times higher for the black population than for the white population.When NEC is diagnosed and treated immediately, the prognosis for babies is generally very good. Most babies recover fully without any additional health problems. Overall, about 70-80% of infants who develop NEC survive. Medical management of NEC shows an increased chance of survival compared to surgical management. Despite a significant mortality risk, long-term prognosis for infants undergoing NEC surgery is improving, with survival rates of 70–80%. However, "Surgical NEC" survivors are still at risk for possible long-term complications, such as narrowing of the intestines or short bowel syndrome and neurodevelopmental disability. References == External links ==
Strain (injury)	A strain is an acute or chronic soft tissue injury that occurs to a muscle, tendon, or both. The equivalent injury to a ligament is a sprain. Generally, the muscle or tendon overstretches and partially tears, under more physical stress than it can withstand, often from a sudden increase in duration, intensity, or frequency of an activity. Strains most commonly occur in the foot, leg, or back. Immediate treatment typically includes five steps abbreviated as P.R.I.C.E.: protection, rest, ice, compression, elevation. Signs and symptoms Typical signs and symptoms of a strain include pain, functional loss of the involved structure, muscle weakness, contusion, and localized inflammation. A strain can range from mild overstretching to severe tears, depending on the extent of injury. Cause A strain can occur as a result of improper body mechanics with any activity (e.g., contact sports, lifting heavy objects) that can induce mechanical trauma or injury. Generally, the muscle or tendon overstretches and is placed under more physical stress than it can withstand. Strains commonly result in a partial or complete tear of a tendon or muscle, or they can be severe in the form of a complete tendon rupture. Strains most commonly occur in the foot, leg, or back. Acute strains are more closely associated with recent mechanical trauma or injury. Chronic strains typically result from repetitive movement of the muscles and tendons over a long period of time.Degrees of Injury (as classified by the American College of Sports Medicine): First degree (mildest) – little tissue tearing; mild tenderness; pain with full range of motion. Second degree – torn muscle or tendon tissues; painful, limited motion; possibly some swelling or depression at the spot of the injury. Third degree (most severe) – limited or no movement; severe acute pain, though sometimes painless straight after the initial injuryTo establish a uniform definition amongst healthcare providers, in 2012 a Consensus Statement on suggested new terminology and classification of muscle injuries was published.The classifications suggested were: The major difference suggested was the use of "indirect" muscle injury verse "grade 1" to provide subclassifications when advanced images were negative.Indirect Muscle Injury FUNCTIONAL (Negative MSK US & MRI) Type 1: Overexertion-related Muscle Disorder Type 1a: Fatigue induced Type 1b: DOMS• Type 2: Neuromuscular muscle disorder Type 2a: Spine-Related Type 2b: Muscle-RelatedSTRUCTURAL MUSCLE INJURY (Positive MSK US & MRI) • Type 3: Partial Muscle Tear • Type 4: (Sub) total tear DIRECT MUSCLE INJURY • Bump or Cut: Contact-related Risk factors Although strains are not restricted to athletes and can happen while doing everyday tasks, people who play sports are more at risk for developing a strain. It is common for an injury to develop when there is a sudden increase in duration, intensity, or frequency of an activity. Treatment The first-line treatment for a muscular strain in the acute phase include five steps commonly known as P.R.I.C.E. Protection: Apply soft padding to minimize impact with objects. Rest: Rest is necessary to accelerate healing and reduce the potential for re-injury. Ice: Apply ice to induce vasoconstriction, which will reduce blood flow to the site of injury. Never ice for more than 20 minutes at a time. Compression: Wrap the strained area with a soft-wrapped bandage to reduce further diapedesis and promote lymphatic drainage. Elevation: Keep the strained area as close to the level of the heart as is possible in order to promote venous blood return to the systemic circulation.Immediate treatment is usually an adjunctive therapy of NSAIDs and Cold compression therapy. Cold compression therapy acts to reduce swelling and pain by reducing leukocyte extravasation into the injured area. NSAIDs such as Ibuprofen/paracetamol work to reduce the immediate inflammation by inhibiting Cox-1 and Cox-2 enzymes, which are the enzymes responsible for converting arachidonic acid into prostaglandin. However, NSAIDs, including aspirin and ibuprofen, affect platelet function (this is why they are known as "blood thinners") and should not be taken during the period when tissue is bleeding because they will tend to increase blood flow, inhibit clotting, and thereby increase bleeding and swelling. After the bleeding has stopped, NSAIDs can be used with some effectiveness to reduce inflammation and pain.A new treatment for acute strains is the use of platelet rich plasma (PRP) injections which have been shown to accelerate recovery from non-surgical muscular injuries.It is recommended that the person injured should consult a medical provider if the injury is accompanied by severe pain, if the limb cannot be used, or if there is noticeable tenderness over an isolated spot. These can be signs of a broken or fractured bone, a sprain, or a complete muscle tear. See also Achilles tendon rupture Pulled hamstring Repetitive strain injury References == External links ==
Hunger	In politics, humanitarian aid, and the social sciences, hunger is defined as a condition in which a person does not have the physical or financial capability to eat sufficient food to meet basic nutritional needs for a sustained period. In the field of hunger relief, the term hunger is used in a sense that goes beyond the common desire for food that all humans experience, also known as an appetite. The most extreme form of hunger, when malnutrition is widespread, and when people have started dying of starvation through lack of access to sufficient, nutritious food, leads to a declaration of famine. Throughout history, portions of the worlds population have often suffered sustained periods of hunger. In many cases, hunger resulted from food supply disruptions caused by war, plagues, or adverse weather. In the decades following World War II, technological progress and enhanced political cooperation suggested it might be possible to substantially reduce the number of people suffering from hunger. While progress was uneven, by 2014, the threat of extreme hunger had receded for a large portion of the worlds population. According to the FAOs 2021 The State of Food Security and Nutrition in the World (SOFI) report, the number of people suffering from chronic hunger began to rise gradually between 2014 and 2019. In 2020, there was a significant increase, resulting in 768 million people suffering from malnutrition.While most of the worlds people continue to live in Asia, much of the increase in hunger since 2015 occurred in Africa and South America. The FAOs 2017 report discussed three principal reasons for the recent increase in hunger: climate, conflict, and economic slowdowns. The 2018 edition focused on extreme weather as a primary driver of the increase in hunger, finding rising rates to be especially severe in countries where agricultural systems were most sensitive to extreme weather variations. The 2019 SOFI report found a strong correlation between increases in hunger and countries that had suffered an economic slowdown. The 2020 edition instead looked at the prospects of achieving the hunger related Sustainable Development Goal (SDG). It warned that if nothing is done to counter the adverse trends of the past six years, the number of people suffering from chronic hunger is on track to rise by over 150 million by 2030. The 2021 report reported a sharp jump in hunger caused by the COVID-19 pandemic. Many thousands of organizations are engaged in the field of hunger relief, operating at local, national, regional, or international levels. Some of these organizations are dedicated to hunger relief, while others may work in several different fields. The organizations range from multilateral institutions to national governments, to small local initiatives such as independent soup kitchens. Many participate in umbrella networks that connect thousands of different hunger relief organizations. At the global level, much of the worlds hunger relief efforts are coordinated by the UN and geared towards achieving SDG 2 of Zero Hunger by 2030. Definition and related terms There is one globally recognized approach for defining and measuring hunger generally used by those studying or working to relieve hunger as a social problem. This is the United Nations FAO measurement, which is typically referred to as chronic undernourishment (or in older publications, as food deprivation, chronic hunger, or just plain hunger.) For the FAO: Hunger or chronic undernourishment exists when "caloric intake is below the minimum dietary energy requirement (MDER). The MDER is the amount of energy needed to perform light activity and to maintain a minimum acceptable weight for attained height." The FAO use different MDER thresholds for different countries, due to variations in climate and cultural factors. Typically a yearly "balance sheet" approach is used, with the minimum dietary energy requirement tallied against the estimated total calories consumed over the year. The FAO definitions differentiate hunger from malnutrition and food insecurity: Malnutrition results from "deficiencies, excesses or imbalances in the consumption of macro- and/or micro-nutrients." In the FAO definition, all hungry people suffer from malnutrition, but people who are malnourished may not be hungry. They may get sufficient raw calories to avoid hunger but lack essential micronutrients, or they may even consume an excess of raw calories and hence suffer from obesity. Food insecurity occurs when people are at risk, or worried about, not being able to meet their preferences for food, including in terms of raw calories and nutritional value. In the FAO definition, all hungry people are food insecure, but not all food-insecure people are hungry (though there is a very strong overlap between hunger and severe food insecurity.). The FAO have reported that food insecurity quite often results in simultaneous stunted growth for children, and obesity for adults. For hunger relief actors operating at the global or regional level, an increasingly commonly used metric for food insecurity is the IPC scale. Acute hunger is typically used to denote famine like hunger, though the phrase lacks a widely accepted formal definition. In the context of hunger relief, people experiencing acute huger may also suffer from chronic hunger. In contrast to the way the word acute is often used elsewhere, the word is used mainly to denote severity, not a lack of long term duration.Not all of the organizations in the hunger relief field use the FAO definition of hunger. Some use a broader definition that overlaps more fully with malnutrition. The alternative definitions do however tend to go beyond the commonly understood meaning of hunger as a painful or uncomfortable motivational condition; the desire for food is something that all humans frequently experience, even the most affluent, and is not in itself a social problem.Very low food supply can be described as "food insecure with hunger." A change in description was made in 2006 at the recommendation of the Committee on National Statistics (National Research Council, 2006) in order to distinguish the physiological state of hunger from indicators of food availability. Food insecure is when food intake of one or more household members was reduced and their eating patterns were disrupted at times during the year because the household lacked money and other resources for food. Food security statistics is measured by using survey data, based on household responses to items about whether the household was able to obtain enough food to meet their needs. World statistics The United Nations publish an annual report on the state of food security and nutrition across the world. Led by the FAO, the 2020 report was joint authored by four other UN agencies: the WFP, IFAD, WHO and UNICEF. Compared to older reports, the 2020 version revised down the numbers of people suffering from severe hunger, though this applied to figures for each year going back to 2000, so the trend for hunger to have increased since 2014 was still evident. The FAOs yearly report provides a statistical overview on the prevalence of hunger around the world, and is widely considered the main global reference for tracking hunger. No simple set of statistics can ever fully capture the multi dimensional nature of hunger however. Reasons include that the FAOs key metric for hunger, "undernourishment", is defined solely in terms of dietary energy availability – disregarding micro-nutrients such as vitamins or minerals. Second, the FAO uses the energy requirements for minimum activity levels as a benchmark; many people would not count as hungry by the FAOs measure yet still be eating too little to undertake hard manual labour, which might be the only sort of work available to them. Thirdly, the FAO statistics do not always reflect short-term undernourishment. An alternative measure of hunger across the world is the Global Hunger Index (GHI). Unlike the FAOs measure, the GHI defines hunger in a way that goes beyond raw calorie intake, to include for example ingestion of micronutrients. GDI is a multidimensional statistical tool used to describe the state of countries’ hunger situation. The GHI measures progress and failures in the global fight against hunger. The GHI is updated once a year. The data from the 2015 report showed that Hunger levels have dropped 27% since 2000. Fifty two countries remained at serious or alarming levels. The 2019 GHI report expresses concern about the increase in hunger since 2015. In addition to the latest statistics on Hunger and Food Security, the GHI also features different special topics each year. The 2019 report includes an essay on hunger and climate change, with evidence suggesting that areas most vulnerable to climate change have suffered much of the recent increases in hunger. The fight against hunger Pre World War II Throughout history, the need to aid those suffering from hunger has been commonly, though not universally, recognized. The philosopher Simone Weil wrote that feeding the hungry when you have resources to do so is the most obvious of all human obligations. She says that as far back as Ancient Egypt, many believed that people had to show they had helped the hungry in order to justify themselves in the afterlife. Weil writes that Social progress is commonly held to be first of all, "...a transition to a state of human society in which people will not suffer from hunger." Social historian Karl Polanyi wrote that before markets became the worlds dominant form of economic organization in the 19th century, most human societies would either starve all together or not at all, because communities would invariably share their food.While some of the principles for avoiding famines had been laid out in the first book of the Bible, they were not always understood. Historical hunger relief efforts were often largely left to religious organizations and individual kindness. Even up to early modern times, political leaders often reacted to famine with bewilderment and confusion. From the first age of globalization, which began in the 19th century, it became more common for the elite to consider problems like hunger in global terms. However, as early globalization largely coincided with the high peak of influence for classical liberalism, there was relatively little call for politicians to address world hunger.In the late nineteenth and early twentieth century, the view that politicians ought not to intervene against hunger was increasingly challenged by campaigning journalists. There were also more frequent calls for large scale intervention against world hunger from academics and politicians, such as U.S. President Woodrow Wilson. Funded both by the government and private donations, the U.S. was able to dispatch millions of tons of food aid to European countries during and in the years immediately after WWI, organized by agencies such as the American Relief Administration. Hunger as an academic and social topic came to further prominence in the U.S. thanks to mass media coverage of the issue as a domestic problem during the Great Depression. Efforts after World War II While there had been increasing attention to hunger relief from the late 19th century, Dr David Grigg has summarised that prior to the end of World War II, world hunger still received relatively little academic or political attention; whereas after 1945 there was an explosion of interest in the topic.After World War II, a new international politico-economic order came into being, which was later described as Embedded liberalism. For at least the first decade after the war, the United States, then by far the periods most dominant national actor, was strongly supportive of efforts to tackle world hunger and to promote international development. It heavily funded the United Nations development programmes, and later the efforts of other multilateral organizations like the International Monetary Fund (IMF) and the World Bank (WB).The newly established United Nations became a leading player in co-ordinating the global fight against hunger. The UN has three agencies that work to promote food security and agricultural development: the Food and Agriculture Organization (FAO), the World Food Programme (WFP) and the International Fund for Agricultural Development (IFAD). FAO is the worlds agricultural knowledge agency, providing policy and technical assistance to developing countries to promote food security, nutrition and sustainable agricultural production, particularly in rural areas. WFPs key mission is to deliver food into the hands of the hungry poor. The agency steps in during emergencies and uses food to aid recovery after emergencies. Its longer term approaches to hunger helps the transition from recovery to development. IFAD, with its knowledge of rural poverty and exclusive focus on poor rural people, designs and implements programmes to help those people access the assets, services and opportunities they need to overcome poverty.Following successful post WWII reconstruction of Germany and Japan, the IMF and WB began to turn their attention to the developing world. A great many civil society actors were also active in trying to combat hunger, especially after the late 1970s when global media began to bring the plight of starving people in places like Ethiopia to wider attention. Most significant of all, especially in the late 1960s and 70s, the Green revolution helped improved agricultural technology propagate throughout the world.The United States began to change its approach to the problem of world hunger from about the mid 1950s. Influential members of the administration became less enthusiastic about methods they saw as promoting an over reliance on the state, as they feared that might assist the spread of communism. By the 1980s, the previous consensus in favour of moderate government intervention had been displaced across the western world. The IMF and World Bank in particular began to promote market-based solutions. In cases where countries became dependent on the IMF, they sometimes forced national governments to prioritize debt repayments and sharply cut public services. This sometimes had a negative effect on efforts to combat hunger. Organizations such as Food First raised the issue of food sovereignty and claimed that every country on earth (with the possible minor exceptions of some city-states) has sufficient agricultural capacity to feed its own people, but that the "free trade" economic order, which from the late 1970s to about 2008 had been associated with such institutions as the IMF and World Bank, had prevented this from happening. The World Bank itself claimed it was part of the solution to hunger, asserting that the best way for countries to break the cycle of poverty and hunger was to build export-led economies that provide the financial means to buy foodstuffs on the world market. However, in the early 21st century the World Bank and IMF became less dogmatic about promoting free market reforms. They increasingly returned to the view that government intervention does have a role to play, and that it can be advisable for governments to support food security with policies favourable to domestic agriculture, even for countries that do not have a Comparative advantage in that area. As of 2012, the World Bank remains active in helping governments to intervene against hunger.Until at least the 1980s—and, to an extent, the 1990s—the dominant academic view concerning world hunger was that it was a problem of demand exceeding supply. Proposed solutions often focused on boosting food production, and sometimes on birth control. There were exceptions to this, even as early as the 1940s, Lord Boyd-Orr, the first head of the UNs FAO, had perceived hunger as largely a problem of distribution, and drew up comprehensive plans to correct this. Few agreed with him at the time, however, and he resigned after failing to secure support for his plans from the US and Great Britain. In 1998, Amartya Sen won a Nobel Prize in part for demonstrating that hunger in modern times is not typically the product of a lack of food. Rather, hunger usually arises from food distribution problems, or from governmental policies in the developed and developing world. It has since been broadly accepted that world hunger results from issues with the distribution as well as the production of food. Sens 1981 essay Poverty and Famines: An Essay on Entitlement and Deprivation played a prominent part in forging the new consensus.In 2007 and 2008, rapidly increasing food prices caused a global food crisis. Food riots erupted in several dozen countries; in at least two cases, Haiti and Madagascar, this led to the toppling of governments. A second global food crisis unfolded due to the spike in food prices of late 2010 and early 2011. Fewer food riots occurred, due in part to greater availability of food stock piles for relief. However, several analysts argue the food crisis was one of the causes of the Arab Spring. Efforts since the global 2008 crisis In the early 21st century, the attention paid to the problem of hunger by the leaders of advanced nations such as those that form the G8 had somewhat subsided. Prior to 2009, large scale efforts to fight hunger were mainly undertaken by governments of the worst affected countries, by civil society actors, and by multilateral and regional organizations. In 2009, Pope Benedict published his third encyclical, Caritas in Veritate, which emphasised the importance of fighting against hunger. The encyclical was intentionally published immediately before the July 2009 G8 Summit to maximise its influence on that event. At the Summit, which took place at LAquila in central Italy, the LAquila Food Security Initiative was launched, with a total of US$22 billion committed to combat hunger.Food prices fell sharply in 2009 and early 2010, though analysts credit this much more to farmers increasing production in response to the 2008 spike in prices, than to the fruits of enhanced government action. However, since the 2009 G8 summit, the fight against hunger became a high-profile issue among the leaders of the worlds major nations and was a prominent part of the agenda for the 2012 G-20 summit.In April 2012, the Food Assistance Convention was signed, the worlds first legally binding international agreement on food aid. The May 2012 Copenhagen Consensus recommended that efforts to combat hunger and malnutrition should be the first priority for politicians and private sector philanthropists looking to maximize the effectiveness of aid spending. They put this ahead of other priorities, like the fight against malaria and AIDS. Also in May 2012, U.S. President Barack Obama launched a "new alliance for food security and nutrition"—a broad partnership between private sector, governmental and civil society actors—that aimed to "...achieve sustained and inclusive agricultural growth and raise 50 million people out of poverty over the next 10 years." The UKs prime minister David Cameron held a hunger summit on 12 August, the last day of the 2012 Summer Olympics.The fight against hunger has also been joined by an increased number of regular people. While folk throughout the world had long contributed to efforts to alleviate hunger in the developing world, there has recently been a rapid increase in the numbers involved in tackling domestic hunger even within the economically advanced nations of the Global North. This had happened much earlier in North America than it did in Europe. In the US, the Reagan administration scaled back welfare the early 1980s, leading to a vast increase of charity sector efforts to help Americans unable to buy enough to eat. According to a 1992 survey of 1000 randomly selected US voters, 77% of Americans had contributed to efforts to feed the hungry, either by volunteering for various hunger relief agencies such as food banks and soup kitchens, or by donating cash or food. Europe, with its more generous welfare system, had little awareness of domestic hunger until the food price inflation that began in late 2006, and especially as austerity-imposed welfare cuts began to take effect in 2010. Various surveys reported that upwards of 10% of Europes population had begun to suffer from food insecurity. Especially since 2011, there has been a substantial increase in grass roots efforts to help the hungry by means of food banks, within both the UK and continental Europe. By July 2012, the 2012 US drought had already caused a rapid increase in the price of grain and soy, with a knock on effect on the price of meat. As well as affecting hungry people in the US, this caused prices to rise on the global markets; the US is the worlds biggest exporter of food. This led to much talk of a possible third 21st century global food crisis. The Financial Times reported that the BRICS may not be as badly affected as they were in the earlier crises of 2008 and 2011. However, smaller developing countries that must import a substantial portion of their food could be hard hit. The UN and G20 has begun contingency planning so as to be ready to intervene if a third global crisis breaks out. By August 2013 however, concerns had been allayed, with above average grain harvests expected from major exporters, including Brazil, Ukraine and the U.S. 2014 also saw a good worldwide harvest, leading to speculation that grain prices could soon begin to fall.In an April 2013 summit held in Dublin concerning Hunger, Nutrition, Climate Justice, and the post 2015 MDG framework for global justice, Irelands President Higgins said that only 10% of deaths from hunger are due to armed conflict and natural disasters, with ongoing hunger being both the "greatest ethical failure of the current global system" and the "greatest ethical challenge facing the global community." $4.15 billion of new commitments were made to tackle hunger at a June 2013 Hunger Summit held in London, hosted by the governments of Britain and Brazil, together with The Childrens Investment Fund Foundation.Despite the hardship caused by the 2007–2009 financial crisis and global increases in food prices that occurred around the same time, the UNs global statistics show it was followed by close to year on year reductions in the numbers suffering from hunger around the world. By 2019 however, evidence had mounted that this progress seemed to have gone into reverse over the last four years. The numbers suffering from hunger had risen both in absolute terms and very slightly even as a percentage of the worlds population.In 2019, FAO its annual edition of The State of Food and Agriculture which asserted that food loss and waste has potential effects on food security and nutrition through changes in the four dimensions of food security: food availability, access, utilization and stability. However, the links between food loss and waste reduction and food security are complex, and positive outcomes are not always certain. Reaching acceptable levels of food security and nutrition inevitably implies certain levels of food loss and waste. Maintaining buffers to ensure food stability requires a certain amount of food to be lost or wasted. At the same time, ensuring food safety involves discarding unsafe food, which then is counted as lost or wasted, while higher-quality diets tend to include more highly perishable foods. How the impacts on the different dimensions of food security play out and affect the food security of different population groups depends on where in the food supply chain the reduction in losses or waste takes place as well as on where nutritionally vulnerable and food-insecure people are located geographically.In April and May 2020, concerns were expressed that the COVID-19 pandemic could result in a doubling in global hunger unless world leaders acted to prevent this. Agencies such as the WFP have warned that this could include the number of people facing acute hunger rising from 135 million to about 265 million by the end of 2020. Indications of extreme hunger have been seen in various cities, such as fatal stampedes when word spread that emergency food aid was being handed out. Letters calling for co-ordinated action to offset the effects of the COVID-19 pandemic have been written to the G20 and G7, by various actors including NGOs, UN staff, corporations, academics and former national leaders. Following the 2022 invasion of Ukraine, concerns have been raised over hunger resulting from rising food prices. This is forecast to risk civil unrest even in many middle income countries, where government capability to protect their populations was largely exhausted by the Covid pandemic, and has not yet recovered. Hunger relief organisations Many thousands of hunger relief organisations exist across the world. Some but not all are entirely dedicated to fighting hunger. They range from independent soup kitchens that serve only one locality, to global organisations. Organisations working at the global and regional level will often focus much of their efforts on helping hungry communities to better feed themselves, for example by sharing agricultural technology. With some exceptions, organisations that work just on the local level tend to focus more on providing food directly to hungry people. Many of the entities are connected by a web of national, regional and global alliances that help them share resources, knowledge, and coordinate efforts. Global The United Nations is central to global efforts to relieve hunger, most especially through the FAO, and also via other agencies: such as WFP, IFAD, WHO and UNICEF. After the Millennium Development Goals expired in 2015, the Sustainable Development Goals (SDGs) became key objectives to shape the worlds response to development challenges such as hunger. In particular Goal 2: Zero Hunger sets globally agreed targets to end hunger, achieve food security and improved nutrition and promote sustainable agriculture.Aside from the UN agencies themselves, hundreds of other actors address the problem of hunger on the global level, often involving participation in large umbrella organisations. These include national governments, religious groups, international charities and in some cases international corporations. Though except perhaps in the cases of dedicated charities, the priority these organisations assign to hunger relief may vary from year to year. In many cases the organisations partner with the UN agencies, though often they pursue independent goals. For example, as consensus began to form for the SDG zero hunger goal to aim to end hunger by 2030, a number of organizations formed initiatives with the more ambitious target to achieve this outcome early, by 2025: In 2013 Caritas International started a Caritas-wide initiative aimed at ending systemic hunger by 2025. The One human family, food for all campaign focuses on awareness raising, improving the impact of Caritas programs and advocating the implementation of the right to food. The partnership Compact2025, led by IFPRI with the involvement of UN organisations, NGOs and private foundations develops and disseminates evidence-based advice to politicians and other decision-makers aimed at ending hunger and undernutrition in the coming 10 years, by 2025. It bases its claim that hunger can be ended by 2025 on a report by Shenggen Fan and Paul Polman that analyzed the experiences from China, Vietnam, Brazil and Thailand and concludes that eliminating hunger and undernutrition was possible by 2025. In June 2015, the European Union and the Bill & Melinda Gates Foundation have launched a partnership to combat undernutrition especially in children. The program will initially be implemented in Bangladesh, Burundi, Ethiopia, Kenya, Laos and Niger and will help these countries to improve information and analysis about nutrition so they can develop effective national nutrition policies. Sustainable Development Goal 2 (SDG 2 or Goal 2) The objective of SDG 2 is to "end hunger, achieve food security and improved nutrition and promote sustainable agriculture" by 2030. SDG2 recognizes that dealing with hunger is not only based on increasing food production but also on proper markets, access to land and technology and increased and efficient incomes for farmers.A report by the International Food Policy Research Institute (IFPRI) of 2013 argued that the emphasis of the SDGs should be on eliminating hunger and under-nutrition, rather than on poverty, and that attempts should be made to do so by 2025 rather than 2030. The argument is based on an analysis of experiences in China, Vietnam, Brazil, and Thailand and the fact that people suffering from severe hunger face extra impediments to improving their lives, whether it be by education or work. Three pathways to achieve this were identified: 1) agriculture-led; 2) social protection- and nutrition- intervention-led; or 3) a combination of both of these approaches. Regional Much of the worlds regional alliances are located in Africa. For example, the Alliance for Food Sovereignty in Africa or the Alliance for a Green Revolution in Africa.The Food and Agriculture Organization of the UN has created a partnership that will act through the African Unions CAADP framework aiming to end hunger in Africa by 2025. It includes different interventions including support for improved food production, a strengthening of social protection and integration of the right to food into national legislation. National Examples of hunger relief organisations that operate on the national level include The Trussell Trust in the United Kingdom, the Nalabothu Foundation in India, and Feeding America in the United States. Local Food bank A food bank (or foodbank) is a non-profit, charitable organization that aids in the distribution of food to those who have difficulty purchasing enough to avoid hunger. Food banks tend to run on different operating models depending on where they are located. In the U.S., Australia, and to some extent in Canada, foodbanks tend to perform a warehouse type function, storing and delivering food to front line food orgs, but not giving it directly to hungry peoples themselves. In much of Europe and elsewhere, food banks operate on the front line model, where they hand out parcels of uncooked food direct to the hungry, typically giving them enough for several meals which they can eat in their homes. In the U.S and Australia, establishments that hand out uncooked food to individual people are instead called food pantries, food shelves or food closets. In Less Developed Countries, there are charity-run food banks that operate on a semi-commercial system that differs from both the more common "warehouse" and "frontline" models. In some rural LDCs such as Malawi, food is often relatively cheap and
Hunger	plentiful for the first few months after the harvest, but then becomes more and more expensive. Food banks in those areas can buy large amounts of food shortly after the harvest, and then as food prices start to rise, they sell it back to local people throughout the year at well below market prices. Such food banks will sometimes also act as centers to provide small holders and subsistence farmers with various forms of support. Soup kitchen A soup kitchen, meal center, or food kitchen is a place where food is offered to the hungry for free or at a below market price. Frequently located in lower-income neighborhoods, they are often staffed by volunteer organizations, such as church or community groups. Soup kitchens sometimes obtain food from a food bank for free or at a low price, because they are considered a charity, which makes it easier for them to feed the many people who require their services. Others Local establishments calling themselves "food banks" or "soup kitchens" are often run either by Christian churches or less frequently by secular civil society groups. Other religions carry out similar hunger relief efforts, though sometimes with slightly different methods. For example, in the Sikh tradition of Langar, food is served to the hungry direct from Sikh temples. There are exceptions to this, for example in the UK Sikhs run some of the food banks, as well as giving out food direct from their Gurdwaras. Hunger and gender In both developing and advanced countries, parents sometimes go without food so they can feed their children. Women, however, seem more likely to make this sacrifice than men. World Bank studies consistently find that about 60% of those who are hungry are female. The apparent explanation for this imbalance is that, compared to men, women often forgo meals in order to feed their children. Older sources sometimes claim this phenomenon is unique to developing countries, due to greater sexual inequality. More recent findings suggested that mothers often miss meals in advanced economies too. For example, a 2012 study undertaken by Netmums in the UK found that one in five mothers sometimes misses out on food to save their children from hunger.In several periods and regions, gender has also been an important factor determining whether or not victims of hunger would make suitable examples for generating enthusiasm for hunger relief efforts. James Vernon, in his Hunger: A Modern History, wrote that in Britain before the 20th century, it was generally only women and children suffering from hunger who could arouse compassion. Men who failed to provide for themselves and their families were often regarded with contempt.This changed after World War I, where thousands of men who had proved their manliness in combat found themselves unable to secure employment. Similarly, female gender could be advantageous for those wishing to advocate for hunger relief, with Vernon writing that being a woman helped Emily Hobhouse draw the plight of hungry people to wider attention during the Second Boer War. Hunger and age The elderly are among some of the most vulnerable populations; increasing their risk of going hungry as well as significantly increasing the negative effects of hunger. The number of seniors experiencing hunger rose 88% between the years of 2001 and 2011. Researchers predict that if this upwards trend continues, the amount of food insecure seniors will increase by 50% by 2025.This age group suffers the most from chronic conditions, including heart disease, diabetes, and respiratory diseases. Eighty percent of this group has a minimum of one chronic condition, and almost 70% have two or more. These illnesses are exacerbated and are more likely to develop under the addition of hunger. A report from 2017 shows that seniors facing this issue are 60% more likely to experience depression than seniors who are not hungry, and 40% are more likely to develop congestive heart failure. The added stress of inconsistent and inadequate feedings make these conditions much more dangerous.Fixed incomes often limit the elderly’s ability to freely purchase food necessities. Medical costs and housing may take priority over quality foods. Limited mobility makes it difficult for these individuals to physically leave their homes, especially in areas lacking public transportation or transportation catering to a disabled body. The COVID-19 pandemic has made things even more difficult, as this group is extremely vulnerable to contracting variants. They are high-risk, and are faced with the threat of this disease, more so than other age groups, when they leave their homes. This continues to limit their food access. The Supplemental Nutrition Assistance Program (SNAP) provides aid to low-income seniors in relation to food security. This is an opportunity for seniors who receive benefits to allocate money in their budgets for other needs, such as medical or housing bills. However, participation is extremely low. Less than half of eligible seniors are enrolled and receive benefits; 3 out of five seniors are qualified but not enrolled. See also Sources This article incorporates text from a free content work. Licensed under CC BY-SA 3.0 License statement/permission. Text taken from The State of Food and Agriculture 2019. Moving forward on food loss and waste reduction, In brief, 24, FAO, FAO. To learn how to add open license text to Wikipedia articles, please see this how-to page. For information on reusing text from Wikipedia, please see the terms of use. References Further reading Michelle Jurkovich. 2020. Feeding the Hungry: Advocacy and Blame in the Global Fight against Hunger. Cornell University Press. External links Action Against Hunger \| ACF-USA Action Against Hunger \| ACF-UK Hunger Relief International \| HRI Hunger Relief research on IssueLab The Global Forum on Food Security and Nutrition (FSN Forum) Ten Things you can do to Fight World Hunger The Nation, 13 May 2009 United Nation 2007 report World Food Programme \| WFP
Acute-phase protein	Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the acute-phase reaction (also called acute-phase response). The acute-phase reaction characteristically involves fever, acceleration of peripheral leukocytes, circulating neutrophils and their precursors. The terms acute-phase protein and acute-phase reactant (APR) are often used synonymously, although some APRs are (strictly speaking) polypeptides rather than proteins. In response to injury, local inflammatory cells (neutrophil granulocytes and macrophages) secrete a number of cytokines into the bloodstream, most notable of which are the interleukins IL1, and IL6, and TNF-α. The liver responds by producing many acute-phase reactants. At the same time, the production of a number of other proteins is reduced; these proteins are, therefore, referred to as "negative" acute-phase reactants. Increased acute-phase proteins from the liver may also contribute to the promotion of sepsis. Regulation of synthesis TNF-α, IL-1β and IFN-γ are important for the expression of inflammatory mediators such as prostaglandins and leukotrienes, and they also cause the production of platelet-activating factor and IL-6. After stimulation with proinflammatory cytokines, Kupffer cells produce IL-6 in the liver and present it to the hepatocytes. IL-6 is the major mediator for the hepatocytic secretion of APPs. Synthesis of APP can also be regulated indirectly by cortisol. Cortisol can enhance expression of IL-6 receptors in liver cells and induce IL-6-mediated production of APPs. Positive Positive acute-phase proteins serve (as part of the innate immune system) different physiological functions within the immune system. Some act to destroy or inhibit growth of microbes, e.g., C-reactive protein, mannose-binding protein, complement factors, ferritin, ceruloplasmin, serum amyloid A and haptoglobin. Others give negative feedback on the inflammatory response, e.g. serpins. Alpha 2-macroglobulin and coagulation factors affect coagulation, mainly stimulating it. This pro-coagulant effect may limit infection by trapping pathogens in local blood clots. Also, some products of the coagulation system can contribute to the innate immune system by their ability to increase vascular permeability and act as chemotactic agents for phagocytic cells. Negative "Negative" acute-phase proteins decrease in inflammation. Examples include albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, transcortin. The decrease of such proteins may be used as markers of inflammation. The physiological role of decreased synthesis of such proteins is generally to save amino acids for producing "positive" acute-phase proteins more efficiently. Theoretically, a decrease in transferrin could additionally be decreased by an upregulation of transferrin receptors, but the latter does not appear to change with inflammation.While the production of C3 (a complement factor) increases in the liver, the plasma concentration often lowers because of an increased turn-over, therefore it is often seen as a negative acute-phase protein. Clinical significance Measurement of acute-phase proteins, especially C-reactive protein, is a useful marker of inflammation in both medical and veterinary clinical pathology. It correlates with the erythrocyte sedimentation rate (ESR), however not always directly. This is due to the ESR being largely dependent on the elevation of fibrinogen, an acute phase reactant with a half-life of approximately one week. This protein will therefore remain higher for longer despite the removal of the inflammatory stimuli. In contrast, C-reactive protein (with a half-life of 6–8 hours) rises rapidly and can quickly return to within the normal range if treatment is employed. For example, in active systemic lupus erythematosus, one may find a raised ESR but normal C-reactive protein.They may also indicate liver failure. References External links http://eclinpath.com/chemistry/proteins/acute-phase-proteins/ Acute-Phase+Proteins at the US National Library of Medicine Medical Subject Headings (MeSH)
Nitrovasodilator	A nitrovasodilator is a pharmaceutical agent that causes vasodilation (widening of blood vessels) by donation of nitric oxide (NO), and is mostly used for the treatment and prevention of angina pectoris. This group of drugs includes nitrates (esters of nitric acid), which are reduced to NO in the body, as well as some other substances. Examples Here is a list of examples of the nitrate type (in alphabetical order): Nitrovasodilators which arent nitrates include molsidomine and its active metabolite linsidomine, as well as sodium nitroprusside. These substances do not need to be reduced to donate NO. Medical uses The nitrates are used for the treatment and prevention of angina and acute myocardial infarction, while molsidomine acts too slowly to be useful for the treatment of acute angina. For quick action in the treatment of angina, glyceryl trinitrate is used in form of a sublingual spray (nitro spray) or as soft capsules to be crunched.Nitroprusside is used intravenously for the treatment of hypertensive crises, heart failure, and lowering of blood pressure during surgery. Contraindications Nitrovasodilators are contraindicated under circumstances where lowering of blood pressure can be dangerous. This includes, with some variation between the individual substances, severe hypotension (low blood pressure), shock including cardiogenic shock, and anaemia. Whether a specific drug is useful or harmful under heart failure and myocardial infarction depends on its speed of action: Fast acting substances such as glyceryl trinitrate and nitroprusside can be helpful for controlling blood pressure and consequently the amount of blood the heart has to pump, if the application is monitored continuously. Slow acting substances would hold the danger of ischaemia due to an uncontrollably low blood pressure and are therefore contraindicated. Depending on the circumstances, even fast acting substances can be contraindicated – for example, glyceryl trinitrate in patients with obstructive heart failure.These drugs are also contraindicated in patients that have recently taken PDE5 inhibitors such as sildenafil (Viagra). Adverse effects Most side effects are direct consequences of the vasodilation and the following low blood pressure. They include headache ("nitrate headache") resulting from the widening of blood vessels in the brain, reflex tachycardia (fast heart rate), flush, dizziness, nausea and vomiting. These effects usually subside after a few days if the treatment is continued.Occasionally, severe hypotension occurs shortly after beginning of treatment, possibly resulting in intensified angina symptoms or syncope, sometimes with bradycardia (slow heart rate). Interactions A number of drugs add to the low blood pressure caused by nitrovasodilators: for example, other vasodilators, antihypertensive drugs, tricyclic antidepressantss, antipsychotics, general anaesthetics, as well as ethanol. Combination with PDE5 inhibitors, including sildenafil (Viagra), is contraindicated because potentially life-threatening hypotension may occur.Nitrates increase the bioavailability of dihydroergotamine (DHE). High DHE levels may result in coronary spasms in patients with coronary disease. This interaction is not described for non-nitrate nitrovasodilators. Mechanism of action Nitrovasodilators are prodrugs that donate NO by various mechanisms. Nitrates undergo chemical reduction, likely mediated by enzymes. Molsidomine and nitroprusside already contain nitrogen in the right oxidation state (+2) and liberate NO without the aid of enzymes.NO stimulates the soluble form of the enzyme guanylate cyclase in the smooth muscle cells of blood vessels. Guanylate cyclase produces cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). cGMP in turn activates cyclic nucleotide-dependent protein kinase G, which phosphorylates various proteins that play a role in decreasing intracellular calcium levels, leading to relaxation of the muscle cells and thus to dilation of blood vessels.The most important effect in angina is the widening of veins, which increases their capacity to hold blood ("venous pooling") and reduces the pressure of the blood returning to the heart (the preload). Widening of the large arteries also reduces the pressure against which the heart has to pump, the afterload. Lower preload and afterload result in the heart needing less energy and thus less oxygen. Besides, NO donated by nitrovasodilators can reduce coronary spasms, increasing the hearts oxygen supply.PDE5 inhibitors block deactivation of cGMP by the enzyme phosphodiesterase-5. In combination with the increased cGMP production caused by nitrovasodilators, this leads to high concentrations of cGMP, extensive venous pooling, and potentially life-threatening hypotension. Nitrate tolerance Nitrates exhibit development of tolerance, or more specifically tachyphylaxis, meaning that repeated application results in a fast decrease of effect, usually within 24 hours. A pause of six to eight hours restores the original effectiveness. This phenomenon was originally thought to be a consequence of depletion of thiol (–SH) groups necessary for the reduction of nitrates. While this theory would fit the fact that molsidomine (which is not reduced) does not exhibit tachyphylaxis, it has meanwhile been refuted. Newer theories include increase of oxidative stress resulting in deactivation of NO to peroxynitrite, and liberation of the vasoconstrictors angiotensin II and endothelin as the blood vessels reaction to NO-mediated vasodilation. Differences in pharmacokinetics Nitrates mainly differ in speed and duration of their action. Glyceryl trinitrate acts fast and short (10 to 30 minutes), while most other nitrates have a slower onset of action, but are effective for up to six hours. Molsidomine, as has been mentioned, not only acts slowly but also differs from the nitrates in exhibiting no tolerance. Nitroprusside, given intravenously, acts immediately, and after stopping the infusion blood pressure returns to its previous level within ten minutes. See also History of glyceryl trinitrate Biological functions of nitric oxide == References ==
Muscle atrophy	Muscle atrophy is the loss of skeletal muscle mass. It can be caused by immobility, aging, malnutrition, medications, or a wide range of injuries or diseases that impact the musculoskeletal or nervous system. Muscle atrophy leads to muscle weakness and causes disability. Disuse causes rapid muscle atrophy and often occurs during injury or illness that requires immobilization of a limb or bed rest. Depending on the duration of disuse and the health of the individual, this may be fully reversed with activity. Malnutrition first causes fat loss but may progress to muscle atrophy in prolonged starvation and can be reversed with nutritional therapy. In contrast, cachexia is a wasting syndrome caused by an underlying disease such as cancer that causes dramatic muscle atrophy and cannot be completely reversed with nutritional therapy. Sarcopenia is age-related muscle atrophy and can be slowed by exercise. Finally, diseases of the muscles such as muscular dystrophy or myopathies can cause atrophy, as well as damage to the nervous system such as in spinal cord injury or stroke. Thus, muscle atrophy is usually a finding (sign or symptom) in a disease rather than being a disease by itself. However, some syndromes of muscular atrophy are classified as disease spectrums or disease entities rather than as clinical syndromes alone, such as the various spinal muscular atrophies. Muscle atrophy results from an imbalance between protein synthesis and protein degradation, although the mechanisms are incompletely understood and are variable depending on the cause. Muscle loss can be quantified with advanced imaging studies but this is not frequently pursued. Treatment depends on the underlying cause but will often include exercise and adequate nutrition. Anabolic agents may have some efficacy but are not often used due to side effects. There are multiple treatments and supplements under investigation but there are currently limited treatment options in clinical practice. Given the implications of muscle atrophy and limited treatment options, minimizing immobility is critical in injury or illness. Signs and symptoms The hallmark sign of muscle atrophy is loss of lean muscle mass. This change may be difficult to detect due to obesity, changes in fat mass or edema. Changes in weight, limb or waist circumference are not reliable indicators of muscle mass changes.The predominant symptom is increased weakness which may result in difficulty or inability in performing physical tasks depending on what muscles are affected. Atrophy of the core or leg muscles may cause difficulty standing from a seated position, walking or climbing stairs and can cause increased falls. Atrophy of the throat muscles may cause difficulty swallowing and diaphragm atrophy can cause difficulty breathing. Muscle atrophy can be asymptomatic and may go undetected until a significant amount of muscle is lost. Causes Skeletal muscle serves as a storage site for amino acids that can be used for energy production when demands are high or supplies are low. If metabolic demands remain greater than protein synthesis, muscle mass is lost. Many diseases and conditions can lead to this imbalance, either through the disease itself or disease associated appetite-changes. Causes of muscle atrophy, include immobility, aging, malnutrition, certain systemic diseases (cancer, congestive heart failure; chronic obstructive pulmonary disease; AIDS, liver disease, etc.), deinnervation, intrinsic muscle disease or medications (such as glucocorticoids). Immobility Disuse is a common cause of muscle atrophy and can be local (due to injury or casting) or general (bed-rest). The rate of muscle atrophy from disuse (10-42 days) is approximately 0.5–0.6% of total muscle mass per day although there is considerable variation between people. The elderly are the most vulnerable to dramatic muscle loss with immobility. Much of the established research has investigated prolonged disuse (>10 days), in which the muscle is compromised primarily by declines in muscle protein synthesis rates rather than changes in muscle protein breakdown. There is evidence to suggest that there may be more active protein breakdown during short term immobility (<10 days). Cachexia Certain diseases can cause a complex muscle wasting syndrome known as cachexia. It is commonly seen in cancer, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease and AIDS although it is associated with many disease processes, usually with a significant inflammatory component. Cachexia causes ongoing muscle loss that is not entirely reversed with nutritional therapy. The pathophysiology is incompletely understood but inflammatory cytokines are considered to play a central role. In contrast to weight loss from inadequate caloric intake, cachexia causes predominantly muscle loss instead of fat loss and it is not as responsive to nutritional intervention. Cachexia can significantly compromise quality of life and functional status and is associated with poor outcomes. Sarcopenia Sarcopenia is the degenerative loss of skeletal muscle mass, quality, and strength associated with aging. This involves muscle atrophy, reduction in number of muscle fibers and a shift towards "slow twitch" or type I skeletal muscle fibers over "fast twitch" or type II fibers. The rate of muscle loss is dependent on exercise level, co-morbidities, nutrition and other factors. There are many proposed mechanisms of sarcopenia and is considered to be the result of changes in muscle synthesis signalling pathways and gradual failure in the satellite cells which help to regenerate skeletal muscle fibers, but is incompletely understood.Sarcopenia can lead to reduction in functional status and cause significant disability but is a distinct condition from cachexia although they may co-exist. In 2016 an ICD code for sarcopenia was released, contributing to its acceptance as a disease entity. Intrinsic muscle diseases Muscle diseases, such as muscular dystrophy, amyotrophic lateral sclerosis (ALS), or myositis such as inclusion body myositis can cause muscle atrophy. Central nervous system damage Damage to neurons in the brain or spinal cord can cause prominent muscle atrophy. This can be localized muscle atrophy and weakness or paralysis such as in stroke or spinal cord injury. More widespread damage such as in traumatic brain injury or cerebral palsy can cause generalized muscle atrophy. Peripheral nervous system damage Injuries or diseases of peripheral nerves supplying specific muscles can also cause muscle atrophy. This is seen in nerve injury due to trauma or surgical complication, nerve entrapment, or inherited diseases such as Charcot-Marie-Tooth disease. Medications Some medications are known to cause muscle atrophy, usually due to direct effect on muscles. This includes glucocorticoids causing glucocorticoid myopathy or medications toxic to muscle such as doxorubicin. Endocrinopathies Disorders of the endocrine system such as Cushings disease or hypothyroidism are known to cause muscle atrophy. Pathophysiology Muscle atrophy occurs due to an imbalance between the normal balance between protein synthesis and protein degradation. This involves complex cell signalling that is incompletely understood and muscle atrophy is likely the result of multiple contributing mechanisms.Mitochondrial function is crucial to skeletal muscle health and detrimental changes at the level of the mitochondria may contribute to muscle atrophy. A decline in mitochondrial density as well as quality is consistently seen in muscle atrophy due to disuse.The ATP-dependent ubiquitin/proteasome pathway is one mechanism by which proteins are degraded in muscle. This involves specific proteins being tagged for destruction by a small peptide called ubiquitin which allows recognition by the proteasome to degrade the protein. Diagnosis Screening for muscle atrophy is limited by a lack of established diagnostic criteria, although many have been proposed. Diagnostic criteria for other conditions such as sarcopenia or cachexia can be used. These syndromes can also be identified with screening questionnaires.Muscle mass and changes can be quantified on imaging studies such as CT scans or Magnetic resonance imaging (MRI). Biomarkers such as urine urea can be used to roughly estimate muscle loss during circumstances of rapid muscle loss. Other biomarkers are currently under investigation but are not used in clinical practice. Treatment Muscle atrophy can be delayed, prevented and sometimes reversed with treatment. Treatment approaches include impacting the signaling pathways that induce muscle hypertrophy or slow muscle breakdown as well as optimizing nutritional status.Physical activity provides a significant anabolic muscle stimulus and is a crucial component to slowing or reversing muscle atrophy. It is still unknown regarding the ideal exercise "dosing." Resistance exercise has been shown to be beneficial in reducing muscle atrophy in older adults. In patients who cannot exercise due to physical limitations such as paraplegia, functional electrical stimulation can be used to externally stimulate the muscles.Adequate calories and protein is crucial to prevent muscle atrophy. Protein needs may vary dramatically depending on metabolic factors and disease state, so high-protein supplementation may be beneficial. Supplementation of protein or branched-chain amino acids, especially leucine, can provide a stimulus for muscle synthesis and inhibit protein breakdown and has been studied for muscle atrophy for sarcopenia and cachexia. β-Hydroxy β-methylbutyrate (HMB), a metabolite of leucine which is sold as a dietary supplement, has demonstrated efficacy in preventing the loss of muscle mass in several muscle wasting conditions in humans, particularly sarcopenia. Based upon a meta-analysis of seven randomized controlled trials that was published in 2015, HMB supplementation has efficacy as a treatment for preserving lean muscle mass in older adults. More research is needed to determine the precise effects of HMB on muscle strength and function in various populations.In severe cases of muscular atrophy, the use of an anabolic steroid such as methandrostenolone may be administered to patients as a potential treatment although use is limited by side effects. A novel class of drugs, called selective androgen receptor modulators, is being investigated with promising results. They would have fewer side effects, while still promoting muscle and bone tissue growth and regeneration. These effects have yet to be confirmed in larger clinical trials. Outcomes Outcomes of muscle atrophy depend on the underlying cause and the health of the patient. Immobility or bed rest in populations predisposed to muscle atrophy, such as the elderly or those with disease states that commonly cause cachexia, can cause dramatic muscle atrophy and impact on functional outcomes. In the elderly, this often leads to decreased biological reserve and increased vulnerability to stressors known as the "frailty syndrome." Loss of lean body mass is also associated with increased risk of infection, decreased immunity, and poor wound healing. The weakness that accompanies muscle atrophy leads to higher risk of falls, fractures, physical disability, need for institutional care, reduced quality of life, increased mortality, and increased healthcare costs. Other animals Inactivity and starvation in mammals lead to atrophy of skeletal muscle, accompanied by a smaller number and size of the muscle cells as well as lower protein content. In humans, prolonged periods of immobilization, as in the cases of bed rest or astronauts flying in space, are known to result in muscle weakening and atrophy. Such consequences are also noted in small hibernating mammals like the golden-mantled ground squirrels and brown bats.Bears are an exception to this rule; species in the family Ursidae are famous for their ability to survive unfavorable environmental conditions of low temperatures and limited nutrition availability during winter by means of hibernation. During that time, bears go through a series of physiological, morphological, and behavioral changes. Their ability to maintain skeletal muscle number and size during disuse is of significant importance.During hibernation, bears spend 4-7 months of inactivity and anorexia without undergoing muscle atrophy and protein loss. A few known factors contribute to the sustaining of muscle tissue. During the summer, bears take advantage of the nutrition availability and accumulate muscle protein. The protein balance at time of dormancy is also maintained by lower levels of protein breakdown during the winter. At times of immobility, muscle wasting in bears is also suppressed by a proteolytic inhibitor that is released in circulation. Another factor that contributes to the sustaining of muscle strength in hibernating bears is the occurrence of periodic voluntary contractions and involuntary contractions from shivering during torpor. The three to four daily episodes of muscle activity are responsible for the maintenance of muscle strength and responsiveness in bears during hibernation. See also References External links Media related to Muscle atrophy at Wikimedia Commons Muscular atrophy at the US National Library of Medicine Medical Subject Headings (MeSH)
Myoclonus	Myoclonus is a brief, involuntary, irregular (lacking rhythm) twitching of a muscle or a group of muscles, different from clonus, which is rhythmic or regular. Myoclonus describes a medical sign and, generally, is not a diagnosis of a disease. These myoclonic twitches, jerks, or seizures are usually caused by sudden muscle contractions (positive myoclonus) or brief lapses of contraction (negative myoclonus). The most common circumstance under which they occur is while falling asleep (hypnic jerk). Myoclonic jerks occur in healthy people and are experienced occasionally by everyone. However, when they appear with more persistence and become more widespread they can be a sign of various neurological disorders. Hiccups are a kind of myoclonic jerk specifically affecting the diaphragm. When a spasm is caused by another person it is known as a provoked spasm. Shuddering attacks in babies fall in this category. Myoclonic jerks may occur alone or in sequence, in a pattern or without pattern. They may occur infrequently or many times each minute. Most often, myoclonus is one of several signs in a wide variety of nervous system disorders such as multiple sclerosis, Parkinsons disease, dystonia, cerebral palsy, Alzheimers disease, Gauchers disease, subacute sclerosing panencephalitis, Creutzfeldt–Jakob disease (CJD), serotonin toxicity, some cases of Huntingtons disease, some forms of epilepsy, and occasionally in intracranial hypotension. In almost all instances in which myoclonus is caused by central nervous system disease it is preceded by other symptoms; for instance, in CJD it is generally a late-stage clinical feature that appears after the patient has already started to exhibit gross neurological deficits. Anatomically, myoclonus may originate from lesions of the cortex, subcortex or spinal cord. The presence of myoclonus above the foramen magnum effectively excludes spinal myoclonus; further localisation relies on further investigation with electromyography (EMG) and electroencephalography (EEG). Types The most common types of myoclonus include action, cortical reflex, essential, palatal, those seen in the progressive myoclonus epilepsies, reticular reflex, sleep and stimulus-sensitive. Epilepsy forms Cortical reflex myoclonus is thought to be a type of epilepsy that originates in the cerebral cortex – the outer layer, or "gray matter", of the brain, responsible for much of the information processing that takes place in the brain. In this type of myoclonus, jerks usually involve only a few muscles in one part of the body, but jerks involving many muscles may occur. Cortical reflex myoclonus can be intensified when patients attempt to move in a certain way or perceive a particular sensation. Essential myoclonus occurs in the absence of epilepsy or other apparent abnormalities in the brain or nerves. It can occur randomly in people with no family history, or among members of the same family, indicating that it sometimes may be an inherited disorder. Essential myoclonus tends to be stable without increasing in severity over time. Some scientists speculate that some forms of essential myoclonus may be a type of epilepsy with no known cause. Juvenile myoclonic epilepsy (JME) usually consists of jerking and muscle twitches of the upper extremities. This may include the arms, shoulders, elbows, and very rarely, the legs. JME is among the most common types of epilepsy and can affect one of every 14 people with the disease. These seizures typically occur shortly after waking up. Onset for JME can be seen around puberty for most patients. Administration of medications that also treat multiple seizure types is usually the most effective form of treatment. Lennox-Gastaut syndrome (LGS), or childhood epileptic encephalopathy, is a rare epileptic disorder accounting for 1–4% of childhood epilepsies. The syndrome has much more severe symptoms ranging from multiple seizures daily, learning disabilities, abnormal findings in electroencephalogram (EEG). Earlier age of seizure onset is correlated with higher risk of cognitive impairment. Progressive myoclonus epilepsy (PME) is a group of diseases characterized by myoclonus, epileptic seizures, tonic-clonic seizures, and other serious symptoms such as trouble walking or speaking. These rare disorders often get worse over time and can be fatal. Studies have identified at least three forms of PME. Lafora disease is inherited as an autosomal recessive disorder, meaning that the disease occurs only when a child inherits two copies of a defective gene, one from each parent. Lafora disease is characterized by myoclonus, epileptic seizures, and dementia (progressive loss of memory and other intellectual functions). A second group of PME diseases belonging to the class of cerebral storage diseases usually involves myoclonus, visual problems, dementia, and dystonia (sustained muscle contractions that cause twisting movements or abnormal postures). Another group of PME disorders in the class of system degenerations often is accompanied by action myoclonus, seizures, and problems with balance and walking. Many of these PME diseases begin in childhood or adolescence. Treatment is not normally successful for any extended period of time. Reticular reflex myoclonus is thought to be a type of generalized epilepsy that originates in the brainstem, the part of the brain that connects to the spinal cord and controls vital functions such as breathing and heartbeat. Myoclonic jerks usually affect the whole body, with muscles on both sides of the body affected simultaneously. In some people, myoclonic jerks occur in only a part of the body, such as the legs, with all the muscles in that part being involved in each jerk. Reticular reflex myoclonus can be triggered by either a voluntary movement or an external stimulus. Diaphragmatic flutter A very rare form includes the diaphragmatic flutter, the Belly Dancers Syndrome,: 2 or Van Leeuwenhoeks disease. It was first described by Antonie van Leeuwenhoek in 1723, who had it.: 2 The condition characterizes spoken communication that sounds like a short-breathed hiccup. These muscle spasms can recur dozens of times per day. Rate of diaphragmatic contraction ranges between 35 and 480 contractions per minute, with the average rate found to be 150.: 3 Studies show that possible causes include disruptions within the central or peripheral nervous systems, anxiety, nutritional disorder, and certain pharmaceuticals. No single treatment has proven effective, though blocking or crushing of the phrenic nerve can provide instantaneous relief when pharmacologic treatment has proven ineffective.: 11 Only about 50 people in the world have been diagnosed with diaphragmatic flutter. Other forms Action myoclonus is characterized by muscular jerking triggered or intensified by voluntary movement or even the intention to move. It may be made worse by attempts at precise, coordinated movements. Action myoclonus is the most disabling form of myoclonus and can affect the arms, legs, face, and even the voice. It is often associated with tonic-clonic seizures and diffuse neuronal disease such as post-hypoxic encephalopathy, uremia, and the various forms of PME, although, in the case of focal cerebral damage, the disease may be restricted to one limb. This type of myoclonus often is caused by brain damage that results from a lack of oxygen and blood flow to the brain when breathing or heartbeat is temporarily stopped. Over-excitement of the sensorimotor cortex (cortical reflex myoclonus) or reticular formation (reticular reflex myoclonus) is also a cause of action myoclonus. Serotonin and GABA neurotransmitters are thought to cause this lack of inhibition, which is a possible explanation as to why improvements are made with the administration of serotonin precursors. Systems involved include the cerebellodentatorubral, pyramidal, extrapyramidal, optic, auditory, posterior columns and gracile and cuneate nuclei, spinocerebellar tracts, motor neurons of cranial nerves and anterior horns, and muscle fibers. Palatal myoclonus is a regular, rhythmic contraction of one or both sides of the rear of the roof of the mouth, called the soft palate. These contractions may be accompanied by myoclonus in other muscles, including those in the face, tongue, throat, and diaphragm. The contractions are very rapid, occurring as often as 150 times a minute, and may persist during sleep. The condition usually appears in adults and can last indefinitely. People with palatal myoclonus usually regard it as a minor problem; some complain of an occasional "clicking" sound, a noise made as the soft palate muscles contract. Middle ear myoclonus occurs in the muscles of the middle ear. These muscles may include the tensor tympani and stapedius muscles. It can involve the muscles surrounding the Eustachian tube, which include the tensor veli palatini, levator veli palatini, and salpingopharyngeus. Those affected describe it as a thumping sound or sensation in the ear. Spinal myoclonus is myoclonus originating in the spinal cord, including segmental and propriospinal myoclonus. The latter is usually due to a thoracic generator producing truncal flexion jerk. It is often stimulus-induced with a delay due to the slow conducting propriospinal nerve fibers. Stimulus-sensitive myoclonus is triggered by a variety of external events, including noise, movement, and light. Surprise may increase the sensitivity of the patient. Sleep myoclonus occurs during the initial phases of sleep, especially at the moment of dropping off to sleep, and include familiar examples of myoclonus such as the hypnic jerk. Some forms appear to be stimulus-sensitive. Some people with sleep myoclonus are rarely troubled by it, or need treatment. If it is a symptom of more complex and disturbing sleep disorders, such as restless legs syndrome, it may require medical treatment. Myoclonus can be associated with patients with Tourette syndrome. Signs and symptoms Myoclonic seizure can be described as "jumps" or "jolts" experienced in a single extremity or even the entire body. The feeling experienced by the individual is described as uncontrollable jolts common to receiving a mild electric shock. The sudden jerks and twitching of the body can often be so severe that it can cause a small child to fall. A myoclonic seizure (myo "muscle", clonic "jerk") is a sudden involuntary contraction of muscle groups. The muscle jerks consist of symmetric, mostly generalized jerks, localized in the arms and in the shoulders and also simultaneously with a head nod; both the arms may fling out together and simultaneously a head nod may occur. Symptoms have some variability amongst subjects. Sometimes the entire body may jerk, just like a startle response. As is the case with all generalised seizures, the patient is not conscious during the event but the seizure is so brief that the person appears to remain fully conscious. In reflex epilepsies, myoclonic seizures can be brought on by flashing lights or other environmental triggers (see photosensitive epilepsy). Familiar examples of normal myoclonus include hiccups and hypnic jerks that some people experience while drifting off to sleep. Severe cases of pathologic myoclonus can distort movement and severely limit a persons ability to sleep, eat, talk, and walk. Myoclonic jerks commonly occur in individuals with epilepsy. Cause Myoclonus in healthy individuals may indicate nothing other than arbitrary muscle contraction. Myoclonus may also develop in response to infection, hyperosmolar hyperglycemic state, head or spinal cord injury, stroke, stress, brain tumors, kidney or liver failure, lipid storage disease, chemical or drug poisoning, as a side effect of certain drugs (such as tramadol, quinolones, benzodiazepine, gabapentin, sertraline, lamotrigine, opioids), or other disorders. Benign myoclonic movements are commonly seen during the induction of general anesthesia with intravenous medications such as etomidate and propofol. These are postulated to result from decreased inhibitory signaling from cranial neurons. Prolonged oxygen deprivation to the brain, hypoxia, may result in posthypoxic myoclonus. People with benign fasciculation syndrome can often experience myoclonic jerking of limbs, fingers and thumbs. Myoclonus can occur by itself, but most often as one of several symptoms associated with a variety of nervous system disorders, including multiple sclerosis, Parkinsons disease, Alzheimers disease, opsoclonus myoclonus, Creutzfeldt–Jakob disease, Lyme disease and lupus. Myoclonic jerks commonly occur in persons with epilepsy, a disorder in which the electrical activity in the brain becomes disordered leading to seizures. It is also found in MERRF (Myoclonic Epilepsy with Ragged Red Fibers), a rare mitochondrial encephalomyopathy. Jerks of muscle groups, much of the body, or a series in rapid succession, which results in the person jerking bolt upright from a more relaxed sitting position is sometimes seen in ambulatory patients being treated with high doses of morphine, hydromorphone, and similar drugs, and is possibly a sign of high and/or rapidly increasing serum levels of these drugs. Myoclonic jerks caused by other opioids, such as tramadol and pethidine, may be less benign. Medications unrelated to opioids, such as anticholinergics, are known to cause myoclonic jerks. Pathophysiology Most myoclonus is caused by a disturbance of the central nervous system. Some are from peripheral nervous system injury. Studies suggest several locations in the brain are involved in myoclonus. One is in the brainstem, close to structures that are responsible for the startle response, an automatic reaction to an unexpected stimulus involving rapid muscle contraction. The specific mechanisms underlying myoclonus are not yet fully understood. Scientists believe that some types of stimulus-sensitive myoclonus may involve overexcitability of the parts of the brain that control movement. These parts are interconnected in a series of feedback loops called motor pathways. These pathways facilitate and modulate communication between the brain and muscles. Key elements of this communication are chemicals known as neurotransmitters, which carry messages from one nerve cell, or neuron, to another. Neurotransmitters are released by neurons and attach themselves to receptors on parts of neighboring cells. Some neurotransmitters may make the receiving cell more sensitive, while others tend to make the receiving cell less sensitive. Laboratory studies suggest that an imbalance between these chemicals may underlie myoclonus. Some researchers speculate that abnormalities or deficiencies in the receptors for certain neurotransmitters may contribute to some forms of myoclonus. Receptors that appear to be related to myoclonus include those for two important inhibitory neurotransmitters: serotonin, which constricts blood vessels and brings on sleep, and gamma-aminobutyric acid (GABA), which helps the brain maintain muscle control. Other receptors with links to myoclonus include those for benzodiazepines, drugs that induce sleep, and for glycine, an inhibitory neurotransmitter that is important for the control of motor and sensory functions in the spinal cord. More research is needed to determine how these receptor abnormalities cause or contribute to myoclonus. Treatment Concerning more serious conditions, the complex origins of myoclonus may be treated with multiple drugs, which have a limited effect individually, but greater when combined with others that act on different brain pathways or mechanisms. Treatment is most effective when the underlying cause is known, and can be treated as such. Some drugs being studied in different combinations include clonazepam, sodium valproate, piracetam, and primidone. Hormonal therapy may improve responses to antimyoclonic drugs in some people. Some studies have shown that doses of 5-hydroxytryptophan (5-HTP) leads to improvement in patients with some types of action myoclonus and PME. These differences in the effect of 5-HTP on patients with myoclonus have not yet been explained. Many of the drugs used for myoclonus, such as barbiturates, phenytoin and primidone, are also used to treat epilepsy. Barbiturates slow down the central nervous system and cause tranquilizing or antiseizure effects. Phenytoin and primidone are effective antiepileptics drugs, although phenytoin can cause liver failure or have other harmful long-term effects in patients with PME. Sodium valproate is an alternative therapy for myoclonus and can be used either alone or in combination with clonazepam. Some people have adverse reactions to clonazepam and/or sodium valproate. When patients are taking multiple medications, the discontinuation of drugs suspected of causing myoclonus and treatment of metabolic derangements may resolve some cases of myoclonus. When pharmacological treatment is indicated anticonvulsants are the main line of treatment. Paradoxical reactions to treatment are notable. Drugs which most people respond to may in other individuals worsen their symptoms. Sometimes this leads to the mistake of increasing the dose, rather than decreasing or stopping the drug. Treatment of myoclonus focuses on medications that may help reduce symptoms. Drugs used include sodium valproate, clonazepam, the anticonvulsant levetiracetam, and piracetam. Dosages of clonazepam usually are increased gradually until the patient improves or side effects become harmful. Drowsiness and loss of coordination are common side effects. The beneficial effects of clonazepam may diminish over time if the patient develops a tolerance to the drug. In forms of myoclonus where only a single area is affected, and even in a few other various forms, Botox injections (OnabotulinumtoxinA) may be helpful. The chemical messenger responsible for triggering the involuntary muscle contractions is blocked by the Botulinum toxins of the Botox.Surgery is also a viable option for treatment if the symptoms are caused by a tumor or lesion in the brain or spinal cord. Surgery may also correct symptoms in those where myoclonus affects parts of the face or ear. While DBS is still being studied for use with myoclonus, Deep Brain Stimulation has also been tried in those with this and other movement disorders. Prognosis The effects of myoclonus in an individual can vary depending on the form and the overall health of the individual. In severe cases, particularly those indicating an underlying disorder in the brain or nerves, movement can be extremely distorted and limit ability to normally function, such as in eating, talking, and walking. In these cases, treatment that is usually effective, such as clonazepam and sodium valproate, may instead cause adverse reaction to the drug, including increased tolerance and a greater need for increase in dosage. However, the prognosis for more simple forms of myoclonus in otherwise healthy individuals may be neutral, as the disease may cause few to no difficulties. Other times the disease starts simply, in one region of the body, and then spreads. Research Research on myoclonus is supported through the National Institute of Neurological Disorders and Stroke (NINDS). The primary focus of research is on the role of neurotransmitters and receptors involved in the disease. Identifying whether or not abnormalities in these pathways cause myoclonus may help in efforts to develop drug treatments and diagnostic tests. Determining the extent that genetics play in these abnormalities may lead to potential treatments for their reversal, potentially correcting the loss of inhibition while enhancing mechanisms in the body that would compensate for their effects. Etymology The word myoclonus uses combining forms of myo- and clonus, indicating muscle contraction dysfunction. It is pronounced or . The prevalence of the variants shows division between American English and British English. The variant stressing the -oc- syllable is the only pronunciation given in a half dozen major American dictionaries (medical and general). The variant stressing the -clo- syllable is given in the British English module of Oxford Dictionaries online but not in the American English module. See also Periodic limb movement disorder Benign fasciculation syndrome Restless legs syndrome Fasciculation Brain Zaps (SSRI withdrawal) Clonus Fahrs syndrome References External links The first version of this article was adapted from the public domain NINDS Myoclonus Information Page. "Why do we twitch while falling asleep?" (The Straight Dope) Myoclonus Fact Sheet, National Institute of Neurological Disorders and Stroke (viewed 5 Apr 2005)
Warfarin resistance	Warfarin resistance is a rare condition in which people have varying degrees of tolerance to the anticoagulant drug warfarin. In incomplete warfarin resistance, people only respond to high doses of warfarin; in complete warfarin resistance, the drug has no effect. This can be because the drug is metabolized quickly or because the clotting cascade does not interact with warfarin as it should. One gene that has been identified in warfarin resistance is VKORC1, a gene responsible for warfarin metabolism. It is inherited in an autosomal dominant pattern. References == External links ==
Pulmonary edema	Pulmonary edema, also known as pulmonary congestion, is excessive liquid accumulation in the tissue and air spaces (usually alveoli) of the lungs. It leads to impaired gas exchange and may cause hypoxemia and respiratory failure. It is due to either failure of the left ventricle of the heart to remove oxygenated blood adequately from the pulmonary circulation (cardiogenic pulmonary edema), or an injury to the lung tissue directly or blood vessels of the lung (non-cardiogenic pulmonary edema).Treatment is focused on three aspects: firstly improving respiratory function, secondly, treating the underlying cause, and thirdly preventing further damage and assuring full recovery to the lung. Pulmonary edema, especially when sudden (acute), can lead to respiratory failure or cardiac arrest due to hypoxia. It is a cardinal feature of congestive heart failure. The term edema is from the Greek οἴδημα (oidēma, "swelling"), from οἰδέω (oidéō, "(I) swell"). Types Classically it is cardiogenic (left ventricular) but fluid may also accumulate due to damage to the lung. This damage may be from direct external injuries or injuries mediated by high pressures within the pulmonary circulation. When directly or indirectly caused by increased left ventricular pressure, pulmonary edema may form when mean pulmonary pressure rises from the normal average of 15 mmHg to above 25 mmHg, where pulmonary fluid may form. Broadly, the causes of pulmonary edema can be divided into cardiogenic and non-cardiogenic. By convention, cardiogenic specifically refers to left ventricular causes. Cardiogenic Congestive heart failure which is due to the hearts inability to pump the blood out of the pulmonary circulation at a sufficient rate resulting in elevation in pulmonary wedge pressure and edema – this usually is due to left ventricular failure, but may also be from arrhythmias, or fluid overload, (e.g. from kidney failure or intravenous therapy). Hypertensive crisis can cause pulmonary edema as the elevation in blood pressure and increased afterload on the left ventricle hinders forward flow in blood vessels and causes the elevation in wedge pressure and subsequent pulmonary edema. Non-cardiogenic Negative pressure pulmonary edema in which a significant negative (internal) pressure in the chest (such as from an inhalation against an upper airway obstruction) ruptures capillaries and floods the alveoli with blood. Negative pressure pulmonary edema has an incidence in the range of 0.05-0.1% in cases of general anesthesia. The negative pressure causes a significant increase in preload, thereby increasing pulmonary blood volume. There is also a significant increase in left ventricular afterload, which causes a decreased cardiac output. The increase in pulmonary blood volume and pressure along with a decrease in cardiac output to the lungs will increase the pulmonary transudative pressures and the risk of pulmonary edema. With all this occurring, pulmonary vascular resistance increases causing a shift of the intraventricular septum. The ventricular septal shift to the left causes a left ventricular diastolic dysfunction, which further increases pulmonary hydrostatic pressures and the risk. Neurogenic causes (seizures, head trauma, strangulation, electrocution). Pulmonary embolismAcute lung injury may also cause pulmonary edema directly through injury to the vasculature and parenchyma of the lung. It includes acute lung injury and acute respiratory distress syndrome. (ALI-ARDS) cover many of these causes, but they may also include: Inhalation of hot or toxic gases Pulmonary contusion, i.e., high-energy trauma (e.g. vehicle accidents) Aspiration, e.g., gastric fluid Reexpansion, i.e. post large volume thoracocentesis, resolution of pneumothorax, post decortication, removal of endobronchial obstruction, effectively a form of negative pressure pulmonary oedema. Reperfusion injury, i.e., postpulmonary thromboendartectomy or lung transplantation Swimming induced pulmonary edema also known as immersion pulmonary edema Transfusion Associated Circulatory Overload occurs when multiple blood transfusions or blood-products (plasma, platelets, etc.) are transfused over a short period of time. Transfusion associated Acute Lung Injury is a specific type of blood-product transfusion injury that occurs when the donors plasma contained antibodies against the recipient, such as anti-HLA or anti-neutrophil antibodies. Severe infection or inflammation which may be local or systemic. This is the classical form of acute lung injury-adult respiratory distress syndrome.Some causes of pulmonary edema are less well characterised and arguably represent specific instances of the broader classifications above. Arteriovenous malformation Hantavirus pulmonary syndrome High altitude pulmonary edema (HAPE) Envenomation, such as with the venom of Atrax robustus Signs and symptoms The most common symptom of pulmonary edema is difficulty breathing (dyspnea), but may include other symptoms such as coughing up blood (classically seen as pink or red, frothy sputum), excessive sweating, anxiety, and pale skin. Shortness of breath can manifest as orthopnea (inability to breath sufficiently when lying down flat due to breathlessness) and/or paroxysmal nocturnal dyspnea (episodes of severe sudden breathlessness at night). These are common presenting symptoms of chronic and cardiogenic pulmonary edema due to left ventricular failure. The development of pulmonary edema may be associated with symptoms and signs of "fluid overload" in the lungs; this is a non-specific term to describe the manifestations of right ventricular failure on the rest of the body and includes peripheral edema (swelling of the legs, in general, of the "pitting" variety, wherein the skin is slow to return to normal when pressed upon due to fluid), raised jugular venous pressure and hepatomegaly, where the liver is excessively enlarged and may be tender or even pulsatile. Other signs include end-inspiratory crackles (crackling sounds heard at the end of a deep breath) on auscultation and the presence of a third heart sound. Flash pulmonary edema Flash pulmonary edema (FPE), is rapid onset acute pulmonary edema. It is most often precipitated by acute myocardial infarction or mitral regurgitation, but can be also caused by aortic regurgitation, heart failure, or almost any cause leading to elevated left ventricular filling pressures. Treatment of FPE should be directed at the underlying cause, but the mainstays are nitroglycerin, ensuring adequate oxygenation with non-invasive ventilation, and decrease of pulmonary circulation pressures while FPE stays.Recurrence of FPE is thought to be associated with hypertension and may signify renal artery stenosis. Prevention of recurrence is based on managing or preventing hypertension, coronary artery disease, renovascular hypertension, and heart failure. Diagnosis There is no single test for confirming that breathlessness is caused by pulmonary edema – there are many causes of shortness of breath; but there are methods to suggest a high probability of an edema. Low oxygen saturation in blood and disturbed arterial blood gas readings support the proposed diagnosis by suggesting a pulmonary shunt. A chest X-ray will show fluid in the alveolar walls, Kerley B lines, increased vascular shadowing in a classical batwing peri-hilum pattern, upper lobe diversion (biased blood flow to the superior parts instead of inferior parts of the lung), and possibly pleural effusions. In contrast, patchy alveolar infiltrates are more typically associated with noncardiogenic edemaLung ultrasounds, employed by a healthcare provider at the point of care, is also a useful tool to diagnose pulmonary edema; not only is it accurate, but it may quantify the degree of lung water, track changes over time, and differentiate between cardiogenic and non-cardiogenic edema.Especially in the case of cardiogenic pulmonary edema, urgent echocardiography may strengthen the diagnosis by demonstrating impaired left ventricular function, high central venous pressures and high pulmonary artery pressures leading to pulmonary edema. Blood tests are performed for electrolytes (sodium, potassium) and markers of renal function (creatinine, urea). Liver enzymes, inflammatory markers (usually C-reactive protein) and a complete blood count as well as coagulation studies (PT, aPTT) are also typically requested as further diagnosis. B-type natriuretic peptide (BNP) is available in many hospitals, sometimes even as a point-of-care test. Low levels of BNP (<100 pg/ml) suggest a cardiac cause is unlikely. Prevention In those with underlying heart or lung disease, effective control of congestive and respiratory symptoms helps prevents pulmonary edema.Dexamethasone is in widespread use for the prevention of high altitude pulmonary edema. Sildenafil is used as a preventive treatment for altitude-induced pulmonary edema and pulmonary hypertension, the mechanism of action is via phosphodiesterase inhibition which raises cGMP, resulting in pulmonary arterial vasodilation and inhibition of smooth muscle cell proliferation and indirectly fluid formation in the lungs. While this effect has only recently been discovered, sildenafil is already becoming an accepted treatment for this condition, in particular in situations where the standard treatment of rapid descent (acclimatization) has been delayed for some reason. Management The initial management of pulmonary edema, irrespective of the type or cause, is supporting vital functions while edema lasts. Therefore, if the level of consciousness is decreased it may be required to proceed to tracheal intubation and mechanical ventilation to prevent airway compromise. Hypoxia (abnormally low oxygen levels) may require supplementary oxygen to balance blood oxygen levels, but if this is insufficient then again mechanical ventilation may be required to prevent complications caused by hypoxia. Treatment of the underlying cause is the next priority; pulmonary edema secondary to infection, for instance, would require the administration of appropriate antibiotics or antivirals. Cardiogenic pulmonary edema Acute cardiogenic pulmonary edema often responds rapidly to medical treatment. Positioning upright may relieve symptoms. A loop diuretic such as furosemide (or Lasix®) is administered, often together with morphine to reduce respiratory distress. Both diuretic and morphine may have vasodilator effects, but specific vasodilators may be used (particularly intravenous glyceryl trinitrate or ISDN) provided the blood pressure is adequate.Continuous positive airway pressure and bilevel positive airway pressure (CPAP/BiPAP) has been demonstrated to reduce mortality and the need of mechanical ventilation in people with severe cardiogenic pulmonary edema.It is possible for cardiogenic pulmonary edema to occur together with cardiogenic shock, in which the cardiac output is insufficient to sustain an adequate blood pressure to the lungs. This can be treated with inotropic agents or by intra-aortic balloon pump, but this is regarded as temporary treatment while the underlying cause is addressed and the lungs recover. == References ==
Fecal impaction	A fecal impaction is a solid, immobile bulk of feces that can develop in the rectum as a result of chronic constipation. A related term is fecal loading which refers to a large volume of stool in the rectum of any consistency. Fecal impaction is a common result of neurogenic bowel dysfunction and causes immense discomfort and pain. Treatment of fecal impaction includes laxatives, enema, and pulsed irrigation evacuation (PIE). Signs and symptoms Symptoms include chronic constipation. There can be fecal incontinence and paradoxical overflow diarrhea (encopresis) as liquid stool passes around the obstruction. Complications may include necrosis and ulcers of the rectal tissue. Abdominal pain and bloating could also be present depending on the severity of the condition. Loss of appetite can also occur. Causes There are many possible causes; for example, physical inactivity, not eating enough fiber, dehydration, and holding in bowel movements. Medications such as opioid pain relievers (fentanyl, buprenorphine, methadone, codeine, oxycodone, hydrocodone, morphine, hydromorphone, etc.) and certain sedatives that reduce intestinal movement may cause fecal matter to become too large, hard and/or dry to expel. Specific conditions, such as irritable bowel syndrome, certain neurological disorders, paralytic ileus, gastroparesis, diabetes, dehydration, enlarged prostate gland, distended colon, ingested foreign object, inflammatory bowel diseases such as Crohns disease and colitis, and autoimmune diseases such as amyloidosis, celiac disease, lupus, and scleroderma can cause constipation. Hypothyroidism can cause chronic constipation because of sluggish, slower, or weaker colon contractions. Iron supplements or increased blood calcium levels are also potential causes. Spinal cord injury is a common cause of constipation, due to ileus. Manual removal of a fecal impaction is often required with obese patients in traction, after a barium enema, and in poorly hydrated older adults. Prevention Reducing opiate-based medication (when possible, tolerable, and safe; prescription medication changes should be done under the supervision of a physician), and adequate intake of liquids (water) and dietary fiber and daily exercise. Treatment The treatment of fecal impaction requires both the remedy of the impaction and treatment to prevent recurrences. Decreased motility of the colon results in dry, hard stools that in the case of fecal impaction become compacted into a large, hard mass of stool that cannot be expelled from the rectum. Various methods of treatment attempt to remove the impaction by softening the stool, lubricating the stool, or breaking it into pieces small enough for removal. Enemas and osmotic laxatives can be used to soften the stool by increasing the water content until it is soft enough to be expelled. Osmotic laxatives such as magnesium citrate work within minutes - eight hours for onset of action, and even then they may not be sufficient to expel the stool. Osmotic laxatives can cause cramping and even severe pain as the patients attempts to evacuate the contents of the rectum are blocked by the fecal mass. Polyethylene glycol (PEG 3350) may be used to increase the water content of the stool without cramping. This may take 24 to 48 hours for it to take effect, and it is not well suited to cases where the impaction needs to be removed immediately due to risk of complications or severe pain. Enemas (such as hyperosmotic saline) and suppositories (such as glycerine suppositories) work by increasing water content and stimulating peristalsis to aid in expulsion, and both work much more quickly than oral laxatives. Because enemas work in 2–15 minutes, they do not allow sufficient time for a large fecal mass to soften. Even if the enema is successful at dislodging the impacted stool, the impacted stool may remain too large to be expelled through the anal canal. Mineral oil enemas can assist by lubricating the stool for easier passage. In cases where enemas fail to remove the impaction, polyethylene glycol can be used to attempt to soften the mass over 24–48 hours, or if immediate removal of the mass is needed, manual disimpaction may be used. Manual disimpaction may be performed by lubricating the anus and using one gloved finger with a scoop-like motion to break up the fecal mass. Most often manual disimpaction is performed without general anaesthesia, although sedation may be used. In more involved procedures, general anaesthesia may be used, although the use of general anaesthesia increases the risk of damage to the anal sphincter. If all other treatments fail, surgery may be necessary. An easier, more comfortable, and more efficient method to enema and manual disimpaction is to use pulsed irrigation evacuation (PIE). This method implemented with PIE MED allows for patients to rest in bed as the procedure takes place. By using pulsating water to enter into the colon to soften and break down the dense mass, PIE effectively treats fecal impaction. Research studies have shown that by the success of the PIE MED treatment prevented patient hospitalization for fecal impaction.Individuals who have had one fecal impaction are at high risk of future impactions. Therefore, preventive treatment should be instituted in patients following the removal of the mass. Increasing dietary fiber, increasing fluid intake, exercising daily, and attempting regularly to defecate every morning after eating should be promoted in all patients.Often underlying medical conditions cause fecal impactions; these conditions should be treated to reduce the risk of future impactions. Many types of medications (most notably opioid pain medications, such as codeine) reduce motility of the colon, increasing the likelihood of fecal impactions. If possible, alternate medications should be prescribed that avoid the side effect of constipation.Given that all opioids can cause constipation, it is recommended that any patient placed on opioid pain medications be given medications to prevent constipation before it occurs. Daily medications can also be used to promote normal motility of the colon and soften stools. Daily use of laxatives or enemas should be avoided by most individuals as it can cause the loss of normal colon motility. However, for patients with chronic complications, daily medication under the direction of a physician may be needed. Polyethylene glycol 3350 can be taken daily to soften the stools without the significant risk of adverse effects that are common with other laxatives. In particular, stimulant laxatives should not be used frequently because they can cause dependence in which an individual loses normal colon function and is unable to defecate without taking a laxative. Frequent use of osmotic laxatives should be avoided as well as they can cause electrolyte imbalances. Research shows that pulsed irrigation evacuation with the PIE MED device is successful in all tested patients in studies, making pulsed irrigation evacuation the most effective and reliable form of fecal impaction treatment. Fecaloma A fecaloma is a more extreme form of fecal impaction, giving the accumulation an appearance of a tumor.A fecaloma can develop as the fecal matter gradually stagnates and accumulates in the intestine and increases in volume until the intestine becomes deformed. It may occur in chronic obstruction of stool transit, as in megacolon and chronic constipation. Some diseases, such as Chagas disease, Hirschsprungs disease and others damage the autonomic nervous system in the colons mucosa (Auerbachs plexus) and may cause extremely large or "giant" fecalomas, which must be surgically removed (disimpaction). Rarely, a fecalith will form around a hairball (Trichobezoar), or other hygroscopic or desiccant nucleus. It can be diagnosed by: CT scan Projectional radiography UltrasoundDistal or sigmoid, fecalomas can often be disimpacted digitally or by a catheter which carries a flow of disimpaction fluid (water or other solvent or lubricant). Surgical intervention in the form of sigmoid colectomy or proctocolectomy and ileostomy may be required only when all conservative measures of evacuation fail. Attempts at removal can have severe and even lethal effects, such as the rupture of the colon wall by catheter or an acute angle of the fecaloma (stercoral perforation), followed by sepsis. It may also lead to stercoral perforation, a condition characterized by bowel perforation due to pressure necrosis from a fecal mass or fecaloma. See also Aerosol impaction Colon Dental impaction Impaction (animals) References Further reading Wrenn K (September 1989). "Fecal impaction". The New England Journal of Medicine. 321 (10): 658–62. doi:10.1056/NEJM198909073211007. PMID 2671728. Dugdale, David C. (January 31, 2011). "Fecal impaction". A.D.A.M., Inc. Gattuso JM, Kamm MA, Halligan SM, Bartram CI (April 1996). "The anal sphincter in idiopathic megarectum: effects of manual disimpaction under general anesthetic". Diseases of the Colon and Rectum. 39 (4): 435–9. doi:10.1007/bf02054060. PMID 8878505. S2CID 40482887. == External links ==
