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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 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) 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 hepatocellular 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 ==

Disinhibition

In psychology, disinhibition is a lack of restraint manifested in disregard of social conventions, impulsivity, and poor risk assessment. Disinhibition affects motor, instinctual, emotional, cognitive, and perceptual aspects with signs and symptoms similar to the diagnostic criteria for mania. Hypersexuality, hyperphagia, and aggressive outbursts are indicative of disinhibited instinctual drives. Clinical concept According to Grafman, et al., "disinhibition" is a lack of restraint manifested in several ways, affecting motor, instinctual, emotional, cognitive, and perceptual aspects with signs and symptoms, e.g., impulsivity, disregard for others and social norms, aggressive outbursts, misconduct and oppositional behaviours, disinhibited instinctual drives including risk taking behaviours and hypersexuality. Disinhibition is a common symptom following brain injury, or lesions, particularly to the frontal lobe and primarily to the orbitofrontal cortex. The neuropsychiatric sequelae following brain injuries could include diffuse cognitive impairment, with more prominent deficits in the rate of information processing, attention, memory, cognitive flexibility, and problem solving. Prominent impulsivity, affective instability, and disinhibition are seen frequently, secondary to injury to frontal, temporal, and limbic areas. In association with the typical cognitive deficits, these sequelae characterise the frequently noted "personality changes" in TBI (Traumatic Brain Injury) patients. Disinhibition syndromes, in brain injuries and insults including brain tumors, strokes and epilepsy range from mildly inappropriate social behaviour, lack of control over ones behaviour to the full-blown mania, depending on the lesions to specific brain regions. Several studies in brain traumas and insults have demonstrated significant associations between disinhibition syndromes and dysfunction of orbitofrontal and basotemporal cortices, affecting visuospatial functions, somatosensation, and spatial memory, motoric, instinctive, affective, and intellectual behaviours.Disinhibition syndromes have also been reported with mania-like manifestations in old age with lesions to the orbito-frontal and basotemporal cortex involving limbic and frontal connections (orbitofrontal circuit), especially in the right hemisphere. Behavioural disinhibition as a result of damage to frontal lobe could be seen as a result of consumption of alcohol and central nervous system depressants drugs, e.g., benzodiazepines that disinhibit the frontal cortex from self-regulation and control. It has also been argued that ADHD, hyperactive/impulsive subtype have a general behavioural disinhibition beyond impulsivity and many morbidities or complications of ADHD, e.g., conduct disorder, anti-social personality disorder, substance abuse, and risk taking behaviours are all consequences of untreated behavioural disinhibition. Treatment approaches Positive Behaviour Support (PBS) is a treatment approach that looks at the best way to work with each individual with disabilities. A behavioural therapist conducts a functional analysis of behaviour which helps to determine ways to improve the quality of life for the person and does not just deal with problem behaviour. A quick guide for staff to remind about key elements of treatment for a person with disabilities is below. There are two main objectives: reacting situationally when the behavior occurs, and then acting proactively to prevent the behaviour from occurring. Reactive Reactive strategies include: Redirection: distracting the person by offering another activity, or changing the topic of conversation. Offer the person a choice of 2 or 3 things, but no more than 3, because this can be overwhelming. In offering a choice, make sure to pause to allow the person time to process the information and give a response. Talking to the person and finding out what the problem is Working out what the persons behaviour is trying to communicate Crisis management Proactive Proactive strategies to prevent problems can include: Change the environment: This can include increasing opportunities for access to a variety of activities, balancing cognitively and physically demanding activities with periods of rest, providing a predictable environment in order to reduce the level of cognitive demands on the person, trying to provide consistent routines (be mindful of events that may not occur, try not to make promises that cannot be kept, if unable to go out at a particular time then say so), checking for safety in the home environment (e.g., changing/moving furniture). Teach a skill: These can include general skills development of useful communication strategies, coping skills (e.g. teach the person what to do when feeling angry, anxious) Individual behaviour support plans: These involve reinforcing specific desirable behavior and ignoring the specific undesirable behavior (unless it is dangerous, the priority is to keep both people safe through a crisis plan which might involve removing sharp objects or weapons, escaping to a safe place, giving the person time to calm down), avoiding things you know upsets the person, strategies to increase engagement in activities.Broadly speaking, when the behavior occurs, assertively in a nonjudgmental, clear, unambiguous way provide feedback that the behavior is inappropriate, and say what you prefer instead. For example, "Jane, youre standing too close when you are speaking to me, I feel uncomfortable, please take a step back", or "I dont like it when you say I look hot in front of your wife, I feel uncomfortable, I am your Attendant Carer/Support Worker, I am here to help you with your shopping" Also in non-verbal communication, communication can appear in other forms, one could say "I dont like it when you dart your eyes at me in that way". Then re-direct to the next activity. Any subsequent behavior ignore. Then generally, as almost all behavior is communication, understand what the behavior is trying to communicate and look at ways to have the need met in more appropriate ways. See also Boldness Frontotemporal dementia Online disinhibition effect Orbitofrontal cortex References External links The Online Disinhibition Effect Archived 2007-07-07 at the Wayback Machine Social Behaviour In Cyberspace External Inhibition & Disinhibition

Substance dependence

Substance dependence, also known as drug dependence, is a biopsychological situation whereby an individuals functionality is dependent on the necessitated re-consumption of a psychoactive substance because of an adaptive state that has developed within the individual from psychoactive substance consumption that results in the experience of withdrawal and that necessitates the re-consumption of the drug. A drug addiction, a distinct concept from substance dependence, is defined as compulsive, out-of-control drug use, despite negative consequences. An addictive drug is a drug which is both rewarding and reinforcing. ΔFosB, a gene transcription factor, is now known to be a critical component and common factor in the development of virtually all forms of behavioral and drug addictions, but not dependence. The International Classification of Diseases classifies substance dependence as a mental and behavioural disorder. Within the framework of the 4th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), substance dependence is redefined as a drug addiction, and can be diagnosed without the occurrence of a withdrawal syndrome. It was described accordingly: "When an individual persists in use of alcohol or other drugs despite problems related to use of the substance, substance dependence may be diagnosed. Compulsive and repetitive use may result in tolerance to the effect of the drug and withdrawal symptoms when use is reduced or stopped. This, along with Substance Abuse are considered Substance Use Disorders." In the DSM-5 (released in 2013), substance abuse and substance dependence have been merged into the category of substance use disorders and they no longer exist as individual diagnoses. Withdrawal Withdrawal is the bodys reaction to abstaining from a substance upon which a person has developed a dependence syndrome. When dependence has developed, cessation of substance-use produces an unpleasant state, which promotes continued drug use through negative reinforcement; i.e., the drug is used to escape or avoid re-entering the associated withdrawal state. The withdrawal state may include physical-somatic symptoms (physical dependence), emotional-motivational symptoms (psychological dependence), or both. Chemical and hormonal imbalances may arise if the substance is not re-introduced. Psychological stress may also result if the substance is not re-introduced.Infants also experience substance withdrawal, known as neonatal abstinence syndrome (NAS), which can have severe and life-threatening effects. Addiction to drugs such as alcohol in expectant mothers not only causes NAS, but also an array of other issues which can continually affect the infant throughout their lifetime. Risk factors Dependence potential The dependence potential of a drug varies from substance to substance, and from individual to individual. Dose, frequency, pharmacokinetics of a particular substance, route of administration, and time are critical factors for developing a drug dependence. 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. Selected results can be seen in the chart below. Capture rates Capture rates enumerate the percentage of users who reported that they had become dependent to their respective drug at some point. Biomolecular mechanisms Psychological dependence Two factors have been identified as playing pivotal roles in psychological dependence: the neuropeptide "corticotropin-releasing factor" (CRF) and the gene transcription factor "cAMP response element binding protein" (CREB). The nucleus accumbens (NAcc) is one brain structure that has been implicated in the psychological component of drug dependence. In the NAcc, CREB is activated by cyclic adenosine monophosphate (cAMP) immediately after a high and triggers changes in gene expression that affect proteins such as dynorphin; dynorphin peptides reduce dopamine release into the NAcc by temporarily inhibiting the reward pathway. A sustained activation of CREB thus forces a larger dose to be taken to reach the same effect. In addition, it leaves the user feeling generally depressed and dissatisfied, and unable to find pleasure in previously enjoyable activities, often leading to a return to the drug for another dose.In addition to CREB, it is hypothesized that stress mechanisms play a role in dependence. Koob and Kreek have hypothesized that during drug use, CRF activates the hypothalamic–pituitary–adrenal axis (HPA axis) and other stress systems in the extended amygdala. This activation influences the dysregulated emotional state associated with psychological dependence. They found that as drug use escalates, so does the presence of CRF in human cerebrospinal fluid. In rat models, the separate use of CRF inhibitors and CRF receptor antagonists both decreased self-administration of the drug of study. Other studies in this review showed dysregulation of other neuropeptides that affect the HPA axis, including enkephalin which is an endogenous opioid peptide that regulates pain. It also appears that µ-opioid receptors, which enkephalin acts upon, is influential in the reward system and can regulate the expression of stress hormones.Increased expression of AMPA receptors in nucleus accumbens MSNs is a potential mechanism of aversion produced by drug withdrawal. Physical dependence Upregulation of the cAMP signal transduction pathway in the locus coeruleus by CREB has been implicated as the mechanism responsible for certain aspects of opioid-induced physical dependence. The temporal course of withdrawal correlates with LC firing, and administration of α2 agonists into the locus coeruleus leads to a decrease in LC firing and norepinephrine release during withdrawal. A possible mechanism involves upregulation of NMDA receptors, which is supported by the attenuation of withdraw by NMDA receptor antagonists. Physical dependence on opioids has been observed to produce an elevation of extracellular glutamate, an increase in NMDA receptor subunits NR1 and NR2A, phosphorylated CaMKII, and c-fos. Expression of CaMKII and c-fos is attenuated by NMDA receptor antagonists, which is associated with blunted withdrawal in adult rats, but not neonatal rats While acute administration of opioids decreases AMPA receptor expression and depresses both NMDA and non-NMDA excitatory postsynaptic potentials in the NAC, withdrawal involves a lowered threshold for LTP and an increase in spontaneous firing in the NAc. Diagnosis DSM classification "Substance dependence", as defined in the DSM-IV, can be diagnosed with physiological dependence, evidence of tolerance or withdrawal, or without physiological dependence. DSM-IV substance dependencies include: 303.90 Alcohol dependence 304.00 Opioid dependence 304.10 Sedative, hypnotic, or anxiolytic dependence (including benzodiazepine dependence and barbiturate dependence) 304.20 Cocaine dependence 304.30 Cannabis dependence 304.40 Amphetamine dependence (or amphetamine-like) 304.50 Hallucinogen dependence 304.60 Inhalant dependence 304.80 Polysubstance dependence 304.90 Phencyclidine (or phencyclidine-like) dependence 304.90 Other (or unknown) substance dependence 305.10 Nicotine dependence Management Addiction is a complex but treatable condition. It is characterized by compulsive drug craving, seeking, and use that persists even if the user is aware of severe adverse consequences. For some people, addiction becomes chronic, with periodic relapses even after long periods of abstinence. As a chronic, relapsing disease, addiction may require continued treatments to increase the intervals between relapses and diminish their intensity. While some with substance issues recover and lead fulfilling lives, others require ongoing additional support. The ultimate goal of addiction treatment is to enable an individual to manage their substance misuse; for some this may mean abstinence. Immediate goals are often to reduce substance abuse, improve the patients ability to function, and minimize the medical and social complications of substance abuse and their addiction; this is called "harm reduction". Treatments for addiction vary widely according to the types of drugs involved, amount of drugs used, duration of the drug addiction, medical complications and the social needs of the individual. Determining the best type of recovery program for an addicted person depends on a number of factors, including: personality, drugs of choice, concept of spirituality or religion, mental or physical illness, and local availability and affordability of programs. Many different ideas circulate regarding what is considered a successful outcome in the recovery from addiction. Programs that emphasize controlled drinking exist for alcohol addiction. Opiate replacement therapy has been a medical standard of treatment for opioid addiction for many years. Treatments and attitudes toward addiction vary widely among different countries. In the US and developing countries, the goal of commissioners of treatment for drug dependence is generally total abstinence from all drugs. Other countries, particularly in Europe, argue the aims of treatment for drug dependence are more complex, with treatment aims including reduction in use to the point that drug use no longer interferes with normal activities such as work and family commitments; shifting the addict away from more dangerous routes of drug administration such as injecting to safer routes such as oral administration; reduction in crime committed by drug addicts; and treatment of other comorbid conditions such as AIDS, hepatitis and mental health disorders. These kinds of outcomes can be achieved without eliminating drug use completely. Drug treatment programs in Europe often report more favorable outcomes than those in the US because the criteria for measuring success are functional rather than abstinence-based. The supporters of programs with total abstinence from drugs as a goal believe that enabling further drug use means prolonged drug use and risks an increase in addiction and complications from addiction. Residential Residential drug treatment can be broadly divided into two camps: 12-step programs and therapeutic communities. 12-step programs are a nonclinical support-group and spiritual-based approach to treating addiction. Therapy typically involves the use of cognitive-behavioral therapy, an approach that looks at the relationship between thoughts, feelings and behaviors, addressing the root cause of maladaptive behavior. Cognitive-behavioral therapy treats addiction as a behavior rather than a disease, and so is subsequently curable, or rather, unlearnable. Cognitive-behavioral therapy programs recognize that, for some individuals, controlled use is a more realistic possibility.One of many recovery methods are 12-step recovery programs, with prominent examples including Alcoholics Anonymous, Narcotics Anonymous, Drug Addicts Anonymous and Pills Anonymous. They are commonly known and used for a variety of addictions for the individual addicted and the family of the individual. Substance-abuse rehabilitation (rehab) centers offer a residential treatment program for some of the more seriously addicted, in order to isolate the patient from drugs and interactions with other users and dealers. Outpatient clinics usually offer a combination of individual counseling and group counseling. Frequently, a physician or psychiatrist will prescribe medications in order to help patients cope with the side effects of their addiction. Medications can help immensely with anxiety and insomnia, can treat underlying mental disorders (cf. self-medication hypothesis, Khantzian 1997) such as depression, and can help reduce or eliminate withdrawal symptomology when withdrawing from physiologically addictive drugs. Some examples are using benzodiazepines for alcohol detoxification, which prevents delirium tremens and complications; using a slow taper of benzodiazepines or a taper of phenobarbital, sometimes including another antiepileptic agent such as gabapentin, pregabalin, or valproate, for withdrawal from barbiturates or benzodiazepines; using drugs such as baclofen to reduce cravings and propensity for relapse amongst addicts to any drug, especially effective in stimulant users, and alcoholics (in which it is nearly as effective as benzodiazepines in preventing complications); using clonidine, an alpha-agonist, and loperamide for opioid detoxification, for first-time users or those who wish to attempt an abstinence-based recovery (90% of opioid users relapse to active addiction within eight months or are multiple relapse patients); or replacing an opioid that is interfering with or destructive to a users life, such as illicitly-obtained heroin, dilaudid, or oxycodone, with an opioid that can be administered legally, reduces or eliminates drug cravings, and does not produce a high, such as methadone or buprenorphine – opioid replacement therapy – which is the gold standard for treatment of opioid dependence in developed countries, reducing the risk and cost to both user and society more effectively than any other treatment modality (for opioid dependence), and shows the best short-term and long-term gains for the user, with the greatest longevity, least risk of fatality, greatest quality of life, and lowest risk of relapse and legal issues including arrest and incarceration.In a survey of treatment providers from three separate institutions, the National Association of Alcoholism and Drug Abuse Counselors, Rational Recovery Systems and the Society of Psychologists in Addictive Behaviors, measuring the treatment providers responses on the "Spiritual Belief Scale" (a scale measuring belief in the four spiritual characteristics of AA identified by Ernest Kurtz); the scores were found to explain 41% of the variance in the treatment providers responses on the "Addiction Belief Scale" (a scale measuring adherence to the disease model or the free-will model of addiction). Behavioral programming Behavioral programming is considered critical in helping those with addictions achieve abstinence. From the applied behavior analysis literature and the behavioral psychology literature, several evidence based intervention programs have emerged: (1) behavioral marital therapy; (2) community reinforcement approach; (3) cue exposure therapy; and (4) contingency management strategies. In addition, the same author suggests that social skills training adjunctive to inpatient treatment of alcohol dependence is probably efficacious. Community reinforcement has both efficacy and effectiveness data. In addition, behavioral treatment such as community reinforcement and family training (CRAFT) have helped family members to get their loved ones into treatment. Motivational intervention has also shown to be an effective treatment for substance dependence. Alternative therapies Alternative therapies, such as acupuncture, are used by some practitioners to alleviate the symptoms of drug addiction. In 1997, the American Medical Association (AMA) adopted, as policy, the following statement after a report on a number of alternative therapies including acupuncture: There is little evidence to confirm the safety or efficacy of most alternative therapies. Much of the information currently known about these therapies makes it clear that many have not been shown to be efficacious. Well-designed, stringently controlled research should be done to evaluate the efficacy of alternative therapies. Treatment and issues Medical professionals need to apply many techniques and approaches to help patients with substance related disorders. Using a psychodynamic approach is one of the techniques that psychologists use to solve addiction problems. In psychodynamic therapy, psychologists need to understand the conflicts and the needs of the addicted person, and also need to locate the defects of their ego and defense mechanisms. Using this approach alone has proven to be ineffective in solving addiction problems. Cognitive and behavioral techniques should be integrated with psychodynamic approaches to achieve effective treatment for substance related disorders. Cognitive treatment requires psychologists to think deeply about what is happening in the brain of an addicted person. Cognitive psychologists should zoom in to neural functions of the brain and understand that drugs have been manipulating the dopamine reward center of the brain. From this particular state of thinking, cognitive psychologists need to find ways to change the thought process of the addicted person. Cognitive approach There are two routes typically applied to a cognitive approach to substance abuse: tracking the thoughts that pull patients to addiction and tracking the thoughts that prevent them from relapsing. Behavioral techniques have the widest application in treating substance related disorders. Behavioral psychologists can use the techniques of "aversion therapy", based on the findings of Pavlovs classical conditioning. It uses the principle of pairing abused substances with unpleasant stimuli or conditions; for example, pairing pain, electrical shock, or nausea with alcohol consumption. The use of medications may also be used in this approach, such as using disulfiram to pair unpleasant effects with the thought of alcohol use. Psychologists tend to use an integration of all these approaches to produce reliable and effective treatment. With the advanced clinical use of medications, biological treatment is now considered to be one of the most efficient interventions that psychologists may use as treatment for those with substance dependence. Medicinal approach Another approach is to use medicines that interfere with the functions of the drugs in the brain. Similarly, one can also substitute the misused substance with a weaker, safer version to slowly taper the patient off of their dependence. Such is the case with Suboxone in the context of opioid dependence. These approaches are aimed at the process of detoxification. Medical professionals weigh the consequences of withdrawal symptoms against the risk of staying dependent on these substances. These withdrawal symptoms can be very difficult and painful times for patients. Most will have steps in place to handle severe withdrawal symptoms, either through behavioral therapy or other medications. Biological intervention should be combined with behavioral therapy approaches and other non-pharmacological techniques. Group therapies including anonymity, teamwork and sharing concerns of daily life among people who also have substance dependence issues can have a great impact on outcomes. However, these programs proved to be more effective and influential on persons who did not reach levels of serious dependence. Vaccines TA-CD is an active vaccine developed by the Xenova Group which is used to negate the effects of cocaine, making it suitable for use in treatment of addiction. It is created by combining norcocaine with inactivated cholera toxin. TA-NIC is a proprietary vaccine in development similar to TA-CD but being used to create human anti-nicotine antibodies in a person to destroy nicotine in the human body so that it is no longer effective. History The phenomenon of drug addiction has occurred to some degree throughout recorded history (see "Opium"). Modern agricultural practices, improvements in access to drugs, advancements in biochemistry, and dramatic increases in the recommendation of drug usage by clinical practitioners have exacerbated the problem significantly in the 20th century. Improved means of active biological agent manufacture and the introduction of synthetic compounds, such as fentanyl and methamphetamine, are also factors contributing to drug addiction.For the entirety of US history, drugs have been used by some members of the population. In the countrys early years, most drug use by the settlers was of alcohol or tobacco.The 19th century saw opium usage in the US become much more common and popular. Morphine was isolated in the early 19th century, and came to be prescribed commonly by doctors, both as a painkiller and as an intended cure for opium addiction. At the time, the prevailing medical opinion was that the addiction process occurred in the stomach, and thus it was hypothesized that patients would not become addicted to morphine if it was injected into them via a hypodermic needle, and it was further hypothesized that this might potentially be able to cure opium addiction. However, many people did become addicted to morphine. In particular, addiction to opium became widespread among soldiers fighting in the Civil War, who very often required painkillers and thus were very often prescribed morphine. Women were also very frequently prescribed opiates, and opiates were advertised as being able to relieve "female troubles".Many soldiers in the Vietnam War were introduced to heroin and developed a dependency on the substance which survived even when they returned to the US. Technological advances in travel meant that this increased demand for heroin in the US could now be met. Furthermore, as technology advanced, more drugs were synthesized and discovered, opening up new avenues to substance dependency. Society and culture Demographics Internationally, the U.S. and Eastern Europe contain the countries with the highest substance abuse disorder occurrence (5-6%). Africa, Asia, and the Middle East contain countries with the lowest worldwide occurrence (1-2%). Across the globe, those that tended to have a higher prevalence of substance dependence were in their twenties, unemployed, and men. The National Survey on Drug Use and Health (NSDUH) reports on substance dependence/abuse rates in various population demographics across the U.S. When surveying populations based on race and ethnicity in those ages 12 and older, it was observed that American Indian/Alaskan Natives were among the highest rates and Asians were among the lowest rates in comparison to other racial/ethnic groups. When surveying populations based on gender in those ages 12 and older, it was observed that males had a higher substance dependence rate than females. However, the difference in the rates are not apparent until after age 17.Drug and Alcohol Dependence reports that older adults abuse drugs including alcohol at a rate of 15-20%. Its estimated that 52 million Americans beyond 12 years old have abused a substance. Alcohol dependence or abuse rates were shown to have no correspondence with any persons education level when populations were surveyed in varying degrees of education from ages 26 and older. However, when it came to illicit drug use there was a correlation, in which those that graduated from college had the lowest rates. Furthermore, dependence rates were greater in unemployed populations ages 18 and older and in metropolitan-residing populations ages 12 and older. The National Opinion Research Center at the University of Chicago reported an analysis on disparities within admissions for substance abuse treatment in the Appalachian region, which comprises 13 states and 410 counties in the Eastern part of the U.S. While their findings for most demographic categories were similar to the national findings by NSDUH, they had different results for racial/ethnic groups which varied by sub-regions. Overall, Whites were the demographic with the largest admission rate (83%), while Alaskan Native, American Indian, Pacific Islander, and Asian populations had the lowest admissions (1.8%). Legislation Depending on the jurisdiction, addictive drugs may be legal, legal only as part of a government sponsored study, illegal to use for any purpose, illegal to sell, or even illegal to merely possess. Most countries have legislation which brings various drugs and drug-like substances under the control of licensing systems. Typically this legislation covers any or all of the opiates, amphetamines, cannabinoids, cocaine, barbiturates, benzodiazepines, anesthetics, hallucinogenics, derivatives and a variety of more modern synthetic drugs. Unlicensed production, supply or possession is a criminal offence. Usually, however, drug classification under such legislation is not related simply to addictiveness. The substances covered often have very different addictive properties. Some are highly prone to cause physical dependency, while others rarely cause any form of compulsive need whatsoever. Also, under legislation specifically about drugs, alcohol and nicotine are not usually included.Although the legislation may be justifiable on moral or public health grounds, it can make addiction or dependency a much more serious issue for the individual: reliable supplies of a drug become difficult to secure, and the individual becomes vulnerable to both criminal abuse and legal punishment. It is unclear whether laws against illegal drug use do anything to stem usage and dependency. In jurisdictions where addictive drugs are illegal, they are generally supplied by drug dealers, who are often involved with organized crime. Even though the cost of producing most illegal addictive substances is very low, their illegality combined with the addicts need permits the seller to command a premium price, often hundreds of times the production cost. As a result, addicts sometimes turn to crime to support their habit. United States In the United States, drug policy is primarily controlled by the federal government. The Department of Justices Drug Enforcement Administration (DEA) enforces controlled substances laws and regulations. The Department of Health and Human Services Food and Drug Administration (FDA) serve to protect and promote public health by controlling the manufacturing, marketing, and distribution of products, like medications. The United States approach to substance abuse has shifted over the last decade, and is continuing to change. The federal government was minimally involved in the 19th century. The federal government transitioned from using taxation of drugs in the early 20th century to criminalizing drug abuse with legislations and agencies like the Federal Bureau of Narcotics (FBN) mid-20th century in response to the nations growing substance abuse issue. These strict punishments for drug offenses shined light on the fact that drug abuse was a multi-faceted problem. The Presidents Advisory Commission on Narcotics and Drug Abuse of 1963 addressed the need for a medical solution to drug abuse. However, drug abuse continued to be enforced by the federal government through agencies such as the DEA and further legislations such as The Controlled Substances Act (CSA), the Comprehensive Crime Control Act of 1984, and Anti-Drug Abuse Acts. In the past decade, there have been growing efforts through state and local legislations to shift from criminalizing drug abuse to treating it as a health condition requiring medical intervention. 28 states currently allow for the establishment of needle exchanges. Florida, Iowa, Missouri and Arizona all introduced bills to allow for the establishment of needle exchanges in 2019. These bills have grown in popularity across party lines since needle exchanges were first introduced in Amsterdam in 1983. In addition, AB-186 Controlled substances: overdose prevention program was introduced to operate safe injection sites in the City and County of San Francisco. The bill was vetoed on September 30, 2018, by California Governor Jerry Brown. The legality of these sites are still in discussion, so there are no such sites in the United States yet. However, there is growing international evidence for successful safe injection facilities. See also Questionnaires References External links American Society of Addiction Medicine website Health-EU Portal – Drugs people, drug addicts Trips Beyond Addiction | Living Hero Radio Show and Podcast special. With Dimitri Mobengo Mugianis, Bovenga Na Muduma, Clare S. Wilkins, Brad Burge, Tom Kingsley Brown, Susan Thesenga, Bruce K. Alexander, PhD ~ the voices of ex-addicts, researchers from The Multidisciplinary Association for Psychedelic Studies and Ibogaine/Iboga/Ayahuasca treatment providers sharing their experiences in breaking addiction with native medicines. January 2013 A social history of Americas most popular drugs. National Institute on Drug Abuse: "NIDA for Teens: Brain and Addiction". "WHO Expert Committee on Drug Dependence – WHO Technical Report Series, No. 915 – Thirty-third Report". apps.who.int. 2003. Archived from the original on 9 October 2012. Retrieved 26 February 2015. - pdf

Cranial nerve disease

Cranial nerve disease is an impaired functioning of one of the twelve cranial nerves. Although it could theoretically be considered a mononeuropathy, it is not considered as such under MeSH. It is possible for a disorder of more than one cranial nerve to occur at the same time, if a trauma occurs at a location where many cranial nerves run together, such as the jugular fossa. A brainstem lesion could also cause impaired functioning of multiple cranial nerves, but this condition would likely also be accompanied by distal motor impairment. A neurological examination can test the functioning of individual cranial nerves, and detect specific impairments. Facial nerve palsy The facial nerve is the seventh of 12 cranial nerves. This cranial nerve controls the muscles in the face. Facial nerve palsy is more abundant in older adults than in children and is said to affect 15-40 out of 100,000 people per year. This disease comes in many forms which include congenital, infectious, traumatic, neoplastic, or idiopathic. The most common cause of this cranial nerve damage is Bells palsy (idiopathic facial palsy) which is a paralysis of the facial nerve. Although Bells palsy is more prominent in adults it seems to be found in those younger than 20 or older than 60 years of age. Bells Palsy is thought to occur by an infection of the herpes virus which may cause demyelination and has been found in patients with facial nerve palsy. Symptoms include flattening of the forehead, sagging of the eyebrow, and difficulty closing the eye and the mouth on the side of the face that is affected. The inability to close the mouth causes problems in feeding and speech. It also causes lack of taste, lacrimation, and sialorrhea.The use of steroids can help in the treatment of Bells Palsy. If in the early stages, steroids can increase the likelihood of a full recovery. This treatment is used mainly in adults. The use of steroids in children has not been proven to work because they seem to recover completely with or without them. Children also tend to have better recovery rates than older adults. Recovery rate also depends on the cause of the facial nerve palsy (e.g. infections, perinatal injury, congenital dysplastic). If the palsy is more severe patients should seek steroids or surgical procedures. Facial nerve palsy may be the indication of a severe condition and when diagnosed a full clinical history and examination are recommended.Although rare, facial nerve palsy has also been found in patients with HIV seroconversion. Symptoms found include headaches (bitemporal or occipital), the inability to close the eyes or mouth, and may cause the reduction of taste. Few cases of bilateral facial nerve palsy have been reported and is said to only effect 1 in every 5 million per year. Others Eyes Oculomotor nerve palsy - Oculomotor nerve (III) Fourth nerve palsy - Trochlear nerve (IV) Sixth nerve palsy - Abducens nerve (VI) Other Trigeminal neuralgia - Trigeminal nerve (V) Facial nerve paralysis, Bells palsy, Melkersson–Rosenthal syndrome, Central seven - Facial nerve (VII) Accessory nerve disorder - Accessory nerve (XI) References == External links ==

Arachnoiditis

Arachnoiditis is an inflammatory condition of the arachnoid mater or arachnoid, one of the membranes known as meninges that surround and protect the nerves of the central nervous system, including the brain and spinal cord. The arachnoid can become inflamed because of adverse reactions to chemicals, infection from bacteria or viruses, as the result of direct injury to the spine, chronic compression of spinal nerves, complications from spinal surgery or other invasive spinal procedures, or the accidental intrathecal injection of steroids intended for the epidural space. Inflammation can sometimes lead to the formation of scar tissue and adhesion that can make the spinal nerves "stick" together, a condition where such tissue develops in and between the leptomeninges. The condition is extremely painful, especially when progressing to adhesive arachnoiditis. Another form of the condition is arachnoiditis ossificans, in which the arachnoid becomes ossified, or turns to bone, and is thought to be a late-stage complication of the adhesive form of arachnoiditis. Signs and symptoms Arachnoid inflammation can lead to many painful and debilitating symptoms which can vary greatly in each case, and not all people experience all symptoms. Chronic pain is common, including neuralgia, while numbness and tingling of the extremities can occur with spinal cord involvement, and bowel, bladder, and sexual functioning can be affected if the lower part of the spinal cord is involved. While arachnoiditis has no consistent pattern of symptoms, it frequently affects the nerves that supply the legs and lower back. Many patients experience difficulty sitting for long (or even short) periods of time due to discomfort or pain, or because of efferent neurological or other motor symptoms, such as difficulties controlling limbs. Difficulty sitting can be problematic for patients who have trouble standing or walking for long periods, as wheelchairs are not always helpful in such cases. Causes The root cause of the condition is not entirely clear, and it appears to have multiple causes, including iatrogenic cause from misplaced epidural steroid injection therapy when accidentally administered intrathecally (inside the dura mater, the sac enveloping the arachnoid mater), or from contrast media used in myelography prior to the development of metrizamide and other water-soluble contrast agents. Other noninfectious inflammatory processes include surgery, intrathecal hemorrhage, and the administration of anesthetics (e.g. chloroprocaine), and steroids (e.g. prednisolone, triamcinolone acetonide). A variety of other causes exist, including infectious, inflammatory, and neoplastic processes. Infectious causes include bacterial, viral, fungal, and parasitic agents. Prior spinal surgery has been documented as a cause of arachnoiditis ossificans, as well as for the adhesive form. It can also be caused by long term pressure from either a severe disc herniation or spinal stenosis. Diagnosis For the ossificans form of the condition, unenhanced CT may better show the presence and extent of arachnoid ossifications, and is complementary to MRI, as MRI can be less specific and findings can be confused with regions of calcification or hemosiderin. Treatment Arachnoiditis is difficult to treat and treatment is generally limited to alleviation of pain and other symptoms. While arachnoiditis may not yet be curable and can be significantly life-altering, management of the condition, including with medication, physical therapy, and if appropriate, psychotherapy, can help patients cope with the difficulties it presents. Surgical intervention generally has a poor outcome and may only provide temporary relief, but some cases of surgical success have been reported. Epidural steroid injections to treat sciatic pain have been linked as a cause of the disease by the U.S. Food and Drug Administration as well as in other research, and are therefore discouraged as a treatment for Arachnoiditis as they will most likely worsen the condition. Some patients benefit from motorized assistance devices such as the Segway or standing wheelchairs, although these types of devices may be beyond the reach of those with limited means. Standing endurance and vibration tolerance are considered before considering such devices in any case. Prognosis Arachnoiditis is a chronic disorder with no known cure, and prognosis may be hard to determine because of an unclear correlation between the beginning of the disease and the appearance of symptoms. For many, arachnoiditis is a disabling disease that causes chronic pain and neurological deficits, and may also lead to other spinal cord conditions, such as syringomyelia. References Further reading Duke RJ; Hashimoto SA (April 1974). "Familial spinal arachnoiditis. A new entity". Arch. Neurol. 30 (4): 300–3. doi:10.1001/archneur.1974.00490340028005. PMID 4816834. External links Arachnoiditis Information Page at NINDS Arachnoiditis; Familial spinal arachnoiditis (subtype); Spinal tuberculous arachnoiditis (subtype) at NIHs Office of Rare Diseases Online Mendelian Inheritance in Man (OMIM): Spinal arachnoiditis - 182950