Sterility	Sterile or sterility may refer to: Asepsis, a state of being free from biological contaminants Sterile (archaeology), a sediment deposit which contains no evidence of human activity Sterilization (microbiology), any process that eliminates or kills all forms of life or removes them from an item or a field Sterility (physiology), an inability of a living organism to effect sexual reproduction Infertility, a medical condition which prevents a person, an animal or a plant from bearing children, especially through natural means Sterile Records, a record label which was formed by Nigel Ayers and Caroline K of the post-industrial music group Nocturnal Emissions in London in 1979 See also Sterilization (disambiguation)
Porphyria cutanea tarda	Porphyria cutanea tarda is the most common subtype of porphyria. The disease is named because it is a porphyria that often presents with skin manifestations later in life. The disorder results from low levels of the enzyme responsible for the fifth step in heme production. Heme is a vital molecule for all of the bodys organs. It is a component of hemoglobin, the molecule that carries oxygen in the blood. Hepatoerythropoietic porphyria has been described as a homozygous form of porphyria cutanea tarda, although it can also be caused if two different mutations occur at the same locus. Symptoms and signs Porphyria cutanea tarda (PCT) is recognized as the most prevalent subtype of porphyritic diseases.PCT is characterized by onycholysis and blistering of the skin in areas that receive higher levels of exposure to sunlight. The primary cause is a deficiency of uroporphyrinogen decarboxylase (UROD), a cytosolic enzyme that is a step in the enzymatic pathway that leads to the synthesis of heme. Behind the direct cause there are a number of genetic and environmental risk factors.Patients who are diagnosed with PCT typically seek treatment following the development of photosensitivities causing blisters and erosions on exposed areas of the skin. This is usually observed in the face, hands, forearms, and lower legs. Healing is slow and leaves scarring. Though blisters are the most common skin manifestations of PCT, other skin manifestations include hyperpigmentation (similar to a tan) and hypertrichosis (mainly on the cheeks) also occur. PCT is a chronic condition, with external symptoms often subsiding and recurring as a result of multiple factors. In addition to the skin lesions, chronic liver disease is very common in patients with sporadic PCT. This involves hepatic fibrosis (scarring of the liver), and inflammation. However, liver problems are less common in patients with the inherited form of the disease. Additionally, patients will often void a wine-red color urine with an increased concentration of uroporphyrin I due to their enzymatic deficiency. Vitamin, mineral, and enzyme deficiencies Certain vitamin and minerals deficiencies are common in people with porphyria cutanea tarda. The most common deficiencies are beta-Carotene, retinol, vitamin A and vitamin C. Beta-Carotene is required to synthesize vitamin A and vitamin A is needed to synthesize retinol. A lack of retinol-binding protein is due to a lack of retinol which is required to trigger its production.Porphyrins interact with iron, absorbing photons to create reactive oxygen species is the mechanism of action causing the itchy, painful blisters of PCT. The reactive oxygen species consume the skin antioxidants beta-carotene, vitamin E, and vitamin C. Supplementation of these three vitamins reduces the oxidation and potentially diminishes the severity of blister formation. No single one of the three vitamins can inhibit the damaging effects of oxidized porphyrins, specifically uroporphyrins and coproporphyrins, but all three working together synergistically are capable of neutralizing their damaging effects. Genetics Inherited mutations in the UROD gene cause about 20% of cases (the other 80% of cases do not have mutations in UROD, and are classified as sporadic). UROD makes an enzyme called uroporphyrinogen III decarboxylase, which is critical to the chemical process that leads to heme production. The activity of this enzyme is usually reduced by 50% in all tissues in people with the inherited form of the condition.Nongenetic factors such as excess iron or partially genetic factors such as alcohol use disorder and others listed above can increase the demand for heme and the enzymes required to make heme. The combination of this increased demand and reduced activity of uroporphyrinogen decarboxylase disrupts heme production and allows byproducts of the process to accumulate in the body, triggering the signs and symptoms of porphyria cutanea tarda.The HFE gene makes a protein that helps cells regulate the absorption of iron from the digestive tract and into the cells of the body. Certain mutations in the HFE gene cause hemochromatosis (an iron overload disorder). People who have these mutations are also at an increased risk of developing porphyria cutanea tarda.In the 20% of cases where porphyria cutanea tarda is inherited, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene is sufficient to decrease enzyme activity and cause the signs and symptoms of the disorder. Other While inherited deficiencies in uroporphyrinogen decarboxylase often lead to the development of PCT, there are a number of risk factors that can both cause and exacerbate the symptoms of this disease. One of the most common risk factors observed is infection with the Hepatitis C virus. One review of a collection of PCT studies noted Hepatitis C infection in 50% of documented cases of PCT. Additional risk factors include alcohol use disorder, excess iron (from iron supplements as well as cooking on cast iron skillets), and exposure to chlorinated cyclic hydrocarbons and Agent Orange.It can be a paraneoplastic phenomenon. Exacerbating factors Alcohol Estrogen Iron Hepatitis C virus Pathogenesis Porphyria cutanea tarda is primarily caused by uroporphyrinogen decarboxylase deficiency (UROD). Uroporphyrinogen decarboxylase occurs in nature as a homodimer of two subunits. It participates in the fifth step in heme synthesis pathway, and is active in the cytosol. This enzymatic conversion results in coproporphyrinogen III as the primary product. This is accomplished by the clockwise removal of the four carboxyl groups present in the cyclic uroporphyrinogen III molecule. Therefore, a deficiency in this enzyme causes the aforementioned buildup of uroporphyrinogen and hepta-carboxylic porphyrinogen, and to a lesser extent hexa-carboxylic porphyrinogen, and penta-carboxylic porphyrinogen in the urine, which can be helpful in the diagnosis of this disorder.The dermatological symptoms of PCT that include blistering and lesions on sun-exposed areas of the skin are caused by a buildup of porphyrin compounds (specifically uroporphyrinogen) close to the surface of the skin that have been oxidized by free radicals or sunlight. The oxidized porphyrins initiate degranulation of dermal mast cells, which release proteases that catabolize the surrounding proteins. This begins a cell-mediated positive feedback loop which matches the description of a type 4 delayed hypersensitivity reaction. The resulting blisters, therefore, do not appear immediately but begin to show up 2–3 days after sun exposure. Due to the highly conjugated structure of porphyrins involving alternating single and double carbon bonds, these compounds exhibit a deep purple color, resulting in the discoloration observed in the skin. Excess alcohol intake decreases hepcidin production which leads to increased iron absorption from the gut and an increase in oxidative stress. This oxidative stress then leads to inhibition of uroporphyrinogen decarboxylase, creating an excess of uroporphyrinogen III which is oxidized from the relatively harmless porphyrinogens into their oxidized porphyrins form. Concentrated instances of oxidative stress (alcohol, physical trauma, psychological stress, etc.) cause the liver to hemorrhage these porphyrins into the blood stream where they are then susceptible to oxidation.The strong association of PCT with Hepatitis C virus infection is not entirely understood. Studies have suggested that the cytopathic effect of the virus on hepatocytes can lead to the release of free iron. This iron can disrupt the activity of cytochrome p450, releasing activated oxygen species. These can oxidize the UROD substrate uroporphyrinogen, which can result in the inhibition of UROD and lead to deficient activity of this key enzyme.Excess alcohol use is frequently associated with both inducing PCT and aggravating a preexisting diagnosis of the disorder. It is thought to do so by causing oxidative damage to liver cells, resulting in oxidized species of uroporphyrinogen that inhibit the activity of hepatic UROD. It is also felt to increase the uptake of iron in liver cells, leading to further oxidation of uroporphyrinogen by the release of activated oxygen species. Additionally, exposure to chlorinated cyclic hydrocarbons can lead to a deficiency in the activity of uroporphyrinogen decarboxylase, causing the buildup of excess uroporphyrinogen. Additionally, alcohol has been shown to increase the activity of the delta-aminolevulinic acid synthetase (ALA synthetase), the rate-limiting enzymatic step in heme synthesis in the mitochondria, in rats. Therefore, alcohol consumption may increase the production of uroporphyrinogen, exacerbating symptoms in individuals with porphyria cutanea tarda. Diagnosis While the most common symptom of PCT is the appearance of skin lesions and blistering, their appearance is not conclusive. Laboratory testing commonly reveals high levels of uroporphyrinogen in the urine, clinically referred to as uroporphyrinogenuria. Additionally, testing for common risk factors such as hepatitis C and hemochromatosis is strongly suggested, as their high prevalence in patients with PCT may require additional treatment. If clinical appearance of PCT is present, but laboratories are negative, the diagnosis of pseudoporphyria should be seriously considered. Classification Some sources divide PCT into two types: sporadic and familial. Other sources include a third type, but this is less common. One study used 74% as the cutoff for UROD activity, with those patients under that number being classified as type II, and those above classified as type III if there was a family history, and type I if there was not.Genetic variants associated with hemochromatosis have been observed in PCT patients, which may help explain inherited PCT not associated with UROD. Treatment Since PCT is a chronic condition, a comprehensive management of the disease is the most effective means of treatment. Primarily, it is key that patients diagnosed with PCT avoid alcohol consumption, iron supplements, excess exposure to sunlight (especially in the summer), as well as estrogen and chlorinated cyclic hydrocarbons, all of which can potentially exacerbate the disorder. Additionally, the management of excess iron (due to the commonality of hemochromatosis in PCT patients) can be achieved through phlebotomy, whereby blood is systematically drained from the patient. A borderline iron deficiency has been found to have a protective effect by limiting heme synthesis. In the absence of iron, which is to be incorporated in the porphyrin formed in the last step of the synthesis, the mRNA of erythroid 5-aminolevulinate synthase (ALAS-2) is blocked by attachment of an iron-responsive element (IRE) binding cytosolic protein, and transcription of this key enzyme is inhibited.Low doses of antimalarials can be used. Orally ingested chloroquine is completely absorbed in the gut and is preferentially concentrated in the liver, spleen, and kidneys. They work by removing excess porphyrins from the liver via increasing the excretion rate by forming a coordination complex with the iron center of the porphyrin as well as an intramolecular hydrogen bond between a propionate side chain of the porphyrin and the protonated quinuclidine nitrogen atom of either alkaloid. Due to the presence of the chlorine atom, the entire complex is more water-soluble allowing the kidneys to preferentially remove it from the blood stream and expel it through urination. Chloroquine treatment can induce porphyria attacks within the first couple of months of treatment due to the mass mobilization of porphyrins from the liver into the blood stream. Complete remission can be seen within 6–12 months as each dose of antimalarial can only remove a finite amount of porphyrins and there are generally decades of accumulation to be cleared. Originally, higher doses were used to treat the condition but are no longer recommended because of liver toxicity. Finally, due to the strong association between PCT and Hepatitis C, the treatment of Hepatitis C (if present) is vital to the effective treatment of PCT. Chloroquine, hydroxychloroquine, and venesection are typically employed in the management strategy. Epidemiology PCT prevalence is estimated at 1 in 10,000. An estimated 80% of porphyria cutanea tarda cases are sporadic. The exact frequency is not clear because many people with the condition never experience symptoms and those that do are often misdiagnosed with anything ranging from idiopathic photodermatitis and seasonal allergies to hives. Society and culture Porphyria cutanea tarda is implicated in the origin of vampire myths. This is because people with the disease tend to avoid the sun due to photosensitivity and may develop disfigurement that eats away their noses, eyelids, lips, and gums giving their teeth a fang-like appearance. It has also been suggested they may have developed a craving for healthy blood to replace their own in a self medicated treatment in prior centuries. Some folklore scholars claim that this is a mistake, first suggested in the 1990s, because vampires of myth did not have photosensitivity, nor were they described as looking like the modern incarnation of vampires. They were described as unintelligent roaming beings who fed on their victims to the point that they became reddened and heavily bloated, fattened on blood. Fangs were very rarely mentioned. Photosensitivity was not added to the vampire mythology until the 1922 film Nosferatu. Count Dracula of Bram Strokers novel could walk about freely in daylight unharmed but not as powerful in the book.Porphyria cutanea tarda is the name of a song by the rock band AFI on their fourth album Black Sails in the Sunset, released on May 18, 1999.Porphyria cutanea tarda is the disease that both Dabney Pratt and Brother Rush suffer from in Virginia Hamiltons childrens novel Sweet Whispers, Brother Rush. References External links Porphyria cutanea tarda at NIHs Office of Rare Diseases
Pyoderma	Pyoderma means any skin disease that is pyogenic (has pus). These include superficial bacterial infections such as impetigo, impetigo contagiosa, ecthyma, folliculitis, Bockharts impetigo, furuncle, carbuncle, tropical ulcer, etc. Autoimmune conditions include pyoderma gangrenosum. Pyoderma affects more than 111 million children worldwide, making it one of the three most common skin disorders in children along with scabies and tinea. See also List of cutaneous conditions References == External links ==
Dopamine dysregulation syndrome	Dopamine dysregulation syndrome (DDS) is a dysfunction of the reward system observed in some individuals taking dopaminergic medications for an extended length of time. It typically occurs in people with Parkinsons disease (PD) who have taken dopamine agonist medications for an extended period of time. It is characterized by self-control problems such as addiction to medication, gambling, or sexual behavior. Signs and symptoms The most common symptom is craving for dopaminergic medication. However other behavioral symptoms can appear independently of craving or co-occur with it. Craving is an intense impulse of the subject to obtain medication even in the absence of symptoms that indicate its intake. To fulfill this need the person will self-administer extra doses. When self-administration is not possible, aggressive outbursts or the use of strategies such as symptom simulation or bribery to access additional medication can also appear.Hypomania, manifesting with feelings of euphoria, omnipotence, or grandiosity, are prone to appear in those moments when medication effects are maximum; dysphoria, characterized by sadness, psychomotor slowing, fatigue or apathy are typical with dopamine replacement therapy (DRT) withdrawal. Different impulse control disorders have been described including gambling, compulsive shopping, eating disorders and hypersexuality. Behavioral disturbances, most commonly aggressive tendencies, are the norm. Psychosis is also common. Causes Parkinsons disease is a common neurological disorder characterized by a degeneration of dopamine neurons in the substantia nigra and a loss of dopamine in the putamen. It is described as a motor disease, but it also produces cognitive and behavioral symptoms. The most common treatment is dopamine replacement therapy, which consists in the administration of levodopa (L-Dopa) or dopamine agonists (such as pramipexole or ropinirole) to patients. Dopamine replacement therapy is well known to improve motor symptoms but its effects in cognitive and behavioral symptoms are more complex. Dopamine has been related to the normal learning of stimuli with behavioral and motivational significance, attention, and most importantly the reward system. In accordance with the role of dopamine in reward processing, addictive drugs stimulate dopamine release. Although the exact mechanism has yet to be elucidated, the role of dopamine in the reward system and addiction has been proposed as the origin of DDS. Models of addiction have been used to explain how dopamine replacement therapy produces DDS. One of these models of addiction proposes that over the usage course of a drug there is a habituation to the rewarding effects that it produces at the initial stages. This habituation is thought to be dopamine mediated. With long-term administration of L-dopa the reward system gets used to it and needs higher quantities. As the user increases drug intake there is a loss of dopaminergic receptors in the striatum which acts in addition to an impairment in goal-direction mental functions to produce an enhancement of sensitization to dopamine therapy. The behavioral and mood symptoms of the syndrome are produced by the dopamine overdose. Diagnosis Diagnosis of the syndrome is clinical since there are no laboratory tests to confirm it. For diagnosis a person with documented responsiveness to medication has to increase medication intake beyond dosage needed to relieve their parkinsonian symptoms in a pathological addiction-like pattern. A current mood disorder (depression, anxiety, hypomanic state or euphoria), behavioral disorder (excessive gambling, shopping or sexual tendency, aggression, or social isolation) or an altered perception about the effect of medication also have to be present. A questionnaire on the typical symptoms of DDS has also been developed and can help in the diagnosis process. Prevention The main prevention measure proposed is the prescription of the lowest possible dose of dopamine replacement therapy to individuals at risk. The minimization of the use of dopamine agonists, and of short duration formulations of L-Dopa can also decrease risk of the syndrome. Management First choice management measure consists in the enforcement of a dopaminergic drug dosage reduction. If this decrease is maintained, dysregulation syndrome features soon decrease. Cessation of dopamine agonists therapy may also be of use. Some behavioral characteristics may respond to psychotherapy; and social support is important to control risk factors. In some cases antipsychotic drugs may also be of use in the presence of psychosis, aggression, gambling or hypersexuality.Based upon five case reports, valproic acid may have efficacy in controlling the symptoms of levodopa-induced DDS that arise from the use of levodopa for the treatment of Parkinsons disease. Epidemiology DDS is not common among PD patients. Prevalence may be around 4%. Its prevalence is higher among males with an early onset of the disease. Previous substance abuse such as heavy drinking or drug intake seems to be the main risk factor along with a history of affective disorder. History PD was first formally described in 1817; however, L-dopa did not enter clinical practice until almost 1970. In these initial works there were already reports of neuropsychiatric complications. During the following decades cases featuring DDS symptoms in relation to dopamine therapy such as hypersexuality, gambling or punding, appeared. DDS was first described as a syndrome in the year 2000. Three years later the first review articles on the syndrome were written, showing an increasing awareness of the DDS importance. Diagnostic criteria were proposed in 2005. == Notes ==
Skin condition	A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of this system is as a barrier against the external environment.Conditions of the human integumentary system constitute a broad spectrum of diseases, also known as dermatoses, as well as many nonpathologic states (like, in certain circumstances, melanonychia and racquet nails). While only a small number of skin diseases account for most visits to the physician, thousands of skin conditions have been described. Classification of these conditions often presents many nosological challenges, since underlying causes and pathogenetics are often not known. Therefore, most current textbooks present a classification based on location (for example, conditions of the mucous membrane), morphology (chronic blistering conditions), cause (skin conditions resulting from physical factors), and so on.Clinically, the diagnosis of any particular skin condition begins by gathering pertinent information of the presenting skin lesion(s), including: location (arms, head, legs); symptoms (pruritus, pain); duration (acute or chronic); arrangement (solitary, generalized, annular, linear); morphology (macules, papules, vesicles); and color (red). Some diagnoses may also require a skin biopsy which yields histologic information that can be correlated with the clinical presentation and any laboratory data. The introduction of cutaneous ultrasound has allowed the detection of cutaneous tumors, inflammatory processes, and skin diseases. Layer of skin involved The skin weighs an average of 4 kg (8.8 lb), covers an area of 2 m2 (22 sq ft), and is made of three distinct layers: the epidermis, dermis, and subcutaneous tissue. The two main types of human skin are glabrous skin, the nonhairy skin on the palms and soles (also referred to as the "palmoplantar" surfaces), and hair-bearing skin. Within the latter type, hairs in structures called pilosebaceous units have a hair follicle, sebaceous gland, and associated arrector pili muscle. In the embryo, the epidermis, hair, and glands are from the ectoderm, which is chemically influenced by the underlying mesoderm that forms the dermis and subcutaneous tissues. Epidermis The epidermis is the most superficial layer of skin, a squamous epithelium with several strata: the stratum corneum, stratum lucidum, stratum granulosum, stratum spinosum, and stratum basale. Nourishment is provided to these layers via diffusion from the dermis, since the epidermis is without direct blood supply. The epidermis contains four cell types: keratinocytes, melanocytes, Langerhans cells, and Merkel cells. Of these, keratinocytes are the major component, constituting roughly 95% of the epidermis. This stratified squamous epithelium is maintained by cell division within the stratum basale, in which differentiating cells slowly displace outwards through the stratum spinosum to the stratum corneum, where cells are continually shed from the surface. In normal skin, the rate of production equals the rate of loss; about two weeks are needed for a cell to migrate from the basal cell layer to the top of the granular cell layer, and an additional two weeks to cross the stratum corneum. Dermis The dermis is the layer of skin between the epidermis and subcutaneous tissue, and comprises two sections, the papillary dermis and the reticular dermis. The superficial papillary dermis interdigitates with the overlying rete ridges of the epidermis, between which the two layers interact through the basement membrane zone. Structural components of the dermis are collagen, elastic fibers, and ground substance also called extra fibrillar matrix. Within these components are the pilosebaceous units, arrector pili muscles, and the eccrine and apocrine glands. The dermis contains two vascular networks that run parallel to the skin surface—one superficial and one deep plexus—which are connected by vertical communicating vessels. The function of blood vessels within the dermis is fourfold: to supply nutrition, to regulate temperature, to modulate inflammation, and to participate in wound healing. Subcutaneous tissue The subcutaneous tissue is a layer of fat between the dermis and underlying fascia. This tissue may be further divided into two components, the actual fatty layer, or panniculus adiposus, and a deeper vestigial layer of muscle, the panniculus carnosus. The main cellular component of this tissue is the adipocyte, or fat cell. The structure of this tissue is composed of septal (i.e. linear strands) and lobular compartments, which differ in microscopic appearance. Functionally, the subcutaneous fat insulates the body, absorbs trauma, and serves as a reserve energy source. Diseases of the skin Diseases of the skin include skin infections and skin neoplasms (including skin cancer). History In 1572, Geronimo Mercuriali of Forlì, Italy, completed De morbis cutaneis (On the diseases of the skin). It is considered the first scientific work dedicated to dermatology. Diagnoses The physical examination of the skin and its appendages, as well as the mucous membranes, forms the cornerstone of an accurate diagnosis of cutaneous conditions. Most of these conditions present with cutaneous surface changes termed "lesions," which have more or less distinct characteristics. Often proper examination will lead the physician to obtain appropriate historical information and/or laboratory tests that are able to confirm the diagnosis. Upon examination, the important clinical observations are the (1) morphology, (2) configuration, and (3) distribution of the lesion(s). With regard to morphology, the initial lesion that characterizes a condition is known as the "primary lesion", and identification of such a lesions is the most important aspect of the cutaneous examination. Over time, these primary lesions may continue to develop or be modified by regression or trauma, producing "secondary lesions". However, with that being stated, the lack of standardization of basic dermatologic terminology has been one of the principal barriers to successful communication among physicians in describing cutaneous findings. Nevertheless, there are some commonly accepted terms used to describe the macroscopic morphology, configuration, and distribution of skin lesions, which are listed below. Lesions Primary lesions Macule: A macule is a change in surface color, without elevation or depression, so nonpalpable, well or ill-defined, variously sized, but generally considered less than either 5 or 10 mm in diameter at the widest point. Patch: A patch is a large macule equal to or greater than either 5 or 10 mm across, depending on ones definition of a macule. Patches may have some subtle surface change, such as a fine scale or wrinkling, but although the consistency of the surface is changed, the lesion itself is not palpable. Papule: A papule is a circumscribed, solid elevation of skin, varying in size from less than either 5 or 10 mm in diameter at the widest point. Plaque: A plaque has been described as a broad papule, or confluence of papules equal to or greater than 10 mm, or alternatively as an elevated, plateau-like lesion that is greater in its diameter than in its depth. Nodule: A nodule is morphologically similar to a papule in that it is also a palpable spherical lesion less than 10 mm in diameter. However, it is differentiated by being centered deeper in the dermis or subcutis. Tumor: Similar to a nodule, but it is larger than 10 mm in diameter. Vesicle: A vesicle is a small blister, a circumscribed, epidermal elevation generally considered less than either 5 or 10 mm in diameter at the widest point. Bulla: A bulla is a large blister, a rounded or irregularly shaped blister equal to or greater than either 5 or 10 mm, depending on ones definition of a vesicle. Pustule: A pustule is a small elevation of the skin usually consisting of necrotic inflammatory cells. Cyst: A cyst is an epithelial-lined cavity. Wheal: A wheal is a rounded or flat-topped, pale red papule or plaque that is characteristically evanescent, disappearing within 24 to 48 hours. The temporary raised skin on the site of a properly delivered intradermal (ID) injection is also called a welt, with the ID injection process itself frequently referred to as simply "raising a wheal" in medical texts. Welts: Welts occur as a result of blunt force being applied to the body with elongated objects without sharp edges. Telangiectasia: A telangiectasia represents an enlargement of superficial blood vessels to the point of being visible. Burrow: A burrow appears as a slightly elevated, grayish, tortuous line in the skin, and is caused by burrowing organisms. Secondary lesions Scale: Dry or greasy laminated masses of keratin, they represent thickened stratum corneum. Crust: Dried sebum usually mixed with epithelial and sometimes bacterial debris Lichenification: Epidermal thickening characterized by visible and palpable thickening of the skin with accentuated skin markings Erosion: An erosion is a discontinuity of the skin exhibiting incomplete loss of the epidermis, a lesion that is moist, circumscribed, and usually depressed. Excoriation: A punctate or linear abrasion produced by mechanical means (often scratching), usually involving only the epidermis, but commonly reaching the papillary dermis Ulcer: An ulcer is a discontinuity of the skin exhibiting complete loss of the epidermis and often portions of the dermis. Fissure is a lesion in the skin that is usually narrow but deep. Induration is dermal thickening causing the cutaneous surface to feel thicker and firmer. Atrophy refers to a loss of skin, and can be epidermal, dermal, or subcutaneous. With epidermal atrophy, the skin appears thin, translucent, and wrinkled. Dermal or subcutaneous atrophy is represented by depression of the skin. Maceration: softening and turning white of the skin due to being consistently wet. Umbilication is formation of a depression at the top of a papule, vesicle, or pustule. Phyma: A tubercle on any external part of the body, such as in phymatous rosacea Configuration "Configuration" refers to how lesions are locally grouped ("organized"), which contrasts with how they are distributed (see next section). Distribution "Distribution" refers to how lesions are localized. They may be confined to a single area (a patch) or may exist in several places. Some distributions correlate with the means by which a given area becomes affected. For example, contact dermatitis correlates with locations where allergen has elicited an allergic immune response. Varicella zoster virus is known to recur (after its initial presentation as chicken pox) as herpes zoster ("shingles"). Chicken pox appears nearly everywhere on the body, but herpes zoster tends to follow one or two dermatomes; for example, the eruptions may appear along the bra line, on either or both sides of the patient. Other related terms Histopathology See also Wound, an injury which damages the epidermis. References == External links ==
Cognitive deficit	Cognitive deficit is an inclusive term to describe any characteristic that acts as a barrier to the cognition process.The term may describe deficits in overall intelligence (as with intellectual disabilities), specific and restricted deficits in cognitive abilities (such as in learning disorders like dyslexia), neuropsychological deficits (such as in attention, working memory or executive function), or it may describe drug-induced impairment in cognition and memory (such as that seen with alcohol, glucocorticoids, and the benzodiazepines.) Cause It usually refers to a durable characteristic, as opposed to altered level of consciousness, which may be acute and reversible. Cognitive deficits may be inborn or caused by environmental factors such as brain injuries, neurological disorders, or mental illness. Screening Screening for cognitive impairment in those over the age of 65 without symptoms is of unclear benefit versus harm as of 2020. In a large population-based cohort study included 579,710 66-year-old adults who were followed for a total of 3,870,293 person-years (average 6.68 ± 1.33 years per person), subjective cognitive decline was significantly associated with an increased risk of subsequent dementia. Treatment Older people with cognitive impairment appear to improve somewhat with light therapy. Other findings Although one would expect cognitive decline to have major effects on job performance, it seems that there is little to no correlation of health with job performance. With the exception of cognitive-dependent jobs such as air-traffic controller, professional athlete, or other elite jobs, age does not seem to impact ones job performance. This obviously conflicts with cognitive tests given, so the matter has been researched further. One possible reason for this conclusion is the rare need for a person to perform at their maximum. There is a difference between typical functioning, that is – the normal level of functioning for daily life, and maximal functioning, that is – what cognitive tests observe as our maximum level of functioning. As the maximum cognitive ability that we are able to achieve decreases, it may not actually affect our daily lives, which only require the normal level.Some studies have indicated that childhood hunger might have a protective effect on cognitive decline. One possible explanation is that the onset of age-related changes in the body can be delayed by calorie restriction. Another possible explanation is the selective survival effect, as the study participants who had a childhood with hunger tend to be the healthiest of their era. See also PASS Theory of Intelligence Fluid and crystallized intelligence References Further reading Das, J.P.; Naglieri, J.A.; Kirby, J.R. (1994). Assessment of Cognitive Processes. Needham Heights, MA: Allyn & Bacon. ISBN 0-205-14164-1. Das, J.P. (2002). A better look at intelligence. Current Directions in Psychology, 11, 28–32. Goldstein, Gerald; Beers, Susan, eds (2004). Comprehensive Handbook of Psychological Assessment: Volume I: Intellectual and Neurological Assessment. Hoboken, NJ: John Wiley & Sons. Kaufman, Alan S. (2000). "Chapter 20: Tests of Intelligence". In Sternberg, Robert J. (ed.). Handbook of Intelligence. Cambridge: Cambridge University Press. pp. 445–476. ISBN 978-0-521-59648-0. Naglieri, Jack A.; Otero, Tulio M. (2012). "Chapter 15: The Cognitive Assessment System: From Theory to Practice". In Flanagan, Dawn P.; Harrison, Patti L. (eds.). Contemporary Intellectual Assessment: Theories, tests, and issues (Third ed.). New York: Guilford Press. pp. 376–399. ISBN 978-1-60918-995-2. ERIC ED530599. Sattler, Jerome M. (2008). Assessment of Children: Cognitive Foundations. La Mesa (CA): Jerome M. Sattler, Publisher. Urbina, Susana (2004). Essentials of Psychological Testing. John Wiley & Sons. ISBN 978-0-471-41978-5. Urbina, Susana (2011). "Chapter 2: Tests of Intelligence". In Sternberg, Robert J.; Kaufman, Scott Barry (eds.). The Cambridge Handbook of Intelligence. Cambridge: Cambridge University Press. pp. 20–38. ISBN 978-0-521-73911-5. == External links ==
Blood type	A blood type (also known as a blood group) is a classification of blood, based on the presence and absence of antibodies and inherited antigenic substances on the surface of red blood cells (RBCs). These antigens may be proteins, carbohydrates, glycoproteins, or glycolipids, depending on the blood group system. Some of these antigens are also present on the surface of other types of cells of various tissues. Several of these red blood cell surface antigens can stem from one allele (or an alternative version of a gene) and collectively form a blood group system.Blood types are inherited and represent contributions from both parents of an individual. As of 2021, a total of 43 human blood group systems are recognized by the International Society of Blood Transfusion (ISBT). The two most important blood group systems are ABO and Rh; they determine someones blood type (A, B, AB, and O, with + or − denoting RhD status) for suitability in blood transfusion. Blood group systems A complete blood type would describe each of the 43 blood groups, and an individuals blood type is one of many possible combinations of blood-group antigens. Almost always, an individual has the same blood group for life, but very rarely an individuals blood type changes through addition or suppression of an antigen in infection, malignancy, or autoimmune disease. Another more common cause of blood type change is a bone marrow transplant. Bone-marrow transplants are performed for many leukemias and lymphomas, among other diseases. If a person receives bone marrow from someone of a different ABO type (e.g., a type A patient receives a type O bone marrow), the patients blood type should eventually become the donors type, as the patients hematopoietic stem cells (HSCs) are destroyed, either by ablation of the bone marrow or by the donors T-cells. Once all the patients original red blood cells have died, they will have been fully replaced by new cells derived from the donor HSCs. Provided the donor had a different ABO type, the new cells surface antigens will be different from those on the surface of the patients original red blood cells.Some blood types are associated with inheritance of other diseases; for example, the Kell antigen is sometimes associated with McLeod syndrome. Certain blood types may affect susceptibility to infections, an example being the resistance to specific malaria species seen in individuals lacking the Duffy antigen. The Duffy antigen, presumably as a result of natural selection, is less common in population groups from areas having a high incidence of malaria. ABO blood group system The ABO blood group system involves two antigens and two antibodies found in human blood. The two antigens are antigen A and antigen B. The two antibodies are antibody A and antibody B. The antigens are present on the red blood cells and the antibodies in the serum. Regarding the antigen property of the blood all human beings can be classified into four groups, those with antigen A (group A), those with antigen B (group B), those with both antigen A and B (group AB) and those with neither antigen (group O). The antibodies present together with the antigens are found as follows: Antigen A with antibody B Antigen B with antibody A Antigen AB with neither antibody A nor B Antigen null (group O) with both antibody A and BThere is an agglutination reaction between similar antigen and antibody (for example, antigen A agglutinates the antibody A and antigen B agglutinates the antibody B). Thus, transfusion can be considered safe as long as the serum of the recipient does not contain antibodies for the blood cell antigens of the donor.The ABO system is the most important blood-group system in human-blood transfusion. The associated anti-A and anti-B antibodies are usually immunoglobulin M, abbreviated IgM, antibodies. It has been hypothesized that ABO IgM antibodies are produced in the first years of life by sensitization to environmental substances such as food, bacteria, and viruses, although blood group compatibility rules are applied to newborn and infants as a matter of practice. The original terminology used by Karl Landsteiner in 1901 for the classification was A/B/C; in later publications "C" became "O". Type O is often called 0 (zero, or null) in other languages. Rh blood group system The Rh system (Rh meaning Rhesus) is the second most significant blood-group system in human-blood transfusion with currently 50 antigens. The most significant Rh antigen is the D antigen, because it is the most likely to provoke an immune system response of the five main Rh antigens. It is common for D-negative individuals not to have any anti-D IgG or IgM antibodies, because anti-D antibodies are not usually produced by sensitization against environmental substances. However, D-negative individuals can produce IgG anti-D antibodies following a sensitizing event: possibly a fetomaternal transfusion of blood from a fetus in pregnancy or occasionally a blood transfusion with D positive RBCs. Rh disease can develop in these cases. Rh negative blood types are much less common in Asian populations (0.3%) than they are in European populations (15%).The presence or absence of the Rh(D) antigen is signified by the + or − sign, so that, for example, the A− group is ABO type A and does not have the Rh (D) antigen. ABO and Rh distribution by country As with many other genetic traits, the distribution of ABO and Rh blood groups varies significantly between populations. Other blood group systems As of 2021, 41 blood-group systems have been identified by the International Society for Blood Transfusion in addition to the ABO and Rh systems. Thus, in addition to the ABO antigens and Rh antigens, many other antigens are expressed on the RBC surface membrane. For example, an individual can be AB, D positive, and at the same time M and N positive (MNS system), K positive (Kell system), Lea or Leb negative (Lewis system), and so on, being positive or negative for each blood group system antigen. Many of the blood group systems were named after the patients in whom the corresponding antibodies were initially encountered. Blood group systems other than ABO and Rh pose a potential, yet relatively low, risk of complications upon mixing of blood from different people.Following is a comparison of clinically relevant characteristics of antibodies against the main human blood group systems: Clinical significance Blood transfusion Transfusion medicine is a specialized branch of hematology that is concerned with the study of blood groups, along with the work of a blood bank to provide a transfusion service for blood and other blood products. Across the world, blood products must be prescribed by a medical doctor (licensed physician or surgeon) in a similar way as medicines. Much of the routine work of a blood bank involves testing blood from both donors and recipients to ensure that every individual recipient is given blood that is compatible and is as safe as possible. If a unit of incompatible blood is transfused between a donor and recipient, a severe acute hemolytic reaction with hemolysis (RBC destruction), kidney failure and shock is likely to occur, and death is a possibility. Antibodies can be highly active and can attack RBCs and bind components of the complement system to cause massive hemolysis of the transfused blood.Patients should ideally receive their own blood or type-specific blood products to minimize the chance of a transfusion reaction. It is also possible to use the patients own blood for transfusion. This is called autologous blood transfusion, which is always compatible with the patient. The procedure of washing a patients own red blood cells goes as follows: The patients lost blood is collected and washed with a saline solution. The washing procedure yields concentrated washed red blood cells. The last step is reinfusing the packed red blood cells into the patient. There are multiple ways to wash red blood cells. The two main ways are centrifugation and filtration methods. This procedure can be performed with microfiltration devices like the Hemoclear filter. Risks can be further reduced by cross-matching blood, but this may be skipped when blood is required for an emergency. Cross-matching involves mixing a sample of the recipients serum with a sample of the donors red blood cells and checking if the mixture agglutinates, or forms clumps. If agglutination is not obvious by direct vision, blood bank technologist usually check for agglutination with a microscope. If agglutination occurs, that particular donors blood cannot be transfused to that particular recipient. In a blood bank it is vital that all blood specimens are correctly identified, so labelling has been standardized using a barcode system known as ISBT 128. The blood group may be included on identification tags or on tattoos worn by military personnel, in case they should need an emergency blood transfusion. Frontline German Waffen-SS had blood group tattoos during World War II. Rare blood types can cause supply problems for blood banks and hospitals. For example, Duffy-negative blood occurs much more frequently in people of African origin, and the rarity of this blood type in the rest of the population can result in a shortage of Duffy-negative blood for these patients. Similarly, for RhD negative people there is a risk associated with travelling to parts of the world where supplies of RhD negative blood are rare, particularly East Asia, where blood services may endeavor to encourage Westerners to donate blood. Hemolytic disease of the newborn (HDN) A pregnant woman may carry a fetus with a blood type which is different from her own. Typically, this is an issue if a Rh- mother has a child with a Rh+ father, and the fetus ends up being Rh+ like the father. In those cases, the mother can make IgG blood group antibodies. This can happen if some of the fetus blood cells pass into the mothers blood circulation (e.g. a small fetomaternal hemorrhage at the time of childbirth or obstetric intervention), or sometimes after a therapeutic blood transfusion. This can cause Rh disease or other forms of hemolytic disease of the newborn (HDN) in the current pregnancy and/or subsequent pregnancies. Sometimes this is lethal for the fetus; in these cases it is called hydrops fetalis. If a pregnant woman is known to have anti-D antibodies, the Rh blood type of a fetus can be tested by analysis of fetal DNA in maternal plasma to assess the risk to the fetus of Rh disease. One of the major advances of twentieth century medicine was to prevent this disease by stopping the formation of Anti-D antibodies by D negative mothers with an injectable medication called Rho(D) immune globulin. Antibodies associated with some blood groups can cause severe HDN, others can only cause mild HDN and others are not known to cause HDN. Blood products To provide maximum benefit from each blood donation and to extend shelf-life, blood banks fractionate some whole blood into several products. The most common of these products are packed RBCs, plasma, platelets, cryoprecipitate, and fresh frozen plasma (FFP). FFP is quick-frozen to retain the labile clotting factors V and VIII, which are usually administered to patients who have a potentially fatal clotting problem caused by a condition such as advanced liver disease, overdose of anticoagulant, or disseminated intravascular coagulation (DIC).Units of packed red cells are made by removing as much of the plasma as possible from whole blood units. Clotting factors synthesized by modern recombinant methods are now in routine clinical use for hemophilia, as the risks of infection transmission that occur with pooled blood products are avoided. Red blood cell compatibility Blood group AB individuals have both A and B antigens on the surface of their RBCs, and their blood plasma does not contain any antibodies against either A or B antigen. Therefore, an individual with type AB blood can receive blood from any group (with AB being preferable), but cannot donate blood to any group other than AB. They are known as universal recipients. Blood group A individuals have the A antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the B antigen. Therefore, a group A individual can receive blood only from individuals of groups A or O (with A being preferable), and can donate blood to individuals with type A or AB. Blood group B individuals have the B antigen on the surface of their RBCs, and blood serum containing IgM antibodies against the A antigen. Therefore, a group B individual can receive blood only from individuals of groups B or O (with B being preferable), and can donate blood to individuals with type B or AB. Blood group O (or blood group zero in some countries) individuals do not have either A or B antigens on the surface of their RBCs, and their blood serum contains IgM anti-A and anti-B antibodies. Therefore, a group O individual can receive blood only from a group O individual, but can donate blood to individuals of any ABO blood group (i.e., A, B, O or AB). If a patient needs an urgent blood transfusion, and if the time taken to process the recipients blood would cause a detrimental delay, O negative blood can be issued. Because it is compatible with anyone, O negative blood is often overused and consequently is always in short supply. According to the American Association of Blood Banks and the British Chief Medical Officers National Blood Transfusion Committee, the use of group O RhD negative red cells should be restricted to persons with O negative blood, women who might be pregnant, and emergency cases in which blood-group testing is genuinely impracticable. Table note 1. Assumes absence of atypical antibodies that would cause an incompatibility between donor and recipient blood, as is usual for blood selected by cross matching. An Rh D-negative patient who does not have any anti-D antibodies (never being previously sensitized to D-positive RBCs) can receive a transfusion of D-positive blood once, but this would cause sensitization to the D antigen, and a female patient would become at risk for hemolytic disease of the newborn. If a D-negative patient has developed anti-D antibodies, a subsequent exposure to D-positive blood would lead to a potentially dangerous transfusion reaction. Rh D-positive blood should never be given to D-negative women of child-bearing age or to patients with D antibodies, so blood banks must conserve Rh-negative blood for these patients. In extreme circumstances, such as for a major bleed when stocks of D-negative blood units are very low at the blood bank, D-positive blood might be given to D-negative females above child-bearing age or to Rh-negative males, providing that they did not have anti-D antibodies, to conserve D-negative blood stock in the blood bank. The converse is not true; Rh D-positive patients do not react to D negative blood. This same matching is done for other antigens of the Rh system as C, c, E and e and for other blood group systems with a known risk for immunization such as the Kell system in particular for females of child-bearing age or patients with known need for many transfusions. Plasma compatibility Blood plasma compatibility is the inverse of red blood cell compatibility. Type AB plasma carries neither anti-A nor anti-B antibodies and can be transfused to individuals of any blood group; but type AB patients can only receive type AB plasma. Type O carries both antibodies, so individuals of blood group O can receive plasma from any blood group, but type O plasma can be used only by type O recipients. Table note 1. Assuming absence of strong atypical antibodies in donor plasma Rh D antibodies are uncommon, so generally neither D negative nor D positive blood contain anti-D antibodies. If a potential donor is found to have anti-D antibodies or any strong atypical blood group antibody by antibody screening in the blood bank, they would not be accepted as a donor (or in some blood banks the blood would be drawn but the product would need to be appropriately labeled); therefore, donor blood plasma issued by a blood bank can be selected to be free of D antibodies and free of other atypical antibodies, and such donor plasma issued from a blood bank would be suitable for a recipient who may be D positive or D negative, as long as blood plasma and the recipient are ABO compatible. Universal donors and universal recipients In transfusions of packed red blood cells, individuals with type O Rh D negative blood are often called universal donors. Those with type AB Rh D positive blood are called universal recipients. However, these terms are only generally true with respect to possible reactions of the recipients anti-A and anti-B antibodies to transfused red blood cells, and also possible sensitization to Rh D antigens. One exception is individuals with hh antigen system (also known as the Bombay phenotype) who can only receive blood safely from other hh donors, because they form antibodies against the H antigen present on all red blood cells.Blood donors with exceptionally strong anti-A, anti-B or any atypical blood group antibody may be excluded from blood donation. In general, while the plasma fraction of a blood transfusion may carry donor antibodies not found in the recipient, a significant reaction is unlikely because of dilution. Additionally, red blood cell surface antigens other than A, B and Rh D, might cause adverse reactions and sensitization, if they can bind to the corresponding antibodies to generate an immune response. Transfusions are further complicated because platelets and white blood cells (WBCs) have their own systems of surface antigens, and sensitization to platelet or WBC antigens can occur as a result of transfusion. For transfusions of plasma, this situation is reversed. Type O plasma, containing both anti-A and anti-B antibodies, can only be given to O recipients. The antibodies will attack the antigens on any other blood type. Conversely, AB plasma can be given to patients of any ABO blood group, because it does not contain any anti-A or anti-B antibodies. Blood typing Typically, blood type tests are performed through addition of a blood sample to a solution containing antibodies corresponding to each antigen. The presence of an antigen on the surface of the blood cells is indicated by agglutination. In these tests, rather than agglutination, a positive result is indicated by decolorization as red blood cells which bind to the nanoparticles are pulled toward a magnet and removed from solution. Blood group genotyping In addition to the current practice of serologic testing of blood types, the progress in molecular diagnostics allows the increasing use of blood group genotyping. In contrast to serologic tests reporting a direct blood type phenotype, genotyping allows the prediction of a phenotype based on the knowledge of the molecular basis of the currently known antigens. This allows a more detailed determination of the blood type and therefore a better match for transfusion, which can be crucial in particular for patients with needs for many transfusions to prevent allo-immunization. History Blood types were first discovered by an Austrian physician, Karl Landsteiner, working at the Pathological-Anatomical Institute of the University of Vienna (now Medical University of Vienna). In 1900, he found that blood sera from different persons would clump together (agglutinate) when mixed in test tubes, and not only that, some human blood also agglutinated with animal blood. He wrote a two-sentence footnote: The serum of healthy human beings not only agglutinates animal red cells, but also often those of human origin, from other individuals. It remains to be seen whether this appearance is related to inborn differences between individuals or it is the result of some damage of bacterial kind. This was the first evidence that blood variation exists in humans. The next year, in 1901, he made a definitive observation that blood serum of an individual would agglutinate with only those of certain individuals. Based on this he classified human bloods into three groups, namely group A, group B, and group C. He defined that group A blood agglutinates with group B, but never with its own type. Similarly, group B blood agglutinates with group A. Group C blood is different in that it agglutinates with both A and B. This was the discovery of blood groups for which Landsteiner was awarded the Nobel Prize in Physiology or Medicine in 1930. (C was later renamed to O after the German Ohne, meaning without, or zero, or null.) Another group (later named AB) was discovered a year later by Landsteiners students Adriano Sturli and Alfred von Decastello without designating the name (simply referring it to as "no particular type"). Thus, after Landsteiner, three blood types were initially recognised, namely A, B, and C.Czech serologist Jan Janský was the first to recognise and designate four blood types in 1907 that he published in a local journal, using the Roman numerical I, II, III, and IV (corresponding to modern O, A, B, and AB respectively). Unknown to Janský, an American physician William L. Moss introduced almost identical classification in 1910; but his I and IV corresponding Janskýs IV and I. Moss came across Janskýs paper as his was being printed, mentioned it in a footnote. Thus the existence of two systems immediately created confusion and potential danger in medical practice. Mosss system was adopted in Britain, France, and the US, while Janskýs was preferred in most other European countries and some parts of the US. It was reported that "The practically universal use of the Moss classification at that time was completely and purposely cast aside. Therefore in place of bringing order out of chaos, chaos was increased in the larger cities." To resolve the confusion, the American Association of Immunologists, the Society of American Bacteriologists, and the Association of Pathologists and Bacteriologists made a joint recommendation in 1921 that the Jansky classification be adopted based on priority. But it was not followed particularly where Mosss system had been used.In 1927, Landsteiner, who had moved to the Rockefeller Institute for Medical Research in New York, and as a member of a committee of the National Research Council concerned with blood grouping suggested to substitute Janskýs and Mosss systems with the letters O, A, B, and AB. There was another confusion on the use of O which was introduced by Polish physicians Ludwik Hirszfeld and German physician Emil von Dungern in 1910. It was never clear whether it was meant for the figure 0, German null for zero or the upper case letter O for ohne, meaning without; Landsteiner chose the latter. In 1928 the Permanent Commission on Biological Standardization adopted Landsteiners proposal and stated:The Commission learns with satisfaction that, on the initiative of the Health Organization of the League of Nations, the nomenclature proposed by von Dungern and Hirszfeld for the classification of blood groups has been generally accepted, and recommends that this nomenclature shall be adopted for international use as follows: 0 A B AB. To facilitate the change from the nomenclature hitherto employed the following is suggested: Jansky ....0(I) A(II) B(III) AB(IV) Moss ... O(IV) A(II) B(III) AB(I)This classification became widely accepted and after the early 1950s it was universally followed.Hirszfeld and Dungern discovered the inheritance of blood types as Mendelian genetics in 1910 and the existence of sub-types of A in 1911. In 1927, Landsteiner, with Philip Levine, discovered the MN blood group system, and the P system. Development of the Coombs test in 1945, the advent of transfusion medicine, and the understanding of ABO hemolytic disease of the newborn led to discovery of more blood groups. As of 2020, the International Society of Blood Transfusion (ISBT) recognizes 41 blood groups. Society and culture A popular pseudoscientific belief in Eastern Asian countries (especially in Japan and South Korea) known as 血液型 ketsuekigata / hyeoraekhyeong is that a persons ABO blood type is predictive of their personality, character, and compatibility with others. Researchers have established no scientific basis exists for blood type personality categorization, and studies have found no "significant relationship between personality and blood type, rendering the theory "obsolete" and concluding that no basis exists to assume that personality is anything more than randomly associated with blood type." See also Blood type (non-human) Human leukocyte antigen hh blood group References Further reading Dean, Laura (2005). Blood Groups and Red Cell Antigens, a guide to the differences in our blood types that complicate blood transfusions and pregnancy. Bethesda MD: National Center for Biotechnology Information. ISBN 1-932811-05-2. NBK2261. Mollison PL, Engelfriet CP, Contreras M (1997). Blood Transfusion in Clinical Medicine (10th ed.). Oxford UK: Blackwell Science. ISBN 0-86542-881-6. External links BGMUT Blood Group Antigen Gene Mutation Database at NCBI, NIH has details of genes and proteins, and variations thereof, that are responsible for blood types Online Mendelian Inheritance in Man (OMIM): ABO Glycosyltransferase; ABO - 110300 Online Mendelian Inheritance in Man (OMIM): Rhesus Blood Group, D Antigen; RHD - 111680 "Blood group test". Gentest.ch GmbH. Archived from the original on 2017-03-24. Retrieved 2017-03-23. "Blood Facts – Rare Traits". LifeShare Blood Centers. Archived from the original on September 26, 2006. Retrieved September 15, 2006. "Modern Human Variation: Distribution of Blood Types". Dr. Dennis ONeil, Behavioral Sciences Department, Palomar College, San Marcos, California. 2001-06-06. Archived from the original on 2001-06-06. Retrieved November 23, 2006. "Racial and Ethnic Distribution of ABO Blood Types – BloodBook.com, Blood Information for Life". bloodbook.com. Archived from the original on 2010-03-04. Retrieved September 15, 2006. "Molecular Genetic Basis of ABO". Retrieved July 31, 2008.
Vaginal lubrication	Vaginal lubrication is a naturally produced fluid that lubricates a vagina. Vaginal lubrication is always present, but production increases significantly near ovulation and during sexual arousal in anticipation of sexual intercourse. Vaginal dryness is the condition in which this lubrication is insufficient, and sometimes artificial lubricants are used to augment it. Without sufficient lubrication, sexual intercourse can be painful. The vaginal lining has no glands, and therefore the vagina must rely on other methods of lubrication. Plasma from vaginal walls due to vascular engorgement is considered to be the chief lubrication source, and the Bartholins glands, located slightly below and to the left and right of the introitus (vaginal opening), also secrete mucus to augment vaginal-wall secretions. Near ovulation, cervical mucus provides additional lubrication. Vaginal discharge Composition The lubricating fluid can vary in consistency, texture, taste, color, and odor, depending on sexual arousal, the phase of the menstrual cycle, the presence of an infection, certain drugs, genetic factors, and diet.Vaginal fluid is slightly acidic and can become more acidic with certain sexually transmitted diseases. The normal pH of vaginal fluid is between 3.8 and 4.5, contrasting with male semen which is typically between 7.2 and 7.8 (neutral pH is 7.0).During arousal, vaginal lubrication, also sometimes called "arousal fluid", is produced. This is clear, thin, and slippery. It typically only lasts up to an hour. Colloquially, this is referred to as "getting wet". Production The human vagina is serviced by nerves that respond to vasoactive intestinal polypeptide (VIP). As a result, VIP induces an increase in vaginal blood flow accompanied by an increase in vaginal lubrication. The findings suggest that VIP may participate in the control of the local physiological changes observed during sexual arousal: genital vasodilation and increase in vaginal lubrication. Vaginal dryness Insufficient lubrication or vaginal dryness can cause dyspareunia, which is a type of sexual pain disorder. While vaginal dryness is considered an indicator for sexual arousal disorder, vaginal dryness may also result from insufficient excitement and stimulation or from hormonal changes caused by menopause (potentially causing atrophic vaginitis), pregnancy, or breast-feeding. Irritation from contraceptive creams and foams can also cause dryness, as can fear and anxiety about sexual intimacy. Vaginal dryness can also be a symptom of Sjögren syndrome (SS), a chronic autoimmune disorder in which the body destroys moisture-producing glands. Certain medications, including some over-the-counter antihistamines, as well as life events such as pregnancy, lactation, menopause, aging or diseases such as diabetes, will inhibit lubrication. Medicines with anticholinergic or sympathomimetic effects will dry out the mucosal or "wet" tissues of the vagina. Such medicines include many common drugs for allergenic, cardiovascular, psychiatric, and other medical conditions. Oral contraceptives may also increase or decrease vaginal lubrication. Older women produce less vaginal lubrication and reduced estrogen levels may be associated with increased vaginal dryness. Artificial lubricants When a woman is experiencing vaginal dryness before sexual activity, sexual intercourse may be uncomfortable or painful for her. A personal lubricant can be applied to the vaginal opening, the penis, or both, to augment the naturally produced lubrication and prevent or reduce the discomfort or pain. More rarely, a vaginal suppository may be inserted prior to intercourse. Oil-based lubricants can weaken latex and reduce the effectiveness of condoms, latex gloves, or dental dams as either forms of birth control or for protection from sexually transmitted diseases, so water- or silicone-based lubricants are often used instead. The use of an artificial lubricant can make sexual intercourse less painful for a woman, but does not address the underlying cause of the vaginal dryness itself. Both canola oil and mineral oil are recommended by the American Society for Reproductive Medicine as fertility-preserving types of personal lubricant. Dry sex Some people practice dry sex, which involves the removal of vaginal lubrication in some way. The rationale for the practice seems to be for cleansing purposes and to enhance the sexual pleasure of the penetrating partner. However, besides making sexual intercourse painful for the female, the practice is believed to increase the risk of transmitting sexually transmitted diseases for both partners, such as HIV, whose risk of transmission is increased by lacerations in the vaginal tissue resulting from the lack of lubrication. See also References External links Mayo Clinic - Vaginal dryness
Amnesia	Amnesia is a deficit in memory caused by brain damage or disease, but it can also be caused temporarily by the use of various sedatives and hypnotic drugs. The memory can be either wholly or partially lost due to the extent of damage that was caused. There are two main types of amnesia: retrograde amnesia and anterograde amnesia. Retrograde amnesia is the inability to retrieve information that was acquired before a particular date, usually the date of an accident or operation. In some cases the memory loss can extend back decades, while in others the person may lose only a few months of memory. Anterograde amnesia is the inability to transfer new information from the short-term store into the long-term store. People with anterograde amnesia cannot remember things for long periods of time. These two types are not mutually exclusive; both can occur simultaneously.Case studies also show that amnesia is typically associated with damage to the medial temporal lobe. In addition, specific areas of the hippocampus (the CA1 region) are involved with memory. Research has also shown that when areas of the diencephalon are damaged, amnesia can occur. Recent studies have shown a correlation between deficiency of RbAp48 protein and memory loss. Scientists were able to find that mice with damaged memory have a lower level of RbAp48 protein compared to normal, healthy mice. In people with amnesia, the ability to recall immediate information is still retained, and they may still be able to form new memories. However, a severe reduction in the ability to learn new material and retrieve old information can be observed. People can learn new procedural knowledge. In addition, priming (both perceptual and conceptual) can assist amnesiacs in the learning of fresh non-declarative knowledge. Individuals with amnesia also retain substantial intellectual, linguistic, and social skill despite profound impairments in the ability to recall specific information encountered in prior learning episodes.The term is from Ancient Greek forgetfulness; from ἀ- (a-) without, and μνήσις (mnesis) memory. Signs and symptoms Individuals with amnesia can learn new information, particularly if the information is non-declarative knowledge. However, in some situations, people with dense anterograde amnesia do not remember the episodes during which they previously learned or observed the information. Some people with amnesia show abnormal amounts of memory loss, confusion, and difficulty recalling other people or places. People who recover often do not remember having amnesia. Declarative information Declarative memory can be broken down into semantic memory and episodic memory, semantic memory being that of facts, episodic memory being that of memory related to events. While a patient with amnesia might have a loss of declarative memory, this loss might vary in severity as well as the declarative information that it affects, depending on many factors. For example, LSJ was a patient that had retrograde declarative memory loss as the result of bilateral medial temporal lobe damage, but she was still able to remember how to perform some declarative skills. She was able to remember how to read music and the techniques used in art. She had preserved skill-related declarative memory for some things even though she had deficits in other declarative memory tasks. She even scored higher on skill-related declarative memory than the control in watercolor techniques, a technique that she used in her professional career before she acquired amnesia. Semantic Information The loss of semantic information in amnesia is most closely related with damage to the medial temporal lobe or to the neocortex.Some patients with anterograde amnesia can still acquire some semantic information, even though it might be more difficult and might remain rather unrelated to more general knowledge. H.M. could accurately draw a floor plan of the home in which he lived after surgery, even though he had not lived there in years. There is evidence that the hippocampus and the medial temporal lobe may help to consolidate semantic memories, but then they are more correlated with the neocortex. While lesions of the hippocampus normally lead to the loss of episodic memory, if there is any effect on semantic memory, it is more varied and usually does not last as long. Episodic Information One reason that patients could not form new episodic memories is likely because the CA1 region of the hippocampus has a lesion, and thus the hippocampus could not make connections to the cortex. After an ischemic episode (an interruption of the blood flow to the brain), an MRI of patient R.B. following surgery showed his hippocampus to be intact except for a specific lesion restricted to the CA1 pyramidal cells. In one instance, transient global amnesia was caused by a hippocampal CA1 lesion. While this was a temporary case of amnesia, it still shows the importance of the CA1 region of the hippocampus in memory. Episodic memory loss is most likely to occur when there has been damage to the hippocampus. There is evidence that damage to the medial temporal lobe correlates to a loss of autobiographical episodic memory. Non-declarative information Some retrograde and anterograde amnesiacs are capable of non-declarative memory, including implicit learning and procedural learning. For example, some patients show improvement on the pseudorandom sequences experiment just as healthy people; therefore, procedural learning can proceed independently of the brain system required for declarative memory. Some patients with amnesia are able to remember skills that they had learned without being able to consciously recall where they had learned that information. For example, they may learn to do a task and then be able to perform the task later without any recollection of learning the task. According to fMRI studies, the acquisition of procedural memories activates the basal ganglia, the premotor cortex and the supplementary motor area, regions which are not normally associated with the formation of declarative memories. This type of dissociation between declarative and procedural memory can also be found in patients with diencephalic amnesia such as Korsakoffs syndrome. Another example demonstrated by some patients, such as K.C. and H.M, who have medial temporal damage and anterograde amnesia, still have perceptual priming. Priming was accomplished in many different experiments of amnesia, and it was found that the patients can be primed; they have no conscious recall of the event, but the response is there. Those patients did well in the word fragment completion task. There is some evidence that non-declarative memory can be held onto in the form of motor skills. This idea was disputed, though, because it is argued that motor skills require both declarative and non-declarative information. Causes There are three generalized categories in which amnesia could be acquired by a person. The three categories are head trauma (example: head injuries), traumatic events (example: seeing something devastating to the mind), or physical deficiencies (example: atrophy of the hippocampus). The majority of amnesia and related memory issues derive from the first two categories as these are more common and the third could be considered a subcategory of the first. Head trauma is a very broad range as it deals with any kind of injury or active action toward the brain which might cause amnesia. Retrograde and anterograde amnesia is more often seen from events like this, an exact example of a cause of the two would be electroconvulsive therapy, which would cause both briefly for the receiving patient. Traumatic events are more subjective. What is traumatic is dependent on what the person finds to be traumatic. Regardless, a traumatic event is an event where something so distressing occurs that the mind chooses to forget rather than deal with the stress. A common example of amnesia that is caused by traumatic events is dissociative amnesia, which occurs when the person forgets an event that has deeply disturbed them. An example would be a person forgetting a fatal and graphic car accident involving their loved ones. Physical deficiencies are different from head trauma because physical deficiencies lean more toward passive physical issues. Examples of physical deficiencies include Alzheimers disease, neurological paraneoplastic syndromes such as anti-NMDA receptor encephalitis, and vitamin B12 deficiency.Among specific causes of amnesia are the following: Electroconvulsive therapy in which seizures are electrically induced in patients for therapeutic effect can have acute effects including both retrograde and anterograde amnesia. Alcohol can both cause blackouts and have deleterious effects on memory formation. Diagnosis Types Anterograde amnesia is the inability to create new memories due to brain damage, while long-term memories from before the event remain intact. The brain damage can be caused by the effects of long-term alcoholism, severe malnutrition, stroke, head trauma, encephalitis, surgery, Wernicke–Korsakoff syndrome, cerebrovascular events, anoxia or other trauma. The two brain regions related with this condition are medial temporal lobe and medial diencephalon. Anterograde amnesia cannot be treated with pharmacological methods due to neuronal loss. However, treatment exists in educating patients to define their daily routines and after several steps they begin to benefit from their procedural memory. Procedural memory can be intact even when other forms of memory is not, although not always the case. Likewise, social and emotional support is critical to improving quality of life for those with anterograde amnesia. Fentanyl use by opioid users has been identified as a potential cause in a cluster of cases that occurred in Boston, MA. Retrograde amnesia is inability to recall memories before onset of amnesia. One may be able to encode new memories after the incident. Retrograde is usually caused by head trauma or brain damage to parts of the brain besides the hippocampus. The hippocampus is responsible for encoding new memory. Episodic memory is more likely to be affected than semantic memory. The damage is usually caused by head trauma, cerebrovascular accident, stroke, tumor, hypoxia, encephalitis, or chronic alcoholism. People with retrograde amnesia are more likely to remember general knowledge rather than specifics. Recent memories are less likely to be recovered, but older memories will be easier to recall due to strengthening over time. Retrograde amnesia is usually temporary and can be treated by exposing them to memories from the loss. Another type of consolidation (process by which memories become stable in the brain) occurs over much longer periods of time/days, weeks, months and years and likely involves transfer of information from the hippocampus to more permanent storage site in the cortex. The operation of this longer-term consolidation process is seen in the retrograde amnesia of patients with hippocampal damage who can recall memories from childhood relatively normally, but are impaired when recalling experiences that occurred just a few years prior to the time they became amnesic. (Kirwan et al.,2008)In the case of LSJ, her case shows that retrograde amnesia can affect many different parts of knowledge. LSJ was not able to remember things from her child or adult life. She was not able to remember things that most people pick up in everyday life such as logos or the names of common songs. Post-traumatic amnesia is generally due to a head injury (example: a fall, a knock on the head). Traumatic amnesia is often transient, but may be permanent or either anterograde, retrograde, or mixed type. The extent of the period covered by the amnesia is related to the degree of injury and may give an indication of the prognosis for recovery of other functions. Mild trauma, such as a car accident that results in no more than mild whiplash, might cause the occupant of a car to have no memory of the moments just before the accident due to a brief interruption in the short/long-term memory transfer mechanism. The patient may also lose knowledge of who people are. Having longer periods of amnesia or consciousness after an injury may be an indication that recovery from remaining concussion symptoms will take much longer. Dissociative amnesia results from a psychological cause as opposed to direct damage to the brain caused by head injury, physical trauma or disease, which is known as organic amnesia. Individuals with organic amnesia have difficulty with emotion expression as well as undermining the seriousness of their condition. The damage to the memory is permanent. Dissociative amnesia can include: Repressed memory is the inability to recall information, usually about stressful or traumatic events in persons lives, such as a violent attack or disaster. The memory is stored in long-term memory, but access to it is impaired because of psychological defense mechanisms. Persons retain the capacity to learn new information and there may be some later partial or complete recovery of memory. Formerly known as "Psychogenic Amnesia". Dissociative fugue (formerly psychogenic fugue) is also known as fugue state. It is caused by psychological trauma, is usually temporary and unresolved, and therefore, may return. It must exist outside the influence of pre-existing medical conditions, such as a lobotomy, and immediate influence of any mind-altering substances, such as alcohol or drugs. An individual with dissociative fugue disorder either completely forgets or is confused about their identity, and may even assume a new one. They can travel hundreds miles from their home or work; they can also engage in other uncharacteristic, and occasionally unsafe, behavior. For example, two men in a study of five individuals with dissociative fugue had engaged in criminal activity while in their fugue state, having had no criminal record before the episodes. While popular in fiction, this type of amnesia is extremely rare. Posthypnotic amnesia occurs when events during hypnosis are forgotten, or where memories are unable to be recalled. The failure to remember those events is induced by suggestions made during the hypnosis. Some characteristics of posthypnotic amnesia include inability to remember specific events while under hypnotic influence, reversibility, and having no relation between the implicit and explicit memory. Research has shown that there could be selectivity with amnesia when posthypnotic amnesia occurs. Lacunar amnesia is the loss of memory about one specific event. It is a type of amnesia that leaves a lacuna (a gap) in the record of memory in the cortex region of the brain. The cause of this type of amnesia is the result of brain damage to the limbic system which control our memories and emotions. Childhood amnesia (also known as infantile amnesia) is the common inability to remember events from ones own childhood. Sigmund Freud notoriously attributed this to sexual repression, while modern scientific approaches generally attribute it to aspects of brain development or developmental psychology, including language development, which may be why people do not easily remember pre-language events. Some research states that most adults cannot remember memories as early as two or three years old. Research suggests there are cultural influences that affect memories that are recalled. Researchers have found that implicit memories cannot be recalled or described. Remembering how to play the piano is a common example of implicit memory, as are walking, speaking, and other everyday activities that would be difficult to focus on if they had to be relearned every time one got up in the morning. Explicit memories, on the other hand, can be recalled and described in words. Remembering the first time meeting a teacher is an example of an explicit memory. Transient global amnesia is a well-described medical and clinical phenomenon. This form of amnesia is distinct in that abnormalities in the hippocampus can sometimes be visualized using a special form of magnetic resonance imaging of the brain known as diffusion-weighted imaging (DWI). Symptoms typically last for less than a day and there is often no clear precipitating factor or any other neurological deficits. The cause of this syndrome is not clear. The hypothesis of the syndrome includes transient reduced blood flow, possible seizure or an atypical type of a migraine. Patients are typically amnestic of events more than a few minutes in the past, though immediate recall is usually preserved. Source amnesia is the inability to remember where, when or how previously learned information has been acquired, while retaining the factual knowledge. When individuals are unable to remember, false memories can occur and cause great confusion. Korsakoffs syndrome can result from long-term alcoholism or malnutrition. It is caused by brain damage due to a vitamin B1 deficiency and will be progressive if alcohol intake and nutrition pattern are not modified. Other neurological problems are likely to be present in combination with this type of Amnesia, such as problems with the medial temporal lobe and frontal lobe dysfunction. Korsakoffs syndrome is also known to be connected with confabulation. The persons short-term memory may appear to be normal, but the person may have a difficult time attempting to recall a past story, or with unrelated words, as well as complicated patterns. Korsakoffs syndrome is unique because it involves both anterograde and retrograde amnesia. Drug-induced amnesia is intentionally caused by injection of an amnestic drug to help a patient forget surgery or medical procedures, particularly those not performed under full anesthesia, or likely to be particularly traumatic. Such drugs are also referred to as "premedicants". Most commonly, a 2-halogenated benzodiazepine such as midazolam or flunitrazepam is the drug of choice, although other strongly amnestic drugs such as propofol or scopolamine may also be used for this application. Memories of the short time-frame in which the procedure was performed are permanently lost or at least substantially reduced, but once the drug wears off, memory is no longer affected. Situation-specific amnesia can arise in a variety of circumstances (for example, committing an offence, child sexual abuse) resulting in PTSD. It has been claimed that it involves a narrowing of consciousness with attention focused on central perceptual details and/or that the emotional or traumatic events are processed differently from ordinary memories. Transient epileptic amnesia is a rare and unrecognized form of temporal lobe epilepsy, which is typically an episodic isolated memory loss. It has been recognized as a treatment-responsive syndrome congenial to anti-epileptic drugs. Semantic amnesia affects semantic memory and primarily expresses itself in the form of problems with language use and acquisition. Semantic amnesia can lead to dementia. Pseudodementia (otherwise known as depression-related cognitive dysfunction) is a condition where mental cognition can be temporarily decreased. The term pseudodementia is applied to the range of functional psychiatric conditions such as depression and schizophrenia, that may mimic organic dementia, but are essentially reversible on treatment. Pseudodementia typically involves three cognitive components: memory issues, deficits in executive functioning, and deficits in speech and language. Specific cognitive symptoms might include trouble recalling words or remembering things in general, decreased attentional control and concentration, difficulty completing tasks or making decisions, decreased speed and fluency of speech, and impaired processing speed. People with pseudodementia are typically very distressed about the cognitive impairment they experience. With in this condition, there are two specific treatments that have been found to be effective for the treatment of depression, and these treatments may also be beneficial in the treatment of pseudodementia. Cognitive behavioral therapy (CBT) involves exploring and changing thought patterns and behaviors in order to improve ones mood. Interpersonal therapy focuses on the exploration of an individuals relationships and identifying any ways in which they may be contributing to feelings of depression. Treatment Many forms of amnesia fix themselves without being treated. However, there are a few ways to cope with memory loss if treatment is needed. Since there are a variety of causes that form different amnesia, it is important to note that there are different methods that response better with the certain type of amnesia. Emotional support and love as well as medication and psychological therapy have been proven effective.One technique for amnesia treatment is cognitive or occupational therapy. In therapy, amnesiacs will develop the memory skills they have and try to regain some they have lost by finding which techniques help retrieve memories or create new retrieval paths. This may also include strategies for organizing information to remember it more easily and for improving understanding of lengthy conversation.Another coping mechanism is taking advantage of technological assistance, such as a personal digital device to keep track of day-to-day tasks. Reminders can be set up for appointments when to take medications, birthdays and other important events. Many pictures can also be stored to help amnesiacs remember names of friends, family, and co-workers. Notebooks, wall calendars, pill reminders and photographs of people and places are low-tech memory aids that can help as well.While there are no medications available to treat amnesia, underlying medical conditions can be treated to improve memory. Such conditions include but are not limited to low thyroid function, liver or kidney disease, stroke, depression, bipolar disorder and blood clots in the brain. Wernicke–Korsakoff syndrome involves a lack of thiamin and replacing this vitamin by consuming thiamin-rich foods such as whole-grain cereals, legumes (beans and lentils), nuts, lean pork, and yeast. Treating alcoholism and preventing alcohol and illicit drug use can prevent further damage, but in most cases will not recover lost memory.Although improvements occur when patients receive certain treatments, there is still no actual cure remedy for amnesia so far. To what extent the patient recovers and how long the amnesia will continue depends on the type and severity of the lesion. History French psychologist Theodule-Armand Ribot was among the first scientists to study amnesia. He proposed Ribots Law which states that there is a time gradient in retrograde amnesia. The law follows a logical progression of memory loss due to disease. First, a patient loses the recent memories, then personal memories, and finally intellectual memories. He implied that the most recent memories were lost first.Case studies have played a large role in the discovery of amnesia and the parts of the brain that were affected. The studies gave important insight into how amnesia affects the brain. The studies also gave scientists the resources into improving their knowledge about amnesia and insight into a cure or prevention. There are several extremely important case studies: Henry Molaison, R.B, and G.D. Henry Molaison Henry Molaison, formerly known as H.M., changed the way people thought of memory. The case was first reported in a paper by William Beecher Scoville and Brenda Milner in 1957. He was a patient who had severe epilepsy attributed to a bicycle accident at the age of nine. Physicians were unable to control his seizures with drugs, so the neurosurgeon Scoville tried a new approach involving brain surgery. He removed his medial temporal lobe bilaterally by doing a temporal lobectomy. His epilepsy did improve, but Molaison lost the ability to form new long-term memories (anterograde amnesia). He exhibited normal short-term memory ability. If he was given a list of words, he would forget them in about a minutes time. In fact, he would forget that he had even been given a list in the first place. However, H.M.s working and short-term memory seemed to be intact. He had a normal digit span and could hold a conversation that did not require him to recall past parts of the conversation. Once Molaison stopped thinking about the lists he was unable to recall them again from long-term memory. This gave researchers evidence that short-term and long-term memory are in fact two different processes. Even though he forgot about the lists, he was still able to learn things through his implicit memory. The psychologists would ask him to draw something on a piece of paper, but to look at the paper using a mirror. Though he could never remember ever doing that task, he would improve after doing it over and over again. This showed the psychologists that he was learning and remembering things unconsciously. In some studies it was found that H.M.s perceptual learning was intact and that his other cognitive skills were working appropriately. It was also found that some people with declarative information amnesia are able to be primed.Studies were completed consistently throughout Molaisons lifetime to discover more about amnesia. Researchers did a 14-year follow-up study on Molaison. They studied him for a period of two weeks to learn more about his amnesia. After 14 years, Molaison still could not recall things that had happened since his surgery. However, he could still remember things that had happened prior to the operation. Researchers also found that, when asked, Molaison could answer questions about national or international events, but he could not remember his own personal memories. After his death Molaison donated his brain to science, where they were able to discover the areas of the brain that had the lesions which caused his amnesia, particularly the medial temporal lobe. This case study provided important insight to the areas of the brain that are affected in anterograde amnesia, as well as how amnesia works. H.M.s case showed us that memory processes are consolidated into different parts of the brain and that short-term and working memory are not usually impaired in cases of amnesia. Clive Wearing Another famous historical case of amnesia was that of Clive Wearing. Clive Wearing was a conductor and musician who contracted herpes simplex virus. This virus affected the hippocampal regions of the brain. Because of this damage, Wearing was unable to remember information for more than a few moments. Wearings non-declarative memory was still functioning but his declarative memory was impaired. To him, he felt that he had just come to consciousness for the first time every time he was unable to hold on to information. This case also can be used as evidence that there are different memory systems for declarative and non-declarative memory. This case was more evidence that the hippocampus is an important part of the brain in remembering past events and that declarative and non-declarative memories have different processes in different parts of the brain. Patient R.B. Patient R.B. was a normally functioning man until the age of 52. At age 50, he had been diagnosed with angina and had surgery for heart problems on two occasions. After an ischemic episode (reduction of blood to the brain) that was caused from a heart bypass surgery, R.B. demonstrated a loss of anterograde memory, but almost no loss of retrograde memory, with the exception of a couple of years before his surgery, and presented no sign of any other cognitive impairment. It wasnt until after his death that researchers had the chance to examine his brain, when they found his lesions were restricted to the CA1 portion of the hippocampus. This case study led to important research involving the role of the hippocampus and the function of memory. Patient G.D. Patient G.D. was a white male born in 1940 who served in the Navy. He was diagnosed with chronic kidney failure and received hemodialysis treatment for the rest of his life. In 1983, he went to the hospital for elective parathyroidectomy. He also had a left thyroid lobectomy because of the severe loss of blood in his left lobe. He began having cardiac problems as a result of the surgery and became very agitated. Even five days after being released from the hospital he was unable to remember what had happened to him. Aside from memory impairment, none of his other cognitive processes seemed to be affected. He did not want to be involved in much research, but through memory tests he took with doctors, they were able to ascertain that his memory problems were present for the next 9.5 years until his death. After he died, his brain was donated to science, photographed, and preserved for future study. In fiction Global amnesia is a common motif in fiction despite being extraordinarily rare in reality. In the introduction to his anthology The Vintage Book of Amnesia, Jonathan Lethem writes: Real, diagnosable amnesia – people getting knocked on the head and forgetting their names – is mostly just a rumor in the world. Its a rare condition, and usually a brief one. In books and movies, though, versions of amnesia lurk everywhere, from episodes of Mission Impossible to metafictional and absurdist masterpieces, with dozens of stops in between. Amnesiacs might not much exist, but amnesiac characters stumble everywhere through comic books, movies, and our dreams. Weve all met them and been them. Lethem traces the roots of literary amnesia to Franz Kafka and Samuel Beckett, among others, fueled in large part by the seeping into popular culture of the work of Sigmund Freud, which also strongly influenced genre films such as film noir. Amnesia is so often used as a plot device in films, that a widely recognized stereotypical dialogue has even developed around it, with the victim melodramatically asking "Where am I? Who am I? What am I?", or sometimes inquiring of their own name, "Bill? Whos Bill?"In movies and television, particularly sitcoms and soap operas, it is often depicted that a second blow to the head, similar to the first one which caused the am
Amnesia	nesia, will then cure it. In reality, however, repeat concussions may cause cumulative deficits including cognitive problems, and in extremely rare cases may even cause deadly swelling of the brain associated with second-impact syndrome.In science fiction involving a masquerade that hides magical or alien societies from humanity, such as Men in Black or the SCP Foundation, fictional organizations can induce deliberate amnesia via drugs or advanced technology to wipe the minds of those that view supernatural phenomena. See also References == External links ==
Ovarian torsion	Ovarian torsion (OT) or adnexal torsion is an abnormal condition where an ovary twists on its attachment to other structures, such that blood flow is decreased. Symptoms typically include pelvic pain on one side. While classically the pain is sudden in onset, this is not always the case. Other symptoms may include nausea. Complications may include infection, bleeding, or infertility.Risk factors include ovarian cysts, ovarian enlargement, ovarian tumors, pregnancy, fertility treatment, and prior tubal ligation. The diagnosis may be supported by an ultrasound done via the vagina or CT scan, but these do not completely rule out the diagnosis. Surgery is the most accurate method of diagnosis.Treatment is by surgery to either untwist and fix the ovary in place or to remove it. The ovary will often recover, even if the condition has been present for some time. In those who have had a prior ovarian torsion, there is a 10% chance the other will also be affected. The diagnosis is relatively rare, affecting about 6 per 100,000 women per year. While it most commonly occurs in those of reproductive age, it can occur at any age. Signs and symptoms Patients with ovarian torsion often present with sudden onset of sharp and usually unilateral lower abdominal pain, in 70% of cases accompanied by nausea and vomiting. Pathophysiology The development of an ovarian mass is related to the development of torsion. In the reproductive years, regular growth of large corpus luteal cysts are a risk factor for rotation. The mass effect of ovarian tumors is also a common cause of torsion. Torsion of the ovary usually occurs with torsion of the fallopian tube as well on their shared vascular pedicle around the broad ligament, although in rare cases the ovary rotates around the mesovarium or the fallopian tube rotates around the mesosalpinx. In 80%, torsion happens unilaterally, with slight predominance on the right. In ovarian torsion, the ovary rotates around both the infundibulopelvic ligament (ie, suspensory ligament) and the utero-ovarian ligament (i.e. ovarian ligament), disrupting blood flow to the ovary. Diagnosis Ovarian torsion is difficult to diagnose accurately, and operation is often performed before certain diagnosis is made. A study at an obstetrics and gynaecology department found that preoperative diagnosis of ovarian torsion was confirmed in only 46% of people. Ultrasound Gynecologic ultrasonography is the imaging modality of choice. Use of doppler ultrasound in the diagnosis has been suggested. However, doppler flow is not always absent in torsion – the definitive diagnosis is often made in the operating room.Lack of ovarian blood flow on doppler sonography seems to be a good predictor of ovarian torsion. Women with pathologically low flow are more likely to have torsion. The sensitivity and specificity of abnormal ovarian flow are 44% and 92%, respectively, with a positive and negative predictive value of 78% and 71%, respectively. Specific flow features on Doppler sonography include: Little or no intra-ovarian venous flow. This is commonly seen in ovarian torsion. Absent arterial flow. This is a less common finding in ovarian torsion Absent or reversed diastolic flowNormal vascularity does not exclude intermittent torsion. There may occasionally be normal Doppler flow because of the ovarys dual blood supply from both the ovarian arteries and uterine arteries.Other ultrasonographic features include: Enlarged hypoechogenic or hyperechogenic ovary Peripherally displaced ovarian follicles Free pelvic fluid. This may be seen in more than 80% of cases Whirlpool sign of twisted vascular pedicle Underlying ovarian lesion can often be found Uterus may be slightly deviated towards the torted ovary. Treatment Surgical treatment of ovarian torsion includes laparoscopy to uncoil the torsed ovary and possibly oophoropexy to fixate the ovary which is likely to twist again. In severe cases, where blood flow is cut off to the ovary for an extended period of time, necrosis of the ovary can occur. In these cases the ovary must be surgically removed. Epidemiology Ovarian torsion accounts for about 3% of gynecologic emergencies. The incidence of ovarian torsion among women of all ages is 5.9 per 100,000 women, and the incidence among women of reproductive age (15–45 years) is 9.9 per 100,000 women. In 70% of cases, it is diagnosed in women between 20 and 39 years of age. The risk is greater during pregnancy and in menopause. Risk factors include increased length of the ovarian ligaments, pathologically enlarged ovaries (more than 6 cm), ovarian masses or cysts, and enlarged corpus luteum in pregnancy. See also Testicular torsion – equivalent condition in males References == External links ==