Hyperosmolar hyperglycemic state

Hyperosmolar hyperglycemic state (HHS) is a complication of diabetes mellitus in which high blood sugar results in high osmolarity without significant ketoacidosis. Symptoms include signs of dehydration, weakness, leg cramps, vision problems, and an altered level of consciousness. Onset is typically over days to weeks. Complications may include seizures, disseminated intravascular coagulopathy, mesenteric artery occlusion, or rhabdomyolysis.The main risk factor is a history of diabetes mellitus type 2. Occasionally it may occur in those without a prior history of diabetes or those with diabetes mellitus type 1. Triggers include infections, stroke, trauma, certain medications, and heart attacks. Diagnosis is based on blood tests finding a blood sugar greater than 30 mmol/L (600 mg/dL), osmolarity greater than 320 mOsm/kg, and a pH above 7.3.Initial treatment generally consists of intravenous fluids to manage dehydration, intravenous insulin in those with significant ketones, low molecular weight heparin to decrease the risk of blood clotting, and antibiotics among those in whom there are concerns of infection. The goal is a slow decline in blood sugar levels. Potassium replacement is often required as the metabolic problems are corrected. Efforts to prevent diabetic foot ulcers are also important. It typically takes a few days for the person to return to baseline.While the exact frequency of the condition is unknown, it is relatively common. Older people are most commonly affected. The risk of death among those affected is about 15%. It was first described in the 1880s. Signs and symptoms Symptoms of high blood sugar including increased thirst (polydipsia), increased volume of urination (polyuria), and increased hunger (polyphagia).Symptoms of HHS include: Altered level of consciousness Neurologic signs including: blurred vision, headaches, focal seizures, myoclonic jerking, reversible paralysis Motor abnormalities including flaccidity, depressed reflexes, tremors or fasciculations Hyperviscosity and increased risk of blood clot formation Dehydration Weight loss Nausea, vomiting, and abdominal pain Weakness Low blood pressure with standing Cause The main risk factor is a history of diabetes mellitus type 2. Occasionally it may occur in those without a prior history of diabetes or those with diabetes mellitus type 1. Triggers include infections, stroke, trauma, certain medications, and heart attacks.Other risk factors: Lack of sufficient insulin (but enough to prevent ketosis) Poor kidney function Poor fluid intake (dehydration) Older age (50–70 years) Certain medical conditions (cerebral vascular injury, myocardial infarction, sepsis) Certain medications (glucocorticoids, beta-blockers, thiazide diuretics, calcium channel blockers, and phenytoin) Pathophysiology HHS is usually precipitated by an infection, myocardial infarction, stroke or another acute illness. A relative insulin deficiency leads to a serum glucose that is usually higher than 33 mmol/L (600 mg/dL), and a resulting serum osmolarity that is greater than 320 mOsm. This leads to excessive urination (more specifically an osmotic diuresis), which, in turn, leads to volume depletion and hemoconcentration that causes a further increase in blood glucose level. Ketosis is absent because the presence of some insulin inhibits hormone-sensitive lipase-mediated fat tissue breakdown. Diagnosis Criteria According to the American Diabetes Association, diagnostic features include: Plasma glucose level >30 mmol/L (>600 mg/dL) Serum osmolality >320 mOsm/kg Profound dehydration, up to an average of 9L (and therefore substantial thirst (polydipsia)) Serum pH >7.30 Bicarbonate >15 mEq/L Small ketonuria (~+ on dipstick) and absent-to-low ketonemia (<3 mmol/L) Some alteration in consciousness BUN > 30 mg/dL (increased) Creatinine > 1.5 mg/dL (increased) Imaging Cranial imaging is not used for diagnosis of this condition. However, if MRI is performed, it may show cortical restricted diffusion with unusual characteristics of reversible T2 hypointensity in the subcortical white matter. Differential diagnosis The major differential diagnosis is diabetic ketoacidosis (DKA). In contrast to DKA, serum glucose levels in HHS are extremely high, usually greater than 40-50 mmol/L (600 mg/dL). Metabolic acidosis is absent or mild. A temporary state of confusion (delirium) is also more common in HHS than DKA. HHS also tends to affect older people more. DKA may have fruity breath, and rapid and deep breathing.DKA often has serum glucose level greater than 300 mg/dL (HHS is >600 mg/dL). DKA usually occurs in type 1 diabetics whereas HHS is more common in type 2 diabetics. DKA is characterized by a rapid onset, and HHS occurs gradually over a few days. DKA also is characterized by ketosis due to the breakdown of fat for energy.Both DKA and HHS may show symptoms of dehydration, increased thirst, increased urination, increased hunger, weight loss, nausea, vomiting, abdominal pain, blurred vision, headaches, weakness, and low blood pressure with standing. Management Intravenous fluids Treatment of HHS begins with reestablishing tissue perfusion using intravenous fluids. People with HHS can be dehydrated by 8 to 12 liters. Attempts to correct this usually take place over 24 hours with initial rates of normal saline often in the range of 1 L/h for the first few hours or until the condition stabilizes. Electrolyte replacement Potassium replacement is often required as the metabolic problems are corrected. It is generally replaced at a rate 10 mEq per hour as long as there is adequate urinary output. Insulin Insulin is given to reduce blood glucose concentration; however, as it also causes the movement of potassium into cells, serum potassium levels must be sufficiently high or dangerously low blood potassium levels may result. Once potassium levels have been verified to be greater than 3.3 mEq/L, then an insulin infusion of 0.1 units/kg/hr is started. The goal for resolution is a blood glucose of less than 200 mg/dL. References == External links ==

Clitoromegaly

Clitoromegaly (or macroclitoris) is an abnormal enlargement of the clitoris that is mostly congenital or acquired, though deliberately induced clitoris enlargement as a form of genital body modification is achieved through various uses of anabolic steroids, including testosterone. Clitoromegaly is not the same as normal enlargement of the clitoris seen during sexual arousal. Presentation The different grade of genital ambiguity is commonly measured by the Prader classification, which ranges, in ascending order of masculinisation, from 1: female external genitalia with clitoromegaly through 5: pseudo-phallus looking like normal male external genitalia. Causes Clitoromegaly is a rare condition and can be either present by birth or acquired later in life. If present at birth, congenital adrenal hyperplasia can be one of the causes, since in this condition the adrenal gland of the female fetus produces additional androgens and the newborn baby has ambiguous genitalia which are not clearly male or female. In pregnant women who received norethisterone during pregnancy, masculinization of the fetus occurs, resulting in hypertrophy of the clitoris; however, this is rarely seen nowadays due to use of safer progestogens. It can also be caused by the autosomal recessive congenital disorder known as Fraser syndrome.In acquired clitoromegaly, the main cause is endocrine hormonal imbalance affecting the adult person, including polycystic ovarian syndrome (PCOS) and hyperthecosis. Acquired clitoromegaly may also be caused by pathologies affecting the ovaries and other endocrine glands. These pathologies may include virulent (such as arrhenoblastoma) and neurofibromatosic tumors. Another cause is clitoral cysts. Sometimes there may be no obvious clinical or hormonal reason.Female bodybuilders and athletes who use androgens, primarily to enhance muscular growth, strength and appearance (see Use of performance-enhancing drugs in sport), may also experience clearly evident enlargement of the clitoris and increases in libido. For transgender men taking testosterone as part of transgender hormone therapy (female-to-male) masculinization of the clitoris may be a desired effect. Women who use testosterone for therapeutic reasons (treating low libido, averting osteoporosis, as part of an anti-depressant regimen, etc.) may experience some enlargement of the clitoris, although the dosages warranted for these conditions are much lower. Pseudoclitoromegaly or pseudohypertrophy of the clitoris "has been reported in small girls due to masturbation: manipulations of the skin of prepuce leads to repeated mechanical trauma, which expands the prepuce and labia minora, thus imitating true clitoral enlargement". Anatomy In Atlas of Human Sex Anatomy (1949) by Robert Latou Dickinson, the typical clitoris is defined as having a crosswise width of 3 to 4 mm (0.12 - 0.16 inches) and a lengthwise width of 4 to 5 mm (0.16 - 0.20 inches). On the other hand, in obstetrics and gynecology medical literature, a frequent definition of clitoromegaly is when there is a clitoral index (product of lengthwise and crosswise widths) of greater than 35 mm2 (0.05 inches2), which is almost twice the size given above for an average sized clitoris. Human rights concerns Early surgical reduction of clitoromegaly via full or partial clitoridectomy is controversial, and intersex people exposed to such treatment have spoken of their loss of physical sensation, and loss of autonomy. In recent years, human rights institutions have criticized early surgical management of such characteristics.In 2013, it was disclosed in a medical journal that four unnamed elite female athletes from developing countries were subjected to gonadectomies and partial clitoridectomies after testosterone testing revealed that they had an intersex condition. In April 2016, the United Nations Special Rapporteur on health, Dainius Pūras, condemned this treatment as a form of female genital mutilation "in the absence of symptoms or health issues warranting those procedures." See also Pseudo-penis, an enlarged clitoris or other penis-like structure that is normally present in some mammal, bird, and insect species References == External links ==

Anasarca

Anasarca is a severe and generalized form of edema, with subcutaneous tissue swelling throughout the body. Unlike typical edema, which almost everyone will experience at some time and can be relatively benign, anasarca is a pathological process reflecting a severe disease state and can involve the cavities of the body in addition to the tissues. Signs and symptoms Physical appearance Can include: Periorbital edema "eye puffiness" Perioral edema Upper extremity edema Ascites Lower extremity edema Pre-tibial edema Pedal edema Physical manifestations Can include: Impaired vision, difficulty opening eyes Shortness of breath (SOB), dyspnea on exertion (DOE), orthopnea Chest pain Extreme discomfort Debilitation Cause Anasarca is often caused by a decreased oncotic pressure. Organ failure Liver failure Kidney failure Right-sided heart failure Malignancy Diet Severe protein deficiency Systemic manifestations of Nephrotic syndrome Protein-losing enteropathies Capillary leak syndrome In utero In Hb Barts, the high oxygen affinity results in poor oxygen delivery to peripheral tissues, resulting in anasarca. Iatrogenic It can also be caused by the administration of exogenous intravenous fluid. Diagnosis Anasarca is a diagnosis made clinically and differentiated from edema by extent of body involvement and severity. Whereas edema is usually graded on a mild/moderate/severe scale and usually affects one or two regions of the body, anasarca affects the entire body and is the most severe form of edema, with subcutaneous tissue swelling from head to feet. Testing Although there is no definitive test to prove anasarca, many tests can be useful to aid in the diagnosis. Anasarca is most often seen in conjunction with a low level of albumin Recent studies have demonstrated a linkage between low-voltage electrocardiogram (ECG) (LVE) (QRS complexes of <5 mm in the limb and <10 mm in the precordial leads) and Anasarca. Treatment Anasarca is a severe symptom, not a pathological process in and of itself; as such, the best treatment is to treat the underlying cause. However, there are a number of things that can be done to help get the fluid off as well as prevent further accumulation of fluid. Diuretics One of the mainstays of any edema treatment, diuretics are a category of medications that help the body excrete fluid by altering the way in which the kidney processes urine. Loop diuretics Thiazide diuretics Thiazide-like diuretics Potassium-sparing diuretics Diet The body more efficiently absorbs fluid from the gut and retains that fluid with the help of sodium and sugar. As such, decreasing salt and simple sugar intake will help prevent accumulation of fluid and potentiate the effect of any diuretics. Following a high protein diet will help provide ones body with the substrates necessary to produce albumin, the major protein in human plasma and the single most important molecule in maintaining the serum oncotic pressure. Fiber Bulking fiber, both soluble and insoluble dietary fiber, absorb water throughout the GI tract. Viscous fiber can thicken the contents of the GI track and slow the absorption of other compounds (like simple sugars). References == External links ==