Hyperchloremia	Hyperchloremia is an electrolyte disturbance in which there is an elevated level of chloride ions in the blood. The normal serum range for chloride is 96 to 106 mEq/L, therefore chloride levels at or above 110 mEq/L usually indicate kidney dysfunction as it is a regulator of chloride concentration. As of now there are no specific symptoms of hyperchloremia; however, it can be influenced by multiple abnormalities that cause a loss of electrolyte-free fluid, loss of hypotonic fluid, or increased administration of sodium chloride. These abnormalities are caused by diarrhea, vomiting, increased sodium chloride intake, renal dysfunction, diuretic use, and diabetes. Hyperchloremia should not be mistaken for hyperchloremic metabolic acidosis as hyperchloremic metabolic acidosis is characterized by two major changes: a decrease in blood pH and bicarbonate levels, as well as an increase in blood chloride levels. Instead those with hyperchloremic metabolic acidosis are usually predisposed to hyperchloremia. Hyperchloremia prevalence in hospital settings has been researched in the medical field since one of the major sources of treatment at hospitals is administering saline solution. Previously, animal models with elevated chloride have displayed more inflammation markers, changes in blood pressure, increased renal vasoconstriction, and less renal blood flow as well at glomerulus filtration, all of which are prompting researchers to investigate if these changes or others may exist in patients. Some studies have reported a possible relationship between increased chloride levels and death or acute kidney injury in severely ill patients that may frequent the hospital or have prolonged visits. There are other studies that have found no relationship. Symptoms Hyperchloremia does not have many noticeable symptoms and can only be confirmed with testing, yet, the causes of hyperchloremia do have symptoms. Symptoms of the above stated abnormalities may include: Dehydration - due to diarrhea, vomiting, sweating Hypertension - due to increased sodium chloride intake Cardiovascular dysfunction - due to increased sodium chloride intake Edema - due to influx in sodium in the body Weakness - due to loss of fluids Thirst - due to loss of fluids Kussmaul breathing - due to high ion concentrations, loss of fluids, or kidney failure High blood sugar - due to diabetes Hyperchloremic metabolic acidosis - due to severe diarrhea and/or kidney failure Respiratory alkalosis - due to renal dysfunction Causes There are many scenarios which may results in hyperchloremia. The first instance is when there is a loss of electrolyte-free fluid. This simply means that the body is losing increased amounts of fluids that do not contain electrolytes, like chloride, resulting in high concentration of these ions in the body. This loss of fluids can be due to sweating (due to exercise or fever), skin burns, lack of adequate water intake, hyper-metabolic state, and diabetes insipidus. Losing fluids can lead to feelings of dehydration and dry mucous membrane.The second scenario that may lead to hyperchloremia is known as loss of hypotonic fluid which can be a direct result of loss of electrolyte fluid. Normally, water in the body is moving from an area of low ion concentration to an area of high ion concentration. In this case, the water is being excreted in the urine, therefore, less water is available to dilute these areas of high ion concentration. This can be due to diuretic use, diarrhea, vomiting, burns, kidney disease, kidney failure, and renal tubular acidosis . This may also lead to feeling of dehydration.The third scenarios that may lead to hyperchloremia is an increase in sodium chloride intake. This can be due to dietary intake or intravenous fluid administration in hospital settings. This can lead to the body experiencing hypertension, edema, and cardiovascular dysfunction. Mechanism The nephrons in the kidney are responsible for regulating the level of chloride in the blood. The general mechanism is that as filtrate fluid passes through the nephrons varying concentrations of ions will be secreted into the interstitial fluid or absorbed into the lumen. All along the nephrons are blood capillaries waiting to reabsorb ions from the interstitial fluid to circulate in the body. The amount of chloride to be released in the urine is due to the receptors lining the nephrons and the glomerulus filtration. Normally, chloride reabsorption begins in the proximal tubule and nearly 60% of chloride is filtered here. In a person with hyperchloremia, the absorption of chloride into the interstitial fluid and subsequently into the blood capillaries is increased. This means the concentration of chloride in the filtrate is decreased, therefore, a decreased amount of chloride is being excreted as waste in the urine. In the proximal tubule chloride reabsorption occurs in two parts. In the 1st phase, organic solutes (such as phosphates, amino acids, glucose and anions), sodium ions, and hydronium ions are reabsorbed from the filtrate fluid into the interstitial fluid. This is an important step because this creates the concentration gradient in which chloride concentration in the lumen will increase in comparison to the chloride concentration in the interstitial fluid. In phase 2, chloride will diffuse along the concentration gradient, which means chloride ions will travel from areas of high concentration to areas of low concentration.One suggested mechanism leading to hyperchloremia, there is a decrease in chloride transporter proteins along the nephron. These proteins may include sodium-potassium-2 chloride co-transporter, chloride anion exchangers, and chloride channels. Another suggested mechanism is a depletion in concentration gradient as a result of the reduced activity in these transporters. Such concentration gradient depletion would allow for the passive diffusion of chloride in and out the tubule. Diagnosis Elevated levels of chloride in the blood can be tested simply by requesting a serum chloride test. A doctor would request this test if there are signs their patient is experiencing an imbalance in acid-base levels for a prolonged period of time. For the test to occur a healthcare provider must draw a sample of blood from the patient. The sample will then be sent to a laboratory and results will be provided to the patients physician. As mentioned earlier a normal serum chloride range is from 96 to 106 mEq/L, and hyperchloremic patients will have levels above this range. Treatment As with most types of electrolyte imbalance, the treatment of high blood chloride levels is based on correcting the underlying cause. If the patient is dehydrated, therapy consists of establishing and maintaining adequate hydration such as drinking 2-3 quarts of water daily. Also, to alleviate symptoms of dehydration like diarrhea or vomiting, it is suggested to take medication. If the condition is caused or exacerbated by medications or treatments, these may be altered or discontinued, if deemed prudent. If there is underlying kidney disease (which is likely if there are other electrolyte disturbances), then the patient will be referred to a nephrologist for further care. If there is an underlying dysfunction of the endocrine or hormone system, the patient will likely be referred to an endocrinologist for further assessment. If the electrolyte imbalance is due to influx of sodium chloride in the body, then it has been suggested to make dietary changes or reduce the rate of administering intravenous fluids. Recent research In patients with sepsis or septic shock they are more susceptible to experience acute kidney injury (AKI) and the factors that may contribute to AKI are still being investigated. In a study conducted by Suetrong et al., (2016) using patients admitted to St. Paul Hospital in Vancouver with sepsis or septic shock had their body concentration of chloride checked over the course of 48 hours to determine if there is a relation between hyperchloremia and AKI. This is an important relationship to study because many times a form of therapy to treat sepsis and septic shock is to administer saline solution, which is a solution containing sodium chloride. Saline has a much higher concentration of chloride than blood. In this study they defined hyperchloremia as concentration of chloride greater than 110 mmol/L. This research demonstrated that hyperchloremia will influence a patient developing AKI. In fact, even patients that had a conservative increase in serum chloride saw some association with developing AKI. This research study suggest that there still needs to be more investigation in the risk of using saline as a form of therapy and the risk of experiencing AKI.In a separate study investigating the relation of critically ill patients and hyperchloremia, researchers found that there seems to be an independent association between ill patients with hyperchloremia and mortality. This study was conducted with septic patients admitted to ICUs for 72 hours. Chloride levels were assessed at baseline and 72 hours, and confounding variables were accounted for. This study is important because this continues to suggest there is increased risk associated with elevated chloride levels in vulnerable populations. Their article also states there needs to be avoidance of using solutions with chloride in specific patient subgroups Several trials have been done comparing balanced fluid (chloride restricted) solution with saline (chloride liberal) with the hypothesis that it may reduce the risk of AKI and mortality. Initial randomized trials in septic shock comparing Plasma-Lyte and 0.9% saline (SPLIT and SALT trials) did not show any risk reduction in AKI. However, the later trials with larger sample size in critically and non critically ill adults (SMART and SALT-ED trials) showed reduction in major adverse kidney events. Extrapolating from the findings of septic shock, a recent trial comparing plasmalyte with 0.9% saline in DKA also did not show any significant difference in AKI. Hence, the causal link between hyperchloremia and AKI is yet to be conclusively established.As studies continue, it is important to include a large patient sample size, a diverse patient population, and a diverse range of hospitals involved in these studies. References == External links ==
Isotonic hyponatremia	Isotonic hyponatremia is a form of hyponatremia with mOsm measured between 280 and 295. It can be associated with pseudohyponatremia, or with isotonic infusion of glucose or mannitol. Pseudohyponatremia Certain conditions, such as extraordinarily high blood levels of lipid (hyperlipidemia/hypertriglyceridemia) or protein (hyperparaproteinemia), magnify the electrolyte exclusion effect. This interferes with the measurement of serum sodium concentration by certain methods, leading to an erroneously low measurement of sodium, or pseudohyponatremia. The methods affected are the flame-photometric and indirect (but not direct) ion-selective electrode assays. This is distinct from a true dilutional hyponatremia that can be caused by an osmotic shift of water from cells to the bloodstream after large infusions of mannitol or intravenous immunoglobulin. It is associated with hyperlipidemia more frequently than with elevated protein. References == External links ==
Hypoventilation	Hypoventilation (also known as respiratory depression) occurs when ventilation is inadequate (hypo meaning "below") to perform needed respiratory gas exchange. By definition it causes an increased concentration of carbon dioxide (hypercapnia) and respiratory acidosis. Hypoventilation is not synonymous with respiratory arrest, in which breathing ceases entirely and death occurs within minutes due to hypoxia and leads rapidly into complete anoxia, although both are medical emergencies. Hypoventilation can be considered a precursor to hypoxia and its lethality is attributed to hypoxia with carbon dioxide toxicity. Causes Hypoventilation may be caused by: A medical condition such as stroke affecting the brainstem Voluntary breath-holding or underbreathing, for example, hypoventilation training or the Buteyko method. Medication or drugs, typically when taken in accidental or intentional overdose. Opioids and benzodiazepines in particular are known to cause respiratory depression. Examples of opioids include pharmaceuticals such as oxycodone and hydromorphone and examples of benzodiazepines include lorazepam and alprazolam. Hypocapnia, which stimulates hypoventilation Obesity; see Obesity hypoventilation syndrome Chronic mountain sickness, a mechanism to conserve energy. Medications As a side effect of medicines or recreational drugs, hypoventilation may become potentially life-threatening. Many different central nervous system (CNS) depressant drugs such as ethanol, benzodiazepines, barbiturates, GHB, sedatives, and opioids produce respiratory depression when taken in large or excessive doses, or mixed with other depressants. Strong opiates (namely fentanyl, heroin, and morphine), barbiturates, and certain benzodiazepines (such as alprazolam) are known for depressing respiration. In an overdose, an individual may cease breathing entirely (go into respiratory arrest) which is rapidly fatal without treatment. Opioids, in overdose or combined with other depressants, are notorious for such fatalities. Treatment Respiratory stimulants such as nikethamide were traditionally used to counteract respiratory depression from CNS depressant overdose, but offered limited effectiveness. A new respiratory stimulant drug called BIMU8 is being investigated which seems to be significantly more effective and may be useful for counteracting the respiratory depression produced by opiates and similar drugs without offsetting their therapeutic effects. If the respiratory depression occurs from opioid overdose, usually an opioid antagonist, most likely naloxone, will be administered. This will rapidly reverse the respiratory depression unless complicated by other depressants. However an opioid antagonist may also precipitate an opioid withdrawal syndrome in chronic users. Mechanical ventilation may still be necessary during initial resuscitation. Associated conditions Disorders like congenital central hypoventilation syndrome (CCHS) and ROHHAD (rapid-onset obesity, hypothalamic dysfunction, hypoventilation, with autonomic dysregulation) are recognized as conditions that are associated with hypoventilation. CCHS may be a significant factor in some cases of sudden infant death syndrome (SIDS), often termed "cot death" or "crib death". The opposite condition is hyperventilation (too much ventilation), resulting in low carbon dioxide levels (hypocapnia), rather than hypercapnia. See also Dyspnea Hyperventilation List of terms of lung size and activity == References ==
Henoch–Schönlein purpura	Henoch–Schönlein purpura (HSP), also known as IgA vasculitis, is a disease of the skin, mucous membranes, and sometimes other organs that most commonly affects children. In the skin, the disease causes palpable purpura (small, raised areas of bleeding underneath the skin), often with joint pain and abdominal pain. With kidney involvement, there may be a loss of small amounts of blood and protein in the urine (hematuria and proteinuria), but this usually goes unnoticed; in a small proportion of cases, the kidney involvement proceeds to chronic kidney disease. HSP is often preceded by an infection, such as a throat infection. HSP is a systemic vasculitis (inflammation of blood vessels) and is characterized by deposition of immune complexes containing the antibody immunoglobulin A (IgA); the exact cause for this phenomenon is unknown. In children, it usually resolves within several weeks and requires no treatment apart from symptom control but may relapse in a third of cases and cause irreversible kidney damage in about one in a hundred cases. In adults, the prognosis is different from in children. The average duration of cutaneous lesions is 27.9 months. For many, it tends to be relapsing–remitting over a long period of time, rather than self-limiting and there tend to be more complications. Signs and symptoms Purpura, arthritis, and abdominal pain are known as the "classic triad" of Henoch–Schönlein purpura. Purpura occur in all cases, joint pains and arthritis in 80%, and abdominal pain in 62%. Some include gastrointestinal hemorrhage as a fourth criterion; this occurs in 33% of cases, sometimes, but not necessarily always, due to intussusception. The purpura typically appear on the legs and buttocks, but may also be seen on the arms, face and trunk. The abdominal pain is colicky in character, and may be accompanied by nausea, vomiting, constipation or diarrhea. There may be blood or mucus in the stools. The joints involved tend to be the ankles, knees, and elbows, but arthritis in the hands and feet is possible; the arthritis is nonerosive and hence causes no permanent deformity. Forty percent have evidence of kidney involvement, mainly in the form of hematuria (blood in the urine), but only a quarter will have this in sufficient quantities to be noticeable without laboratory tests. Problems in other organs, such as the central nervous system (brain and spinal cord) and lungs may occur, but is much less common than in the skin, bowel and kidneys.Of the 40% of patients who develop kidney involvement, almost all have evidence (visible or on urinalysis) of blood in the urine. More than half also have proteinuria (protein in the urine), which in one eighth is severe enough to cause nephrotic syndrome (generalised swelling due to low protein content of the blood). While abnormalities on urinalysis may continue for a long time, only 1% of all HSP patients develop chronic kidney disease. Hypertension (high blood pressure) may occur. Protein loss and high blood pressure, as well as the features on biopsy of the kidney if performed, may predict progression to advanced kidney disease. Adults are more likely than children to develop advanced kidney disease. Pathophysiology Henoch–Schönlein purpura is a small-vessel vasculitis in which complexes of immunoglobulin A (IgA) and complement component 3 (C3) are deposited on arterioles, capillaries, and venules (hence it is a type III hypersensitivity reaction). The activation of the alternative complement pathway results in the deposition of IgA aggregates or IgA complexes in target organs (with deposition of C3). This leads to the production of inflammatory mediators, including vascular prostaglandins like prostacyclin, which may play a key role in the development of IgAV and its organ-specific clinical manifestations. As with IgA nephropathy, serum levels of IgA are high in HSP and there are identical findings on renal biopsy; however, IgA nephropathy has a predilection for young adults while HSP is more predominant among children. Further, IgA nephropathy typically only affects the kidneys while HSP is a systemic disease. HSP involves the skin and connective tissues, scrotum, joints, gastrointestinal tract and kidneys. The genetic basis remains unclear except for involvement of the human leukocyte antigen region of the genome. It is hypothesized to involve autoimmunity triggered by infections. Streptococcus strains and Parainfluenza virus are the most commonly associated pathogens, and in children Human Parvovirus B19 is a frequent viral trigger Diagnosis The diagnosis is based on the combination of the symptoms, as very few other diseases cause the same symptoms together. Blood tests may show elevated creatinine and urea levels (in kidney involvement), raised IgA levels (in about 50%), and raised C-reactive protein (CRP) or erythrocyte sedimentation rate (ESR) results; none are specific for Henoch–Schönlein purpura. The platelet count may be raised, and distinguishes it from diseases where low platelets are the cause of the purpura, such as idiopathic thrombocytopenic purpura and thrombotic thrombocytopenic purpura.If there is doubt about the cause of the skin lesions, a biopsy of the skin may be performed to distinguish the purpura from other diseases that cause it, such as vasculitis due to cryoglobulinemia; on microscopy, the appearances are of a hypersensitivity vasculitis, and immunofluorescence demonstrates IgA and C3 (a protein of the complement system) in the blood vessel wall. However, overall serum complement levels are normal. On the basis of symptoms, it is possible to distinguish HSP from hypersensitivity vasculitis (HV). In a series comparing 85 HSP patients with 93 HV patients, five symptoms were found to be indicative of HSP: palpable purpura, abdominal angina, digestive tract hemorrhage (not due to intussussception), hematuria and age less than 20. The presence of three or more of these indicators has an 87% sensitivity for predicting HSP.Biopsy of the kidney may be performed both to establish the diagnosis or to assess the severity of already suspected kidney disease. The main findings on kidney biopsy are increased cells and Ig deposition in the mesangium (part of the glomerulus, where blood is filtered), white blood cells, and the development of crescents. The changes are indistinguishable from those observed in IgA nephropathy. HSP can develop after infections with streptococci (β-haemolytic, Lancefield group A), hepatitis B, herpes simplex virus, parvovirus B19, Coxsackievirus, adenovirus, Helicobacter pylori, measles, mumps, rubella, Mycoplasma and numerous others. Drugs linked to HSP, usually as an idiosyncratic reaction, include the antibiotics vancomycin and cefuroxime, ACE inhibitors enalapril and captopril, anti-inflammatory agent diclofenac, as well as ranitidine and streptokinase. Several diseases have been reported to be associated with HSP, often without a causative link. Only in about 35% of cases can HSP be traced to any of these causes.The exact cause of HSP is unknown, but most of its features are due to the deposition of abnormal antibodies in the wall of blood vessels, leading to vasculitis. These antibodies are of the subclass IgA1 in polymers; it is uncertain whether the main cause is overproduction (in the digestive tract or the bone marrow) or decreased removal of abnormal IgA from the circulation. It is suspected that abnormalities in the IgA1 molecule may provide an explanation for its abnormal behaviour in both HSP and the related condition IgA nephropathy. One of the characteristics of IgA1 (and IgD) is the presence of an 18 amino acid-long "hinge region" between complement-fixating regions 1 and 2. Of the amino acids, half is proline, while the others are mainly serine and threonine. The majority of the serines and the threonines have elaborate sugar chains, connected through oxygen atoms (O-glycosylation). This process is thought to stabilise the IgA molecule and make it less prone to proteolysis. The first sugar is always N-acetyl-galactosamine (GalNAc), followed by other galactoses and sialic acid. In HSP and IgAN, these sugar chains appear to be deficient. The exact reason for these abnormalities is not known. Classification Multiple standards exist for defining Henoch–Schönlein purpura, including the 1990 American College of Rheumatology (ACR) classification and the 1994 Chapel Hill Consensus Conference (CHCC). Some have reported the ACR criteria to be more sensitive than those of the CHCC.More recent classifications, the 2006 European League Against Rheumatism (EULAR) and Pediatric Rheumatology Society (PReS) classification, include palpable purpura as a mandatory criterion, together with at least one of the following findings: diffuse abdominal pain, predominant IgA deposition (confirmed on skin biopsy), acute arthritis in any joint, and renal involvement (as evidenced by the presence of blood and/or protein in the urine). Differential diagnosis Henoch–Schönlein purpura may present with an atypical manifestation, which can be confused with papular urticaria, systemic lupus erythematosus, meningococcemia, dermatitis herpetiformis, and acute hemorrhagic edema of infancy. Treatment As of 2017, the optimal way to treat Henoch–Schönlein purpura remains controversial. Analgesics may be needed for the abdominal and joint pains. Wound care is warranted if the skin death and ulcerations occur. It is uncertain as to whether HSP needs treatment beyond controlling the symptoms. Most people do not receive therapy because of the high spontaneous recovery rate. Experts disagree on whether to routinely use corticosteroids as treatment for HSP. However, if they are given early in the disease episode, the duration of symptoms may be shortened, and abdominal pain can improve significantly. Moreover, the chance of severe kidney problems may be reduced. A systematic review did not find any evidence that steroid treatment (prednisone) is effective at decreasing the likelihood of developing long-term kidney disease.Evidence of worsening kidney damage would normally prompt a kidney biopsy. Treatment may be indicated on the basis of the appearance of the biopsy sample; various treatments may be used, ranging from steroids by mouth to a combination of intravenous methylprednisolone (steroid), cyclophosphamide and dipyridamole followed by prednisone. Other regimens include steroids/azathioprine, and steroids/cyclophosphamide (with or without heparin and warfarin). Intravenous immunoglobulin (IVIG) is occasionally used.There is no good evidence that treating children who have HSP with antiplatelet agent prevents persistent kidney disease. There is also no evidence that treating children or adults with cyclophosphamide prevents severe kidney disease. Heparin treatment is not justified. Prognosis Overall prognosis is good in most patients, with one study showing recovery occurring in 94% and 89% of children and adults, respectively (some having needed treatment). In children under ten, the condition recurs in about a third of all cases, usually within the four months of the initial attack. Recurrence is more common in older children and adults. Kidney involvement In adults, kidney involvement progresses to end-stage kidney disease (ESKD) more often than in children. In a UK series of 37 patients, 10 (27%) developed advanced kidney disease. Proteinuria, hypertension at presentation, and pathology features (crescentic changes, interstitial fibrosis and tubular atrophy) predicted progression. About 20% of children that exhibit nephrotic or nephritic features experience long permanent renal impairment.The findings on renal biopsy correlate with the severity of symptoms: those with asymptomatic hematuria may only have focal mesangial proliferation while those with proteinuria may have marked cellular proliferation or even crescent formation. The number of crescentic glomeruli is an important prognostic factor in determining whether the patient will develop chronic renal disease.In ESKD, some eventually need hemodialysis or equivalent renal replacement therapy (RRT). If a kidney transplant is found for a patient on RRT, the disease will recur in the graft (transplanted kidney) in about 35% of cases, and in 11%, the graft will fail completely (requiring resumption of the RRT and a further transplant). Epidemiology HSP occurs more often in children than in adults, and usually follows an upper respiratory tract infection. Half of affected patients are below the age of six, and 90% are under ten. It occurs about twice as often in boys as in girls. The incidence of HSP in children is about 20 per 100,000 children per year, making it the most common vasculitis in children.Cases of HSP may occur anytime throughout the year, but some studies have found that fewer cases occur during the summer months. History The disease is named after Eduard Heinrich Henoch (1820–1910), a German pediatrician (nephew of Moritz Heinrich Romberg) and his teacher Johann Lukas Schönlein (1793–1864), who described it in the 1860s. Schönlein associated the purpura and arthritis, and Henoch the purpura and gastrointestinal involvement. The English physician William Heberden (1710–1801) and the dermatologist Robert Willan (1757–1812) had already described the disease in 1802 and 1808, respectively, but the name Heberden–Willan disease has fallen into disuse. William Osler was the first to recognise the underlying allergic mechanism of HSP. See also Cutaneous small-vessel vasculitis References == External links ==
Erythema	Erythema (from the Greek erythros, meaning red) is redness of the skin or mucous membranes, caused by hyperemia (increased blood flow) in superficial capillaries. It occurs with any skin injury, infection, or inflammation. Examples of erythema not associated with pathology include nervous blushes. Types Erythema ab igne Erythema chronicum migrans Erythema induratum Erythema infectiosum (or fifth disease) Erythema marginatum Erythema migrans Erythema multiforme (EM) Erythema nodosum Erythema toxicum Erythema elevatum diutinum Erythema gyratum repens Keratolytic winter erythema Palmar erythema Causes It can be caused by infection, massage, electrical treatment, acne medication, allergies, exercise, solar radiation (sunburn), photosensitization, acute radiation syndrome, mercury toxicity, blister agents, niacin administration, or waxing and tweezing of the hairs—any of which can cause the capillaries to dilate, resulting in redness. Erythema is a common side effect of radiotherapy treatment due to patient exposure to ionizing radiation. Diagnosis Erythema disappears on finger pressure (blanching), while purpura or bleeding in the skin and pigmentation do not. There is no temperature elevation, unless it is associated with the dilation of arteries in the deeper layer of the skin. See also Hyperemia Flushing (physiology) List of cutaneous conditions References == External links ==
Bacterial vaginosis	Bacterial vaginosis (BV) is a disease of the vagina caused by excessive growth of bacteria. Common symptoms include increased vaginal discharge that often smells like fish. The discharge is usually white or gray in color. Burning with urination may occur. Itching is uncommon. Occasionally, there may be no symptoms. Having BV approximately doubles the risk of infection by a number of sexually transmitted infections, including HIV/AIDS. It also increases the risk of early delivery among pregnant women.BV is caused by an imbalance of the naturally occurring bacteria in the vagina. There is a change in the most common type of bacteria and a hundred to thousand fold increase in total numbers of bacteria present. Typically, bacteria other than Lactobacilli become more common. Risk factors include douching, new or multiple sex partners, antibiotics, and using an intrauterine device, among others. However, it is not considered a sexually transmitted infection and, unlike gonorrhoea and chlamydia, sexual partners are not treated. Diagnosis is suspected based on the symptoms, and may be verified by testing the vaginal discharge and finding a higher than normal vaginal pH, and large numbers of bacteria. BV is often confused with a vaginal yeast infection or infection with Trichomonas.Usually treatment is with an antibiotic, such as clindamycin or metronidazole. These medications may also be used in the second or third trimesters of pregnancy. However, the condition often recurs following treatment. Probiotics may help prevent re-occurrence. It is unclear if the use of probiotics or antibiotics affects pregnancy outcomes.BV is the most common vaginal infection in women of reproductive age. The percentage of women affected at any given time varies between 5% and 70%. BV is most common in parts of Africa and least common in Asia and Europe. In the United States about 30% of women between the ages of 14 and 49 are affected. Rates vary considerably between ethnic groups within a country. While BV-like symptoms have been described for much of recorded history, the first clearly documented case occurred in 1894. Signs and symptoms Although about 50% of women with BV are asymptomatic, common symptoms include increased vaginal discharge that usually smells like fish. The discharge is often white or gray in color. There may be burning with urination. Occasionally, there may be no symptoms.The discharge coats the walls of the vagina, and is usually without significant irritation, pain, or erythema (redness), although mild itching can sometimes occur. By contrast, the normal vaginal discharge will vary in consistency and amount throughout the menstrual cycle and is at its clearest at ovulation—about two weeks before the period starts. Some practitioners claim that BV can be asymptomatic in almost half of affected women, though others argue that this is often a misdiagnosis. Complications Although previously considered a mere nuisance infection, untreated bacterial vaginosis may cause increased susceptibility to sexually transmitted infections, including HIV, and pregnancy complications.It has been shown that HIV-infected women with bacterial vaginosis (BV) are more likely to transmit HIV to their sexual partners than those without BV. There is evidence of an association between BV and increased rates of sexually transmitted infections such as HIV/AIDS. BV is associated with up to a six-fold increase in HIV shedding. BV is a risk factor for viral shedding and herpes simplex virus type 2 infection. BV may increase the risk of infection with or reactivation of human papillomavirus (HPV).In addition, bacterial vaginosis as either pre-existing, or acquired, may increase the risk of pregnancy complications, most notably premature birth or miscarriage. Pregnant women with BV have a higher risk of chorioamnionitis, miscarriage, preterm birth, premature rupture of membranes, and postpartum endometritis. Women with BV who are treated with in vitro fertilization have a lower implantation rate and higher rates of early pregnancy loss. Causes Healthy vaginal microbiota consists of species that neither cause symptoms or infections, nor negatively affect pregnancy. It is dominated mainly by Lactobacillus species. BV is defined by the disequilibrium in the vaginal microbiota, with decline in the number of lactobacilli. While the infection involves a number of bacteria, it is believed that most infections start with Gardnerella vaginalis creating a biofilm, which allows other opportunistic bacteria to thrive.One of the main risks for developing BV is douching, which alters the vaginal microbiota and predisposes women to developing BV. Douching is strongly discouraged by the U.S. Department of Health and Human Services and various medical authorities, for this and other reasons.BV is a risk factor for pelvic inflammatory disease, HIV, sexually transmitted infections (STIs), and reproductive and obstetric disorders or negative outcomes. Although BV can be associated with sexual activity, there is no clear evidence of sexual transmission. It is possible for sexually inactive persons to develop bacterial vaginosis.Also, subclinical iron deficiency may correlate with bacterial vaginosis in early pregnancy. A longitudinal study published in February 2006, in the American Journal of Obstetrics and Gynecology, showed a link between psychosocial stress and bacterial vaginosis persisted even when other risk factors were taken into account. Exposure to the spermicide nonoxynol-9 does not affect the risk of developing bacterial vaginosis. Diagnosis To make a diagnosis of bacterial vaginosis, a swab from inside the vagina should be obtained. These swabs can be tested for: Gram stain which shows the depletion of lactobacilli and overgrowth of Gardnerella vaginalis bacteria. Bacterial vaginosis is usually confirmed by a Gram stain of vaginal secretions. A characteristic "fishy" odor on wet mount. This test, called the whiff test, is performed by adding a small amount of potassium hydroxide to a microscope slide containing the vaginal discharge. A characteristic fishy odor is considered a positive whiff test and is suggestive of bacterial vaginosis. Loss of acidity. To control bacterial growth, the vagina is normally slightly acidic with a pH of 3.8–4.2. A swab of the discharge is put onto litmus paper to check its acidity. A pH greater than 4.5 is considered alkaline and is suggestive of bacterial vaginosis. The presence of clue cells on wet mount. Similar to the whiff test, the test for clue cells is performed by placing a drop of sodium chloride solution on a slide containing vaginal discharge. If present, clue cells can be visualized under a microscope. They are so-named because they give a clue to the reason behind the discharge. These are epithelial cells that are coated with bacteria.Differential diagnosis for bacterial vaginosis includes the following: Normal vaginal discharge. Candidiasis (thrush, or a yeast infection). Trichomoniasis, an infection caused by Trichomonas vaginalis. Aerobic vaginitisThe Center for Disease Control (CDC) defines STIs as "a variety of clinical syndromes and infections caused by pathogens that can be acquired and transmitted through sexual activity." But the CDC does not specifically identify BV as sexually transmitted infection. Amsel criteria In clinical practice BV can be diagnosed using the Amsel criteria: Thin, white, yellow, homogeneous discharge Clue cells on microscopy pH of vaginal fluid >4.5 Release of a fishy odor on adding alkali—10% potassium hydroxide (KOH) solution.At least three of the four criteria should be present for a confirmed diagnosis. A modification of the Amsel criteria accepts the presence of two instead of three factors and is considered equally diagnostic. Gram stain An alternative is to use a Gram-stained vaginal smear, with the Hay/Ison criteria or the Nugent criteria. The Hay/Ison criteria are defined as follows: Grade 1 (Normal): Lactobacillus morphotypes predominate. Grade 2 (Intermediate): Some lactobacilli present, but Gardnerella or Mobiluncus morphotypes also present. Grade 3 (Bacterial Vaginosis): Predominantly Gardnerella and/or Mobiluncus morphotypes. Few or absent lactobacilli. (Hay et al., 1994)Gardnerella vaginalis is the main culprit in BV. Gardnerella vaginalis is a short, Gram-variable rod (coccobacillus). Hence, the presence of clue cells and gram variable coccobacilli are indicative or diagnostic of bacterial vaginosis. Nugent score The Nugent score is now rarely used by physicians due to the time it takes to read the slides and requires the use of a trained microscopist. A score of 0-10 is generated from combining three other scores. The scores are as follows: 0–3 is considered negative for BV 4–6 is considered intermediate 7+ is considered indicative of BV.At least 10–20 high power (1000× oil immersion) fields are counted and an average determined. DNA hybridization testing with Affirm VPIII was compared to the Gram stain using the Nugent criteria. The Affirm VPIII test may be used for the rapid diagnosis of BV in symptomatic women but uses expensive proprietary equipment to read results, and does not detect other pathogens that cause BV, including Prevotella spp, Bacteroides spp, and Mobiluncus spp. The cervicovaginal microbiome measured using 16S rRNA sequencing has the capacity to increase throughput of the Nugent Score and has demonstrate to be directly comparable to clinical Nugent Score measurement. Screening Screening during pregnancy is not recommended in the United States as of 2020. Prevention Some steps suggested to lower the risk include: not douching, avoiding sex, or limiting the number of sex partners.One review concluded that probiotics may help prevent re-occurrence. Another review found that, while there is tentative evidence, it is not strong enough to recommend their use for this purpose.Early evidence suggested that antibiotic treatment of male partners could re-establish the normal microbiota of the male urogenital tract and prevent the recurrence of infection. However, a 2016 Cochrane review found high-quality evidence that treating the sexual partners of women with bacterial vaginosis had no effect on symptoms, clinical outcomes, or recurrence in the affected women. It also found that such treatment may lead treated sexual partners to report increased adverse events. Treatment Antibiotics Treatment is typically with the antibiotics metronidazole or clindamycin. They can be either given by mouth or applied inside the vagina with similar efficacy. About 10% to 15% of people, however, do not improve with the first course of antibiotics and recurrence rates of up to 80% have been documented. Recurrence rates are increased with sexual activity with the same pre-/posttreatment partner and inconsistent condom use although estrogen-containing contraceptives decrease recurrence. When clindamycin is given to pregnant women symptomatic with BV before 22 weeks of gestation the risk of pre-term birth before 37 weeks of gestation is lower.Other antibiotics that may work include macrolides, lincosamides, nitroimidazoles, and penicillins.Bacterial vaginosis is not considered a sexually transmitted infection, and treatment of a male sexual partner of a woman with bacterial vaginosis is not recommended. Probiotics A 2009 Cochrane review found tentative but insufficient evidence for probiotics as a treatment for BV. A 2014 review reached the same conclusion. A 2013 review found some evidence supporting the use of probiotics during pregnancy. The preferred probiotics for BV are those containing high doses of lactobacilli (around 109 CFUs) given in the vagina. Intravaginal administration is preferred to taking them by mouth. Prolonged repetitive courses of treatment appear to be more promising than short courses.The lack of effectiveness of commercially available Lactobacillus probiotics may be because most do not actually contain vaginal lactobacilli strains. LACTIN-V is a live biopharmaceutical medication containing the vaginally important Lactobacillus crispatus which is under development for the treatment of bacterial vaginosis and recurrent urinary tract infections. It has shown initial effectiveness in considerably reducing recurrence of bacterial vaginosis following antibiotic treatment. LACTIN-V is not yet Food and Drug Administration (FDA)-approved or commercially available. Antiseptics Topical antiseptics, for example dequalinium chloride, policresulen, hexetidine or povidone-iodine vaginal suppositories may be applied, if the risk of ascending infections is low (outside of pregnancy and in immunocompetent people without histories of upper genital tract infections). One study found that vaginal irrigations with hydrogen peroxide (3%) resulted in a slight improvement but this was much less than with the use of oral metronidazole. Intravaginal boric acid in conjunction with other medications may be helpful in the treatment of recurrent BV. TOL-463, a formulation of boric acid enhanced with ethylenediaminetetraacetic acid (EDTA), is under development as an intravaginal medication for the treatment of BV and has shown preliminary effectiveness. Epidemiology BV is the most common infection of the vagina in women of reproductive age. The percentage of women affected at any given time varies between 5% and 70%. BV is most common in parts of Africa, and least common in Asia and Europe. In the United States, about 30% of those between the ages of 14 and 49 are affected. Rates vary considerably between ethnic groups within a country. References == External links ==
Thyroid adenoma	A thyroid adenoma is a benign tumor of the thyroid gland, that may be inactive or active (functioning autonomously) as a toxic adenoma. Signs and symptoms A thyroid adenoma may be clinically silent ("cold" adenoma), or it may be a functional tumor, producing excessive thyroid hormone ("warm" or "hot" adenoma). In this case, it may result in symptomatic hyperthyroidism, and may be referred to as a toxic thyroid adenoma. Diagnosis Morphology Thyroid follicular adenoma ranges in diameter from 3 cm on an average, but sometimes is larger (up to 10 cm) or smaller. The typical thyroid adenoma is solitary, spherical and encapsulated lesion that is well demarcated from the surrounding parenchyma. The color ranges from gray-white to red-brown, depending upon the cellularity of the adenoma the colloid content.Areas of hemorrhage, fibrosis, calcification, and cystic change, similar to what is found in multinodular goiters, are common in thyroid (follicular) adenoma, particularly in larger lesions. Types Almost all thyroid adenomata are follicular adenomata. Follicular adenomata can be described as "cold", "warm" or "hot" depending on their level of function. Histopathologically, follicular adenomata can be classified according to their cellular architecture and relative amounts of cellularity and colloid into the following types: Fetal (microfollicular) - these have the potential for microinvasion. These consist of small, closely packed follicles lined with epithelium. Colloid (macrofollicular) - these do not have any potential for microinvasion Embryonal (atypical) - have the potential for microinvasion. Hürthle cell adenoma (oxyphil or oncocytic tumor) - have the potential for microinvasion. Hyalinizing trabecular adenomaPapillary adenomata are very rare. Differential diagnosis A thyroid adenoma is distinguished from a multinodular goiter of the thyroid in that an adenoma is typically solitary, and is a neoplasm resulting from a genetic mutation (or other genetic abnormality) in a single precursor cell. In contrast, a multinodular goiter is usually thought to result from a hyperplastic response of the entire thyroid gland to a stimulus, such as iodine deficiency. Careful pathological examination may be necessary to distinguish a thyroid adenoma from a minimally invasive follicular thyroid carcinoma. Management Most patients with thyroid adenoma can be managed by watchful waiting (without surgical excision) with regular monitoring. However, some patients still choose surgery after being fully informed of the risks. Regular monitoring mainly consists of watching for changes in nodule size and symptoms, and repeat ultrasonography or needle aspiration biopsy if the nodule grows. For patients with benign thyroid adenomata, thyroid lobectomy and isthmusectomy is a sufficient surgical treatment. This procedure is also adequate for patients with minimally invasive thyroid cancer. When histological examination shows no signs of malignancy, then no further intervention is required. These patients should continue to have their thyroid hormone status regularly checked. References == External links ==
Lymphadenopathy	Lymphadenopathy or adenopathy is a disease of the lymph nodes, in which they are abnormal in size or consistency. Lymphadenopathy of an inflammatory type (the most common type) is lymphadenitis, producing swollen or enlarged lymph nodes. In clinical practice, the distinction between lymphadenopathy and lymphadenitis is rarely made and the words are usually treated as synonymous. Inflammation of the lymphatic vessels is known as lymphangitis. Infectious lymphadenitis affecting lymph nodes in the neck is often called scrofula. Lymphadenopathy is a common and nonspecific sign. Common causes include infections (from minor causes such as the common cold and post-vaccination swelling to serious ones such as HIV/AIDS), autoimmune diseases, and cancer. Lymphadenopathy is frequently idiopathic and self-limiting. Causes Lymph node enlargement is recognized as a common sign of infectious, autoimmune, or malignant disease. Examples may include: Reactive: acute infection (e.g., bacterial, or viral), or chronic infections (tuberculous lymphadenitis, cat-scratch disease). The most distinctive sign of bubonic plague is extreme swelling of one or more lymph nodes that bulge out of the skin as "buboes." The buboes often become necrotic and may even rupture. Infectious mononucleosis is an acute viral infection usually caused by Epstein-Barr virus and may be characterized by a marked enlargement of the cervical lymph nodes. It is also a sign of cutaneous anthrax and Human African trypanosomiasis Toxoplasmosis, a parasitic disease, gives a generalized lymphadenopathy (Piringer-Kuchinka lymphadenopathy). Plasma cell variant of Castlemans disease - associated with HHV-8 infection and HIV infection Mesenteric lymphadenitis after viral systemic infection (particularly in the GALT in the appendix) can commonly present like appendicitis.Infectious causes of lymphadenopathy may include bacterial infections such as cat scratch disease, tularemia, brucellosis, or prevotella, as well as fungal infections such as paracoccidioidomycosis. Tumoral: Primary: Hodgkin lymphoma and non-Hodgkin lymphoma give lymphadenopathy in all or a few lymph nodes. Secondary: metastasis, Virchows Node, neuroblastoma, and chronic lymphocytic leukemia. Autoimmune: systemic lupus erythematosus and rheumatoid arthritis may have a generalized lymphadenopathy. Immunocompromised: AIDS. Generalized lymphadenopathy is an early sign of infection with human immunodeficiency virus (HIV), the virus that causes acquired immunodeficiency syndrome (AIDS). "Lymphadenopathy syndrome" has been used to describe the first symptomatic stage of HIV progression, preceding a diagnosis of AIDS. Bites from certain venomous snakes such as the pit viper Unknown: Kikuchi disease, progressive transformation of germinal centers, sarcoidosis, hyaline-vascular variant of Castlemans disease, Rosai-Dorfman disease, Kawasaki disease, Kimura disease Benign (reactive) lymphadenopathy Benign lymphadenopathy is a common biopsy finding, and may often be confused with malignant lymphoma. It may be separated into major morphologic patterns, each with its own differential diagnosis with certain types of lymphoma. Most cases of reactive follicular hyperplasia are easy to diagnose, but some cases may be confused with follicular lymphoma. There are seven distinct patterns of benign lymphadenopathy: Follicular hyperplasia: This is the most common type of reactive lymphadenopathy. Paracortical hyperplasia/Interfollicular hyperplasia: It is seen in viral infections, skin diseases, and nonspecific reactions. Sinus histiocytosis: It is seen in lymph nodes draining limbs, inflammatory lesions, and malignancies. Nodal extensive necrosis Nodal granulomatous inflammation Nodal extensive fibrosis (Connective tissue framework) Nodal deposition of interstitial substanceThese morphological patterns are never pure. Thus, reactive follicular hyperplasia can have a component of paracortical hyperplasia. However, this distinction is important for the differential diagnosis of the cause. Diagnosis In cervical lymphadenopathy (of the neck), it is routine to perform a throat examination including the use of a mirror and an endoscope.On ultrasound, B-mode imaging depicts lymph node morphology, whilst power Doppler can assess the vascular pattern. B-mode imaging features that can distinguish metastasis and lymphoma include size, shape, calcification, loss of hilar architecture, as well as intranodal necrosis. Soft tissue edema and nodal matting on B-mode imaging suggests tuberculous cervical lymphadenitis or previous radiation therapy. Serial monitoring of nodal size and vascularity are useful in assessing treatment response.Fine needle aspiration cytology (FNAC) has sensitivity and specificity percentages of 81% and 100%, respectively, in the histopathology of malignant cervical lymphadenopathy. PET-CT has proven to be helpful in identifying occult primary carcinomas of the head and neck, especially when applied as a guiding tool prior to panendoscopy, and may induce treatment related clinical decisions in up to 60% of cases. Classification Lymphadenopathy may be classified by: Size, where lymphadenopathy in adults is often defined as a short axis of one or more lymph nodes is greater than 10mm. By extent: Localized lymphadenopathy: due to localized spot of infection e.g., an infected spot on the scalp will cause lymph nodes in the neck on that same side to swell up Generalized lymphadenopathy: due to a systemic infection of the body e.g., influenza or secondary syphilis Persistent generalized lymphadenopathy (PGL): persisting for a long time, possibly without an apparent cause By localization: Hilar lymphadenopathy. Mediastinal lymphadenopathy Bilateral hilar lymphadenopathy Dermatopathic lymphadenopathy: lymphadenopathy associated with skin disease. By malignancy: Benign lymphadenopathy is distinguished from malignant types which mainly refer to lymphomas or lymph node metastasis. Size By size, where lymphadenopathy in adults is often defined as a short axis of one or more lymph nodes is greater than 10mm. However, there is regional variation as detailed in this table:Lymphadenopathy of the axillary lymph nodes can be defined as solid nodes measuring more than 15 mm without fatty hilum. Axillary lymph nodes may be normal up to 30 mm if consisting largely of fat.In children, a short axis of 8 mm can be used. However, inguinal lymph nodes of up to 15 mm and cervical lymph nodes of up to 20 mm are generally normal in children up to age 8–12.Lymphadenopathy of more than 1.5–2 cm increases the risk of cancer or granulomatous disease as the cause rather than only inflammation or infection. Still, an increasing size and persistence over time are more indicative of cancer. See also Adenitis Lymphovascular invasion References External links HPC:13820 on humpath.com (Digital slides)
Pseudohyperaldosteronism	Pseudohyperaldosteronism (also pseudoaldosteronism) is a medical condition which mimics the effects of elevated aldosterone (hyperaldosteronism) by presenting with high blood pressure (hypertension), low blood potassium levels (hypokalemia), metabolic alkalosis, and low levels of plasma renin activity (PRA). However, unlike hyperaldosteronism, this conditions exhibits low or normal levels of aldosterone in the blood. Causes include genetic disorders (e.g. Apparent mineralocorticoid excess syndrome, Liddles syndrome, and types of Congenital adrenal hyperplasia), acquired conditions (e.g. Cushings syndrome and mineralocorticoid-producing adrenal tumors), metabolic disorders, and dietary imbalances including excessive consumption of licorice. Confirmatory diagnosis depends on the specific root cause and may involve blood tests, urine tests, or genetic testing; however, all forms of this condition exhibit abnormally low concentrations of both plasma renin activity (PRA) and plasma aldosterone concentration (PAC) which differentiates this group of conditions from other forms of secondary hypertension. Treatment is tailored to the specific cause and focuses on symptom control, blood pressure management, and avoidance of triggers. Presentation The presentation of pseudohyperaldosteronism varies depending on the cause. The genetic conditions such as Liddles syndrome and Congenital adrenal hyperplasia present in childhood or earlier in life than the acquired causes which can present at any age. Adult patients present with clinical history of resistant hypertension despite typical medical therapy and lifestyle changes. Hypertension may be asymptomatic or may lead to symptoms such as headache, dizziness, vision changes, or kidney disease. Symptoms of hypokalemia include fatigue, muscular weakness, and increased urine production. Causes This condition has several known causes including genetic disorders, acquired conditions, metabolic derangements, and dietary imbalances. All causes mimic the effects of elevated aldosterone without raising aldosterone levels but achieve this through varying mechanisms. Genetic forms Genetic disorders that lead to this condition include Liddles syndrome, Apparent mineralocorticoid excess (AME), and two types of Congenital adrenal hyperplasia (CAH). Liddles syndrome is autosomal dominant disorder affecting epithelial sodium channels (ENaC) in the distal tubules of the kidneys. In this disorder, a gain of function mutation decreases ENaC degradation leading to increased renal absorption of sodium and water. Apparent mineralocorticoid excess genetic forms include autosomal recessive disorders with mutations lowering the activity of the enzyme 11-beta-hydroxysteroid dehydrogenase type 2 (11-β-HSD2). These mutations limit the ability of 11-β-HSD2 to transform active cortisol to the less active cortisone. Excess cortisol is then able to bind and activate mineralocorticoid receptors due to receptor cross-reactivity leading to aldosterone-like effects. Congenital Adrenal Hyperplasia is an autosomal recessive disorder with multiple types, two of which lead to pseudohyperaldosteronism. Deficiency of 11-beta-hydroxylase blocks the conversion of 11-deoxycorticosterone (DOC) to corticosterone leading to an excess of DOC which acts as a mineralocorticoid similar to aldosterone. Deficiency of 17-alpha-hydroxylase blocks the conversion of pregnenolone and progesterone to their 17-a-hydroxy forms leading to increased mineralocorticoid production. Acquired forms Some causes of pseudohyperaldosteronism can be acquired throughout life with examples including adrenal tumors and Ectopic ACTH syndrome. Adrenal tumor subtypes include adrenal adenomas that produce 11-deoxycorticosterone (DOC) leading to increased mineralocorticoid activity without elevated aldosterone. Ectopic ACTH syndrome describes conditions leading to excess production of adrenocorticotropic hormone (ACTH) subsequently leading to mineralocorticoid production. This can arise in ectopic forms of Cushings syndrome associated with small-cell lung cancers and other ACTH-producing tumors. The excess ACTH can saturate the 11-β-HSD2 enzyme leading to decreased conversion of cortisol to cortisone and increased mineralocorticoid effects. Metabolic and dietary forms Metabolic causes include conditions of glucocorticoid resistance and from mineralocorticoid excess which can occur following high-dose corticosteroid therapy. Dietary causes include overconsumption of licorice-containing products. Glycyrrhetinic acid in licorice inhibits the 11-β-HSD2 enzyme resulting in inappropriate stimulation of the mineralocorticoid receptor by cortisol leading to aldosterone-like effects. Diagnosis In patients with hypertension, diagnostic clues pointing to pseudohyperaldosteronism can be found on routine labwork. These include low serum potassium (hypokalemia), elevated serum sodium (hypernatremia), and elevated serum bicarbonate (metabolic alkalosis). Urine studies may show elevated urine potassium (kaliuresis). To further differentiate between hyperaldosteronism and pseudohyperaldosteronism, studies including plasma renin activity (PRA) and plasma aldosterone concentration (PAC) can be obtained. Pseudohyperaldosteronism will exhibit low levels of both PRA and PAC while hyperaldosteronism will demonstrate elevated PAC. Confirmatory tests to diagnose the specific forms of pseudohyperaldosteronism vary depending on the cause. The genetic conditions such as Liddles syndrome and CAH can be confirmed with genetic tests for the affected genes. CAH can also be confirmed by analyzing enzyme levels following ACTH stimulation testing. AME can be diagnosed with a 24 hour urine collection exhibiting an increased ratio of urinary cortisol to urinary cortisone. Treatment Specific treatment of pseudohyperaldosteronism depends on the inciting cause. General management focuses on countering the effects of excess mineralocorticoid activity to achieve adequate blood pressure control and avoid end-organ damage and cardiovascular mortality. In some cases, specific antihypertensive medications may be recommended. In Liddles syndrome, ENaC-binding potassium-sparing diuretics (e.g. amiloride or triamterene) are used to counter the excess ENaC activity. In AME, the mineralocorticoid receptor-binding potassium-sparing diuretics (e.g. spironolactone or eplerenone) are used to limit aldosterone receptor activity. Other medications such as glucocorticoids are added in AME and CAH to inhibit ACTH and further cortisol production. Lifestyle changes such as a low sodium diet are also used for managing hypertension, and cessation of licorice intake is recommended in cases of licorice overconsumption. See also Apparent mineralocorticoid excess syndrome Primary aldosteronism Secondary hypertension References == External links ==
Vaginal bleeding	Vaginal bleeding is any expulsion of blood from the vagina. This bleeding may originate from the uterus, vaginal wall, or cervix. Generally, it is either part of a normal menstrual cycle or is caused by hormonal or other problems of the reproductive system, such as abnormal uterine bleeding. Vaginal bleeding during pregnancy can be normal, especially in early pregnancy. However, bleeding may also indicate a pregnancy complication that needs to be medically addressed. During pregnancy bleeding is usually, but not always, related to the pregnancy itself. Regular monthly vaginal bleeding during the reproductive years, menstruation, is a normal physiologic process. During the reproductive years, bleeding that is excessively heavy (menorrhagia or heavy menstrual bleeding), occurs between monthly menstrual periods (intermenstrual bleeding), occurs more frequently than every 21 days (abnormal uterine bleeding), occurs too infrequently (oligomenorrhea), or occurs after vaginal intercourse (postcoital bleeding) should be evaluated.The causes of abnormal vaginal bleeding vary by age, and such bleeding can be a sign of specific medical conditions ranging from hormone imbalances or anovulation to malignancy (cervical cancer, vaginal cancer or uterine cancer). In young children, or elderly adults with cognitive impairment, the source of bleeding may not be obvious, and may be from the urinary tract (hematuria) or the rectum rather than the vagina, although most adult women can identify the site of bleeding. When vaginal bleeding occurs in prepubertal children or in postmenopausal women, it always needs medical attention. Differential diagnosis The parameters for normal menstruation have been defined as a result of an international process designed to simplify terminologies and definitions for abnormalities of menstrual bleeding. The causes of abnormal vaginal bleeding vary by age. In children Bleeding in children is of concern if it occurs before the expected time of menarche and in the absence of appropriate pubertal development. Bleeding before the onset of pubertal development deserves evaluation. It could result from local causes or from hormonal factors. In children, it may be challenging to determine the source of bleeding, and "vaginal" bleeding may actually arise from the bladder or urethra, or from the rectum.Vaginal bleeding in the first week of life after birth is a common observation, and pediatricians typically discuss this with new mothers at the time of hospital discharge. During childhood, other possible causes include the presence of a foreign body in the vagina, trauma (either accidental or non accidental, i.e. child sexual abuse or molestation), urethral prolapse, vaginal infection (vaginitis), vulvar ulcers, vulvar skin conditions such as lichen sclerosus, and rarely, a tumor (benign or malignant vaginal tumors, or hormone-producing ovarian tumors). Hormonal causes include central precocious puberty, or peripheral precocious puberty (McCune–Albright syndrome), or primary hypothyroidism.While the symptom is typically alarming to parents, most causes are benign, although sexual abuse or tumor are particularly important to exclude. An examination under anesthesia (EUA) may be necessary to exclude a vaginal foreign body or tumor, although instruments designed for office hysteroscopy can sometimes be used in children with topical anesthesia for office vaginoscopy, precluding the need for sedation or general anesthesia and operating room time. Premenopausal Background In premenopausal women, bleeding can be from the uterus, from vulvar or vaginal lesions, or from the cervix. A gynecologic examination can be performed to determine the source of bleeding. Bleeding may also occur as a result of a pregnancy complication, such as a spontaneous abortion (miscarriage), ectopic pregnancy, or abnormal growth of the placenta, even if the woman is not aware of the pregnancy. This possibility must be kept in mind with regard to diagnosis and management. Generally, the causes of abnormal uterine bleeding in premenopausal women who are not pregnant include fibroids, polyps, hormonal disorders such as polycystic ovary syndrome (PCOS), blood clotting disorders, and cancer. Infections such as cervicitis or pelvic inflammatory disease (PID) can also result in vaginal bleeding. Postcoital bleeding is bleeding that occurs after sexual intercourse. Lastly, a normal and common side effect of birth control includes vaginal spotting or bleeding. Clinical guidelines (FIGO classification) A more specific clinical guideline, called the PALM-COEIN system, has been developed by FIGO (International Federation of Gynecology and Obstetrics) to classify the causes of abnormal uterine bleeding. This acronym stands for Polyp, Adenomyosis, Leiomyoma, Malignancy and Hyperplasia, Coagulopathy, Ovulatory Disorders, Endometrial Disorders, Iatrogenic Causes, and Not Classified. The FIGO Menstrual Disorders Group, with input from international experts, recommended a simplified description of abnormal bleeding that discarded imprecise terms such as menorrhagia, metrorrhagia, hypermenorrhea, and dysfunctional uterine bleeding (DUB) in favor of plain English descriptions of bleeding that describe the vaginal bleeding in terms of cycle regularity, frequency, duration, and volume.The PALM causes are related to uterine structural, anatomic, and histolopathologic causes that can be assessed with imaging techniques such as ultrasound or biopsy to view the histology of a lesion. The COEIN causes of abnormal bleeding are not related to structural causes. Polyps: Endometrial polyps are benign growths that are typically detected during gynecologic ultrasonography and confirmed using saline infusion sonography or hysteroscopy, often in combination with an endometrial biopsy providing histopathologic confirmation. Endocervical polyps are visible at the time of a gynecologic examination using a vaginal speculum, and can often be removed with a minor office procedure. Adenomyosis: Adenomyosis is a condition in which endometrial glands are present within the muscle of the uterus (myometrium), and the pathogenesis and mechanism by which it causes abnormal bleeding have been debated. Leiomyoma (fibroids): Uterine leiomyoma, commonly termed uterine fibroids, are common, and most fibroids are asymptomatic. The presence of leiomyomas may not be the cause of abnormal bleeding, although fibroids that are submucosal in location are the most likely to cause abnormal bleeding. Malignancy (pre-cancer and cancer): The Malignancy and Hyperplasia category of the PALM-COEIN system includes malignancies of the genital tract, including cancers of the vulva, the vagina, the cervix, and the uterus. Endometrial hyperplasia, included in this PALM category of abnormal bleeding, is more common in women who are obese or who have a history of chronic anovulation. When endometrial hyperplasia is associated with atypical cells, it can progress to cancer or occur concurrently with it. While endometrial hyperplasia and endometrial cancer occur most commonly among post-menopausal women, most patients with endometrial cancer have abnormal bleeding, and thus the diagnosis must be considered in women during the reproductive years. Coagulopathies (blood clotting disorders): Heavy menstrual bleeding can be related to coagulopathies. Von Willebrand disease is the most common coagulopathy, and most women with von Willebrand disease have heavy menstrual bleeding. Of women with heavy menstrual bleeding, up to 20% will have a bleeding disorder. Heavy menstrual bleeding since menarche is a common symptom for women with bleeding disorders, and in retrospective studies, bleeding disorders have been found in up to 62% of adolescents with heavy menstrual bleeding. Ovulatory dysfunction: Ovulatory dysfunction or anovulation is a common cause of abnormal bleeding that may lead to irregular and unpredictable bleeding, as well as variations in the amount of flow including heavy bleeding. Endocrine, or hormonal, causes of ovulatory disorders include polycystic ovary syndrome (PCOS), thyroid disorders, hyperprolactinemia, obesity, eating disorders including anorexia nervosa or bulimia, or to an imbalance between exercise and caloric intake. Endometrial: Endometrial causes of abnormal bleeding include infection of the endometrium, endometritis, which may occur after a miscarriage (spontaneous abortion) or a delivery, or may be related to a sexually-transmitted infection of the uterus, fallopian tubes or pelvis generally termed pelvic inflammatory disease (PID). Other endometrial causes of abnormal bleeding may relate to the ways that the endometrium heals itself or develops blood vessels. Iatrogenic (caused by medical treatment or procedures): The most common Iatrogenic cause of abnormal bleeding relates to treatment with hormonal medications such as birth control pills, patches, rings, injections, implants, and intrauterine devices (IUDs). Hormone therapy for treatment of menopausal symptoms can also cause abnormal bleeding. Unscheduled bleeding that occurs during such hormonal treatment is termed "breakthrough bleeding" (BTB) Breakthrough bleeding may result from inconsistent use of hormonal treatment, although in the initial months after initiation of a method, it may occur even with perfect use, and may ultimately affect adherence to the medication regimen. The risk of breakthrough bleeding with oral contraceptives is greater if pills are missed. Not classified: The Not Classified category of the PALM-COEIN system includes conditions that may be rare, or whose contribution to abnormal bleeding has not been well established or understood. Pregnancy Vaginal bleeding occurs during 15–25% of first trimester pregnancies. Of these, half go on to miscarry and half bring the fetus to term. There are a number of causes including complications to the placenta, such as placental abruption and placenta previa. Other causes include miscarriage, ectopic pregnancy, molar pregnancy, incompetent cervix, uterine rupture, and preterm labor. Bleeding in early pregnancy may be a sign of a threatened or incomplete miscarriage. In the second or third trimester a placenta previa (a placenta partially or completely overlying the cervix) may bleed quite severely. Placental abruption is often associated with uterine bleeding as well as uterine pain. Postmenopausal Endometrial atrophy, uterine fibroids, and endometrial cancer are common causes of postmenopausal vaginal bleeding. About 10% of cases are due to endometrial cancer. Uterine fibroids are benign tumors made of muscle cells and other tissues located in and around the wall of the uterus. Women with fibroids do not always have symptoms, but some experience vaginal bleeding between periods, pain during sex, and lower back pain. Diagnostic evaluation The cause of the bleeding can often be discerned on the basis of the bleeding history, physical examination, and other medical tests as appropriate. The physical examination for evaluating vaginal bleeding typically includes visualization of the cervix with a speculum, a bimanual exam, and a rectovaginal exam. These are focused on finding the source of the bleeding and looking for any abnormalities that could cause bleeding. In addition, the abdomen is examined and palpated to ascertain if the bleeding is abdominal in origin. Typically a pregnancy test is performed as well. If bleeding was excessive or prolonged, a CBC may be useful to check for anemia. Abnormal endometrium may have to be investigated by a hysteroscopy with a biopsy or a dilation and curettage. Postmenopausal bleeding In postmenopausal vaginal bleeding, the primary goal of any diagnostic evaluations is to exclude endometrial hyperplasia and malignancy. Transvaginal ultrasonography and endometrial sampling are common methods for an initial evaluation. Guidelines from the American College of Obstetricians and Gynecologists (ACOG) recommend transvaginal ultrasonography as an appropriate first-line procedure to identify which patients are at higher risk of endometrial cancer. Endometrial sampling is indicated if having the following findings and/or symptoms: Endometrial thickness greater than 4 mm Diffuse or focal increased echogenicity (heterogeneity) Failure to visualize the endometrium Persistent or recurrent bleeding regardless of endometrial thicknessEndometrial sampling can be obtained either by an endometrial biopsy using an endometrium sampling device such as a pipelle or by dilation and curettage (D&C) with or without a hysteroscopy. FIGO classification In 2011, the International Federation of Gynaecology and Obstetrics (FIGO) recognized two systems designed to aid research, education, and clinical care of women with abnormal uterine bleeding (AUB) in the reproductive years. Complications Severe acute bleeding, such as caused by ectopic pregnancy and post-partum hemorrhage, leads to hypovolemia (the depletion of blood from the circulation), progressing to shock. This is a medical emergency and requires hospital attendance and intravenous fluids, usually followed by blood transfusion. Once the circulating volume has been restored, investigations are performed to identify the source of bleeding and address it. Uncontrolled life-threatening bleeding may require uterine artery embolization (occlusion of the blood vessels supplying the uterus), laparotomy (surgical opening of the abdomen), occasionally leading to hysterectomy (removal of the uterus) as a last resort.A possible complication from protracted vaginal blood loss is iron deficiency anemia, which can develop insidiously. Eliminating the cause will resolve the anemia, although some women require iron supplements or blood transfusions to improve the anemia. Epidemiology Prepubertal The most common cause of vaginal bleeding is usually considered to be a foreign body inserted into the vaginal canal, which is frequently associated with pelvic pain, foul discharge, or recurrent genitourinary infections. This event can be due to normal self-exploration or can be indicative of sexual abuse.Genitourinary injury is also a common cause, and is often the most common cause of hospitalization or emergency department visits for prepubertal vaginal bleeding, comprising up to 45% of such cases. The most common genitourinary injury is the straddle injury, which often occurs during a fall, often on a sharp edge, and can cause lacerations between the labial folds. Treatment While many forms of vaginal bleeding are normal and do not require treatment, other forms will require medical attention. Hormonal management is usually the first option used to treat acute abnormal uterine bleeding. These hormonal medications include birth control pills, medroxyprogesterone acetate (brand name Depo-Provera), and conjugated equine estrogen. Long-term treatments include hormonal IUD insertion, birth control pills, progestin pills or progestin shots (Depo-Provera), and NSAIDs such as ibuprofen Certain medications may not be safe for certain women. Women with blood clotting disorders may also need to see a hematologist.Surgical treatments may also be considered if the bleeding is severe or if there are reasons patients cannot take the hormonal medications listed above. These options include dilation & curettage, endometrial ablation, and hysterectomy (removal of the uterus). Hysterectomy will result in infertility, so surgical decisions will include womens preferences regarding future fertility when possible. See also Istihadha Abnormal uterine bleeding Implantation bleeding References == External links ==
Periostitis	Periostitis, also known as periostalgia, is a medical condition caused by inflammation of the periosteum, a layer of connective tissue that surrounds bone. The condition is generally chronic, and is marked by tenderness and swelling of the bone and pain. Causes Acute periostitis is due to infection, characterized by diffuse formation of pus, severe pain, constitutional symptoms, and usually results in necrosis. It can be caused by excessive physical activity as well, as in the case of medial tibial stress syndrome (also referred to as tibial periostalgia, soleus periostalgia, or shin splints). Congenital infection with syphilis can also cause periostitis in newborn infants. History Evidence for periostitis found in the fossil record is studied by paleopathologists, specialists in ancient disease and injury. Periostitis has been seen in the late Cretaceous-Eocene crocodile Borealosuchus formidabilis, once known as Leidyosuchus. In one study, periostitis was the most common pathology in this species, with 134 instances of the condition out of 7,154 bones the scientists examined showing evidence for the condition. Periostitis has also been documented in dinosaurs, including a forelimb referred to the long-necked Camarasaurus grandis, as well as the shoulder blade of a horned dinosaur. See also Periosteal reaction References == External links ==
Aphonia	Aphonia is defined as the inability to produce voiced sound. Damage to the nerve may be the result of surgery (e.g., thyroidectomy) or a tumor.Aphonia means "no sound". In other words, a person with this disorder has lost their voice. Causes Injuries are often the cause of aphonia. Minor injuries can affect the second and third dorsal area in such a manner that the lymph patches concerned with coordination become either atrophic or relatively nonfunctioning. Tracheotomy can also cause aphonia.Any injury or condition that prevents the vocal cords, the paired bands of muscle tissue positioned over the trachea, from coming together and vibrating will have the potential to make a person unable to speak. When a person prepares to speak, the vocal folds come together over the trachea and vibrate due to the airflow from the lungs. This mechanism produces the sound of the voice. If the vocal folds cannot meet together to vibrate, sound will not be produced. Aphonia can also be caused by and is often accompanied by fear. Psychogenic Psychogenic aphonia is often seen in patients with underlying psychological problems. Laryngeal examination will usually show bowed vocal folds that fail to adduct to the midline during phonation. However, the vocal folds will adduct when the patient is asked to cough. Treatment should involve consultation and counseling with a speech pathologist and, if necessary, a psychologist.In this case, the patients history and the observed unilateral immobility rules out function aphonia. See also Muteness Lists of language disorders References External links Muscle Tension Aphonia Video Example
Bronchiolitis obliterans	Bronchiolitis obliterans (BO), also known as obliterative bronchiolitis, constrictive bronchiolitis and popcorn lung, is a disease that results in obstruction of the smallest airways of the lungs (bronchioles) due to inflammation. Symptoms include a dry cough, shortness of breath, wheezing and feeling tired. These symptoms generally get worse over weeks to months. It is not related to cryptogenic organizing pneumonia, previously known as bronchiolitis obliterans organizing pneumonia.Causes include breathing in toxic fumes, respiratory infections, connective tissue disorder or complications following a bone marrow or heart-lung transplant. Symptoms may not occur until two to eight weeks following toxic exposure or infection. The underlying mechanism involves inflammation that results in scar tissue formation. Diagnosis is by CT scan, pulmonary function tests or lung biopsy. A chest X-ray is often normal.While the disease is not reversible, treatments can slow further worsening. This may include the use of corticosteroids or immunosuppressive medication. A lung transplant may be offered. Outcomes are often poor, with most people dying in months to years.Bronchiolitis obliterans is rare in the general population. It, however, affects about 75% of people by ten years following a lung transplant and up to 10% of people who have received a bone marrow transplant from someone else. The condition was first clearly described in 1981. Prior descriptions occurred as early as 1956, with the term "bronchiolitis obliterans" used first by Reynaud in 1835. Signs and symptoms Bronchiolitis obliterans results in worsening shortness of breath, wheezing, and a dry cough. The symptoms can start gradually, or severe symptoms can occur suddenly. These symptoms represent an obstructive pattern that is non-reversible with bronchodilator therapy, and need to be related to various lung insults. These insults include inhalation damage, post transplant auto-immune injury, post-infectious disease, drug reactions, and several auto-immune diseases. Cause Bronchiolitis obliterans has many possible causes, including collagen vascular disease, transplant rejection in organ transplant patients, viral infection (adenovirus, respiratory syncytial virus, influenza, HIV, cytomegalovirus), Stevens–Johnson syndrome, Pneumocystis pneumonia, drug reaction, aspiration and complications of prematurity (bronchopulmonary dysplasia), and exposure to toxic fumes. Toxins implicated in the condition include diacetyl, sulfur dioxide, nitrogen dioxide, ammonia, chlorine, thionyl chloride, methyl isocyanate, hydrogen fluoride, hydrogen bromide, hydrogen chloride, hydrogen sulfide, phosgene, polyamide-amine dyes, mustard gas and ozone. It can also be present in patients with IBD, systemic lupus erythematosus, juvenile idiopathic arthritis, rheumatoid arthritis, GERD, IgA nephropathy, and ataxia telangiectasia. Activated charcoal has been known to cause it when aspirated. The ingestion of large doses of papaverine in the vegetable Sauropus androgynus has caused it. Additionally, the disorder may be idiopathic (without known cause). Lung transplant Bronchiolitis obliterans is a common complication in lung transplants because transplanted lungs are at greater risk of alloimmunization as compared to healthy lungs. The disease is often termed bronchiolitis obliterans syndrome (BOS) in the setting of post lung transplantation and hematopoietic stem cell transplant (HSCT). Patients who develop BOS post lung transplant vary in disease latency and severity. Patients often initially have normal lung function on pulmonary function testing and have normal chest radiographs. As the disease progresses they begin to have symptoms of shortness of breath, cough, and wheezing as their lung function declines. The Journal of Heart and Lung Transplantation published updated guidelines in 2001 for grading the severity of BOS. The original guidelines and classification system were published in 1993 by the International Society for Heart and Lung Transplantation. Their scoring system is based on the changes in FEV1 in patients from their baseline. When patients are first diagnosed with BOS they have their baseline lung function established by doing pulmonary function testing at the time of diagnosis. The BOS scoring system is as follows: BOS 0: FEV1 > 90% of baseline and FEF25-75 > 75% of baseline BOS 0-p: FEV1 81-89% of baseline and/or FEF25-75 <= 75% of baseline BOS 1: FEV1 66-80% of baseline BOS 2: FEV1 51-65% of baseline BOS 3: FEV1 50% or less of baseline The scoring system shows an increased severity of the disease as the BOS number increases. Hematopoietic stem cell transplant Bronchiolitis obliterans affects up to 5.5% of people who have received HSCT. One of the biggest risk factors after HSCT is the development of GVHD with a 14% risk. Other risk factors post transplant including tobacco use, age of donor, age of recipient, lower baseline FEV1/FVC ratio, non-caucasian race, peripheral and lower circulating IgG levels. Studies have, however, shown mixed results regarding these other risk factors. There has been an association shown between the increased use of peripheral stem cells and the risk of developing bronchiolitis obliterans. Also, research has shown an increased risk for developing the disease within the first year of transplant if the person is infected with respiratory syncytial virus or parainfluenza virus within the first 100 days post transplant. Inhalants There are many industrial inhalants that are known to cause various types of bronchiolitis, including bronchiolitis obliterans.Industrial workers who have presented with bronchiolitis: nylon-flock workers workers who spray prints onto textiles with polyamide-amine dyes battery workers who are exposed to thionyl chloride fumes workers at plants that use or manufacture flavorings such as diacetylDiacetyl is a chemical used to produce the artificial butter flavoring in many foods such as candy and microwave popcorn and occurring naturally in wines. This first came to public attention when eight former employees of the Gilster-Mary Lee popcorn plant in Jasper, Missouri developed bronchiolitis obliterans. Due to this event, bronchiolitis obliterans began to be referred to in the popular media as "popcorn lung" or "popcorn workers lung". It is also referred to as "flavorings-related lung disease". Post-infectious Typically found in young children and is the most common cause at this age. Generally occurs after a viral infection of adenovirus (types 3, 7, and 21), measles (rubeola), mycoplasma, CMV, influenza, and parainfluenza. Swyer-James syndrome is a rare complication of bronchiolitis obliterans caused by measles or adenovirus. Post-infectious bronchiolitis obliterans is most common in the southern hemisphere particularly in countries such as Brazil, Argentina, Australia, Chile and New Zealand. There was a large prevalence of the disease in these areas during the 1990s and early 2000s. In one hospital in Buenos Aires, the Ricardo Gutiérrez Childrens hospital, the disease accounted for 14% of their inpatient respiratory population from 1993 to 2002. As such, much of the information about post-infectious bronchiolitis obliterans has come from research out of South America. The most significant risk factors for the disease are infection with adenovirus and the need for ventilator support. In contrast with another cause of bronchiolitis obliterans in children, Stevens Johnsons syndrome, post-infectious bronchiolitis obliterans tends to be a chronic but non-progressive disease. The disease can have varying impact on children and their quality of life, which has been studied by lung function tests, as well as their exercise tolerance. Children with lower lung function based on their pulmonary function testing, have lower exercise tolerance, which compounds the impact of the disease on cardiovascular function as they are not able to maintain age appropriate aerobic fitness. This ultimately affects their activities of daily living (ADLs) and their quality of life going forward. Burn pits A form of constrictive bronchiolitis is starting to present in Iraq and Afghanistan veterans. It has been attributed to veterans being exposed to trash burn pits. Veterans present with shortness of breath and other asthma-like symptoms. The only way to diagnose this condition is by doing a lung biopsy as chest X-rays and CT scans come back as normal. The government still denies that there is any correlation between burn pits and health problems but the government has started an "Airborne Hazards and Open Burn Pit Registry" to begin tracking the health of veterans who were exposed to burn pits to see if there is a connection. E-cigarettes The American Lung Association lists flavored e-cigarettes as a risk in 2016. Health Canada has, however seen no cases as of 2019. Public Health England writes that the association has come about as "some flavourings used in e-liquids to provide a buttery flavour contain the chemical diacetyl... however, diacetyl is banned as an ingredient from e-cigarettes and e-liquids in the UK." Mechanism The underlying mechanism involves injury and inflammation of epithelial and sub-epithelial cells. These cells then lose the ability to repair the tissue, in particular they lose the ability to regenerate the epithelial or outermost layer, leading to the excess growth of cells that cause scarring. There are multiple pathways of the disease including fibrotic, lymphocytic, and antibody-mediated that have been described. However, while each pathway has a more unique starting point and cause, the result is still injury and inflammation leading to scarring of the lung tissue. The scarred tissue then makes the expiration phase of respiration more difficult, leading to air not being expelled from the lungs. This is termed "air-trapping", which can be seen on medical imaging. Since the scarring is non-reversible, the disease generally does not improve over time, and depending on the inciting can progress to death. Diagnosis Bronchiolitis obliterans is often diagnosed based on the symptoms of obstructive lung disease following lung injury. The definitive diagnosis is through biopsy, but due to the variable distribution of lesions, leading to falsely negative tests, and invasive nature of this procedure it is often not performed. Several tests are often needed to diagnose bronchiolitis obliterans, including spirometry, diffusing capacity of the lung tests (DLCO), lung volume tests, chest X-rays, high-resolution CT (HRCT), and lung biopsy. Pulmonary function testing Spirometry tests usually show an obstructive pattern and is the most common presentation. A slightly reduced to normal forced vital capacity (FVC), and a reduced FEV1 to FVC ratio and forced expiratory volume (FEV) with little to no correction with the use of bronchodialators are common findings. Lung volume tests may show hyperinflation (excessive air in lungs caused by air trapping). Diffusing capacity of the lung (DLCO) tests are usually normal; people with early-stage OB are more likely to have normal DLCO.FEV1 (forced expiratory volume in 1 second) should be above 80% of predicted values to be considered normal. Bronchiolitis obliterans reduces this to between 16% and 21%. Medical imaging Early in the disease chest radiography is typically normal but may show hyperinflation. As the disease progresses a reticular pattern with thickening of airway walls may be present. HRCT can also show air trapping when the person being scanned breathes out completely; it can also show thickening in the airway and haziness in the lungs. A common finding on HRCT is patchy areas of decreased lung density, signifying reduced vascular caliber and air trapping. This pattern is often described as a "mosaic pattern", and may indicate bronchiolitis obliterans. Lung biopsy Transthoracic lung biopsies are preferable for diagnosis of constrictive BO compared to transbronchial biopsies; regardless of the type of biopsy, a diagnosis may only be achieved by examination of multiple samples. Transthoracic biopsies are preferred over transbronchial due to the heterogeneity and distribution of the lesions. OB can be further classified into two categories: constrictive or proliferative. The constrictive pattern is demonstrated by peribronchiolar cellular infiltrates which eventually causes small airway damage and leads to subepithelial fibrosis. The bronchial muscle can eventually become fibrosed which can be identified with trichrome staining. In regards to proliferative disease, intraluminal buds called "Masson bodies" fill the lumen, which results in bronchiolar plugging. Often people with proliferative disease will show butterfly wing-like appearance under microscopy. One key determinate that can be seen on biopsy to differentiate constrictive from proliferative disease is the extent of lesions. Both lesions are localized from the small bronchi to the membranous bronchi, but in constrictive disease, the lesions are intermittent while proliferative disease has a continuous distribution. Differential diagnosis Other conditions that can present similarly include chronic obstructive pulmonary disease, asthma, bronchiectasis, hypersensitivity pneumonitis, and pneumonia. Prevention Inhalants Disease caused by exposure to industrial inhalants and burn pits can be prevented with the use of engineering controls (e.g., exhaust hoods or closed systems), personal protective equipment, monitoring of potentially affected personnel, worker education and training. Transplant The primary prevention of bronchiolitis obliterans in people who have received either lung transplant or HSCT therapy is immunosuppression. In regards to post lung transplantation, the combination of calcineurin inhibitor combined with a purine synthesis inhibitor and a glucocorticoid is the general regimen used. People also have a baseline post-transplant lung function testing done in order to determine if their lung function is declining over time. People who are post-HSCT their immunosuppressive regimen typically includes methotrexate in combination with a calcineurin inhibitor to prevent GVHD, a risk factor for developing bronchiolitis obliterans. Treatment While the disease is not reversible, treatments can slow further worsening. This may include the use of corticosteroids or immunosuppressive medication which may have an effect on the ability to receive a lung transplant if offered. If patients have difficulty breathing (hypoxemia) oxygen can be supplemented. Routine vaccinations are recommended for patients with chronic lung disease to prevent complications from secondary infections due to pneumonia and influenza.Transplant recipients are at risk for re-developing the disease, as bronchiolitis obliterans is a form of chronic rejection. Evaluation of interventions for its prevention relies on early detection of abnormal spirometry results or unusual decreases in repeated measurements. Terminology "Bronchiolitis obliterans" was originally a term used by pathologists to describe two patterns of airway disease, the other was bronchiolitis obliterans organizing pneumonia (BOOP), now known as cryptogenic organizing pneumonia. The name cryptogenic bronchiolitis obliterans is used when a cause is unknown.Bronchiolitis obliterans when it occurs following a lung transplant is known as bronchiolitis obliterans syndrome(BOS). BOS is defined as a person who has had either a HSCT or lung transplant and develops symptoms or radiographic findings consistent with bronchiolitis obliterans, but has not been confirmed by biopsy. References Further reading == External links ==
Hypohidrosis	Hypohidrosis is a disorder in which a person exhibits diminished sweating in response to appropriate stimuli. In contrast with hyperhidrosis, which is a socially troubling yet often benign condition, the consequences of untreated hypohidrosis include hyperthermia, heat stroke and death. An extreme case of hypohidrosis in which there is a complete absence of sweating and the skin is dry is termed anhidrosis. Causes Diagnosis Sweat is readily visualized by a topical indicator such as iodinated starch (Minor test) or sodium alizarin sulphonate, both of which undergo a dramatic colour change when moistened by sweat. A thermoregulatory sweat test can evaluate the body’s response to a thermal stimulus by inducing sweating through a hot box ⁄ room, thermal blanket or exercise. Failure of the topical indicator to undergo a colour change during thermoregulatory sweat testing indicates hypohidrosis, and further tests may be required to localize the lesion. Magnetic resonance imaging of the brain and ⁄ or spinal cord is the best modality for evaluation when the lesion is suspected to be localized to the central nervous system. Skin biopsies are useful when anhidrosis occurs as part of a dermatological disorder. Biopsy results may reveal the sweat gland destruction, necrosis or fibrosis, in addition to the findings of the primary dermatological disorder. Management The treatment options for hypohidrosis and anhidrosis are limited. Those with hypohidrosis should avoid drugs that can aggravate the condition (see "Medications", under § Causes). They should limit activities that raise the core body temperature and if exercises are to be performed, they should be supervised and be performed in a cool, sheltered and well-ventilated environment. In instances where the cause is known, treatment should be directed at the primary pathology. In autoimmune diseases, such as Sjögren syndrome and systemic sclerosis, treatment of the underlying disease using immunosuppressive drugs may lead to improvement in hypohidrosis. In neurological diseases, the primary pathology is often irreversible. In these instances, prevention of further neurological damage, such as good glycaemic control in diabetes, is the cornerstone of management. In acquired generalized anhidrosis, spontaneous remission may be observed in some cases. Numerous cases have been reported to respond effectively to systemic corticosteroids. Although an optimum dose and regime has not been established, pulse methylprednisolone (up to 1000 mg/day) has been reported to have good effect. Citations General references http://www.mayoclinic.com/health/anhidrosis/DS01050 MedlinePlus Encyclopedia: Sweating - absent
Miliaria	Miliaria, also called heat rash, sweat rash, or prickly heat, is a skin disease marked by small, itchy rashes due to sweat trapped under the skin by clogged sweat-gland ducts. Miliaria is a common ailment in hot and humid conditions, such as in the tropics and during the summer. Although it affects people of all ages, it is especially common in children and infants due to their underdeveloped sweat glands. Signs and symptoms Symptoms of miliaria include small, red rashes, called papules, which are irritated and itchy. These may simultaneously occur at a number of areas on a patients body, the most common including the upper chest, neck, elbow creases, under the breasts, and under the scrotum. Other areas include skin folds and areas of the body that may rub against clothing, such as the back, chest, and stomach. A related and sometimes simultaneous condition is folliculitis, where hair follicles become plugged with foreign matter, resulting in inflammation. The symptoms relating to miliaria should not be confused with shingles, as they can be very similar. Shingles is limited to one side of the body, but also has a rash-like appearance. It is also accompanied by a prickly sensation and pain throughout the region. Those who suspect they have shingles and not miliaria should seek medical advice immediately as the sooner antivirals are taken, the better. Types Miliaria can be classified according to the top level at which obstruction occurs in the sweat glands. Miliaria crystalline The most superficial obstruction (with the most mild clinical presentation), is known as miliaria crystalline; instead of a rash, the patient presents with multiple, tiny, blister-like lesions that look like beads of perspiration and essentially cause no symptoms.: 23 Miliaria crystalline is also known as miliaria crystallina, and sudamina. The superficial vesicles are not associated with an inflammatory reaction.: 23 Miliaria rubra The most commonly encountered form of the illness is miliaria rubra, in which obstruction causes leakage of sweat into the deeper layers of the epidermis, provoking a local inflammatory reaction and giving rise to the typical appearance of redness (hence rubra) and larger (but still only a few millimetres), blister-like lesions. This form of the illness is often accompanied by the typical symptoms—intense itching or "pins and needles" with a lack of sweating (anhidrosis) to affected areas.: 23 A small risk of heat exhaustion exists due to inability to sweat if the rash affects a large proportion of the bodys surface area or the patient continues to engage in heat-producing activity. Miliaria rubra is also known as prickly heat and heat rash. Differential diagnosis should be used to rule out polycythemia vera, which is a rare hematological disorder and appears more often in males than females, generally not before the age of 40. Both disorders share a common trait of appearing after taking a hot shower. Miliaria profunda The most severe form of miliaria, miliaria profunda, sometimes referred to as "wildfire" due to the rapid spread and severe burning sensations, generally occurs as a complication of repeated episodes of miliaria rubra. The obstruction is deep in the structure of the sweat gland, causing the glands secretions to leak between the superficial and deep layers of the skin. The rash and associated symptoms tend to appear within hours of an activity provoking sweating, but similarly fade within hours when the stimulus for the sweating is removed. Miliaria profunda is characterised by nonpruritic, flesh-coloured, deep-seated, whitish papules.: 24 The rash tends to be flesh-coloured as opposed to the prominent redness of miliaria rubra, and the risk of heat exhaustion is larger. Miliaria profunda is also less commonly known as "mammillaria": chapter 40 Miliaria pustulosa Miliaria pustulosa describes pustules due to inflammation and bacterial infection. Miliaria pustulosa is preceded by another dermatitis that has produced injury, destruction, or blocking of the sweat ducts.: 23 Postmiliarial hypohidrosis Postmiliarial hypohidrosis is a skin condition that results from occlusion of sweat ducts and pores, and may be severe enough to impair an individuals ability to perform sustained work in a hot environment.: 24 Tropical anhidrotic asthenia Tropical anhidrotic asthenia is a skin condition, a rare form of miliaria, with long-lasting poral occlusion, which produces anhidrosis and heat retention.: 24 Occlusion miliaria Occlusion miliaria is a skin condition that is accompanied by anhidrosis and increased heat-stress susceptibility, all after the application of extensive polyethylene film occlusion for 48 hours or longer.: 24 Colloid milium Colloid milium is a skin condition characterized by a translucent, flesh-colored, or slightly yellow, 1 to 5 mm papules.: 31 Pathophysiology Miliaria occurs when the sweat gland ducts get clogged due to dead skin cells or bacteria such as Staphylococcus epidermidis, a common bacterium that occurs on the skin, which is also associated with acne. The trapped sweat leads to irritation (prickling), itching, and a rash of very small blisters, usually in a localized area of the skin. Prevention Prickly heat can be prevented by avoiding activities that induce sweating, using air conditioning to cool the environment, wearing light clothing, and in general, avoiding hot and humid weather. Frequent cool showers or cool baths with mild soap can help to prevent heat rash. Treatment The primary remedy for prickly heat or rash is to wear lighter clothing, or otherwise avoid overheating ones body. The immediate treatment of the involved skin areas involves the use of a soothing ointment such as calamine lotion. Talcum powder may be used in some cases. Medical assistance should be sought for the first episode of a rash with the appearance of miliaria. The differential diagnosis includes several conditions that an experienced practitioner should be able to recognise and may require treatment distinct from the usual measures taken for miliaria. In most cases, the rash of miliaria resolves without intervention, but severe cases can last for weeks and cause significant disability. General measures should be recommended for all patients, including moving to an air-conditioned environment if possible, avoiding sweat-provoking activities and occlusive clothing, and taking frequent, cool showers. The use of topical antibacterials (including antibacterial soaps) may shorten the duration of symptoms in miliaria rubra even in the absence of obvious superinfection. Other topical agents that may reduce the severity of symptoms include anti-itch preparations such as calamine or menthol- or camphor-based preparations, and topical steroid creams. Caution should be used, however, with oil-based preparations (ointments and oily creams as opposed to water-based or aqueous lotions) that may increase blockage of the sweat glands and prolong the duration of illness. Other agents have been investigated including supplemental vitamin A and C and vitamin A based medications, but little scientific evidence supports any of the above treatments in reducing the duration of symptoms or frequency of complications. In most tropical areas, the local dispensaries sell prickly heat powder, a talc admixture containing drying milk proteins (labilin) and Triclosan to fight bacterial infection. These include cooling menthol to help alleviate difficulty getting to sleep. This is an effective treatment; the powder stays on the skin longer and treats bacteria dispersed into bed linens, providing a reasonably dry refuge area for healing. Miliaria often covers large areas, and generous use of cortisone may be contraindicated for reasons stated on package warnings. Regular talcum powder does not reduce the rash, but can alleviate burning and itching. In cases where the rash has developed into open blisters or pustular lesions, a doctor should be consulted since more aggressive, medically monitored treatment may be required. See also Cholinergic urticaria Sweat allergy References External links DermNet hair-nails-sweat/miliariaPrickly Heat at Merck Manual of Diagnosis and Therapy Home Edition - with pictures WebMd Description Clinical pictures of heat rash/prickly heat - Skinsight