Overactive bladder

Overactive bladder (OAB) is a condition where there is a frequent feeling of needing to urinate to a degree that it negatively affects a persons life. The frequent need to urinate may occur during the day, at night, or both. If there is loss of bladder control then it is known as urge incontinence. More than 40% of people with overactive bladder have incontinence. Conversely, about 40% to 70% of urinary incontinence is due to overactive bladder. Overactive bladder is not life-threatening, but most people with the condition have problems for years.The cause of overactive bladder is unknown. Risk factors include obesity, caffeine, and constipation. Poorly controlled diabetes, poor functional mobility, and chronic pelvic pain may worsen the symptoms. People often have the symptoms for a long time before seeking treatment and the condition is sometimes identified by caregivers. Diagnosis is based on a persons signs and symptoms and requires other problems such as urinary tract infections or neurological conditions to be excluded. The amount of urine passed during each urination is relatively small. Pain while urinating suggests that there is a problem other than overactive bladder.Specific treatment is not always required. If treatment is desired pelvic floor exercises, bladder training, and other behavioral methods are initially recommended. Weight loss in those who are overweight, decreasing caffeine consumption, and drinking moderate fluids, can also have benefits. Medications, typically of the anti-muscarinic type, are only recommended if other measures are not effective. They are no more effective than behavioral methods; however, they are associated with side effects, particularly in older people. Some non-invasive electrical stimulation methods appear effective while they are in use. Injections of botulinum toxin into the bladder is another option. Urinary catheters or surgery are generally not recommended. A diary to track problems can help determine whether treatments are working.Overactive bladder is estimated to occur in 7-27% of men and 9-43% of women. It becomes more common with age. Some studies suggest that the condition is more common in women, especially when associated with loss of bladder control. Economic costs of overactive bladder were estimated in the United States at US$12.6 billion and 4.2 billion Euro in 2000. Signs and symptoms Overactive bladder is characterized by a group of four symptoms: urgency, urinary frequency, nocturia, and urge incontinence. Urge incontinence is not present in the "dry" classification.Urgency is considered the hallmark symptom of OAB, but there are no clear criteria for what constitutes urgency and studies often use other criteria. Urgency is currently defined by the International Continence Society (ICS), as of 2002, as "Sudden, compelling desire to pass urine that is difficult to defer." The previous definition was "Strong desire to void accompanied by fear of leakage or pain." The definition does not address the immediacy of the urge to void and has been criticized as subjective.Urinary frequency is considered abnormal if the person urinates more than eight times in a day. This frequency is usually monitored by having the person keep a voiding diary where they record urination episodes. The number of episodes varies depending on sleep, fluid intake, medications, and up to seven is considered normal if consistent with the other factors.Nocturia is a symptom where the person complains of interrupted sleep because of an urge to void and, like the urinary frequency component, is affected by similar lifestyle and medical factors. Individual waking events are not considered abnormal, one study in Finland established two or more voids per night as affecting quality of life.Urge incontinence is a form of urinary incontinence characterized by the involuntary loss of urine occurring for no apparent reason while feeling urinary urgency as discussed above. Like frequency, the person can track incontinence in a diary to assist with diagnosis and management of symptoms. Urge incontinence can also be measured with pad tests, and these are often used for research purposes. Some people with urge incontinence also have stress incontinence and this can complicate clinical studies.It is important that the clinician and the person with overactive bladder both reach a consensus on the term, urgency. Some common phrases used to describe OAB include, When Ive got to go, Ive got to go, or When I have to go, I have to rush, because I think I will wet myself. Hence the term, fear of leakage, is an important concept to people. Causes The cause of OAB is unclear, and indeed there may be multiple causes. It is often associated with overactivity of the detrusor urinae muscle, a pattern of bladder muscle contraction observed during urodynamics. It is also possible that the increased contractile nature originates from within the urothelium and lamina propria, and abnormal contractions in this tissue could stimulate dysfunction in the detrusor or whole bladder. Catheter-related irritation If bladder spasms occur or there is no urine in the drainage bag when a catheter is in place, the catheter may be blocked by blood, thick sediment, or a kink in the catheter or drainage tubing. Sometimes spasms are caused by the catheter irritating the bladder, prostate or penis. Such spasms can be controlled with medication such as butylscopolamine, although most people eventually adjust to the irritation and the spasms go away. Diagnosis Diagnosis of OAB is made primarily on the persons signs and symptoms and by ruling out other possible causes such as an infection. Urodynamics, a bladder scope, and ultrasound are generally not needed. Additionally, urine culture may be done to rule out infection. The frequency/volume chart may be maintained and cystourethroscopy may be done to exclude tumor and kidney stones. If there is an underlying metabolic or pathologic condition that explains the symptoms, the symptoms may be considered part of that disease and not OAB.Psychometrically robust self-completion questionnaires are generally recognized as a valid way of measuring a persons signs and symptoms, but there does not exist a single ideal questionnaire. These surveys can be divided into two groups: general surveys of lower urinary tract symptoms and surveys specific to overactive bladder. General questionnaires include: American Urological Association Symptom Index (AUASI), Urogenital Distress Inventory (UDI), Incontinence Impact Questionnaire (IIQ), and Bristol Female Lower Urinary Tract Symptoms (BFLUTS). Overactive bladder questionnaires include: Overactive Bladder Questionnaire (OAB-q), Urgency Questionnaire (UQ), Primary OAB Symptom Questionnaire (POSQ), and the International Consultation on Incontinence Questionnaire (ICIQ). OAB causes similar symptoms to some other conditions such as urinary tract infection (UTI), bladder cancer, and benign prostatic hyperplasia (BPH). Urinary tract infections often involve pain and hematuria (blood in the urine) which are typically absent in OAB. Bladder cancer usually includes hematuria and can include pain, both not associated with OAB, and the common symptoms of OAB (urgency, frequency, and nocturia) may be absent. BPH frequently includes symptoms at the time of voiding as well as sometimes including pain or hematuria, and all of these are not usually present in OAB. Diabetes insipidus, which causes high frequency and volume, though not necessarily urgency. Classification There is some controversy about the classification and diagnosis of OAB. Some sources classify overactive bladder into two different variants: "wet" (i.e., an urgent need to urinate with involuntary leakage) or "dry" (i.e., an urgent need to urinate but no involuntary leakage). Wet variants are more common than dry variants. The distinction is not absolute; one study suggested that many classified as "dry" were actually "wet" and that people with no history of any leakage may have had other syndromes.OAB is distinct from stress urinary incontinence, but when they occur together, the condition is usually known as mixed incontinence. Management A recent (2019) systematic review of studies related to urinary incontinence in women found that behavioral therapy, alone or combined with other treatments, is generally more effective than any other single treatment alone. Behavioral therapy as a treatment has been used to improve or cure urgency urinary incontinence, including improving patient satisfaction. Lifestyle Treatment for OAB includes nonpharmacologic methods such as lifestyle modification (fluid restriction, avoidance of caffeine), bladder retraining, and pelvic floor muscle (PFM) exercise. Timed voiding is a form of bladder training that uses biofeedback to reduce the frequency of accidents resulting from poor bladder control. This method is aimed at improving the persons control over the time, place and frequency of urination. Timed voiding programs involve establishing a schedule for urination. To do this, a person fills in a chart of voiding and leaking. From the patterns that appear in the chart, the person can plan to empty his or her bladder before he or she would otherwise leak. Some individuals find it helpful to use a vibrating reminder watch to help them remember to use the bathroom. Vibrating watches can be set to go off at certain intervals or at specific times throughout the day, depending on the watch. Through this bladder training exercise, the person can alter their bladders schedule for storing and emptying urine. Medications A number of antimuscarinic drugs (e.g., darifenacin, hyoscyamine, oxybutynin, tolterodine, solifenacin, trospium, fesoterodine) are frequently used to treat overactive bladder. Long term use, however, has been linked to dementia. β3 adrenergic receptor agonists (e.g., mirabegron, vibegron), may be used, as well. However, both antimuscarinic drugs and β3 adrenergic receptor agonists constitute a second-line treatment due to the risk of side effects.Few people get complete relief with medications and all medications are no more than moderately effective.A typical person with overactive bladder may urinate 12 times per day. Medication may reduce this number by 2-3 and reduce urinary incontinence events by 1-2 per day. Procedures Various devices (Urgent PC Neuromodulation System) may also be used. Botulinum toxin A (Botox) is approved by the Food and Drug Administration in adults with neurological conditions, including multiple sclerosis and spinal cord injury. Botulinum Toxin A injections into the bladder wall can suppress involuntary bladder contractions by blocking nerve signals and may be effective for up to 9 months. The growing knowledge of pathophysiology of overactive bladder fuelled a huge amount of basic and clinical research in this field of pharmacotherapy. A surgical intervention involves the enlargement of the bladder using bowel tissues, although generally used as a last resort. This procedure can greatly enlarge urine volume in the bladder.OAB may be treated with electrical stimulation, which aims to reduce the contractions of the muscle that tenses around the bladder and causes urine to pass out of it. There are invasive and non-invasive electrical stimulation options. Non-invasive options include the introduction of a probe into the vagina or anus, or the insertion of an electrical probe into a nerve near the ankle with a fine needle. These non-invasive options appear to reduce symptoms while they are in use, and are better than no treatment, or treatment with drugs, or pelvic floor muscle treatment, but the quality of evidence is low. It is unknown which electrical stimulation option works best. Also, it is unknown whether the benefits last after treatment stops. Prognosis Many people with OAB symptoms had those symptoms subside within a year, with estimates as high as 39%, but most have symptoms for several years. Epidemiology Earlier reports estimated that about one in six adults in the United States and Europe had OAB. The number of people affected with OAB increases with age, thus it is expected that OAB will become more common in the future as the average age of people living in the developed world is increasing. However, a recent Finnish population-based survey suggested that the number of people affected had been largely overestimated due to methodological shortcomings regarding age distribution and low participation (in earlier reports). It is suspected, then, that OAB affects approximately half the number of individuals as earlier reported.The American Urological Association reports studies showing rates as low as 7% to as high as 27% in men and rates as low as 9% to 43% in women. Urge incontinence was reported as higher in women. Older people are more likely to be affected, and the number of symptoms increases with age. See also National Association For Continence Underactive bladder References External links Sacco E, Bientinesi R, Marangi F, DAddessi A, Racioppi M, Gulino G, Pinto F, Totaro A, Bassi P (2011). "[Overactive bladder syndrome: the social and economic perspective]". Urologia (in Italian). 78 (4): 241–56. doi:10.5301/RU.2011.8886. PMID 22237808. S2CID 36693916. "Overactive Bladder". MedlinePlus. U.S. National Library of Medicine.

Stomach

The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach is involved in the gastric phase of digestion, following chewing. It performs a chemical breakdown by means of enzymes and hydrochloric acid. In humans and many other animals, the stomach is located between the oesophagus and the small intestine. The stomach secretes digestive enzymes and gastric acid to aid in food digestion. The pyloric sphincter controls the passage of partially digested food (chyme) from the stomach into the duodenum, where peristalsis takes over to move this through the rest of intestines. Structure In the human digestive system, the stomach lies between the oesophagus and the duodenum (the first part of the small intestine). It is in the left upper quadrant of the abdominal cavity. The top of the stomach lies against the diaphragm. Lying behind the stomach is the pancreas. A large double fold of visceral peritoneum called the greater omentum hangs down from the greater curvature of the stomach. Two sphincters keep the contents of the stomach contained; the lower oesophageal sphincter (found in the cardiac region), at the junction of the oesophagus and stomach, and the pyloric sphincter at the junction of the stomach with the duodenum. The stomach is surrounded by parasympathetic (stimulant) and sympathetic (inhibitor) plexuses (networks of blood vessels and nerves in the anterior gastric, posterior, superior and inferior, celiac and myenteric), which regulate both the secretory activity of the stomach and the motor (motion) activity of its muscles. Because it is a distensible organ, it normally expands to hold about one litre of food. The stomach of a newborn human baby will only be able to retain about 30 millilitres. The maximum stomach volume in adults is between 2 and 4 litres. Sections In classical anatomy the human stomach is divided into four sections, beginning at the cardia. The cardia is where the contents of the oesophagus empty into the stomach. The fundus (from Latin bottom) is formed in the upper curved part. The body is the main, central region of the stomach. The pylorus (from Greek gatekeeper) is the lower section of the stomach that empties contents into the duodenum.The cardia is defined as the region following the "z-line" of the gastroesophageal junction, the point at which the epithelium changes from stratified squamous to columnar. Near the cardia is the lower oesophageal sphincter. Research has shown that the cardia is not an anatomically distinct region of the stomach but a region of the oesophageal lining damaged by reflux. Anatomical proximity The stomach bed refers to the structures upon which the stomach rests in mammals. These include the tail of the pancreas, splenic artery, left kidney, left suprarenal gland, transverse colon and its mesocolon, and the left crus of diaphragm, and the left colic flexure. The term was introduced around 1896 by Philip Polson of the Catholic University School of Medicine, Dublin. However this was brought into disrepute by surgeon anatomist J Massey. Blood supply The lesser curvature of the human stomach is supplied by the right gastric artery inferiorly and the left gastric artery superiorly, which also supplies the cardiac region. The greater curvature is supplied by the right gastroepiploic artery inferiorly and the left gastroepiploic artery superiorly. The fundus of the stomach, and also the upper portion of the greater curvature, is supplied by the short gastric arteries, which arise from the splenic artery. Microanatomy Wall Like the other parts of the gastrointestinal tract, the human stomach walls consist of a mucosa, submucosa, muscularis externa, subserosa and serosa.The inner part of the lining of the stomach, the gastric mucosa, consists of an outer layer of column-shaped cells, a lamina propria, and a thin layer of smooth muscle called the muscularis mucosa. Beneath the mucosa lies the submucosa, consisting of fibrous connective tissue. Meissners plexus is in this layer interior to the oblique muscle layer.Outside of the submucosa lies another muscular layer, the muscularis externa. It consists of three layers of muscular fibres, with fibres lying at angles to each other. These are the inner oblique, middle circular, and outer longitudinal layers. The presence of the inner oblique layer is distinct from other parts of the gastrointestinal tract, which do not possess this layer. Stomach contains the thickest muscularis layer consisting of three layers, thus maximum peristalsis occurs here. The inner oblique layer: This layer is responsible for creating the motion that churns and physically breaks down the food. It is the only layer of the three which is not seen in other parts of the digestive system. The antrum has thicker skin cells in its walls and performs more forceful contractions than the fundus. The middle circular layer: At this layer, the pylorus is surrounded by a thick circular muscular wall, which is normally tonically constricted, forming a functional (if not anatomically discrete) pyloric sphincter, which controls the movement of chyme into the duodenum. This layer is concentric to the longitudinal axis of the stomach. Auerbachs plexus (myenteric plexus) is found between the outer longitudinal and the middle circular layer and is responsible for the innervation of both (causing peristalsis and mixing).The outer longitudinal layer is responsible for moving the bolus towards the pylorus of the stomach through muscular shortening. To the outside of the muscularis externa lies a serosa, consisting of layers of connective tissue continuous with the peritoneum. Glands The mucosa lining the stomach is lined with a number of these pits, which receive gastric juice, secreted by between 2 and 7 gastric glands. Gastric juice is an acidic fluid containing hydrochloric acid and the digestive enzyme pepsin. The glands contains a number of cells, with the function of the glands changing depending on their position within the stomach.Within the body and fundus of the stomach lie the fundic glands. In general, these glands are lined by column-shaped cells that secrete a protective layer of mucus and bicarbonate. Additional cells present include parietal cells that secrete hydrochloric acid and intrinsic factor, chief cells that secrete pepsinogen (this is a precursor to pepsin- the highly acidic environment converts the pepsinogen to pepsin), and neuroendocrine cells that secrete serotonin.Glands differ where the stomach meets the esophagus and near the pylorus. Near the junction between the stomach and the oesophagus lie cardiac glands, which primarily secrete mucus. They are fewer in number than the other gastric glands and are more shallowly positioned in the mucosa. There are two kinds - either simple tubular with short ducts or compound racemose resembling the duodenal Brunners glands. Near the pylorus lie pyloric glands located in the antrum of the pylorus. They secrete mucus, as well as gastrin produced by their G cells. Gene and protein expression About 20,000 protein coding genes are expressed in human cells and nearly 70% of these genes are expressed in the normal stomach. Just over 150 of these genes are more specifically expressed in the stomach compared to other organs, with only some 20 genes being highly specific. The corresponding specific proteins expressed in stomach are mainly involved in creating a suitable environment for handling the digestion of food for uptake of nutrients. Highly stomach-specific proteins include GKN1, expressed in the mucosa; pepsinogen PGC and the lipase LIPF, expressed in chief cells; and gastric ATPase ATP4A and gastric intrinsic factor GIF, expressed in parietal cells. Development In early human embryogenesis, the ventral part of the embryo abuts the yolk sac. During the third week of development, as the embryo grows, it begins to surround parts of the sac. The enveloped portions form the basis for the adult gastrointestinal tract. The sac is surrounded by a network of vitelline arteries and veins. Over time, these arteries consolidate into the three main arteries that supply the developing gastrointestinal tract: the celiac artery, superior mesenteric artery, and inferior mesenteric artery. The areas supplied by these arteries are used to define the foregut, midgut, and hindgut. The surrounded sac becomes the primitive gut. Sections of this gut begin to differentiate into the organs of the gastrointestinal tract, and the esophagus, and stomach form from the foregut. Function Digestion In the human digestive system, a bolus (a small rounded mass of chewed up food) enters the stomach through the esophagus via the lower esophageal sphincter. The stomach releases proteases (protein-digesting enzymes such as pepsin) and hydrochloric acid, which kills or inhibits bacteria and provides the acidic pH of 2 for the proteases to work. Food is churned by the stomach through muscular contractions of the wall called peristalsis – reducing the volume of the bolus, before looping around the fundus and the body of stomach as the boluses are converted into chyme (partially digested food). Chyme slowly passes through the pyloric sphincter and into the duodenum of the small intestine, where the extraction of nutrients begins. Gastric juice in the stomach also contains pepsinogen. Hydrochloric acid activates this inactive form of enzyme into the active form, pepsin. Pepsin breaks down proteins into polypeptides. Absorption Although the absorption in the human digestive system is mainly a function of the small intestine, some absorption of certain small molecules nevertheless does occur in the stomach through its lining. This includes: Water, if the body is dehydrated Medication, such as aspirin Amino acids 10–20% of ingested ethanol (e.g. from alcoholic beverages) Caffeine To a small extent water-soluble vitamins (most are absorbed in the small intestine)The parietal cells of the human stomach are responsible for producing intrinsic factor, which is necessary for the absorption of vitamin B12. B12 is used in cellular metabolism and is necessary for the production of red blood cells, and the functioning of the nervous system. Control of secretion and motility The movement and the flow of chemicals into the stomach are controlled by both the autonomic nervous system and by the various digestive hormones of the digestive system: Other than gastrin, these hormones all act to turn off the stomach action. This is in response to food products in the liver and gall bladder, which have not yet been absorbed. The stomach needs to push food into the small intestine only when the intestine is not busy. While the intestine is full and still digesting food, the stomach acts as storage for food. Other Effects of EGFEpidermal growth factor (EGF) results in cellular proliferation, differentiation, and survival. EGF is a low-molecular-weight polypeptide first purified from the mouse submandibular gland, but since then found in many human tissues including the submandibular gland, and the parotid gland. Salivary EGF, which also seems to be regulated by dietary inorganic iodine, also plays an important physiological role in the maintenance of oro-oesophageal and gastric tissue integrity. The biological effects of salivary EGF include healing of oral and gastroesophageal ulcers, inhibition of gastric acid secretion, stimulation of DNA synthesis, and mucosal protection from intraluminal injurious factors such as gastric acid, bile acids, pepsin, and trypsin and from physical, chemical, and bacterial agents. Stomach as nutrition sensorThe human stomach can "taste" sodium glutamate using glutamate receptors and this information is passed to the lateral hypothalamus and limbic system in the brain as a palatability signal through the vagus nerve. The stomach can also sense, independently of tongue and oral taste receptors, glucose, carbohydrates, proteins, and fats. This allows the brain to link nutritional value of foods to their tastes. Thyrogastric syndromeThis syndrome defines the association between thyroid disease and chronic gastritis, which was first described in the 1960s. This term was coined also to indicate the presence of thyroid autoantibodies or autoimmune thyroid disease in patients with pernicious anemia, a late clinical stage of atrophic gastritis. In 1993, a more complete investigation on the stomach and thyroid was published, reporting that the thyroid is, embryogenetically and phylogenetically, derived from a primitive stomach, and that the thyroid cells, such as primitive gastroenteric cells, migrated and specialized in uptake of iodide and in storage and elaboration of iodine compounds during vertebrate evolution. In fact, the stomach and thyroid share iodine-concentrating ability and many morphological and functional similarities, such as cell polarity and apical microvilli, similar organ-specific antigens and associated autoimmune diseases, secretion of glycoproteins (thyroglobulin and mucin) and peptide hormones, the digesting and readsorbing ability, and lastly, similar ability to form iodotyrosines by peroxidase activity, where iodide acts as an electron donor in the presence of H2O2. In the following years, many researchers published reviews about this syndrome. Clinical significance Diseases A series of radiographs can be used to examine the stomach for various disorders. This will often include the use of a barium swallow. Another method of examination of the stomach, is the use of an endoscope. A gastric emptying scan is considered the gold standard to assess gastric emptying rate.A large number of studies have indicated that most cases of peptic ulcers, and gastritis, in humans are caused by Helicobacter pylori infection, and an association has been seen with the development of stomach cancer.A stomach rumble is actually noise from the intestines. Surgery In humans, many bariatric surgery procedures involve the stomach, in order to lose weight. A gastric band may be placed around the cardia area, which can adjust to limit intake. The anatomy of the stomach may be modified, or the stomach may be bypassed entirely. Surgical removal of the stomach is called a gastrectomy, and removal of the cardia area is a called a cardiectomy. "Cardiectomy" is a term that is also used to describe the removal of the heart. A gastrectomy may be carried out because of gastric cancer or severe perforation of the stomach wall. Fundoplication is stomach surgery in which the fundus is wrapped around the lower esophagus and stitched into place. It is used to treat gastroesophageal reflux disease (GERD). History There were previously conflicting statements in the academic anatomy community over whether the cardia is part of the stomach, part of the oesophagus or a distinct entity. Modern surgical and medical textbooks have agreed that "the gastric cardia is now clearly considered to be part of the stomach." Etymology The word stomach is derived from the Latin stomachus which has roots from the Greek word stomachos (στόμαχος), ultimately from stoma (στόμα), "mouth". Gastro- and gastric (meaning "related to the stomach") are both derived from the Greek word gaster (γαστήρ, meaning "belly"). Other animals Although the precise shape and size of the stomach varies widely among different vertebrates, the relative positions of the oesophageal and duodenal openings remain relatively constant. As a result, the organ always curves somewhat to the left before curving back to meet the pyloric sphincter. However, lampreys, hagfishes, chimaeras, lungfishes, and some teleost fish have no stomach at all, with the oesophagus opening directly into the intestine. These animals all consume diets that require little storage of food, no predigestion with gastric juices, or both.The gastric lining is usually divided into two regions, an anterior portion lined by fundic glands and a posterior portion lined with pyloric glands. Cardiac glands are unique to mammals, and even then are absent in a number of species. The distributions of these glands vary between species, and do not always correspond with the same regions as in humans. Furthermore, in many non-human mammals, a portion of the stomach anterior to the cardiac glands is lined with epithelium essentially identical to that of the oesophagus. Ruminants, in particular, have a complex stomach, the first three chambers of which are all lined with oesophageal mucosa.In birds and crocodilians, the stomach is divided into two regions. Anteriorly is a narrow tubular region, the proventriculus, lined by fundic glands, and connecting the true stomach to the crop. Beyond lies the powerful muscular gizzard, lined by pyloric glands, and, in some species, containing stones that the animal swallows to help grind up food.In insects there is also a crop. The insect stomach is called the midgut. Information about the stomach in echinoderms or molluscs can be found under the respective articles. Additional images See also Gastroesophageal reflux disease Human gastrointestinal microbiota Proton-pump inhibitor References External links Stomach at the Human Protein Atlas "Stomach" article from the Encyclopedia of Nursing & Allied Health, from enotes.com Digestion of proteins in the stomach or tiyan Site with details of how ruminants process food Control of Gastric Emptying Archived 2019-11-12 at the Wayback Machine