Acute liver failure	Acute liver failure is the appearance of severe complications rapidly after the first signs (such as jaundice) of liver disease, and indicates that the liver has sustained severe damage (loss of function of 80–90% of liver cells). The complications are hepatic encephalopathy and impaired protein synthesis (as measured by the levels of serum albumin and the prothrombin time in the blood). The 1993 classification defines hyperacute as within 1 week, acute as 8–28 days, and subacute as 4–12 weeks; both the speed with which the disease develops and the underlying cause strongly affect outcomes. Signs and symptoms The main features of acute liver failure are rapid-onset jaundice, weakness, and eventually, changes in mental status that can begin as mild confusion but progress to coma. Encephalopathy and cerebral edema In ALF, hepatic encephalopathy leads to cerebral edema, coma, brain herniation, and eventually death. Detection of encephalopathy is central to the diagnosis of ALF. It may vary from subtle deficit in higher brain function (e.g. mood, concentration in grade I) to deep coma (grade IV). Patients presenting as acute and hyperacute liver failure are at greater risk of developing cerebral edema and grade IV encephalopathy. The pathogenesis remains unclear, but is likely to be a consequence of several phenomena. There is a buildup of toxic substances like ammonia, mercaptan, serotonin and tryptophan in the brain. This affects neurotransmitter level and neuroreceptor activation. Autoregulation of cerebral blood flow is impaired, and is associated with anaerobic glycolysis and oxidative stress. Neuronal cell astrocytes are susceptible to these changes, and they swell up, resulting in increased intracranial pressure. Inflammatory mediators also play important role.Unfortunately, signs of elevated intracranial pressure, such as papilledema and loss of pupillary reflexes, are not reliable, and occur late in the disease process. CT imaging of the brain is also unhelpful in detecting early cerebral oedema, but is often performed to rule out intra-cerebral bleeding. Invasive intracranial pressure monitoring via subdural route is often recommended; however, the risk of complications must be weighed against the possible benefit (1% fatal haemorrhage). The aim is to maintain intracranial pressures below 25 mm Hg, and cerebral perfusion pressures above 50 mm Hg. Coagulopathy Coagulopathy is another cardinal feature of ALF. The liver has the central role in the synthesis of almost all coagulation factors and some inhibitors of coagulation and fibrinolysis. Hepatocellular necrosis leads to impaired synthesis of many coagulation factors and their inhibitors. The former produces a prolongation in prothrombin time which is widely used to monitor the severity of hepatic injury. There is significant platelet dysfunction (with both quantitative and qualitative platelet defects). Progressive thrombocytopenia with the loss of larger and more active platelets is almost universal. Thrombocytopenia with or without DIC increases risk of intracerebral bleeding. Kidney failure Kidney failure is common, present in more than 50% of ALF patients, either due to original insult such as paracetamol resulting in acute tubular necrosis or from hyperdynamic circulation leading to hepatorenal syndrome or functional kidney failure. Because of impaired production of urea, blood urea does not represent the degree of kidney impairment. Inflammation and infection About 60% of all ALF patients fulfil the criteria for systemic inflammatory syndrome irrespective of presence or absence of infection. This often contributes towards multi organ failure. Impaired host defence mechanism, due to impaired opsonization, chemotaxis and intracellular killing, substantially increases risk of sepsis. Bacterial sepsis mostly due to gram positive organisms and fungal sepsis are observed in up to 80% and 30% patients, respectively. Metabolic derangements Hyponatraemia is an almost universal finding due to water retention and a shift in intracellular sodium transport from inhibition of Na/K ATPase. Hypoglycaemia (due to depleted hepatic glycogen store and hyperinsulinaemia), hypokalaemia, hypophosphataemia and metabolic alkalosis are often present, independent of renal function. Lactic acidosis occurs predominantly in paracetamol (also known as acetaminophen) overdose. Haemodynamic and cardio-respiratory compromise Hyperdynamic circulation, with peripheral vasodilatation from low systemic vascular resistance, leads to hypotension. There is a compensatory increase in cardiac output. Adrenal insufficiency has been documented in 60% of ALF cases, and is likely to contribute in haemodynamic compromise. There is also abnormal oxygen transport and utilization. Although delivery of oxygen to the tissues is adequate, there is a decrease in tissue oxygen uptake, resulting in tissue hypoxia and lactic acidosis.Pulmonary complications occur in up to 50% of patients. Severe lung injury and hypoxemia result in high mortality. Most cases of severe lung injury are due to ARDS, with or without sepsis. Pulmonary haemorrhage, pleural effusions, atelectasis, and intrapulmonary shunts also contribute to respiratory difficulty. Late pregnancy In late pregnancy liver function decreases significantly, which can be easily monitored by blood tests. Early clinical manifestations of ALF in late pregnancy include hypodynamia, decrease in appetite, dark amber urine, deep jaundice, nausea, vomiting, and abdominal distention. Among patients whose deaths were attributed to ALF in late pregnancy, the majority had experienced vaginal deliveries. Causes Common causes for acute liver failure are paracetamol (acetaminophen) overdose, idiosyncratic reaction to medication (e.g. tetracycline, troglitazone), excessive alcohol consumption (severe alcoholic hepatitis), viral hepatitis (hepatitis A or B—it is extremely uncommon in hepatitis C), acute fatty liver of pregnancy, and idiopathic (without an obvious cause). Reye syndrome is acute liver failure in a child with a viral infection (e.g. chickenpox); it appears that aspirin use may play a significant role. Wilsons disease (hereditary copper accumulation) may infrequently present with acute liver failure. Acute liver failure also results from poisoning by the death cap mushroom (Amanita phalloides) as well as other amatoxin-producing fungus species. Certain strains of Bacillus cereus—a common species of bacterium implicated as a frequent cause of food poisoning—can cause fulminant liver failure through the production of cereulide, a toxin which destroys the mitochondria in affected hepatocytes, resulting in cell death. While most instances of B. cereus infection are resolved by the bodys immune system and do not affect the liver, severe cases resulting in liver damage can be fatal without immediate treatment or liver transplantation. Pathophysiology In the majority of acute liver failure (ALF) there is widespread hepatocellular necrosis beginning in the centrizonal distribution and progressing towards portal tracts. The degree of parenchymal inflammation is variable and is proportional to duration of disease.Zone 1 (periportal) occurs in phosphorus poisoning or eclampsia. Zone 2 (mid-zonal), although rare, is seen in yellow fever. Zone 3 (centrilobular) occurs with ischemic injury, toxic effects, carbon tetrachloride exposure, or chloroform ingestion. In acute acetaminophen overdose, toxification occurs, mostly in Zone III which has the highest level of P450 micro-enzymes. That fact along with Zone IIIs decreased oxygen level helps to explain why it is preferentially one of the initial sites of damage. Diagnosis All patients with clinical or laboratory evidence of moderate to severe acute hepatitis should have an immediate measurement of prothrombin time and careful evaluation of mental status. If the prothrombin time is prolonged by ≈ 4–6 seconds or more (INR ≥ 1.5), and there is any evidence of altered sensorium, the diagnosis of ALF should be strongly suspected, and hospital admission is mandatory. Initial laboratory examination must be extensive in order to evaluate both the etiology and severity. Initial laboratory analysisProthrombin time/INR Complete blood count Chemistries Liver function test: AST, ALT, alkaline phosphatase, GGT, total bilirubin, albumin Creatinine, urea/blood urea nitrogen, sodium, potassium, chloride, bicarbonate, calcium, magnesium, phosphate Glucose Amylase and lipase Arterial blood gas, lactate Blood type and screen Paracetamol (acetaminophen) level, toxicology screen Viral hepatitis serologies: anti-HAV IgM, HBSAg, anti-HBc IgM, anti-HCV Autoimmune markers: ANA, ASMA, LKMA, immunoglobulin levels Ceruloplasmin level (when Wilsons disease suspected) Pregnancy test (females) Ammonia (arterial if possible) HIV status (has implication for transplantation)History taking should include a careful review of possible exposures to viral infection and drugs or other toxins. From history and clinical examination, the possibility of underlying chronic disease should be ruled out as it may require different management. A liver biopsy done via the transjugular route because of coagulopathy is not usually necessary, other than in occasional malignancies. As the evaluation continues, several important decisions have to be made; such as whether to admit the patient to an ICU, or whether to transfer the patient to a transplant facility. Consultation with the transplant center as early as possible is critical due to the possibility of rapid progression of ALF. Definition Acute liver failure is defined as "the rapid development of hepatocellular dysfunction, specifically coagulopathy and mental status changes (encephalopathy) in a patient without known prior liver disease".page 1557The diagnosis of acute liver failure is based on physical exam, laboratory findings, patient history, and past medical history to establish mental status changes, coagulopathy, rapidity of onset, and absence of known prior liver disease respectively.page 1557The exact definition of "rapid" is somewhat questionable, and different sub-divisions exist which are based on the time from onset of first hepatic symptoms to onset of encephalopathy. One scheme defines "acute hepatic failure" as the development of encephalopathy within 26 weeks of the onset of any hepatic symptoms. This is sub-divided into "fulminant hepatic failure", which requires onset of encephalopathy within 8 weeks, and "subfulminant", which describes onset of encephalopathy after 8 weeks but before 26 weeks. Another scheme defines "hyperacute" as onset within 7 days, "acute" as onset between 7 and 28 days, and "subacute" as onset between 28 days and 24 weeks.page 1557 Treatment General concerns Because ALF often involves the rapid deterioration of mental status and the potential for multiorgan failure, patients should be managed in the intensive care unit. For patients not at a transplant center, the possibility of rapid progression of ALF makes early consultation with a transplant facility critical. Accordingly, plans for transfer to a transplant center should begin in patients with any abnormal mentation. Early institution of antidotes or specific therapy may prevent the need for liver transplantation and reduce the likelihood of poor outcome. Measures appropriate for specific causes of ALF are described in detail later in this chapter. Neurologic complications Patients with grade I–II encephalopathy should be transferred to a liver transplant facility and listed for transplantation. Consider a brain computed tomography (CT) scan to rule out other causes of altered or impaired mental status. Stimulation and overhydration can cause elevations in intracranial pressure (ICP) and should be avoided. Unmanageable agitation may be treated with short-acting benzodiazepines in small doses. Lactulose can be considered at this stage. A preliminary report from the ALFSG on 117 patients suggests that use of lactulose in the first 7 days after diagnosis is associated with a small increase in survival time, but with no difference in severity of encephalopathy or in the overall outcome. For patients who progress to grade III–IV encephalopathy, intubation for airway protection is generally required. Many centers use propofol for sedation because it may reduce cerebral blood. The head of the bed should be elevated to 30 degrees, and electrolytes, blood gasses, glucose, and neurologic status monitored frequently. Cardiovascular complications Increased cardiac output and low systemic vascular resistance are characteristic of ALF. Pulmonary artery catheterization should be considered. Hypotension should be treated preferentially with fluids, but systemic vasopressor support with agents such as epinephrine, norepinephrine, or dopamine should be used if fluid replacement fails to maintain mean arterial pressure of 50–60 mm Hg. Vasoconstrictive agents (especially vasopressin) should be avoided. Pulmonary complications Pulmonary edema and pulmonary infections are commonly seen in patients with ALF. Mechanical ventilation may be required. However, positive end-expiratory pressure can worsen cerebral edema. Coagulopathy and gastrointestinal bleeding Impaired liver synthesis of clotting factors, low-grade fibrinolysis, and intravascular coagulation are typical of ALF. Thrombocytopenia is common and may also be dysfunctional. Replacement therapy is recommended only in the setting of bleeding or prior to an invasive procedure. Vitamin K can be given to treat an abnormal prothrombin time, regardless of whether there is poor nutritional status. Administration of recombinant factor VIIa has shown promise; however, this treatment approach requires further study. The use of gastrointestinal hemorrhage prophylaxis with a histamine-2 (H2) blocker, proton pump inhibitor, or sucralfate is recommended. Nutrition, electrolytes, and metabolic derangements In patients with grade I or II encephalopathy, enteral feeding should be initiated early. Parenteral nutrition should be used only if enteral feeding is contraindicated as it increases the risk of infection. Severe restriction of protein is not beneficial; 60 g/day of protein is generally reasonable. Fluid replacement with colloid (e.g. albumin) is preferred rather than crystalloid (e.g. saline); all solutions should contain dextrose to maintain euglycemia. Multiple electrolyte abnormalities are common in ALF. Correction of hypokalemia is essential as hypokalemia increases the kidneys ammonia production, potentially exacerbating encephalopathy. Hypophosphatemia is especially common in patients with acetaminophen-induced ALF and in those with intact renal function. Hypoglycemia occurs in many patients with ALF and is often due to depletion of hepatic glycogen stores and impaired gluconeogenesis. Plasma glucose concentration should be monitored and hypertonic glucose administered as needed. Infection Bacterial and fungal infections are common in ALF, with one study demonstrating culture-proven infection in 80% of ALF patients. Defective cellular and humoral immunity as well as presence of indwelling catheters, coma, broad-spectrum antibiotics, and medications that suppress immunity all predispose to infection. Localizing symptoms of infection such as fever and sputum production are frequently absent and the only clues to an underlying infectious process may be worsening of encephalopathy or renal function. There must be a low threshold for obtaining frequent cultures (blood, urine, and sputum), chest radiographs, and paracentesis. Bacteria that enter through the skin, such as streptococci and staphylococci, tend to predominate. Aggressive surveillance is essential as prophylactic antibiotics have shown little benefit. Fungal infections, particularly in the setting of broad-spectrum antibiotics, are also common, and disseminated fungemia is a poor prognostic sign. Liver transplantation The advent of transplantation has changed survival from as low as 15% in the pretransplant era to more than 60% today. Liver transplantation is indicated for many patients with ALF, and survival rates of 56–90% can be achieved. In addition to transplantation, better critical care and the trend toward more benign causes, such as acetaminophen, all contribute to improved survival rates. Spontaneous survival is now around 40%. The application of transplantation among patients with ALF remains low, suggesting that the full potential of this modality may not be realized. Timely availability of an allograft is one of the major factors determining transplant outcomes. In the largest U.S. study, only 29% of patients received a liver graft, while 10% of the overall group (one fourth of patients listed for transplantation) died on the waiting list. Other series have reported death rates of those listed for transplant as high as 40%. In the ALFSG, the transplantation rate was higher in the groups with lower short-term spontaneous survival, making overall survival similar in all groups: acetaminophen, 73%; drug induced, 70%; indeterminate group, 64%; and other causes, 61%. Causes of death for the 101 patients who died within the 3-week period included cerebral edema, multiorgan failure, sepsis, cardiac arrhythmia or arrest and respiratory failure. The median time to death after admission was 5 days. Acetylcysteine Intravenous N-acetylcysteine has been found to be beneficial in both acetaminophen toxicity and non-acetaminophen-related acute liver failure. Prognosis Historically mortality has been high, being in excess of 80%. In recent years the advent of liver transplantation and multidisciplinary intensive care support have improved survival significantly. At present overall short-term survival with transplant is more than 65%.Several prognostic scoring systems have been devised to predict mortality and to identify who will require an early liver transplant. These include Kings College Hospital criteria, MELD score, APACHE II, and Clichy criteria. Terminology To date, no universally accepted nomenclature has been adopted. Trey and Davidson introduced the phrase fulminant hepatic failure in 1970, which they described as a "... potentially reversible condition, the consequence of severe liver injury, with an onset of encephalopathy within 8 weeks of the appearance of the first symptoms and in the absence of pre-existing liver disease". Later, it was suggested that the term fulminant should be confined to patients who develop jaundice to encephalopathy within 2 weeks. Phrases subfulminant hepatic failure and late onset hepatic failure were coined for onset between 2 weeks to 3 months and for 8 weeks to 24 weeks, respectively. The umbrella phrase of acute liver failure was proposed by Kings College group, which has been adopted in this article. Paradoxically, in this classification, the best prognosis is in the hyperacute group. References External links Fulminant Hepatic Failure at eMedicine
Perioral dermatitis	Perioral dermatitis, also known as periorificial dermatitis, is a common type of skin rash. Symptoms include multiple small (1–2 mm) bumps and blisters sometimes with background redness and scale, localized to the skin around the mouth and nostrils. Less commonly the eyes and genitalia may be involved. It can be persistent or recurring and resembles particularly rosacea and to some extent acne and allergic dermatitis. The term "dermatitis" is a misnomer because this is not an eczematous process.The cause is unclear. Topical steroids are associated with the condition and moisturizers and cosmetics may contribute. The underlying mechanism may involve blockage of the skin surface followed by subsequent excessive growth of skin flora. Fluoridated toothpaste and some micro-organisms including Candida may also worsen the condition, but their roles in this condition is unclear. It is considered a disease of the hair follicle with biopsy samples showing microscopic changes around the hair follicle. Diagnosis is based on symptoms.Treatment is typically by stopping topical steroids, changing cosmetics, and in more severe cases, taking tetracyclines by mouth. Stopping steroids may initially worsen the rash. The condition is estimated to affect 0.5-1% of people a year in the developed world. Up to 90% of those affected are women between the ages of 16 and 45 years, though it also affects children and the elderly, and has an increasing incidence in men. History The disorder appears to have made a sudden appearance with a case of light sensitive seborrhoeid in 1957, which is said to be the first nearest description of the condition. By 1964, the condition in adults became popularly known as perioral dermatitis, but without clear clinical criteria. In 1970, the condition was recognised in children. That all rashes around the mouth are perioral dermatitis has since been frequently debated. That this condition should be renamed periorificial dermatitis has been proposed. Darrell Wilkinson, 1919–2009, was a British dermatologist who gave one of the earliest definitive descriptions of perioral dermatitis and noted that the condition was not always associated with the use of fluoridated steroid creams. Signs and symptoms A stinging and burning sensation with rash is often felt and noticed, but itching is less common. Often the rash is steroid responsive, initially improving with application of topical steroid. The redness caused by perioral dermatitis has been associated with variable level of depression and anxiety.Initially, there may be small pinpoint papules either side of the nostrils. Multiple small (1-2mm) papules and pustules then occur around the mouth, nose and sometimes cheeks. The area of skin directly adjacent to the lips, also called the vermillion border, is spared and looks normal. There may be some mild background redness and occasional scale. These areas of skin are felt to be drier and therefore there is a tendency to moisturise them more frequently. Hence, they do not tolerate drying agents well and the rash can be worsened by them.Perioral dermatitis is also known by other names including rosacea-like dermatoses, periorofacial dermatitis and periorificial dermatitis. Unlike rosacea which involves mainly the nose and cheeks, there is no telangiectasia in perioral dermatitis. Rosacea also has a tendency to be present in older people. Acne can be distinguished by the presence of comedones and by its wider distribution on the face and chest. There are no comedones in perioral dermatitis. Causes The cause of perioral dermatitis is unclear. The use of topical steroids and cosmetics have the most important role. Although light exposure has been discounted as a causal factor, some reports of perioral dermatitis have been made by some patients receiving Psoralen and ultraviolet A therapy. Corticosteroids Perioral dermatitis often happens after the use of topical steroids on the face, and is more likely to occur the greater the strength of topical steroid used. Discontinuing the steroids often initially worsens the dermatitis, and dependency on the steroids can occur as people believe the steroids were initially controlling the condition. Inhaled corticosteroids may also trigger perioral dermatitis. Perioral dermatitis has a tendency to occur on the drier parts of the face and can be aggravated by drying agents including topical benzoyl peroxide, tretinoin and lotions with an alcohol base. Immunosuppressants Reports of perioral dermatitis in renal transplant recipients treated with oral corticosteroids and azathioprine have been documented. Cosmetics Cosmetics play an important role as causal factors for perioral dermatitis. Regular generous applications of moisturising creams cause persistent hydration of the layer causing impairment and occlusion of the barrier function, irritation of the hair follicle, and proliferation of skin flora. Combining this with night cream and foundation significantly increases risk of perioral dermatitis 13-fold. Micro-organisms Topical corticosteroids may lead to increase micro-organism density in the hair follicle. The role of infectious agents such as Candida species, Demodex folliculorum, and fusiform bacteria has not been confirmed. Psychosocial As a cosmetic impairment, perioral dermatitis is increasingly documented to have psychosocial aspects to its cause and clinical findings. Specific personality structures, professions and social habits have been implicated in the type of person the condition occurs in. Other potential causes The condition may be potentially worsened by fluoridated toothpaste and inhaled corticosteroids. A high prevalence of atopy has been found in those with perioral dermatitis. The possibility of an association with the wearing of the veil in Arab women has been documented. Pathophysiology The pathophysiology of perioral dermatitis is related to disease of the hair follicle as is now included in the ICD-11 due to be finalised in 2018. Lip lickers dermatitis or perioral irritant contact dermatitis due to lip-licking is considered a separate disease categorised under irritant contact dermatitis due to saliva.Perioral dermatitis is frequently histologically similar to rosacea with the two conditions overlapping considerably. There is a lymphohistiocytic infiltrate with perifollicular localization and marked granulomatous inflammation. Occasionally, perifollicular abscesses may be present when pustules and papules are the dominant clinical findings. Diagnosis A diagnosis of perioral dermatitis is typically made based on the characteristics of the rash. A skin biopsy is usually not required to make the diagnosis but can be helpful to rule out other skin diseases which may resemble perioral dermatitis. Extended patch testing may be useful to also rule out allergic contact causes.Other skin diseases that may resemble perioral dermatitis include: Rosacea Acne vulgaris Seborrheic dermatitis Allergic contact dermatitis Irritant contact dermatitis Angular cheilitis Treatment Multiple treatment regimes are available and treatment algorithms have been proposed.Perioral dermatitis will usually resolve within a few months without medication, by limiting the use of irritants, including products with fragrance, cosmetics, benzoyl peroxide, occlusive sunscreens, and various acne products. This is called zero treatment. Topical corticosteroids should be stopped entirely if possible. If the flare proves intolerable, temporary use of a less potent topical corticosteroid can often be helpful. Medication A number of medications, either applied directly to the skin or taken by mouth, may hasten recovery. These include tetracycline, doxycycline, and erythromycin. Erythromycin may be used as a cream. Doxycycline is most often the first antibiotic drug choice, given at a daily dosage of 100 mg for up to a month before considering tapering off or stopping. Sometimes, longer duration of low doses of doxycycline are required.Metronidazole is less effective, but is available in a gel and can be applied twice daily. If the perioral dermatitis was triggered by a topical steroid then pimecrolimus cream has been suggested as effective in improving symptoms. However, this has also been documented to cause the condition. Prognosis Perioral dermatitis is likely to fully resolve with short courses of antibiotics but if left untreated it can persist for years and take a chronic form.Improvement with tetracyclines is usually seen after 4 days and significantly so after 2 weeks. Epidemiology Most commonly in women between the ages of 16 and 45 years, perioral dermatitis also occurs equally in all racial and ethnic backgrounds and include children as young as three months and is increasingly reported in men. In children, females are more likely affected. It has an incidence of up to 1% in developed countries. See also Childhood granulomatous periorificial dermatitis Seborrhoeic dermatitis Eczema herpeticum, condition that primarily manifests in childhood == References ==
Hemolytic anemia	Hemolytic anemia is a form of anemia due to hemolysis, the abnormal breakdown of red blood cells (RBCs), either in the blood vessels (intravascular hemolysis) or elsewhere in the human body (extravascular). This most commonly occurs within the spleen, but also can occur in the reticuloendothelial system or mechanically (prosthetic valve damage). Hemolytic anemia accounts for 5% of all existing anemias. It has numerous possible consequences, ranging from general symptoms to life-threatening systemic effects. The general classification of hemolytic anemia is either intrinsic or extrinsic. Treatment depends on the type and cause of the hemolytic anemia.Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition, the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications, such as gallstones and pulmonary hypertension. Signs and symptoms Symptoms of hemolytic anemia are similar to the general signs of anemia. General signs and symptoms include: fatigue, pallor, shortness of breath, and tachycardia. In small children, failure to thrive may occur in any form of anemia. In addition, symptoms related to hemolysis may be present such as chills, jaundice, dark urine, and an enlarged spleen. Certain aspects of the medical history can suggest a cause for hemolysis, such as drugs, medication side effects, autoimmune disorders, blood transfusion reactions, the presence of prosthetic heart valve, or other medical illness.Chronic hemolysis leads to an increased excretion of bilirubin into the biliary tract, which in turn may lead to gallstones. The continuous release of free hemoglobin has been linked with the development of pulmonary hypertension (increased pressure over the pulmonary artery); this, in turn, leads to episodes of syncope (fainting), chest pain, and progressive breathlessness. Pulmonary hypertension eventually causes right ventricular heart failure, the symptoms of which are peripheral edema (fluid accumulation in the skin of the legs) and ascites (fluid accumulation in the abdominal cavity). Causes They may be classified according to the means of hemolysis, being either intrinsic in cases where the cause is related to the red blood cell (RBC) itself, or extrinsic in cases where factors external to the RBC dominate. Intrinsic effects may include problems with RBC proteins or oxidative stress handling, whereas external factors include immune attack and microvascular angiopathies (RBCs are mechanically damaged in circulation). Intrinsic causes Hereditary (inherited) hemolytic anemia can be due to : Defects of red blood cell membrane production (as in hereditary spherocytosis and hereditary elliptocytosis). Defects in hemoglobin production (as in thalassemia, sickle-cell disease and congenital dyserythropoietic anemia). Defective red cell metabolism (as in glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency). Wilsons disease may infrequently present with hemolytic anemia without due to excessive inorganic copper in blood circulation, which destroys red blood cells (though the mechanism of hemolysis is still unclear). Extrinsic causes Acquired hemolytic anemia may be caused by immune-mediated causes, drugs, and other miscellaneous causes. Immune-mediated causes could include transient factors as in Mycoplasma pneumoniae infection (cold agglutinin disease) or permanent factors as in autoimmune diseases like autoimmune hemolytic anemia (itself more common in diseases such as systemic lupus erythematosus, rheumatoid arthritis, Hodgkins lymphoma, and chronic lymphocytic leukemia). Spur cell hemolytic anemia Any of the causes of hypersplenism (increased activity of the spleen), such as portal hypertension. Acquired hemolytic anemia is also encountered in burns and as a result of certain infections (e.g. malaria). Paroxysmal nocturnal hemoglobinuria (PNH), sometimes referred to as Marchiafava-Micheli syndrome, is a rare, acquired, potentially life-threatening disease of the blood characterized by complement-induced intravascular hemolytic anemia. Lead poisoning resulting from the environment causes non-immune hemolytic anemia. Similarly, poisoning by arsine or stibine also causes hemolytic anemia. Runners can develop hemolytic anemia due to "footstrike hemolysis", owing to the destruction of red blood cells in feet at foot impact. Low-grade hemolytic anemia occurs in 70% of prosthetic heart valve recipients, and severe hemolytic anemia occurs in 3%. Mechanism In hemolytic anemia, there are two principal mechanisms of hemolysis; intravascular and extravascular. Intravascular hemolysis Intravascular hemolysis describes hemolysis that happens mainly inside the vasculature. As a result, the contents of the red blood cell are released into the general circulation, leading to hemoglobinemia and increasing the risk of ensuing hyperbilirubinemia.Intravascular hemolysis may occur when red blood cells are targeted by autoantibodies, leading to complement fixation, or by damage by parasites such as Babesia. Extravascular hemolysis Extravascular hemolysis refers to hemolysis taking place in the liver, spleen, bone marrow, and lymph nodes. In this case little hemoglobin escapes into blood plasma. The macrophages of the reticuloendothelial system in these organs engulf and destroy structurally-defective red blood cells, or those with antibodies attached, and release unconjugated bilirubin into the blood plasma circulation. Typically, the spleen destroys mildly abnormal red blood cells or those coated with IgG-type antibodies, while severely abnormal red blood cells or those coated with IgM-type antibodies are destroyed in the circulation or in the liver.If extravascular hemolysis is extensive, hemosiderin can be deposited in the spleen, bone marrow, kidney, liver, and other organs, resulting in hemosiderosis.In a healthy person, a red blood cell survives 90 to 120 days in the circulation, so about 1% of human red blood cells break down each day. The spleen (part of the reticulo-endothelial system) is the main organ that removes old and damaged RBCs from the circulation. In healthy individuals, the breakdown and removal of RBCs from the circulation is matched by the production of new RBCs in the bone marrow.In conditions where the rate of RBC breakdown is increased, the body initially compensates by producing more RBCs; however, breakdown of RBCs can exceed the rate that the body can make RBCs, and so anemia can develop. Bilirubin, a breakdown product of hemoglobin, can accumulate in the blood, causing jaundice.In general, hemolytic anemia occurs as a modification of the RBC life cycle. That is, instead of being collected at the end of its useful life and disposed of normally, the RBC disintegrates in a manner allowing free iron-containing molecules to reach the blood. With their complete lack of mitochondria, RBCs rely on pentose phosphate pathway (PPP) for the materials needed to reduce oxidative damage. Any limitations of PPP can result in more susceptibility to oxidative damage and a short or abnormal lifecycle. If the cell is unable to signal to the reticuloendothelial phagocytes by externalizing phosphatidylserine, it is likely to lyse through uncontrolled means.The distinguishing feature of intravascular hemolysis is the release of RBC contents into the blood stream. The metabolism and elimination of these products, largely iron-containing compounds capable of doing damage through Fenton reactions, is an important part of the condition. Several reference texts exist on the elimination pathways, for example. Free hemoglobin can bind to haptoglobin, and the complex is cleared from the circulation; thus, a decrease in haptoglobin can support a diagnosis of hemolytic anemia. Alternatively, hemoglobin may oxidize and release the heme group that is able to bind to either albumin or hemopexin. The heme is ultimately converted to bilirubin and removed in stool and urine. Hemoglobin may be cleared directly by the kidneys resulting in fast clearance of free hemoglobin but causing the continued loss of hemosiderin loaded renal tubular cells for many days. Additional effects of free hemoglobin seem to be due to specific reactions with NO. Diagnosis The diagnosis of hemolytic anemia can be suspected on the basis of a constellation of symptoms and is largely based on the presence of anemia, an increased proportion of immature red cells (reticulocytes) and a decrease in the level of haptoglobin, a protein that binds free hemoglobin. Examination of a peripheral blood smear and some other laboratory studies can contribute to the diagnosis. Symptoms of hemolytic anemia include those that can occur in all anemias as well as the specific consequences of hemolysis. All anemias can cause fatigue, shortness of breath, decreased ability to exercise when severe. Symptoms specifically related to hemolysis include jaundice and dark colored urine due to the presence of hemoglobin (hemoglobinuria). When restricted to the morning hemoglobinuria may suggest paroxysmal nocturnal haemoglobinuria. Direct examination of blood under a microscope in a peripheral blood smear may demonstrate red blood cell fragments called schistocytes, red blood cells that look like spheres (spherocytes), and/or red blood cells missing small pieces (bite cells). An increased number of newly made red blood cells (reticulocytes) may also be a sign of bone marrow compensation for anemia. Laboratory studies commonly used to investigate hemolytic anemia include blood tests for breakdown products of red blood cells, bilirubin and lactate dehydrogenase, a test for the free hemoglobin binding protein haptoglobin, and the direct Coombs test to evaluate antibody binding to red blood cells suggesting autoimmune hemolytic anemia. Treatment Definitive therapy depends on the cause: Symptomatic treatment can be given by blood transfusion, if there is marked anemia. A positive Coombs test is a relative contraindication to transfuse the patient. In cold hemolytic anemia there is advantage in transfusing warmed blood. In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary. In steroid resistant cases, consideration can be given to rituximab or addition of an immunosuppressant (azathioprine, cyclophosphamide). Association of methylprednisolone and intravenous immunoglobulin can control hemolysis in acute severe cases. Sometimes splenectomy can be helpful where extravascular hemolysis, or hereditary spherocytosis, is predominant (i.e., most of the red blood cells are being removed by the spleen).Mitapivat was approved for medical use in the United States in February 2022. Other animals Hemolytic anemia affects nonhuman species as well as humans. It has been found, in a number of animal species, to result from specific triggers.Some notable cases include hemolytic anemia found in black rhinos kept in captivity, with the disease, in one instance, affecting 20% of captive rhinos at a specific facility. The disease is also found in wild rhinos.Dogs and cats differ slightly from humans in some details of their RBC composition and have altered susceptibility to damage, notably, increased susceptibility to oxidative damage from consumption of onion. Garlic is less toxic to dogs than onion. References == External links ==
Cardiac fibrosis	Cardiac fibrosis commonly refers to the excess deposition of extracellular matrix in the cardiac muscle, but the term may also refer to an abnormal thickening of the heart valves due to inappropriate proliferation of cardiac fibroblasts. Fibrotic cardiac muscle is stiffer and less compliant and is seen in the progression to heart failure. The description below focuses on a specific mechanism of valvular pathology but there are other causes of valve pathology and fibrosis of the cardiac muscle. Fibrocyte cells normally secrete collagen, and function to provide structural support for the heart. When over-activated this process causes thickening and fibrosis of the valve, with white tissue building up primarily on the tricuspid valve, but also occurring on the pulmonary valve. The thickening and loss of flexibility eventually may lead to valvular dysfunction and right-sided heart failure. Types Following are types of myocardial fibrosis: Interstitial fibrosis, which is unspecific, and has been described in congestive heart failure, hypertension, and normal aging. Subepicardial fibrosis, also unspecific, and is associated with non-infarction diagnoses such as myocarditis and non-ischemic cardiomyopathy. Replacement fibrosis, which indicates an older infarction. Connection with excess blood serotonin (5-HT) Certain diseases such as neuroendocrine tumor of the small intestine (also known by the obsolete term carcinoid), which sometimes release large amounts of 5-hydroxytryptamine, commonly known as 5-HT or serotonin into the blood, may produce a characteristic pattern of mostly right-sided cardiac fibrosis which can be identified with echocardiography. Cardiac fibrosis is a significant source of morbidity and mortality in patients with functional neuroendocrine tumors. This pathology has also been seen in certain East-African tribes who eat foods (Matoke —a green banana) containing excess amounts of serotonin. Connection with direct serotonergic agonist drugs Elevated prevalence of cardiac fibrosis and related valvopathies was found to be associated with use of a number of unrelated drugs following long-term statistical analysis once the drugs had been on the market for some time. The cause of this was unknown at the time, but eventually it was realised that all the implicated drugs acted as agonists at 5-HT2B receptors in the heart in addition to their intended sites of action elsewhere in the body.The precise mechanisms involved remain elusive however, as while the cardiotoxicity shows some dose–response relationship, it does not always develop, and consistent daily use over an extended period tends to be most strongly predictive of development of valvopathy.The drugs most classically associated with the condition are weight loss drugs such as fenfluramine and chlorphentermine, and antiparkinson drugs such as pergolide and cabergoline, which are prescribed for chronic use.The heart valve changes seen with moderate and intermittent use can result in permanent damage and life-threatening heart problems if use of the causative drug is increased or continued, however longitudinal studies of former patients suggest that the damage will heal over time to some extent at least. Anorectics Some appetite suppressant drugs such as fenfluramine (which in combination with phentermine was marketed as Pondimin and commonly referred to as fen-phen), chlorphentermine, and aminorex (along with its analogue 4-Methylaminorex which has seen sporadic use as a recreational drug) induce a similar pattern of cardiac fibrosis (and pulmonary hypertension), apparently by overstimulating 5HT2B receptors on the cardiac fibroblast cells.These drugs consequently tend to cause increased risk of heart valve damage and subsequent heart failure, which eventually led to them being withdrawn from the market. Antimigraine drugs Certain antimigraine drugs which are targeted at serotonin receptors as vasoconstrictive agents, have long been known to be associated with pulmonary hypertension and Raynauds phenomenon (both vasoconstrictive effects), as well as retroperitoneal fibrosis (a fibrotic cell/fibrocyte proliferation effect, thought to be similar to cardiac valve fibrosis).These drugs include ergotamine and methysergide and both drugs can also cause cardiac fibrosis. Antiparkinson drugs Certain antiparkinson drugs, although targeted at dopaminergic receptors, cross-react with serotoninergic 5-HT2B receptors as well, and have been reported to cause cardiac fibrosis. These drugs include pergolide and cabergoline. Antihypertensive drugs Guanfacine may be a 5-HT2B agonist, based on the results of theoretical modeling and high-throughput screening. Pergolide Pergolide was an antiparkinson medications that was in decreasing use since reported in 2003 to be associated with cardiac fibrosis. In March 2007, pergolide was withdrawn from the U.S. market due to serious valvular damage that was shown in two independent studies. Cabergoline Like pergolide, cabergoline has been linked to cardiac damage. Among similar antiparkinsonian drugs, cabergoline exhibits the same type of serotonin receptor binding as pergolide. Although lisuride, a related drug, also binds to the 5-HT2B receptor, it acts as an antagonist rather than as an agonist.In January 2007, cabergoline (Dostinex) was reported also to be associated with valvular proliferation heart damage. Recreational drugs Several serotonergic recreational drugs, including the empathogens MDA and MDMA ("ecstasy"), and some hallucinogens such as DOI and Bromo-DragonFLY, have all been shown to act as 5-HT2B agonists in vitro, but how significant this may be as a risk factor associated with their recreational use is unclear. The piperazine derivative mCPP (a major metabolite of trazodone) is a 5-HT2B agonist in animal models, but actually behaves as a 5-HT2B antagonist in humans. MDMA One study of human users of MDMA ("ecstasy") found that they did have heart valve changes suggestive of early cardiac fibrosis, which were not present in non-MDMA using controls, suggesting that MDMA use certainly has the potential to cause this kind of heart damage.On the other hand, there is as yet no statistical evidence to establish or negate significant increases in rates of cardiac valvopathies in current or former MDMA users. Absent studies on point, it may be speculated that as with other 5-HT2B agonists, development of heart valve damage may be dependent on the frequency and duration of use and the total cumulative exposure over time. If that is the case, then the heaviest users are likely to face the greatest risk of heart damage. Other serotonergic pharmacologics in question The SSRI antidepressants raise blood serotonin levels, and thus may be capable of the same risks, though it is thought that the risk is substantially lower with such drugs. The amino acid L-tryptophan also raises blood serotonin, and may present the same risk as well; though, again, the risk is considered to be low.However, the tryptophan derivative 5-HTP (5-hydroxytryptophan), used in the treatment of depression, raises blood serotonin level considerably. It has yet to be reported to be associated with valve disease or other fibrosis, but for the previous theoretical reasons, it has been suggested as a possible danger.When 5-HTP is used in medicine, it is generally administered along with carbidopa, which prevents the peripheral decarboxylation of 5-HTP to serotonin and so ensures that only brain serotonin levels are increased without producing peripheral side effects, however 5-HTP is also sold without carbidopa as a dietary supplement, and may have increased risks when taken by itself without carbidopa. In non-human great apes Cardiac fibrosis is common in non-human great apes in human care. The term idiopathic myocardial fibrosis was coined to emphasize this disease is likely different from the above described forms of cardiac fibrosis in humans. The etiology is not known, though vitamin D deficiency is a potential suspected cause at least in chimpanzees. Possible treatments The most obvious treatment for cardiac valve fibrosis or fibrosis in other locations, consists of stopping the stimulatory drug or production of serotonin. In the case of a functional neuroendocrine tumor, somatostatin analogs such as octreotide are used to reduce the production of serotonin by tumor cells, which often highly express inhibitory somatostatin receptors.Surgical tricuspid valve replacement, sometimes combined with a pulmonary valve replacement, can be necessary in some patients.A compound found in red wine, resveratrol has been found to slow the development of cardiac fibrosis. More sophisticated approaches of countering cardiac fibrosis like microRNA inhibition (miR-21, for example) are being tested in animal models. == References ==
Retroperitoneal fibrosis	Retroperitoneal fibrosis or Ormonds disease is a disease featuring the proliferation of fibrous tissue in the retroperitoneum, the compartment of the body containing the kidneys, aorta, renal tract, and various other structures. It may present with lower back pain, kidney failure, hypertension, deep vein thrombosis, and other obstructive symptoms. It is named after John Kelso Ormond, who rediscovered the condition in 1948. Causes The association of idiopathic retroperitoneal fibrosis with various immune-related conditions and response to immunosuppression led to a search for an autoimmune cause of idiopathic RPF. Many of these previously idiopathic cases can now be attributed to IgG4-related disease, an autoimmune disorder proposed in 2003. Otherwise, one-third of cases are secondary to malignancy, medication (methysergide, hydralazine, beta blockers), prior radiotherapy, or certain infections.Other associations include: connective tissue disease Riedels thyroiditis sclerosing cholangitis membranous nephropathy ankylosing spondylitis inflammatory bowel disease ANCA-associated vasculitis autoimmune pancreatitis sarcoidosis primary biliary cirrhosis inflammatory abdominal aortic aneurysm Diagnosis The diagnosis of retroperitoneal fibrosis cannot be made on the basis of the results of laboratory studies. CT is the best diagnostic modality: a confluent mass surrounding the aorta and common iliac arteries can be seen. On MRI, it has low T1 signal intensity and variable T2 signal. Malignant retroperitoneal fibrosis usually gives uneven MRI signals, is bulky, extends above the origins of renal arteries, or displaces the aorta anteriorly. Additionally, malignant retroperitoneal fibrosis less frequently displaces the ureters medially when compared to other causes of retroperitoneal fibrosis.On fludeoxyglucose (18F) (FDG) positron emission tomography (PET) scan, FDG accumulation is shown in the affected area.Although biopsy is not usually recommended, it is appropriate when malignancy or infection is suspected. Biopsy should also be done if the location of fibrosis is atypical or if there is an inadequate response to initial treatment. Treatment In the absence of severe urinary tract obstruction (which generally requires surgery with omental wrapping), treatment is generally with glucocorticoids initially, followed by DMARDs either as steroid-sparing agents or if refractory on steroids. The selective estrogen receptor modulator tamoxifen has shown to improve the condition in various small trials, although the exact mechanism of its action remains unclear. References == External links ==
Rhabdomyolysis	Rhabdomyolysis is a condition in which damaged skeletal muscle breaks down rapidly. Symptoms may include muscle pains, weakness, vomiting, and confusion. There may be tea-colored urine or an irregular heartbeat. Some of the muscle breakdown products, such as the protein myoglobin, are harmful to the kidneys and may lead to kidney failure.The muscle damage is most often the result of a crush injury, strenuous exercise, medications, or a substance use disorder. Other causes include infections, electrical injury, heat stroke, prolonged immobilization, lack of blood flow to a limb, or snake bites. Statins (prescription drugs to lower cholesterol) are considered a small risk. Some people have inherited muscle conditions that increase the risk of rhabdomyolysis. The diagnosis is supported by a urine test strip which is positive for "blood" but the urine contains no red blood cells when examined with a microscope. Blood tests show a creatine kinase activity greater than 1,000 U/L, with severe disease being above 5,000-15,000 U/L.The mainstay of treatment is large quantities of intravenous fluids. Other treatments may include dialysis or hemofiltration in more severe cases. Once urine output is established, sodium bicarbonate and mannitol are commonly used but they are poorly supported by the evidence. Outcomes are generally good if treated early. Complications may include high blood potassium, low blood calcium, disseminated intravascular coagulation, and compartment syndrome.Rhabdomyolysis occurs in about 26,000 people a year in the United States. While the condition has been commented on throughout history, the first modern description was following an earthquake in 1908. Important discoveries as to its mechanism were made during the Blitz of London in 1941. It is a significant problem for those injured in earthquakes, and relief efforts for such disasters often include medical teams equipped to treat survivors with rhabdomyolysis. Signs and symptoms The symptoms of rhabdomyolysis depend on its severity and whether kidney failure develops. Milder forms may not cause any muscle symptoms, and the diagnosis is based on abnormal blood tests in the context of other problems. More severe rhabdomyolysis is characterized by muscle pain, tenderness, weakness and swelling of the affected muscles. If the swelling is very rapid, as may happen with a crush injury after someone is released from under heavy collapsed debris, the movement of fluid from the bloodstream into damaged muscle may cause low blood pressure and shock. Other symptoms are nonspecific and result either from the consequences of muscle tissue breakdown or from the condition that originally led to the muscle breakdown. Release of the components of muscle tissue into the bloodstream causes electrolyte disturbances, which can lead to nausea, vomiting, confusion, coma or abnormal heart rate and rhythm. The urine may be dark, often described as "tea-colored", due to the presence of myoglobin. Damage to the kidneys may give rise to decreased or absent urine production, usually 12 to 24 hours after the initial muscle damage.Swelling of damaged muscle occasionally leads to compartment syndrome—compression of surrounding tissues, such as nerves and blood vessels, in the same fascial compartment—leading to the loss of blood supply and damage or loss of function in the part(s) of the body supplied by these structures. Symptoms of this complication include pain or reduced sensation in the affected limb. A second recognized complication is disseminated intravascular coagulation (DIC), a severe disruption in blood clotting that may lead to uncontrollable bleeding. Causes Any form of muscle damage of sufficient severity can cause rhabdomyolysis. Multiple causes can be present simultaneously in one person. Some have an underlying muscle condition, usually hereditary in nature, that makes them more prone to rhabdomyolysis. Genetic predisposition Recurrent rhabdomyolysis may result from intrinsic muscle enzyme deficiencies, which are usually inherited and often appear during childhood. Many structural muscle diseases feature episodes of rhabdomyolysis that are triggered by exercise, general anesthesia or any of the other causes of rhabdomyolysis listed above. Inherited muscle disorders and infections together cause the majority of rhabdomyolysis in children.The following hereditary disorders of the muscle energy supply may cause recurrent and usually exertional rhabdomyolysis: Glycolysis and glycogenolysis defects: McArdles disease, phosphofructokinase deficiency, glycogen storage diseases VIII, IX, X and XI Lipid metabolism defects: carnitine palmitoyltransferase I and II deficiency, deficiency of subtypes of acyl CoA dehydrogenase (LCAD, SCAD, MCAD, VLCAD, 3-hydroxyacyl-coenzyme A dehydrogenase deficiency), thiolase deficiency Mitochondrial myopathies: deficiency of succinate dehydrogenase, cytochrome c oxidase and coenzyme Q10 Others: glucose-6-phosphate dehydrogenase deficiency, myoadenylate deaminase deficiency and muscular dystrophies Mechanism Damage to skeletal muscle may take various forms. Crush and other physical injuries cause damage to muscle cells directly or interfere with blood supply, while non-physical causes interfere with muscle cell metabolism. When damaged, muscle tissue rapidly fills with fluid from the bloodstream, including sodium ions. The swelling itself may lead to destruction of muscle cells, but those cells that survive are subject to various disruptions that lead to rise in intracellular calcium ions; the accumulation of calcium outside the sarcoplasmic reticulum leads to continuous muscle contraction and depletion of ATP, the main carrier of energy in the cell. ATP depletion can itself lead to uncontrolled calcium influx. The persistent contraction of the muscle cell leads to breakdown of intracellular proteins and disintegration of the cell.Neutrophil granulocytes—the most abundant type of white blood cell—enter the muscle tissue, producing an inflammatory reaction and releasing reactive oxygen species, particularly after crush injury. Crush syndrome may also cause reperfusion injury when blood flow to decompressed muscle is suddenly restored.The swollen, inflamed muscle may directly compress structures in the same fascial compartment, causing compartment syndrome. The swelling may also further compromise blood supply into the area. Finally, destroyed muscle cells release potassium ions, phosphate ions, the heme-containing protein myoglobin, the enzyme creatine kinase and uric acid (a breakdown product of purines from DNA) into the blood. Activation of the coagulation system may precipitate disseminated intravascular coagulation. High potassium levels may lead to potentially fatal disruptions in heart rhythm. Phosphate binds to calcium from the circulation, leading to low calcium levels in the blood.Rhabdomyolysis may cause kidney failure by several mechanisms. The most important is the accumulation of myoglobin in the kidney tubules. Normally, the blood protein haptoglobin binds circulating myoglobin and other heme-containing substances, but in rhabdomyolysis the quantity of myoglobin exceeds the binding capacity of haptoglobin. Myoglobinuria, the presence of myoglobin in the urine, occurs when the level in plasma exceeds 0.5–1.5 mg/dL; once plasma levels reach 100 mg/dL, the concentration in the urine becomes sufficient for it to be visibly discolored and corresponds with the destruction of about 200 grams of muscle. As the kidneys reabsorb more water from the filtrate, myoglobin interacts with Tamm–Horsfall protein in the nephron to form casts (solid aggregates) that obstruct the normal flow of fluid; the condition is worsened further by high levels of uric acid and acidification of the filtrate, which increase cast formation. Iron released from the heme generates reactive oxygen species, damaging the kidney cells. In addition to the myoglobinuria, two other mechanisms contribute to kidney impairment: low blood pressure leads to constriction of the blood vessels and therefore a relative lack of blood flow to the kidney, and finally uric acid may form crystals in the tubules of the kidneys, causing obstruction. Together, these processes lead to acute tubular necrosis, the destruction of the cells of tubules. Glomerular filtration rate falls and the kidney is unable to perform its normal excretory functions. This causes disruption of electrolyte regulation, leading to a further rise in potassium levels, and interferes with vitamin D processing, further worsening the low calcium levels. Diagnosis A diagnosis of rhabdomyolysis may be suspected in anyone who has sustained trauma, crush injury or prolonged immobilization, but it may also be identified at a later stage due to deteriorating kidney function (abnormally raised or increasing creatinine and urea levels, falling urine output) or reddish-brown discoloration of the urine. General investigations The most reliable test in the diagnosis of rhabdomyolysis is the level of creatine kinase (CK) in the blood. This enzyme is released by damaged muscle, and levels above 1000 U/L (5 times the upper limit of normal (ULN)) indicate rhabdomyolysis. More than 5,000 U/L indicates severe disease but depending on the extent of the rhabdomyolysis, concentrations up to 100,000 U/l are not unusual. CK concentrations rise steadily for 12 hours after the original muscle injury, remain elevated for 1–3 days and then fall gradually. Initial and peak CK levels have a linear relationship with the risk of acute kidney failure: the higher the CK, the more likely it is that kidney damage will occur. There is no specific concentration of CK above which kidney impairment definitely occurs; concentrations below 20,000 U/L are unlikely to be associated with a risk of kidney impairment, unless there are other contributing risk factors. Mild rises without kidney impairment are referred to as "hyperCKemia". Myoglobin has a short half-life, and is therefore less useful as a diagnostic test in the later stages. Its detection in blood or urine is associated with a higher risk of kidney impairment. Despite this, use of urine myoglobin measurement is not supported by evidence as it lacks specificity and the research studying its utility is of poor quality.Elevated concentrations of the enzyme lactate dehydrogenase (LDH) may be detected. Other markers of muscle damage, such as aldolase, troponin, carbonic anhydrase type 3 and fatty acid-binding protein (FABP), are mainly used in chronic muscle diseases. The transaminases, enzymes abundant in both liver and muscle tissue, are also usually increased; this can lead to the condition being confused with acute liver injury, at least in the early stages. The incidence of actual acute liver injury is 25% in people with non-traumatic rhabdomyolysis; the mechanism for this is uncertain.High potassium levels tend to be a feature of severe rhabdomyolysis. Electrocardiography (ECG) may show whether the elevated potassium levels are affecting the conduction system of the heart, as suggested by the presence of T wave changes or broadening of the QRS complex. Low calcium levels may be present in the initial stage due to binding of free calcium to damaged muscle cells.As detectable levels of myoglobinemia and myoglobinuria occur, blood tests and urine tests may show elevated levels of myoglobin. For example, a urine test strip may reveal a positive result for "blood", even though no red blood cells can be identified on microscopy of the urine; this occurs because the reagent on the test strip reacts with myoglobin. The same phenomenon may happen in conditions that lead to hemolysis, the destruction of red blood cells; in hemolysis the blood serum is also visibly discolored, while in rhabdomyolysis it is normal. If kidney damage has occurred, microscopy of the urine also reveals urinary casts that appear pigmented and granular. Complications Compartment syndrome is a clinical diagnosis, i.e., no diagnostic test conclusively proves its presence or absence, but direct measurement of the pressure in a fascial compartment, and the difference between this pressure and the blood pressure, may be used to assess its severity. High pressures in the compartment and a small difference between compartment pressure and blood pressure indicate that the blood supply is likely to be insufficient, and that surgical intervention may be needed.Disseminated intravascular coagulation, another complication of rhabdomyolysis and other forms of critical illness, may be suspected on the basis of unexpected bleeding or abnormalities in hematological tests, such as a decreasing platelet count or prolongation of the prothrombin time. The diagnosis can be confirmed with standard blood tests for DIC, such as D-dimer. Underlying disorders If an underlying muscle disease is suspected, for instance, if there is no obvious explanation or there have been multiple episodes, it may be necessary to perform further investigations. During an attack, low levels of carnitine in the blood and high levels of acylcarnitine in blood and urine may indicate a lipid metabolism defect, but these abnormalities revert to normal during convalescence. Other tests may be used at that stage to demonstrate these disorders. Disorders of glycolysis can be detected by various means, including the measurement of lactate after exercise; a failure of the lactate to rise may be indicative of a disorder in glycolysis, while an exaggerated response is typical of mitochondrial diseases. Electromyography (EMG) may show particular patterns in specific muscle diseases; for instance, McArdles disease and phosphofructokinase deficiency show a phenomenon called cramp-like contracture. There are genetic tests available for many of the hereditary muscle conditions that predispose to myoglobinuria and rhabdomyolysis.Muscle biopsy can be useful if an episode of rhabdomyolysis is thought to be the result of an underlying muscle disorder. A biopsy sample taken during an episode is often uninformative, as it will show only evidence of cell death or may appear normal. Taking the sample is therefore delayed for several weeks or months. The histopathological appearance on the biopsy indicates the nature of the underlying disorder. For instance, mitochondrial diseases are characterized by ragged red fibers. Biopsy sites may be identified by medical imaging, such as magnetic resonance imaging, as the muscles may not be uniformly affected. Treatment The main goal of treatment is to treat shock and preserve kidney function. Initially this is done through the administration of generous amounts of intravenous fluids, usually isotonic saline (0.9% weight per volume sodium chloride solution). In victims of crush syndrome, it is recommended to administer intravenous fluids even before they are extracted from collapsed structures. This will ensure sufficient circulating volume to deal with the muscle cell swelling (which typically commences when blood supply is restored), and to prevent the deposition of myoglobin in the kidneys. Amounts of 6 to 12 liters over 24 hours are recommended. The rate of fluid administration may be altered to achieve a high urine output (200–300 mL/h in adults), unless there are other reasons why this might lead to complications, such as a history of heart failure.While many sources recommend additional intravenous agents to reduce damage to the kidney, most of the evidence supporting this practice comes from animal studies, and is inconsistent and conflicting. Mannitol acts by osmosis to enhance urine production and is thought to prevent myoglobin deposition in the kidney, but its efficacy has not been shown in studies and there is a risk of worsening kidney function. The addition of bicarbonate to the intravenous fluids may alleviate acidosis (high acid level of the blood) and make the urine more alkaline to prevent cast formation in the kidneys; evidence suggesting that bicarbonate has benefits above saline alone is limited, and it can worsen hypocalcemia by enhancing calcium and phosphate deposition in the tissues. If urine alkalinization is used, the pH of the urine is kept at 6.5 or above. Furosemide, a loop diuretic, is often used to ensure sufficient urine production, but evidence that this prevents kidney failure is lacking. Electrolytes In the initial stages, electrolyte levels are often abnormal and require correction. High potassium levels can be life-threatening, and respond to increased urine production and renal replacement therapy (see below). Temporary measures include the administration of calcium to protect against cardiac complications, insulin or salbutamol to redistribute potassium into cells, and infusions of bicarbonate solution.Calcium levels initially tend to be low, but as the situation improves calcium is released from where it has precipitated with phosphate, and vitamin D production resumes, leading to hypercalcemia (abnormally high calcium levels). This "overshoot" occurs in 20–30% of those people who have developed kidney failure. Acute kidney impairment Kidney dysfunction typically develops 1–2 days after the initial muscle damage. If supportive treatment is inadequate to manage this, renal replacement therapy (RRT) may be required. RRT removes excess potassium, acid and phosphate that accumulate when the kidneys are unable to function normally and is required until kidney function is regained.Three main modalities of RRT are available: hemodialysis, continuous hemofiltration and peritoneal dialysis. The former two require access to the bloodstream (a dialysis catheter) and peritoneal dialysis is achieved by instilling fluid into the abdominal cavity and later draining it. Hemodialysis, which is normally done several times a week in chronic kidney disease, is often required on a daily basis in rhabdomyolysis. Its advantage over continuous hemofiltration is that one machine can be used multiple times a day, and that continuous administration of anticoagulant drugs is not necessary. Hemofiltration is more effective at removing large molecules from the bloodstream, such as myoglobin, but this does not seem to confer any particular benefit. Peritoneal dialysis may be difficult to administer in someone with severe abdominal injury, and it may be less effective than the other modalities. Other complications Compartment syndrome is treated with surgery to relieve the pressure inside the muscle compartment and reduce the risk of compression on blood vessels and nerves in that area. Fasciotomy is the incision of the affected compartment. Often, multiple incisions are made and left open until the swelling has reduced. At that point, the incisions are closed, often requiring debridement (removal of non-viable tissue) and skin grafting in the process. The need for fasciotomy may be decreased if mannitol is used, as it can relieve muscle swelling directly.Disseminated intravascular coagulation generally resolves when the underlying causes are treated, but supportive measures are often required. For instance, if the platelet count drops significantly and there is resultant bleeding, platelets may be administered. Prognosis The prognosis depends on the underlying cause and whether any complications occur. Rhabdomyolysis complicated by acute kidney impairment in patients with traumatic injury may have a mortality rate of 20%. Admission to the intensive care unit is associated with a mortality of 22% in the absence of acute kidney injury, and 59% if kidney impairment occurs. Most people who have sustained kidney impairment due to rhabdomyolysis fully recover their kidney function. Epidemiology The exact number of cases of rhabdomyolysis is difficult to establish because different definitions have been used. In 1995, hospitals in the U.S. reported 26,000 cases of rhabdomyolysis. Up to 85% of people with major traumatic injuries will experience some degree of rhabdomyolysis. Of those with rhabdomyolysis, 10–50% develop acute kidney injury. The risk is higher in people with a history of illicit drug use, alcohol misuse or trauma when compared to muscle diseases, and it is particularly high if multiple contributing factors occur together. Rhabdomyolysis accounts for 7–10% of all cases of acute kidney injury in the U.S.Crush injuries are common in major disasters, especially in earthquakes. The aftermath of the 1988 Spitak earthquake prompted the establishment, in 1995, of the Renal Disaster Relief Task Force, a working group of the International Society of Nephrology (a worldwide body of kidney experts). Its volunteer doctors and nurses assisted for the first time in the 1999 İzmit earthquake in Turkey, where 17,480 people died, 5392 were hospitalized and 477 received dialysis, with positive results. Treatment units are generally established outside the immediate disaster area, as aftershocks could potentially injure or kill staff and make equipment unusable.Acute exertional rhabdomyolysis happens in 2% to 40% of people going through basic training for the United States military. In 2012, the United States military reported 402 cases. Another group at increased risk is firefighters. History The Bible may contain an early account of rhabdomyolysis. In Numbers 11:4–6,31–33, the Pentateuch says that the Jews demanded meat while traveling in the desert; God sent quail in response to the complaints, and people ate large quantities of quail meat. A plague then broke out, killing numerous people. Rhabdomyolysis after consuming quail was described in more recent times and called coturnism (after Coturnix, the main quail genus). Migrating quail consume large amounts of hemlock, a known cause of rhabdomyolysis.In modern times, early reports from the 1908 Messina earthquake and World War I on kidney failure after injury were followed by studies by London physicians Eric Bywaters and Desmond Beall, working at the Royal Postgraduate Medical School and the National Institute for Medical Research, on four victims of The Blitz in 1941. Myoglobin was demonstrated in the urine of victims by spectroscopy, and it was noted that the kidneys of victims resembled those of patients who had hemoglobinuria (hemoglobin rather than myoglobin being the cause of the kidney damage). In 1944 Bywaters demonstrated experimentally that the kidney failure was mainly caused by myoglobin. Already during the war, teams of doctors traveled to bombed areas to provide medical support, chiefly with intravenous fluids, as dialysis was not yet available. The prognosis of acute kidney failure improved markedly when dialysis was added to supportive treatment, which first happened during the 1950–1953 Korean War. Etymology and pronunciation The word rhabdomyolysis ( ) uses the combining forms rhabdo- + myo- + -lysis, yielding "striated muscle breakdown". Other animals Rhabdomyolysis is recognized in horses. Horses can develop a number of muscle disorders, many of which may progress to rhabdomyolysis. Of these, some cause isolated attacks of rhabdomyolysis (e.g., dietary deficiency in vitamin E and selenium, poisoning associated with pasture or agricultural poisons such as organophosphates), while others predispose to exertional rhabdomyolysis (e.g., the hereditary condition equine polysaccharide storage myopathy). 5–10% of thoroughbred horses and some standardbred horses have the condition equine exertional rhabdomyolysis; no specific cause has been identified, but an underlying muscle calcium regulation disorder is suspected.Rhabdomyolysis affecting horses may also occur in outbreaks; these have been reported in many European countries, and later in Canada, Australia, and the United States. It has been referred to as "atypical myopathy" or "myoglobinuria of unknown etiology". No single cause has yet been found, but various mechanisms have been proposed, and a seasonal pattern has been observed. Very high creatine kinase levels are detected, and mortality from this condition is 89%. == References ==
Photodermatitis	Photodermatitis, sometimes referred to as sun poisoning or photoallergy, is a form of allergic contact dermatitis in which the allergen must be activated by light to sensitize the allergic response, and to cause a rash or other systemic effects on subsequent exposure. The second and subsequent exposures produce photoallergic skin conditions which are often eczematous. It is distinct from sunburn. Signs and symptoms Photodermatitis may result in swelling, difficulty breathing, a burning sensation, a red itchy rash sometimes resembling small blisters, and peeling of the skin. Nausea may also occur. There may also be blotches where the itching may persist for long periods of time. In these areas an unsightly orange to brown tint may form, usually near or on the face. Causes Many medications and conditions can cause sun sensitivity, including: Sulfa used in some drugs, among them some antibiotics, diuretics, COX-2 inhibitors, and diabetes drugs. Psoralens, coal tars, photo-active dyes (eosin, acridine orange) Musk ambrette, methylcoumarin, lemon oil (may be present in fragrances) PABA (found in sunscreens) Oxybenzone (UVA and UVB chemical blocker also in sunscreens) Salicylanilide (found in industrial cleaners) St Johns Wort Hexachlorophene (found in some prescription antibacterial soaps) Tetracycline antibiotics (e.g., tetracycline, doxycycline, minocycline) Benzoyl peroxide Retinoids (e.g., isotretinoin) Some NSAIDs (e.g., ibuprofen, naproxen sodium) Fluoroquinolone antibiotic: Sparfloxacin in 2% of cases Amiodarone, used to treat atrial fibrillation PellagraPhotodermatitis can also be caused by plants such as Ammi majus, parsnip, giant hogweed (Heracleum mantegazzianum), common rue (Ruta graveolens), and Dictamnus, a genus of flowering plants in the family Rutaceae with a single species Dictamnus albus, commonly called the burning bush. Photodermatitis caused by plants is called phytophotodermatitis. Prevention Prevention includes avoiding exposure to chemicals that can trigger the reaction, such as by wearing gloves, or avoiding sunlight or wearing sunscreen preferably with at least factor 30 and with a high UVA protection level on the affected area. See also Phytophotodermatitis Photosensitivity Solar urticaria References == External links ==
Multiple birth	A multiple birth is the culmination of one multiple pregnancy, wherein the mother gives birth to two or more babies. A term most applicable to vertebrate species, multiple births occur in most kinds of mammals, with varying frequencies. Such births are often named according to the number of offspring, as in twins and triplets. In non-humans, the whole group may also be referred to as a litter, and multiple births may be more common than single births. Multiple births in humans are the exception and can be exceptionally rare in the largest mammals. A multiple pregnancy may be the result of the fertilization of a single egg that then splits to create identical fetuses, or it may be the result of the fertilization of multiple eggs that create fraternal ("non-identical") fetuses, or it may be a combination of these factors. A multiple pregnancy from a single zygote is called monozygotic, from two zygotes is called dizygotic, or from three or more zygotes is called polyzygotic. Similarly, the siblings themselves from a multiple birth may be referred to as monozygotic if they are identical or as dizygotic (in cases of twins) or polyzygotic (for three or more siblings) if they are fraternal, i.e., non-identical. Each fertilized ovum (zygote) may produce a single embryo, or it may split into two or more embryos, each carrying the same genetic material. Fetuses resulting from different zygotes are called fraternal and share only 50% of their genetic material, as ordinary full siblings from separate births do. Fetuses resulting from the same zygote share 100% of their genetic material and hence are called identical. Identical twins are always the same sex. Terminology Terms used for the number of offspring in a multiple birth, where a number higher than three ends with the suffix -uplet: two offspring – twins three offspring – triplets four offspring – quadruplets five offspring – quintuplets six offspring – sextuplets seven offspring – septuplets eight offspring – octuplets nine offspring – nonuplets ten offspring – decupletsTerms used for multiple births or the genetic relationships of their offspring are based on the zygosity of the pregnancy: Monozygotic – multiple (typically two) fetuses produced by the splitting of a single zygote Polyzygotic – multiple fetuses produced by two or more zygotes: Dizygotic – multiple (typically two) fetuses produced by two zygotes Trizygotic – three or more fetuses produced by three zygotes Sesquizygotic – an egg which is fertilized by 2 sperms, which produce 2 fetusesMultiple pregnancies are also classified by how the fetuses are surrounded by one or more placentas (chorionicity) and amniotic sacs (amnionicity). Human multiple births In humans, the average length of pregnancy (two weeks fewer than gestation) is 38 weeks with a single fetus. This average decreases for each additional fetus: to thirty-six weeks for twin births, thirty-two weeks for triplets, and thirty weeks for quadruplets. With the decreasing gestation time, the risks from immaturity at birth and subsequent viability increase with the size of the sibling group. Only as of the twentieth century have more than four all survived infancy. Recent history has also seen increasing numbers of multiple births. In the United States, it has been estimated that by 2011, 36% of twin births and 78% of triplet and higher-order births resulted from conception by assisted reproductive technology. Twins Twins are by far the most common form of multiple births in humans. The U.S. Centers for Disease Control and Prevention report more than 132,000 sets of twins out of 3.9 million births of all kinds each year, about 3.4%, or 1 in 30. Without fertility treatments, the probability is about 1 in 60; with fertility treatments, it can be as high as 20-25%.Dizygotic (fraternal) twins run in families; however, the male does not influence the chances of his partner having twins, even if there are twins in his family. The hyperovulation gene is the cause for having twins and is only a factor for the mother. Although the male does not influence his partners chances of having twins, he could influence his childrens chances for having twins. If a male carries the gene for hyperovulation and has a daughter, she may also have the gene for hyperovulation and then have twins herself. Monozygotic (identical) twins do not run in families. The twinning is random, due to the egg splitting, so all parents have an equal chance of conceiving identical twins. Triplets Triplets can be either fraternal, identical, or a combination of both. The most common are strictly fraternal triplets, which come from a polyzygotic pregnancy of three eggs. Less common are triplets from a dizygotic pregnancy, where one zygote divides into two identical fetuses, and the other does not. Least common are identical triplets, three fetuses from one egg. In this case, the original zygote divides into two and then one of those two zygotes divides again but the other does not. Triplets are far less common than twins, according to the U.S. Centers for Disease Control and Prevention, accounting for only about 4300 sets in 3.9 million births, just a little more than 0.1%, or 1 in 1000. According to the American Society of Reproductive Medicine, only about 10% of these are identical triplets: about 1 in ten thousand. Nevertheless, only 4 sets of identical triplets were reported in the U.S. during 2015, about one in a million. According to Victor Khouzami, Chairman of Obstetrics at Greater Baltimore Medical Center, "No one really knows the incidence".Identical triplets or quadruplets are very rare and result when the original fertilized egg splits and then one of the resultant cells splits again (for triplets) or, even more rarely, a further split occurs (for quadruplets). The odds of having identical triplets is unclear. News articles and other non-scientific organizations give odds from one in 60,000 to one in 200 million pregnancies. Quadruplets Quadruplets are much rarer than twins or triplets. As of 2007, there were approximately 3,556 sets recorded worldwide. Quadruplet births are becoming increasingly common due to fertility treatments. There are around 70 sets of all-identical quadruplets worldwide. Many sets of quadruplets contain a mixture of identical and fraternal siblings, such as three identical and one fraternal, two identical and two fraternal, or two pairs of identicals. One famous set of identical quadruplets was the Genain quadruplets, all of whom developed schizophrenia. Quadruplets are sometimes referred to as "quads" in Britain. Quintuplets Quintuplets occur naturally in 1 in 55,000,000 births. The first quintuplets known to survive infancy were the identical female Canadian Dionne Quintuplets, born in 1934. Quintuplets are sometimes referred to as "quins" in the UK and "quints" in North America. A famous set of all-girl quintuplets are the Busby quints from the TV series OutDaughtered. Sextuplets Born in Liverpool, England, on 18 November 1983, the Walton sextuplets were the worlds first all-female surviving sextuplets, and the worlds fourth known set of surviving sextuplets. Another well-known set of sextuplets is the Gosselin sextuplets, born on May 10, 2004, in Hershey, Pennsylvania. Reality television shows Jon & Kate Plus 8 and later Kate Plus 8 have chronicled the lives of these sextuplets. Other shows of this nature include Table for 12 and Sweet Home Sextuplets. Very high-order multiple births In 1997, the McCaughey septuplets, born in Des Moines, Iowa, became the first septuplets known to survive infancy. Multiple births of as many as eight babies have been born alive, the first surviving set on record goes to the Suleman octuplets, born in 2009 in Bellflower, California. As of 2019, all of them were alive and turned 10 years old. In May 2021, the Cissé nonuplets were born in Morocco to Halima Cissé, a 25-year-old woman from Mali. As of May 2022, one year since their births, all nine are still living and reportedly in good health. The list of multiple births covers notable examples. Causes and frequency The frequency of N multiple births from natural pregnancies has been given as approximately 1:89N−1 (Hellins law) and as about 1:80N−1. This gives: 1:89 (= 1.1%) or 1:80 (= 1.25%) for twins 1:892 (= 1:7921, about 0.013%) or 1:802 (= 1:6400) for triplets 1:893 (= approx. 0.000142%, less than 1:700,000) or 1:803 for quadrupletsNorth American dizygotic twinning occurs about once in 83 conceptions, and triplets about once in 8000 conceptions. US figures for 2010 were: Twins, 132,562, 3.31% Triplets, 5,503, 0.14% Quadruplets, 313, 0.0078% Quintuplets and more, 37, 0.00092%Human multiple births can occur either naturally (the woman ovulates multiple eggs or the fertilized egg splits into two) or as the result of infertility treatments such as in vitro fertilization (several embryos are often transferred to compensate for lower quality) or fertility drugs (which can cause multiple eggs to mature in one ovulatory cycle). For reasons that are not yet known, the older a woman is, the more likely she is to have a multiple birth naturally. It is theorized that this is due to the higher level of follicle-stimulating hormone that older women sometimes have as their ovaries respond more slowly to FSH stimulation.The number of multiple births has increased over the last decade. For example, in Canada between 1979 and 1999, the number of multiple birth babies increased 35%. Before the advent of ovulation-stimulating drugs, triplets were quite rare (approximately 1 in 8000 births) and higher-order births much rarer still. Much of the increase can probably be attributed to the impact of fertility treatments, such as in-vitro fertilization. Younger patients who undergo treatment with fertility medication containing artificial FSH, followed by intrauterine insemination, are particularly at risk for multiple births of higher order. Certain factors appear to increase the likelihood that a woman will naturally conceive multiples. These include: mothers age: women over 35 are more likely to have multiples than younger women mothers use of fertility drugs: approximately 35% of pregnancies arising through the use of fertility treatments such as IVF involve more than one childThe increasing use of fertility drugs and consequent increased rate of multiple births has made the phenomenon of multiples more frequent and hence more visible. In 2004 the birth of sextuplets, six children, to Pennsylvania couple Kate and Jon Gosselin helped them to launch their television series, originally Jon & Kate Plus 8 and (following their divorce) Kate Plus 8, which became the highest-rated show on the TLC network. Risks Premature birth and low birth weight Babies born from multiple-birth pregnancies are much more likely to result in premature birth than those from single pregnancies. 51% of twins and 91% of triplets are born preterm, compared to 9.4% in singletons. 14% of twins and 41% of triplets are even born very preterm, compared to 1.7% in singletons.Drugs known as betamimetics can be used to relax the muscles of the uterus and delay birth in singleton pregnancies. There is some evidence that these drugs can also reduce the risk of preterm birth for twin pregnancies, but existing studies are small. More data is required before solid conclusions can be drawn. Likewise, existing studies are too small to determine if a cervical suture is effective for reducing prematurity in cases of multiple birth.As a result of preterm birth, multiples tend to have lower birth weight than singletons. Exceptions are possible, however, as with the Kupresak triplets, born in 2008 in Mississauga, Ontario, Canada. Their combined weight was 17 lbs, 2.7 oz, which set a world record. Two of the triplets were similar in size and, as expected, moderately low birth weight. The two combined weighed 9 lbs, 2.7 oz. The third triplet, however, was much larger and weighed 8 lbs. individually. Cerebral palsy Cerebral palsy is more common among multiple births than single births, being 2.3 per 1,000 survivors in singletons, 13 in twins, and 45 in triplets in North West England. This is likely a side effect of premature birth and low birth weight. Incomplete separation Multiples may be monochorionic, sharing the same chorion, with resultant risk of twin-to-twin transfusion syndrome. Monochorionic multiples may even be monoamniotic, sharing the same amniotic sac, resulting in risk of umbilical cord compression and nuchal cord. In very rare cases, there may be conjoined twins, possibly impairing function of internal organs. Mortality rate (stillbirth) Multiples are also known to have a higher mortality rate. It is more common for multiple births to be stillborn, while for singletons the risk is not as high. A literary review on multiple pregnancies shows a study done on one set each of septuplets and octuplets, two sets of sextuplets, 8 sets of quintuplets, 17 sets of quadruplets, and 228 sets of triplets. By doing this study, Hammond found that the mean gestational age (how many weeks when birthed) at birth was 33.4 weeks for triplets and 31 weeks for quadruplets. This shows that stillbirth happens usually 3–5 weeks before the woman reaches full term and also that for sextuplets or higher it almost always ends in death of the fetuses. Though multiples are at a greater risk of being stillborn, there is inconclusive evidence whether the actual mortality rate is higher in multiples than in singletons. Prevention in IVF Today many multiple pregnancies are the result of in vitro fertilisation (IVF). In a 1997 study of 2,173 embryo transfers performed as part of in vitro fertilisation (IVF), 34% were successfully delivered pregnancies. The overall multiple pregnancy rate was 31.3% (24.7% twins, 5.8% triplets, and .08% quadruplets). Because IVFs are producing more multiples, a number of efforts are being made to reduce the risk of multiple births- specifically triplets or more. Medical practitioners are doing this by limiting the number of embryos per embryo transfer to one or two. That way, the risks for the mother and fetuses are decreased. The appropriate number of embryos to be transferred depends on the age of the woman, whether it is the first, second or third full IVF cycle attempt and whether there are top-quality embryos available. According to a guideline from The National Institute for Health and Care Excellence (NICE) in 2013, the number of embryos transferred in a cycle should be chosen as in following table: Also, it is recommended to use single embryo transfer in all situations if a top-quality blastocyst is available. Management Bed rest has not been found to change outcomes and therefore is not generally recommended outside of a research study. Selective reduction (procedure) Selective reduction is the practice of reducing the number of fetuses in a multiple pregnancy; it is also called "multifetal reduction".The procedure generally takes two days; the first day for testing in order to select which fetuses to remove, and the second day for the procedure itself, in which potassium chloride is injected into the heart of each selected fetus under the guidance of ultrasound imaging. Risks of the procedure include bleeding requiring transfusion, rupture of the uterus, retained placenta, infection, a miscarriage, and prelabor rupture of membranes. Each of these appears to be rare. There are also ethical concerns about this procedure, since it is a form of abortion, and also because of concerns over which fetuses are terminated and why.Selective reduction was developed in the mid-1980s, as people in the field of assisted reproductive technology became aware of the risks that multiple pregnancies carried for the mother and for the fetuses. Care in pregnancy Women with a multiple pregnancy are usually seen more regularly by midwives or doctors than those with singleton pregnancies because of the higher risks of complications. However, there is currently no evidence to suggest that specialised antenatal services produce better outcomes for mother or babies than ‘normal’ antenatal care. Nutrition As preterm birth is such a risk for women with multiple pregnancies, it has been suggested that these women should be encouraged to follow a high-calorie diet to increase the birth weights of the babies. Evidence around this subject is not yet good enough to advise women to do this because the long term effects of the high-calorie diets on the mother are not known. Cesarean section or vaginal delivery A study in 2013 involving 106 participating centers in 25 countries came to the conclusion that, in a twin pregnancy of a gestational age between 32 weeks 0 days and 38 weeks 6 days, and the first twin is in cephalic presentation, planned Cesarean section does not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal disability, as compared with planned vaginal delivery. In this study, 44% of the women planned for vaginal delivery still ended up having Cesarean section for unplanned reasons such as pregnancy complications. In comparison, it has been estimated that 75% of twin pregnancies in the United States were delivered by Cesarean section in 2008. Also in comparison, the rate of Cesarean section for all pregnancies in the general population varies between 40% and 14%.Fetal position (the way the babies are lying in the womb) usually determines if they are delivered by caesarean section or vaginally. A review of good quality research on this subject found that if the twin that will be born first (i.e. is lowest in the womb) is head down there is no good evidence that caesarean section will be safer than a vaginal birth for the mother or babies.Monoamniotic twins (twins that form after the splitting of a fertilised egg and share the same amniotic fluid sac) are at more risk of complications than twins that have their own sacs. There is also insufficient evidence around whether to deliver the babies early by caesarean section or to wait for labour to start naturally while running checks on the babies’ wellbeing. The birth of this type of twins should therefore be decided with the mother and her family and should take into account the need for good neonatal care services.Cesarean delivery is needed when first twin is in non cephalic presentation or when it is a monoamniotic twin pregnancy. Neonatal intensive care Multiple-birth infants are usually admitted to neonatal intensive care immediately after being born. The records for all the triplet pregnancies managed and delivered from 1992 to 1996 were looked over to see what the neonatal statistics were. Kaufman found from reviewing these files that during a five-year period, 55 triplet pregnancies, which is 165 babies, were delivered. Of the 165 babies 149 were admitted to neonatal intensive care after the delivery. Society and culture Insurance coverage United States A study by the U.S. Agency for Healthcare Research and Quality found that, in 2011, pregnant women covered by private insurance in the United States were older and more likely to have multiple gestation than women covered by Medicaid. Cultural aspects Certain cultures consider multiple births a portent of either good or evil.Mayan culture saw twins as a blessing, and was fascinated by the idea of two bodies looking alike. The Mayans used to believe that twins were one soul that had fragmented.In Ancient Rome, the legend of the twin brothers who founded the city (Romulus and Remus) made the birth of twin boys a blessing, while twin girls were seen as an unlucky burden, since both would have to be provided with an expensive dowry at about the same time. In Greek mythology, fraternal twins Castor and Polydeuces, and Heracles and Iphicles, are sons of two different fathers. One of the twins (Polydeuces, Heracles) is the illegitimate son of the god Zeus; his brother is the son of their mothers mortal husband. A similar pair of twin sisters are Helen (of Troy) and Clytemnestra (who are also sisters of Castor and Polydeuces). The theme occurs in other mythologies as well, and is called superfecundation. In certain medieval European chivalric romances, such as Marie de Frances Le Fresne, a woman cites a multiple birth (often to a lower-class woman) as proof of adultery on her part; while this may reflect a widespread belief, it is invariably treated as malicious slander, to be justly punished by the accuser having a multiple birth of her own, and the events of the romance are triggered by her attempt to hide one or more of the children. A similar effect occurs in the Knight of the Swan romance, in the Beatrix variants of the Swan-Children; her taunt is punished by giving birth to seven children at once, and her wicked mother-in-law returns her taunt before exposing the children. Ethics of multiple births Medically assisted procreation In vitro fertilization: In vitro fertilization (IVF) was first successfully completed in the 1970s as a form of assisted reproductive technology. Out of all the assisted reproductive technology available that is currently in practice, in vitro fertilization has the highest chance of producing multiple offspring. Per each female egg, IVF currently has a 60-70% chance of conceiving. Fertilization is made possible by administering a fertility drug to the eggs or by directly injecting semen into the eggs. There is an increased chance for women over the age of 35 to have multiple births. IVF is a common genetic and ethical topic. Through IVF individuals can produce offspring successfully when natural procreation is not viable. However, in vitro can become genetically specific and allow for the selection of particular genes or expressible traits to be dominantly present in the formed embryo. Ethical dilemmas arise when determining health care coverage and the deviation from natural selection and gene variations. In regards to multiple births different ethical concerns arise from the use of in vitro fertilization. Overall, multiple pregnancies can cause potential harm to the mother and children due to potential complications. Such complications can include uterine bleeding and children not receiving equal nutrients. IVF has also revealed some pre term deliveries and lower birth weights in babies. While some view medically assisted procreation as a saving grace to have children, others consider these procedure to be unnatural and costly to the community. Multifetal pregnancy reduction Multifetal pregnancy reduction is the reduction of one or more embryos from the bearing woman. Selective reduction usually occurs for pregnancies assisted by assisted reproductive technology (ART). The first multifetal pregnancy reductions to occur in a clinical setting took place in the 1980s. The procedure aims to reduce pregnancies down to approximately one to two fetuses. The overarching purpose of the procedure is not primarily to simply terminate life, but to increase the survival and success of the mother and babies. However, multifetal pregnancy reduction raises some ethical questions. The main argument is similar to abortion ethics (Abortion debate) in reduction of fetus versus fetus life. The protection of maternal well being versus harm of newly formed fetal life is an extension of the aforementioned ethical question. It can be viewed that all life is important and that no life should be terminated without consent from the life that is being terminated. A polar opposite viewpoint advocates for the right of choice, that being the choice to terminate a pregnancy due to desire or pregnancy risks. Overall, most multifetal pregnancy reductions that occur as a result of ART are being done for the protection of the child-bearers health and to maximize the health of the remaining fetuses. See also Biological reproduction Conjoined twins Feodor Vassilyev "Grávida de Taubaté" (pt), a Brazilian woman who pretended to be pregnant with quadruplets in 2012 and gained national media attention before her pregnancy was revealed to be a hoax Half a Dozen Babies, a 1999 drama film about the 1993-born Dilley sextuplets List of multiple births List of twins Only child Quints, a Disney Channel movie about a teenage girl becoming the older sister to quintuplets Superfecundation (multiple pregnancy resulting from separate acts of sexual intercourse) Three Identical Strangers Twin References External links Facts About Multiples HFEA consultation on multiple births after IVF D. L. Ashliman, Multiple Births in Legend and Folklore Twins and Multiple Births Association
Hypervitaminosis	Hypervitaminosis is a condition of abnormally high storage levels of vitamins, which can lead to various symptoms as over excitement, irritability, or even toxicity. Specific medical names of the different conditions are derived from the given vitamin involved: an excess of vitamin A, for example, is called hypervitaminosis A. Hypervitaminoses are primarily caused by fat-soluble vitamins (D and A), as these are stored by the body for longer than the water-soluble vitamins.Generally, toxic levels of vitamins stem from high supplement intake and not always from natural sources but rather the mix of natural, derived vitamins and enhancers (vitamin boosters). Toxicities of fat-soluble vitamins can also be caused by a large intake of highly fortified foods, but natural food in modest levels rarely deliver extreme or dangerous levels of fat-soluble vitamins. The Dietary Reference Intake recommendations from the United States Department of Agriculture define a "tolerable upper intake level" for most vitamins. For those who are entirely healthy and do not experience long periods of avitaminosis, vitamin overdose can be avoided by not taking more than the normal or recommended amount of multi-vitamin supplement shown on the bottle and not ingesting multiple vitamin-containing supplements concurrently. Signs and symptoms A few described symptoms: Causes With few exceptions, like some vitamins from B-complex, hypervitaminosis usually occurs with the fat-soluble vitamins A and D, which are stored, respectively, in the liver and fatty tissues of the body. These vitamins build up and remain for a longer time in the body than water-soluble vitamins. Conditions include: Hypervitaminosis A Hypervitaminosis D Vitamin B3 § Toxicity Megavitamin-B6 syndrome Prevention Prevention in healthy individuals not having any periods of avitaminosis or vitamin (vegetables) lack for 2 years at least is by not taking more than the expected normal or recommended amount of vitamin supplements. Epidemiology In the United States, overdose exposure to all formulations of "vitamins" (which includes multi-vitamin/mineral products) was reported by 62,562 individuals in 2004 with nearly 80% of these exposures in children under the age of 6, leading to 53 "major" life-threatening outcomes and 3 deaths (2 from vitamins D and E; 1 from a multivitamin with iron). This may be compared to the 19,250 people who died of unintentional poisoning of all kinds in the U.S. in the same year (2004). In 2016, overdose exposure to all formulations of vitamins and multi-vitamin/mineral formulations was reported by 63,931 individuals to the American Association of Poison Control Centers with 72% of these exposures in children under the age of five. No deaths were reported. See also Avitaminosis Megavitamin therapy Vitamin C megadosage References External links Dietary reference intakes, official website.
Hemangioma	A hemangioma or haemangioma is a usually benign vascular tumor derived from blood vessel cell types. The most common form, seen in infants, is an infantile hemangioma, known colloquially as a "strawberry mark", most commonly presenting on the skin at birth or in the first weeks of life. A hemangioma can occur anywhere on the body, but most commonly appears on the face, scalp, chest or back. They tend to grow for up to a year before gradually shrinking as the child gets older. A hemangioma may need to be treated if it interferes with vision or breathing or is likely to cause long-term disfigurement. In rare cases internal hemangiomas can cause or contribute to other medical problems. The first line treatment option is beta blockers, which are highly effective in the majority of cases. Types Hemangiomas are benign (noncancerous) vascular tumors, and many different types occur. The correct terminology for these hemangioma types is constantly being updated by the International Society for the Study of Vascular Anomalies (ISSVA). The most common are infantile hemangiomas, and congenital hemangiomas. Infantile hemangiomas Infantile hemangiomas are the most common benign tumor found in children. They are made up of blood vessels, often called strawberry marks, and are more common in girls than in boys. They usually appear on the skin of infants in the days or weeks after birth. They tend to grow quickly for up to a year. Most then shrink or involute without further problem, however some can ulcerate and form scabs which can be painful. Depending on their location and size, they may also be disfiguring. Rarely, they may be related to disorders of the central nervous system or spine. They may also occur in the internal organs of the body, such as the liver, airway or brain.The color of the hemangioma depends on how deep it is in the skin: superficial (near the skins surface) hemangiomas tend to be bright red; deep (furthest from the skins surface) hemangiomas are often blue or purple; mixed hemangiomas may have colors of both superficial and deep. Congenital hemangiomas Congenital hemangiomas are present on the skin at birth, unlike infantile hemangiomas, which appear later. They are fully formed at birth, meaning that they do not grow after a child is born, as infantile hemangiomas do. They are less common than infantile hemangiomas. Congenital hemangiomas can be coloured from pink to blue. Congenital hemangiomas are classified according to whether they shrink and go away, or do not shrink, and do not go away, or partially shrink. Those that shrink are known as rapidly involuting congenital hemangiomas (RICH) and go away quickly. Those that do not shrink, and remain are known as noninvoluting congenital hemangiomas (NICH). Others that partially shrink are known as partially involuting congenital hemangiomas (PICH). Other types Other types of hemangioma include cavernous hemangiomas such as cavernous hemangioma of the liver. Cavernous liver hemangioma A cavernous liver hemangioma or hepatic hemangioma is a benign tumour of the liver composed of hepatic endothelial cells. It is the most common liver tumour, and is usually asymptomatic and diagnosed incidentally on radiological imaging. Liver hemangiomas are thought to be congenital in origin. Several subtypes exist, including the giant hepatic hemangioma, which can cause significant complications. Drug-induced hemangioma Drug-induced hemangiomas are reported side-effects for some drugs in nonclinical toxicology animal models, studying carcinogenesis. For example, hemangiomas of the mesenteric lymph node were increased significantly at 700 mg/kg/day of Empagliflozin in male rats, or approximately 42 times the exposure from a 25 mg clinical dose. It is inferred from nonclinical animal studies that some drugs can also produce hemangiomas in humans, and careful dosing during therapeutic drug design can ensure their safe use. Diagnosis Diagnosis is usually clinical. Paediatric Dermatologists are experts in diagnosing and treating hemangiomas. Depending on the location of the hemangioma, tests such as MRIs or ultrasounds can be done to see how far the hemangioma goes under the skin and whether it affects any internal organs. Treatment Hemangiomas usually fade gradually over time, and many do not require treatment. However, hemangiomas that may be disfiguring or that are located at sites that can cause impairment (eyelids, airway) require early treatment intervention, typically with beta blockers. Management options may include: Oral beta blockers such as propranolol or atenolol have been used since 2008 and are the first-line treatment of hemangiomas. Beta blockers have repeatedly been shown to be effective and safe in treating hemangiomas that cause complications. Beta blockers work via multiple mechanisms including narrowing the hemangiomas blood vessels, stopping them from proliferating and bringing forward their natural cell death. These correspond with hemangiomas fading and shrinking. Approximately 97% of hemangiomas respond to propanolol, with patients under 2 months old showing the greatest improvement. Topical beta blockers such as timolol. They are most helpful for thin superficial hemangiomas. These should not be used in conjunction with oral beta blockers given systemic absorption of topical timolol is known to occur Corticosteroids Laser surgery Physiotherapy for muscular skeletal pain management. == References ==
Aortic aneurysm	An aortic aneurysm is an enlargement (dilatation) of the aorta to greater than 1.5 times normal size. They usually cause no symptoms except when ruptured. Occasionally, there may be abdominal, back, or leg pain. The prevalence of abdominal aortic aneurysm ("AAA") has been reported to range from 2 to 12% and is found in about 8% of men more than 65 years of age. The mortality rate attributable to AAA is about 15,000 per year in the United States and 6,000 to 8,000 per year in the United Kingdom and Ireland. Between 2001 and 2006, there were approximately 230,000 AAA surgical repairs performed on Medicare patients in the United States. The etiology remains the topic of continued investigation. Known causes include trauma, infection, and inflammatory disorders. Risk factors include cigarette smoking, advanced age, dyslipidemia, hypertension, and coronary artery disease. The pathophysiology of the disease is related to an initial arterial insult causing a cascade of inflammation and extracellular matrix protein breakdown by proteinases leading to arterial wall weakening. They are most commonly located in the abdominal aorta, but can also be located in the thoracic aorta. Aortic aneurysms result from a weakness in the wall of the aorta and increase the risk of aortic rupture. When rupture occurs, massive internal bleeding results and, unless treated immediately, shock and death can occur. Screening with ultrasound is indicated in those at high risk. Prevention is by decreasing risk factors, such as smoking, and treatment is either by open or endovascular surgery. Aortic aneurysms resulted in about 152,000 deaths worldwide in 2013, up from 100,000 in 1990. Classification Aortic aneurysms are classified by their location on the aorta. An aortic root aneurysm, or aneurysm of the sinus of Valsalva. Thoracic aortic aneurysms are found within the chest; these are further classified as ascending, aortic arch, or descending aneurysms. Abdominal aortic aneurysms, "AAA" or "Triple A", the most common form of aortic aneurysm, involve that segment of the aorta within the abdominal cavity. Thoracoabdominal aortic aneurysms involve both the thoracic and abdominal aorta. Thoracoabdominal aortic aneurysms comprise some or all of the aorta in both the chest and abdomen, and have components of both thoracic and abdominal aortic aneurysms. Signs and symptoms Most intact aortic aneurysms do not produce symptoms. As they enlarge, symptoms such as abdominal pain and back pain may develop. Compression of nerve roots may cause leg pain or numbness. Untreated, aneurysms tend to become progressively larger, although the rate of enlargement is unpredictable for any individual. Rarely, clotted blood which lines most aortic aneurysms can break off and result in an embolus.Aneurysms cannot be found on physical examination. Medical imaging is necessary to confirm the diagnosis and to determine the anatomic extent of the aneurysm. In patients presenting with aneurysm of the arch of the aorta, a common sign is a hoarse voice from stretching of the left recurrent laryngeal nerve, a branch of the vagus nerve that winds around the aortic arch to supply the muscles of the larynx. Abdominal aortic aneurysm Abdominal aortic aneurysms (AAAs) are more common than their thoracic counterpart. One reason for this is that elastin, the principal load-bearing protein present in the wall of the aorta, is reduced in the abdominal aorta as compared to the thoracic aorta. Another is that the abdominal aorta does not possess vasa vasorum, the nutrient-supplying blood vessels within the wall of the aorta. Most AAA are true aneurysms that involve all three layers (tunica intima, tunica media and tunica adventitia). The prevalence of AAAs increases with age, with an average age of 65–70 at the time of diagnosis. AAAs have been attributed to atherosclerosis, though other factors are involved in their formation. The risk of rupture of an AAA is related to its diameter; once the aneurysm reaches about 5 cm, the yearly risk of rupture may exceed the risks of surgical repair for an average-risk patient. Rupture risk is also related to shape; so-called "fusiform" (long) aneurysms are considered less rupture-prone than "saccular" (shorter, bulbous) aneurysms, the latter having more wall tension in a particular location in the aneurysm wall.Before rupture, an AAA may present as a large, pulsatile mass above the umbilicus. A bruit may be heard from the turbulent flow in the aneurysm. Unfortunately, however, rupture may be the first hint of AAA. Once an aneurysm has ruptured, it presents with classic symptoms of abdominal pain which is severe, constant, and radiating to the back.The diagnosis of an abdominal aortic aneurysm can be confirmed at the bedside by the use of ultrasound. Rupture may be indicated by the presence of free fluid in the abdomen. A contrast-enhanced abdominal CT scan is the best test to diagnose an AAA and guide treatment options.Only 10–25% of patients survive rupture due to large pre-and postoperative mortality. Annual mortality from ruptured aneurysms in the United States is about 15,000. Most are due to abdominal aneurysms, with thoracic and thoracoabdominal aneurysms making up 1% to 4% of the total. Aortic rupture An aortic aneurysm can rupture from wall weakness. Aortic rupture is a surgical emergency and has a high mortality even with prompt treatment. Weekend admission for a ruptured aortic aneurysm is associated with increased mortality compared with admission on a weekday, and this is likely due to several factors including a delay in prompt surgical intervention. Risk factors Coronary artery disease Hypertension Loeys-Dietz Syndrome Hypercholesterolemia Hyperhomocysteinemia Elevated C-reactive protein Tobacco use Alcohol use Peripheral vascular disease Marfan syndrome Ehlers-Danlos type IVO Bicuspid Aortic Valve Syphilis IgG4-related disease Pregnancy Chronic obstructive sleep apnea Psoriasis Pathophysiology An aortic aneurysm can occur as a result of trauma, infection, or, most commonly, from an intrinsic abnormality in the elastin and collagen components of the aortic wall. While definite genetic abnormalities were identified in true genetic syndromes (Marfan, Elher-Danlos and others) associated with aortic aneurysms, both thoracic and abdominal aortic aneurysms demonstrate a strong genetic component in their aetiology. Prevention The risk of aneurysm enlargement may be diminished with attention to the patients blood pressure, smoking and cholesterol levels. There have been proposals to introduce ultrasound scans as a screening tool for those most at risk: men over the age of 65. The tetracycline antibiotic doxycycline is currently being investigated for use as a potential drug in the prevention of aortic aneurysm due to its metalloproteinase inhibitor and collagen stabilizing properties.Anacetrapib is a cholesteryl ester transfer protein inhibitor that raises high-density lipoprotein (HDL) cholesterol and reduces low-density lipoprotein (LDL) cholesterol. Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin Elevating the amount of HDL cholesterol in the abdominal area of the aortic artery in mice both reduced the size of aneurysms that had already grown and prevented abdominal aortic aneurysms from forming at all. In short, raising HDL cholesterol is beneficial because it induces programmed cell death. The walls of a failing aorta are replaced and strengthened. New lesions should not form at all when using this drug. Screening Screening for an aortic aneurysm so that it may be detected and treated prior to rupture is the best way to reduce the overall mortality of the disease. The most cost-efficient screening test is an abdominal aortic ultrasound study. Noting the results of several large, population-based screening trials, the US Centers for Medicare and Medicaid Services (CMS) now provides payment for one ultrasound study in male or female smokers aged 65 years or older ("SAAAVE Act"). Management Surgery (open or endovascular) is the definitive treatment of an aortic aneurysm. Medical therapy is typically reserved for smaller aneurysms or for elderly, frail patients where the risks of surgical repair exceed the risks of non-operative therapy (observation alone). Medical therapy Medical therapy of aortic aneurysms involves strict blood pressure control. This does not treat the aortic aneurysm per se, but control of hypertension within tight blood pressure parameters may decrease the rate of expansion of the aneurysm. The medical management of patients with aortic aneurysms, reserved for smaller aneurysms or frail patients, involves cessation of smoking, blood pressure control, use of statins and occasionally beta blockers. Ultrasound studies are obtained on a regular basis (i.e. every 6 or 12 months) to follow the size of the aneurysm. Despite optimal medical therapy, patients with large aneurysms are likely to have continued aneurysm growth and risk of aneurysm rupture without surgical repair. Surgery Decisions about repairing an aortic aneurysm are based on the balance between the risk of aneurysm rupture without treatment versus the risks of the treatment itself. For example, a small aneurysm in an elderly patient with severe cardiovascular disease would not be repaired. The chance of the small aneurysm rupturing is overshadowed by the risk of cardiac complications from the procedure to repair the aneurysm. The risk of the repair procedure is two-fold. First, there is consideration of the risk of problems occurring during and immediately after the procedure itself ("peri-procedural" complications). Second, the effectiveness of the procedure must be taken into account, namely whether the procedure effectively protects the patient from aneurysm rupture over the long term, and whether the procedure is durable so that secondary procedures, with their attendant risks, are not necessary over the life of the patient. A less invasive procedure (such as endovascular aneurysm repair) may be associated with fewer short-term risks to the patient (fewer peri-procedural complications) but secondary procedures may be necessary over long-term follow-up. The determination of surgical intervention is determined on a per-case basis. The diameter of the aneurysm, its rate of growth, the presence or absence of Marfan syndrome, Ehlers–Danlos syndromes or similar connective tissue disorders, and other co-morbidities are all important factors in the overall treatment. A large, rapidly expanding, or symptomatic aneurysm should be repaired, as it has a greater chance of rupture. Slowly expanding aortic aneurysms may be followed by routine diagnostic testing (i.e.: CT scan or ultrasound imaging). For abdominal aneurysms, the current treatment guidelines for abdominal aortic aneurysms suggest elective surgical repair when the diameter of the aneurysm is greater than 5 cm (2 in). However, recent data on patients aged 60–76 suggest medical management for abdominal aneurysms with a diameter of less than 5.5 cm (2 in). Open surgery Open surgery starts with exposure of the dilated portion of the aorta via an incision in the abdomen or abdomen and chest, followed by insertion of a synthetic (Dacron or Gore-Tex) graft (tube) to replace the diseased aorta. The graft is sewn in by hand to the non-diseased portions of the aorta, and the aneurysmal sac is closed around the graft. The aorta and its branching arteries are cross-clamped during open surgery. This can lead to inadequate blood supply to the spinal cord, resulting in paraplegia. A 2004 systematic review and meta analysis found that cerebrospinal fluid drainage (CFSD), when performed in experienced centers, reduces the risk of ischemic spinal cord injury by increasing the perfusion pressure to the spinal cord. A 2012 Cochrane systematic review noted that further research regarding the effectiveness of CFSD for preventing a spinal cord injury is required. Endovascular Endovascular treatment of aortic aneurysms is a minimally invasive alternative to open surgery repair. It involves the placement of an endo-vascular stent through small incisions at the top of each leg into the aorta. As compared to open surgery, EVAR has a lower risk of death in the short term and a shorter hospital stay but may not always be an option. There does not appear to be a difference in longer term outcomes between the two. After EVAR, repeat procedures are more likely to be needed. Epidemiology Aortic aneurysms resulted in about 152,000 deaths in 2013 up from 100,000 in 1990. See also Aortic valve repair Aortic dissection Cardarellis sign References == External links ==
Reticulocytosis	Reticulocytosis is a condition where there is an increase in reticulocytes, immature red blood cells. It is commonly seen in anemia. They are seen on blood films when the bone marrow is highly active in an attempt to replace red blood cell loss such as in haemolytic anaemia, haemorrhage. == External links ==
Lipomatosis	Lipomatosis is believed to be an autosomal dominant condition in which multiple lipomas are present on the body. Many discrete, encapsulated lipomas form on the trunk and extremities, with relatively few on the head and shoulders. In 1993, a genetic polymorphism within lipomas was localized to chromosome 12q15, where the HMGIC gene encodes the high-mobility-group protein isoform I-C. This is one of the most commonly found mutations in solitary lipomatous tumors but lipomas often have multiple mutations. Reciprocal translocations involving chromosomes 12q13 and 12q14 have also been observed within.Although this condition is benign, it can sometimes be very painful depending on location of the lipomas. Some patients who are concerned with cosmetics seek removal of individual lipomas. Removal can include simple excision, endoscopic removal, or liposuction.Other entities which are accompanied by multiple lipomas include Proteus syndrome, Cowden syndrome and related disorders due to PTEN gene mutations, benign symmetric lipomatosis (Madelung disease), Dercums Disease, familial lipodystrophy, hibernomas, epidural steroid injections with epidural lipomatosis, and familial angiolipomatosis. See also Pelvic lipomatosis — A rare disease most often seen in older obese black men with hypertension. Virchows metamorphosis — lipomatosis in the heart and salivary glands. Dercums — A rare condition characterized by generalized obesity and painful fatty tumors in the adipose tissue. References == External links ==
Genital ulcer	A genital ulcer is an open sore located on the genital area, which includes the vulva, penis, perianal region, or anus. Genital ulcers are most commonly caused by infectious agents (fungal infections, secondary bacterial infections, or sexually transmitted diseases such as genital herpes, syphilis or chancroid). However, this is not always the case, as a genital ulcer may have noninfectious causes as well. Overview A genital ulcer may be located on the vulva, penis, perianal region, or anus. Globally, the incidence of genital ulcers is estimated to be approximately 20 million cases annually. The most likely cause of a genital ulcer varies depending on the characteristics of a population and location. The most common cause of genital ulcers in the United States is herpes simplex infections, with syphilis the second most common cause, and chancroid the third. These common causes of genital ulcer disease (HSV-1, HSV-2 and treponema pallidum) can all be efficiently transmitted through oral sex.Important signs associated with genital ulcers that may assist in the diagnosis of the cause of the genital ulcer may include the presence of tender or non-tender enlarged lymph nodes in the groin area, a painful or non-painful genital ulcer, or the presence of vesicular lesions, which are small, painful, elevated blisters.The most common causes of a genital ulcer include infectious agents, with sexually transmitted diseases being the most common, but which can also include fungal infections and secondary bacterial infections. While infectious agents are the most common cause, a genital ulcer may also be the result of non-infectious causes such as Behcets syndrome, lupus, or psoriasis.Since it is difficult to determine a cause of a genital ulcer from history, examination, and population characteristics alone, further testing is often needed. The most common diagnostic tools used are targeted towards the most common etiologies of genital ulcers: syphilis (syphilis serology, PCR testing, or dark-field examination), herpes simplex virus (PCR, culture, or type specific HSV antibodies), and haemophilus ducreyi (culture on special media currently not widely available in most hospital systems) if the individual is in a known endemic region. Further diagnostic tools such as a biopsy or culture are often utilized if ulcers appear unusual or do not respond as expected to therapy.Since genital ulcers are often infectious in origin, there is an increased risk of acquiring HIV in a HIV negative patient through viral introduction through the open sore Conversely, there is an increased risk of HIV transmission through increased shedding of viral HIV in the presence of a genital ulcer in a patient with a history of HIV. The CDC recommends testing for HIV in any individual presenting for a genital ulcer who does not already have a history of HIV. Infectious sexually transmitted causes Risk factors for sexually transmitted genital ulcers are similar to the risk factors for most sexually transmitted diseases which include multiple sex partners, alcohol, illicit drug use, homelessness, poverty, inmates, men who have sex with men, sexually active teenagers, sexual contact without contraceptive use, and unstable housing. The most common cause of genital ulcers in the North America and Western Europe are the result of HSV or syphilis infections, while the most common cause in other parts of the world is chancroid. Most sexually active adolescents with genital ulcers have a herpes simplex virus infection, more commonly type 2. Meanwhile, according to 2017 CDC reports, syphilis is more common in men who have sex with men populations although rates of syphilis have been rising in heterosexual men and women in the United States. Following syphilis and genital herpes infections, a chancroid is the third most common cause but tends to occur in focused outbreaks over time. While rates of H. ducreyi infection seem to be declining according to a 2017 report, it is possible this may be due to lack of testing since H. ducreyi requires a very specialized culture medium which is not commonly available. Less common causes include lymphogranuloma venereum, which is more common in men who have sex with men, and granuloma inguinale, which is more common in tropical regions globally. rather than in the United States. Non-infectious causes Genital ulcers are not strictly a sign of a sexually transmitted illness, although non-infectious sources are significantly more infrequent in comparison. The most common non-infectious sources of genital ulcers are first Behcets disease, and second drug reaction.Behcets syndrome is a chronic systemic vasculitis infection that is defined by recurrent oral and genital aphthous ulcers but can also affect many other organ systems, such as the eyes, ears, nervous system, heart, lungs, joints, and intestines. Behcets syndrome commonly presents in the 30-40 age range and is more common in the Middle East and Asia. There is a familial component to Behcets syndrome since it has associations with the HLA-B51 gene.Causes of drug induced genital ulcers take the form of Stevens–Johnson syndrome, toxic epidermal necrolysis, erythema multiforme, and fixed drug eruptions in response to a diverse list of medications. Stevens–Johnson syndrome and toxic epidermal necrolysis are more likely than erythema multiforme to have genital manifestations although all present with a toxic appearing patient. A fixed drug eruption in comparison does not present as a toxic appearing patient but rather single or multiple erythematous patches that vary in size and shape which eventually turn dark brown in color and become itchy. The defining characteristic is that these drug eruptions appear in the same location each time the offending medication is used, and will resolve on their own.Other potential causes of non-infectious genital ulcers are diverse, but can include sexual trauma, Lipschutz ulcers, inflammatory bowel diseases such as Crohns disease, lichen planus, lichen sclerosis, and immunobullous disease such as pemphigous vulgaris, since bullous pemphigoid is less likely to occur on the genitals. Cancers of the vulva and penis, with the most common subtype being squamous cell carcinoma, can also present as genital ulcers, but leukemias such as chronic lymphocytic leukemia and acute promyelotic leukemia have also been identified. Infectious non-sexually transmitted causes Even lesser common etiologies of genital ulcers include fungal infection, secondary bacterial infections, and parasitic infections.Fungal infections are rare causes of genital ulcers, but candida albicans infection is typically the most common source, and is more prevalent in patients with a history of diabetes mellitus, chronic steroid use, or other immunodeficiencies. There have also been rare case reports of paracoccidioidomycosis, zygomycosis and histoplasmosis infections causing genital ulcers.Parasitic infections such as amoebiasis and leishmaniasis can present in cutaneous form in the genital regions. This can be confused with a sexually transmitted disease or sepsis due to their tendency to present with additional systemic symptoms.Genital tuberculosis can also present as a genital ulcer, either in the form of cutaneous tuberculosis from a systemic infection, or a primary tuberculosis chancre at the site of inoculation via direct genital contact with infected sputum. Cutaneous tuberculosis typically presents initially as red or yellow nodules that eventually break down to form soft, painful, and roughly circular ulcers, which as a rule are covered in a pseudomembrane. Primary tuberculosis chancre, on the other hand, often presents as a painless ulcer with well defined edges that appears rather nonspecific. References External links Genital herpes - self-care, A.D.A.M. Genital herpes treatment, WebMD Diseases Characterized by Genital, Anal, or Perianal Ulcers, Centers for Disease Control and Prevention Diagnosis and Management of Genital Ulcers, American Family Physician
Macrocytosis	Macrocytosis is the enlargement of red blood cells with near-constant hemoglobin concentration, and is defined by a mean corpuscular volume (MCV) of greater than 100 femtolitres (the precise criterion varies between laboratories). The enlarged erythrocytes are called macrocytes or megalocytes (both words have roots meaning "big cell"). As a symptom its cause may be relatively benign and need no treatment or it may indicate a serious underlying illness. Causes In humans, most commonly (especially when the increase in size is mild, and just above normal range) the cause is bone marrow dysplasia secondary to alcohol use disorder. Poor absorption of vitamin B12 in the digestive tract can also cause macrocytosis. Gastrointestinal diseases that may cause macrocytosis include celiac disease (severe sensitivity to gluten from wheat and other grains that causes intestinal damage) and Crohns disease (inflammatory bowel disease that can affect any part of the gastrointestinal tract). Other causes may include: megaloblastosis (vitamin B12 or folate deficiency) because slowly dividing erythrocytes accumulate cytoplasmic components, resulting in larger-than-normal cells. hypothyroidism chronic obstructive pulmonary disease (COPD) aplastic anemia reticulocytosis (commonly from hemolysis or a recent history of blood loss). liver disease because of an increase in circulating phospholipids and cholesterol, which bind on erythrocytes and induce membrane expansion myeloproliferative disease myelodysplastic syndrome which most commonly presents with macrocytic anemia chronic exposure to benzene pregnancy (most common, and requires no treatment as the person affected will return to normal post-partum) Certain anti-inflammatory drugs, e.g. salazopyrin, azathioprine. Complications No complications arise from macrocytosis itself and a prognosis will be determined from its cause. See also Macrocytic anemia References == External links ==
Propofol infusion syndrome	Propofol infusion syndrome (PRIS) is a rare syndrome which affects patients undergoing long-term treatment with high doses of the anaesthetic and sedative drug propofol. It can lead to cardiac failure, rhabdomyolysis, metabolic acidosis, and kidney failure, and is often fatal. High blood potassium, high blood triglycerides, and liver enlargement, proposed to be caused by either "a direct mitochondrial respiratory chain inhibition or impaired mitochondrial fatty acid metabolism" are also key features. It is associated with high doses and long-term use of propofol (> 4 mg/kg/h for more than 24 hours). It occurs more commonly in children, and critically ill patients receiving catecholamines and glucocorticoids are at high risk. Treatment is supportive. Early recognition of the syndrome and discontinuation of the propofol infusion reduces morbidity and mortality. Presentation The syndrome clinically presents as acute refractory bradycardia that leads to asystole, in the presence of one or more of the following conditions: metabolic acidosis, rhabdomyolysis, hyperlipidemia, and enlarged liver. The association between PRIS and propofol infusions is generally noted at infusions higher than 4 mg.kg for greater than 48 hours. Mechanism of Action The mechanism of action is poorly understood but may involve the impairment of mitochondrial fatty acid metabolism by propofol.PRIS is a rare complication of propofol infusion. It is generally associated with high doses (>4 mg/kg per hour or >67 mcg/kg per minute) and prolonged use (>48 hours) though it has been reported with high-dose short-term infusions.Additional proposed risk factors include a young age, critical illness, high fat and low carbohydrate intake, inborn errors of mitochondrial fatty acid oxidation, and concomitant catecholamine infusion or steroid therapy. Characteristics of PRIS include acute refractory bradycardia, severe metabolic acidosis, cardiovascular collapse, rhabdomyolysis, hyperlipidemia, renal failure, and hepatomegaly.The incidence of PRIS is unknown, but it is probably less than 1 percent. Mortality is variable but high (33 to 66 percent). Treatment involves discontinuation of the propofol infusion and supportive care. Risk Factors Predisposing factors seem to include young age, severe critical illness of central nervous system or respiratory origin, exogenous catecholamine or glucocorticoid administration, inadequate carbohydrate intake and subclinical mitochondrial disease. Treatment Treatment options are limited and are usually supportive, including hemodialysis with cardiorespiratory support. == References ==
Brachial plexus injury	A brachial plexus injury (BPI), also known as brachial plexus lesion, is an injury to the brachial plexus, the network of nerves that conducts signals from the spinal cord to the shoulder, arm and hand. These nerves originate in the fifth, sixth, seventh and eighth cervical (C5–C8), and first thoracic (T1) spinal nerves, and innervate the muscles and skin of the chest, shoulder, arm and hand.Brachial plexus injuries can occur as a result of shoulder trauma, tumours, or inflammation, or obstetric. Obstetric injuries may occur from mechanical injury involving shoulder dystocia during difficult childbirth, with a prevalence of 1 in 1000 births."The brachial plexus may be injured by falls from a height on to the side of the head and shoulder, whereby the nerves of the plexus are violently stretched. The brachial plexus may also be injured by direct violence or gunshot wounds, by violent traction on the arm, or by efforts at reducing a dislocation of the shoulder joint".The rare Parsonage–Turner syndrome causes brachial plexus inflammation without obvious injury, but with nevertheless disabling symptoms. Signs and symptoms Signs and symptoms may include a limp or paralyzed arm, lack of muscle control in the arm, hand, or wrist, and lack of feeling or sensation in the arm or hand. Although several mechanisms account for brachial plexus injuries, the most common is nerve compression or stretch. Infants, in particular, may experience brachial plexus injuries during delivery and these present with typical patterns of weakness, depending on which portion of the brachial plexus is involved. The most severe form of injury is nerve root avulsion, which usually accompanies high-velocity impacts that commonly occur during motor-vehicle collisions or bicycle accidents. Disabilities Based on the location of the nerve damage, brachial plexus injuries can affect part of or the entire arm. For example, musculocutaneous nerve damage weakens elbow flexors, median nerve damage causes proximal forearm pain, and paralysis of the ulnar nerve causes weak grip and finger numbness. In some cases, these injuries can cause total and irreversible paralysis. In less severe cases, these injuries limit use of these limbs and cause pain.The cardinal signs of brachial plexus injury then, are weakness in the arm, diminished reflexes, and corresponding sensory deficits. Erbs palsy. "The position of the limb, under such conditions, is characteristic: the arm hangs by the side and is rotated medially; the forearm is extended and pronated. The arm cannot be raised from the side; all power of flexion of the elbow is lost, as is also supination of the forearm". In Klumpkes paralysis, a form of paralysis involving the muscles of the forearm and hand, a characteristic sign is the clawed hand, due to loss of function of the ulnar nerve and the intrinsic muscles of the hand it supplies. Causes In most cases, the nerve roots are stretched or torn from their origin, since the meningeal covering of a nerve root is thinner than the sheath enclosing the nerve. The epineurium of the nerve is contiguous with the dura mater, providing extra support to the nerve.Brachial plexus lesions typically result from excessive stretching; from rupture injury where the nerve is torn but not at the spinal cord; or from avulsion injuries, where the nerve is torn from its attachment at the spinal cord. A bony fragment, pseudoaneurysm, hematoma, or callus formation of fractured clavicle can also put pressure on the injured nerve, disrupting innervation of the muscles. A trauma directly on the shoulder and neck region can crush the brachial plexus between the clavicle and the first rib.Although injuries can occur at any time, many brachial plexus injuries happen during birth: the babys shoulders may become impacted during the birth process causing the brachial plexus nerves to stretch or tear. Obstetric injuries may occur from mechanical injury involving shoulder dystocia during difficult childbirth, the most common of which result from injurious stretching of the childs brachial plexus during birth, most often during vaginal birth, but occasionally Caesarean section. The excessive stretch results in incomplete sensory and/or motor function of the injured nerve.Injuries to the brachial plexus result from excessive stretching or tearing of the C5-T1 nerve fibers. These injuries can be located in front of or behind the clavicle, nerve disruptions, or root avulsions from the spinal cord. These injuries are diagnosed based on clinical exams, axon reflex testing, and electrophysiological testing. Brachial plexus injuries require quick treatment in order for the patient to make a full functional recovery (Tung, 2003). These types of injuries are most common in young adult males.Traumatic brachial plexus injuries may arise from several causes, including sports, high-velocity motor vehicle accidents, especially in motorcyclists, but also all-terrain-vehicle (ATV) and other accidents. Injury from a direct blow to the lateral side of the scapula is also possible. The severity of nerve injuries may vary from a mild stretch to the nerve root tearing away from the spinal cord (avulsion). "The brachial plexus may be injured by falls from a height on to the side of the head and shoulder, whereby the nerves of the plexus are violently stretched… The brachial plexus may also be injured by direct violence or gunshot wounds, by violent traction on the arm, or by efforts at reducing a dislocation of the shoulder joint".Brachial plexus lesions can be divided into three types: An upper brachial plexus lesion, which occurs from excessive lateral neck flexion away from the shoulder. Most commonly, improper use of forceps during delivery or falling on the neck at an angle causes upper plexus lesions leading to Erbs palsy. This type of injury produces a very characteristic sign called Waiters tip deformity due to loss of the lateral rotators of the shoulder, arm flexors, and hand extensor muscles. Less frequently, the whole brachial plexus lesion occurs; most infrequently, sudden upward pulling on an abducted arm (as when someone breaks a fall by grasping a tree branch) produces a lower brachial plexus lesion, in which the eighth cervical (C8) and first thoracic (T1) nerves are injured "either before or after they have joined to form the lower trunk. The subsequent paralysis affects, principally, the intrinsic muscles of the hand and the flexors of the wrist and fingers". This results in a form of paralysis known as Klumpkes paralysis.Backpack palsy is caused by much use of a heavy backpack whose pack-straps chronically press on the brachial plexus. Mechanism Injury to the brachial plexus can happen in numerous environments. These may include contact sports, motor vehicle accidents, and birth. Although these are but a common few events, there is one of two mechanisms of injury that remain constant during the point of injury. The two mechanisms that can occur are traction and heavy impact. Anatomy The brachial plexus is made up of spinal nerves that are part of the peripheral nervous system. It includes sensory and motor nerves that innervate the upper limbs. The brachial plexus includes the last four cervical nerves (C5-C8) and the 1st thoracic nerve (T1). Each of those nerves splits into smaller trunks, divisions, and cords. The lateral cord includes the musculocutaneous nerve and lateral branch of the median nerve. The medial cord includes the medial branch of the median nerve and the ulnar nerve. The posterior cord includes the axillary nerve and radial nerve. Traction Traction occurs from severe movement and causes a pull or tension among the nerves. There are two types of traction: downward traction and upward traction. In downward traction there is tension of the arm which forces the angle of the neck and shoulder to become broader. This tension is forced and can cause lesions of the upper roots and trunk of the nerves of the brachial plexus. Motorcycle accidents and sports injuries usually cause this type of injury to brachial plexus. Upward traction also results in the broadening of the scapulo-humoral angle but this time the nerves of T1 and C8 are torn away. Humeral fractures and shoulder dislocations can also cause this type of injury with high energy injuries.Root avulsion or nerve rupture may occur during severe trauma, inappropriate surgical positioning, or inappropriate use of surgical retractors. There are two mechanisms for root avulsion injury: peripheral and central mechanism. In peripheral mechanism, traction is transmitted to the rootlet, however dura mater will be torn with the rootlet intact because the dura is less elastic when compared to the rootlet. Pseudomeningocele can be shown on cervical myelography. On the other hand, through central mechanism, the head and neck is pushed along with the spinal roots of the brachial plexus to the opposite site of the body, leading to direct nerve root injury but the dura sheath remains intact. In this case, anterior roots are more prone than posterior roots for avulsion, thus the C8 and T1 nerve roots are more prone to injury. Root avulsion injury can be further divided based on the location of the lesion: pre- and postganglionic lesions. In a preganglionic lesion, the sensory fibre remain attached to the cell body of the sensory ganglion, thus there is no wallerian degeneration of the sensory fibre, thus sensory action potential can still be detected at the distal end of the spinal nerve. However, those who get this type of lesion have sensory loss over the affected nerve roots. In this case, surgical repair of the lesion is not possible because the proximal nerve tissue is too short for stitching to be possible. For postganglionic lesions, the cell body of the sensory ganglion is detached from the spinal nerve, leading to wallerian degeneration of the sensory fibre. Thus, no action potential detected at the distal end of spinal nerve. However, surgical repair is possible because proximal nerve tissue has enough length for stitching. Impact Heavy impact to the shoulder is the second common mechanism to causing injury to the brachial plexus. Depending on the severity of the impact, lesions can occur at all nerves in the brachial plexus. The location of impact also affects the severity of the injury and depending on the location the nerves of the brachial plexus may be ruptured or avulsed. When passing through between the clavicle and first rib, the brachial plexus may be crushed in the costoclavicular space. This is usually due to direct trauma to the shoulder or neck region as a result of motorvehicular accidents, occupational injuries or sports injuries. The brachial plexus may also be compressed by surrounding damaged structures such as bone fragments or callus from the clavicular fracture, and hematoma or pseudoaneurysm from vascular injury. Cervical rib, prominent transverse process, and congenital fibrous bands can also compress the brachial plexus and cause thoracic outlet syndrome.During the delivery of a baby, the shoulder of the baby may graze against the pelvic bone of the mother. During this process, the brachial plexus can receive damage resulting in injury. The incidence of this happening at birth is 1 in 1000. This is very low compared to the other identified brachial plexus injuries. Diagnosis The most accurate test for diagnosing a brachial plexus injury is operative exploration of the potentially injured segments from the spinal roots to end-organs. Nerves should be evaluated under an operative microscope, with or without intraoperative electrical studies (e.g. bipolar stimulation, SEPs or MEPs) to supplement. Operative evaluation of the rootlets within the spinal canal and intraforaminal portion of the spinal roots proximal to the dorsal root ganglia (e.g. via hemilamiinectomy or otherwise) is difficult and rarely clinically justifiable, so in the context of an apparently in-continuity root, preoperative imaging studies are the only method of evaluating this section of nerve.The best non-invasive test for BPI is magnetic resonance imaging (MRI). MRI aids in the assessment of the injuries and is used to provide information on the portion of the plexus which cannot be operatively explored (the rootlets and roots). In addition, assessment of the cervical cord, post-traumatic changes in soft tissues and associated injuries (e.g. fractures, cuff tears, etc.) may be appreciated. Although superior to nerve conduction studies, ultrasound and other tests, conventional MRI has a poor specificity (72%) meaning that the false-positive rate is high and surgeons cant rely upon the test to guide treatment. Consequently, the future of peripheral nerve MR imaging (including imaging brachial plexus injuries) is likely to be based on diffusion-weighted imaging, such as diffusion tensor techniques, which are of significant potential clinical utility and can enable the production of easily interpreted 3D reconstructions of the spinal cord and brachial plexus such as this. Several weeks/months after BPI, EMG examination can provide additional information about whether the muscle is denervated. These examinations are painful, highly user-dependent and lack normal values so cannot be relied upon. Classification The severity of brachial plexus injury is determined by the type of nerve damage. There are several different classification systems for grading the severity of nerve and brachial plexus injuries. Most systems attempt to correlate the degree of injury with symptoms, pathology and prognosis. Seddons classification, devised in 1943, continues to be used, and is based on three main types of nerve fiber injury, and whether there is continuity of the nerve. Neurapraxia: The mildest form of nerve injury. It involves an interruption of the nerve conduction without loss of continuity of the axon. Recovery takes place without wallerian degeneration. Axonotmesis: Involves axonal degeneration, with loss of the relative continuity of the axon and its covering of myelin, but preservation of the connective tissue framework of the nerve (the encapsulating tissue, the epineurium and perineurium, are preserved). Neurotmesis: The most severe form of nerve injury, in which the nerve is completely disrupted by contusion, traction or laceration. Not only the axon, but the encapsulating connective tissue lose their continuity. The most extreme degree of neurotmesis is transsection, although most neurotmetic injuries do not produce gross loss of continuity of the nerve but rather, internal disruption of the nerve architecture sufficient to involve perineurium and endoneurium as well as axons and their covering. It requires surgery, with unpredictable recovery.A more recent and commonly used system described by the late Sir Sydney Sunderland, divides nerve injuries into five degrees: first degree or neurapraxia, following on from Seddon, in which the insulation around the nerve called myelin is damaged but the nerve itself is spared, and second through fifth degree, which denotes increasing severity of injury. With fifth degree injuries, the nerve is completely divided. Treatment Treatment for brachial plexus injuries includes orthosis/splinting, occupational or physical therapy and, in some cases, surgery. Some brachial plexus injuries may heal without treatment. Many infants improve or recover within 6 months, but those that do not, have a very poor outlook and will need further surgery to try to compensate for the nerve deficits. The ability to bend the elbow (biceps function) by the third month of life is considered an indicator of probable recovery, with additional upward movement of the wrist, as well as straightening of thumb and fingers an even stronger indicator of excellent spontaneous improvement. Gentle range of motion exercises performed by parents, accompanied by repeated examinations by a physician, may be all that is necessary for patients with strong indicators of recovery.The exercises mentioned above can be done to help rehabilitate from mild cases of the injury. However, in more serious brachial plexus injuries surgical interventions can be used. Function can be restored by nerve repairs, nerve replacements, and surgery to remove tumors causing the injury. Another crucial factor to note is that psychological problems can hinder the rehabilitation process due to a lack of motivation from the patient. On top of promoting a lifetime process of physical healing, it is important to not overlook the psychological well-being of a patient. This is due to the possibility of depression or complications with head injuries. Rehabilitation There are many treatments to facilitate the process of recovery in people who have brachial plexus injuries. Improvements occur slowly and the rehabilitation process can take up to many years. Many factors should be considered when estimating recovery time, such as initial diagnosis of the injury, severity of the injury, and type of treatments used. Some forms of treatment include nerve grafts, medication, surgical decompression, nerve transfer, physical therapy, and occupational therapy. Therapy Physical and occupational therapy is important when dealing with a brachial plexus injuries. One of the main goals of rehabilitation is to prevent muscle atrophy until the nerves regain function. Electrical stimulation is an effective treatment to help patients reach this fundamental goal. Exercises that involve shoulder extension, flexion, elevation, depression, abduction and adduction facilitate healing by engaging the nerves in the damaged sites as well as improve muscle function. Stretching is done on a daily basis to improve or maintain range of motion. Stretching is important in order to rehabilitate since it increases the blood flow to the injury as well as facilitates nerves in functioning properly.A study has also shown that a sensory-motor deficit in the upper limbs after a brachial plexus injury can affect the corporal balance in the vertical positioning. Examined patients had a lower score in the Berg balance scale, a greater difficulty in maintaining in the unipodal stance during one minute and leaned the body weight distribution to the side affected by the lesion. Patients also exhibited a greater variability in the postural oscillation, evaluated by the directional stability index. The results alert the clinical community about the necessity to prevent and treat secondary effects of this condition. Epidemiology Brachial plexus injury is found in both children and adults, but there is a difference between children and adults with BPI. Adults The prevalence of brachial plexus injuries in North American adults in the 1900s was about 1.2%. BPI is most commonly found in young healthy adults, from ages 14 to 63 years old, with 50% of patients between 19 and 34 years old. 89% of BPI patients are male. The rate of brachial plexus injury has been increasing. Children OBPP, also known as obstetrical brachial plexus palsy, occurs primarily in young children at a rate of 0.38 to 1.56 per 1000 live births depending on the type of care and the average birth weight of infants in different regions of the world. For example, a study in the United States showed and incidence of OBPP of about 1.51 cases per 1000 live births, in a Canadian study, the incidence was between 0.5 and 3 injuries per 1000 live births, a Dutch study reported an incidence of 4.6 per 1000 live births. The risk of BPI at birth is highest for infants weighing more than 4.5 kg at birth born to diabetic women. Type of delivery also affects the risk of BPI. Brachial plexus injury risks for newborns are increased with gained birth weight, birth delivery where a vacuum is assisted, and not being able to handle glucose. Traumatic injuries BPI has shown to occur in 44% to 70% of traumatic injuries, such as motorcycle accidents, sporting activities, or workplace accidents. With 22% being motorcycle injuries and about 4.2% having plexus damage. People who have accidents with riding motorcycles and snowmobiles have higher risks of getting a BPI and with ihg-injury injuries such as motorcycle accidents, root avulsion from the spinal cord is the most common pattern of injury (~72% prevalence of at least 1 root avulsion) which requires surgery to reanimate the arm. Prognosis The site and type of brachial plexus injury determine the prognosis. Avulsion and rupture injuries require timely surgical intervention for any chance of recovery. For milder injuries involving buildup of scar tissue and for neurapraxia, the potential for improvement varies, but there is a fair prognosis for spontaneous recovery, with a 90–100% return of function. References == External links ==
Hepatic artery thrombosis	Hepatic artery thrombosis occurs when a blood clot forms in the artery that provides blood flow to the liver. Hepatic artery thrombosis may occur as a complication after liver transplantation, and represents the most common complication of liver transplantation. Smoking tobacco increases the risk of hepatic artery thrombosis in people who have undergone liver transplantation.Hepatic artery thrombosis may cause severe elevations in serum aminotransferases, alanine transaminase (ALT) and aspartate transaminase (AST). Often the AST is greater than the ALT. Hepatic artery thrombosis is usually diagnosed with ultrasound with doppler, although it may be diagnosed using computed tomography (CT) or magnetic resonance imaging (MRI). The treatment for recently developed or acute hepatic artery thrombosis include anticoagulant medications, fibrinolytic therapy to break up the blood clot, or surgical revascularization. If acute hepatic artery thrombosis occurs after liver transplantation, then retransplantation with a new liver may be necessary. Signs and symptoms Hepatic artery thrombosis can cause severe elevations in serum liver enzymes, AST and ALT. Often the AST is greater than the ALT. When it occurs after liver transplantation, it usually develops within 4 months after surgery. Diagnosis Hepatic artery thrombosis is diagnosed with ultrasound with doppler, which shows a lack of blood flow through the hepatic artery. Hepatic artery thrombosis may also be diagnosed using CT or MR imaging, which would show evidence of a blood clot within the hepatic artery. Treatment Treatment for acute hepatic artery thrombosis include anticoagulant medications, fibrinolysis therapies to break up the blood clot, or surgical revascularization. If acute hepatic artery thrombosis occurs after liver transplantation, then retransplantation with a new liver may be necessary.However, chronic hepatic artery thrombosis may not require therapy, as the gradual development of additional blood vessels (collateral circulation) may be adequate for the metabolic needs of the liver. Prognosis The development of hepatic artery thrombosis soon after liver transplantation is associated with higher risk of death (mortality) and transplanted liver failure (graft loss). Epidemiology Hepatic artery thrombosis is the most common complication that occurs after liver transplantation. Hepatic artery thrombosis may also occur after other surgeries. Hepatic artery thrombosis and primary non-function are the two most common reason that a transplanted liver fails to work (graft failure). Among people who receive liver transplants, smoking tobacco increases the risk of hepatic artery thrombosis. == References ==
Gynecologic hemorrhage	Gynecologic hemorrhage represents excessive bleeding of the female reproductive system. Such bleeding could be visible or external, namely bleeding from the vagina, or it could be internal into the pelvic cavity or form a hematoma. Normal menstruation is not considered a gynecologic hemorrhage, as it is not excessive. Hemorrhage associated with a pregnant state or during delivery is an obstetrical hemorrhage. Types Metrorrhagia (metro = womb, -rrhagia = excessive flow) is uterine bleeding at irregular intervals, particularly between the expected menstrual periods. Postcoital bleeding is vaginal bleeding after sexual intercourse. Causes Causes of gynecologic bleeding include: Hormonal Anovulation is a common cause of gynecological hemorrhage. Under the influence of estrogen the endometrium (uterine lining) is stimulated and eventually such lining will be shed off (estrogen breakthrough bleeding). The anovulation chapter discusses its multiple possible causes. Longstanding anovulation can also lead to endometrial hyperplasia and facilitate the development of endometrial cancer. Neoplasm Cancer of the uterus is always a concern, specifically when the bleeding occurs after menopause. Other types of cancer include cervical cancer; bleeding in that case can sometimes be triggered by postcoital bleeding. Cancers of the vagina or fallopian tubes are rare causes of hemorrhage. Uterine fibroids represent a common, benign condition that may lead to bleeding, specifically if the lesion affects the uterine cavity. Polyps of the uterine lining are a common cause of bleeding, but such bleeding tends to be light. Trauma Sexual assault and rape can lead to injury and gynecological hemorrhage. Accidents to the lower abdomen may lead to internal or external bleeding. Bleeding disorder Women with a bleeding disorder may be prone to more excessive bleeding. A hematologic work-up should discover the cause. Other On occasion an ovarian cyst can rupture and give rise to internal hemorrhage. This may occur during ovulation or as a result of endometriosis. If the pregnancy test is positive, consider pregnancy related bleeding (see obstetrical hemorrhage), including miscarriage and ectopic pregnancy. Diagnosis A history will establish if the condition is acute or chronic, and if external circumstances are involved. A gynecologic examination is usually complemented by a gynecologic ultrasonography. A blood count determines the degree of anemia and may point out bleeding problems. The pregnancy test is important, particularly as bleeding in early pregnancy presents as gynecological hemorrhage and ectopic pregnancy can be fatal. Diagnosis is broadly classified into supportive and definitive investigations: Supportive Complete blood count to assess degree of anemia. Ultrasonography to rule out uterine lesions, PID. Definitive Pregnancy test for those who are not yet post menopausal mandatory. Speculum examination to take samples for pap smear. Dilation and curettage to get samples for histology and also control the bleeding if associated with abortion. Colposcopy. Definition Menstruation occurs typically monthly, lasts 3–7 days, and involves up to 80 ml blood. Bleeding in excess of this norm in a nonpregnant woman constitutes gynecologic hemorrhage. In addition, early pregnancy bleeding has sometimes been included as gynecologic hemorrhage, namely bleeding from a miscarriage or an ectopic pregnancy, while it actually represents obstetrical bleeding. However, from a practical view, early pregnancy bleeding is usually handled like a gynecological hemorrhage. First aid Gynecologic hemorrhage needs to be evaluated as soon as possible by a physician. The amount and duration of bleeding will dictate whether a bleeding event is an emergency event. Treatment Treatment depends on diagnosis and may include hormonal therapy, iv fluids, blood transfusion, and/or a dilation and curettage. Internal bleeding requires laparoscopy or abdominal surgery, in rare and extreme cases a hysterectomy is performed. See also Medical emergency Istihadha == References ==
Eosinophilia	Eosinophilia is a condition in which the eosinophil count in the peripheral blood exceeds 5×108/L (500/μL). Hypereosinophilia is an elevation in an individuals circulating blood eosinophil count above 1.5 x 109/L (i.e. 1,500/μL). The hypereosinophilic syndrome is a sustained elevation in this count above 1.5 x 109/L (i.e. 1,500/μL) that is also associated with evidence of eosinophil-based tissue injury. Eosinophils usually account for less than 7% of the circulating leukocytes. A marked increase in non-blood tissue eosinophil count noticed upon histopathologic examination is diagnostic for tissue eosinophilia. Several causes are known, with the most common being some form of allergic reaction or parasitic infection. Diagnosis of eosinophilia is via a complete blood count (CBC), but diagnostic procedures directed at the underlying cause vary depending on the suspected condition(s). An absolute eosinophil count is not generally needed if the CBC shows marked eosinophilia. The location of the causal factor can be used to classify eosinophilia into two general types: extrinsic, in which the factor lies outside the eosinophil cell lineage; and intrinsic eosinophilia, which denotes etiologies within the eosiniphil cell line. Specific treatments are dictated by the causative condition, though in idiopathic eosinophilia, the disease may be controlled with corticosteroids. Eosinophilia is not a disorder (rather, only a sign) unless it is idiopathic.Informally, blood eosinophil levels are often regarded as mildly elevated at counts of 500–1,500/μL, moderately elevated between 1,500 and 5,000/μL, and severely elevated when greater than 5,000/μL. Elevations in blood eosinophil counts can be transient, sustained, recurrent, or cyclical.Eosinophil counts in human blood normally range between 100 and 500 per/μL. Maintenance of these levels results from a balance between production of eosinophils by bone marrow eosinophil precursor cells termed CFU-Eos and the emigration of circulating eosinophils out of the blood through post-capillary venules into tissues. Eosinophils represent a small percentage of peripheral blood leucocytes (usually less than 8%), have a half-life in the circulation of only 8–18 hours, but persist in tissues for at least several weeks.Eosinophils are one form of terminally differentiated granulocytes; they function to neutralize invading microbes, primarily parasites and helminthes but also certain types of fungi and viruses. They also participate in transplant rejection, Graft-versus-host disease, and the killing of tumor cells. In conducting these functions, eosinophils produce and release on demand a range of toxic reactive oxygen species (e.g. hypobromite, hypobromous acid, superoxide, and peroxide) and they also release on demand a preformed armamentarium of cytokines, chemokines, growth factors, lipid mediators (e.g. leukotrienes, prostaglandins, platelet activating factor), and toxic proteins (e.g. metalloproteinases, major basic protein, eosinophil cationic protein, eosinophil peroxidase, and eosinophil-derived neurotoxin). These agents serve to orchestrate robust immune and inflammatory responses that destroy invading microbes, foreign tissue, and malignant cells. When overproduced and over-activated, which occurs in certain cases of hypereosinophilia and to a lesser extent eosinophilia, eosinophils may misdirect their reactive oxygen species and armamentarium of preformed molecules toward normal tissues. This can result in serious damage to such organs as the lung, heart, kidneys, and brain. Classification Based on their causes, hypereosinophilias can be sorted into subtypes. However, cases of eosinophilia, which exhibit eosinophil counts between 500 and 1,500/μL, may fit the clinical criteria for, and thus be regarded as falling into, one of these hypereosinophilia categories: the cutoff of 1,500/μL between hypereosinophilia and eosinophilia is somewhat arbitrary. There are at least two different guidelines for classifying hypereosinophilia/eosinophilia into subtypes. The General Haematoloy and Haemato-oncology Task Forces for the British Committee for Standards in Haematology classifies these disorders into a) Primary, i.e. caused by abnormalities in the eosinophil cell line; b) Secondary, i.e. caused by non-eosinophil disorders; and c) Idiopathic, cause unknown. The World Health Organization classifies these disorders into a) Myeloid and lymphoid neoplasms with eosinophilia and abnormalities of PDGFRA, PDGFRB, or FGFR1 (i.e. high eosinophil blood counts caused by mutations in the eosinophil cell line of one of these three genes), b) Chronic eosinophilic leukemia, and c) the Idiopathic hypereosinophiic syndrome. In the latter classification, secondary hypereosinophilia/eosinophilia is not viewed as a true disorder of eosinophils. Here these two classifications are merged and expanded to include the many forms of secondary, i.e. reactive hypereosinophilia/eosinophilia, disorders and also includes another subtype, organ-restricted hypereosinophilias, a disorder in which eosinophil-mediated tissue damage is restricted to one organ and is often but not always associated with increased blood eosinophil counts. Primary hypereosinophilia Primary hypereosinophilia is due to the development of a clone of eosinophils, i.e. a group of genetically identical eosinophils derived from a significantly mutated ancestor cell. The clone may prove to be benign, pre-malignant, or overtly malignant. The fundamental driver of these hypereosinophilic (or uncommonly eosinophilic) disorders is the mutation which increases the proliferation, survival, and further mutation of cells descendant from the originally mutated cell. There are several subtypes of primary hypereosinophilia. Clonal hypereosinophilia Clonal hypereosinophilia is hypereosinophilia caused by a pre-malignant or malignant clone of eosinophils that bear mutations in genes for PDGFRA, PDGFRB, or FGFR1 or, alternatively, a chromosome translocation that creates the PCM1-JAK2 fusion gene. These genes code for dysfunctional protein products capable of enhancing proliferation and/or survival of their parent cells which, in consequence, become an evolving and constantly growing clone of eosinophils. These mutations are recognized by the World Health Association as causing distinct entities differing from idiopathic hypereosinophilia and the idiopathic hypereosinophilic syndrome. Presence of these clones may be associated with tissue injury but in any case suggests specific therapy be directed at reducing the size and suppressing the growth of the eosinophil clone. More recently, mutations in other genes have been described as causing a similar type of clonal hypereosinophilia but have not yet been recognized as entities distinct from idiopathic hypereosinophilia and the idiopathic hyperesoniphilic syndrome. These include gene mutations in JAK2, ABL1, and FLT2 and chromosomal translocations that create the ETV6-ACSL6 fusion gene. Chronic eosinophilic leukemia (NOS) Chronic eosinophilic leukemia, not otherwise specified (i.e. CEL, NOS), is a leukemia-inducing disorder in the eosinophil cell lineage that causes eosinophil blood counts greater than 1,500/μL. The most recent (2017) World health organization criteria specifically excludes from this disorder hypereosinophilia/eosinophilia associated with BCR-ABL1 fusion gene-positive chronic myeloid leukemia, polycythemia vera, essential thrombocytosis, primary myelofibrosis, chronic neutrophilic leukemia, chronic myelomonocytic leukemia, atypical chronic myelogenous leukemia, clonal eosinophilias involving gene rearrangements of PDGFRA, PDGFRB, or FGFR1, and chromosome translocations that form PCM1-JAK2, ETV6-JAK2, or BCR-JAK2 fusion genes. For this diagnosis, immature eosinophil (e.g. myeloblast) cell counts in the bone marrow and peripheral blood must be less than 20% and the chromosomal alterations (inv(16)(p13.1q22)) and t(16;16)(p13;q22) as well as other features diagnostic of acute myelogenous leukemia must be absent. The latter diagnostic features include clonal cytogenetic abnormalities and molecular genetic abnormalities diagnostic for other forms of leukemia or the presence of myeloblast counts greater than 55% in bone marrow or 2% in blood. Chronic eosinophilic leukemia may transform into acute eosinophilic or other types of acute myelogenous leukemia. Familial eosinophilia Familial eosinophilia is a rare congenital disorder characterized by the presence of sustained elevations in blood eosinophil levels that reach ranges diagnostic of eosinophilia or, far more commonly, hypereosinophilia. It is an autosomal dominant disorder in which genetic linkage gene mapping family studies localize the gene responsible for it to chromosome 5 at position q31–q33, between markers D5S642 and D5S816. This region contains a cytokine gene cluster which includes three genes whose protein products function in regulating the development and proliferation of eosinophils viz., interleukin 3, interleukin 5, and colony stimulating factor 2. However, no functional sequence genetic polylmophisms are found within the promoter, exons, or introns, of these genes or within the common gene enhancer for interleukin 3 or colony stimulating factor 2. This suggests that the primary defect in familial eosinophilia is not a mutation in one of these genes but rather in another gene within this chromosome area. Clinical manifestations and tissue destruction related to the eosinophilia in this disorder are uncommon: familial eosinophilia typically has a benign phenotype compared to other congenital and acquired eosinophilic diseases. Idiopathic hypereosinophilia Idiopathic hypereosinophilia (also termed hypereosinophilia of undetermined significance, i.e. HEUS) is a disorder characterized by an increase in eosinophil blood counts above 1,500/μL, as detected on at least 2 separate examinations. The disorder cannot be associated with eosinophil-based tissue damage or a primary or secondary cause of eosinophilia. That is, it is a diagnosis of exclusion and has no known cause. Over time, this disorder can resolve into a primary hypereosinophilia, typically clonal hypereosinophilia, chronic eosinphilic leukemia, or an eosinophilia associated with another hematological leukemia. The disorder may also become associated with tissue or organ damage and therefore be diagnosed as the hypereosinophilic syndrome. Idiopathic hypereosinophilia is treated by observation to detect development of the cited more serious disorders. Idiopathic hypereosiophilic syndrome The idiopathic hypereosinophilic syndrome is a disorder characterized by hypereosiophilia that is associated with eosinophil-based tissue or organ damage. While almost any organ or tissue may be damaged, the lung, skin, heart, blood vessels, sinuses, kidneys, and brain are the most commonly affected. The World Health Organization restrict this diagnosis to cases which have no well-defined cause. That is, all cases of secondary (i.e. reactive) eosinophilia (including lymphocyte-variant hypereosinophilia) and primary hypereosinophilia (including chronic eosinophilic leukemia (NOS), clonal eosinophilia, and hypereosinophilia associated with hematological malignancies) are excluded from this diagnosis. Secondary hypereosinophilia Secondary (or reactive) eosinophilias are non-clonal increases in blood eosinophil levels caused by an underlying disease. The pathogenesis of the hypereosinophilia in these diseases is thought to be the release of one or more cytokines (e.g. granulocyte macrophage colony stimulating factor, interleukin 3, interleukin 5) that: a) cause bone marrow precursor cells, i.e. CFU-Eos, to proliferate and mature into eosinophils; b) promote release of bone marrow eosinophils into the circulation, c) stimulate circulating eosinophils to enter tissues and release tissue-injuring agents. These cytokines may be released by the diseased cells or the diseased cells may cause the release of these cytokines by non-diseased cells. Primary disorders associated with and known or presumed to cause hypereosinophilia or eosinophilia are given below. Infections Helminths are common causes of hypereosinophilia and eosinophilia in areas endemic to these parasites. Helminths infections causing increased blood eosinophil counts include: 1) nematodes, (i.e. Angiostrongylus cantonensis and Hookworm infections), ascariasis, strongyloidiasis trichinosis, visceral larva migrans, Gnathostomiasis, cysticercosis, and echinococcosis; 2) filarioidea, i.e. tropical pulmonary eosinophilia, loiasis, and onchocerciasis; and 3) flukes, i.e. schistosomiasis, fascioliasis, clonorchiasis, paragonimiasis, and fasciolopsiasis. Other infections associated with increased eosinophil blood counts include: protozoan infections, i.e. Isospora belli and Dientamoeba fragilis) and sarcocystis); fungal infections (i.e. disseminated histoplasmosis, cryptococcosis [especially in cases with central nervous system involvement]), and coccidioides); and viral infections, i.e. Human T-lymphotropic virus 1 and HIV. Autoimmune diseases Hypereosiophilia or eosinophilia may be associated with the following autoimmune diseases: systemic lupus erythematosus eosinophilic fasciitis, eosinophilic granulomatosis with polyangiitis, dermatomyositis, severe rheumatoid arthritis, progressive systemic sclerosis, Sjögren syndrome, thromboangiitis obliterans, Behçets disease, IgG4-related disease, inflammatory bowel diseases, sarcoidosis, bullous pemphigoid, and dermatitis herpetiformis. Allergic diseases Eosinophilia and comparatively fewer cases of hypereosinophilia are associated with the following known diseases that are known or thought to have an allergic basis: allergic rhinitis, asthma, atopic dermatitis, eosinophilic esophagitis, chronic sinusitis, aspirin-induced asthma, allergic bronchopulmonary aspergillosis, chronic eosinophilic pneumonia, and Kimuras disease.Certain types of food allergy disorders may also be associated with eosinophilia or, less commonly, hypereosinophilia. Allergic eosinophilic esophagitis and the Food protein-induced enterocolitis syndrome are commonly associated with increased blood eosinophil levels. Drugs A wide range of drugs are known to cause hypereosinophilia or eosinophilia accompanied by an array of allergic symptoms. Rarely, these reactions are severe causing, for example, the drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome. Drug- induced hepatitis marked by immunoallergic pathology, which has much bidirectional crossover with DRESS syndrome, is typically accompanied by some severity of eosinophilia. While virtually any drug should be considered as a possible cause of these signs and symptoms, the following drugs and drug classes are some of the most frequently reported causes: penicillins, cephalosporins, dapsone, sulfonamides, carbamazepine, phenytoin, lamotrigine, valproic acid, nevirapine, efavirenz, and ibuprofen. These drugs may cause severely toxic reactions such as the DRESS syndrome. Other drugs and drug classes often reported to cause increased blood eosinophil levels accompanied by less severe (e.g. non-DRESS syndrome) symptoms include tetracyclins, doxycycline, linezolid, nitrofurantoin, metronidazole, carbamazepine, phenobarbital, lamotrigine, valproate, desipramine, amitriptyline, fluoxetine, piroxicam, diclofenac, ACE inhibitors, abacavir, nevirapine, ranitidine, cyclosporin, and hydrochlorothiazide.The toxic oil syndrome is associated with hypereosinophilia/eosinophilia and systemic symptoms due to one or more contaminants in rapeseed oil and the Eosinophilia–myalgia syndrome, also associated with hypereosinophilia, appears due to trace contaminants in certain commercial batches of the amino acid, L-tryptophan.Allergic reactions to drugs are a common cause of eosinophilia, with manifestations ranging from diffuse maculopapular rash, to severe life-threatening drug reactions with eosinophilia and systemic symptoms (DRESS). Drugs that has, allopurinol, nonsteroidal anti-inflammatory drugs (NSAIDs), some antipsychotics such as risperidone, and certain antibiotics. Phenibut, an analogue of the neurotransmitter GABA, has also been implicated in high doses. The reaction which has been shown to be T-cell mediated may also cause eosinophilia-myalgia syndrome. Malignancies Certain malignancies cause a secondary eosinophilia or, less commonly, hypereosinophilia. These increases in blood eosinophils appear due to the release of stimulatory cytokines or invasion of the bone marrow and thereby irritation of resident eosinophils or their precursors. Malignancies associated with these effects include gastric, colorectal, lung, bladder, and thyroid cancers, as well as squamous cell cancers of the cervix, vagina, penis, skin, and nasopharyrnx. Some hematological malignancies are likewise associated with secondary rises in blood eosinophil counts; these include Hodgkin disease, certain T-cell lymphomas, acute myeloid leukemia, the myelodysplastic syndromes, many cases of systemic mastocytosis, chronic myeloid leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, chronic myelomonocytic leukemia, and certain cases of T-lymphoblastic leukemia/lymphoma-associated or myelodysplastic–myeloproliferative syndrome-associated eosinophilias.Hodgkin lymphoma (Hodgkins disease) often elicits severe eosinophilia; however, non-Hodgkin lymphoma and leukemia produce less marked eosinophilia. Of solid tumor neoplasms, ovarian cancer is most likely to provoke eosinophilia, though any other cancer can cause the condition. Solid epithelial cell tumors have been shown to cause both tissue and blood eosinophilia, with some reports indicating that this may be mediated by interleukin production by tumor cells, especially IL-5 or IL-3. This has also been shown to occur in Hodgkin lymphoma, in the form of IL-5 secreted by Reed-Sternberg cells. In primary cutaneous T cell lymphoma, blood and dermal eosinophilia are often seen. Lymphoma cells have also been shown to produce IL-5 in these disorders. Other types of lymphoid malignancies have been associated with eosinophilia, as in lymphoblastic leukemia with a translocation between chromosomes 5 and 14 or alterations in the genes which encode platelet-derived growth factor receptors alpha or beta. Patients displaying eosinophilia overexpress a gene encoding an eosinophil hematopoietin. A translocation between chromosomes 5 and 14 in patients with acute B lymphocytic leukemia resulted in the juxtaposition of the IL-3 gene and the immunoglobulin heavy-chain gene, causing overproduction production of IL-3, leading to blood and tissue eosinophilia. Primary immunodeficiency diseases Primary immunodeficiency diseases are inborn errors in the immune system due to defective genes. Certain of these disorders are sometimes or often associated with hypereosinophilia. The list of such disorders includes ZAP70 deficiency (defective ZAP70 gene), CD3gamma chain deficiency (defective CD3G gene), MCHII deficiency (defective RFXANK gene), Wiskott–Aldrich syndrome (defective WAS gene), IPEX syndrome (defective IPEX gene), CD40 gene defect, and autoimmune lymphoproliferative syndrome (defective Fas receptor gene). More than 30 other primary immunodeficiency diseases are sometimes associated with modest increases in eosinophil counts, i.e. eosinophilia. The hyperimmunoglobulin E syndrome is associated with hypereosinophilia or eosinophilia due to mutations in any one of the following genes: STAT3, DOCK8, PGM3, SPINK5, and TYK2 (see mutations in the hymperimmoglobulin E syndrome). Omenn syndrome is a severe combined immunodeficiency disease characterized by skin rash, slenomegaly, and lymphadenopathy due to a causative mutation in RAG1, RAG2, or, more rarely, one of several other genes. Lymphocyte-variant hypereosinophilia Lymphocyte-variant hypereosinophilia is a disorder attributed to the expansion of a cytokine-producing, aberrant population of a particular T-cell phenotype. The disorder is clonal with regard to the production of abnormal T-cell lymphocytes not eosinophils which appear phenotypically normal. The phenotypically aberrant lymphocytes function abnormally by stimulating the proliferation and maturation of bone marrow eosinophil-precursor cells which in studied cases appears due to their excess production of interleukin 5, interleukin 3, or interleukin 13. The disorder is usually indolent but infrequently progresses to T-cell lymphoma or Sezary syndrome. Accumulation of partial deletions in the short arm of chromosome 6, the long arm of chromosome 10, or the acquirement of an extra chromosome (i.e. trisomy) 7) in T-cells or the proliferation of lymphocytes with the CD3 negative, CD41 positive immunophenotype may occur during the disorders progression to lymphoma. Reports on treatment of the disorder are rare. In on study of 16 lymphocyte-variant hypereosinophilia patients with the aberrant CD3 negative, CD41 positive immunophenotype, good responds to corticosteroid drugs were uniform but 16 ultimately required corticosteroid-sparing agents. Hydroxyurea and imatinib are less likely to have efficacy in this variant of hypereosinophilia than in many cases of clonal eosinophilia or chronic eosinophilic leukemia. Gleichs syndrome Gleichs syndrome, which may be a form of lymphocyte-variant hypereosinophilia, involves hypereosinophilia, elevated blood levels of IgM antibodies, and clonal expansion of T cells. Similar to lymphocyte=variant hypereosinophilia, the increased levels of blood eosinophils in Gleichs syndrome is thought to be secondary to the secretion of eosinophil-stimulating cytokines by a T cell clones. IgG4-related disease IgG4-related disease or Immunoglobulin G4-related disease is a condition dacryoadenitis, sialadenitis, lymphadentitis, and pancreatitis (i.e. inflammation of the lacrimal glands, salivary glands, lymph nodes, and pancreas, respectively) plus retroperitoneal fibrosis. Less commonly, almost any other organ or tissue except joints and brain may be beleaguered by the inflammatory disorder. About 1/3 of cases exhibit eosinophilia or, rarely, hypereosinophilia. This increase in blood eosinophil count is often associated with abnormal T-lymphocyte clones (e.g. increased numbers of CD4 negative, CD7 positive T cells, CD3 negative, CD4 positive T cells, or CD3 positive, CD4 negative, CD8 negative T cells) and is thought to be secondary to these immunological disturbances. The disorder often exhibits are recurrent-relapsing course and is highly responsive to corticosteroids or rituximab as first-line therapy and interferon gamma as second-line therapy. Angiolymphoid hyperplasia with eosinophilia Angiolymphoid hyperplasia with eosinophilia is a disorder initially classified as a form of IgG4-related diseases but now considered a distinct entity. The disorder involves inflamed benign tumors of the vasculature in skin and, less commonly, other tissues. The tumors consist of histiocytoid endothelial cells prominently infiltrated by lymphocytes and eosinophils and is associated with hypereosinophilia or eosinophilia. Cholesterol embolism Transient, fluctuating hypereosinophilia occurs in 60%-80% of individuals with cholesterol embolisms. In this disorder, cholesterol crystals located in an atherosclerotic plaque of a large artery dislodge, travel downstream in the blood, and clog smaller arteries. This results in obstructive damage to multiple organs and tissues. Affected tissues exhibit acute inflammation involving eosinophils, neutrophils, monocytes, lymphocytes, and plasma cells. The cause for this hypereosinophilic response is not known. Adrenal insufficiency A class of steroid hormones secreted by the adrenal gland, glucocorticoids, inhibit eosinophil proliferation and survival. In adrenal insufficiency, low levels of these hormones allow increased eosinophil proliferation and survival. This leads to increases in blood eosinophil levels, typically eosinophilia and, less commonly, hypereosinophilia. Organ-restricted hypereosinophilias Hypereosinophilia may occur in the setting of damage to a single specific organ due to a massive infiltration by eosinophils. This disorder is sub-classified based on the organ involved and is not considered to be a form of primary hypereosinophilia, secondary hypereosinophilia, or the idiopathic hypereosinophilic syndrome because: a) the eosinophils associated with the disorder have not been shown to be clonal in nature; b) a reason for the increase in blood eosinophils has not been determined; c) organ damage has not been shown to be due to eosinophils; and d) the disorder in each individual case typically is limited to the affected organ. Examples of organ-restricted hypereosinophilia include eosinophilic myocarditis, eosinophilic esophagitis, eosinophilic gastroenteritis, eosinophilic cystitis, eosinophilic pneumonia, eosinophilic fasciitis, eosinophilic folliculitis, eosinophilic cellulitis, eosinophilic vasculitis, and eosinophilic ulcer of the oral mucosa. Other examples of organ-restricted hepereosinophilia include those involving the heart, kidney, liver, colon, pulmonary pleurae, peritoneum, fat tissue, myometrium, and synovia. Pathophysiology IgE-mediated eosinophil production is induced by compounds released by basophils and mast cells, including eosinophil chemotactic factor of anaphylaxis, leukotriene B4 and serotonin mediated release of eosinophil granules occur, complement complex (C5-C6-C7), interleukin 5, and histamine (though this has a narrow range of concentration).Harm resulting from untreated eosinophilia potentially varies with cause. During an allergic reaction, the release of histamine from mast cells causes vasodilation which allows eosinophils to migrate from the blood and localize in affected tissues. Accumulation of eosinoph
Eosinophilia	ils in tissues can be significantly damaging. Eosinophils, like other granulocytes, contain granules (or sacs) filled with digestive enzymes and cytotoxic proteins which under normal conditions are used to destroy parasites but in eosinophilia these agents can damage healthy tissues. In addition to these agents, the granules in eosinophils also contain inflammatory molecules and cytokines which can recruit more eosinophils and other inflammatory cells to the area and hence amplify and perpetuate the damage. This process is generally accepted to be the major inflammatory process in the pathophysiology of atopic or allergic asthma. Diagnosis Diagnosis is by complete blood count (CBC). However, in some cases, a more accurate absolute eosinophil count may be needed. Medical history is taken, with emphasis on travel, allergies and drug use. Specific test for causative conditions are performed, often including chest x-ray, urinalysis, liver and kidney function tests, and serologic tests for parasitic and connective tissue diseases. The stool is often examined for traces of parasites (i.e. eggs, larvae, etc.) though a negative test does not rule out parasitic infection; for example, trichinosis requires a muscle biopsy. Elevated serum B12 or low white blood cell alkaline phosphatase, or leukocytic abnormalities in a peripheral smear indicates a disorder of myeloproliferation. In cases of idiopathic eosinophilia, the patient is followed for complications. A brief trial of corticosteroids can be diagnostic for allergic causes, as the eosinophilia should resolve with suppression of the immune over-response. Neoplastic disorders are diagnosed through the usual methods, such as bone marrow aspiration and biopsy for the leukemias, MRI/CT to look for solid tumors, and tests for serum LDH and other tumor markers. Treatment Treatment is directed toward the underlying cause. However, in primary eosinophilia, or if the eosinophil count must be lowered, corticosteroids such as prednisone may be used. However, immune suppression, the mechanism of action of corticosteroids, can be fatal in patients with parasitosis. List of causes Eosinophilia can be idiopathic (primary) or, more commonly, secondary to another disease. In the Western World, allergic or atopic diseases are the most common causes, especially those of the respiratory or integumentary systems. In the developing world, parasites are the most common cause. A parasitic infection of nearly any bodily tissue can cause eosinophilia. Diseases that feature eosinophilia as a sign include: Allergic disorders Asthma Hay fever Drug allergies Allergic skin diseasesPemphigus Dermatitis herpetiformis IgG4-related disease Parasitic infections Addisons disease and stress-induced suppression of adrenal gland function Some forms of malignancy Acute lymphoblastic leukemia Chronic myelogenous leukemia Eosinophilic leukemia Clonal eosinophilia Hodgkin lymphoma Some forms of non-Hodgkin lymphoma Lymphocyte-variant hypereosinophilia Systemic mastocytosis Systemic autoimmune diseasesSystemic lupus erythematosus Kimura disease Eosinophilic granulomatosis with polyangiitis Eosinophilic fasciitis Eosinophilic myositis Eosinophilic myocarditis Eosinophilic esophagitis Eosinophilic gastroenteritis Cholesterol embolism (transiently) Coccidioidomycosis (Valley fever), a fungal disease prominent in the US Southwest. Human immunodeficiency virus infection Interstitial nephropathy Hyperimmunoglobulin E syndrome, an immune disorder characterized by high levels of serum IgE Idiopathic hypereosinophilic syndrome. Congenital disorders Hyperimmunoglobulin E syndrome Omenn syndrome Familial eosinophilia See also Eosinophilia-myalgia syndrome References External links Hypereosinophilic Syndrome research in UK Hypereosinophilic Syndrome on patient.info Hypereosinophilic Syndrome on eMedicine Hypereosinophilic Syndrome (HES) on American Academy of Allergy, Asthma & Immunology Hypereosinophilic syndrome on Mayo Clinic
Amniotic fluid embolism	An amniotic fluid embolism (AFE) is a very uncommon childbirth (obstetric) emergency in which amniotic fluid enters the blood stream of the mother, triggering a serious reaction, which results in cardiorespiratory (heart and lung) collapse and massive bleeding (coagulopathy). The rate at which it occurs is 1 instance per 20,000 births and it comprises 10% of all maternal deaths. This condition is unpredictable and no risk factors have been verified. Signs and symptoms Amniotic fluid embolism is suspected when a woman giving birth experiences very sudden insufficient oxygen to body tissues, low blood pressure, and profuse bleeding due to defects in blood coagulation. Though symptoms and signs can be profound, they also can be entirely absent. There is much variation in how each instance progresses. Causes AFE is very rare and complex. The disorder occurs during the last stages of labor when amniotic fluid enters the circulatory system of the mother via tears in the placental membrane or uterine vein rupture. Upon later analysis, fetal cells are found in the maternal circulation. When the fetal cells and amniotic fluid enter the bloodstream, reactions occur that cause severe changes in the mechanisms that affect blood clotting. Disseminated intravascular coagulation occurs and results in serious bleeding. The condition can also develop after elective abortion, amniocentesis, cesarean delivery, or trauma. Small lacerations in the lower reproductive tract are associated with AFE.According to one study, induction of labor may double the risk of AFE. However, other studies have refuted this claim. A maternal age of 35 years or older is associated with AFE. Diagnosis AFE is diagnosed when all other causes have been excluded. The presence of fetal squamous cells or other fetal tissues, including meconium, have been found in the maternal circulation after the event. Diagnosis is also based upon the signs and symptoms observed during the birth or procedures. Treatment A case report on Amniotic Fluid Embolism published in the A & A Practice Journal in 2020 has revealed that when milrinone is administered as an aerosol, selective pulmonary vasodilation occurs without significant changes in mean arterial pressure or systemic vascular resistance; and if used immediately after Amniotic Fluid Embolism, inhaled milrinone may mitigate the pulmonary vasoconstriction.However, since the circumstances that lead to this complication are difficult to influence, treatment to resolve the symptoms and deteriorating vascular conditions can improve outcomes. Epidemiology Amniotic fluid embolism is very uncommon and the rate at which it occurs is 1 instance per 20,000 births. Though rare, it comprises 10% of all maternal deaths. History This rare complication has been recorded seventeen times prior to 1950. The complication was originally described in 1926 by J. R. Meyer at the University of Sao Paulo. A 1941 case study of eight autopsies of pregnant women who died suddenly during childbirth by Clarence Lushbaugh and Paul Steiner enabled widespread recognition of the diagnosis within the medical community, and was eventually republished as a landmark paper in the Journal of the American Medical Association. References == External links ==