Hypokinesia

Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinsons disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases. The other category of movement disorder is hyperkinesia that features an exaggeration of unwanted movement, such as twitching or writhing in Huntingtons disease or Tourette syndrome. Spectrum of disorders Hypokinesia describes a variety of more specific disorders: Causes The most common cause of Hypokinesia is Parkinsons disease, and conditions related to Parkinsons disease. Other conditions may also cause slowness of movements. These include hypothyroidism and severe depression. These conditions need to be carefully ruled out, before a diagnosis of Parkinsonism is made. The remainder of this article describes Hypokinesia associated with Parkinsons disease, and conditions related to Parkinsons disease. Pathophysiology Associated neurotransmitters Dopamine The main neurotransmitter thought to be involved in hypokinesia is dopamine. Essential to the basal ganglionic-thalamocortical loop, which processes motor function, dopamine depletion is common in these areas of hypokinesic patients. Bradykinesia is correlated with lateralized dopaminergic depletion in the substantia nigra. The dopamine pathway in the substantia nigra is essential to motor function, and commonly a lesion in this area correlates with displayed hypokinesia. Tremor and rigidity, however, seem to be only partially due to dopamine deficits in the substantia nigra, suggesting other processes are involved in motor control. Treatments for hypokinesia often either attempt to prevent dopamine degradation by MAO-B or increase the amount of neurotransmitter present in the system.GABA and glutamate The inhibitory neurotransmitter GABA and the excitatory glutamate are found in many parts of the central nervous system, including in the motor pathways that involve hypokinesia. In one pathway, glutamate in the substantia nigra excites the release of GABA into the thalamus, which then inhibits the release of glutamate in the cortex and thereby reduces motor activity. If too much glutamate is initially in the substantia nigra, then through interaction with GABA in the thalamus and glutamate in the cortex, movements will be reduced or will not occur at all.Another direct pathway from the basal ganglia sends GABA inhibitory messages to the globus pallidus and substantia nigra, which then send GABA to the thalamus. In the indirect pathway, the basal ganglia send GABA to the globus pallidus which then sends it to the subthalamic nucleus, which then disinhibited sends glutamate to the output structures of the basal ganglia. Inhibition of GABA release could disrupt the feedback loop to the basal ganglia and produce hypokinesic movements.GABA and glutamate often interact with each other and with dopamine directly. In the basal ganglia, the nigrostriatal pathway is where GABA and dopamine are housed in the same neurons and released together. Neurobiology Hypokinetic symptoms arise from damage to the basal ganglia, which plays a role in producing force and computing the effort necessary to make a movement. Two possible neural pathways enable the basal ganglia to produce movement. When activated, the direct pathway sends sensory and motor information from the cerebral cortex to the first structure of the basal ganglia, the putamen. That information directly inhibits the globus pallidus internal and allows free movement. The indirect pathway, traveling through the putamen, globus pallidus external, and subthalamic nucleus, activates the globus pallidus internal threshold and inhibits the thalamus from communicating with the motor cortex, producing hypokinetic symptoms. When levels of dopamine decrease, the normal wave-firing pattern of basal ganglia neural oscillations changes and the tendency for oscillations increases, particularly in the beta wave of the basal ganglia. Recent research indicates, when oscillations fire simultaneously, processing is disrupted at the thalamus and cortex, affecting activities such as motor planning and sequence learning, as well as causing hypokinetic tremors. Treatments Dopaminergic drugs Dopaminergic drugs are commonly used in the early stages of the hypokinesia to treat patients. With increased intake, though, they can become ineffective because of the development of noradrenergic lesions. While initially the dopaminergic drugs may be effective, these noradrenergic lesions are associated with hypokinesic gait disorder development later on.Some Parkinsons patients are unable to move during sleep, prompting the diagnosis of "nocturnal hypokinesia". Physicians have experienced success treating this sleep disorder with slow-release or night-time dopaminergic drugs, and in some cases, continuous stimulation by the dopamine agonist rotigotine. Despite improved mobility during sleep, many Parkinsons patients report an extremely uncomfortable sleeping experience even after dopaminergic treatments. Deep brain stimulation Once the reaction to dopaminergic drugs begins to fluctuate in Parkinsons patients, deep brain stimulation (DBS) of the subthalamic nucleus and internal globus pallidus is often used to treat hypokinesia. DBS, like dopaminergic drugs, initially provides relief, but chronic use causes worse hypokinesia and freezing of gait. Lower-frequency DBS in irregular patterns has been shown to be more effective and less detrimental in treatment. Posteroventral pallidotomy (PVP) is a specific kind of DBS that destroys a small part of the globus pallidus by scarring the neural tissue, reducing brain activity and therefore tremors and rigidity. PVP is suspected to recalibrate basal ganglia activity in the thalamocortical pathway. PVP in the dominant hemisphere has been reported to disrupt executive function verbal processing abilities, and bilateral PVP may disturb processes of focused attention.Many akinesia patients also form a linguistic akinesia in which their ability to produce verbal movements mirrors their physical akinesia symptoms, especially after unsuccessful PVP. Patients are usually able to maintain normal levels of fluency, but often stop midsentence, unable to remember or produce a desired word. According to a study of Parkinsons patients with articulatory hypokinesia, subjects with faster rates of speech experienced more problems trying to produce conversational language than those who normally spoke at slower rates. Methylphenidate Methylphenidate, commonly used to treat ADHD, has been used in conjunction with levodopa to treat hypokinesia in the short term. The two work together to increase dopamine levels in the striatum and prefrontal cortex. Methylphenidate mainly inhibits dopamine and noradrenaline reuptake by blocking presynaptic transporters, and levodopa increases the amount of dopamine, generally improving hypokinesic gait. Some patients, however, have adverse reactions of nausea and headache to the treatment and the long-term effects of the drug treatment still need to be assessed. Stem cells New treatments include increasing the number of dopamine cells by transplanting stem cells into the basal ganglia or stimulating endogenous stem cell production and movement to the basal ganglia. The successful integration of stem cells can relieve hypokinetic symptoms and decrease the necessary dose of dopaminergic drugs. However, a variety of complications, including possible tumor formation, inappropriate cell migration, rejection of cells by the immune system, and cerebral hemorrhage are possible, causing many physicians to believe the risks outweigh the possible benefits. NOP receptor antagonists Another treatment, still in an experimental stage, is the administration of nociception FQ peptide (NOP) receptor antagonists. This treatment has been shown to reduce hypokinesia in animal studies when increasing nociception FQ in the substantia nigra and subthalamic nucleus. Low doses can be taken with dopaminergic treatment to decrease the amount of L-dopa needed, which can reduce its long-term side effects and improve motor performance. Dance therapy Dance therapy has also been shown to reduce hypokinesic movements and rigidity, though targeted more at the muscular aspects of the disorder than the neural activity. Associations Cognitive impairment Bradykinesia has been shown to precede impairment of executive functions, working memory, and attention. These cognitive deficiencies can be tied to nonfunction of the basal ganglia and prefrontal cortex, which is also linked to the motor-dysfunction of hypokinesia. Tremor and rigidity have not had observable connections to cognitive impairments, supporting the idea that they are not as involved in the dopamine pathway in the basal ganglionic-thalamocortical loop. Dopaminergic treatments have shown improvement in cognitive functions associated with hypokinesia, suggesting they are also dependent on dopamine levels in the system. Motor motivation Often debated is whether the efficiency, vigor, and speed of movements in patients with hypokinesia are tied to motivation for rewarding and against punishing stimuli. The basal ganglia have been tied to the incentives behind movement, therefore suggesting a cost/benefit analysis of planned movement could be affected in hypokinesia. Rewards have not been shown to change the aspects of a hypokinesic individuals movement. In fact, the motor planning and control of a patient with hypokinesia is already as efficient as possible (as shown by slightly faster, but generally the same movement after deep brain stimulation of the subthalamic nucleus). This suggests that hypokinetic individuals simply have a narrower range of movement that does not increase relative to motivation.Other studies have come to the same conclusion about rewards and hypokinesia, but have shown that aversive stimuli can, in fact, reduce hypokinesic movement. Dopamine is either less involved or has a more complex role in the response to punishment than it does to rewards, as the hypodopaminergic striatum allows more movement in response to aversive stimuli. Demographic differentiation Gender More men than women typically develop hypokinesia, which is reflected in young and middle-aged populations where females have displayed higher levels of nigrostriatal dopamine than males. In the elderly, however, this differentiation is not present. Typically, women exhibit more tremor in the beginning development of hypokinesia. In the disorder, men tend to display more rigidity and women more bradykinesic motor behavior.Age of onset Hypokinesia is displayed in the brain and outwardly slightly different depending on when an individual is first affected. In young-onset hypokinesia (younger than 45 years of age), typically slightly more cell loss occurs in the substantia nigra with more displayed dystonia and muscle stiffness. In old-onset hypokinesia (older than 70 years of age), typically more of a hypokinesic gait and difficulty walking and no dystonia are seen. Both onsets can display resting tremor, although more generally found in old-onset cases. Symptoms Stress causes alterations of cerebral circulation, increasing blood flow in the supramarginal gyrus and angular gyrus of the parietal lobe, the frontal lobe, and the superior temporal gyrus of the left hemisphere. Also, an increase in cardiac activity and change in the tonus of the heart vessels occurs, which is an elementary indication of stress development. In patients with normal stress, an adaptive fight-or-flight response is usually triggered by sympathetic nervous system activation. Hypokinesia patients experience these typical stress symptoms on a regular basis because of damage to the basal ganglia system. Therefore, when a hypokinesia victim is under stress, he or she does not display a typical fight-or-flight response, placing the patient under greater danger from potentially harmful stimuli. Low-impact exercise, elimination of drug and alcohol use, and regular meditation can help to restore normal stress responses in hypokinesia patients. Connections to other medical conditions Though it is often most associated with Parkinsons disease, hypokinesia can be present in a wide variety of other conditions. See also Akinetic mutism Hyperkinesia == References ==