Bells palsy	Bells palsy is a type of facial paralysis that results in a temporary inability to control the facial muscles on the affected side of the face. In most cases, the weakness is temporary and significantly improves over weeks. Symptoms can vary from mild to severe. They may include muscle twitching, weakness, or total loss of the ability to move one or, in rare cases, both sides of the face. Other symptoms include drooping of the eyelid, a change in taste, and pain around the ear. Typically symptoms come on over 48 hours. Bells palsy can trigger an increased sensitivity to sound known as hyperacusis.The cause of Bells palsy is unknown and it can occur in any age. Risk factors include diabetes, a recent upper respiratory tract infection, and pregnancy. It results from a dysfunction of cranial nerve VII (the facial nerve). Many believe that this is due to a viral infection that results in swelling. Diagnosis is based on a persons appearance and ruling out other possible causes. Other conditions that can cause facial weakness include brain tumor, stroke, Ramsay Hunt syndrome type 2, myasthenia gravis, and Lyme disease.The condition normally gets better by itself, with most achieving normal or near-normal function. Corticosteroids have been found to improve outcomes, while antiviral medications may be of a small additional benefit. The eye should be protected from drying up with the use of eye drops or an eyepatch. Surgery is generally not recommended. Often signs of improvement begin within 14 days, with complete recovery within six months. A few may not recover completely or have a recurrence of symptoms.Bells palsy is the most common cause of one-sided facial nerve paralysis (70%). It occurs in 1 to 4 per 10,000 people per year. About 1.5% of people are affected at some point in their lives. It most commonly occurs in people between ages 15 and 60. Males and females are affected equally. It is named after Scottish surgeon Charles Bell (1774–1842), who first described the connection of the facial nerve to the condition. Signs and symptoms Bells palsy is characterized by a one-sided facial droop that comes on within 72 hours. In rare cases (<1%), it can occur on both sides resulting in total facial paralysis.The facial nerve controls a number of functions, such as blinking and closing the eyes, smiling, frowning, lacrimation, salivation, flaring nostrils and raising eyebrows. It also carries taste sensations from the anterior two-thirds of the tongue, through the chorda tympani nerve (a branch of the facial nerve). Because of this, people with Bells palsy may present with loss of taste sensation in the anterior 2⁄3 of the tongue on the affected side.Although the facial nerve innervates the stapedius muscle of the middle ear (through the tympanic branch), sound sensitivity, causing normal sounds to be perceived as very loud (hyperacusis), and dysacusis are possible but hardly ever clinically evident.Although defined as a mononeuritis (involving only one nerve), people diagnosed with Bells palsy may have "myriad neurological symptoms" including "facial tingling, moderate or severe headache/neck pain, memory problems, balance problems, ipsilateral limb paresthesias, ipsilateral limb weakness, and a sense of clumsiness" that are "unexplained by facial nerve dysfunction". Cause The cause of Bells palsy is unknown. Risk factors include diabetes, a recent upper respiratory tract infection, and pregnancy.Some viruses are thought to establish a persistent (or latent) infection without symptoms, e.g., the varicella zoster virus and the Epstein–Barr virus, both of the herpes family. Reactivation of an existing (dormant) viral infection has been suggested as a cause of acute Bells palsy. As the facial nerve swells and becomes inflamed in reaction to the infection, it causes pressure within the Fallopian canal, resulting in the restriction of blood and oxygen to the nerve cells. Other viruses and bacteria that have been linked to the development of Bells palsy include HIV, sarcoidosis and Lyme Disease. This new activation could be triggered by trauma, environmental factors, and metabolic or emotional disorders.Familial inheritance has been found in 4–14% of cases. There may also be an association with migraines.In December 2020, the U.S. FDA recommended that recipients of the Pfizer and Moderna COVID-19 vaccines should be monitored for symptoms of Bells palsy after several cases were reported among clinical trial participants, though the data were not sufficient to determine a causal link. Genetics A meta-analysis of genome-wide association study (GWAS) identified the first unequivocal association with Bells palsy. Pathophysiology Bells palsy is the result of a malfunction of the facial nerve (cranial nerve VII), which controls the muscles of the face. Facial palsy is typified by inability to move the muscles of facial expression. The paralysis is of the infranuclear/lower motor neuron type. It is thought that as a result of inflammation of the facial nerve, pressure is produced on the nerve where it exits the skull within its bony canal (the stylomastoid foramen), blocking the transmission of neural signals or damaging the nerve. Patients with facial palsy for which an underlying cause can be found are not considered to have Bells palsy per se. Possible causes of facial paralysis include tumor, meningitis, stroke, diabetes mellitus, head trauma and inflammatory diseases of the cranial nerves (sarcoidosis, brucellosis, etc.). In these conditions, the neurologic findings are rarely restricted to the facial nerve. Babies can be born with facial palsy. In a few cases, bilateral facial palsy has been associated with acute HIV infection. In some research, the herpes simplex virus type 1 (HSV-1) has been identified in a majority of cases diagnosed as Bells palsy through endoneurial fluid sampling. Other research, however, identified, out of a total of 176 cases diagnosed as Bells palsy, HSV-1 in 31 cases (18%) and herpes zoster in 45 cases (26%).In addition, HSV-1 infection is associated with demyelination of nerves. This nerve damage mechanism is different from the above-mentioned—that edema, swelling and compression of the nerve in the narrow bone canal is responsible for nerve damage. Demyelination may not even be directly caused by the virus, but by an unknown immune response. Diagnosis Bells palsy is a diagnosis of exclusion, meaning it is diagnosed by elimination of other reasonable possibilities. By definition, no specific cause can be determined. There are no routine lab or imaging tests required to make the diagnosis. The degree of nerve damage can be assessed using the House-Brackmann score. One study found that 45% of patients are not referred to a specialist, which suggests that Bells palsy is considered by physicians to be a straightforward diagnosis that is easy to manage.Other conditions that can cause similar symptoms include herpes zoster, Lyme disease, sarcoidosis, stroke, and brain tumors. Differential diagnosis Once the facial paralysis sets in, many people may mistake it as a symptom of a stroke; however, there are a few subtle differences. A stroke will usually cause a few additional symptoms, such as numbness or weakness in the arms and legs. And unlike Bells palsy, a stroke will usually let patients control the upper part of their faces. A person with a stroke will usually have some wrinkling of their forehead.In areas where Lyme disease is common, it accounts for about 25% of cases of facial palsy. In the U.S., Lyme is most common in the New England and Mid-Atlantic states and parts of Wisconsin and Minnesota. The first sign of about 80% of Lyme infections, typically one or two weeks after a tick bite, is usually an expanding rash that may be accompanied by headaches, body aches, fatigue, or fever. In up to 10–15% of Lyme infections, facial palsy appears several weeks later, and may be the first sign of infection that is noticed as the Lyme rash typically does not itch and is not painful. The likelihood that the facial palsy is caused by Lyme disease should be estimated, based on recent history of outdoor activities in likely tick habitats during warmer months, recent history of rash or symptoms such as headache and fever, and whether the palsy affects both sides of the face (much more common in Lyme than in Bells palsy). If that likelihood is more than negligible, a serological test for Lyme disease should be performed, and if it exceeds 10%, empiric therapy with antibiotics should be initiated, without corticosteroids, and reevaluated upon completion of laboratory tests for Lyme disease. Corticosteroids have been found to harm outcomes for facial palsy caused by Lyme disease.One disease that may be difficult to exclude in the differential diagnosis is involvement of the facial nerve in infections with the herpes zoster virus. The major differences in this condition are the presence of small blisters, or vesicles, on the external ear, significant pain in the jaw, ear face, and/or neck and hearing disturbances, but these findings may occasionally be lacking (zoster sine herpete). Reactivation of existing herpes zoster infection leading to facial paralysis in a Bells palsy type pattern is known as Ramsay Hunt syndrome type 2. The prognosis for Bells palsy patients is generally much better than for Ramsay Hunt syndrome type 2 patients. Treatment Steroids have been shown to be effective at improving recovery in Bells palsy while antivirals have not. In those who are unable to close their eyes, eye protective measures are required. Management during pregnancy is similar to management in the non-pregnant. Steroids Corticosteroids such as prednisone improve recovery at 6 months and are thus recommended. Early treatment (within 3 days after the onset) is necessary for benefit with a 14% greater probability of recovery. Antivirals One review found that antivirals (such as aciclovir) are ineffective in improving recovery from Bells palsy beyond steroids alone in mild to moderate disease. Another review found a benefit when combined with corticosteroids but stated the evidence was not very good to support this conclusion.In severe disease it is also unclear. One 2015 review found no effect regardless of severity. Another review found a small benefit when added to steroids.They are commonly prescribed due to a theoretical link between Bells palsy and the herpes simplex and varicella zoster virus. There is still the possibility that they might result in a benefit less than 7% as this has not been ruled out. Eye protection When Bells palsy affects the blink reflex and stops the eye from closing completely, frequent use of tear-like eye drops or eye ointments is recommended during the day and protecting the eyes with patches or taping them shut is recommended for sleep and rest periods. Physiotherapy Physiotherapy can be beneficial to some individuals with Bells palsy as it helps to maintain muscle tone of the affected facial muscles and stimulate the facial nerve. It is important that muscle re-education exercises and soft tissue techniques be implemented prior to recovery in order to help prevent permanent contractures of the paralyzed facial muscles. To reduce pain, heat can be applied to the affected side of the face. There is no high quality evidence to support the role of electrical stimulation for Bells palsy. Surgery Surgery may be able to improve outcomes in facial nerve palsy that has not recovered. A number of different techniques exist. Smile surgery or smile reconstruction is a surgical procedure that may restore the smile for people with facial nerve paralysis. Adverse effects include hearing loss which occurs in 3–15% of people. A Cochrane review (updated in 2021), after reviewing applicable randomized and quasi-randomized controlled trials was unable to determine if early surgery is beneficial or harmful. As of 2007 the American Academy of Neurology did not recommend surgical decompression. Alternative medicine The efficacy of acupuncture remains unknown because the available studies are of low quality (poor primary study design or inadequate reporting practices). There is very tentative evidence for hyperbaric oxygen therapy in severe disease. Prognosis Most people with Bells palsy start to regain normal facial function within 3 weeks—even those who do not receive treatment. In a 1982 study, when no treatment was available, of 1,011 patients, 85% showed first signs of recovery within 3 weeks after onset. For the other 15%, recovery occurred 3–6 months later. After a follow-up of at least one year or until restoration, complete recovery had occurred in more than two-thirds (71%) of all patients. Recovery was judged moderate in 12% and poor in only 4% of patients. Another study found that incomplete palsies disappear entirely, nearly always in the course of one month. The patients who regain movement within the first two weeks nearly always remit entirely. When remission does not occur until the third week or later, a significantly greater part of the patients develop sequelae. A third study found a better prognosis for young patients, aged below 10 years old, while the patients over 61 years old presented a worse prognosis.Major possible complications of the condition are chronic loss of taste (ageusia), chronic facial spasm, facial pain and corneal infections. Another complication can occur in case of incomplete or erroneous regeneration of the damaged facial nerve. The nerve can be thought of as a bundle of smaller individual nerve connections that branch out to their proper destinations. During regrowth, nerves are generally able to track the original path to the right destination—but some nerves may sidetrack leading to a condition known as synkinesis. For instance, regrowth of nerves controlling muscles attached to the eye may sidetrack and also regrow connections reaching the muscles of the mouth. In this way, movement of one also affects the other. For example, when the person closes the eye, the corner of the mouth lifts involuntarily. Around 9% of people have some sort of ongoing problems after Bells palsy, typically the synkinesis already discussed, or spasm, contracture, tinnitus or hearing loss during facial movement or crocodile-tear syndrome. This is also called gustatolacrimal reflex or Bogorads syndrome and results in shedding tears while eating. This is thought to be due to faulty regeneration of the facial nerve, a branch of which controls the lacrimal and salivary glands. Gustatorial sweating can also occur. Epidemiology The number of new cases of Bells palsy ranges from about one to four cases per 10,000 population per year. The rate increases with age. Bells palsy affects about 40,000 people in the United States every year. It affects approximately 1 person in 65 during a lifetime. A range of annual incidence rates have been reported in the literature: 15, 24, and 25–53 (all rates per 100,000 population per year). Bells palsy is not a reportable disease, and there are no established registries for people with this diagnosis, which complicates precise estimation. Frequency About 40,000 people are affected by Bells Palsy in the United States every year. It can affect anyone of any gender and age, but its incidence seems to be highest in those in the 15- to 45-year-old age group. History The Persian physician Muhammad ibn Zakariya al-Razi (865–925) detailed the first known description of peripheral and central facial palsy.Cornelis Stalpart van der Wiel (1620–1702) in 1683 gave an account of Bells palsy and credited the Persian physician Ibn Sina (980–1037) for describing this condition before him. James Douglas (1675–1742) and Nicolaus Anton Friedreich (1761–1836) also described it. Scottish neurophysiologist Sir Charles Bell read his paper to the Royal Society of London on July 12, 1821, describing the role of the facial nerve. He became the first to detail the neuroanatomical basis of facial paralysis. Since then, idiopathic peripheral facial paralysis has been referred to as Bells palsy, named after him.A notable person with Bells palsy is former Prime Minister of Canada Jean Chrétien. During the 1993 Canadian federal election, Chrétiens first as leader of the Liberal Party of Canada, the opposition Progressive Conservative Party of Canada ran an attack ad in which voice actors criticized him over images that seemed to highlight his abnormal facial expressions. The ad was interpreted as an attack on Chrétiens physical appearance and garnered widespread anger among the public, while Chrétien used the ad to make himself more sympathetic to voters. The ad had the adverse effect of increasing Chrétiens lead in the polls and the subsequent backlash clinched the election for the Liberals, which the party won in a landslide. References External links Bells palsy at Curlie
Toxic leukoencephalopathy	Toxic leukoencephalopathy is a rare condition that is characterized by progressive damage (-pathy) to white matter (-leuko-) in the brain (-encephalo-), particularly myelin, due to causes such as exposure to substance use, environmental toxins, or chemotherapeutic drugs. The prevalence of this disease is infrequent and often goes unreported, especially in cases resulting from substance use. Magnetic resonance imaging (MRI) is a popular method to study and diagnose the disease. However, even with technological advances, the exact mechanism and underlying pathophysiology of toxic leukoencephalopathy remains unknown and is thought to vary between sources of toxicity. The clinical severity of toxic leukoencephalopathy also varies among patients, exposure time, concentration, and purity of the toxic agent. Some reversibility of the condition has been seen in many cases when the toxic agent is removed. Signs and symptoms Symptoms vary widely between sources of toxicity, dosage, length of time patient was exposed to the toxic substance, patient history, and patient genetics. Especially in the case of leukoencephalopathy developing due to substance use or environmental toxins, symptoms typically do not develop until several days to months after exposure to the pharmacological agent. Clinical features range from inattention, forgetfulness, and changes in personality to dementia, coma, and even death. Obvious signs of the condition are difficulty with cognitive function and equilibrioception. Common initial symptoms include confusion, somnolence, generalized seizures, headaches, and vision impairment.Young acute lymphoblastic leukemia patients with methotrexate-induced leukoencephalopathy appear asymptomatic. However, toxic leukoencephalopathy induced by substance use or environmental toxins have had more damaging side effects. Heroin-induced leukoencephalopathy has had three stages described. The first stage features soft (pseudobulbar) speech, cerebellar ataxia, motor restlessness, and apathy/bradyphrenia. The intermediate stage includes pyramidal tract and pseudobulbar signs, spastic paresis, myoclonic jerks, and choreoathetoid movements. The final or terminal stage is characterized by stretching spasms, akinetic mutism, hypotonic paresis, central pyrexia, and death. Similarly, leukoencephalopathy induced by orally administered methotrexate for arthritis patients presents similar symptoms including ataxia, dysarthria, and seizures; however, long-term cognitive effects remain unknown. Symptoms of leukoencephalopathy caused by overdose of metronidazole medication include dysarthria, gait disturbance, weakness of extremities, and mental confusion. Despite the pharmacological agent or source of toxicity, some patients completely recover from toxic leukoencephalopathy. Related disorders Posterior reversible encephalopathy syndrome (PRES) can also result from medication toxicity. Symptoms similar to those of leukoencephalopathy patients have been seen in PRES patients. However, the prognosis of toxic leukoencephalopathy is typically slightly worse than that of PRES because toxic leukoencephalopathy is more likely to lead to ataxia, dementia, or coma.Hypoglycemic encephalopathy is often seen in diabetics as a result to accidental overdose with the long-acting sulfonylurea drug group. Brain regions affected by toxic leukoencephalopathy have been seen to be affected by this disease as well; however, hypoglycaemic encephalopathy has been known to involve both white and grey matter abnormalities. Causes Various pharmacological agents have been known to cause toxic leukoencephalopathy. The most common causes are substance use and chemotherapy; however, the disease has also occurred on the rare occasion as a side effect of certain medications and environmental toxins. Substance use Leukoencephalopathy may result from the inhalation, intravenous injection, or ingestion of addictive substances. However, such occurrences are rare, sporadic, and often go undocumented. Leukoencephalopathy caused by inhalation of heroin, also known as "chasing the dragon" syndrome, is one of the most studied of these rare occurrences and has even been recognized for over twenty five years.It is believed by some researchers that heroin-induced leukoencephalopathy may be caused by a contaminant, or “cutting agent,” in the heroin. However, no such agent has been identified; and indeed, toxic leukoencephalopathy has been observed as a result of intoxication with contaminant-free opiates. Cases include a 65-year-old woman who had mistakenly been taking three times the dose of methadone that had been prescribed for pain management, and a young girl intoxicated with pure morphine sulfate tablets.Other drugs that have been associated with toxic leukoencephalopathy in much more rare occurrences include psychoactive drug 2C-E ("Europa"), oxycodone, cocaine, and methadone. The dose–response relationship for these substances remains unclear. Chemotherapy Various chemotherapy drugs have shown increased risk of cancer patients developing leukoencephalopathy. High doses of intravenous methotrexate, or intrathecal (injection into the spinal fluid) methotrexate are both necessary components of chemotherapy for acute lymphoblastic leukemia. However, these are known to cause asymptomatic leukoencephalopathy in children and young adults. Methotrexate-related leukoencephalopathy prevalence has been reported to decline with time and dosage. Other chemotherapeutic agents that have induced neurotoxicity include 5-fluorouracil and fludarabine. Medication neurotoxicity Besides its role in chemotherapy, methotrexate is also used as an orally administered treatment for rheumatoid arthritis. Leukoencephalopathy can develop from long-term treatment of methotrexate even at low doses. In contrast to intravenous methotrexate for cancer patients, leukoencephalopathy induced by orally taken methotrexate may be associated with cognitive dysfunction and even death.Oxycodone is the main active ingredient in various oral pain relief medications. High doses of opiates such as oxycodone can lead to leukoencephalopathy. The activity of various opioid and nociceptive receptors appear to play a role in the disease; however, the exact mechanism remains unknown.Metronidazole, an antibiotic used to treat anaerobic and protozoal infections, has been known at high doses to produce neurologic symptoms associated with toxic leukoencephalopathy. Other Toxic leukoencephalopathy may also result from carbon monoxide poisoning, ingestion of methanol, ingestion of ethylene, toluene toxicity, ethanol poisoning, ingestion of methylenedioxymethamphetamine (MDMA or "ecstasy"), or ingestion of paradichlorobenzene, which is a toxic agent in mothballs. Diagnosis Due to advances in MRI, this neurological disorder has been characterized more successfully in more recent years. MRI can aid in the detection of injured brain tissue; however, the severity and extent of the damage demonstrated by imaging does not always reflect patient clinical status. Toxic leukoencephalopathy encompasses the degeneration of white matter tracts devoted to higher cerebral function; however, white matter can appear normal until the disease has progressed more intensely. Toxic leukoencephalopathy-related damage to central nervous system (CNS) white matter, typically of the periventricular nucleus, and other structures in the brain is often bilateral and symmetric. Heroin-induced leukoencephalopathy often involves damage to cerebellar white matter, posterior cerebral white matter, posterior limb of internal capsule, and cerebellar peduncles. The occipital lobe is typically most affected though the frontal, parietal, and temporal lobes have shown involvement as well. Other toxins have been shown to extend damage to other structures of the brain, including the hippocampus, dorsal medulla, and brainstem. Treatment With such a wide array of causes and unclear understanding of the pathophysiology, there is no known cure or treatment for the disease. In some cases of leukoencephalopathy induced by medications, such as methotrexate and metronidazole, the disease will reduce gradually once the medication is no longer distributed to the patient. Depending on the source of toxicity or pharmacological substance and severity of the white matter damage, many patients can have complete clinical recovery.Coenzyme Q and vitamin supplements, typically vitamin C and vitamin E, and other antioxidant therapies have been suggested to treat heroin-induced leukoencephalopathy patients. However, such treatments have rarely been trialed. See also Leukoencephalopathy References Further reading Hill MD, Cooper PW, Perry JR (January 2000). "Chasing the dragon – neurological toxicity associated with inhalation of heroin vapour: case report". CMAJ. 162 (2): 236–8. PMC 1232277. PMID 10674060.
Colitis	Colitis is an inflammation of the colon. Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label colitis (without qualification) is used if: The cause of the inflammation in the colon is undetermined; for example, colitis may be applied to Crohns disease at a time when the diagnosis is unknown, or The context is clear; for example, an individual with ulcerative colitis is talking about their disease with a physician who knows the diagnosis. Signs and symptoms The signs and symptoms of colitis are quite variable and dependent on the cause of the given colitis and factors that modify its course and severity.Common symptoms of colitis may include: mild to severe abdominal pains and tenderness (depending on the stage of the disease), persistent hemorrhagic diarrhea with pus either present or absent in the stools, fecal incontinence, flatulence, fatigue, loss of appetite and unexplained weight loss.More severe symptoms may include: shortness of breath, a fast or irregular heartbeat and fever.Other less common or rare non-specific symptoms that may accompany colitis include: arthritis, mouth ulcers, painful, red and swollen skin and irritated, bloodshot eyes.Signs seen on colonoscopy include: colonic mucosal erythema (redness of the colons inner surface), ulcerations and hemorrhage. Diagnosis Symptoms suggestive of colitis are worked-up by obtaining the medical history, a physical examination and laboratory tests (CBC, electrolytes, stool culture and sensitivity, stool ova and parasites et cetera). Additional tests may include medical imaging (e.g. abdominal computed tomography, abdominal X-rays) and an examination with a camera inserted into the rectum (sigmoidoscopy, colonoscopy).An important investigation in the assessment of colitis is biopsy. A very small piece of tissue (usually about 2mm) is removed from the bowel mucosa during endoscopy and examined under the microscope by a histopathologist. It can provide important information regarding the cause of the disease and the extent of bowel damage. Types There are many types of colitis. They are usually classified by the cause. Types of colitis include: Autoimmune Inflammatory bowel disease (IBD) – a group of chronic colitides. Ulcerative colitis (UC) – a chronic colitis that affects the large intestine. Crohns disease (CD) – another type of IBD that often leads to colitis. Unknown Microscopic colitis – a colitis diagnosed by microscopic examination of colonic tissue; macroscopically ("to the eye") it appears normal. Lymphocytic colitis Collagenous colitis Treatment-caused Diversion colitis Chemical colitis Chemotherapy-induced colitis Radiation colitis Checkpoint inhibitor induced colitis Vascular disease Ischemic colitis Infectious Infectious colitisA subtype of infectious colitis is Clostridioides difficile colitis, which is informally abbreviated as "C-diff colitis". It classically forms pseudomembranes and is often referred to as pseudomembranous colitis, which is its (nonspecific) histomorphologic description. Enterohemorrhagic colitis may be caused by Shiga toxin in Shigella dysenteriae or Shigatoxigenic group of Escherichia coli (STEC), which includes serotype O157:H7 and other enterohemorrhagic E. coli.Parasitic infections, like those caused by Entamoeba histolytica, can also cause colitis. Unclassifiable colitides Indeterminate colitis is the classification for colitis that has features of both Crohns disease and ulcerative colitis. Indeterminate colitis behaviour is usually closer to ulcerative colitis than Crohns disease.Atypical colitis is a phrase that is occasionally used by physicians for a colitis that does not conform to criteria for accepted types of colitis. It is not an accepted diagnosis per se and, as such, a colitis that cannot be definitively classified. Treatment Some people may be admitted into the hospital following the colonoscopy depending on results. It is sometimes necessary to get the patient started on a steroid to speed up the healing of the colon. It may also be necessary to get the patient hydrated from the fluid loss and iron replaced from the loss of blood. After a hospital stay, the patient may be put on a daily medication to manage their chronic colitis. The medication can be an anti-inflammatory or an immunosuppressant. There are many different types of medication used and the doctor will prescribe the one they see fit. If the patient doesnt respond, new medications will be tried until there is a good fit.Moreover, several studies recently have found significant relationship between colitis and dairy allergy (including: cow milk, cow milk UHT and casein), suggesting some patients may benefit from an elimination diet. Research In the lab, the CRISPR-Cas systems effectively killed C. difficile bacteria. Researchers tested this approach in mice infected with C. difficile. Two days after the CRISPR treatment, the mice showed reduced C. difficile levels. Next steps include retooling the phage to prevent C. difficile from returning after the initial effective killing. References == External links ==
Ascending cholangitis	Ascending cholangitis, also known as acute cholangitis or simply cholangitis, is inflammation of the bile duct, usually caused by bacteria ascending from its junction with the duodenum (first part of the small intestine). It tends to occur if the bile duct is already partially obstructed by gallstones.Cholangitis can be life-threatening, and is regarded as a medical emergency. Characteristic symptoms include yellow discoloration of the skin or whites of the eyes, fever, abdominal pain, and in severe cases, low blood pressure and confusion. Initial treatment is with intravenous fluids and antibiotics, but there is often an underlying problem (such as gallstones or narrowing in the bile duct) for which further tests and treatments may be necessary, usually in the form of endoscopy to relieve obstruction of the bile duct. The word is from Greek chol-, bile + ang-, vessel + -itis, inflammation. Signs and symptoms A person with cholangitis may complain of abdominal pain (particularly in the right upper quadrant of the abdomen), fever, rigors (uncontrollable shaking) and a feeling of uneasiness (malaise). Some may report jaundice (yellow discoloration of the skin and the whites of the eyes).Physical examination findings typically include jaundice and right upper quadrant tenderness. Charcots triad is a set of three common findings in cholangitis: abdominal pain, jaundice, and fever. This was assumed in the past to be present in 50–70% of cases, although more recently the frequency has been reported as 15–20%. Reynolds pentad includes the findings of Charcots triad with the presence of septic shock and mental confusion. This combination of symptoms indicates worsening of the condition and the development of sepsis, and is seen less commonly still.In the elderly, the presentation may be atypical; they may directly collapse due to sepsis without first showing typical features. Those with an indwelling stent in the bile duct (see below) may not develop jaundice. Causes Bile duct obstruction, which is usually present in acute cholangitis, is generally due to gallstones. 10–30% of cases, however, are due to other causes such as benign stricturing (narrowing of the bile duct without an underlying tumor), postoperative damage or an altered structure of the bile ducts such as narrowing at the site of an anastomosis (surgical connection), various tumors (cancer of the bile duct, gallbladder cancer, cancer of the ampulla of Vater, pancreatic cancer, cancer of the duodenum), anaerobic organisms such as Clostridium and Bacteroides (especially in the elderly and those who have undergone previous surgery of the biliary system).Parasites which may infect the liver and bile ducts may cause cholangitis; these include the roundworm Ascaris lumbricoides and the liver flukes Clonorchis sinensis, Opisthorchis viverrini and Opisthorchis felineus. In people with AIDS, a large number of opportunistic organisms has been known to cause AIDS cholangiopathy, but the risk has rapidly diminished since the introduction of effective AIDS treatment. Cholangitis may also complicate medical procedures involving the bile duct, especially ERCP. To prevent this, it is recommended that those undergoing ERCP for any indication receive prophylactic (preventative) antibiotics.The presence of a permanent biliary stent (e.g. in pancreatic cancer) slightly increases the risk of cholangitis, but stents of this type are often needed to keep the bile duct patent under outside pressure. Pathogenesis Bile is produced by the liver, and serves to eliminate cholesterol and bilirubin from the body, as well as emulsifying of fats to make them more soluble in water and aid in their digestion. Bile is formed in the liver by hepatocytes (liver cells) and excreted into the common hepatic duct. Part of the bile is stored in the gall bladder because of back pressure (exerted by the sphincter of Oddi), and may be released at the time of digestion. The gallbladder also concentrates the bile by absorbing water and dissolved salts from it. All bile reaches the duodenum (first part of the small intestine) through the common bile duct and the ampulla of Vater. The sphincter of Oddi, located at the junction of the ampulla of Vater and the duodenum, is a circular muscle that controls the release of both bile and pancreatic secretions into the digestive tract.The biliary tree is normally relatively free of bacteria because of certain protective mechanisms. The sphincter of Oddi acts as a mechanical barrier. The biliary system normally has low pressure (8 to 12 cmH2O) and allows bile to flow freely through. The continuous forward flow of the bile in the duct flushes bacteria, if present, into the duodenum, and does not allow the establishment of an infection. The constitution of bile—bile salts and immunoglobulin secreted by the epithelium of the bile duct also has a protective role. Bacterial contamination alone in absence of obstruction does not usually result in cholangitis. However increased pressure within the biliary system (above 20 cmH2O) resulting from obstruction in the bile duct widens spaces between the cells lining the duct, bringing bacterially contaminated bile in contact with the blood stream. It also adversely affects the function of Kupffer cells, which are specialized macrophage cells that assist in preventing bacteria from entering the biliary system. Finally, increased biliary pressure decreases production of IgA immunoglobulins in the bile. This results in bacteremia (bacteria in the blood stream) and gives rise to the systemic inflammatory response syndrome (SIRS) comprising fever (often with rigors), tachycardia, increased respiratory rate and increased white blood cell count; SIRS in the presence of suspected or confirmed infection is called sepsis. Biliary obstruction itself disadvantages the immune system and impairs its capability to fight infection, by impairing the function of certain immune system cells (neutrophil granulocytes) and modifying the levels of immune hormones (cytokines).In ascending cholangitis, it is assumed that organisms migrate backwards up the bile duct as a result of partial obstruction and decreased function of the sphincter of Oddi. Other theories about the origin of the bacteria, such as through the portal vein or transmigration from the colon, are considered less likely. Diagnosis Blood tests Routine blood tests show features of acute inflammation (raised white blood cell count and elevated C-reactive protein level), and usually abnormal liver function tests (LFTs). In most cases the LFTs will be consistent with obstruction: raised bilirubin, alkaline phosphatase and γ-glutamyl transpeptidase. In the early stages, however, pressure on the liver cells may be the main feature and the tests will resemble those in hepatitis, with elevations in alanine transaminase and aspartate transaminase.Blood cultures are often performed in people with fever and evidence of acute infection. These yield the bacteria causing the infection in 36% of cases, usually after 24–48 hours of incubation. Bile, too, may be sent for culture during ERCP (see below). The most common bacteria linked to ascending cholangitis are gram-negative bacilli: Escherichia coli (25–50%), Klebsiella (15–20%) and Enterobacter (5–10%). Of the gram-positive cocci, Enterococcus causes 10–20%. Medical imaging Given that ascending cholangitis usually occurs in the setting of bile duct obstruction, various forms of medical imaging may be employed to identify the site and nature of this obstruction. The first investigation is usually ultrasound, as this is the most easily available. Ultrasound may show dilation of the bile duct and identifies 38% of bile duct stones; it is relatively poor at identifying stones farther down the bile duct. Ultrasound can help distinguish between cholangitis and cholecystitis (inflammation of the gallbladder), which has similar symptoms to cholangitis but appears differently on ultrasound. A better test is magnetic resonance cholangiopancreatography (MRCP), which uses magnetic resonance imaging (MRI); this has a comparable sensitivity to ERCP. Smaller stones, however, can still be missed on MRCP depending on the quality of the hospitals facilities.The gold standard test for biliary obstruction is still endoscopic retrograde cholangiopancreatography (ERCP). This involves the use of endoscopy (passing a tube through the mouth into the esophagus, stomach and thence to the duodenum) to pass a small cannula into the bile duct. At that point, radiocontrast is injected to opacify the duct, and X-rays are taken to get a visual impression of the biliary system. On the endoscopic image of the ampulla, one can sometimes see a protuberant ampulla from an impacted gallstone in the common bile duct or the frank extrusion of pus from the common bile duct orifice. On the X-ray images (known as cholangiograms), gallstones are visible as non-opacified areas in the contour of the duct. For diagnostic purposes, ERCP has now generally been replaced by MRCP. ERCP is only used first-line in critically ill patients in whom delay for diagnostic tests is not acceptable; however, if the index of suspicion for cholangitis is high, an ERCP is typically done to achieve drainage of the obstructed common bile duct.If other causes rather than gallstones are suspected (such as a tumor), computed tomography and endoscopic ultrasound (EUS) may be performed to identify the nature of the obstruction. EUS may be used to obtain biopsy (tissue sample) of suspicious masses. EUS may also replace diagnostic ERCP for stone disease, although this depends on local availability. Treatment Fluids and antibiotics Cholangitis requires admission to hospital. Intravenous fluids are administered, especially if the blood pressure is low, and antibiotics are commenced. Empirical treatment with broad-spectrum antibiotics is usually necessary until it is known for certain which pathogen is causing the infection, and to which antibiotics it is sensitive. Combinations of penicillins and aminoglycosides are widely used, although ciprofloxacin has been shown to be effective in most cases, and may be preferred to aminoglycosides because of fewer side effects. Metronidazole is often added to specifically treat the anaerobic pathogens, especially in those who are very ill or at risk of anaerobic infections. Antibiotics are continued for 7–10 days. Drugs that increase the blood pressure (vasopressors) may also be required to counter the low blood pressure. Endoscopy The definitive treatment for cholangitis is relief of the underlying biliary obstruction. This is usually deferred until 24–48 hours after admission, when the patient is stable and has shown some improvement with antibiotics, but may need to happen as an emergency in case of ongoing deterioration despite adequate treatment, or if antibiotics are not effective in reducing the signs of infection (which happens in 15% of cases).Endoscopic retrograde cholangiopancreatography (ERCP) is the most common approach in unblocking the bile duct. This involves endoscopy (passing a fiberoptic tube through the stomach into the duodenum), identification of the ampulla of Vater and insertion of a small tube into the bile duct. A sphincterotomy (making a cut in the sphincter of Oddi) is typically done to ease the flow of bile from the duct and to allow insertion of instruments to extract gallstones that are obstructing the common bile duct; alternatively or additionally, the common bile duct orifice can be dilated with a balloon. Stones may be removed either by direct suction or by using various instruments, including balloons and baskets to trawl the bile duct in order to pull stones into the duodenum. Obstructions that are caused by larger stones may require the use of an instrument known as a mechanical lithotriptor in order to crush the stone prior to removal. Obstructing stones that are too large to be removed or broken mechanically by ERCP may be managed by extracorporeal shock wave lithotripsy. This technique uses acoustic shock waves administered outside the body to break down the stones. An alternative technique to remove very large obstructing stones is electrohydraulic lithotripsy, where a small endoscope known as a cholangioscope is inserted by ERCP to directly visualize the stone. A probe uses electricity to generate shock waves that break down the obstructing stone. Rarely, surgical exploration of the common bile duct (termed choledochotomy), which can be performed with laparoscopy, is required to remove the stone.Narrowed areas may be bridged by a stent, a hollow tube that keeps the duct open. Removable plastic stents are used in uncomplicated gallstone disease, while permanent self-expanding metal stents with a longer lifespan are used if the obstruction is due to pressure from a tumor such as pancreatic cancer. A nasobiliary drain may be left behind; this is a plastic tube that passes from the bile duct through the stomach and the nose and allows continuous drainage of bile into a receptible. It is similar to a nasogastric tube, but passes into the common bile duct directly, and allows for serial x-ray cholangiograms to be done to identify the improvement of the obstruction. The decision on which of the aforementioned treatments to apply is generally based on the severity of the obstruction, findings on other imaging studies, and whether the patient has improved with antibiotic treatment. Certain treatments may be unsafe if blood clotting is impaired, as the risk of bleeding (especially from sphincterotomy) is increased in the use of medication such as clopidogrel (which inhibits platelet aggregation) or if the prothrombin time is significantly prolonged. For a prolonged prothrombin time, vitamin K or fresh frozen plasma may be administered to reduce bleeding risk. Percutaneous biliary drainage In cases where a person is too ill to tolerate endoscopy or when a retrograde endoscopic approach fails to access the obstruction, a percutaneous transhepatic cholangiogram (PTC) may be performed to evaluate the biliary system for placement of a percutaneous biliary drain (PBD). This is often necessary in the case of a proximal stricture or a bilioenteric anastomosis (a surgical connection between the bile duct and small bowel, such as the duodenum or jejunum). Once access across the stricture is obtained, balloon dilation can be performed and stones can be swept forward into the duodenum. Due to potential complications of percutaneous biliary drain placement and the necessity of regular drain maintenance, a retrograde approach via ERCP remains first-line therapy. Cholecystectomy Not all gallstones implicated in ascending cholangitis actually originate from the gallbladder, but cholecystectomy (surgical removal of the gallbladder) is generally recommended in people who have been treated for cholangitis due to gallstone disease. This is typically delayed until all symptoms have resolved and ERCP or MRCP have confirmed that the bile duct is clear of gallstones. Those who do not undergo cholecystectomy have an increased risk of recurrent biliary pain, jaundice, further episodes of cholangitis, and need for further ERCP or cholecystostomy; the risk of death is also significantly increased. Prognosis Acute cholangitis carries a significant risk of death, the leading cause being irreversible shock with multiple organ failure (a possible complication of severe infections). Improvements in diagnosis and treatment have led to a reduction in mortality: before 1980, the mortality rate was greater than 50%, but after 1980 it was 10–30%. Patients with signs of multiple organ failure are likely to die unless they undergo early biliary drainage and treatment with systemic antibiotics. Other causes of death following severe cholangitis include heart failure and pneumonia.Risk factors indicating an increased risk of death include older age, female gender, a history of liver cirrhosis, biliary narrowing due to cancer, acute kidney injury and the presence of liver abscesses. Complications following severe cholangitis include kidney failure, respiratory failure (inability of the respiratory system to oxygenate blood and/or eliminate carbon dioxide), abnormal heart rhythms, wound infection, pneumonia, gastrointestinal bleeding and myocardial ischemia (lack of blood flow to the heart, leading to heart attacks). Epidemiology In the Western world, about 15% of all people have gallstones in their gallbladder but the majority are unaware of this and have no symptoms. Over ten years, 15–26% will have one or more episodes of biliary colic (abdominal pain due to the passage of gallstones through the bile duct into the digestive tract), and 2–3% will develop complications of obstruction: acute pancreatitis, cholecystitis or acute cholangitis. Prevalence of gallstone disease increases with age and body mass index (a marker of obesity). However, the risk is also increased in those who lose weight rapidly (e.g. after weight loss surgery) due to alterations in the composition of the bile that makes it prone to form stones. Gallstones are slightly more common in women than in men, and pregnancy increases the risk further. History Dr Jean-Martin Charcot, working at the Salpêtrière Hospital in Paris, France, is credited with early reports of cholangitis, as well as his eponymous triad, in 1877. He referred to the condition as "hepatic fever" (fièvre hépatique). Dr Benedict M. Reynolds, an American surgeon, reignited interest in the condition in his 1959 report with colleague Dr Everett L. Dargan, and formulated the pentad that carries his name. It remained a condition generally treated by surgeons, with exploration of the bile duct and excision of gallstones, until the ascendancy of ERCP in 1968. ERCP is generally performed by internal medicine or gastroenterology specialists. In 1992 it was shown that ERCP was generally safer than surgical intervention in ascending cholangitis. See also Primary sclerosing cholangitis (an autoimmune disease leading to narrowing of the bile ducts) Gallstone-related pancreatitis References == External links ==
Cutaneous small-vessel vasculitis	Cutaneous small-vessel vasculitis (CSVV), also known as hypersensitivity vasculitis, cutaneous leukocytoclastic vasculitis, hypersensitivity angiitis, cutaneous leukocytoclastic angiitis, cutaneous necrotizing vasculitis and cutaneous necrotizing venulitis, is inflammation of small blood vessels (usually post-capillary venules in the dermis), characterized by palpable purpura.: 831 It is the most common vasculitis seen in clinical practice. "Leukocytoclastic" refers to the damage caused by nuclear debris from infiltrating neutrophils in and around the vessels. Signs and symptoms Skin lesions Initially red to pink, flat spots (formally, "macules") and raised bumps (formally, "papules") may be seen on the skin.Once fully developed, the classic appearance is "non-blanching, palpable purpura". This appears as deep red to purple spots that feel raised to the touch. Purpura refers to the red-purple discolored spots, while palpable implies that these spots can be felt as raised from the surrounding skin. Additionally, when gently pressed, the color does not fade to a lighter color ("non-blanching"). The red-purple color of the lesions is due to the inflammation in the blood vessels causing red blood cells to escape into the dermis skin layer.Small fluid-filled blisters (or "vesicles"), pus-filled bumps resembling a pimple (or "pustules"), or shallow ulcers may also develop but are less common.The location of skin lesions varies but are most commonly found symmetrically below the waist, primarily on the buttocks and legs. Other distributions include localized areas on the upper body or over several areas of the body.With treatment, the lesions typically resolve in weeks to months and leave behind flat spots that are darker than the surrounding skin (see "Postinflammatory hyperpigmentation" on "Hyperpigmentation"). A portion of cases may be persistent or recurrent. This tends to occur when the vasculitis is associated with chronic conditions such as connective tissue diseases. Associated symptoms In most cases skin lesions do not cause symptoms, however itching, burning, or pain may occur.Frequently reported symptoms include mild fever, muscle pain, joint pain, or an overall feeling of discomfort. Additional symptoms depend on the cause of the vasculitis and if other organ systems are involved. For example, if the vasculitis is a manifestation of Henoch–Schönlein purpura, individuals may also experience abdominal pain or blood in the urine. Cause Cutaneous vasculitis can have various causes including but not limited to medications, bacterial and viral infections or allergens. It is estimated that 45–55% of cases are idiopathic, meaning the cause is unknown. In cases where a cause can be determined, medications and infectious pathogens are most common in adults, while IgA vasculitis (Henoch–Schönlein purpura) frequently affects children. Other etiologies include autoimmune conditions and malignancies, usually hematologic (related to the blood). The small vessels in the skin affected are located in the superficial dermis and include arterioles (small arteries carrying blood to capillaries), capillaries, and venules (small veins receiving blood from capillaries). In general, immune complexes deposit in vessel walls leading to activation of the complement system. C3a and C5a, proteins produced from the complement system, attract neutrophils to the vessels. Once activated, neutrophils then release preformed substances, including enzymes causing damage to vessel tissue. Evidence of this process can be seen with a sample of removed skin tissue, or biopsy, viewed under a microscope. Neutrophils are seen surrounding blood vessels and their debris within vessel walls, causing fibrinoid necrosis. This finding on histological examination is termed "leukocytoclastic vasculitis".Considering the wide range of potential causes leading to cutaneous small vessel vasculitis, there are subtle variations in the underlying pathophysiology for each cause. For example, medications are metabolized to smaller molecules that can attach to proteins in the blood or vessel walls. The immune system senses these altered proteins as foreign and produces antibodies in efforts to eliminate them from the body. A similar process occurs with infectious agents, such as bacteria, in which antibodies target microbial components. Diagnosis The diagnostic testing for vasculitis should be guided by the patients history and physical exam. The clinician should ask about the duration, onset, and presence any associated symptoms such as weight loss or fatigue (that would indicate a systemic cause). It is important to distinguish between IgA and non-IgA vasculitis. IgA vasculitis is more likely to present with abdominal pain, bloody urine, and joint pain. In the case that the cause is not obvious, a reasonable initial workup would include a complete blood count, urinalysis, basic metabolic panel, fecal occult blood testing, erythrocyte sedimentation rate (ESR), and C-reactive protein level. Small vessel cutaneous vasculitis is a diagnosis of exclusion and requires ruling out systemic causes of the skin findings. Skin biopsy (punch or excisional) is the most definitive diagnostic test and should be performed with 48 hours of appearance of the vasculitis. A skin biopsy will be able to determine if the clinical findings are truly due to a vasculitis or due to some other cause. Classification Subtypes of small-vessel vasculitis include:: 833–6 IgA vasculitis (Henoch-Schönlein purpura) Acute hemorrhagic edema of infancy Urticarial vasculitis Cryoglobulinemic vasculitis Erythema elevatum diutinum Granuloma faciale ANCA-associated vasculitis Arthropod bites Platelet dysfunction or deficiency Cholesterol emboli Septic emboli Livedoid vasculopathy Treatment Treatment should be directed towards the specific underlying cause of the vasculitis. If no underlying cause is found and the vasculitis is truly limited to the skin then treatment is primarily supportive. Such treatment involves measures such as leg elevation, stockings, and topical steroids to relieve itching/burning. If the vasculitis does not self-resolve within 3–4 weeks, more aggressive treatment may be warranted. Oral colchicine or dapsone are often used for this purpose. If rapid control of symptoms is needed, a short course of high-dose oral steroids may be given. Immunosuppressive agents such as methotrexate and azathioprine may be used in truly refractory cases not responsive to colchicine or dapsone. Additional images See also Skin lesion List of cutaneous conditions References == External links ==
Fissure	A fissure is a long, narrow crack opening along the surface of Earth. The term is derived from the Latin word fissura, which means cleft or crack. Fissures emerge in Earths crust, on ice sheets and glaciers, and on volcanoes. Ground fissure A ground fissure, also called an earth fissure, is a long, narrow crack or linear opening in the Earths crust. Ground fissures can form naturally, such as from tectonic faulting and earthquakes, or as a consequence of human activity, such as oil mining and groundwater pumping. Once formed, ground fissures can be extended and eroded by torrential rain. They can be hazardous to people and livestock living on the affected surfaces and damaging to property and infrastructure, such as roads, underground pipes, canals, and dams.In circumstances where there is the extensive withdrawal of groundwater, the earth above the water table can subside causing fissures to form at the surface. This typically occurs at the floor of arid valleys having rock formations and compacted soils with a high percentage of fine-grained material. Crevasse A crevasse, also called an ice fissure, is a deep linear crack in an ice sheet or glacier resulting from the opposing force produced by their movement at different rates of speed. The force builds until their associated shear stress is sufficient to break the ice along the faces. The breakage often forms vertical or near-vertical walls, which can melt and create seracs, arches, and other ice formations. A crevasse may be as deep as 45 metres (148 ft) and as wide as 20 metres (66 ft). A crevasse may be covered, but not necessarily filled, by a snow bridge made of the previous years accumulation and snow drifts. The result is that crevasses are rendered invisible, and extremely dangerous to anyone attempting to traverse a glacier. Types of crevasses Longitudinal crevasses form parallel to the ice flow where the glacier width is expanding. Splaying crevasses appear along the edges of a glacier. Transverse crevasses form in a zone of longitudinal extension where the principal stresses are parallel to the direction of glacier flow. Fissure vent A fissure vent, also known as a volcanic fissure or eruption fissure, is a long volcanic vent through which lava erupts. Fissure vents are connected to deep magma reservoirs and are typically found in and along rifts and rift zones. They are commonly associated with shield volcanoes. Over time fissure vents form spatter cones and can feed lava channels and lava tubes. Karst terrain Karst terrain or simply karst are vast regions of barren land with rocky ground and generally consisting of nearby caves, fissured ground, and sinkholes. Although these regions normally have moderate to heavy rainfall, they are noticeably devoid of vegetation and characteristically have no lakes, rivers, or streams on their surface. They form when large to massive veins of soluble aggregate like limestone, gypsum, or dolomite are excavated by underground torrents of flowing water. Karst aquifers In the United States, about 40% of the groundwater used for drinking comes from karst aquifers. Some of these areas are well known vacation destinations like Carlsbad Caverns and Mammoth Cave. Karst aquifers are a vital resource in the US; about 20 percent of the land surface in the US is classified as karst. Other parts of the world with large areas of karst include the Caribbean, China, and Australia. Typical karst hydrogeology consists of a network of interconnected fissures, fractures, and conduits emplaced within permeable rock. Most of the groundwater flow occurs through a network of openings, while groundwater is held in storage within the geological structures themselves. List of karst aquifers in North America Arbuckle-Simpson aquifer Basin and Range and Bear River range carbonate aquifers Colorado Plateau karst Edwards Balcones Fault Zone aquifer Edwards-Trinity Plateau aquifer Upper Floridan and Biscayne aquifers Madison aquifer Midwest Paleozoic Carbonate aquifers New England karst aquifers Ozark Plateau karst aquifers Roswell Basin aquifer Pacific Northwest basalt aquifers Valley and Ridge, Piedmont, and Blue Ridge aquifers See also Fabric (geology) Fissure vein Thermokarst Topography References External links External images of Almannagja fissures
Refeeding syndrome	Refeeding syndrome is a metabolic disturbance that occurs as a result of reinstitution of nutrition in people and animals who are starved, severely malnourished, or metabolically stressed because of severe illness. When too much food or liquid nutrition supplement is eaten during the initial four to seven days following a malnutrition event, the production of glycogen, fat and protein in cells may cause low serum concentrations of potassium, magnesium and phosphate. Cardiac, pulmonary and neurological symptoms can be signs of refeeding syndrome. The low serum minerals, if severe enough, can be fatal. Cause Any individual who has had a negligible nutrient intake for many consecutive days and/or is metabolically stressed from a critical illness or major surgery is at risk of refeeding syndrome. Refeeding syndrome usually occurs within four days of starting to re-feed. Patients can develop fluid and electrolyte imbalance, especially hypophosphatemia, along with neurologic, pulmonary, cardiac, neuromuscular, and hematologic complications.During fasting, the body switches its main fuel source from carbohydrates to fat tissue fatty acids and amino acids as the main energy sources. The spleen decreases its rate of red blood cell breakdown thus conserving red blood cells. Many intracellular minerals become severely depleted during this period, although serum levels remain normal. Importantly, insulin secretion is suppressed in this fasting state, and glucagon secretion is increased.During refeeding, insulin secretion resumes in response to increased blood sugar, resulting in increased glycogen, fat, and protein synthesis. Refeeding increases the basal metabolic rate. The process requires phosphates, magnesium and potassium which are already depleted, and the stores rapidly become used up. Formation of phosphorylated carbohydrate compounds in the liver and skeletal muscle depletes intracellular ATP and 2,3-diphosphoglycerate in red blood cells, leading to cellular dysfunction and inadequate oxygen delivery to the bodys organs. Intracellular movement of electrolytes occurs along with a fall in the serum electrolytes, including phosphate and magnesium. Levels of serum glucose may rise, and B1 vitamin thiamine may fall. Abnormal heart rhythms are the most common cause of death from refeeding syndrome, with other significant risks including confusion, coma and convulsions and cardiac failure. Clinical situations The syndrome can occur at the beginning of treatment for anorexia nervosa when patients have an increase in calorie intake and can be fatal. It can also occur after the onset of a severe illness or major surgery. The shifting of electrolytes and fluid balance increases cardiac workload and heart rate. This can lead to acute heart failure. Oxygen consumption is increased which strains the respiratory system and can make weaning from ventilation more difficult. Diagnosis Refeeding syndrome can be fatal if not recognized and treated properly. An awareness of the condition and a high index of suspicion are required in order to make the diagnosis. The electrolyte disturbances of the refeeding syndrome can occur within the first few days of refeeding. Close monitoring of blood biochemistry is therefore necessary in the early refeeding period. Treatment In critically ill patients admitted to an intensive care unit, if phosphate drops to below 0.65 mmol/L (2.0 mg/dL) from a previously normal level within three days of starting enteral or parenteral nutrition, caloric intake should be reduced to 480 kcals per day for at least two days while electrolytes are replaced. Daily doses of thiamine, vitamin B complex (strong) and a multivitamin and mineral preparation are strongly recommended. Blood biochemistry should be monitored regularly until it is stable. Although clinical trials are lacking in patients other than those admitted to intensive care, it is commonly recommended that energy intake should remain lower than that normally required for the first 3–5 days of treatment of refeeding syndrome for all patients. History In his 5th century BC work On Fleshes (De Carnibus), Hippocrates writes, "if a person goes seven days without eating or drinking anything, in this period most die; but there are some who survive that time but still die, and others are persuaded not to starve themselves to death but to eat and drink: however, the cavity no longer admits anything because the jejunum (nêstis) has grown together in that many days, and these people too die." Though Hippocrates misidentifies the cause of death, this passage likely represents an early description of refeeding syndrome. The Roman Historian Flavius Josephus writing in the first century described classic symptoms of the syndrome among survivors of the siege of Jerusalem. He described the death of those who overindulged in food after the famine, whereas those who ate at a more restrained pace survived.There were numerous cases of refeeding syndrome in the Siege of Leningrad during World War II, with Soviet civilians trapped in the city having becoming malnourished due to the German blockade. (Machado).A common error, repeated in multiple papers, is that "The syndrome was first described after World War II in Americans who, held by the Japanese as prisoners of war, had become malnourished during captivity and who were then released to the care of United States personnel in the Philippines." However, closer inspection of the 1951 paper by Schnitker reveals the prisoners under study were not American POWs but Japanese soldiers who, already malnourished, surrendered in the Philippines during 1945, after the war was over.It is difficult to ascertain when the syndrome was first discovered and named, but it is likely the associated electrolyte disturbances were identified perhaps in Holland, the Netherlands during the closing months of World War II. See also Minnesota Starvation Experiment References Bibliography Shils, M.E., Shike, M., Ross, A.C., Caballero, B. & Cousins, R.J. (2006). Modern nutrition in health and disease, 10th ed. Lippincott, Williams & Wilkins. Baltimore, MD. Mahan, L.K. & Escott-Stump, S.E. (2004) Krauses Food, Nutrition, & Diet Therapy, 11th ed. Saunders, Philadelphia, PA. Hearing S (2004). "Refeeding syndrome: Is underdiagnosed and undertreated, but treatable". BMJ. 328 (7445): 908–9. doi:10.1136/bmj.328.7445.908. PMC 390152. PMID 15087326. Crook M, Hally V, Panteli J (2001). "The importance of the refeeding syndrome". Nutrition. 17 (7–8): 632–7. doi:10.1016/S0899-9007(01)00542-1. PMID 11448586. Lauts N (2005). "Management of the patient with refeeding syndrome". J Infus Nurs. 28 (5): 337–42. doi:10.1097/00129804-200509000-00007. PMID 16205500. S2CID 39877542. Kraft M, Btaiche I, Sacks G (2005). "Review of the refeeding syndrome" (PDF). Nutr Clin Pract. 20 (6): 625–33. doi:10.1177/0115426505020006625. hdl:2027.42/142310. PMID 16306300. National Institute for Clinical Excellence (2008). CG32 Nutrition support in adults: full guideline. http://guidance.nice.org.uk/CG32/Guidance/pdf/English == External links ==
Paraplegia	Paraplegia, or paraparesis, is an impairment in motor or sensory function of the lower extremities. The word comes from Ionic Greek (παραπληγίη) "half-stricken". It is usually caused by spinal cord injury or a congenital condition that affects the neural (brain) elements of the spinal canal. The area of the spinal canal that is affected in paraplegia is either the thoracic, lumbar, or sacral regions. If four limbs are affected by paralysis, tetraplegia or quadriplegia is the correct term. If only one limb is affected, the correct term is monoplegia. Spastic paraplegia is a form of paraplegia defined by spasticity of the affected muscles, rather than flaccid paralysis. The American Spinal Injury Association classifies spinal cord injury severity in the following manner. ASIA A is the complete loss of sensory function and motor skills below the injury. ASIA B is having some sensory function below the injury, but no motor function. In ASIA C, there is some motor function below the level of injury, but half of the muscles cannot move against gravity. In ASIA D, more than half of the muscles below the level of injury can move against gravity. ASIA E is the restoration of all neurologic function. Treatment Individuals with paraplegia can range in their level of disability, requiring treatments to vary from case to case. Rehabilitation aims to help the patient regain as much functionality and independence as possible. Physiotherapy may help to improve strength, range of motion, stretching and transfer skills. Most paraplegics will be reliant on a wheelchair as a mode of transportation. Activities of daily living (ADLs) can be quite challenging at first for those with a spinal cord injury (SCI). With the aid of physiotherapists and occupational therapists, individuals with an SCI can learn new skills and adapt previous ones to maximize independence, often living independently within the community. Regeneration of the spinal cord Olfactory ensheathing cells (OEC) have been transplanted with success into the spinal cord of Polish man named Darek Fidyka, who was the survivor of a knife attack that left him paraplegic in 2010. In 2014, Fidyka underwent pioneering spinal surgery that used nerve grafts, from his ankle, to bridge the gap in his severed spinal cord and OECs to stimulate the spinal cord cells. The surgery was performed in Poland in collaboration with Prof. Geoff Raisman, chair of neural regeneration at University College Londons Institute of Neurology, and his research team. The olfactory cells were taken from the patients olfactory bulbs in his brain and then grown in the lab, these cells were then injected above and below the impaired spinal tissue. Fidyka regained sensory and motor function in his lower limbs, notably on the side of the transplanted OECs. Fidyka first noticed the success three months after the procedure, when his left thigh started gaining muscle mass. MRIs suggest that the gap in his spinal cord has been closed up. He is believed to be the first person in the world to recover sensory function from a complete severing of the spinal nerves. See also References External links Spinal Cord Injury at The Mayo Clinic Types of Paralysis at Spinalcord.com
Congenital afibrinogenemia	Congenital afibrinogenemia is a rare, genetically inherited blood fibrinogen disorder in which the blood does not clot normally due to the lack of fibrinogen, a blood protein necessary for coagulation. This disorder is autosomal recessive, meaning that two unaffected parents can have a child with the disorder. The lack of fibrinogen expresses itself with excessive and, at times, uncontrollable bleeding. Signs and symptoms As this is a disorder that is present in an individual from birth, there are no warning signs to look for. The first symptom usually seen is hemorrhage from the umbilical cord that is difficult to stop.Other symptoms include: Nasal and oral mucosa bleeds Gastrointestinal bleeding Excessive/spontaneous bleeding or bruising from minor injury Prolonged menstruation in women Spontaneous abortion during pregnancy CNS hemorrhagingSpontaneous bleeding of the mouth, nose, and gastrointestinal tract are common. Since blood clots can not be formed, minor injuries tend to lead to excessive bleeding or bruising. The biggest concern for individuals with afibrinogenemia is CNS hemorrhage, bleeding in the brain, which can be fatal. Many of these symptoms are chronic, and will continue to occur for the entirety of the affected individuals life. Causes A missense or nonsense mutation to the genes that code for the fibrinogen protein are affected. Usually the mutation leads to an early stop in the production of the protein. Due to the problem being genetically based, there is no way to prevent the disease. Individuals can get genetic testing done to see if they are a carrier of the trait, and if so may choose to complete genetic counseling to better understand the disorder and help manage family planning. Parents can choose to do prenatal genetic testing for the disorder to determine if their child will have the disease. The only risk factor is if both parents of a child carry the recessive allele linked to the disorder. Mechanism Individuals with the disorder have a mutation to their fibrinogen gene that prevents the formation of the protein. In normal conditions, fibrinogen is converted to fibrin when it is cleaved by the enzyme thrombin in the blood. The newly formed fibrin forms a fiber-rich network that helps trap red blood cells to start the coagulation process and form a clot. Since there is no fibrinogen present during afibrinogenemia, fibrin can not be formed to aid in this process. Diagnosis Diagnostic tests When a problem of fibrinogen is suspected, the following tests can be ordered: PT PTT Fibrinogen level in blood (total and clottable) Reptilase time Thrombin timeBlood fibrinogen levels of less than 0.1 g/L and prolonged bleeding test times are indicators of an individual having afibrinogenemia.A suspicion of congenital afibrinogenemia may appear on a platelet aggregation function test. Treatment The most common treatment is fibrinogen replacement therapy, including cryoprecipitate, blood plasma, and fibrinogen concentration transfusions to help with bleeding episodes or prior to surgery. Although some thrombotic complications have been reported following replacement theory, transfusions of fibrinogen concentrate are widely considered to be the most beneficial. Fibrinogen concentrate is pure, contains a known quantity of fibrinogen, is virally inactivated, and is transfused in small amounts. There is a lower chance of allergic reaction in response to transfusion. Alternatively, cryoprecipitate contains other coagulation factors, factors VIII, XIII, and von Willebrand factor. There are no known cures or forms of holistic care to date. Most complications arise from the symptoms of the disorder. Prognosis As there is not much data out on the life expectancy of an individual with afibrinogenemia, it is difficult to determine the average lifespan. However, the leading cause of death thus far is linked to CNS hemorrhage and postoperative bleeding. History It was first described in 1920 by German doctors, Fritz Rabe and Eugene Salomon, studying a bleeding disorder presenting itself in a child from birth. This disorder may also be simply called afibrinogenemia or familial afibrinogenemia. About 1 in 1 million individuals are diagnosed with the disease; typically at birth. Both males and females seem to be affected equally, but it has a higher occurrence in regions where consanguinity is prevalent. Research Currently research is based in pharmacological treatments. A case from 2015 was seen in which congenital afibrinogenemia was resolved in a patient after receiving a liver transplant. See also Factor I Deficiency References == External links ==
Breast cyst	A breast cyst is a fluid-filled sac within the breast. One breast can have one or more breast cysts. They are often described as round or oval lumps with distinct edges. In texture, a breast cyst usually feels like a soft grape or a water-filled balloon, but sometimes a breast cyst feels firm.Breast cysts can be painful and may be worrisome but are generally benign. They are most common in pre-menopausal women in their 30s or 40s. They usually disappear after menopause, but may persist or reappear when using hormone therapy. They are also common in adolescents. Breast cysts can be part of fibrocystic disease. The pain and swelling is usually worse in the second half of the menstrual cycle or during pregnancy. Treating breast cysts is usually not necessary unless they are painful or cause discomfort. In most cases, the discomfort they cause may be alleviated by draining the fluid from the cyst. The cysts form as a result of the growth of the milk glands and their size may range from smaller than a pea to larger than a ping pong ball. While some large cysts feel like lumps, most cysts cannot be identified during physical examinations. Breast cysts are not to be confused with "milk cysts" (galactoceles), which usually appear during weaning. Signs and symptoms Signs and symptoms of breast cysts include: A smooth, easily movable round or oval breast lump with distinct edges Breast pain or tenderness in the area of the lump Increased lump size and tenderness just before menstruation Decreased lump size and resolution of other signs and symptoms after menstruation Having one or many simple breast cysts does not increase a persons risk of breast cancer.Lumps in the breast are often not found during self-examinations or physical exams. However, in some cases they can be felt at touch, especially if they are larger. Breasts are usually lumpy or nodular as a result of the hormonal changes that women go through during their menstrual cycle. However, new breast lumps should always be referred to a specialist. Cysts can also be confused with infections that form on the nipple or the areola. A common cyst look-alike is a localised infection of a duct in the nipple. These can happen whether youre breast feeding or not, (if you are breast feeding it could also be a bleb) this becomes a bump that may then start to look yellow and white (pus filled). Check with your doctor if you are unsure or have other symptoms that are worrying you. Fluid leaking from a cyst, as may happen due to puncture or vigorous compression during mammography, or due to seat belt injury in the course of an automobile accident, may trigger an aseptic inflammation in the surrounding breast tissue. Diagnosis The cystic nature of a breast lump can be confirmed by ultrasound examination, aspiration (removal of contents with needle), or mammogram. Ultrasound can also show if the cyst contains solid nodules, a sign that the lesion may be pre-cancerous or cancerous. Examination by a cytopathologist of the fluid aspirated from the cyst may also help with this diagnosis. In particular, it should be sent to a laboratory for testing if it is blood-stained. Commonly, cysts are detected with the help of mammograms. However, the medical history and physical examination also play an important role in establishing an accurate diagnosis. During these tests, the doctor will try to find out as much information as possible regarding the symptoms the patient has experienced, their intensity and duration and the physical examination is performed regularly to check for other abnormalities that may exist within the breast. As mentioned above, cysts are often undetectable at touch. Therefore, a mammogram can provide valuable and clear images of the breast tissue. Generally, if there is any abnormality within the breast tissue, it will be shown on the mammogram. There are two types of mammograms available. One of them is primarily used in screening, and are ordered for patients who do not show any symptoms and these are called screening mammograms. Diagnostic mammograms are used on patients who developed certain symptoms of a breast condition or in patients whose screening mammograms showed abnormalities. Patients suspected of breast cysts will normally be given a diagnosing mammogram, although they are not suspected of cancer. This type of mammogram provides the doctor with the possibility of performing a breast ultrasound at the same time and this is the reason why they are often preferred over the screening mammograms. Breast ultrasound is considered the best option when diagnosing breast cysts because it is 95 to 100% accurate, it provides a clear image on the cysts appearance (simple or complex) and it may also distinguish between solid lumps and fluid-filled cysts, which a mammogram cannot do. Breast ultrasounds are performed with the help of a handheld medical instrument which is placed on the skin, after a special type of fluid has been applied on it. The instruments picks up the echo resulted from the sound waves it sends to the breast. These echoes are transmitted to a computer which translates it into a picture. Breast cysts may remain stable for many years or may resolve spontaneously. Most simple cysts are benign and do not require any treatment or further diagnostic workup. Some complex cysts may require further diagnostic measures such as fine needle aspiration or biopsy to exclude breast cancer however the overwhelming majority is of benign nature. Aspiration both diagnoses and removes cysts at the same time. That is, cysts will usually resolve on their own after the fluid is drained. Otherwise, if the lump is not a cyst, the fluid aspirated may contain blood or there may not be fluid at all. Whereas in the first case, the fluid is sent to the laboratory for further examination, the latter circumstance is a sign that the breast lump is solid. This type of tumor needs to be biopsied in order to determine whether it is malignant or benign. Prevention The development of breast cysts may be prevented to some degree, according to the majority of the specialists. The recommended measures one is able to take in order to avoid the formation of the cysts include practicing good health and avoiding certain medications, eating a balanced diet, taking necessary vitamins and supplements, getting exercise, and avoiding stress.Although caffeine consumption does not have a scientifically proved connection with the process of cyst development, many women claim that their symptoms are relieved if avoiding it. Some doctors recommend reducing the amount of caffeine in ones diet in terms of both beverages and foods (such as chocolate). Also reducing salt intake may help in alleviating the symptoms of breast cysts, although, again, there is no scientific linkage between these two. Excessive sugar consumption as well as undetected food allergies, such as to gluten or lactose, may also contribute to cyst development. Treatment Breast cysts do not require treatment unless a cyst is large and painful or otherwise uncomfortable. In that case, draining the fluid from a breast cyst can ease symptoms.Nipple cysts (commonly duct infections) may benefit from a hot compress to draw out the pus and antibacterial cream. These infected ducts typically clear up within a few days. Typical treatment involves a Needle aspiration biopsy which is typically done with a 10 cc syringe attached to a fine needle aspiration needle. Fine needle aspiration allows retrieval of cytological samples that can be sent for pathological review to determine if the cyst is benign or malignant. Aspirated cysts often recur (come back); definitive treatment may require surgery. During an excisional biopsy an incision is made around the mass creating a superior and inferior flap. The mass is dissected out followed by confirmation of hemostasis. Once hemostasis is confirmed the wound is closed with an absorbable suture. The mass is then sent to pathology for review. Pathology can help determine if the surgeon needs to dissect a bigger margin. Draining the fluid and then waiting for the cyst to resolve is the main treatment applied in these cases. Moreover, if cysts are aspirated and the fluid looks normal, they do not require any other medical attention apart from following-up to make sure they have completely disappeared. Hormone therapy, by the means of oral contraceptives, is sometimes prescribed to reduce their recurrence and to regulate the menstrual cycle of the patient (which is likely to cause them in the first place). Danazol may also be prescribed to treat this condition and it is usually considered in patients on whom the non-medical treatment fails and the symptoms are intense. Surgical removal of a breast cyst is necessary only in a few unusual circumstances. If an uncomfortable breast cyst recurs month after month, or if a breast cyst contains blood-tinged fluid and displays other worrisome signs, surgery may be considered. Epidemiology It is estimated that 7% of women in the western world develop palpable breast cysts.In males, the occurrence of breast cysts is rare and may (but need not) be an indication of malignancy. Cysts and bra support Some women experience breast pain, especially when engaging in vigorous physical activity. A properly fitted sports bra, which compresses or encapsulates breast tissue, is designed to reduce pain caused by exercise. References == External links ==
Uterine contraction	Uterine contractions are muscle contractions of the uterine smooth muscle that occur during the menstrual cycle and labour. Uterine contractions occur throughout the menstrual cycle in the non-pregnant state and throughout gestation. Throughout menstrual cycle Uterine contractions that occur throughout the menstrual cycle, also termed endometrial waves or contractile waves, appear to involve only the sub-endometrial layer of the myometrium. Follicular and luteal phase In the early follicular phase, uterine contractions in the non-pregnant woman occur 1—2 times per minute and last 10–15 seconds with a low intensity of usually 30 mmHg or less. This sub-endometrial layer is rich in estrogen and progesterone receptors. The frequency of contractions increases to 3–4 per minute towards ovulation. During the luteal phase, the frequency and intensity decrease, possibly to facilitate any implantation. Menstruation If implantation does not occur, the frequency of contractions remains low; but at menstruation the intensity increases dramatically to between 50 and 200 mmHg producing labor-like contractions. These contractions are sometimes termed menstrual cramps, although that term is also used for menstrual pain in general. These contractions may be uncomfortable or even painful, but they are generally significantly less painful than contractions during labour. Painful contractions are called dysmenorrhea. Directionality of contractions A shift in the myosin expression of the uterine smooth muscle has been hypothesized as arising for changes in the directions of uterine contractions during the menstrual cycle. Labour Uterine contractions are part of the process of natural childbirth (i.e., not by Caesarean section). During labor, uterine contractions changes from episodic and uncoordinated to highly-coordinated. This change typically occurs at night, suggesting neural control, and significantly increases intrauterine pressure. Some women may experience contractions before labour is due. These are Braxton Hicks contractions, which are sometimes referred to as "false labour." There are several endogenous compounds involved in coordinating uterine contractility in labour, including oxytocin and prostaglandins. Oxytocin The hormone oxytocin has been identified as inducing uterine contractions, and labour in general. Oxytocin is produced by the body naturally and since the 1950s has also been available in synthetic pharmaceutical form. In either form, oxytocin stimulates uterine contractions to accelerate the process of childbirth. Production and secretion of oxytocin is controlled by a positive feedback mechanism, where its initial release, either naturally or in pharmaceutical form, stimulates production and release of further oxytocin. For example, when oxytocin is released during a contraction of the uterus at the start of childbirth, this stimulates production and release of more oxytocin and an increase in the duration, intensity and frequency of contractions. This process compounds in intensity and frequency and continues until the triggering activity ceases. Prostaglandins The concentration of prostaglandins in the blood plasma and amniotic fluid increases during labor. These inflammatory mediators encourage myometrial contractions to induce labor. Prostaglandins are also related to the changes in gap junction formation and connexin-43 expression during labor. In orgasm Uterine and vaginal contractions usually take place during female sexual stimulation, including sexual arousal, and orgasm. Monitors Uterine contractions can be monitored by cardiotocography, in which a device is affixed to the skin of the mother or directly to the fetal scalp. The pressure required to flatten a section of the uterine wall correlates with the internal pressure, thereby providing an estimate of it.A type of monitoring technology under development at Drexel University embeds conductive threads in the knitted fabric of a bellyband. When the fibers stretch in response to a contraction, the threads function like an antenna, and send the signals they pick up to an embedded RFID (radio-frequency identification device) chip that reports the data. Mechanism Resting state The resting membrane potential (Vrest) of uterine smooth muscle has been recorded to be between −35 and −80 mV. As with the resting membrane potential of other cell types, it is maintained by a Na+/K+ pump that causes a higher concentration of Na+ ions in the extracellular space than in the intracellular space, and a higher concentration of K+ ions in the intracellular space than in the extracellular space. Subsequently, having K+ channels open to a higher degree than Na+ channels results in an overall efflux of positive ions, resulting in a negative potential. This resting potential undergoes rhythmic oscillations, which have been termed slow waves, and reflect intrinsic activity of slow wave potentials. These slow waves are caused by changes in the distribution of Ca2+, Na+, K+ and Cl− ions between the intracellular and extracellular spaces, which, in turn, reflects the permeability of the plasma membrane to each of those ions. K+ is the major ion responsible for such changes in ion flux, reflecting changes in various K+ channels. Excitation-contraction As the uterus becomes essentially denervated during gestation, it is unlikely that any coordinated nervous regulation of the myometrium is centrally orchestrated. Excitation The excitation-contraction coupling of uterine smooth muscle is also very similar to that of other smooth muscle in general, with intracellular increase in calcium (Ca2+) leading to contraction. Nitric oxide (NO) is particularly effective in relaxing the myometrium and in fact has a lower inhibitory concentration 50% (Ki) in human than guinea pig or non-human primate myometrium. Restoration to resting state Uterine smooth muscle mechanisms of relaxation differ significantly from those of other human smooth muscles. Removal of Ca2+ after contraction induces relaxation of the smooth muscle, and restores the molecular structure of the sarcoplasmic reticulum for the next contractile stimulus. Measuring uterine contractility ex vivo Ethically-donated human uterine tissues can be used to measure uterine contractility ex vivo. In these experiments, sections of myometrium are set up in an organ bath system that to measure changes in isometric force production. Following functional checks to ensure the tissue is physiologically active, compounds can be added to the organ bath in increasing concentrations to create a cumulative concentration-response curve (CCRC).A key advantage of measuring uterine contractility ex vivo is the ability to eliminate species differences. For example, while magnesium reduces myometrial contractility in animal studies and in vitro, it does not demonstrate the same effect in clinical studies. And while the peptide hormone relaxin has been shown to inhibit uterine contractility in rats, mice, and pigs, it does not prevent uterine contractility in humans. See also Involution (medicine) == References ==
Ovarian torsion	Ovarian torsion (OT) or adnexal torsion is an abnormal condition where an ovary twists on its attachment to other structures, such that blood flow is decreased. Symptoms typically include pelvic pain on one side. While classically the pain is sudden in onset, this is not always the case. Other symptoms may include nausea. Complications may include infection, bleeding, or infertility.Risk factors include ovarian cysts, ovarian enlargement, ovarian tumors, pregnancy, fertility treatment, and prior tubal ligation. The diagnosis may be supported by an ultrasound done via the vagina or CT scan, but these do not completely rule out the diagnosis. Surgery is the most accurate method of diagnosis.Treatment is by surgery to either untwist and fix the ovary in place or to remove it. The ovary will often recover, even if the condition has been present for some time. In those who have had a prior ovarian torsion, there is a 10% chance the other will also be affected. The diagnosis is relatively rare, affecting about 6 per 100,000 women per year. While it most commonly occurs in those of reproductive age, it can occur at any age. Signs and symptoms Patients with ovarian torsion often present with sudden onset of sharp and usually unilateral lower abdominal pain, in 70% of cases accompanied by nausea and vomiting. Pathophysiology The development of an ovarian mass is related to the development of torsion. In the reproductive years, regular growth of large corpus luteal cysts are a risk factor for rotation. The mass effect of ovarian tumors is also a common cause of torsion. Torsion of the ovary usually occurs with torsion of the fallopian tube as well on their shared vascular pedicle around the broad ligament, although in rare cases the ovary rotates around the mesovarium or the fallopian tube rotates around the mesosalpinx. In 80%, torsion happens unilaterally, with slight predominance on the right. In ovarian torsion, the ovary rotates around both the infundibulopelvic ligament (ie, suspensory ligament) and the utero-ovarian ligament (i.e. ovarian ligament), disrupting blood flow to the ovary. Diagnosis Ovarian torsion is difficult to diagnose accurately, and operation is often performed before certain diagnosis is made. A study at an obstetrics and gynaecology department found that preoperative diagnosis of ovarian torsion was confirmed in only 46% of people. Ultrasound Gynecologic ultrasonography is the imaging modality of choice. Use of doppler ultrasound in the diagnosis has been suggested. However, doppler flow is not always absent in torsion – the definitive diagnosis is often made in the operating room.Lack of ovarian blood flow on doppler sonography seems to be a good predictor of ovarian torsion. Women with pathologically low flow are more likely to have torsion. The sensitivity and specificity of abnormal ovarian flow are 44% and 92%, respectively, with a positive and negative predictive value of 78% and 71%, respectively. Specific flow features on Doppler sonography include: Little or no intra-ovarian venous flow. This is commonly seen in ovarian torsion. Absent arterial flow. This is a less common finding in ovarian torsion Absent or reversed diastolic flowNormal vascularity does not exclude intermittent torsion. There may occasionally be normal Doppler flow because of the ovarys dual blood supply from both the ovarian arteries and uterine arteries.Other ultrasonographic features include: Enlarged hypoechogenic or hyperechogenic ovary Peripherally displaced ovarian follicles Free pelvic fluid. This may be seen in more than 80% of cases Whirlpool sign of twisted vascular pedicle Underlying ovarian lesion can often be found Uterus may be slightly deviated towards the torted ovary. Treatment Surgical treatment of ovarian torsion includes laparoscopy to uncoil the torsed ovary and possibly oophoropexy to fixate the ovary which is likely to twist again. In severe cases, where blood flow is cut off to the ovary for an extended period of time, necrosis of the ovary can occur. In these cases the ovary must be surgically removed. Epidemiology Ovarian torsion accounts for about 3% of gynecologic emergencies. The incidence of ovarian torsion among women of all ages is 5.9 per 100,000 women, and the incidence among women of reproductive age (15–45 years) is 9.9 per 100,000 women. In 70% of cases, it is diagnosed in women between 20 and 39 years of age. The risk is greater during pregnancy and in menopause. Risk factors include increased length of the ovarian ligaments, pathologically enlarged ovaries (more than 6 cm), ovarian masses or cysts, and enlarged corpus luteum in pregnancy. See also Testicular torsion – equivalent condition in males References == External links ==
Uterine perforation	Uterine perforation is a potential complication of any intrauterine procedure. It may be associated with injury to surrounding blood vessels or viscera such as the bladder or intestine. If not diagnosed at the time of the procedure it can occasionally result in massive hemorrhage or sepsis; however, the majority of uterine perforations are sub-clinical and safely resolve by themselves without treatment and do not cause any significant long-term damage. Risk factors include cervical stenosis during trans-cervical procedures or decreased strength of the myometrial wall as in pregnancy or menopause. See also Uterine rupture References == External links ==
Pediculosis	Pediculosis is an infestation of lice from the sub-order Anoplura, family Pediculidae. Accordingly, the infestation with head lice is named pediculosis capitis, while this with body lice, pediculosis corporis. Although pediculosis in humans may properly refer to lice infestation of any part of the body, the term is sometimes used loosely to refer to pediculosis capitis, the infestation of the human head with the specific head louse. Classification Pediculosis may be divided into the following types:: 446–8 Pediculosis capitis (Head lice infestation) Pediculosis corporis (Body louse infestation, also known as Pediculosis vestimenti, Vagabonds disease) Pediculosis pubis (Pubic louse infestation, also known as phthiriasis) Head lice Presentation Head-lice infestation is most frequent on children aged 3–10 and their families. Approximately 3% of school children in the United States contract head lice. Females aged 3–12 years are most commonly infested. Those of African descent rarely experience infestation due to differences in hair texture.Head lice are spread through direct head-to-head contact with an infested person. From each egg or "nit" may hatch one nymph that will grow and develop to the adult louse. Lice feed on blood once or more often each day by piercing the skin with their tiny needle-like mouthparts. While feeding they excrete saliva, which irritates the skin and causes itching. Lice cannot burrow into the skin. Diagnosis To diagnose infestation, the entire scalp should be combed thoroughly with a louse comb and the teeth of the comb should be examined for the presence of living lice after each time the comb passes through the hair. The use of a louse comb is the most effective way to detect living lice.The most characteristic symptom of infestation is pruritus (itching) on the head which normally intensifies 3 to 4 weeks after the initial infestation. The bite reaction is very mild and it can be rarely seen between the hairs. Excessive scratching of the infested areas can cause sores, which may become infected. Treatment The number of diagnosed cases of human louse infestations (or pediculosis) has increased worldwide since the mid-1960s, reaching hundreds of millions annually. There is no product or method which assures 100% destruction of the eggs and hatched lice after a single treatment. However, there are a number of treatment methods that can be employed with varying degrees of success. These methods include chemical treatments, natural products, combs, shaving, hot air, silicone-based lotions, and ethanol (ethyl alcohol).Pediculosis is commonly treated with permethrin lotion. Epidemiology About 14 million people, mainly children, are treated annually for head lice in the United States alone. Only a small proportion of those treated, however, may have objective evidence of an extant infestation. High levels of louse infestations have also been reported from all over the world including Denmark, Sweden, U.K., France and Australia. Normally head lice infest a new host only by close contact between individuals, making social contacts among children and parent child interactions more likely routes of infestation than shared combs, brushes, towels, clothing, beds or closets. Head-to-head contact is by far the most common route of lice transmission.The United Kingdoms National Health Service, and many American health agencies, report that lice "prefer" clean hair, because its easier to attach eggs and to cling to the strands.Head lice (Pediculus humanus capitis) are not known to be vectors of diseases, unlike body lice (Pediculus humanus humanus), which are known vectors of epidemic or louse-borne typhus (Rickettsia prowazekii), trench fever (Rochalimaea quintana) and louse-borne relapsing fever (Borrelia recurrentis). Body lice This condition is caused by body louse (Pediculus humanus humanus, sometimes called Pediculus humanus corporis), a louse which infests humans and is adapted to lay eggs in clothing, rather than at the base of hairs, and is thus of recent evolutionary origin. Pediculosis is a more serious threat due to possible contagion of diseases such as typhus. Epidemiology and treatment of human body lice is described in the article on body lice. Pubic lice The pubic or crab louse (Pthirus pubis) is a parasitic insect which spends its entire life on human hair and feeds exclusively on blood. Humans are the only known host of this parasite, although it is more closely related to the louse parasites in other primate species, than are human head or body lice which probably evolved from it as the "original" louse infestation of humans. Epidemiology and treatment of pubic lice is discussed in the article on pubic lice. Other animals Pediculosis is more common in cattle than any other type of domesticated animal. This is a significant problem, as it can cause weight loss of 55 to 75 pounds per animal. Some species of lice infesting cattle include the cattle biting louse (Bovicola bovis), the shortnosed cattle louse (Haematopinus eurysternus), the longnosed cattle louse (Linognathus vituli), and the little blue cattle louse (Solenopotes capillatus). Treatment Cattle infested with bovine pediculosis are generally treated chemically, by drugs like ivermectin and cypermethrin. History In the 15th century, topical mercury treatment was used to treat pediculosis. See also Nitpicking References External links Head louse infestations: Biology, prevention and control by Prof. Kosta Y. Mumcuoglu Head lice: Biology and Management at IdentifyUS LLC National Pediculosis Association Frankowski BL, Weiner LB (September 2002). "Head lice". Pediatrics. 110 (3): 638–643. doi:10.1542/peds.110.3.638. PMID 12205271. S2CID 245074002. Archived from the original on 2008-10-13. Retrieved 2004-07-12. Morewitz H (2005). "A Brief History of Head Lice". Speare R (2007). "Head Lice Information Sheet". James Cook University, N. Queensland, Australia. Archived from the original on 2014-05-29. Pediculus humanus Head Lice Infestation: Symptoms, Causes & Diagnosis
Laxative	Laxatives, purgatives, or aperients are substances that loosen stools and increase bowel movements. They are used to treat and prevent constipation. Laxatives vary as to how they work and the side effects they may have. Certain stimulant, lubricant and saline laxatives are used to evacuate the colon for rectal and bowel examinations, and may be supplemented by enemas under certain circumstances. Sufficiently high doses of laxatives may cause diarrhea. Some laxatives combine more than one active ingredient. Laxatives may be administered orally or rectally. Types Bulk-forming agents Bulk-forming laxatives, also known as roughage, are substances, such as fiber in food and hydrophilic agents in over-the-counter drugs, that add bulk and water to stools so that they can pass more easily through the intestines (lower part of the digestive tract).Properties Site of action: small and large intestines Onset of action: 12–72 hours Examples: dietary fiber, Metamucil, Citrucel, FiberConBulk-forming agents generally have the gentlest of effects among laxatives, making them ideal for long-term maintenance of regular bowel movements. Dietary fiber Foods that help with laxation include fiber-rich foods. Dietary fiber includes insoluble fiber and soluble fiber, such as: Fruits, such as bananas, though this depends on their ripeness, kiwifruits, prunes, apples (with skin), pears (with skin), and raspberries Vegetables, such as broccoli, string beans, kale, spinach, cooked winter squash, cooked taro and poi, cooked peas, and baked potatoes (with skin) Whole grains Bran products Nuts Legumes, such as beans, peas, and lentils Emollient agents (stool softeners) Emollient laxatives, also known as stool softeners, are anionic surfactants that enable additional water and fats to be incorporated in the stool, making it easier for them to move through the gastrointestinal tract. Properties Site of action: small and large intestines Onset of action: 12–72 hours Examples: Docusate (Colace, Diocto), Gibs-EzeEmollient agents prevent constipation rather than treating long-term constipation. Lubricant agents Lubricant laxatives are substances that coat the stool with slippery lipids and decrease colonic absorption of water so that the stool slides through the colon more easily. Lubricant laxatives also increase the weight of stool and decrease intestinal transit time.Properties Site of action: colon Onset of action: 6–8 hours Example: mineral oilMineral oil is the only nonprescription lubricant. Mineral oil may decrease the absorption of fat-soluble vitamins and some minerals.One example is Liquid paraffin. Hyperosmotic agents Hyperosmotic laxatives are substances that cause the intestines to hold more water within and create an osmotic effect that stimulates a bowel movement.Properties Site of action: colon Onset of action: 12–72 hours (oral), 0.25–1 hour (rectal) Examples: glycerin suppositories (Hallens), sorbitol, lactulose, and PEG (Colyte, MiraLax)Lactulose works by the osmotic effect, which retains water in the colon; lowering the pH through bacterial fermentation to lactic, formic and acetic acid; and increasing colonic peristalsis. Lactulose is also indicated in portal-systemic encephalopathy. Glycerin suppositories work mostly by hyperosmotic action, but the sodium stearate in the preparation also causes local irritation to the colon. Solutions of polyethylene glycol and electrolytes (sodium chloride, sodium bicarbonate, potassium chloride, and sometimes sodium sulfate) are used for whole bowel irrigation, a process designed to prepare the bowel for surgery or colonoscopy and to treat certain types of poisoning. Brand names for these solutions include GoLytely, GlycoLax, Cosmocol, CoLyte, Miralax, Movicol, NuLytely, Suprep, and Fortrans. Solutions of sorbitol (SoftLax) have similar effects. Saline laxative agents Saline laxatives are non-absorbable osmotically active substances that attract and retain water in the intestinal lumen, increasing intraluminal pressure that mechanically stimulates evacuation of the bowel. Magnesium-containing agents also cause the release of cholecystokinin, which increases intestinal motility and fluid secretion. Saline laxatives may alter a patients fluid and electrolyte balance. Properties Site of action: small and large intestines Onset of action: 0.5–3 hours (oral), 2–15 minutes (rectal) Examples: sodium phosphate (and variants), magnesium citrate, magnesium hydroxide (milk of magnesia), and magnesium sulfate (Epsom salt) Stimulant agents Stimulant laxatives are substances that act on the intestinal mucosa or nerve plexus, altering water and electrolyte secretion. They also stimulate peristaltic action and can be dangerous under certain circumstances.Properties Site of action: colon Onset of action: 6–10 hours Examples: senna, bisacodylProlonged use of stimulant laxatives can create drug dependence by damaging the colons haustral folds, making a user less able to move feces through the colon on their own. A study of patients with chronic constipation found that 28% of chronic stimulant laxative users lost haustral folds over the course of one year, while none of the control group did. Miscellaneous Castor oil is a glyceride that is hydrolyzed by pancreatic lipase to ricinoleic acid, which produces laxative action by an unknown mechanism. Properties Site of action: colon,small intestine (see below) Onset of action: 2–6 hours Examples: castor oilLong-term use of castor oil may result in loss of fluid, electrolytes, and nutrients. Serotonin agonist These are motility stimulants that work through activation of 5-HT4 receptors of the enteric nervous system in the gastrointestinal tract. However, some have been discontinued or restricted due to potentially harmful cardiovascular side-effects. Tegaserod (brand name Zelnorm) was removed from the general U.S. and Canadian markets in 2007, due to reports of increased risks of heart attack or stroke. It is still available to physicians for patients in emergency situations that are life-threatening or require hospitalization.Prucalopride (brand name Resolor) is a current drug approved for use in the EU since October 15, 2009, in Canada (brand name Resotran) since December 7, 2011, and in the United States since December 2018. Chloride channel activators Lubiprostone is used in the management of chronic idiopathic constipation and irritable bowel syndrome. It causes the intestines to produce a chloride-rich fluid secretion that softens the stool, increases motility, and promotes spontaneous bowel movements (SBM). Comparison of available agents Effectiveness For adults, a randomized controlled trial found PEG (MiraLax or GlycoLax) 17 grams once per day to be superior to tegaserod at 6 mg twice per day. A randomized controlled trial found greater improvement from two sachets (26 grams) of PEG versus two sachets (20 grams) of lactulose. 17 grams per day of PEG has been effective and safe in a randomized controlled trial for six months. Another randomized controlled trial found no difference between sorbitol and lactulose.For children, PEG was found to be more effective than lactulose. Problems with use Laxative abuse Some of the less significant adverse effects of laxative abuse include dehydration (which causes tremors, weakness, fainting, blurred vision, kidney damage), low blood pressure, fast heart rate, postural dizziness and fainting; however, laxative abuse can lead to potentially fatal acid-base and electrolyte imbalances. For example, severe hypokalaemia has been associated with distal renal tubular acidosis from laxative abuse. Metabolic alkalosis is the most common acid-base imbalance observed. Other significant adverse effects include rhabdomyolysis, steatorrhoea, inflammation and ulceration of colonic mucosa, pancreatitis, kidney failure, factitious diarrhea and other problems. The colon will need more quantities of laxatives to keep functioning, this will result in a lazy colon, infections, irritable bowel syndrome, and potential liver damages. Although some patients with eating disorders such as anorexia nervosa and bulimia nervosa abuse laxatives in an attempt to lose weight, laxatives act to speed up the transit of feces through the large intestine, which occurs after the absorption of nutrients in the small intestine is already complete. Thus, studies of laxative abuse have found that effects on body weight reflect primarily temporary losses of body water rather than energy (calorie) loss. Laxative gut Physicians warn against the chronic use of stimulant laxatives due to concern that chronic use could cause the colonic tissues to get worn out over time and not be able to expel feces due to long-term overstimulation. A common finding in patients having used stimulant laxatives is a brown pigment deposited in the intestinal tissue, known as melanosis coli. Historical and health fraud uses Laxatives, once called physicks or purgatives, were used extensively in pre-modern medicine to treat many conditions for which they are now generally regarded as ineffective in evidence-based medicine. Likewise, laxatives (often termed colon cleanses) may be promoted in alternative medicine for various conditions of quackery, such as "mucoid plaque". See also == References ==
Hemorrhagic cystitis	Hemorrhagic cystitis or haemorrhagic cystitis is an inflammation of the bladder defined by lower urinary tract symptoms that include dysuria, hematuria, and hemorrhage. The disease can occur as a complication of cyclophosphamide, ifosfamide and radiation therapy. In addition to hemorrhagic cystitis, temporary hematuria can also be seen in bladder infection or in children as a result of viral infection. Causes Causes of hemorrhagic cystitis include chemotherapy (e.g. cyclophosphamide, Ifosfamide), radiation, or infection. Ifosfamide is the most common cause of hemorrhagic cystitis. Radiation-induced hemorrhagic cystitis develops in similar or smaller patient numbers when compared to cyclophosphamide-induced cases.Adenovirus (particularly serotypes 11 and 21 of subgroup B) is the most common cause of acute viral hemorrhagic cystitis in children, though it can result from BK virus as well. A chemical hemorrhagic cystitis can develop when vaginal products are inadvertently placed in the urethra. Gentian violet douching to treat candidiasis has resulted in hemorrhagic cystitis when the drug was misplaced in the urethra, but this hemorrhagic cystitis resolved spontaneously with cessation of treatment. Accidental urethral placement of contraceptive suppositories has also caused hemorrhagic cystitis in several patients. The bladder irritation was thought to be caused by the spermicidal detergent nonoxynol-9. In the acute setting, the bladder can be copiously irrigated with alkalinized normal saline to minimize bladder irritation.Although hemorrhagic cystitis post-transplantation/bone marrow transplantation is not technically infectious, a short discussion is in order for completeness. Patients undergoing therapy to suppress the immune system are at risk for hemorrhagic cystitis due to either the direct effects of chemotherapy or activation of dormant viruses in the kidney, ureter, or bladder. Diagnosis Diagnosis is made by history and examination.In immunocompromised patients, pus is present in the urine but often no organism can be cultured. In children, polymerase chain reaction sequencing of urine can detect fragments of the infectious agent.The procedure differs somewhat for women and men. Laboratory testing of urine samples now can be performed with dipsticks that indicate immune system responses to infection, as well as with microscopic analysis of samples. The presence of hematuria, or blood in the urine, may indicate acute UTIs, kidney disease, kidney stones, inflammation of the prostate (in men), endometriosis (in women), or cancer of the urinary tract. In some cases, blood in the urine results from athletic training, particularly in runners. Treatment Unfortunately mesna is ineffective as a treatment once hemorrhagic cystitis has developed. Although rare, once a case of radiation-induced hemorrhagic cystitis is diagnosed there is no empirically-proven treatments to heal this type of condition, which can severely degrade a patients quality of life and might possibly lead to kidney failure with risk of death. Viral hemorrhagic cystitis in children generally spontaneously resolves within a few days. The first step in the treatment of HC should be directed toward clot evacuation. Bladder outlet obstruction from clots can lead to urosepsis, bladder rupture, and kidney failure. Clot evacuation can be performed by placing a wide-lumen bladder catheter at bedside. The bladder can be irrigated with water or sodium chloride solution. The use of water is preferable because water can help with clot lysis. Care must be taken to not overdistend the bladder and cause a perforation. Hyperbaric oxygen (HBO2) therapy has been proven to be effective in treating radiation-induced hemorrhagic cystitis. == References ==
Placental abruption	Placental abruption is when the placenta separates early from the uterus, in other words separates before childbirth. It occurs most commonly around 25 weeks of pregnancy. Symptoms may include vaginal bleeding, lower abdominal pain, and dangerously low blood pressure. Complications for the mother can include disseminated intravascular coagulopathy and kidney failure. Complications for the baby can include fetal distress, low birthweight, preterm delivery, and stillbirth.The cause of placental abruption is not entirely clear. Risk factors include smoking, pre-eclampsia, prior abruption (most important and predictive risk factor), trauma during pregnancy, cocaine use, and previous cesarean section. Diagnosis is based on symptoms and supported by ultrasound. It is classified as a complication of pregnancy.For small abruption, bed rest may be recommended, while for more significant abruptions or those that occur near term, delivery may be recommended. If everything is stable, vaginal delivery may be tried, otherwise cesarean section is recommended. In those less than 36 weeks pregnant, corticosteroids may be given to speed development of the babys lungs. Treatment may require blood transfusion or emergency hysterectomy.Placental abruption occurs in about 1 in 200 pregnancies. Along with placenta previa and uterine rupture it is one of the most common causes of vaginal bleeding in the later part of pregnancy. Placental abruption is the reason for about 15% of infant deaths around the time of birth. The condition was described at least as early as 1664. Signs and symptoms In the early stages of placental abruption, there may be no symptoms. When symptoms develop, they tend to develop suddenly. Common symptoms include: sudden-onset abdominal pain contractions that seem continuous and do not stop vaginal bleeding enlarged uterus (disproportionate to the gestational age of the fetus) decreased fetal movement decreased fetal heart rate.Vaginal bleeding, if it occurs, may be bright red or dark.A placental abruption caused by arterial bleeding at the center of the placenta leads to sudden development of severe symptoms and life-threatening conditions including fetal heart rate abnormalities, severe maternal hemorrhage, and disseminated intravascular coagulation (DIC). Those abruptions caused by venous bleeding at the periphery of the placenta develop more slowly and cause small amounts of bleeding, intrauterine growth restriction, and oligohydramnios (low levels of amniotic fluid). Risk factors Pre-eclampsia Chronic hypertension Short umbilical cord Premature rupture of membranes Prolonged rupture of membranes (>24 hours). Thrombophilia Polyhydramnios Multiparity Multiple pregnancy Maternal age: pregnant women who are younger than 20 or older than 35 are at greater riskRisk factors for placental abruption include disease, trauma, history, anatomy, and exposure to substances. The risk of placental abruption increases sixfold after severe maternal trauma. Anatomical risk factors include uncommon uterine anatomy (e.g. bicornuate uterus), uterine synechiae, and leiomyoma. Substances that increase risk of placental abruption include cocaine and tobacco when consumed during pregnancy, especially the third trimester. History of placental abruption or previous Caesarian section increases the risk by a factor of 2.3. Pathophysiology In the vast majority of cases, placental abruption is caused by the maternal vessels tearing away from the decidua basalis, not the fetal vessels. The underlying cause is often unknown. A small number of abruptions are caused by trauma that stretches the uterus. Because the placenta is less elastic than the uterus, it tears away when the uterine tissue stretches suddenly. When anatomical risk factors are present, the placenta does not attach in a place that provides adequate support, and it may not develop appropriately or be separated as it grows. Cocaine use during the third trimester has a 10% chance of causing abruption. Though the exact mechanism is not known, cocaine and tobacco cause systemic vasoconstriction, which can severely restrict the placental blood supply (hypoperfusion and ischemia), or otherwise disrupt the vasculature of the placenta, causing tissue necrosis, bleeding, and therefore abruption.In most cases, placental disease and abnormalities of the spiral arteries develop throughout the pregnancy and lead to necrosis, inflammation, vascular problems, and ultimately, abruption. Because of this, most abruptions are caused by bleeding from the arterial supply, not the venous supply. Production of thrombin via massive bleeding causes the uterus to contract and leads to DIC.The accumulating blood pushes between the layers of the decidua, pushing the uterine wall and placenta apart. When the placenta is separated, it is unable to exchange waste, nutrients, and oxygen, a necessary function for the fetuss survival. The fetus dies when it no longer receives enough oxygen and nutrients to survive. Diagnosis Placental abruption is suspected when a pregnant mother has sudden localized abdominal pain with or without bleeding. The fundus may be monitored because a rising fundus can indicate bleeding. An ultrasound may be used to rule out placenta praevia but is not diagnostic for abruption. The diagnosis is one of exclusion, meaning other possible sources of vaginal bleeding or abdominal pain have to be ruled out in order to diagnose placental abruption. Of note, use of magnetic resonance imaging has been found to be highly sensitive in depicting placental abruption, and may be considered if no ultrasound evidence of placental abruption is present, especially if the diagnosis of placental abruption would change management. Classification Based on severity: Class 0: Asymptomatic. Diagnosis is made retrospectively by finding an organized blood clot or a depressed area on a delivered placenta. Class 1: Mild and represents approximately 48% of all cases. Characteristics include the following: No vaginal bleeding to mild vaginal bleeding Slightly tender uterus Normal maternal blood pressure and heart rate No coagulopathy No fetal distress Class 2: Moderate and represents approximately 27% of all cases. Characteristics include the following: No vaginal bleeding to moderate vaginal bleeding Moderate-to-severe uterine tenderness with possible tetanic contractions Maternal tachycardia with orthostatic changes in blood pressure and heart rate Fetal distress Hypofibrinogenemia (i.e., 50–250 mg/dL) Class 3: Severe and represents approximately 24% of all cases. Characteristics include the following: No vaginal bleeding to heavy vaginal bleeding Very painful tetanic uterus Maternal shock Hypofibrinogenemia (i.e., <150 mg/dL) Coagulopathy Fetal death Prevention Although the risk of placental abruption cannot be eliminated, it can be reduced. Avoiding tobacco, alcohol and cocaine during pregnancy decreases the risk. Staying away from activities which have a high risk of physical trauma is also important. Women who have high blood pressure or who have had a previous placental abruption and want to conceive must be closely supervised by a doctor.The risk of placental abruption can be reduced by maintaining a good diet including taking folate, regular sleep patterns and correction of pregnancy-induced hypertension.Use of aspirin before 16 weeks of pregnancy to prevent pre-eclampsia also appears effective at preventing placental abruption. Management Treatment depends on the amount of blood loss and the status of the fetus. If the fetus is less than 36 weeks, and neither mother or fetus are in any distress, then they may simply be monitored in hospital until a change in condition or fetal maturity whichever comes first. Immediate delivery of the fetus may be indicated if the fetus is mature or if the fetus or mother is in distress. Blood volume replacement to maintain blood pressure and blood plasma replacement to maintain fibrinogen levels may be needed. Vaginal birth is usually preferred over Caesarean section unless there is fetal distress. Caesarean section carries an increased risk in cases of disseminated intravascular coagulation. People should be monitored for 7 days for postpartum hemorrhage. Excessive bleeding from uterus may necessitate hysterectomy. The mother may be given Rhogam if she is Rh negative. Prognosis The prognosis of this complication depends on whether treatment is received by the patient, on the quality of treatment, and on the severity of the abruption. Outcomes for the baby also depend on the gestational age.In the Western world, maternal deaths due to placental abruption are rare. The fetal prognosis is worse than the maternal prognosis; approximately 12% of fetuses affected by placental abruption die. 77% of fetuses that die from placental abruption die before birth; the remainder die due to complications of preterm birth.Without any form of medical intervention, as often happens in many parts of the world, placental abruption has a high maternal mortality rate. Mother A large loss of blood may require a blood transfusion. If the mothers blood loss cannot be controlled, an emergency hysterectomy may become necessary. The uterus may not contract properly after delivery so the mother may need medication to help her uterus contract. The mother may develop a blood clotting disorder, disseminated intravascular coagulation. A severe case of shock may affect other organs, such as the liver, kidney, and pituitary gland. Diffuse cortical necrosis in the kidney is a serious and often fatal complication. Placental abruption may cause bleeding through the uterine muscle and into the mothers abdominal cavity, a condition called Couvelaire uterus. Maternal death. Baby The baby may be born at a low birthweight. Preterm delivery (prior to 37 weeks gestation). The baby may be deprived of oxygen and thus develop asphyxia. Placental abruption may also result in death of the baby, or stillbirth. The newborn infant may have learning issues at later development stages, often requiring professional pedagogical aid. Epidemiology Placental abruption occurs in approximately 0.2–1% of all pregnancies. Though different causes change when abruption is most likely to occur, the majority of placental abruptions occur before 37 weeks gestation, and 12–14% occur before 32 weeks gestation. == References ==
Fasciculation	A fasciculation, or muscle twitch, is a spontaneous, involuntary muscle contraction and relaxation, involving fine muscle fibers. They are common, with as many as 70% of people experiencing them. They can be benign, or associated with more serious conditions. When no cause or pathology is identified, they are diagnosed as benign fasciculation syndrome. Diagnosis The most effective way to detect fasciculations may be surface electromyography (EMG). Surface EMG is more sensitive than needle electromyography and clinical observation in the detection of fasciculation in people with amyotrophic lateral sclerosis.Deeper areas of contraction can be detected by electromyography (EMG) testing, though they can happen in any skeletal muscle in the body. Fasciculations arise as a result of spontaneous depolarization of a lower motor neuron leading to the synchronous contraction of all the skeletal muscle fibers within a single motor unit. An example of normal spontaneous depolarization is the constant contractions of cardiac muscle, causing the heart to beat. Usually, intentional movement of the involved muscle causes fasciculations to cease immediately, but they may return once the muscle is at rest again. Tics must also be distinguished from fasciculations. Small twitches of the upper or lower eyelid, for example, are not tics, because they do not involve a whole muscle, rather are twitches of a few muscle fibre bundles, that are not suppressible. Causes Fasciculations have a variety of causes, the majority of which are benign, but can also be due to disease of the motor neurons. They are encountered by up to 70% of all healthy people, though for most, it is quite infrequent. In some cases, the presence of fasciculations can be annoying and interfere with quality of life. If a neurological examination is otherwise normal and EMG testing does not indicate any additional pathology, a diagnosis of benign fasciculation syndrome is usually made. Risk factors Risk factors for benign fasciculations are age, stress, fatigue, and strenuous exercise. Fasciculations can be caused by anxiety, caffeine or alcohol and thyroid disease. Magnesium deficiency is a common cause of fasciculation.Other factors may include the use of anticholinergic drugs over long periods. In particular, these include ethanolamines such as diphenhydramine (brand names Benadryl, Dimedrol, Daedalon and Nytol), used as an antihistamine and sedative, and dimenhydrinate (brand names Dramamine, Driminate, Gravol, Gravamin, Vomex, and Vertirosan) for nausea and motion sickness. Persons with benign fasciculation syndrome (BFS) may experience paraesthesia (especially numbness) shortly after taking such medication; fasciculation episodes begin as the medication wears off. Stimulants can cause fasciculations directly. These include caffeine, pseudoephedrine (Sudafed), amphetamines, and the asthma bronchodilator salbutamol (brand names Proventil, Combivent, Ventolin). Medications used to treat attention deficit disorder (ADHD) often contain stimulants as well, and are common causes of benign fasciculations. Since asthma and ADHD are much more serious than the fasciculations themselves, this side effect may have to be tolerated by the patient after consulting a physician or pharmacist. The depolarizing neuromuscular blocker succinylcholine causes fasciculations. It is a normal side effect of the drugs administration, and can be prevented with a small dose of a nondepolarizing neuromuscular blocker prior to the administration of succinylcholine, often 10% of a nondepolarizing NMBs induction dose. Even if a drug such as caffeine causes fasciculations, that does not necessarily mean it is the only cause. For example, a very slight magnesium deficiency by itself (see below) might not be enough for fasciculations to occur, but when combined with caffeine, the two factors together could be enough. Treatment Reducing stress and anxiety is therefore another useful treatment.There is no proven treatment for fasciculations in people with ALS. Among patients with ALS, fasciculation frequency is not associated with the duration of ALS and is independent of the degree of limb weakness and limb atrophy. No prediction of ALS disease duration can be made based on fasciculation frequency alone. Epidemiology Fasciculations are observed more often in males, and clinicians are overrepresented in study samples. See also Blepharospasm Carnitine palmitoyltransferase II deficiency Myokymia References == External links ==
Uterus	The uterus (from Latin "uterus", plural uteri) or womb () is the main hormone-responsive, secondary sex organ of the female reproductive system in humans, and most other mammals. Events occurring within the uterus are described with the term in utero. In the human, the lower end of the uterus, the cervix, opens into the vagina, while the upper end, the fundus, is connected to the fallopian tubes. It is within the uterus that the embryo and later fetus develops during gestation. In the human embryo, the uterus develops from the paramesonephric ducts which fuse into the single organ known as a simplex uterus. The uterus has different forms in many other animals and in some it exists as two separate uteri known as a duplex uterus. In medicine, and related professions the term uterus is consistently used, while the Germanic-derived term womb is commonly used in everyday contexts. Structure in humans The human uterus is located within the pelvic region immediately behind and almost overlying the bladder, and in front of the sigmoid colon. The human uterus is pear-shaped and about 7.6 cm (3.0 in) long, 4.5 cm (1.8 in) broad (side to side), and 3.0 cm (1.2 in) thick. A typical adult uterus weighs about 60 grams. The uterus can be divided anatomically into four regions: the fundus – the uppermost rounded portion of the uterus, the corpus (body), the cervix, and the cervical canal. The cervix protrudes into the vagina. The uterus is held in position within the pelvis by ligaments, which are part of the endopelvic fascia. These ligaments include the pubocervical ligaments, the cardinal ligaments, and the uterosacral ligaments. It is covered by a sheet-like fold of peritoneum, the broad ligament. From outside to inside, regions of the uterus include: Cervix uteri – "neck of uterus" External orifice of the uterus Cervical canal Internal orifice of the uterus Body (Latin: Corpus) Uterine cavity Fundus Layers The uterus has three layers, which together form the uterine wall. From innermost to outermost, these layers are the endometrium, myometrium, and perimetrium.The endometrium is the inner epithelial layer, along with its mucous membrane, of the mammalian uterus. It has a basal layer and a functional layer; the functional layer thickens and then is sloughed during the menstrual cycle or estrous cycle. During pregnancy, the uterine glands and blood vessels in the endometrium further increase in size and number and form the decidua. Vascular spaces fuse and become interconnected, forming the placenta, which supplies oxygen and nutrition to the embryo and fetus.The myometrium of the uterus mostly consists of smooth muscle. The innermost layer of myometrium is known as the junctional zone, which becomes thickened in adenomyosis.The perimetrium is a serous layer of visceral peritoneum. It covers the outer surface of the uterus.Surrounding the uterus is a layer or band of fibrous and fatty connective tissue called the parametrium that connects the uterus to other tissues of the pelvis. Commensal organisms are present in the uterus and form the uterine microbiome. Support The uterus is primarily supported by the pelvic diaphragm, perineal body, and urogenital diaphragm. Secondarily, it is supported by ligaments, including the peritoneal ligament and the broad ligament of uterus. Major ligaments It is held in place by several peritoneal ligaments, of which the following are the most important (there are two of each): Axis Normally, the human uterus lies in anteversion and anteflexion. In most women, the long axis of the uterus is bent forward on the long axis of the vagina, against the urinary bladder. This position is referred to as anteversion of the uterus. Furthermore, the long axis of the body of the uterus is bent forward at the level of the internal os with the long axis of the cervix. This position is termed anteflexion of the uterus. The uterus assumes an anteverted position in 50% of women, a retroverted position in 25% of women, and a midposed position in the remaining 25% of women. Position The uterus is located in the middle of the pelvic cavity, in the frontal plane (due to the broad ligament of the uterus). The fundus does not extend above the linea terminalis, while the vaginal part of the cervix does not extend below the interspinal line. The uterus is mobile and moves posteriorly under the pressure of a full bladder, or anteriorly under the pressure of a full rectum. If both are full, it moves upwards. Increased intra-abdominal pressure pushes it downwards. The mobility is conferred to it by a musculo-fibrous apparatus that consists of suspensory and sustentacular parts. Under normal circumstances, the suspensory part keeps the uterus in anteflexion and anteversion (in 90% of women) and keeps it "floating" in the pelvis. The meanings of these terms are described below: The sustentacular part supports the pelvic organs and comprises the larger pelvic diaphragm in the back and the smaller urogenital diaphragm in the front. The pathological changes of the position of the uterus are: retroversion/retroflexion, if it is fixed hyperanteflexion – tipped too forward; most commonly congenital, but may be caused by tumors anteposition, retroposition, lateroposition – the whole uterus is moved; caused by parametritis or tumors elevation, descensus, prolapse rotation (the whole uterus rotates around its longitudinal axis), torsion (only the body of the uterus rotates around) inversionIn cases where the uterus is "tipped", also known as retroverted uterus, the woman may have symptoms of pain during sexual intercourse, pelvic pain during menstruation, minor incontinence, urinary tract infections, fertility difficulties, and difficulty using tampons. A pelvic examination by a doctor can determine if a uterus is tipped. Blood supply The human uterus is supplied by arterial blood both from the uterine artery and the ovarian artery. Another anastomotic branch may also supply the uterus from anastomosis of these two arteries. Nerve supply Afferent nerves supplying the uterus are T11 and T12. Sympathetic supply is from the hypogastric plexus and the ovarian plexus. Parasympathetic supply is from the S2, S3 and S4 nerves. Development Bilateral Müllerian ducts form during early human fetal life. In males, anti-müllerian hormone (AMH) secreted from the testes leads to the ducts regression. In females, these ducts give rise to the Fallopian tubes and the uterus. In humans, the lower segments of the two ducts fuse to form a single uterus; in cases of uterine malformations this fusion may be disturbed. The different uterine morphologies among the mammals are due to varying degrees of fusion of the Müllerian ducts. Various congenital conditions of the uterus can develop in utero. Though uncommon, some of these are didelphic uterus, bicornate uterus and others. Function The reproductive function of the human uterus is to accept a fertilized ovum, which passes through the utero-tubal junction from the fallopian tube. The fertilized ovum divides mitotically to become a blastocyst, which implants into the endometrium and derives nourishment from blood vessels which develop exclusively for this purpose. The fertilized ovum becomes an embryo, attaches to the wall of the uterus, creates a placenta, and develops into a fetus (gestates) until childbirth occurs. Due to anatomical barriers such as the pelvis, the uterus is pushed partially into the abdomen due to its expansion during pregnancy. Even during pregnancy, the mass of a human uterus amounts to only about a kilogram (2.2 pounds). The uterus also plays a role in sexual response, by directing blood flow to the pelvis and ovaries, and to the external genitalia There is also some evidence from rat studies that the uterus plays a role in cognition in a similar way to the ovaries. A study on rat models found that when the uterus was removed, the rats performed more poorly on spatial memory tasks. Prof. Bimonte-Nelson, the co-author of the study, explained: "the bodys autonomic nervous system, which regulates automated metabolic processes, such as heart rate, breathing, digestion, and sexual arousal, also has links to the uterus and brain." No similar studies have yet been conducted on humans. Clinical significance A hysterectomy is the surgical removal of the uterus which may be carried out for a number of reasons including the ridding of tumours both benign and malignant. A complete hysterectomy involves the removal of the body, fundus, and cervix of the uterus. A partial hysterectomy may just involve the removal of the uterine body while leaving the cervix intact. It is the most commonly performed gynecological surgical procedure. During pregnancy the growth rate of the fetus can be assessed by measuring the fundal height. Some pathological states include: Prolapse of the uterus Carcinoma of the cervix – malignant neoplasm Carcinoma of the uterus – malignant neoplasm Fibroids – benign neoplasms Adenomyosis – ectopic growth of endometrial tissue within the myometrium Endometritis, infection at the uterine cavity Pyometra – infection of the uterus, most commonly seen in dogs Uterine malformations mainly congenital malformations including Uterine Didelphys, bicornuate uterus and septate uterus. It also includes congenital absence of the uterus Rokitansky syndrome Ashermans syndrome, also known as intrauterine adhesions, occurs when the basal layer of the endometrium is damaged by instrumentation (e.g., D&C) or infection (e.g., endometrial tuberculosis) resulting in endometrial scarring followed by adhesion formation that partially or completely obliterates the uterine cavity Hematometra, which is accumulation of blood within the uterus. Accumulation of fluids other than blood or of unknown constitution. One study came to the conclusion that postmenopausal women with endometrial fluid collection on gynecologic ultrasonography should undergo endometrial biopsy if the endometrial lining is thicker than 3 mm or if the endometrial fluid is echogenic. In cases of a lining 3 mm or less and clear endometrial fluid, endometrial biopsy was not regarded to be necessary, but endocervical curettage to rule out endocervical cancer was recommended. Myometritis – inflammation of the muscular uterine wall. Other animals Most animals that lay eggs, such as birds and reptiles, including most ovoviviparous species, have an oviduct instead of a uterus. However, recent research into the biology of the viviparous (not merely ovoviviparous) skink Trachylepis ivensi has revealed development of a very close analogue to eutherian mammalian placental development.In monotremes, mammals which lay eggs, namely the platypus and the echidnas, either the term uterus or oviduct is used to describe the same organ, but the egg does not develop a placenta within the mother and thus does not receive further nourishment after formation and fertilization. Marsupials have two uteri, each of which connect to a lateral vagina and which both use a third, middle "vagina" which functions as the birth canal. Marsupial embryos form a choriovitelline placenta (which can be thought of as something between a monotreme egg and a "true" placenta), in which the eggs yolk sac supplies a large part of the embryos nutrition but also attaches to the uterine wall and takes nutrients from the mothers bloodstream. However, bandicoots also have a rudimentary chorioallantoic placenta, similar to those of placental mammals. The fetus usually develops fully in placental mammals and only partially in marsupials including kangaroos and opossums. In marsupials the uterus forms as a duplex organ of two uteri. In monotremes (egg-laying mammals) such as the platypus, the uterus is duplex and rather than nurturing the embryo, secretes the shell around the egg. It is essentially identical with the shell gland of birds and reptiles, with which the uterus is homologous.In mammals, the four main forms of the uterus are: duplex, bipartite, bicornuate and simplex. Duplex There are two wholly separate uteri, with one fallopian tube each. Found in marsupials (such as kangaroos, Tasmanian devils, opossums, etc.), rodents (such as mice, rats, and guinea pigs), and lagomorpha (rabbits and hares). Bipartite The two uteri are separate for most of their length, but share a single cervix. Found in ruminants (deer, moose, elk etc.), hyraxes, cats, and horses. Bicornuate The upper parts of the uterus remain separate, but the lower parts are fused into a single structure. Found in dogs, pigs, elephants, whales, dolphins, and tarsiers, and strepsirrhine primates among others. Simplex The entire uterus is fused into a single organ. Found in higher primates (including humans and chimpanzees). Occasionally, some individual females (including humans) may have a bicornuate uterus, a uterine malformation where the two parts of the uterus fail to fuse completely during fetal development.Two uteri usually form initially in a female and usually male fetus, and in placental mammals they may partially or completely fuse into a single uterus depending on the species. In many species with two uteri, only one is functional. Humans and other higher primates such as chimpanzees, usually have a single completely fused uterus, although in some individuals the uteri may not have completely fused. Additional images See also Menopause Artificial uterus Social uterus Unicornuate uterus Uterus-like mass References External links Anatomy photo:43:01-0102 at the SUNY Downstate Medical Center – "The Female Pelvis: Organs in the Female and male Pelvis in situ" Encyclopedia.com Uterus Anatomy Uterus Pregnancy
Stenosis	A stenosis (from Ancient Greek στενός, "narrow") is an abnormal narrowing in a blood vessel or other tubular organ or structure such as foramina and canals. It is also sometimes called a stricture (as in urethral stricture).Stricture as a term is usually used when narrowing is caused by contraction of smooth muscle (e.g. achalasia, prinzmetal angina); stenosis is usually used when narrowing is caused by lesion that reduces the space of lumen (e.g. atherosclerosis). The term coarctation is another synonym, but is commonly used only in the context of aortic coarctation.Restenosis is the recurrence of stenosis after a procedure. Types The resulting syndrome depends on the structure affected. Examples of vascular stenotic lesions include: Intermittent claudication (peripheral artery stenosis) Angina (coronary artery stenosis) Carotid artery stenosis which predispose to (strokes and transient ischaemic episodes) Renal artery stenosis The types of stenoses in heart valves are: Pulmonary valve stenosis, which is the thickening of the pulmonary valve, therefore causing narrowing Mitral valve stenosis, which is the thickening of the mitral valve (of the left heart), therefore causing narrowing Tricuspid valve stenosis, which is the thickening of the tricuspid valve (of the right heart), therefore causing narrowing Aortic valve stenosis, which is the thickening of the aortic valve, therefore causing narrowingStenoses/strictures of other bodily structures/organs include: Pyloric stenosis (gastric outflow obstruction) Lumbar, cervical or thoracic spinal stenosis Subglottic stenosis (SGS) Tracheal stenosis Obstructive jaundice (biliary tract stenosis) Bowel obstruction Phimosis Non-communicating hydrocephalus due to aqueductal stenosis Stenosing tenosynovitis Atherosclerosis Esophageal stricture Achalasia Prinzmetal angina Vaginal stenosis Meatal stenosis Causes alcohol atherosclerosis causes stenotic lesions in arteries. birth defects calcification diabetes headbanging – as in the case of Dave Mustaine iatrogenic, e.g. secondary to radiation therapy infection inflammation ischemia neoplasm – in such cases, the stenosis is often said to be "malignant" or "benign", although this attribute actually refers to the neoplasm itself. smoking ureteral urethral Diagnosis Stenoses of the vascular type are often associated with unusual blood sounds resulting from turbulent flow over the narrowed blood vessel. This sound can be made audible by a stethoscope, but diagnosis is generally made or confirmed with some form of medical imaging. See also Atresia References External links "Tracheal Stenosis Audio and Video". Archived from the original on 2007-01-12. "Symptoms of Urethral Stricture". 20 May 2011. Archived from the original on July 17, 2016.
Opioid use disorder	Opioid use disorder (OUD) is a substance use disorder relating to the use of an opioid. Any such disorder causes significant impairment or distress. Signs of the disorder include a strong desire to use opioids, increased tolerance to opioids, difficulty fulfilling obligations, trouble reducing use, and withdrawal symptoms with discontinuation. Opioid withdrawal symptoms may include nausea, muscle aches, diarrhea, trouble sleeping, agitation, and a low mood. Addiction and dependence are components of a substance use disorder. Complications may include opioid overdose, suicide, HIV/AIDS, hepatitis C, and problems at school, work, or home.An article in The Lancet compared the harm and dependence liability of 20 drugs, using a scale from zero to three for physical dependence, psychological dependence, and pleasure to create a mean score for dependence. The 20 drugs were several opioids (morphine, heroin, methadone, hydromorphone, oxycodone), barbiturates (pentobarbital, secobarbital, amobarbital, phenobarbital), benzodiazepines (diazepam, temazepam, nitrazepam, lorazepam, triazolam), nicotine, cocaine, amphetamine, MDMA (ecstasy), alcohol, and cannabis. Selected results can be seen in the chart below. Diacetylmorphine and morphine both scored a 3.0 and ranked highest. Hydromorphone followed with a mean of 2.76, cocaine scoring 2.4, oxycodone 2.31, and methadone at 1.75. The mean benzodiazepine score was elevated to due to high scores exhibited by triazolam and temazepam for pleasure and psychological dependence. Opioids include substances such as heroin, morphine, fentanyl, codeine, dihydrocodeine, oxycodone, and hydrocodone. In the United States, a majority of heroin users begin by using prescription opioids that may also be bought illegally. Risk factors for misuse include a history of substance use, substance use among family and friends, mental illness, low socioeconomic status, and race. Diagnosis may be based on criteria by the American Psychiatric Association in the DSM-5. If more than two of eleven criteria are present during a year, the diagnosis is said to be present.Individuals with an opioid use disorder are often treated with opioid replacement therapy using methadone or buprenorphine. Being on such treatment reduces the risk of death. Additionally, individuals may benefit from cognitive behavioral therapy, other forms of support from mental health professionals such as individual or group therapy, twelve-step programs, and other peer support programs. The medication naltrexone may also be useful to prevent relapse. Naloxone is useful for treating an opioid overdose and giving those at risk naloxone to take home is beneficial.In 2013, opioid use disorders affected about 0.4% of people. As of 2016, about 27 million people are affected. Long term opioid use occurs in about 4% of people following their use for trauma or surgery-related pain. Onset is often in young adulthood. Males are affected more often than females. It resulted in 122,000 deaths worldwide in 2015, up from 18,000 deaths in 1990. In the United States during 2020 alone, there were more than 65,000 deaths due to opioid overdose, of which more than 15,000 were the result of heroin use. Signs and symptoms Signs and symptoms include: Drug seeking behavior Increased use over time Legal or social ramifications secondary to drug use Multiple prescriptions from different providers Multiple medical complications from drug use (HIV/AIDS, hospitalizations, abscesses) Opioid cravings Withdrawal symptomsAddiction and dependence are components of a substance use disorder and addiction represents the more severe form. Opioid dependence can occur as physical dependence, psychological dependence, or both. Withdrawal Opioid withdrawal can occur with a sudden decrease in, or the cessation of, opioids after prolonged use. Onset of withdrawal depends on which opioid was used last. With heroin this typically occurs five hours after use, while with methadone it might not occur until two days later. The length of time that major symptoms occur also depends on the opioid used. For heroin withdrawal, symptoms are typically greatest at two to four days, and can last for up to two weeks. Less significant symptoms may remain for an even longer period, in which case the withdrawal is known as post-acute-withdrawal syndrome. Treatment of withdrawal may include methadone and buprenorphine. Medications for nausea or diarrhea may also be used. Opioid intoxication Signs and symptoms of opioid intoxication include: Opioid overdose Signs and symptoms of opioid overdose include, but are not limited to: Pin-point pupils may occur. Patient presenting with dilated pupils may still be experiencing an opioid overdose. Decreased heart rate Decreased body temperature Decreased breathing Altered level of consciousness. People may be unresponsive or unconscious. Pulmonary edema (fluid accumulation in the lungs) Shock Death Cause Opioid use disorder can develop as a result of self-medication. Scoring systems have been derived to assess the likelihood of opiate addiction in chronic pain patients. Prescription opioids are the source of nearly half of misused opioids and the majority of these are initiated for trauma or surgery pain management. Further to this, healthcare practitioners have long been aware that despite the effective use of opioids for managing pain, the empirical evidence that supports the use of opioids long term is minimal. In addition to this, many studies that involved patients with chronic pain have failed to show any sustained improvement in their pain or ability to function with long term opioid use.According to position papers on the treatment of opioid dependence published by the United Nations Office on Drugs and Crime and the World Health Organization, care providers should not treat opioid use disorder as the result of a weak moral character or will but as a medical condition. Some evidence suggests the possibility that opioid use disorders occur due to genetic or other chemical mechanisms which may be difficult to identify or change, such as dysregulation of brain circuitry involving reward and volition. However, the exact mechanisms involved are unclear, leading to debate regarding the influence of biology and free will. Mechanism Addiction Addiction is a brain disorder characterized by compulsive drug use despite adverse consequences. Addiction is a component of a substance use disorder and represents the most severe form of the disorder.Overexpression of the gene transcription factor ΔFosB in the nucleus accumbens plays a crucial role in the development of an addiction to opioids and other addictive drugs by sensitizing drug reward and amplifying compulsive drug-seeking behavior. Like other addictive drugs, overuse of opioids leads to increased ΔFosB expression in the nucleus accumbens. Opioids affect dopamine neurotransmission in the nucleus accumbens via the disinhibition of dopaminergic pathways as a result of inhibiting the GABA-based projections to the ventral tegmental area (VTA) from the rostromedial tegmental nucleus (RMTg), which negatively modulate dopamine neurotransmission. In other words, opioids inhibit the projections from the RMTg to the VTA, which in turn disinhibits the dopaminergic pathways that project from the VTA to the nucleus accumbens and elsewhere in the brain.The differences in the genetic regions encoding the dopamine receptors for each individual may help to elucidate part of the risk for opioid addiction and general substance abuse. Studies of the D2 Dopamine Receptor, in particular, have shown some promising results. One specific SNP is at the TaqI RFLP (rs1800497). In a study of 530 Han Chinese heroin-addicted individuals from a Methadone Maintenance Treatment Program, those with the specific genetic variation showed higher mean heroin consumption by around double those without the SNP. This study showed a p-value of.003 and along with several other works, this helps to show the contribution of dopamine receptors to substance addiction and more specifically, to opioid abuse. Neuroimaging has shown functional and structural alterations in the brain. A 2017 study showed that chronic intake of opioids, such as heroin, may cause long-term effects in the orbitofrontal area (OFC), which is essential for regulating reward-related behaviors, emotional responses, and anxiety. Moreover, neuroimaging and neuropsychological studies demonstrated dysregulation of circuits associated with emotion, stress and high impulsivity. Dependence Drug dependence is an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake). Dependence is a component of a substance use disorder. Opioid dependence can manifest as physical dependence, psychological dependence, or both.Increased brain-derived neurotrophic factor (BDNF) signaling in the ventral tegmental area (VTA) has been shown to mediate opioid-induced withdrawal symptoms via downregulation of insulin receptor substrate 2 (IRS2), protein kinase B (AKT), and mechanistic target of rapamycin complex 2 (mTORC2). As a result of downregulated signaling through these proteins, opiates cause VTA neuronal hyperexcitability and shrinkage (specifically, the size of the neuronal soma is reduced). It has been shown that when an opiate-naive person begins using opiates in concentrations that induce euphoria, BDNF signaling increases in the VTA.Upregulation of the cyclic adenosine monophosphate (cAMP) signal transduction pathway by cAMP response element binding protein (CREB), a gene transcription factor, in the nucleus accumbens is a common mechanism of psychological dependence among several classes of drugs of abuse. Upregulation of the same pathway in the locus coeruleus is also a mechanism responsible for certain aspects of opioid-induced physical dependence. Opioid receptors A genetic basis for the efficacy of opioids in the treatment of pain has been demonstrated for several specific variations; however, the evidence for clinical differences in opioid effects is ambiguous. The pharmacogenomics of the opioid receptors and their endogenous ligands have been the subject of intensive activity in association studies. These studies test broadly for a number of phenotypes, including opioid dependence, cocaine dependence, alcohol dependence, methamphetamine dependence/psychosis, response to naltrexone treatment, personality traits, and others. Major and minor variants have been reported for every receptor and ligand coding gene in both coding sequences, as well as regulatory regions. Newer approaches shift away from analysis of specific genes and regions, and are based on an unbiased screen of genes across the entire genome, which have no apparent relationship to the phenotype in question. These GWAS studies yield a number of implicated genes, although many of them code for seemingly unrelated proteins in processes such as cell adhesion, transcriptional regulation, cell structure determination, and RNA, DNA, and protein handling/modifying. 118A>G variant While over 100 variants have been identified for the opioid mu-receptor, the most studied mu-receptor variant is the non-synonymous 118A>G variant, which results in functional changes to the receptor, including lower binding site availability, reduced mRNA levels, altered signal transduction, and increased affinity for beta-endorphin. In theory, all of these functional changes would reduce the impact of exogenous opioids, requiring a higher dose to achieve the same therapeutic effect. This points to a potential for greater addictive capacity in these individuals who require higher dosages to achieve pain control. However, evidence linking the 118A>G variant to opioid dependence is mixed, with associations shown in a number of study groups, but negative results in other groups. One explanation for the mixed results is the possibility of other variants which are in linkage disequilibrium with the 118A>G variant and thus contribute to different haplotype patterns that more specifically associated with opioid dependence. Non-opioid receptor genes The preproenkephalin gene, PENK, encodes for the endogenous opiates that modulate pain perception, and are implicated in reward and addiction. (CA) repeats in the 3 flanking sequence of the PENK gene was associated with greater likelihood of opiate dependence in repeated studies. Variability in the MCR2 gene, encoding melanocortin receptor type 2 has been associated with both protective effects and increased susceptibility to heroin addiction. The CYP2B6 gene of the cytochrome P450 family also mediates breakdown of opioids and thus may play a role in dependence and overdose. Diagnosis The DSM-5 guidelines for the diagnosis of opioid use disorder require that the individual has a significant impairment or distress related to opioid uses. To make the diagnosis two or more of eleven criteria must be present in a given year: More opioids are taken than intended The individual is unable to decrease the number of opioids used Large amounts of time are spent trying to obtain opioids, use opioids, or recover from taking them The individual has cravings for opioids Difficulty fulfilling professional duties at work or school Continued use of opioids leading to social and interpersonal consequences Decreased social or recreational activities Using opioids despite being in physically dangerous settings Continued use despite opioids worsening physical or psychological health (i.e. depression, constipation) Tolerance WithdrawalThe severity can be classified as mild, moderate, or severe based on the number of criteria present. Prevention The CDC gives specific recommendations for prescribers regarding initiation of opioids, clinically appropriate use of opioids, and assessing possible risks associated with opioid therapy. Large retail pharmacy chains in the US are implementing protocols, guidelines, and initiatives to take back unused opioids, providing naloxone kits, and being vigilant for suspicious prescriptions. Insurance programs can help limit opioid use by setting quantity limits on prescriptions or requiring prior authorizations for certain medications. Opioid related deaths Naloxone is used for the emergency treatment of an overdose. It can be given by many routes (e.g., intramuscular, intravenous, subcutaneous, intranasal, and inhalation) and acts quickly by displacing opioids from opioid receptors and preventing activation of these receptors by opioids. Naloxone kits are recommended for laypersons who may witness an opioid overdose, for individuals with large prescriptions for opioids, those in substance use treatment programs, or who have been recently released from incarceration. Since this is a life-saving medication, many areas of the United States have implemented standing orders for law enforcement to carry and give naloxone as needed. In addition, naloxone could be used to challenge a persons opioid abstinence status prior to starting a medication such as naltrexone, which is used in the management of opioid addiction.Good Samaritan laws typically protect bystanders that administer naloxone. In the United States, at least 40 states have Good Samaritan laws to encourage bystanders to take action without fear of prosecution. As of 2019, 48 states allow for a pharmacist to have the authority to distribute naloxone without an individual prescription.Homicide, suicide, accidents and liver disease are also opioid related causes of death for those with OUD. Many of these opioid related causes of death are unnoticed due to the often limited information provided on death certificates. Management Opioid use disorders typically require long-term treatment and care with the goal of reducing risks for the individual, reducing criminal behaviour, and improving the long-term physical and psychological condition of the person. Some strategies aim to reduce drug use and lead to abstinence from opioids, while others attempt to stabilize on prescribed methadone or buprenorphine with continued replacement therapy indefinitely. No single treatment works for everyone, so several strategies have been developed including therapy and drugs. As of 2013 in the US, there was a significant increase of prescription opioid abuse compared to illegal opiates like heroin. This development has also implications for the prevention, treatment and therapy of opioid dependence. Though treatment reduces mortality rates, the period during the first four weeks after treatment begins and the four weeks after treatment ceases are the times that carry the highest risk for drug-related deaths. These periods of increased vulnerability are significant because many of those in treatment leave programs during these critical periods. Medications Opioid replacement therapy (ORT) involves replacing an opioid, such as heroin, with a longer acting but less euphoric opioid. Commonly used drugs for ORT are methadone or buprenorphine which are taken under medical supervision. As of 2018, buprenorphine/naloxone is preferentially recommended, as the addition of the opioid antagonist naloxone is believed to reduce the risk of abuse via injection or insufflation without causing impairment.The driving principle behind ORT is the programs capacity to facilitate a resumption of stability in the users life, while the patient experiences reduced symptoms of drug withdrawal and less intense drug cravings; a strong euphoric effect is not experienced as a result of the treatment drug. In some countries (not the US, or Australia), regulations enforce a limited time for people on ORT programs that conclude when a stable economic and psychosocial situation is achieved. (People with HIV/AIDS or hepatitis C are usually excluded from this requirement.) In practice, 40–65% of patients maintain abstinence from additional opioids while receiving opioid replacement therapy and 70–95% can reduce their use significantly. Along with this is a concurrent elimination or reduction in medical (improper diluents, non-sterile injecting equipment), psychosocial (mental health, relationships), and legal (arrest and imprisonment) issues that can arise from the use of illegal opioids. Clonidine or lofexidine can help treat the symptoms of withdrawal.Participation in methadone and buprenorphine treatment reduces the risk of mortality due to overdose. The starting of methadone and the time immediately after leaving treatment with both drugs are periods of particularly increased mortality risk, which should be dealt with by both public health and clinical strategies. ORT has proven to be the most effective treatment for improving the health and living condition of people experiencing illegal opiate use or dependence, including mortality reduction and overall societal costs, such as the economic loss from drug-related crime and healthcare expenditure. ORT is endorsed by the World Health Organization, United Nations Office on Drugs and Crime and UNAIDS as being effective at reducing injection, lowering risk for HIV/AIDS, and promoting adherence to antiretroviral therapy.Buprenorphine and methadone work by reducing opioid cravings, easing withdrawal symptoms, and blocking the euphoric effects of opioids via cross-tolerance, and in the case of buprenorphine, a high-affinity partial agonist, also due to opioid receptor saturation. It is this property of buprenorphine that can induce acute withdrawal when administered before other opioids have left the body. Naltrexone, a μ-opioid receptor antagonist, also blocks the euphoric effects of opioids by occupying the opioid receptor, but it does not activate it, so it does not produce sedation, analgesia, or euphoria, and thus it has no potential for abuse or diversion.In the United States, since March 2020 as a result of the COVID-19 pandemic, buprenorphine may be dispensed via telemedicine.The ultimate aim of methadone maintenance is for the individual to return to a more normal life. They could be eligible for drug dependency care, career counseling, and educational assistance once they start taking methadone under medical supervision. They can self-refer to social service providers as they continue to feel better and want to get back on their feet. Methadone may even be able to assist these individuals in avoiding relapse. Methadone is a long-acting drug, which means it sticks to the same opioid receptors in the brain as opium and prescription painkillers. As a result, patients who are taking methadone as part of an overdose treatment procedure will not feel opioid cravings or the severe withdrawal effects that come with it. This will encourage people in rehab to concentrate more on medication, laying a solid foundation for healing, rather than constantly fighting cravings and relapse impulses. Methadone is a long-acting drug that can last up to 56 hours in the body. This means it fits better as a preventive drug so it doesnt require regular dosing during the day. Methadone users in detox also find more luck in therapy because they dont have to deal with constant opioid cravings or the severity of acute withdrawal symptoms. Advantages of methadone include: Reduction in infectious disease due to the cessation of opiate misuse, especially injection drug abuse Reduction in illegal crime due to the cessation in illicit drug usage Overall increase in quality of life Improved social functioning More attendance in alcohol therapy since withdrawal symptoms arent a diversionMethadone replacement therapy will also help people achieve stabilization early on in their rehabilitation. People should devote 100% of their time to recovery, helping them to solve the underlying problems that lead to their opiate addiction. They will get a career and start to find a better balance in their lives. It also enables parents to continue raising their children in a safe home environment. When their conditions improve and they want to refrain from taking methadone, they must be properly weaned off the medication, which must be done under medical observation. Although other medication-assisted therapies for opiate addiction, such as buprenorphine, are available, methadone is often seen as the most promising alternative for people who are heavily addicted to opiates. Methadone has a number of serious side effects, including: Slowed breathing Sexual dysfunction Nausea Vomiting Restlessness Itchy eyesDosages can be adjusted after 1–2 days, or another medication may be recommended for your situation if you experience side effects. Lung and breathing complications are possible long-term side effects of methadone use. Methadone, as an opiate, has the potential to be addictive. Many opponents believe that replacement drugs only substitute one addiction with another, and that methadone can be manipulated and exploited in some cases. Long-term usage has the ability to cause brain changes. Methadone causes changes in thought, cognitive performance, and memory by influencing nerve cells in the brain. An initial review is performed during alcohol therapy. The person will be evaluated and interviewed during this evaluation, and then the treatment team will then devise the optimal treatment plan for that individual. Methadone Methadone is a drug used for both opioid overuse treatment and for chronic pain, it is known as a full opioid agonist. Methadone is the most common prescribed out of all the medications used for addiction; this is due to the fact that it has more advantages and less disadvantages than the other medications. Due to methadones longer half life, it is much more challenging to prescribe dosage amounts compared to others. The long half life has good benefits, one of these benefits being the fact that if a dose is missed in the 24 hours of the last, the patient will not typically struggle with withdrawal symptoms quite yet. Methadone can be found in a couple different forms: tablet, oral solution, or an injection. The first time this medication was put to use was during World War II, it was a safer alternative to morphine. Buprenorphine Buprenorphine is a partial opioid receptor agonist. Unlike methadone and other full opioid receptor agonists, buprenorphine is less likely to cause respiratory depression due to its ceiling effect. Buprenorphine is known to be more at a risk of misuse or overdose compared to buprenorphine-naloxone and methadone, but treatment with buprenorphine may be associated with reduced mortality. Buprenorphine under the tongue is often used to manage opioid dependence. Preparations were approved for this use in the United States in 2002. Some formulations of buprenorphine incorporate the opiate antagonist naloxone during the production of the pill form to prevent people from crushing the tablets and injecting them, instead of using the sublingual (under the tongue) route of administration. Other opioids Evidence of effects of heroin maintenance compared to methadone are unclear as of 2010. A Cochrane review found some evidence in opioid users who had not improved with other treatments. In Switzerland, Germany, the Netherlands, and the United Kingdom, long-term injecting drug users who do not benefit from methadone and other medication options may be treated with injectable heroin that is administered under the supervision of medical staff. Other countries where it is available include Spain, Denmark, Belgium, Canada, and Luxembourg.Dihydrocodeine in both extended-release and immediate-release form are also sometimes used for maintenance treatment as an alternative to methadone or buprenorphine in some European countries. Dihydrocodeine is an opioid agonist. It may be used as a second line treatment. A 2020 systematic review found low quality evidence that dihydrocodeine may be no more effective than other routinely used medication interventions in reducing illicit opiate use.An extended-release morphine confers a possible reduction of opioid use and with fewer depressive symptoms but overall more adverse effects when compared to other forms of long-acting opioids. Retention in treatment was not found to be significantly different. It is used in Switzerland and more recently in Canada. Naltrexone Naltrexone is an opioid receptor antagonist used for the treatment of opioid addiction. Naltrexone is not as widely used as buprenorphine or methadone for OUD due to low rates of patient acceptance, non-adherence due to daily dosing, and difficulty achieving abstinence from opioids before beginning treatment. Additionally, dosing naltrexone after recent opioid use could lead to precipitated withdrawal. Conversely, naltrexone antagonism at the opioid receptor can be overcome with higher doses of opioids. Naltrexone monthly IM injections received FDA approval in 2010, for the treatment of opioid dependence in abstinent opioid users. Behavioral therapy Cognitive behavioral therapy Cognitive behavioral therapy (CBT), a form of psychosocial intervention that is used to improve mental health, may not be as effective as other forms of treatment. CBT primarily focuses on an individuals coping strategies to help change their cognition, behaviors and emotions about the problem. This intervention has demonstrated success in many psychiatric conditions (e.g., depression) and substance use disorders (e.g., tobacco). However, the use of CBT alone in opioid dependence has declined due to the lack of efficacy, and many are relying on medication therapy or medication therapy with CBT, since both were found to be more efficacious than CBT alone. A form of CBT therapy known as motivational interviewing (MI) is often used opioid use disorder. MI leverages a person intrinsic motivation to recover through education, formulation of relapse prevention strategies, reward for adherence to treatment guidelines, and positive thinking to keep motivation high—which are based on a persons socioeconomic status, gender, race, ethnicity, sexual orientation, and their readiness to recover. Twelve-step programs While medical treatment may help with the initial symptoms of opioid withdrawal, once the first stages of withdrawal are through, a method for long-term preventative care is attendance at 12-step groups such as Narcotics Anonymous. Narcotics Anonymous is a global service that provides multilingual recovery information and public meetings free of charge. Some evidence supports the use of these programs in adolescents as well.The 12-step program is an adapted form of the Alcoholics Anonymous program. The program strives to help create behavioural change by fostering peer-support and self-help programs. The model helps assert the gravity of addiction by enforcing the idea that addicts must surrender to the fact that they are addicted and be able to recognize the problem. It also helps maintain self-control and restraint to help promote ones capabilities. Digital care programs Digital care programs (see telehealth or digital health) have increased in number since the Coronavirus pandemic mandated the increased usage of remote healthcare options. These programs offer treatment and continuing care remotely, via smartphone and desktop applications. This often includes remote substance testing, access to peer support meetings, recovery coaching or therapy, and self-guided learning modules. Examples of digital care programs for opioid use disorder include: Chess, Pear Therapeutics, DynamiCare Health, Kaden Health and WeConnect. Epidemiology Globally, the number of people with opioid dependence increased from 10.4 million in 1990 to 15.5 million in 2010. In 2016, the numbers rose to 27 million people who experienced this disorder. Opioid use disorders resulted in 122,000 deaths worldwide in 2015, up from 18,000 deaths in 1990. Deaths from all causes rose from 47.5 million in 1990 to 55.8 million in 2013. United States The current epidemic of opioid abuse is the most lethal drug
Opioid use disorder	epidemic in American history. In 2008, there were four times as many deaths due to overdose than there were in 1999. In 2017, in the US, "the age-adjusted drug poisoning death rate involving opioid analgesics increased from 1.4 to 5.4 deaths per 100,000 population between 1999 and 2010, decreased to 5.1 in 2012 and 2013, then increased to 5.9 in 2014, and to 7.0 in 2015. The age-adjusted drug poisoning death rate involving heroin doubled from 0.7 to 1.4 deaths per 100,000 resident population between 1999 and 2011 and then continued to increase to 4.1 in 2015."In 2017, the U.S. Department of Health and Human Services (HHS) announced a public health emergency due to an increase in the misuse of opioids. The administration introduced a strategic framework called the Five-Point Opioid Strategy, which includes providing access recovery services, increasing the availability of reversing agents for overdose, funding opioid misuse and pain research, changing treatments of people managing pain, and updating public health reports related to combating opioid drug misuse.The US epidemic in the 2000s is related to a number of factors. Rates of opioid use and dependency vary by age, sex, race, and socioeconomic status. With respect to race the discrepancy in deaths is thought to be due to an interplay between physician prescribing and lack of access to healthcare and certain prescription drugs. Men are at higher risk for opioid use and dependency than women, and men also account for more opioid overdoses than women, although this gap is closing. Women are more likely to be prescribed pain relievers, be given higher doses, use them for longer durations, and may become dependent upon them faster.Deaths due to opioid use also tend to skew at older ages than deaths from use of other illicit drugs. This does not reflect opioid use as a whole, which includes individuals in younger age demographics. Overdoses from opioids are highest among individuals who are between the ages of 40 and 50, in contrast to heroin overdoses, which are highest among individuals who are between the ages of 20 and 30. 21- to 35-year-olds represent 77% of individuals who enter treatment for opioid use disorder, however, the average age of first-time use of prescription painkillers was 21.2 years of age in 2013. Among the middle class means of acquiring funds have included Elder financial abuse through a vulnerability of financial transactions of selling items and international dealers noticing a lack of enforcement in their transaction scams throughout the Caribbean.In 2018, the Massachusetts Supreme Judicial Court found that a probationer with opioid use disorder could be detained for a parole violation after she tested positive for fentanyl.In October 2021, New York Governor Kathy Hochul signed legislation to combat the opioid crisis. This included establishing a program for the use of medication-assisted substance use disorder treatment for incarcerated individuals in state and local correctional facilities, decriminalizing the possession and sale of hypodermic needles and syringes, establishing an online directory for distributors of opioid antagonists, and expanding the number of eligible crimes committed by individuals with a substance use disorder that may be considered for diversion to a substance use treatment program. Until these laws were signed, incarcerated New Yorkers did not reliably have access to medication-assisted treatment and syringe possession was still a class A misdemeanor despite New York authorizing and funding syringe exchange and access programs. This legislation acknowledges the ways New York State laws have contributed to opioid deaths: in 2020 more than 5112 people died from overdoses in New York State, with 2192 deaths in New York City. Charts of deaths involving specific opioids and classes of opioids History Opiate misuse has been recorded at least since 300 BC. Greek mythology describes Nepenthe (Greek “free from sorrow”) and how it was used by the hero of the Odyssey. Opioids have been used in the Near East for centuries. The purification of and isolation of opiates occurred in the early 19th century.Levacetylmethadol was previously used to treat opioid dependence. In 2003 the drugs manufacturer discontinued production. There are no available generic versions. LAAM produced long-lasting effects, which allowed the person receiving treatment to visit a clinic only three times per week, as opposed to daily as with methadone. In 2001, levacetylmethadol was removed from the European market due to reports of life-threatening ventricular rhythm disorders. In 2003, Roxane Laboratories, Inc. discontinued Orlaam in the US. See also Benzodiazepine withdrawal syndrome Doctor shopping Hyperkatifeia, hypersensitivity to emotional distress in the context of opioid abuse Physical dependence Post-acute-withdrawal syndrome Prescription drug abuse References External links Heroin information from the National Institute on Drug Abuse Opioid information at Opioids.Net Opioid Dependence Treatment and Guidelines Opioid Risk Tool (ORT) for Narcotic Abuse
Testicular pain	Testicular pain, also known as scrotal pain, occurs when part or all of either one or both testicles hurt. Pain in the scrotum is also often included. Testicular pain may be of sudden onset or of long duration.Causes range from non serious muscular skeletal problems to emergency conditions such as Fournier gangrene and testicular torsion. The diagnostic approach involves making sure no serious conditions are present. Diagnosis may be supported by ultrasound, urine tests, and blood tests.Pain management is typically given with definitive management depending on the underlying cause. Definition Testicular pain is when part or all of either one or both testicles hurt. Pain of the scrotum is often included. It may be either acute, subacute or chronic depending on its duration. Chronic scrotal pain Chronic scrotal pain (pain for greater than 3 months) may occur due to a number of underlying conditions. It occurs in 15-19% of men post vasectomy, due to infections such as epididymitis, prostatitis, and orchitis, as well as varicocele, hydrocele, spermatocele, polyarteritis nodosa, testicular torsion, previous surgery and trauma. In 25% of cases the cause is never determined. The pain can persist for a long and indefinite period of time following the vasectomy, in which case it is termed post-vasectomy pain syndrome (PVPS). Differential diagnosis The differential diagnosis of testicular pain is broad and involves conditions from benign to life-threatening. The most common causes of pain in children presenting to the emergency room are testicular torsion (16%), torsion of a testicular appendage (46%), and epididymitis (35%). In adults, the most common cause is epididymitis. Testicular torsion Testicular torsion usually presents with an acute onset of diffuse testicular pain and tenderness of less than 6 hrs of duration. There is often an absent or decreased cremasteric reflex, the testicle is elevated, and often is horizontal. It occurs annually in about 1 in 4,000 males before 25 years of age, is most frequent among adolescents (65% of cases presenting between 12 – 18 years of age), and is rare after 35 years of age. Because it can lead to necrosis within a few hours, it is considered a surgical emergency. Another version of this condition is a chronic illness called intermittent testicular torsion (ITT) which is characterized by recurrent rapid acute onset of pain in one testis which will temporarily assume a horizontal or elevated position in the scrotum similar to that of a full torsion followed by eventual spontaneous detortion and rapid solution of pain. Nausea or vomiting may also occur. Epididymitis and orchitis Epididymitis occurs when there is inflammation of the epididymis (a curved structure at the back of the testicle). This condition usually presents with gradual onset of varying degrees of pain, and the scrotum may be red, warm and swollen. It is often accompanied by symptoms of a urinary tract infection, fever, and in over half of cases it presents in combination with orchitis. In those between the ages of 14 to 35 it is usually caused by either gonorrhea or chlamydia. In people either older or younger E. coli is the most common bacterial infection. Treatment involves the use of antibiotics. Fourniers gangrene Fourniers gangrene (an aggressive and rapidly spreading infection of the perineum) usually presents with fever and intense pain. It is a rare condition but fatal if not identified and aggressively treated with a combination of surgical debridement and broad spectrum antibiotics. Others Many other less common conditions can lead to testicular pain. These include inguinal hernias, injury, hydroceles, degenerative disease of lumbar spine, disc herniations, and varicoceles among others. Testicular cancer is usually painless. Another potential cause is epididymal hypertension (also known as "blue balls"). Diagnostic approach Physical findings The cremaster reflex (elevation of the testicle in response to stroking the upper inner thigh) is typically present in epididymitis but absent in testicular torsion as the testis is already elevated. Prehns sign (the relief of pain with elevation) though a classic physical exam finding has not been found to be reliable in distinguishing torsion from other causes of testicular pain such as epididymitis. Laboratory tests Useful tests that may help in the determination of the cause include a urinalysis (usually normal in testicular torsion). Pyuria and bacteriuria (white blood cells and bacteria in the urine) in patients with acute scrotum suggests an infectious cause such as epididymitis or orchitis and specific testing for gonorrhea and chlamydia should be done. All people with chronic pain should be tested for gonorrhea and chlamydia. Imaging Ultrasound is useful if the cause is not certain based on the above measures. If the diagnosis of torsion is certain, imaging should not delay definitive management such as physical maneuvers and surgery. References == External links ==
Telangiectasia	Telangiectasias, also known as spider veins, are small dilated blood vessels that can occur near the surface of the skin or mucous membranes, measuring between 0.5 and 1 millimeter in diameter. These dilated blood vessels can develop anywhere on the body, but are commonly seen on the face around the nose, cheeks and chin. Dilated blood vessels can also develop on the legs, although when they occur on the legs, they often have underlying venous reflux or "hidden varicose veins" (see Venous hypertension section below). When found on the legs, they are found specifically on the upper thigh, below the knee joint and around the ankles. Many patients with spider veins seek the assistance of physicians who specialize in vein care or peripheral vascular disease. These physicians are called vascular surgeons or phlebologists. More recently, interventional radiologists have started treating venous problems. Some telangiectasias are due to developmental abnormalities that can closely mimic the behaviour of benign vascular neoplasms. They may be composed of abnormal aggregations of arterioles, capillaries or venules. Because telangiectasias are vascular lesions, they blanch when tested with diascopy. Telangiectasias, aside from presenting in many other conditions, are one of the features of the acronymically named CREST syndrome, a form of systemic scleroderma. The syndrome recognises the significantly co-presenting symptoms of calcinosis, Raynauds phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia. Causes The causes of telangiectasia can be divided into congenital and acquired factors. Genetic Goldman states that "numerous inherited or congenital conditions display cutaneous telangiectasia". These include: Bloom syndrome (homozygous null mutation in BLM DNA repair enzyme. similar mechanism and etiology to ataxia telangiectasia) Naevus flammeus (port-wine stain) Klippel–Trenaunay syndrome Maffucci syndrome (multiple enchondromas and hemangiomas) Hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu syndrome) Ataxia–telangiectasia Sturge–Weber syndrome, a nevus formation in the skin supplied by the trigeminal nerve and associated with facial port-wine stains, glaucoma, meningeal angiomas and intellectual disabilities Hypotrichosis–lymphedema–telangiectasia syndrome, caused by mutation in transcription factor SOX18 Venous hypertension In the past, it was believed that leg varicose veins or telangectasia were caused by high venous pressure or "venous hypertension". However it is now understood that venous reflux disease is usually the cause of these problems.Telangiectasia in the legs is often related to the presence of venous reflux within underlying varicose veins. Flow abnormalities within the medium-sized veins of the leg (reticular veins) can also lead to the development of telangiectasia. Factors that predispose to the development of varicose and telangiectatic leg veins include Age Sex: It used to be thought that females were affected far more than males. However, research has shown 79% of adult males and 88% of adult females have leg telangectasia (spider veins). Pregnancy: Pregnancy is a key factor contributing to the formation of varicose and spider veins. Changes in hormone levels are one of the most important reasons women are more likely to develop varicose veins during pregnancy. There is an increase in progesterone, which causes the veins to relax and potentially swell more easily. Theres also a significant increase in the blood volume during pregnancy, which tends to distend veins, causing valve dysfunction which leads to blood pooling in the veins. Moreover, later in pregnancy, the enlarged uterus can compress veins, causing higher vein pressure leading to dilated veins. Varicose veins that form during pregnancy may spontaneously improve or even disappear a few months after delivery. Life-style/occupation: Those who are involved with prolonged sitting or standing in their daily activities have an increased risk of developing varicose veins. The weight of the blood continuously pressing against the closed valves causes them to fail, leading to vein distention. Other acquired causes Acquired telangiectasia, not related to other venous abnormalities, for example on the face and trunk, can be caused by factors such as Cushings syndrome Rosacea Blepharitis Environmental damage such as that caused by sun or cold exposure Age Trauma to skin such as contusions or surgical incisions. Radiation exposure such as that experienced during radiotherapy for the treatment of cancer, e.g., radiation proctitis Chemotherapy Carcinoid syndrome Limited systemic sclerosis/scleroderma (a scleroderma sub-type) Chronic treatment with topical corticosteroids may lead to telangiectasia. Spider angiomas are a radial array of tiny arterioles that commonly occur in pregnant women and in patients with hepatic cirrhosis and are associated with palmar erythema. In men, they are related to high estrogen levels secondary to liver disease. Tempi syndrome Tobacco smoking Cutaneous collagenous vasculopathy Treatment Before any treatment of leg telangectasia (spider veins) is considered, it is essential to have duplex ultrasonography, the test that has replaced Doppler ultrasound. The reason for this is that there is a clear association between leg telangectasia (spider veins) and underlying venous reflux. Research has shown that 88% to 89% of women with telangectasia (spider veins) have refluxing reticular veins close, and 15% have incompetent perforator veins nearby. As such, it is essential to both find and treat underlying venous reflux before considering any treatment at all. Sclerotherapy is the "gold standard" and is preferred over laser for eliminating telangiectasiae and smaller varicose leg veins. A sclerosant medication is injected into the diseased vein so it hardens and eventually shrinks away. Recent evidence with foam sclerotherapy shows that the foam containing the irritating sclerosant quickly appears in the patients heart and lungs, and then in some cases travels through a patent foramen ovale to the brain. This has led to concerns about the safety of sclerotherapy for telangectasias and spider veins. In some cases stroke and transient ischemic attacks have occurred after sclerotherapy. Varicose veins and reticular veins are often treated before treating telangiectasia, although treatment of these larger veins in advance of sclerotherapy for telangiectasia may not guarantee better results. Varicose veins can be treated with foam sclerotherapy, endovenous laser treatment, radiofrequency ablation, or open surgery. The biggest risk, however, seems to occur with sclerotherapy, especially in terms of systemic risk of DVT, pulmonary embolism, and stroke.Other issues which arise with the use of sclerotherapy to treat spider veins are staining, shadowing, telangetatic matting, and ulceration. In addition, incompleteness of therapy is common, requiring multiple treatment sessions.Telangiectasias on the face are often treated with a laser. Laser therapy uses a light beam that is pulsed onto the veins in order to seal them off, causing them to dissolve. These light-based treatments require adequate heating of the veins. These treatments can result in the destruction of sweat glands, and the risk increases with the number of treatments. == References ==
Ophthalmoparesis	Ophthalmoparesis refers to weakness (-paresis) or paralysis (-plegia) of one or more extraocular muscles which are responsible for eye movements. It is a physical finding in certain neurologic, ophthalmologic, and endocrine disease. Internal ophthalmoplegia means involvement limited to the pupillary sphincter and ciliary muscle. External ophthalmoplegia refers to involvement of only the extraocular muscles. Complete ophthalmoplegia indicates involvement of both. Causes Ophthalmoparesis can result from disorders of various parts of the eye and nervous system: Infection around the eye. Ophthalmoplegia is an important finding in orbital cellulitis. The orbit of the eye, including mechanical restrictions of eye movement, as in Graves disease. The muscle, as in progressive external ophthalmoplegia or Kearns–Sayre syndrome. The neuromuscular junction, as in myasthenia gravis. The relevant cranial nerves (specifically the oculomotor, trochlear, and abducens), as in cavernous sinus syndrome or raised intracranial pressure. The brainstem nuclei of these nerves, as in certain patterns of brainstem stroke such as Fovilles syndrome. White matter tracts connecting these nuclei, as in internuclear ophthalmoplegia, an occasional finding in multiple sclerosis. Dorsal midbrain structures, as in Parinauds syndrome. Certain parts of the cerebral cortex (including the frontal eye fields), as in stroke. Toxic envenomation by mambas, taipans, and kraits.Thiamine deficiency can cause ophthalmoparesis in susceptible persons; this is part of the syndrome called Wernicke encephalopathy. The causal pathway by which this occurs is unknown. Intoxication with certain substances, such as phenytoin, can also cause ophthalmoparesis. Diagnosis Classification Ophthalmoparesis can involve any or all of the extraocular muscles, which include the superior recti, inferior recti, medial recti, lateral recti, inferior oblique and superior oblique muscles. It can also be classified by the directions of affected movements, e.g. "vertical ophthalmoparesis". Treatment Treatment and prognosis depend on the underlying condition. For example, in thiamine deficiency, treatment would be the immediate administration of vitamin B1. See also Paresis References == External links ==
Body odor	Body odor or body odour (BO) is present in all animals and its intensity can be influenced by many factors (behavioral patterns, survival strategies). Body odor has a strong genetic basis, but can also be strongly influenced by various diseases and physiological conditions. Though body odor has played an important role (and continues to do so in many life forms) in early humankind, it is generally considered to be an unpleasant odor amongst many human cultures. Causes In humans, the formation of body odors is caused by factors such as diet, sex, health, and medication, but the major contribution comes from bacterial activity on skin gland secretions. Humans have three types of sweat glands: eccrine sweat glands, apocrine sweat glands and sebaceous glands. Eccrine sweat glands are present from birth, while the latter two become activated during puberty. Among the different types of human skin glands, body odor is primarily the result of the apocrine sweat glands, which secrete the majority of chemical compounds that the skin flora metabolize into odorant substances. This happens mostly in the axillary (armpit) region, although the gland can also be found in the areola, anogenital region, and around the navel. In humans, the armpit regions seem more important than the genital region for body odor, which may be related to human bipedalism. The genital and armpit regions also contain springy hairs which help diffuse body odors.The main components of human axillary odor are unsaturated or hydroxylated branched fatty acids with E-3M2H (E-3-methylhex-2-enoic acid) and HMHA (3-hydroxy-3-methylhexanoic acid), sulfanylalkanols and particularly 3M3SH (3-methyl-3-sulfanylhexan-1-ol), and the odoriferous steroids androstenone (5α-androst-16-en-3-one) and androstenol (5α-androst-16-en-3α-ol). E-3M2H is bound and carried by two apocrine secretion odor-binding proteins, ASOB1 and ASOB2, to the skin surface.Body odor is influenced by the actions of the skin flora, including members of Corynebacterium, which manufacture enzymes called lipases that break down the lipids in sweat to create smaller molecules like butyric acid. Greater bacteria populations of Corynebacterium jeikeium are found more in the armpits of men, whereas greater population numbers of Staphylococcus haemolyticus are found in the armpits of women. This causes male armpits to give off a rancid/cheese-like smell, whereas female armpits give off a more fruity/onion-like smell. Staphylococcus hominis is also known for producing thioalcohol compounds that contribute to odors. These smaller molecules smell, and give body odor its characteristic aroma. Propionic acid (propanoic acid) is present in many sweat samples. This acid is a breakdown product of some amino acids by propionibacteria, which thrive in the ducts of adolescent and adult sebaceous glands. Because propionic acid is chemically similar to acetic acid, with similar characteristics including odor, body odors may be identified as having a vinegar-like smell by certain people. Isovaleric acid (3-methyl butanoic acid) is the other source of body odor as a result of actions of the bacteria Staphylococcus epidermidis, which is also present in several types of strong cheese. Factors such as food, drink, and diseases can affect body odor, as can lifestyle and genetics. Function Animals In many animals, body odor plays an important survival function. Strong body odor can be a warning signal for predators to stay away (such as porcupine stink), or it can also be a signal that the prey animal is unpalatable. For example, some animals species, who feign death to survive (like opossums), in this state produce a strong body odor to deceive a predator that the prey animal has been dead for a long time and is already in the advanced stage of decomposing. Some animals with strong body odor are rarely attacked by most predators, although they can still be killed and eaten by birds of prey, which are tolerant of carrion odors.Body odor is an important feature of animal physiology. It plays a different role in different animal species. For example, in some predator species that hunt by stalking (such as big and small cats), the absence of body odor is important, and they spend plenty of time and energy to keep their body free of odor. For other predators, such as those that hunt by visually locating prey and running for long distances after it (such as dogs and wolves), the absence of body odor is not critical. In most animals, body odor intensifies in moments of stress and danger. Humans Sebaceous and apocrine glands become active at puberty. This, as well as many apocrine glands being close to the sex organs, points to a role related to mating. Compared to other primates, humans have extensive axillary hair and have many odor producing sources, in particular many apocrine glands. In women, the sense of olfaction is strongest around the time of ovulation, significantly stronger than during other phases of the menstrual cycle and also stronger than the sense in males.Humans can olfactorily detect blood-related kin. Mothers can identify by body odor their biological children, but not their stepchildren. Preadolescent children can olfactorily detect their full siblings, but not half-siblings or step-siblings, and this might explain incest avoidance and the Westermarck effect. Babies can recognize their mothers by smell while mothers, fathers, and other relatives can identify a baby by smell.Humans have few olfactory receptor cells compared to dogs and few functional olfactory receptor genes compared to rats. This is in part due to a reduction of the size of the snout in order to achieve depth perception as well as other changes related to bipedalism. However, it has been argued that humans may have larger brain areas associated with olfactory perception compared to other species.Studies have suggested that people might be using odor cues associated with the immune system to select mates. Using a brain-imaging technique, Swedish researchers have shown that homosexual and heterosexual males brains respond in different ways to two odors that may be involved in sexual arousal, and that homosexual men respond in the same way as heterosexual women, though it could not be determined whether this was cause or effect. When the study was expanded to include lesbian women, the results were consistent with previous findings – meaning that lesbian women were not as responsive to male-identified odors, while responding to female odors in a similar way as heterosexual males. According to the researchers, this research suggests a possible role for human pheromones in the biological basis of sexual orientation. Genes affecting body odor MHC Body odor is largely influenced by major histocompatibility complex (MHC) molecules. These are genetically determined and play an important role in immunity of the organism. The vomeronasal organ contains cells sensitive to MHC molecules in a genotype-specific way.Experiments on animals and volunteers have shown that potential sexual partners tend to be perceived more attractive if their MHC composition is substantially different. Married couples are more different regarding MHC genes than would be expected by chance. This behavior pattern promotes variability of the immune system of individuals in the population, thus making the population more robust against new diseases. Another reason may be to prevent inbreeding. ABCC11 The ABCC11 gene determines axillary body odor and the type of earwax. The loss of a functional ABCC11 gene is caused by a 538G>A single-nucleotide polymorphism, resulting in a loss of body odor in people who are specifically homozygous for it. Firstly, it affects apocrine sweat glands by reducing secretion of odorous molecules and its precursors. The lack of ABCC11 function results in a decrease of the odorant compounds 3M2H, HMHA, and 3M3SH via a strongly reduced secretion of the precursor amino-acid conjugates 3M2H–Gln, HMHA–Gln, and Cys–Gly–(S) 3M3SH; and a decrease of the odoriferous steroids androstenone and androstenol, possibly due to the reduced levels and secretion of DHEAS and DHEA (possibly bacterial substrates for odoriferous steroids). Secondly, it is also associated with a strongly reduced/atrophic size of apocrine sweat glands and a decreased protein (such as ASOB2) concentration in axillary sweat.The non-functional ABCC11 allele is predominant among East Asians (80–95%), but very low in other ancestral groups (0–3%). Most of the worlds population has the gene that codes for the wet-type earwax and average body odor; however, East Asians are more likely to inherit the allele associated with the dry-type earwax and a reduction in body odor. The hypothesized reduction in body odor may be due to adaptation to colder climates by their ancient Northeast Asian ancestors.However, research has observed that this allele is not solely responsible for ethnic differences in scent. A 2016 study analyzed differences across ethnicities in volatile organic compounds (VOCs), across racial groups and found that while they largely did not differ significantly qualitatively, they did differ quantitatively. Of the observed differences, they were found to vary with ethnic origin, but not entirely with ABCC11 genotype.It has been noted that there is currently no evidence that sweat secretion glands nor sweat production varies across ethnicities. One large study failed to find any significant differences across ethnicity in residual compounds on the skin, including those located in sweat. If there were observed ethnic variants in skin odor, one would find sources to be much more likely in diet, hygiene, microbiome, and other environmental factors.Research has indicated a strong association between people with axillary osmidrosis and the ABCC11-genotypes GG or GA at the SNP site (rs17822931) in comparison to the genotype AA. * ND indicates that no detectable peak is found on the [M+H]+ ion trace of the selected analyte at the correct retention time. * HMHA: 3-hydroxy-3-methyl-hexanoic acid; 3M2H: (E)-3-methyl-2-hexenoic acid; 3M3SH: 3-methyl-3-sulfanylhexan-1-ol. Alterations Body odor may be reduced or prevented or even aggravated by using deodorants, antiperspirants, disinfectants, underarm liners, triclosan, special soaps or foams with antiseptic plant extracts such as ribwort and liquorice, chlorophyllin ointments and sprays topically, and chlorophyllin supplements internally. Although body odor is commonly associated with hygiene practices, its presentation can be affected by changes in diet as well as the other factors. Skin spectrophotometry analysis found that males who consumed more fruits and vegetables were significantly associated with more pleasant smelling sweat, which was described as "floral, fruity, sweet and medicinal qualities". Industry As many as 90% of Americans and 92% of teenagers use antiperspirants or deodorants. In 2014, the global market for deodorants was estimated at US$13.00 billion with a compound annual growth rate of 5.62% between 2015 and 2020. Medical conditions Osmidrosis or bromhidrosis is defined by a foul odor due to a water-rich environment that supports bacteria, which is caused by an abnormal increase in perspiration (hyperhidrosis). This can be particularly strong when it happens in the axillary region (underarms). In this case, the condition may be referred to as axillary osmidrosis. The condition can also be known medically as apocrine bromhidrosis, ozochrotia, fetid sweat, body smell, or malodorous sweating.Trimethylaminuria (TMAU), also known as fish odor syndrome or fish malodor syndrome, is a rare metabolic disorder where trimethylamine is released in the persons sweat, urine, and breath, giving off a strong fishy odor or strong body odor. See also References External links Flores, Graciela (November 4, 2004). "Immunity, smell linked". The Scientist Magazine.