Intellectual disability

Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation (MR), is a generalized neurodevelopmental disorder characterized by significantly impaired intellectual and adaptive functioning. It is defined by an IQ under 70, in addition to deficits in two or more adaptive behaviors that affect everyday, general living. Intellectual functions are defined under DSM-V as reasoning, problem‑solving, planning, abstract thinking, judgment, academic learning, and learning from instruction and experience, and practical understanding confirmed by both clinical assessment and standardized tests. Adaptive behavior is defined in terms of conceptual, social, and practical skills involving tasks performed by people in their everyday lives.Intellectual disability is subdivided into syndromic intellectual disability, in which intellectual deficits associated with other medical and behavioral signs and symptoms are present, and non-syndromic intellectual disability, in which intellectual deficits appear without other abnormalities. Down syndrome and fragile X syndrome are examples of syndromic intellectual disabilities. Intellectual disability affects about 2 to 3% of the general population. Seventy-five to ninety percent of the affected people have mild intellectual disability. Non-syndromic, or idiopathic cases account for 30 to 50% of these cases. About a quarter of cases are caused by a genetic disorder, and about 5% of cases are inherited from a persons parents. Cases of unknown cause affect about 95 million people as of 2013. Signs and symptoms Intellectual disability (ID) becomes apparent during childhood and involves deficits in mental abilities, social skills, and core activities of daily living (ADLs) when compared to same-aged peers. There often are no physical signs of mild forms of ID, although there may be characteristic physical traits when it is associated with a genetic disorder (e.g., Down syndrome).The level of impairment ranges in severity for each person. Some of the early signs can include: Delays in reaching, or failure to achieve milestones in motor skills development (sitting, crawling, walking) Slowness learning to talk, or continued difficulties with speech and language skills after starting to talk Difficulty with self-help and self-care skills (e.g., getting dressed, washing, and feeding themselves) Poor planning or problem-solving abilities Behavioral and social problems Failure to grow intellectually, or continued infant childlike behavior Problems keeping up in school Failure to adapt or adjust to new situations Difficulty understanding and following social rulesIn early childhood, mild ID (IQ 50–69) may not be obvious or identified until children begin school. Even when poor academic performance is recognized, it may take expert assessment to distinguish mild intellectual disability from specific learning disability or emotional/behavioral disorders. People with mild ID are capable of learning reading and mathematics skills to approximately the level of a typical child aged nine to twelve. They can learn self-care and practical skills, such as cooking or using the local mass transit system. As individuals with intellectual disability reach adulthood, many learn to live independently and maintain gainful employment. About 85% of persons with ID are likely to have mild ID. Moderate ID (IQ 35–49) is nearly always apparent within the first years of life. Speech delays are particularly common signs of moderate ID. People with moderate intellectual disabilities need considerable supports in school, at home, and in the community in order to fully participate. While their academic potential is limited, they can learn simple health and safety skills and to participate in simple activities. As adults, they may live with their parents, in a supportive group home, or even semi-independently with significant supportive services to help them, for example, manage their finances. As adults, they may work in a sheltered workshop. About 10% of persons with ID are likely to have moderate ID. People with Severe ID (IQ 20–34), accounting for 3.5% of persons with ID, or Profound ID (IQ 19 or below), accounting for 1.5% of persons with ID, need more intensive support and supervision for their entire lives. They may learn some ADLs, but an intellectual disability is considered severe or profound when individuals are unable to independently care for themselves without ongoing significant assistance from a caregiver throughout adulthood. Individuals with profound ID are completely dependent on others for all ADLs and to maintain their physical health and safety. They may be able to learn to participate in some of these activities to a limited degree. Co-morbidity Autism and intellectual disability Intellectual disability and autism spectrum disorder (ASD) share clinical characteristics which can result in confusion while diagnosing. Overlapping these two disorders, while common, can be detrimental to a persons well-being. Those with ASD that hold symptoms of ID may be grouped into a co-diagnosis in which they are receiving treatment for a disorder they do not have. Likewise, those with ID that are mistaken to have ASD may be treated for symptoms of a disorder they do not have. Differentiating between these two disorders will allow clinicians to deliver or prescribe the appropriate treatments. Comorbidity between ID and ASD is very common; roughly 40% of those with ID also have ASD and roughly 70% of those with ASD also have ID. Both ASD and ID require shortfalls in communication and social awareness as defining criteria. Both ASD and ID are classified by severity: mild, moderate, severe. In addition to those three levels, ID has a fourth classification known as profound. Defining differences In a study conducted in 2016 surveying 2816 cases, it was found that the top subsets that help differentiate between those with ID and ASD are, "impaired non-verbal social behavior and lack of social reciprocity, [...] restricted interests, strict adherence to routines, stereotyped and repetitive motor mannerisms, and preoccupation with parts of objects". Those with ASD tend to show more deficits in non-verbal social behavior such as body language and understanding social cues. In a study done in 2008 of 336 individuals with varying levels of ID, it was found that those with ID display fewer instances of repetitive or ritualistic behaviors. It also recognized that those with ASD, when compared to those with ID, were more likely to isolate themselves and make less eye contact. When it comes to classification ID and ASD have very different guidelines. ID has a standardized assessment called the Supports Intensity Scale (SIS); this measures severity on a system built around how much support an individual will need. While ASD also classifies severity by support needed, there is no standard assessment; clinicians are free to diagnose severity at their own judgment. Causes Among children, the cause of intellectual disability is unknown for one-third to one-half of cases. About 5% of cases are inherited from a persons parents. Genetic defects that cause intellectual disability, but are not inherited, can be caused by accidents or mutations in genetic development. Examples of such accidents are development of an extra chromosome 18 (trisomy 18) and Down syndrome, which is the most common genetic cause. Velocardiofacial syndrome and fetal alcohol spectrum disorders are the two next most common causes. However, there are many other causes. The most common are: Genetic conditions. Sometimes disability is caused by abnormal genes inherited from parents, errors when genes combine, or other reasons like de novo mutations in genes associated with intellectual disability. The most prevalent genetic conditions include Down syndrome, Klinefelter syndrome, Fragile X syndrome (common among boys), neurofibromatosis, congenital hypothyroidism, Williams syndrome, phenylketonuria (PKU), and Prader–Willi syndrome. Other genetic conditions include Phelan-McDermid syndrome (22q13del), Mowat–Wilson syndrome, genetic ciliopathy, and Siderius type X-linked intellectual disability (OMIM: 300263) as caused by mutations in the PHF8 gene (OMIM: 300560). In the rarest of cases, abnormalities with the X or Y chromosome may also cause disability. Tetrasomy X and pentasomy X syndrome affect a small number of girls worldwide, while boys may be affected by 49, XXXXY, or 49, XYYYY. 47, XYY is not associated with significantly lowered IQ though affected individuals may have slightly lower IQs than non-affected siblings on average. Problems during pregnancy. Intellectual disability can result when the fetus does not develop properly. For example, there may be a problem with the way the fetuss cells divide as it grows. A pregnant woman who drinks alcohol (see fetal alcohol spectrum disorder) or gets an infection like rubella during pregnancy may also have a baby with an intellectual disability. Problems at birth. If a baby has problems during labor and birth, such as not getting enough oxygen, he or she may have a developmental disability due to brain damage. The group of proteins known as histones have an essential part in gene regulation, and sometimes these proteins becomes modified and are prevented from working properly. When the genes responsible for the development of neurons are affected, it affects the brain and behavior in the individual. Exposure to certain types of disease or toxins. Diseases like whooping cough, measles, or meningitis can cause intellectual disability if medical care is delayed or inadequate. Exposure to poisons like lead or mercury may also affect mental ability. Iodine deficiency, affecting approximately 2 billion people worldwide, is the leading preventable cause of intellectual disability in areas of the developing world where iodine deficiency is endemic. Iodine deficiency also causes goiter, an enlargement of the thyroid gland. More common than full-fledged congenital iodine deficiency syndrome (formerly cretinism), as intellectual disability caused by severe iodine deficiency is called, is mild impairment of intelligence. Residents of certain areas of the world, due to natural deficiency and governmental inaction, are severely affected by iodine deficiency. India has 500 million people with a deficiency, 54 million with goiter, and 2 million with congenital iodine deficiency. Among other nations affected by iodine deficiency, China and Kazakhstan have instituted widespread salt iodization programs. But, as of 2006, Russia had not. Malnutrition is a common cause of reduced intelligence in parts of the world affected by famine, such as Ethiopia and nations struggling with extended periods of warfare that disrupt agriculture production and distribution. Absence of the arcuate fasciculus. Diagnosis According to both the American Association on Intellectual and Developmental Disabilities and the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), three criteria must be met for a diagnosis of intellectual disability: significant limitation in general mental abilities (intellectual functioning), significant limitations in one or more areas of adaptive behavior across multiple environments (as measured by an adaptive behavior rating scale, i.e. communication, self-help skills, interpersonal skills, and more), and evidence that the limitations became apparent in childhood or adolescence. In general, people with intellectual disabilities have an IQ below 70, but clinical discretion may be necessary for individuals who have a somewhat higher IQ but severe impairment in adaptive functioning.It is formally diagnosed by an assessment of IQ and adaptive behavior. A third condition requiring onset during the developmental period is used to distinguish intellectual disability from other conditions, such as traumatic brain injuries and dementias (including Alzheimers disease). Intelligence quotient The first English-language IQ test, the Stanford–Binet Intelligence Scales, was adapted from a test battery designed for school placement by Alfred Binet in France. Lewis Terman adapted Binets test and promoted it as a test measuring "general intelligence". Termans test was the first widely used mental test to report scores in "intelligence quotient" form ("mental age" divided by chronological age, multiplied by 100). Current tests are scored in "deviation IQ" form, with a performance level by a test-taker two standard deviations below the median score for the test-takers age group defined as IQ 70. Until the most recent revision of diagnostic standards, an IQ of 70 or below was a primary factor for intellectual disability diagnosis, and IQ scores were used to categorize degrees of intellectual disability. Since the current diagnosis of intellectual disability is not based on IQ scores alone, but must also take into consideration a persons adaptive functioning, the diagnosis is not made rigidly. It encompasses intellectual scores, adaptive functioning scores from an adaptive behavior rating scale based on descriptions of known abilities provided by someone familiar with the person, and also the observations of the assessment examiner who is able to find out directly from the person what he or she can understand, communicate, and such like. IQ assessment must be based on a current test. This enables a diagnosis to avoid the pitfall of the Flynn effect, which is a consequence of changes in population IQ test performance changing IQ test norms over time. Distinction from other disabilities Clinically, intellectual disability is a subtype of cognitive deficit or disabilities affecting intellectual abilities, which is a broader concept and includes intellectual deficits that are too mild to properly qualify as intellectual disability, or too specific (as in specific learning disability), or acquired later in life through acquired brain injuries or neurodegenerative diseases like dementia. Cognitive deficits may appear at any age. Developmental disability is any disability that is due to problems with growth and development. This term encompasses many congenital medical conditions that have no mental or intellectual components, although it, too, is sometimes used as a euphemism for intellectual disability. Limitations in more than one area Adaptive behavior, or adaptive functioning, refers to the skills needed to live independently (or at the minimally acceptable level for age). To assess adaptive behavior, professionals compare the functional abilities of a child to those of other children of similar age. To measure adaptive behavior, professionals use structured interviews, with which they systematically elicit information about persons functioning in the community from people who know them well. There are many adaptive behavior scales, and accurate assessment of the quality of someones adaptive behavior requires clinical judgment as well. Certain skills are important to adaptive behavior, such as: Daily living skills, such as getting dressed, using the bathroom, and feeding oneself Communication skills, such as understanding what is said and being able to answer Social skills with peers, family members, spouses, adults, and othersOther specific skills can be critical to an individuals inclusion in the community and to develop appropriate social behaviors, as for example being aware of the different social expectations linked to the principal lifespan stages (i.e., childhood, adulthood, old age). The results of a Swiss study suggest that the performance of adults with ID in recognizing different lifespan stages is related to specific cognitive abilities and to the type of material used to test this performance. Management By most definitions, intellectual disability is more accurately considered a disability rather than a disease. Intellectual disability can be distinguished in many ways from mental illness, such as schizophrenia or depression. Currently, there is no "cure" for an established disability, though with appropriate support and teaching, most individuals can learn to do many things. Causes, such as congenital hypothyroidism, if detected early may be treated to prevent the development of an intellectual disability.There are thousands of agencies around the world that provide assistance for people with developmental disabilities. They include state-run, for-profit, and non-profit, privately run agencies. Within one agency there could be departments that include fully staffed residential homes, day rehabilitation programs that approximate schools, workshops wherein people with disabilities can obtain jobs, programs that assist people with developmental disabilities in obtaining jobs in the community, programs that provide support for people with developmental disabilities who have their own apartments, programs that assist them with raising their children, and many more. There are also many agencies and programs for parents of children with developmental disabilities. Beyond that, there are specific programs that people with developmental disabilities can take part in wherein they learn basic life skills. These "goals" may take a much longer amount of time for them to accomplish, but the ultimate goal is independence. This may be anything from independence in tooth brushing to an independent residence. People with developmental disabilities learn throughout their lives and can obtain many new skills even late in life with the help of their families, caregivers, clinicians and the people who coordinate the efforts of all of these people. There are four broad areas of intervention that allow for active participation from caregivers, community members, clinicians, and of course, the individual(s) with an intellectual disability. These include psychosocial treatments, behavioral treatments, cognitive-behavioral treatments, and family-oriented strategies. Psychosocial treatments are intended primarily for children before and during the preschool years as this is the optimum time for intervention. This early intervention should include encouragement of exploration, mentoring in basic skills, celebration of developmental advances, guided rehearsal and extension of newly acquired skills, protection from harmful displays of disapproval, teasing, or punishment, and exposure to a rich and responsive language environment. A great example of a successful intervention is the Carolina Abecedarian Project that was conducted with over 100 children from low socioeconomic status families beginning in infancy through pre-school years. Results indicated that by age 2, the children provided the intervention had higher test scores than control group children, and they remained approximately 5 points higher 10 years after the end of the program. By young adulthood, children from the intervention group had better educational attainment, employment opportunities, and fewer behavioral problems than their control-group counterparts.Core components of behavioral treatments include language and social skills acquisition. Typically, one-to-one training is offered in which a therapist uses a shaping procedure in combination with positive reinforcements to help the child pronounce syllables until words are completed. Sometimes involving pictures and visual aids, therapists aim at improving speech capacity so that short sentences about important daily tasks (e.g. bathroom use, eating, etc.) can be effectively communicated by the child. In a similar fashion, older children benefit from this type of training as they learn to sharpen their social skills such as sharing, taking turns, following instruction, and smiling. At the same time, a movement known as social inclusion attempts to increase valuable interactions between children with an intellectual disability and their non-disabled peers. Cognitive-behavioral treatments, a combination of the previous two treatment types, involves a strategical-metastrategical learning technique that teaches children math, language, and other basic skills pertaining to memory and learning. The first goal of the training is to teach the child to be a strategical thinker through making cognitive connections and plans. Then, the therapist teaches the child to be metastrategical by teaching them to discriminate among different tasks and determine which plan or strategy suits each task. Finally, family-oriented strategies delve into empowering the family with the skill set they need to support and encourage their child or children with an intellectual disability. In general, this includes teaching assertiveness skills or behavior management techniques as well as how to ask for help from neighbors, extended family, or day-care staff. As the child ages, parents are then taught how to approach topics such as housing/residential care, employment, and relationships. The ultimate goal for every intervention or technique is to give the child autonomy and a sense of independence using the acquired skills he/she has. In a 2019 Cochrane review on beginning reading interventions for children and adolescents with intellectual disability small to moderate improvements in phonological awareness, word reading, decoding, expressive and receptive language skills and reading fluency were noted when these elements were part of the teaching intervention.Although there is no specific medication for intellectual disability, many people with developmental disabilities have further medical complications and may be prescribed several medications. For example, autistic children with developmental delay may be prescribed antipsychotics or mood stabilizers to help with their behavior. Use of psychotropic medications such as benzodiazepines in people with intellectual disability requires monitoring and vigilance as side effects occur commonly and are often misdiagnosed as behavioral and psychiatric problems. Epidemiology Intellectual disability affects about 2–3% of the general population. 