Hepatitis	Hepatitis is inflammation of the liver tissue. Some people or animals with hepatitis have no symptoms, whereas others develop yellow discoloration of the skin and whites of the eyes (jaundice), poor appetite, vomiting, tiredness, abdominal pain, and diarrhea. Hepatitis is acute if it resolves within six months, and chronic if it lasts longer than six months. Acute hepatitis can resolve on its own, progress to chronic hepatitis, or (rarely) result in acute liver failure. Chronic hepatitis may progress to scarring of the liver (cirrhosis), liver failure, and liver cancer.Hepatitis is most commonly caused by the virus hepatovirus A, B, C, D, and E. Other viruses can also cause liver inflammation, including cytomegalovirus, Epstein–Barr virus, and yellow fever virus. Other common causes of hepatitis include heavy alcohol use, certain medications, toxins, other infections, autoimmune diseases, and non-alcoholic steatohepatitis (NASH). Hepatitis A and E are mainly spread by contaminated food and water. Hepatitis B is mainly sexually transmitted, but may also be passed from mother to baby during pregnancy or childbirth and spread through infected blood. Hepatitis C is commonly spread through infected blood such as may occur during needle sharing by intravenous drug users. Hepatitis D can only infect people already infected with hepatitis B.Hepatitis A, B, and D are preventable with immunization. Medications may be used to treat chronic viral hepatitis. Antiviral medications are recommended in all with chronic hepatitis C, except those with conditions that limit their life expectancy. There is no specific treatment for NASH; physical activity, a healthy diet, and weight loss are recommended. Autoimmune hepatitis may be treated with medications to suppress the immune system. A liver transplant may be an option in both acute and chronic liver failure.Worldwide in 2015, hepatitis A occurred in about 114 million people, chronic hepatitis B affected about 343 million people and chronic hepatitis C about 142 million people. In the United States, NASH affects about 11 million people and alcoholic hepatitis affects about 5 million people. Hepatitis results in more than a million deaths a year, most of which occur indirectly from liver scarring or liver cancer. In the United States, hepatitis A is estimated to occur in about 2,500 people a year and results in about 75 deaths. The word is derived from the Greek hêpar (ἧπαρ), meaning "liver", and -itis (-ῖτις), meaning "inflammation". Signs and symptoms Hepatitis has a broad spectrum of presentations that range from a complete lack of symptoms to severe liver failure. The acute form of hepatitis, generally caused by viral infection, is characterized by constitutional symptoms that are typically self-limiting. Chronic hepatitis presents similarly, but can manifest signs and symptoms specific to liver dysfunction with long-standing inflammation and damage to the organ. Acute hepatitis Acute viral hepatitis follows three distinct phases: The initial prodromal phase (preceding symptoms) involves non-specific and flu-like symptoms common to many acute viral infections. These include fatigue, nausea, vomiting, poor appetite, joint pain, and headaches. Fever, when present, is most common in cases of hepatitis A and E. Late in this phase, people can experience liver-specific symptoms, including choluria (dark urine) and clay-colored stools. Yellowing of the skin and whites of the eyes follow the prodrome after about 1–2 weeks and can last for up to 4 weeks. The non-specific symptoms seen in the prodromal typically resolve by this time, but people will develop an enlarged liver and right upper abdominal pain or discomfort. 10–20% of people will also experience an enlarged spleen, while some people will also experience a mild unintentional weight loss. The recovery phase is characterized by resolution of the clinical symptoms of hepatitis with persistent elevations in liver lab values and potentially a persistently enlarged liver. All cases of hepatitis A and E are expected to fully resolve after 1–2 months. Most hepatitis B cases are also self-limiting and will resolve in 3–4 months. Few cases of hepatitis C will resolve completely.Both drug-induced hepatitis and autoimmune hepatitis can present very similarly to acute viral hepatitis, with slight variations in symptoms depending on the cause. Cases of drug-induced hepatitis can manifest with systemic signs of an allergic reaction including rash, fever, serositis (inflammation of membranes lining certain organs), elevated eosinophils (a type of white blood cell), and suppression of bone marrow activity. Fulminant hepatitis Fulminant hepatitis, or massive hepatic cell death, is a rare and life-threatening complication of acute hepatitis that can occur in cases of hepatitis B, D, and E, in addition to drug-induced and autoimmune hepatitis. The complication more frequently occurs in instances of hepatitis B and D co-infection at a rate of 2–20% and in pregnant women with hepatitis E at rate of 15–20% of cases. In addition to the signs of acute hepatitis, people can also demonstrate signs of coagulopathy (abnormal coagulation studies with easy bruising and bleeding) and encephalopathy (confusion, disorientation, and sleepiness). Mortality due to fulminant hepatitis is typically the result of various complications including cerebral edema, gastrointestinal bleeding, sepsis, respiratory failure, or kidney failure. Chronic hepatitis Acute cases of hepatitis are seen to be resolved well within a six-month period. When hepatitis is continued for more than six months it is termed chronic hepatitis. Chronic hepatitis is often asymptomatic early in its course and is detected only by liver laboratory studies for screening purposes or to evaluate non-specific symptoms. As the inflammation progresses, patients can develop constitutional symptoms similar to acute hepatitis, including fatigue, nausea, vomiting, poor appetite, and joint pain. Jaundice can occur as well, but much later in the disease process and is typically a sign of advanced disease. Chronic hepatitis interferes with hormonal functions of the liver which can result in acne, hirsutism (abnormal hair growth), and amenorrhea (lack of menstrual period) in women. Extensive damage and scarring of the liver over time defines cirrhosis, a condition in which the livers ability to function is permanently impeded. This results in jaundice, weight loss, coagulopathy, ascites (abdominal fluid collection), and peripheral edema (leg swelling). Cirrhosis can lead to other life-threatening complications such as hepatic encephalopathy, esophageal varices, hepatorenal syndrome, and liver cancer. Causes Causes of hepatitis can be divided into the following major categories: infectious, metabolic, ischemic, autoimmune, genetic, and other. Infectious agents include viruses, bacteria, and parasites. Metabolic causes include prescription medications, toxins (most notably alcohol), and non-alcoholic fatty liver disease. Autoimmune and genetic causes of hepatitis involve genetic predispositions and tend to affect characteristic populations. Infectious Viral hepatitis Viral hepatitis is the most common type of hepatitis worldwide, especially in Asia and Africa. Viral hepatitis is caused by five different viruses (hepatitis A, B, C, D, and E). Hepatitis A and hepatitis E behave similarly: they are both transmitted by the fecal–oral route, are more common in developing countries, and are self-limiting illnesses that do not lead to chronic hepatitis.Hepatitis B, hepatitis C, and hepatitis D are transmitted when blood or mucous membranes are exposed to infected blood and body fluids, such as semen and vaginal secretions. Viral particles have also been found in saliva and breastmilk. Kissing, sharing utensils, and breastfeeding do not lead to transmission unless these fluids are introduced into open sores or cuts. Many families who do not have safe drinking water or live in unhygienic homes have contracted hepatitis because saliva and blood droplets are often carried through the water and blood-borne illnesses spread quickly in unsanitary settings.Hepatitis B and C can present either acutely or chronically. Hepatitis D is a defective virus that requires hepatitis B to replicate and is only found with hepatitis B co-infection. In adults, hepatitis B infection is most commonly self-limiting, with less than 5% progressing to chronic state, and 20 to 30% of those chronically infected developing cirrhosis or liver cancer. Infection in infants and children frequently leads to chronic infection.Unlike hepatitis B, most cases of hepatitis C lead to chronic infection. Hepatitis C is the second most common cause of cirrhosis in the US (second to alcoholic hepatitis). In the 1970s and 1980s, blood transfusions were a major factor in spreading hepatitis C virus. Since widespread screening of blood products for hepatitis C began in 1992, the risk of acquiring hepatitis C from a blood transfusion has decreased from approximately 10% in the 1970s to 1 in 2 million currently. Parasitic hepatitis Parasites can also infect the liver and activate the immune response, resulting in symptoms of acute hepatitis with increased serum IgE (though chronic hepatitis is possible with chronic infections). Of the protozoans, Trypanosoma cruzi, Leishmania species, and the malaria-causing Plasmodium species all can cause liver inflammation. Another protozoan, Entamoeba histolytica, causes hepatitis with distinct liver abscesses.Of the worms, the cestode Echinococcus granulosus, also known as the dog tapeworm, infects the liver and forms characteristic hepatic hydatid cysts. The liver flukes Fasciola hepatica and Clonorchis sinensis live in the bile ducts and cause progressive hepatitis and liver fibrosis. Bacterial hepatitis Bacterial infection of the liver commonly results in pyogenic liver abscesses, acute hepatitis, or granulomatous (or chronic) liver disease. Pyogenic abscesses commonly involve enteric bacteria such as Escherichia coli and Klebsiella pneumoniae and are composed of multiple bacteria up to 50% of the time. Acute hepatitis is caused by Neisseria meningitidis, Neisseria gonorrhoeae, Bartonella henselae, Borrelia burgdorferi, salmonella species, brucella species and campylobacter species. Chronic or granulomatous hepatitis is seen with infection from mycobacteria species, Tropheryma whipplei, Treponema pallidum, Coxiella burnetii, and rickettsia species. Metabolic Alcoholic hepatitis Excessive alcohol consumption is a significant cause of hepatitis and is the most common cause of cirrhosis in the U.S. Alcoholic hepatitis is within the spectrum of alcoholic liver disease. This ranges in order of severity and reversibility from alcoholic steatosis (least severe, most reversible), alcoholic hepatitis, cirrhosis, and liver cancer (most severe, least reversible). Hepatitis usually develops over years-long exposure to alcohol, occurring in 10 to 20% of alcoholics. The most important risk factors for the development of alcoholic hepatitis are quantity and duration of alcohol intake. Long-term alcohol intake in excess of 80 grams of alcohol a day in men and 40 grams a day in women is associated with development of alcoholic hepatitis (1 beer or 4 ounces of wine is equivalent to 12g of alcohol). Alcoholic hepatitis can vary from asymptomatic hepatomegaly (enlarged liver) to symptoms of acute or chronic hepatitis to liver failure. Toxic and drug-induced hepatitis Many chemical agents, including medications, industrial toxins, and herbal and dietary supplements, can cause hepatitis. The spectrum of drug-induced liver injury varies from acute hepatitis to chronic hepatitis to acute liver failure. Toxins and medications can cause liver injury through a variety of mechanisms, including direct cell damage, disruption of cell metabolism, and causing structural changes. Some drugs such as paracetamol exhibit predictable dose-dependent liver damage while others such as isoniazid cause idiosyncratic and unpredictable reactions that vary by person. There are wide variations in the mechanisms of liver injury and latency period from exposure to development of clinical illness.Many types of drugs can cause liver injury, including the analgesic paracetamol; antibiotics such as isoniazid, nitrofurantoin, amoxicillin-clavulanate, erythromycin, and trimethoprim-sulfamethoxazole; anticonvulsants such as valproate and phenytoin; cholesterol-lowering statins; steroids such as oral contraceptives and anabolic steroids; and highly active anti-retroviral therapy used in the treatment of HIV/AIDS. Of these, amoxicillin-clavulanate is the most common cause of drug-induced liver injury, and paracetamol toxicity the most common cause of acute liver failure in the United States and Europe.Herbal remedies and dietary supplements are another important cause of hepatitis; these are the most common causes of drug-induced hepatitis in Korea. The United-States-based Drug Induced Liver Injury Network linked more than 16% of cases of hepatotoxicity to herbal and dietary supplements. In the United States, herbal and dietary supplements – unlike pharmaceutical drugs – are unregulated by the Food and Drug Administration. The National Institutes of Health maintains the LiverTox Archived 2019-07-24 at the Wayback Machine database for consumers to track all known prescription and non-prescription compounds associated with liver injury.Exposure to other hepatotoxins can occur accidentally or intentionally through ingestion, inhalation, and skin absorption. The industrial toxin carbon tetrachloride and the wild mushroom Amanita phalloides are other known hepatotoxins. Non-alcoholic fatty liver disease Non-alcoholic hepatitis is within the spectrum of non-alcoholic liver disease (NALD), which ranges in severity and reversibility from non-alcoholic fatty liver disease (NAFLD) to non-alcoholic steatohepatitis (NASH) to cirrhosis to liver cancer, similar to the spectrum of alcoholic liver disease.Non-alcoholic liver disease occurs in people with little or no history of alcohol use, and is instead strongly associated with metabolic syndrome, obesity, insulin resistance and diabetes, and hypertriglyceridemia. Over time, non-alcoholic fatty liver disease can progress to non-alcoholic steatohepatitis, which additionally involves liver cell death, liver inflammation and possible fibrosis. Factors accelerating progression from NAFLD to NASH are obesity, older age, non-African American ethnicity, female gender, diabetes mellitus, hypertension, higher ALT or AST level, higher AST/ALT ratio, low platelet count, and an ultrasound steatosis score.In the early stages (as with NAFLD and early NASH), most patients are asymptomatic or have mild right upper quadrant pain, and diagnosis is suspected on the basis of abnormal liver function tests. As the disease progresses, symptoms typical of chronic hepatitis may develop. While imaging can show fatty liver, only liver biopsy can demonstrate inflammation and fibrosis characteristic of NASH. 9 to 25% of patients with NASH develop cirrhosis. NASH is recognized as the third most common cause of liver disease in the United States. Autoimmune Autoimmune hepatitis is a chronic disease caused by an abnormal immune response against liver cells. The disease is thought to have a genetic predisposition as it is associated with certain human leukocyte antigens involved in the immune response. As in other autoimmune diseases, circulating auto-antibodies may be present and are helpful in diagnosis. Auto-antibodies found in patients with autoimmune hepatitis include the sensitive but less specific anti-nuclear antibody (ANA), smooth muscle antibody (SMA), and atypical perinuclear antineutrophil cytoplasmic antibody (p-ANCA). Other autoantibodies that are less common but more specific to autoimmune hepatitis are the antibodies against liver kidney microsome 1 (LKM1) and soluble liver antigen (SLA). Autoimmune hepatitis can also be triggered by drugs (such as nitrofurantoin, hydralazine, and methyldopa), after liver transplant, or by viruses (such as hepatitis A, Epstein-Barr virus, or measles).Autoimmune hepatitis can present anywhere within the spectrum from asymptomatic to acute or chronic hepatitis to fulminant liver failure. Patients are asymptomatic 25–34% of the time, and the diagnosis is suspected on the basis of abnormal liver function tests. Some studies show between 25% and 75% of cases present with signs and symptoms of acute hepatitis. As with other autoimmune diseases, autoimmune hepatitis usually affects young females (though it can affect patients of either sex of any age), and patients can exhibit classic signs and symptoms of autoimmunity such as fatigue, anemia, anorexia, amenorrhea, acne, arthritis, pleurisy, thyroiditis, ulcerative colitis, nephritis, and maculopapular rash. Autoimmune hepatitis increases the risk for cirrhosis, and the risk for liver cancer is increased by about 1% for each year of the disease.Many people with autoimmune hepatitis have other autoimmune diseases. Autoimmune hepatitis is distinct from the other autoimmune diseases of the liver, primary biliary cirrhosis and primary sclerosing cholangitis, both of which can also lead to scarring, fibrosis, and cirrhosis of the liver. Genetic Genetic causes of hepatitis include alpha-1-antitrypsin deficiency, hemochromatosis, and Wilsons disease. In alpha-1-antitrypsin deficiency, a co-dominant mutation in the gene for alpha-1-antitrypsin results in the abnormal accumulation of the mutant AAT protein within liver cells, leading to liver disease. Hemochromatosis and Wilsons disease are both autosomal recessive diseases involving abnormal storage of minerals. In hemochromatosis, excess amounts of iron accumulate in multiple body sites, including the liver, which can lead to cirrhosis. In Wilsons disease, excess amounts of copper accumulate in the liver and brain, causing cirrhosis and dementia.When the liver is involved, alpha-1-antitrypsin deficiency and Wilsons disease tend to present as hepatitis in the neonatal period or in childhood. Hemochromatosis typically presents in adulthood, with the onset of clinical disease usually after age 50. Ischemic hepatitis Ischemic hepatitis (also known as shock liver) results from reduced blood flow to the liver as in shock, heart failure, or vascular insufficiency. The condition is most often associated with heart failure but can also be caused by shock or sepsis. Blood testing of a person with ischemic hepatitis will show very high levels of transaminase enzymes (AST and ALT). The condition usually resolves if the underlying cause is treated successfully. Ischemic hepatitis rarely causes permanent liver damage. Other Hepatitis can also occur in neonates and is attributable to a variety of causes, some of which are not typically seen in adults. Congenital or perinatal infection with the hepatitis viruses, toxoplasma, rubella, cytomegalovirus, and syphilis can cause neonatal hepatitis. Structural abnormalities such as biliary atresia and choledochal cysts can lead to cholestatic liver injury leading to neonatal hepatitis. Metabolic diseases such as glycogen storage disorders and lysosomal storage disorders are also implicated. Neonatal hepatitis can be idiopathic, and in such cases, biopsy often shows large multinucleated cells in the liver tissue. This disease is termed giant cell hepatitis and may be associated with viral infection, autoimmune disorders, and drug toxicity. Mechanism The specific mechanism varies and depends on the underlying cause of the hepatitis. Generally, there is an initial insult that causes liver injury and activation of an inflammatory response, which can become chronic, leading to progressive fibrosis and cirrhosis. Viral hepatitis The pathway by which hepatic viruses cause viral hepatitis is best understood in the case of hepatitis B and C. The viruses do not directly activate apoptosis (cell death). Rather, infection of liver cells activates the innate and adaptive arms of the immune system leading to an inflammatory response which causes cellular damage and death, including viral-induced apoptosis via the induction of the death receptor-mediated signaling pathway. Depending on the strength of the immune response, the types of immune cells involved and the ability of the virus to evade the bodys defense, infection can either lead to clearance (acute disease) or persistence (chronic disease) of the virus. The chronic presence of the virus within liver cells results in multiple waves of inflammation, injury and wound healing that over time lead to scarring or fibrosis and culminate in hepatocellular carcinoma. People with impaired immune response are at greater risk of developing chronic infection. Natural killer cells are the primary drivers of the initial innate response and create a cytokine environment that results in the recruitment of CD4 T-helper and CD8 cytotoxic T-cells. Type I interferons are the cytokines that drive the antiviral response. In chronic Hepatitis B and C, natural killer cell function is impaired. Steatohepatitis Steatohepatitis is seen in both alcoholic and non-alcoholic liver disease and is the culmination of a cascade of events that began with injury. In the case of non-alcoholic steatohepatitis, this cascade is initiated by changes in metabolism associated with obesity, insulin resistance, and lipid dysregulation. In alcoholic hepatitis, chronic excess alcohol use is the culprit. Though the inciting event may differ, the progression of events is similar and begins with accumulation of free fatty acids (FFA) and their breakdown products in the liver cells in a process called steatosis. This initially reversible process overwhelms the hepatocytes ability to maintain lipid homeostasis leading to a toxic effect as fat molecules accumulate and are broken down in the setting of an oxidative stress response. Over time, this abnormal lipid deposition triggers the immune system via toll-like receptor 4 (TLR4) resulting in the production of inflammatory cytokines such as TNF that cause liver cell injury and death. These events mark the transition to steatohepatitis and in the setting of chronic injury, fibrosis eventually develops setting up events that lead to cirrhosis and hepatocellular carcinoma. Microscopically, changes that can be seen include steatosis with large and swollen hepatocytes (ballooning), evidence of cellular injury and cell death (apoptosis, necrosis), evidence of inflammation in particular in zone 3 of the liver, variable degrees of fibrosis and Mallory bodies. Diagnosis Diagnosis of hepatitis is made on the basis of some or all of the following: a persons signs and symptoms, medical history including sexual and substance use history, blood tests, imaging, and liver biopsy. In general, for viral hepatitis and other acute causes of hepatitis, the persons blood tests and clinical picture are sufficient for diagnosis. For other causes of hepatitis, especially chronic causes, blood tests may not be useful. In this case, liver biopsy is the gold standard for establishing the diagnosis: histopathologic analysis is able to reveal the precise extent and pattern of inflammation and fibrosis. Biopsy is typically not the initial diagnostic test because it is invasive and is associated with a small but significant risk of bleeding that is increased in people with liver injury and cirrhosis.Blood testing includes liver enzymes, serology (i.e. for autoantibodies), nucleic acid testing (i.e. for hepatitis virus DNA/RNA), blood chemistry, and complete blood count. Characteristic patterns of liver enzyme abnormalities can point to certain causes or stages of hepatitis. Generally, AST and ALT are elevated in most cases of hepatitis regardless of whether the person shows any symptoms. The degree of elevation (i.e. levels in the hundreds vs. in the thousands), the predominance for AST vs. ALT elevation, and the ratio between AST and ALT are informative of the diagnosis.Ultrasound, CT, and MRI can all identify steatosis (fatty changes) of the liver tissue and nodularity of the liver surface suggestive of cirrhosis. CT and especially MRI are able to provide a higher level of detail, allowing visualization and characterize such structures as vessels and tumors within the liver. Unlike steatosis and cirrhosis, no imaging test is able to detect liver inflammation (i.e. hepatitis) or fibrosis. Liver biopsy is the only definitive diagnostic test that is able to assess inflammation and fibrosis of the liver. Viral hepatitis Viral hepatitis is primarily diagnosed through blood tests for levels of viral antigens (such as the hepatitis B surface or core antigen), anti-viral antibodies (such as the anti-hepatitis B surface antibody or anti-hepatitis A antibody), or viral DNA/RNA. In early infection (i.e. within 1 week), IgM antibodies are found in the blood. In late infection and after recovery, IgG antibodies are present and remain in the body for up to years. Therefore, when a patient is positive for IgG antibody but negative for IgM antibody, he is considered immune from the virus via either prior infection and recovery or prior vaccination.In the case of hepatitis B, blood tests exist for multiple virus antigens (which are different components of the virion particle) and antibodies. The combination of antigen and antibody positivity can provide information about the stage of infection (acute or chronic), the degree of viral replication, and the infectivity of the virus. Alcoholic versus non-alcoholic The most apparent distinguishing factor between alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH) is a history of excessive alcohol use. Thus, in patients who have no or negligible alcohol use, the diagnosis is unlikely to be alcoholic hepatitis. In those who drink alcohol, the diagnosis may just as likely be alcoholic or nonalcoholic hepatitis especially if there is concurrent obesity, diabetes, and metabolic syndrome. In this case, alcoholic and nonalcoholic hepatitis can be distinguished by the pattern of liver enzyme abnormalities; specifically, in alcoholic steatohepatitis AST>ALT with ratio of AST:ALT>2:1 while in nonalcoholic steatohepatitis ALT>AST with ratio of ALT:AST>1.5:1.Liver biopsies show identical findings in patients with ASH and NASH, specifically, the presence of polymorphonuclear infiltration, hepatocyte necrosis and apoptosis in the form of ballooning degeneration, Mallory bodies, and fibrosis around veins and sinuses. Virus screening The purpose of screening for viral hepatitis is to identify people infected with the disease as early as possible, even before symptoms and transaminase elevations may be present. This allows for early treatment, which can both prevent disease progression and decrease the likelihood of transmission to others. Hepatitis A Hepatitis A causes an acute illness that does not progress to chronic liver disease. Therefore, the role of screening is to assess immune status in people who are at high risk of contracting the virus, as well as in people with known liver disease for whom hepatitis A infection could lead to liver failure. People in these groups who are not already immune can receive the hepatitis A vaccine. Those at high risk and in need of screening include: People with poor sanitary habits such as not washing hands after using the restroom or changing diapers People who do not have access to clean water People in close contact (either living with or having sexual contact) with someone who has hepatitis A People who use illicit drugs People with liver disease People traveling to an area with endemic hepatitis AThe presence of anti-hepatitis A IgG in the blood indicates past infection with the virus or prior vaccination. Hepatitis B The CDC, WHO, USPSTF, and ACOG recommend routine hepatitis B screening for certain high-risk populations. Specifically, these populations include people who are: Born in countries where the prevalence of hepatitis B is high (defined as ≥2% of the population), whether or not they have been vaccinated Born in the United States whose parents are from countries where the prevalence of hepatitis B is very high (defined as ≥8% of the population), and who were not vaccinated HIV positive Intravenous drug users Men who have sex with men In close contact with (i.e. live or have sex with) people known to have hepatitis B Pregnant Beginning immunosuppressive or cytotoxic therapy Found to have elevated liver enzymes without a known cause Blood, organ, or tissue donors Incarcerated On hemodialysisScreening consists of a blood test that detects hepatitis B surface antigen (HBsAg). If HBsAg is present, a second test – usually done on the same blood sample – that detects the antibody for the hepatitis B core antigen (anti-HBcAg
Hepatitis	) can differentiate between acute and chronic infection. People who are high-risk whose blood tests negative for HBsAg can receive the hepatitis B vaccine to prevent future infection. Hepatitis C The CDC, WHO, USPSTF, AASLD, and ACOG recommend screening people at high risk for hepatitis C infection. These populations include people who are: Intravenous drug users (past or current) Intranasal illicit drug users HIV-positive Men who have sex with men Incarcerated, or who have been in the past On long-term hemodialysis, or who have been in the past Recipients of tattoos in an "unregulated setting" Recipients of blood products or organs prior to 1992 in the United States Adults in the United States born between 1945 and 1965 Born to HCV-positive mothers Pregnant, and engaging in high-risk behaviors Workers in a healthcare setting who have had a needlestick injury Blood or organ donors. Sex workersFor people in the groups above whose exposure is ongoing, screening should be periodic, though there is no set optimal screening interval. The AASLD recommends screening men who have sex with men who are HIV-positive annually. People born in the US between 1945 and 1965 should be screened once (unless they have other exposure risks).Screening consists of a blood test that detects anti-hepatitis C virus antibody. If anti-hepatitis C virus antibody is present, a confirmatory test to detect HCV RNA indicates chronic disease. Hepatitis D The CDC, WHO, USPSTF, AASLD, and ACOG recommend screening people at high risk for hepatitis D infection. These populations include people who are: Intravenous drug users (past or current) Intranasal illicit drug users Incarcerated, or who have been in the past Workers in a healthcare setting who have had a needlestick injury Blood or organ donors. Sex workersHepatitis D is extremely rare. Symptoms include chronic diarrhea, anal and intestinal blisters, purple urine, and burnt popcorn scented breath. Screening consists of a blood test that detects the anti-hepitits D virus antibbody. If anti-hepitits D virus antibody is present, a confirmatory test to detect HDV RNA DNA inidicates chronic disease. Prevention Vaccines Hepatitis A The CDC recommends the hepatitis A vaccine for all children beginning at age one, as well as for those who have not been previously immunized and are at high risk for contracting the disease.For children 12 months of age or older, the vaccination is given as a shot into the muscle in two doses 6–18 months apart and should be started before the age 24 months. The dosing is slightly different for adults depending on the type of the vaccine. If the vaccine is for hepatitis A only, two doses are given 6–18 months apart depending on the manufacturer. If the vaccine is combined hepatitis A and hepatitis B, up to 4 doses may be required. Hepatitis B The CDC recommends the routine vaccination of all children under the age of 19 with the hepatitis B vaccine. They also recommend it for those who desire it or are at high risk.Routine vaccination for hepatitis B starts with the first dose administered as a shot into the muscle before the newborn is discharged from the hospital. An additional two doses should be administered before the child is 18 months.For babies born to a mother with hepatitis B surface antigen positivity, the first dose is unique – in addition to the vaccine, the hepatitis immune globulin should also be administered, both within 12 hours of birth. These newborns should also be regularly tested for infection for at least the first year of life.There is also a combination formulation that includes both hepatitis A and B vaccines. Other There are currently no vaccines available in the United States for hepatitis C or E. In 2015, a group in China published an article regarding the development of a vaccine for hepatitis E. As of March 2016, the United States government was in the process of recruiting participants for the phase IV trial of the hepatitis E vaccine. Behavioral changes Hepatitis A Because hepatitis A is transmitted primarily through the oral-fecal route, the mainstay of prevention aside from vaccination is good hygiene, access to clean water and proper handling of sewage. Hepatitis B and C As hepatitis B and C are transmitted through blood and multiple bodily fluids, prevention is aimed at screening blood prior to transfusion, abstaining from the use of injection drugs, safe needle and sharps practices in healthcare settings, and safe sex practices. Hepatitis D The hepatitis D virus requires that a person first be infected with hepatitis B virus, so prevention efforts should focus on limiting the spread of hepatitis B. In people who have chronic hepatitis B infection and are at risk for superinfection with the hepatitis D virus, the preventive strategies are the same as for hepatitis B. Hepatitis E Hepatitis E is spread primarily through the oral-fecal route but may also be spread by blood and from mother to fetus. The mainstay of hepatitis E prevention is similar to that for hepatitis A (namely, good hygiene and clean water practices). Alcoholic hepatitis As excessive alcohol consumption can lead to hepatitis and cirrhosis, the following are maximal recommendations for alcohol consumption: Women – ≤ 3 drinks on any given day and ≤ 7 drinks per week Men – ≤ 4 drinks on any given day and ≤ 14 drinks per week Successes Hepatitis A In the United States, universal immunization has led to a two-thirds decrease in hospital admissions and medical expenses due to hepatitis A. Hepatitis B In the United States new cases of hepatitis B decreased 75% from 1990 to 2004. The group that saw the greatest decrease was children and adolescents, likely reflecting the implementation of the 1999 guidelines. Hepatitis C Hepatitis C infections each year had been declining since the 1980s, but began to increase again in 2006. The data are unclear as to whether the decline can be attributed to needle exchange programmes. Alcoholic hepatitis Because people with alcoholic hepatitis may have no symptoms, it can be difficult to diagnose and the number of people with the disease is probably higher than many estimates. Programs such as Alcoholics Anonymous have been successful in decreasing death due to cirrhosis, but it is difficult to evaluate their success in decreasing the incidence of alcoholic hepatitis. Treatment The treatment of hepatitis varies according to the type, whether it is acute or chronic, and the severity of the disease. Activity: Many people with hepatitis prefer bed rest, though it is not necessary to avoid all physical activity while recovering. Diet: A high-calorie diet is recommended. Many people develop nausea and cannot tolerate food later in the day, so the bulk of intake may be concentrated in the earlier part of the day. In the acute phase of the disease, intravenous feeding may be needed if patients cannot tolerate food and have poor oral intake subsequent to nausea and vomiting. Drugs: People with hepatitis should avoid taking drugs metabolized by the liver. Glucocorticoids are not recommended as a treatment option for acute viral hepatitis and may even cause harm, such as development of chronic hepatitis. Precautions: Universal precautions should be observed. Isolation is usually not needed, except in cases of hepatitis A and E who have fecal incontinence, and in cases of hepatitis B and C who have uncontrolled bleeding. Hepatitis A Hepatitis A usually does not progress to a chronic state, and rarely requires hospitalization. Treatment is supportive and includes such measures as providing intravenous (IV) hydration and maintaining adequate nutrition.Rarely, people with the hepatitis A virus can rapidly develop liver failure, termed fulminant hepatic failure, especially the elderly and those who had a pre-existing liver disease, especially hepatitis C. Mortality risk factors include greater age and chronic hepatitis C. In these cases, more aggressive supportive therapy and liver transplant may be necessary. Hepatitis B Acute In healthy patients, 95–99% recover with no long-lasting effects, and antiviral treatment is not warranted. Age and comorbid conditions can result in a more prolonged and severe illness. Certain patients warrant hospitalization, especially those who present with clinical signs of ascites, peripheral edema, and hepatic encephalopathy, and laboratory signs of hypoglycemia, prolonged prothrombin time, low serum albumin, and very high serum bilirubin.In these rare, more severe acute cases, patients have been successfully treated with antiviral therapy similar to that used in cases of chronic hepatitis B, with nucleoside analogues such as entecavir or tenofovir. As there is a dearth of clinical trial data and the drugs used to treat are prone to developing resistance, experts recommend reserving treatment for severe acute cases, not mild to moderate. Chronic Chronic hepatitis B management aims to control viral replication, which is correlated with progression of disease. Seven drugs are approved in the United States: Injectable interferon alpha was the first therapy approved for chronic hepatitis B. It has several side effects, most of which are reversible with removal of therapy, but it has been supplanted by newer treatments for this indication. These include long-acting interferon bound to polyethylene glycol (pegylated interferon) and the oral nucleoside analogues. Pegylated interferon (PEG IFN) is dosed just once a week as a subcutaneous injection and is both more convenient and effective than standard interferon. Although it does not develop resistance as do many of the oral antivirals, it is poorly tolerated and requires close monitoring. PEG IFN is estimated to cost about $18,000 per year in the United States, compared to $2,500–8,700 for the oral medications. Its treatment duration is 48 weeks, unlike oral antivirals which require indefinite treatment for most patients (minimum one year). PEG IFN is not effective in patients with high levels of viral activity and cannot be used in immunosuppressed patients or those with cirrhosis. Lamivudine was the first approved oral nucleoside analogue. While effective and potent, lamivudine has been replaced by newer, more potent treatments in the Western world and is no longer recommended as first-line treatment. It is still used in areas where newer agents either have not been approved or are too costly. Generally, the course of treatment is a minimum of one year with a minimum of six additional months of "consolidation therapy." Based on viral response, longer therapy may be required, and certain patients require indefinite long-term therapy. Due to a less robust response in Asian patients, consolidation therapy is recommended to be extended to at least a year. All patients should be monitored for viral reactivation, which if identified, requires restarting treatment. Lamivudine is generally safe and well tolerated. Many patients develop resistance, which is correlated with longer treatment duration. If this occurs, an additional antiviral is added. Lamivudine as a single treatment is contraindicated in patients coinfected with HIV, as resistance develops rapidly, but it can be used as part of a multidrug regimen. Adefovir dipivoxil, a nucleotide analogue, has been used to supplement lamivudine in patients who develop resistance, but is no longer recommended as first-line therapy. Entecavir is safe, well tolerated, less prone to developing resistance, and the most potent of the existing hepatitis B antivirals; it is thus a first-line treatment choice. It is not recommended for lamivudine-resistant patients or as monotherapy in patients who are HIV positive. Telbivudine is effective but not recommended as first-line treatment; as compared to entecavir, it is both less potent and more resistance prone. Tenofovir is a nucleotide analogue and an antiretroviral drug that is also used to treat HIV infection. It is preferred to adefovir both in lamivudine-resistant patients and as initial treatment since it is both more potent and less likely to develop resistance.First-line treatments currently used include PEG IFN, entecavir, and tenofovir, subject to patient and physician preference. Treatment initiation is guided by recommendations issued by The American Association for the Study of Liver Diseases (AASLD) and the European Association for the Study of the Liver (EASL) and is based on detectable viral levels, HBeAg positive or negative status, ALT levels, and in certain cases, family history of HCC and liver biopsy. In patients with compensated cirrhosis, treatment is recommended regardless of HBeAg status or ALT level, but recommendations differ regarding HBV DNA levels; AASLD recommends treating at DNA levels detectable above 2x103 IU/mL; EASL and WHO recommend treating when HBV DNA levels are detectable at any level. In patients with decompensated cirrhosis, treatment and evaluation for liver transplantation are recommended in all cases if HBV DNA is detectable. Currently, multidrug treatment is not recommended in treatment of chronic HBV as it is no more effective in the long term than individual treatment with entecavir or tenofovir. Hepatitis C The American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLD-IDSA) recommend antiviral treatment for all patients with chronic hepatitis C infection except for those with additional chronic medical conditions that limit their life expectancy.Once it is acquired, persistence of the hepatitis C virus is the rule, resulting in chronic hepatitis C. The goal of treatment is prevention of hepatocellular carcinoma (HCC). The best way to reduce the long-term risk of HCC is to achieve sustained virological response (SVR). SVR is defined as an undetectable viral load at 12 weeks after treatment completion and indicates a cure. Currently available treatments include indirect and direct acting antiviral drugs. The indirect acting antivirals include pegylated interferon (PEG IFN) and ribavirin (RBV), which in combination have historically been the basis of therapy for HCV. Duration of and response to these treatments varies based on genotype. These agents are poorly tolerated but are still used in some resource-poor areas. In high-resource countries, they have been supplanted by direct acting antiviral agents, which first appeared in 2011; these agents target proteins responsible for viral replication and include the following three classes: NS3/4A protease inhibitors, including telaprevir, boceprevir, simeprevir, and others NS5A inhibitors, including ledipasvir, daclatasvir, and others NS5B polymerase inhibitors, including sofosbuvir, dasabuvir, and othersThese drugs are used in various combinations, sometimes combined with ribavirin, based on the patients genotype, delineated as genotypes 1–6. Genotype 1 (GT1), which is the most prevalent genotype in the United States and around the world, can now be cured with a direct acting antiviral regimen. First-line therapy for GT1 is a combination of sofosbuvir and ledipasvir (SOF/LDV) for 12 weeks for most patients, including those with advanced fibrosis or cirrhosis. Certain patients with early disease need only 8 weeks of treatment while those with advanced fibrosis or cirrhosis who have not responded to prior treatment require 24 weeks. Cost remains a major factor limiting access to these drugs, particularly in low-resource nations; the cost of the 12-week GT1 regimen (SOF/LDV) has been estimated at US$94,500. Hepatitis D Hepatitis D is difficult to treat, and effective treatments are lacking. Interferon alpha has proven effective at inhibiting viral activity but only on a temporary basis. Hepatitis E Similar to hepatitis A, treatment of hepatitis E is supportive and includes rest and ensuring adequate nutrition and hydration. Hospitalization may be required for particularly severe cases or for pregnant women. Alcoholic hepatitis First-line treatment of alcoholic hepatitis is treatment of alcoholism. For those who abstain completely from alcohol, reversal of liver disease and a longer life are possible; patients at every disease stage have been shown to benefit by prevention of additional liver injury. In addition to referral to psychotherapy and other treatment programs, treatment should include nutritional and psychosocial evaluation and treatment. Patients should also be treated appropriately for related signs and symptoms, such as ascites, hepatic encephalopathy, and infection.Severe alcoholic hepatitis has a poor prognosis and is notoriously difficult to treat. Without any treatment, 20-50% of patients may die within a month, but evidence shows treatment may extend life beyond one month (i.e., reduce short-term mortality). Available treatment options include pentoxifylline (PTX), which is a nonspecific TNF inhibitor, corticosteroids, such as prednisone or prednisolone (CS), corticosteroids with N-acetylcysteine (CS with NAC), and corticosteroids with pentoxifylline (CS with PTX). Data suggest that CS alone or CS with NAC are most effective at reducing short-term mortality. Unfortunately, corticosteroids are contraindicated in some patients, such as those who have active gastrointestinal bleeding, infection, kidney failure, or pancreatitis. In these cases PTX may be considered on a case-by-case basis in lieu of CS; some evidence shows PTX is better than no treatment at all and may be comparable to CS while other data show no evidence of benefit over placebo. Unfortunately, there are currently no drug treatments that decrease these patients risk of dying in the longer term, at 3–12 months and beyond.Weak evidence suggests milk thistle extracts may improve survival in alcoholic liver disease and improve certain liver tests (serum bilirubin and GGT) without causing side effects, but a firm recommendation cannot be made for or against milk thistle without further study. The modified Maddreys discriminant function may be used to evaluate the severity and prognosis in alcoholic hepatitis and evaluates the efficacy of using alcoholic hepatitis corticosteroid treatment. Autoimmune hepatitis Autoimmune hepatitis is commonly treated by immunosuppressants such as the corticosteroids prednisone or prednisolone, the active version of prednisolone that does not require liver synthesis, either alone or in combination with azathioprine, and some have suggested the combination therapy is preferred to allow for lower doses of corticosteroids to reduce associated side effects, although the result of treatment efficacy is comparative.Treatment of autoimmune hepatitis consists of two phases; an initial and maintenance phase. The initial phase consists of higher doses of corticosteroids which are tapered down over a number of weeks to a lower dose. If used in combination, azathioprine is given during the initial phase as well. Once the initial phase has been completed, a maintenance phase that consists of lower dose corticosteroids, and in combination therapy, azathioprine until liver blood markers are normalized. Treatment results in 66-91% of patients achieving normal liver test values in two years, with the average being 22 months. Prognosis Acute hepatitis Nearly all patients with hepatitis A infections recover completely without complications if they were healthy prior to the infection. Similarly, acute hepatitis B infections have a favorable course towards complete recovery in 95–99% of patients. Certain factors may portend a poorer outcome, such as co-morbid medical conditions or initial presenting symptoms of ascites, edema, or encephalopathy. Overall, the mortality rate for acute hepatitis is low: ~0.1% in total for cases of hepatitis A and B, but rates can be higher in certain populations (super infection with both hepatitis B and D, pregnant women, etc.).In contrast to hepatitis A & B, hepatitis C carries a much higher risk of progressing to chronic hepatitis, approaching 85–90%. Cirrhosis has been reported to develop in 20–50% of patients with chronic hepatitis C.Other rare complications of acute hepatitis include pancreatitis, aplastic anemia, peripheral neuropathy, and myocarditis. Fulminant hepatitis Despite the relatively benign course of most viral cases of hepatitis, fulminant hepatitis represents a rare but feared complication. Fulminant hepatitis most commonly occurs in hepatitis B, D, and E. About 1–2% of cases of hepatitis E can lead to fulminant hepatitis, but pregnant women are particularly susceptible, occurring in up to 20% of cases. Mortality rates in cases of fulminant hepatitis rise over 80%, but those patients that do survive often make a complete recovery. Liver transplantation can be life-saving in patients with fulminant liver failure.Hepatitis D infections can transform benign cases of hepatitis B into severe, progressive hepatitis, a phenomenon known as superinfection. Chronic hepatitis Acute hepatitis B infections become less likely to progress to chronic forms as the age of the patient increases, with rates of progression approaching 90% in vertically transmitted cases of infants compared to 1% risk in young adults. Overall, the five-year survival rate for chronic hepatitis B ranges from 97% in mild cases to 55% in severe cases with cirrhosis.Most patients who acquire hepatitis D at the same time as hepatitis B (co-infection) recover without developing a chronic infection. In people with hepatitis B who later acquire hepatitis D (superinfection), chronic infection is much more common at 80-90%, and liver disease progression is accelerated.Chronic hepatitis C progresses towards cirrhosis, with estimates of cirrhosis prevalence of 16% at 20 years after infection. While the major causes of mortality in hepatitis C is end stage liver disease, hepatocellular carcinoma is an important additional long term complication and cause of death in chronic hepatitis. Rates of mortality increase with progression of the underlying liver disease. Series of patients with compensated cirrhosis due to HCV have shown 3,5, and 10-year survival rates of 96, 91, and 79% respectively. The 5-year survival rate drops to 50% upon if the cirrhosis becomes decompensated. Epidemiology Viral hepatitis Hepatitis A Hepatitis A is found throughout the world and manifests as large outbreaks and epidemics associated with fecal contamination of water and food sources. Hepatitis A viral infection is predominant in children ages 5–14 with rare infection of infants. Infected children have little to no apparent clinical illness, in contrast to adults in whom greater than 80% are symptomatic if infected. Infection rates are highest in low resource countries with inadequate public sanitation and large concentrated populations. In such regions, as much as 90% of children younger than 10 years old have been infected and are immune, corresponding both to lower rates of clinically symptomatic disease and outbreaks. The availability of a childhood vaccine has significantly reduced infections in the United States, with incidence declining by more than 95% as of 2013. Paradoxically, the highest rates of new infection now occur in young adults and adults who present with worse clinical illness. Specific populations at greatest risk include: travelers to endemic regions, men who have sex with men, those with occupational exposure to non-human primates, people with clotting disorders who have received clotting factors, people with history of chronic liver disease in whom co-infection with hepatitis A can lead to fulminant hepatitis, and intravenous drug users (rare). Hepatitis B Hepatitis B is the most common cause of viral hepatitis in the world with more than 240 million chronic carriers of the virus, 1 million of whom are in the United States. In approximately two-thirds of patients who develop acute hepatitis B infection, no identifiable exposure is evident. Of those acutely infected, 25% become lifetime carriers of the virus. Risk of infection is highest among intravenous drug users, people with high-risk sexual behaviors, healthcare workers, people who had multiple transfusions, organ transplant patients, dialysis patients and newborns infected during the birthing process. Close to 780,000 deaths in the world are attributed to hepatitis B. The most endemic regions are in sub-Saharan Africa and East Asia, where as many as 10% of adults are chronic carriers. Carrier rates in developed nations are significantly lower, encompassing less than 1% of the population. In endemic regions, transmission is thought to be associated with exposure during birth and close contact between young infants. Hepatitis C Chronic hepatitis C is a major cause of liver cirrhosis and hepatocellular carcinoma. It is a common medical reason for liver transplantation due to its severe complications. It is estimated that 130–180 million people in the world are affected by this disease representing a little more than 3% of the world population. In the developing regions of Africa, Asia and South America, prevalence can be as high as 10% of the population. In Egypt, rates of hepatitis C infection as high as 20% have been documented and are associated with iatrogenic contamination related to schistosomiasis treatment in the 1950s–1980s. Currently in the United States, approximately 3.5 million adults are estimated to be infected. Hepatitis C is particularly prevalent among people born between 1945 and 1965, a group of about 800,000 people, with prevalence as high as 3.2% versus 1.6% in the general U.S. population. Most chronic carriers of hepatitis C are unaware of their infection status. The most common mode of transmission of hepatitis C virus is exposure to blood products via blood transfusions (prior to 1992) and intravenous drug injection. A history of intravenous drug injection is the most important risk factor for chronic hepatitis C. Other susceptible populations include those engaged in high-risk sexual behavior, infants of infected mothers, and healthcare workers. Hepatitis D The hepatitis D virus causes chronic and fulminant hepatitis in the context of co-infection with the hepatitis B virus. It is primarily transmitted via non-sexual contact and via needles. Susceptibility to hepatitis D differs by geographic region. In the United States and Northern Europe, populations at risk are intravenous drug users and people who receive multiple transfusions. In the Mediterranean, hepatitis D is predominant among hepatitis B virus co-infected people. Hepatitis E Similar to Hepatitis A, hepatitis E manifests as large outbreaks and epidemics associated with fecal contamination of water sources. It accounts for more than 55,000 deaths annually with approximately 20 million people worldwide thought to be infected with the virus. It affects predominantly young adults, causing acute hepatitis. In infected pregnant women, Hepatitis E infection can lead to fulminant hepatitis with third trimester mortality rates as high as 30%. Those with weakened immune systems, such as organ transplant recipients, are also susceptible. Infection is rare in the United States but rates are high in the developing world (Africa, Asia, Central America, Middle East). Many genotypes exist and are differentially distributed around the world. There is some evidence of hepatitis E infection of animals, serving as a reservoir for human infection. Alcoholic hepatitis Alcoholic hepatitis (AH) in its severe form has a one-month mortality as high as 50%. Most people who develop AH are men but women are at higher risk of developing AH and its complications likely secondary to high body fat and differences in alcohol metabolism. Other contributing factors include younger age <60, binge pattern drinking, poor nutritional status, obesity and hepatitis C co-infection. It is estimated that as much as 20% of people with AH are also infected with hepatitis C. In this population, the presence of hepatitis C virus leads to more severe disease with faster progression to cirrhosis, hepatocellular carcinoma and increased mortality. Obesity increases the likelihood of progression to cirrhosis in cases of alcoholic hepatitis. It is estimated that 70% of people who have AH will progress to cirrhosis. Non-alcoholic steatohepatitis Non-alcoholic steatohepatitis (NASH) is projected to become the top reason for liver transplantation in the United States by 2020, supplanting chronic liver disease due to hepatitis C. About 20–45% of the U.S. population have NAFLD and 6% have NASH. The estimated prevalence of NASH in the world is 3–5%. Of NASH patients who develop cirrhosis, about 2% per year will likely progress to hepatocellular carcinoma. Worldwide, the estimated prevalence of hepat
Hepatitis	ocellular carcinoma related to NAFLD is 15–30%. NASH is thought to be the primary cause of cirrhosis in approximately 25% of patients in the United States, representing 1–2% of the general population. History Early observations Initial accounts of a syndrome that we now think is likely to be hepatitis begin to occur around 3000 B.C. Clay tablets that served as medical handbooks for the ancient Sumerians described the first observations of jaundice. The Sumerians believed that the liver was the home of the soul, and attributed the findings of jaundice to the attack of the liver by a devil named Ahhazu.Around 400 B.C., Hippocrates recorded the first documentation of an epidemic jaundice, in particular noting the uniquely fulminant course of a cohort of patients who all died within two weeks. He wrote, "The bile contained in the liver is full of phlegm and blood, and erupts...After such an eruption, the patient soon raves, becomes angry, talks nonsense and barks like a dog."Given the poor sanitary conditions of war, infectious jaundice played a large role as a major cause of mortality among troops in the Napoleonic Wars, the American Revolutionary War, and both World Wars. During World War II, estimates of soldiers affected by hepatitis were upwards of 10 million. During World War II, soldiers received vaccines against diseases such as yellow fever, but these vaccines were stabilized with human serum, presumably contaminated with hepatitis viruses, which often created epidemics of hepatitis. It was suspected these epidemics were due to a separate infectious agent, and not due to the yellow fever virus itself, after noting 89 cases of jaundice in the months after vaccination out of a total 3,100 patients that were vaccinated. After changing the seed virus strain, no cases of jaundice were observed in the subsequent 8,000 vaccinations. Willowbrook State School experiments A New York University researcher named Saul Krugman continued this research into the 1950s and 1960s, most infamously with his experiments on mentally disabled children at the Willowbrook State School in New York, a crowded urban facility where hepatitis infections were highly endemic to the student body. Krugman injected students with gamma globulin, a type of antibody. After observing the temporary protection against infection this antibody provided, he then tried injected live hepatitis virus into students. Krugman also controversially took feces from infected students, blended it into milkshakes, and fed it to newly admitted children.His research was received with much controversy, as people protested the questionable ethics surrounding the chosen target population. Henry Beecher was one of the foremost critics in an article in the New England Journal of Medicine in 1966, arguing that parents were unaware to the risks of consent and that the research was done to benefit others at the expense of children. Moreover, he argued that poor families with mentally disabled children often felt pressured to join the research project to gain admission to the school, with all of the educational and support resources that would come along with it. Others in the medical community spoke out in support of Krugmans research in terms of its widespread benefits and understanding of the hepatitis virus, and Willowbrook continues to be a commonly cited example in debates about medical ethics. Australia antigen The next insight regarding hepatitis B was a serendipitous one by Dr. Baruch Blumberg, a researcher at the NIH who did not set out to research hepatitis, but rather studied lipoprotein genetics. He travelled across the globe collecting blood samples, investigating the interplay between disease, environment, and genetics with the goal of designing targeted interventions for at-risk people that could prevent them from getting sick. He noticed an unexpected interaction between the blood of a patient with hemophilia that had received multiple transfusions and a protein found in the blood of an indigenous Australian person. He named the protein the "Australia antigen" and made it the focus of his research. He found a higher prevalence of the protein in the blood of patients from developing countries, compared to those from developed ones, and noted associations of the antigen with other diseases like leukemia and Down Syndrome. Eventually, he came to the unifying conclusion that the Australia antigen was associated with viral hepatitis. In 1970, David Dane first isolated the hepatitis B virion at Londons Middlesex Hospital, and named the virion the 42-nm "Dane particle". Based on its association with the surface of the hepatitis B virus, the Australia antigen was renamed to "hepatitis B surface antigen" or HBsAg. Blumberg continued to study the antigen, and eventually developed the first hepatitis B vaccine using plasma rich in HBsAg, for which he received the Nobel Prize in Medicine in 1976. Society and culture Economic burden Overall, hepatitis accounts for a significant portion of healthcare expenditures in both developing and developed nations, and is expected to rise in several developing countries. While hepatitis A infections are self-limited events, they are associated with significant costs in the United States. It has been estimated that direct and indirect costs are approximately $1817 and $2459 respectively per case, and that an average of 27 work days is lost per infected adult. A 1997 report demonstrated that a single hospitalization related to hepatitis A cost an average of $6,900 and resulted in around $500 million in total annual healthcare costs. Cost effectiveness studies have found widespread vaccination of adults to not be feasible, but have stated that a combination hepatitis A and B vaccination of children and at risk groups (people from endemic areas, healthcare workers) may be.Hepatitis B accounts for a much larger percentage of health care spending in endemic regions like Asia. In 1997 it accounted for 3.2% of South Koreas total health care expenditures and resulted in $696 million in direct costs. A large majority of that sum was spent on treating disease symptoms and complications. Chronic hepatitis B infections are not as endemic in the United States, but accounted for $357 million in hospitalization costs in the year 1990. That number grew to $1.5 billion in 2003, but remained stable as of 2006, which may be attributable to the introduction of effective drug therapies and vaccination campaigns.People infected with chronic hepatitis C tend to be frequent users of the health care system globally. It has been estimated that a person infected with hepatitis C in the United States will result in a monthly cost of $691. That number nearly doubles to $1,227 for people with compensated (stable) cirrhosis, while the monthly cost of people with decompensated (worsening) cirrhosis is almost five times as large at $3,682. The wide-ranging effects of hepatitis make it difficult to estimate indirect costs, but studies have speculated that the total cost is $6.5 billion annually in the United States. In Canada, 56% of HCV related costs are attributable to cirrhosis and total expenditures related to the virus are expected to peak at CAD$396 million in the year 2032. 2003 Monaca outbreak The largest outbreak of hepatitis A virus in United States history occurred among people who ate at a now-defunct Mexican food restaurant located in Monaca, Pennsylvania in late 2003. Over 550 people who visited the restaurant between September and October 2003 were infected with the virus, three of whom died as a direct result. The outbreak was brought to the attention of health officials when local emergency medicine physicians noticed a significant increase in cases of hepatitis A in the county. After conducting its investigation, the CDC attributed the source of the outbreak to the use of contaminated raw green onion. The restaurant was purchasing its green onion stock from farms in Mexico at the time. It is believed that the green onions may have been contaminated through the use of contaminated water for crop irrigation, rinsing, or icing or by handling of the vegetables by infected people. Green onion had caused similar outbreaks of hepatitis A in the southern United States prior to this, but not to the same magnitude. The CDC believes that the restaurants use of a large communal bucket for chopped raw green onion allowed non-contaminated plants to be mixed with contaminated ones, increasing the number of vectors of infection and amplifying the outbreak. The restaurant was closed once it was discovered to be the source, and over 9,000 people were given hepatitis A immune globulin because they had either eaten at the restaurant or had been in close contact with someone who had. Special populations HIV co-infection Persons infected with HIV have a particularly high burden of HIV-HCV co-infection. In a recent study by the WHO, the likelihood of being infected with hepatitis C virus was six times greater in those who also had HIV. The prevalence of HIV-HCV co-infection worldwide was estimated to be 6.2% representing more than 2.2 million people. Intravenous drug use was an independent risk factor for HCV infection. In the WHO study, the prevalence of HIV-HCV co-infection was markedly higher at 82.4% in those who injected drugs compared to the general population (2.4%). In a study of HIV-HCV co-infection among HIV positive men who have sex with men (MSM), the overall prevalence of anti-hepatitis C antibodies was estimated to be 8.1% and increased to 40% among HIV positive MSM who also injected drugs. Pregnancy Hepatitis B Vertical transmission is a significant contributor of new HBV cases each year, with 35–50% of transmission from mother to neonate in endemic countries. Vertical transmission occurs largely via a neonates exposure to maternal blood and vaginal secretions during birth. While the risk of progression to chronic infection is approximately 5% among adults who contract the virus, it is as high as 95% among neonates subject to vertical transmission. The risk of viral transmission is approximately 10–20% when maternal blood is positive for HBsAg, and up to 90% when also positive for HBeAg.Given the high risk of perinatal transmission, the CDC recommends screening all pregnant women for HBV at their first prenatal visit. It is safe for non-immune pregnant women to receive the HBV vaccine. Based on the limited available evidence, the American Association for the Study of Liver Diseases (AASLD) recommends antiviral therapy in pregnant women whose viral load exceeds 200,000 IU/mL. A growing body of evidence shows that antiviral therapy initiated in the third trimester significantly reduces transmission to the neonate. A systematic review of the Antiretroviral Pregnancy Registry database found that there was no increased risk of congenital anomalies with Tenofovir; for this reason, along with its potency and low risk of resistance, the AASLD recommends this drug. A 2010 systematic review and meta-analysis found that Lamivudine initiated early in the third trimester also significantly reduced mother-to-child transmission of HBV, without any known adverse effects.The ACOG states that the evidence available does not suggest any particular mode of delivery (i.e. vaginal vs. cesarean) is better at reducing vertical transmission in mothers with HBV.The WHO and CDC recommend that neonates born to mothers with HBV should receive hepatitis B immune globulin (HBIG) as well as the HBV vaccine within 12 hours of birth. For infants who have received HBIG and the HBV vaccine, breastfeeding is safe. Hepatitis C Estimates of the rate of HCV vertical transmission range from 2–8%; a 2014 systematic review and meta-analysis found the risk to be 5.8% in HCV-positive, HIV-negative women. The same study found the risk of vertical transmission to be 10.8% in HCV-positive, HIV-positive women. Other studies have found the risk of vertical transmission to be as high as 44% among HIV-positive women. The risk of vertical transmission is higher when the virus is detectable in the mothers blood.Evidence does not indicate that mode of delivery (i.e. vaginal vs. cesarean) has an effect on vertical transmission.For women who are HCV-positive and HIV-negative, breastfeeding is safe. CDC guidelines suggest avoiding it if a womans nipples are cracked or bleeding to reduce the risk of transmission. Hepatitis E Pregnant women who contract HEV are at significant risk of developing fulminant hepatitis with maternal mortality rates as high as 20–30%, most commonly in the third trimester. A 2016 systematic review and meta-analysis of 47 studies that included 3968 people found maternal case-fatality rates (CFR) of 20.8% and fetal CFR of 34.2%; among women who developed fulminant hepatic failure, CFR was 61.2%. See also World Hepatitis Day References External links WHO fact sheet of hepatitis Viral Hepatitis at the Centers for Disease Control
Hypoesthesia	Hypoesthesia or numbness is a common side effect of various medical conditions that manifests as a reduced sense of touch or sensation, or a partial loss of sensitivity to sensory stimuli. In everyday speech this is generally referred to as numbness.Hypoesthesia primarily results from damage to nerves, and from blockages in blood vessels, resulting in ischemic damage to tissues supplied by the blocked blood vessels. This damage is detectable through the use of various imaging studies. Damage in this way is caused by a variety of different illnesses and diseases. A few examples of the most common illnesses and diseases that can cause hypoesthesia as a side effect are as follows: Decompression sickness Trigeminal schwannoma Rhombencephalitis Intradural extramedullary tuberculoma of the spinal cord Cutaneous sensory disorder Beriberi Diseases Decompression sickness Decompression sickness occurs during rapid ascent, spanning 20 or more feet (typically from underwater). Decompression sickness may express itself in a variety of ways, including hypoesthesia. Hypoesthesia results because of air bubbles that form in blood, which prevents oxygenation of downstream tissue. In cases of decompression sickness, treatment to relieve hypoesthesia symptoms is quick and efficient. Hyperbaric oxygen is used to maintain long term stability, which includes breathing of oxygen at a level of 100%. Trigeminal schwannoma Trigeminal schwannoma is a condition in which a tumor forms on the trigeminal nerve (also known as cranial nerve five). This prevents sensation in the area associated with the nerve. In the case of the trigeminal nerve, this is the face, meaning hypoesthesia of the face is experienced. Excision is the only effective treatment of trigeminal schwannoma, though this may not treat the associated hypoesthesia if damage has already occurred. Following surgery, many patients still experienced hypoesthesia and some even experienced increased effects. Rhombencephalitis Rhombencephalitis involves bacterial invasion of the brainstem and trigeminal nerve, and has a wide variety of symptoms that may vary between patients. Similarly to the trigeminal schwanonoma mentioned above, this can result in facial hypoesthesia. Rhombencephalitis may also result in hypoesthesia of the V1 through V3 dermatomes. The main treatment option for this infection is antibiotics, such as ampicillin, to remove the bacteria. Intradural extramedullary tuberculoma of the spinal cord (IETSC) IETSC is a cancer of the spinal cord that involves hypoesthesia of all parts of the body associated with the affected spinal nerves. The inability to convey information from the body to the central nervous system will cause a total lack of feeling in the associated regions. Cutaneous sensory disorder Hypoesthesia is one of the negative sensory symptoms associated with cutaneous sensory disorder (CSD). In this condition, patients have abnormal disagreeable skin sensations that can be due to increased nervous system activity (stinging, itching or burning) or decreased nervous system activity (numbness or hypoesthesia). Beriberi Hypoesthesia originating in (and extending centrally from) the feet, fingers, navel, and/or lips is one of the common symptoms of beriberi, which is a set of symptoms caused by thiamine deficiency. Diagnosis A patient experiencing symptoms of hypoesthesia is often asked a series of questions to pinpoint the location and severity of the sensory disruption. A physical examination may follow where a doctor may tap lightly on the skin to determine how much feeling is present. Depending upon the location of the symptoms occurring, a doctor may recommend some tests to determine the overlying cause of the hypoesthesia. These tests include imaging computerized axial tomography (CT) and magnetic resonance imaging (MRI) scans, nerve conduction studies to measure electrical impulses passing through the nerves in search of damage to the nerves, and various reflex tests. An example of a reflex test would be the patellar reflex test. Treatment Treatment of hypoethesia are aimed at targeting the more broad disease or illnesses that has caused the side effect of sensation loss. See also Anaphia Dysesthesia Hyperesthesia Paresthesia Raynaud syndrome == References ==

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