75–90% of the affected people have mild intellectual disability. Non-syndromic or idiopathic ID accounts for 30–50% of cases. About a quarter of cases are caused by a genetic disorder. Cases of unknown cause affect about 95 million people as of 2013. It is more common in males and in low to middle income countries. History Intellectual disability has been documented under a variety of names throughout history. Throughout much of human history, society was unkind to those with any type of disability, and people with intellectual disability were commonly viewed as burdens on their families. Greek and Roman philosophers, who valued reasoning abilities, disparaged people with intellectual disability as barely human. The oldest physiological view of intellectual disability is in the writings of Hippocrates in the late fifth century BCE, who believed that it was caused by an imbalance in the four humors in the brain. In ancient Rome people with intellectual disabilities had limited rights and were generally looked down upon. They were considered property and could be kept slaves by their father. These people could also not marry, hold office, or raise children. Many of them were killed early in the childhood, and then dumped into the Tiber in order to avoid them burdening society. However, they were exempt from their crimes under Roman law, and they were also used to perform menial labor.Caliph Al-Walid (r. 705–715) built one of the first care homes for individuals with intellectual disabilities and built the first hospital which accommodated intellectually disabled individuals as part of its services. In addition, Al-Walid assigned each intellectually disabled individual a caregiver.Until the Enlightenment in Europe, care and asylum was provided by families and the church (in monasteries and other religious communities), focusing on the provision of basic physical needs such as food, shelter, and clothing. Negative stereotypes were prominent in social attitudes of the time. In the 13th century, England declared people with intellectual disabilities to be incapable of making decisions or managing their affairs. Guardianships were created to take over their financial affairs. In the 17th century, Thomas Willis provided the first description of intellectual disability as a disease. He believed that it was caused by structural problems in the brain. According to Willis, the anatomical problems could be either an inborn condition or acquired later in life. In the 18th and 19th centuries, housing and care moved away from families and towards an asylum model. People were placed by, or removed from, their families (usually in infancy) and housed in large professional institutions, many of which were self-sufficient through the labor of the residents. Some of these institutions provided a very basic level of education (such as differentiation between colors and basic word recognition and numeracy), but most continued to focus solely on the provision of basic needs of food, clothing, and shelter. Conditions in such institutions varied widely, but the support provided was generally non-individualized, with aberrant behavior and low levels of economic productivity regarded as a burden to society. Individuals of higher wealth were often able to afford higher degrees of care such as home care or private asylums. Heavy tranquilization and assembly-line methods of support were the norm, and the medical model of disability prevailed. Services were provided based on the relative ease to the provider, not based on the needs of the individual. A survey taken in 1891 in Cape Town, South Africa shows the distribution between different facilities. Out of 2046 persons surveyed, 1,281 were in private dwellings, 120 in jails, and 645 in asylums, with men representing nearly two-thirds of the number surveyed. In situations of scarcity of accommodation, preference was given to white men and Black men (whose insanity threatened white society by disrupting employment relations and the taboo sexual contact with white women).In the late 19th century, in response to Charles Darwins On the Origin of Species, Francis Galton proposed selective breeding of humans to reduce intellectual disability. Early in the 20th century, the eugenics movement became popular throughout the world. This led to forced sterilization and prohibition of marriage in most of the developed world and was later used by Adolf Hitler as a rationale for the mass murder of people with intellectual disability during the Holocaust. Eugenics was later abandoned as an violation of human rights, and the practice of forced sterilization and prohibition from marriage was discontinued by most of the developed world by the mid-20th century. In 1905, Alfred Binet produced the first standardized test for measuring intelligence in children.Although ancient Roman law had declared people with intellectual disability to be incapable of the deliberate intent to harm that was necessary for a person to commit a crime, during the 1920s, Western society believed they were morally degenerate.Ignoring the prevailing attitude, Civitans adopted service to people with developmental disabilities as a major organizational emphasis in 1952. Their earliest efforts included workshops for special education teachers and daycamps for children with disabilities, all at a time when such training and programs were almost nonexistent. The segregation of people with developmental disabilities was not widely questioned by academics or policy-makers until the 1969 publication of Wolf Wolfensbergers seminal work "The Origin and Nature of Our Institutional Models", drawing on some of the ideas proposed by S. G. Howe 100 years earlier. This book posited that society characterizes people with disabilities as deviant, sub-human and burdens of charity, resulting in the adoption of that "deviant" role. Wolfensberger argued that this dehumanization, and the segregated institutions that result from it, ignored the potential productive contributions that all people can make to society. He pushed for a shift in policy and practice that recognized the human needs of those with intellectual disability and provided the same basic human rights as for the rest of the population. The publication of this book may be regarded as the first move towards the widespread adoption of the social model of disability in regard to these types of disabilities, and was the impetus for the development of government strategies for desegregation. Successful lawsuits against governments and increasing awareness of human rights and self-advocacy also contributed to this process, resulting in the passing in the U.S. of the Civil Rights of Institutionalized Persons Act in 1980. From the 1960s to the present, most states have moved towards the elimination of segregated institutions. Normalization and deinstitutionalization are dominant. Along with the work of Wolfensberger and others including Gunnar and Rosemary Dybwad, a number of scandalous revelations around the horrific conditions within state institutions created public outrage that led to change to a more community-based method of providing services.By the mid-1970s, most governments had committed to de-institutionalization and had started preparing for the wholesale movement of people into the general community, in line with the principles of normalization. In most countries, this was essentially complete by the late 1990s, although the debate over whether or not to close institutions persists in some states, including Massachusetts.In the past, lead poisoning and infectious diseases were significant causes of intellectual disability. Some causes of intellectual disability are decreasing, as medical advances, such as vaccination, increase. Other causes are increasing as a proportion of cases, perhaps due to rising maternal age, which is associated with several syndromic forms of intellectual disability.Along with the changes in terminology, and the downward drift in acceptability of the old terms, institutions of all kinds have had to repeatedly change their names. This affects the names of schools, hospitals, societies, government departments, and academic journals. For example, the Midlands Institute of Mental Sub-normality became the British Institute of Mental Handicap and is now the British Institute of Learning Disability. This phenomenon is shared with mental health and motor disabilities, and seen to a lesser degree in sensory disabilities. Terminology Over the past two decades, the term intellectual disability has become preferred by most advocates and researchers in most English-speaking countries. In a 2012 survey of 101 Canadian healthcare professionals, 78% said they would use the term developmental delay with parents over intellectual disability (8%). Expressions like developmentally disabled, special, special needs, or challenged are sometimes used by, but have been criticized for "reinforc[ing] the idea that people cannot deal honestly with their disabilities".The term mental retardation, which stemmed from the understanding that such conditions arose as a result of delays or retardation of a childs natural development, was used in the American Psychiatric Associations DSM-IV (1994) and in the World Health Organizations ICD-10 (codes F70–F79). In the next revision, ICD-11, it was replaced by the term "disorders of intellectual development" (codes 6A00–6A04; 6A00.Z for the "unspecified" diagnosis code). The term "intellectual disability (intellectual developmental disorder)" is used in the DSM-5 (2013). The term "mental retardation" is still used in some professional settings such as governmental aid programs or health insurance paperwork, where "mental retardation" is specifically covered but not "intellectual disability" is not.Historical terms for intellectual disability eventually become perceived as an insult, in a process commonly known as the euphemism treadmill. The terms mental retardation and mentally retarded became popular in the middle of the 20th century to replace the previous set of terms, which included "imbecile", "idiot", "feeble-minded", and "moron", among others, and are now considered offensive. By the end of the 20th century, retardation and retard become widely seen as disparaging, politically incorrect, and in need of replacement.Usage has changed over the years and differed from country to country. For example, mental retardation in some contexts covers the whole field, but previously applied to what is now the mild MR group. Feeble-minded used to mean mild MR in the UK, and once applied in the US to the whole field. "Borderline intellectual functioning" is not currently defined, but the term may be used to apply to people with IQs in the 70s. People with IQs of 70 to 85 used to be eligible for special consideration in the US public education system on grounds of intellectual disability. United States In North America, intellectual disability is subsumed into the broader term developmental disability, which also includes epilepsy, autism, cerebral palsy, and other disorders that develop during the developmental period (birth to age 18). Because service provision is tied to the designation "developmental disability", it is used by many parents, direct support professionals, and physicians. In the United States, however, in school-based settings, the more specific term mental retardation or, more recently (and preferably), intellectual disability, is still typically used, and is one of 13 categories of disability under which children may be identified for special education services under Public Law 108–446. The phrase intellectual disability is increasingly being used as a synonym for people with significantly below-average cognitive ability. These terms are sometimes used as a means of separating general intellectual limitations from specific, limited deficits as well as indicating that it is not an emotional or psychological disability. It is not specific to congenital disorders such as Down syndrome.The American Association on Mental Retardation changed its name to the American Association on Intellectual and Developmental Disabilities (AAIDD) in 2007, and soon thereafter changed the names of its scholarly journals to reflect the term "intellectual disability". In 2010, the AAIDD released its 11th edition of its terminology and classification manual, which also used the term intellectual disability. United Kingdom In the UK, mental handicap had become the common medical term, replacing mental subnormality in Scotland and mental deficiency in England and Wales, until Stephen Dorrell, Secretary of State for Health for the United Kingdom from 1995 to 1997, changed the NHSs designation to learning disability. The new term is not yet widely understood, and is often taken to refer to problems affecting schoolwork (the American usage), which are known in the UK as "learning difficulties". British social workers may use "learning difficulty" to refer to both people with intellectual disability and those with conditions such as dyslexia. In education, "learning difficulties" is applied to a wide range of conditions: "specific learning difficulty" may refer to dyslexia, dyscalculia or developmental coordination disorder, while "moderate learning difficulties", "severe learning difficulties" and "profound learning difficulties" refer to more significant impairments.In England and Wales between 1983 and 2008, the Mental Health Act 1983 defined "mental impairment" and "severe mental impairment" as "a state of arrested or incomplete development of mind which includes significant/severe impairment of intelligence and social functioning and is associated with abnormally aggressive or seriously irresponsible conduct on the part of the person concerned." As behavior was involved, these were not necessarily permanent conditions: they were defined for the purpose of authorizing detention in hospital or guardianship. The term mental impairment was removed from the Act in November 2008, but the grounds for detention remained. However, English statute law uses mental impairment elsewhere in a less well-defined manner—e.g. to allow exemption from taxes—implying that intellectual disability without any behavioral problems is what is meant. A BBC poll conducted in the United Kingdom came to the conclusion that retard was the most offensive disability-related word. On the reverse side of that, when a contestant on Celebrity Big Brother live used the phrase "walking like a retard", despite complaints from the public and the charity Mencap, the communications regulator Ofcom did not uphold the complaint saying "it was not used in an offensive context [...] and had been used light-heartedly". It was, however, noted that two previous similar complaints from other shows were upheld. Australia In the past, Australia has used British and American terms interchangeably, including "mental retardation" and "mental handicap". Today, "intellectual disability" is the preferred and more commonly used descriptor. Society and culture People with intellectual disabilities are often not seen as full citizens of society. Person-centered planning and approaches are seen as methods of addressing the continued labeling and exclusion of socially devalued people, such as people with disabilities, encouraging a focus on the person as someone with capacities and gifts as well as support needs. The self-advocacy movement promotes the right of self-determination and self-direction by people with intellectual disabilities, which means allowing them to make decisions about their own lives. Until the middle of the 20th century, people with intellectual disabilities were routinely excluded from public education, or educated away from other typically developing children. Compared to peers who were segregated in special schools, students who are mainstreamed or included in regular classrooms report similar levels of stigma and social self-conception, but more ambitious plans for employment. As adults, they may live independently, with family members, or in different types of institutions organized to support people with disabilities. About 8% currently live in an institution or a group home.In the United States, the average lifetime cost of a person with an intellectual disability amounts to $223,000 per person, in 2003 US dollars, for direct costs such as medical and educational expenses. The indirect costs were estimated at $771,000, due to shorter lifespans and lower than average economic productivity. The total direct and indirect costs, which amount to a little more than a million dollars, are slightly more than the economic costs associated with cerebral palsy, and double that associated with serious vision or hearing impairments. Of the costs, about 14% is due to increased medical expenses (not including what is normally incurred by the typical person), and 10% is due to direct non-medical expenses, such as the excess cost of special education compared to standard schooling. The largest amount, 76%, is indirect costs accounting for reduced productivity and shortened lifespans. Some expenses, such as ongoing costs to family caregivers or the extra costs associated with living in a group home, were excluded from this calculation. Human rights and legal status The law treats person with intellectual disabilities differently than those without intellectual disabilities. Their human rights and freedoms, including the right to vote, the right to conduct business, enter into a contract, enter into marriage, right to education, are often limited. The courts have upheld some of these limitations and found discrimination in others. The UN Convention on the Rights of Persons with Disabilities, which sets minimum standards for the rights of persons with disabilities, has been ratified by more than 180 countries. In several U.S. states, and several European Union states, persons with intellectual disabilities are disenfranchised. The European Court of Human Rights ruled in Alajos Kiss v. Hungary (2010) that Hungary cannot restrict voting rights only on the basis of guardianship due to a psychosocial disability. Health disparities People with intellectual disabilities are usually at a higher risk of living with complex health conditions such as epilepsy and neurological disorders, gastrointestinal disorders, and behavioral and psychiatric problems compared to people without disabilities. Adults also have a higher prevalence of poor social determinants of health, behavioral risk factors, depression, diabetes, and poor or fair health status than adults without intellectual disability. In the United Kingdom people with intellectual disability live on average 16 years less than the general population. Some of the barriers that exist for people with ID accessing quality healthcare include: communication challenges, service eligibility, lack of training for healthcare providers, diagnostic overshadowing, and absence of targeted health promotion services. Key recommendations from the CDC for improving the health status for people with intellectual disabilities include: improve access to health care, improve data collection, strengthen the workforce, include people with ID in public health programs, and prepare for emergencies with people with disabilities in mind. See also Future planning History of psychiatric institutions IQ classification Intermediate Care Facilities for Individuals with Intellectual Disabilities Secondary handicap Severe mental impairment References Further reading Adkins, B.; Summerville, J.; Knox, M.; Brown, A. R.; Dillon, S. (2012). "Digital technologies and musical participation for people with intellectual disabilities". New Media & Society. 15 (4): 501–518. doi:10.1177/1461444812457338. hdl:10072/47764. OCLC 829241491. Carey C. Allison On the Margins of Citizenship: Intellectual Disability and Civil Rights in Twentieth-Century America. Temple University Press 2010 Rights of People with Intellectual Disabilities: Access to Education and Employment, bilingual reports on 14 European countries Dalton, A. J.; Janicki, Matthew P., editors. (1999). Dementia, aging, and intellectual disabilities: a handbook. Philadelphia, PA: Brunner/Mazel. p. 12. ISBN 0-87630-916-3. OCLC 39223703. Australian Institute of Health and Welfare paper The Definition and Prevalence of Intellectual Disability in Australia Harris, James C. (2010). Intellectual Disability: A Guide for Families and Professionals. Oxford University Press. 2001 New Zealand Snapshot of Intellectual Disability Kovago, Emese. (2003). People with Intellectual Disabilities: from Invisible to Visible Citizens of the EU Accession Countries Archived Copy Endicott, Orville (1991). Persons with intellectual disability who are incarcerated for criminal offences: A literature review (PDF). Communications and Corporate Development, Research Branch.: Correctional Service of Canada. Archived from the original (PDF) on 1 July 2013. Retrieved 30 June 2022. "John F. Kennedy and people with intellectual disabilities". Presidential Library and Museum. Archived from the original on 21 January 2022. Jones, Jessica (December 2007). "Persons with intellectual disabilities in the criminal justice system: Review of issues". International Journal of Offender Therapy and Comparative Criminology. Sage. 51 (6): 723–733. doi:10.1177/0306624X07299343. eISSN 1552-6933. ISSN 0306-624X. PMID 17636203. S2CID 27995011. Petersilia, Joan (2000). "Invisible Victims Violence against persons with developmental disabilities". Human Rights. American Bar Association. 27 (1): 9–12. Archived from the original on 1 September 2000. Retrieved 12 July 2022. Søndenaa, Erik; Linaker, Olav Martin; Nøttestad, Jim Aage (September 2009). "Effects of the changes in legislation governing offenders with intellectual disabilities in Norway: A descriptive study". Journal of Policy and Practice in Intellectual Disabilities. International Association for the Scientific Study of Intellectual Disabilities. 6 (3): 229–235. doi:10.1111/j.1741-1130.2009.00206.x. ISSN 1741-1130. Wehmeyer, Michael L. (2013). The Story of Intellectual Disability: An Evolution of Meaning, Understanding, and Public Perception. Brookes Publishing. Smith, Philip. (2010). Whatever Happened to Inclusion?: The Place of Students with Intellectual Disabilities in Education. New York: Peter Lang Publishing. ISBN 978-1433104343 LCCN 2009-44580 OCLC 460711867. External links Facts about intellectual disabilities from the US Centers for Disease Controls National Center on Birth Defects and Developmental Disabilities

Anabolic steroid

Anabolic steroids, also known more properly as anabolic–androgenic steroids (AAS), are steroidal androgens that include natural androgens like testosterone as well as synthetic androgens that are structurally related and have similar effects to testosterone. They increase protein within cells, especially in skeletal muscles, and also have varying degrees of virilizing effects, including induction of the development and maintenance of masculine secondary sexual characteristics such as the growth of facial and body hair. The word anabolic, referring to anabolism, comes from the Greek ἀναβολή anabole, "that which is thrown up, mound". Androgens or AAS are one of three types of sex hormone agonists, the others being estrogens like estradiol and progestogens like progesterone. AAS were synthesized in the 1930s, and are now used therapeutically in medicine to stimulate muscle growth and appetite, induce male puberty and treat chronic wasting conditions, such as cancer and AIDS. The American College of Sports Medicine acknowledges that AAS, in the presence of adequate diet, can contribute to increases in body weight, often as lean mass increases and that the gains in muscular strength achieved through high-intensity exercise and proper diet can be additionally increased by the use of AAS in some individuals.Health risks can be produced by long-term use or excessive doses of AAS. These effects include harmful changes in cholesterol levels (increased low-density lipoprotein and decreased high-density lipoprotein), acne, high blood pressure, liver damage (mainly with most oral AAS), and dangerous changes in the structure of the left ventricle of the heart. These risks are further increased when, as they often do, athletes take steroids alongside other drugs, causing significantly more damage to their bodies. The effect of anabolic steroids on the heart can cause myocardial infarction and strokes. Conditions pertaining to hormonal imbalances such as gynecomastia and testicular size reduction may also be caused by AAS. In women and children, AAS can cause irreversible masculinization.Ergogenic uses for AAS in sports, racing, and bodybuilding as performance-enhancing drugs are controversial because of their adverse effects and the potential to gain unfair advantage in physical competitions. Their use is referred to as doping and banned by most major sporting bodies. Athletes have been looking for drugs to enhance their athletic abilities since the Olympics started in Ancient Greece. For many years, AAS have been by far the most detected doping substances in IOC-accredited laboratories. In countries where AAS are controlled substances, there is often a black market in which smuggled, clandestinely manufactured or even counterfeit drugs are sold to users. Uses Medical Since the discovery and synthesis of testosterone in the 1930s, AAS have been used by physicians for many purposes, with varying degrees of success. These can broadly be grouped into anabolic, androgenic, and other uses. Anabolic Bone marrow stimulation: For decades, AAS were the mainstay of therapy for hypoplastic anemias due to leukemia, kidney failure or aplastic anemia. Growth stimulation: AAS can be used by pediatric endocrinologists to treat children with growth failure. However, the availability of synthetic growth hormone, which has fewer side effects, makes this a secondary treatment. Stimulation of appetite and preservation and increase of muscle mass: AAS have been given to people with chronic wasting conditions such as cancer and AIDS. Stimulation of lean body mass and prevention of bone loss in elderly men, as some studies indicate. However, a 2006 placebo-controlled trial of low-dose testosterone supplementation in elderly men with low levels of testosterone found no benefit on body composition, physical performance, insulin sensitivity, or quality of life. Prevention or treatment of osteoporosis in postmenopausal women. Nandrolone decanoate is approved for this use. Although they have been indicated for this indication, AAS saw very little use for this purpose due to their virilizing side effects. Aiding weight gain following surgery or physical trauma, during chronic infection, or in the context of unexplained weight loss. Counteracting the catabolic effect of long-term corticosteroid therapy. Oxandrolone improves both short-term and long-term outcomes in people recovering from severe burns and is well-established as a safe treatment for this indication. Treatment of idiopathic short stature, hereditary angioedema, alcoholic hepatitis, and hypogonadism. Methyltestosterone is used in the treatment of delayed puberty, hypogonadism, cryptorchidism, and erectile dysfunction in males, and in low doses to treat menopausal symptoms (specifically for osteoporosis, hot flashes, and to increase libido and energy), postpartum breast pain and engorgement, and breast cancer in women. Androgenic Androgen replacement therapy for men with low levels of testosterone; also effective in improving libido for elderly males. Induction of male puberty: Androgens are given to many boys distressed about extreme delay of puberty. Testosterone is now nearly the only androgen used for this purpose and has been shown to increase height, weight, and fat-free mass in boys with delayed puberty. Masculinizing hormone therapy for transgender men, other transmasculine people, and intersex people, by producing masculine secondary sexual characteristics such as a voice deepening, increased bone and muscle mass, masculine fat distribution, facial and body hair, and clitoral enlargement, as well as mental changes such as alleviation of gender dysphoria and increased sex drive. Other Treatment of breast cancer in women, although they are now very rarely used for this purpose due to their marked virilizing side effects. In low doses as a component of hormone therapy for postmenopausal and transgender women, for instance to increase energy, well-being, libido, and quality of life, as well as to reduce hot flashes. Testosterone is usually used for this purpose, although methyltestosterone is also used. Male hormonal contraception; currently experimental, but potential for use as effective, safe, reliable, and reversible male contraceptives. Enhancing performance Most steroid users are not athletes. In the United States, between 1 million and 3 million people (1% of the population) are thought to have used AAS. Studies in the United States have shown that AAS users tend to be mostly middle-class men with a median age of about 25 who are noncompetitive bodybuilders and non-athletes and use the drugs for cosmetic purposes. "Among 12- to 17-year-old boys, use of steroids and similar drugs jumped 25 percent from 1999 to 2000, with 20 percent saying they use them for looks rather than sports, a study by insurer Blue Cross Blue Shield found."(Eisenhauer) Another study found that non-medical use of AAS among college students was at or less than 1%. According to a recent survey, 78.4% of steroid users were noncompetitive bodybuilders and non-athletes, while about 13% reported unsafe injection practices such as reusing needles, sharing needles, and sharing multidose vials, though a 2007 study found that sharing of needles was extremely uncommon among individuals using AAS for non-medical purposes, less than 1%. Another 2007 study found that 74% of non-medical AAS users had post-secondary degrees and more had completed college and fewer had failed to complete high school than is expected from the general populace. The same study found that individuals using AAS for non-medical purposes had a higher employment rate and a higher household income than the general population. AAS users tend to research the drugs they are taking more than other controlled-substance users; however, the major sources consulted by steroid users include friends, non-medical handbooks, internet-based forums, blogs, and fitness magazines, which can provide questionable or inaccurate information.AAS users tend to be unhappy with the portrayal of AAS as deadly in the media and in politics. According to one study, AAS users also distrust their physicians and in the sample 56% had not disclosed their AAS use to their physicians. Another 2007 study had similar findings, showing that, while 66% of individuals using AAS for non-medical purposes were willing to seek medical supervision for their steroid use, 58% lacked trust in their physicians, 92% felt that the medical communitys knowledge of non-medical AAS use was lacking, and 99% felt that the public has an exaggerated view of the side-effects of AAS use. A recent study has also shown that long term AAS users were more likely to have symptoms of muscle dysmorphia and also showed stronger endorsement of more conventional male roles. A recent study in the Journal of Health Psychology showed that many users believed that steroids used in moderation were safe.AAS have been used by men and women in many different kinds of professional sports to attain a competitive edge or to assist in recovery from injury. These sports include bodybuilding, weightlifting, shot put and other track and field, cycling, baseball, wrestling, mixed martial arts, boxing, football, and cricket. Such use is prohibited by the rules of the governing bodies of most sports. AAS use occurs among adolescents, especially by those participating in competitive sports. It has been suggested that the prevalence of use among high-school students in the U.S. may be as high as 2.7%. Dosages Available forms The AAS that have been used most commonly in medicine are testosterone and its many esters (but most typically testosterone undecanoate, testosterone enanthate, testosterone cypionate, and testosterone propionate), nandrolone esters (typically nandrolone decanoate and nandrolone phenylpropionate), stanozolol, and metandienone (methandrostenolone). Others that have also been available and used commonly but to a lesser extent include methyltestosterone, oxandrolone, mesterolone, and oxymetholone, as well as drostanolone propionate (dromostanolone propionate), metenolone (methylandrostenolone) esters (specifically metenolone acetate and metenolone enanthate), and fluoxymesterone. Dihydrotestosterone (DHT), known as androstanolone or stanolone when used medically, and its esters are also notable, although they are not widely used in medicine. Boldenone undecylenate and trenbolone acetate are used in veterinary medicine.Designer steroids are AAS that have not been approved and marketed for medical use but have been distributed through the black market. Examples of notable designer steroids include 1-testosterone (dihydroboldenone), methasterone, trenbolone enanthate, desoxymethyltestosterone, tetrahydrogestrinone, and methylstenbolone. Routes of administration There are four common forms in which AAS are administered: oral pills; injectable steroids; creams/gels for topical application; and skin patches. Oral administration is the most convenient. Testosterone administered by mouth is rapidly absorbed, but it is largely converted to inactive metabolites, and only about one-sixth is available in active form. In order to be sufficiently active when given by mouth, testosterone derivatives are alkylated at the 17α position, e.g. methyltestosterone and fluoxymesterone. This modification reduces the livers ability to break down these compounds before they reach the systemic circulation. Testosterone can be administered parenterally, but it has more irregular prolonged absorption time and greater activity in muscle in enanthate, undecanoate, or cypionate ester form. These derivatives are hydrolyzed to release free testosterone at the site of injection; absorption rate (and thus injection schedule) varies among different esters, but medical injections are normally done anywhere between semi-weekly to once every 12 weeks. A more frequent schedule may be desirable in order to maintain a more constant level of hormone in the system. Injectable steroids are typically administered into the muscle, not into the vein, to avoid sudden changes in the amount of the drug in the bloodstream. In addition, because estered testosterone is dissolved in oil, intravenous injection has the potential to cause a dangerous embolism (clot) in the bloodstream. Transdermal patches (adhesive patches placed on the skin) may also be used to deliver a steady dose through the skin and into the bloodstream. Testosterone-containing creams and gels that are applied daily to the skin are also available, but absorption is inefficient (roughly 10%, varying between individuals) and these treatments tend to be more expensive. Individuals who are especially physically active and/or bathe often may not be good candidates, since the medication can be washed off and may take up to six hours to be fully absorbed. There is also the risk that an intimate partner or child may come in contact with the application site and inadvertently dose themselves; children and women are highly sensitive to testosterone and can develop unintended masculinization and health effects, even from small doses. Injection is the most common method used by individuals administering AAS for non-medical purposes.The traditional routes of administration do not have differential effects on the efficacy of the drug. Studies indicate that the anabolic properties of AAS are relatively similar despite the differences in pharmacokinetic principles such as first-pass metabolism. However, the orally available forms of AAS may cause liver damage in high doses. Adverse effects Known possible side effects of AAS include: Dermatological/integumental: oily skin, acne vulgaris, acne conglobata, seborrhea, stretch marks (due to rapid muscle enlargement), hypertrichosis (excessive body hair growth), androgenic alopecia (pattern hair loss; scalp baldness), fluid retention/edema. Reproductive/endocrine: libido changes, reversible infertility, hypogonadotropic hypogonadism. Male-specific: spontaneous erections, nocturnal emissions, priapism, erectile dysfunction, gynecomastia (mostly only with aromatizable and hence estrogenic AAS), oligospermia/azoospermia, testicular atrophy, intratesticular leiomyosarcoma, prostate hypertrophy, prostate cancer. Female-specific: masculinization, irreversible voice deepening, hirsutism (excessive facial/body hair growth), menstrual disturbances (e.g., anovulation, oligomenorrhea, amenorrhea, dysmenorrhea), clitoral enlargement, breast atrophy, uterine atrophy, teratogenicity (in female fetuses). Child-specific: premature epiphyseal closure and associated short stature, precocious puberty in boys, delayed puberty and contrasexual precocity in girls. Psychiatric/neurological: mood swings, irritability, aggression, violent behavior, impulsivity/recklessness, hypomania/mania, euphoria, depression, anxiety, dysphoria, suicidality, delusions, psychosis, withdrawal, dependence, neurotoxicity, cognitive impairment. Musculoskeletal: muscle hypertrophy, muscle strains, tendon ruptures, rhabdomyolysis. Cardiovascular: dyslipidemia (e.g., increased LDL levels, decreased HDL levels, reduced apo-A1 levels), atherosclerosis, hypertension, left ventricular hypertrophy, cardiomyopathy, myocardial hypertrophy, polycythemia/erythrocytosis, arrhythmias, thrombosis (e.g., embolism, stroke), myocardial infarction, sudden death. Hepatic: elevated liver function tests (AST, ALT, bilirubin, LDH, ALP), hepatotoxicity, jaundice, hepatic steatosis, hepatocellular adenoma, hepatocellular carcinoma, cholestasis, peliosis hepatis; all mostly or exclusively with 17α-alkylated AAS. Renal: renal hypertrophy, nephropathy, acute renal failure (secondary to rhabdomyolysis), focal segmental glomerulosclerosis, renal cell carcinoma. Others: glucose intolerance, insulin resistance, immune dysfunction. Physiological Depending on the length of drug use, there is a chance that the immune system can be damaged. Most of these side-effects are dose-dependent, the most common being elevated blood pressure, especially in those with pre-existing hypertension. In addition to morphological changes of the heart which may have a permanent adverse effect on cardiovascular efficiency. AAS have been shown to alter fasting blood sugar and glucose tolerance tests. AAS such as testosterone also increase the risk of cardiovascular disease or coronary artery disease. Acne is fairly common among AAS users, mostly due to stimulation of the sebaceous glands by increased testosterone levels. Conversion of testosterone to DHT can accelerate the rate of premature baldness for males genetically predisposed, but testosterone itself can produce baldness in females.A number of severe side effects can occur if adolescents use AAS. For example, AAS may prematurely stop the lengthening of bones (premature epiphyseal fusion through increased levels of estrogen metabolites), resulting in stunted growth. Other effects include, but are not limited to, accelerated bone maturation, increased frequency and duration of erections, and premature sexual development. AAS use in adolescence is also correlated with poorer attitudes related to health. Cancer WHO organization International Agency for Research on Cancer (IARC) list AAS under Group 2A: Probably carcinogenic to humans. Cardiovascular Other side-effects can include alterations in the structure of the heart, such as enlargement and thickening of the left ventricle, which impairs its contraction and relaxation, and therefore reducing ejected blood volume. Possible effects of these alterations in the heart are hypertension, cardiac arrhythmias, congestive heart failure, heart attacks, and sudden cardiac death. These changes are also seen in non-drug-using athletes, but steroid use may accelerate this process. However, both the connection between changes in the structure of the left ventricle and decreased cardiac function, as well as the connection to steroid use have been disputed.AAS use can cause harmful changes in cholesterol levels: Some steroids cause an increase in LDL cholesterol and a decrease in HDL cholesterol. Growth defects AAS use in adolescents quickens bone maturation and may reduce adult height in high doses. Low doses of AAS such as oxandrolone are used in the treatment of idiopathic short stature, but this may only quicken maturation rather than increasing adult height. Feminization There are also sex-specific side effects of AAS. Development of breast tissue in males, a condition called gynecomastia (which is usually caused by high levels of circulating estradiol), may arise because of increased conversion of testosterone to estradiol by the enzyme aromatase. Reduced sexual function and temporary infertility can also occur in males. Another male-specific side-effect that can occur is testicular atrophy, caused by the suppression of natural testosterone levels, which inhibits production of sperm (most of the mass of the testes is developing sperm). This side-effect is temporary; the size of the testicles usually returns to normal within a few weeks of discontinuing AAS use as normal production of sperm resumes. Masculinization Female-specific side effects include increases in body hair, permanent deepening of the voice, enlarged clitoris, and temporary decreases in menstrual cycles. Alteration of fertility and ovarian cysts can also occur in females. When taken during pregnancy, AAS can affect fetal development by causing the development of male features in the female fetus and female features in the male fetus. Kidney problems Kidney tests revealed that nine of the ten steroid users developed a condition called focal segmental glomerulosclerosis, a type of scarring within the kidneys. The kidney damage in the bodybuilders has similarities to that seen in morbidly obese patients, but appears to be even more severe. Liver problems High doses of oral AAS compounds can cause liver damage. Peliosis hepatis has been increasingly recognised with the use of AAS. Neuropsychiatric A 2005 review in CNS Drugs determined that "significant psychiatric symptoms including aggression and violence, mania, and less frequently psychosis and suicide have been associated with steroid abuse. Long-term steroid abusers may develop symptoms of dependence and withdrawal on discontinuation of AAS". High concentrations of AAS, comparable to those likely sustained by many recreational AAS users, produce apoptotic effects on neurons, raising the specter of possibly irreversible neurotoxicity. Recreational AAS use appears to be associated with a range of potentially prolonged psychiatric effects, including dependence syndromes, mood disorders, and progression to other forms of substance abuse, but the prevalence and severity of these various effects remains poorly understood. There is no evidence that steroid dependence develops from therapeutic use of AAS to treat medical disorders, but instances of AAS dependence have been reported among weightlifters and bodybuilders who chronically administered supraphysiologic doses. Mood disturbances (e.g. depression, [hypo-]mania, psychotic features) are likely to be dose- and drug-dependent, but AAS dependence or withdrawal effects seem to occur only in a small number of AAS users.Large-scale long-term studies of psychiatric effects on AAS users are not currently available. In 2003, the first naturalistic long-term study on ten users, seven of which having completed the study, found a high incidence of mood disorders and substance abuse, but few clinically relevant changes in physiological parameters or laboratory measures were noted throughout the study, and these changes were not clearly related to periods of reported AAS use. A 13-month study, which was published in 2006 and which involved 320 body builders and athletes suggests that the wide range of psychiatric side-effects induced by the use of AAS is correlated to the severity of abuse. Diagnostic Statistical Manual assertion DSM-IV lists General diagnostic criteria for a personality disorder guideline that "The pattern must not be better accounted for as a manifestation of another mental disorder, or to the direct physiological effects of a substance (e.g. drug or medication) or a general medical condition (e.g. head trauma).". As a result, AAS users may get misdiagnosed by a psychiatrist not told about their habit. Personality profiles Cooper, Noakes, Dunne, Lambert, and Rochford identified that AAS-using individuals are more likely to score higher on borderline (4.7 times), antisocial (3.8 times), paranoid (3.4 times), schizotypal (3.1 times), histrionic (2.9 times), passive-aggressive (2.4 times), and narcissistic (1.6 times) personality profiles than non-users. Other studies have suggested that antisocial personality disorder is slightly more likely among AAS users than among non-users (Pope & Katz, 1994). Bipolar dysfunction, substance dependency, and conduct disorder have also been associated with AAS use. Mood and anxiety Affective disorders have long been recognised as a complication of AAS use. Case reports describe both hypomania and mania, along with irritability, elation, recklessness, racing thoughts and feelings of power and invincibility that did not meet the criteria for mania/hypomania. Of 53 bodybuilders who used AAS, 27 (51%) reported unspecified mood disturbance. Aggression and hypomania From the mid-1980s onward, the media reported "roid rage" as a side effect of AAS.: 23 A 2005 review determined that some, but not all, randomized controlled studies have found that AAS use correlates with hypomania and increased aggressiveness, but pointed out that attempts to determine whether AAS use triggers violent behavior have failed, primarily because of high rates of non-participation. A 2008 study on a nationally representative sample of young adult males in the United States found an association between lifetime and past-year self-reported AAS use and involvement in violent acts. Compared with individuals that did not use steroids, young adult males that used AAS reported greater involvement in violent behaviors even after controlling for the effects of key demographic variables, previous violent behavior, and polydrug use. A 1996 review examining the blind studies available at that time also found that these had demonstrated a link between aggression and steroid use, but pointed out that with estimates of over one million past or current steroid users in the United States at that time, an extremely small percentage of those using steroids appear to have experienced mental disturbance severe enough to result in clinical treatments or medical case reports.A 1996 randomized controlled trial, which involved 43 men, did not find an increase in the occurrence of angry behavior during 10 weeks of administration of testosterone enanthate at 600 mg/week, but this study screened out subjects that had previously abused steroids or had any psychiatric antecedents. A trial conducted in 2000 using testosterone cypionate at 600 mg/week found that treatment significantly increased manic scores on the YMRS, and aggressive responses on several scales. The drug response was highly variable. However: 84% of subjects exhibited minimal psychiatric effects, 12% became mildly hypomanic, and 4% (2 subjects) became markedly hypomanic. The mechanism of these variable reactions could not be explained by demographic, psychological, laboratory, or physiological measures.A 2006 study of two pairs of identical twins, in which one twin used AAS and the other did not, found that in both cases the steroid-using twin exhibited high levels of aggressiveness, hostility, anxiety, and paranoid ideation not found in the "control" twin. A small-scale study of 10 AAS users found that cluster B personality disorders were confounding factors for aggression.The relationship between AAS use and depression is inconclusive. There have been anecdotal reports of depression and suicide in teenage steroid users, but little systematic evidence. A 1992 review found that AAS may both relieve and cause depression, and that cessation or diminished use of AAS may also result in depression, but called for additional studies due to disparate data. In the case of suicide, 3.9% of a sample of 77 those classified as AAS users reported attempting suicide during withdrawal (Malone, Dimeff, Lombardo, & Sample, 1995). Reproductive Androgens such as testosterone, androstenedione and dihydrotestosterone are required for the development of organs in the male reproductive system, including the seminal vesicles, epididymis, vas deferens, penis and prostate. AAS are testosterone derivatives designed to maximize the anabolic effects of testosterone. AAS are consumed by elite athletes competing in sports like weightlifting, bodybuilding, and track and field. Male recreational athletes take AAS to achieve an "enhanced" physical appearance.AAS consumption disrupts the hypothalamic–pituitary–gonadal axis (HPG axis) in males. In the HPG axis, gonadotropin-releasing hormone (GnRH) is secreted from the arcuate nucleus of the hypothalamus and stimulates the anterior pituitary to secrete the two gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). In adult males, LH stimulates the Leydig cells in the testes to produce testosterone which is required to form new sperm through spermatogenesis. AAS consumption leads to dose-dependent suppression of gonadotropin release through suppression of GnRH from the hypothalamus (long-loop mechanism) or from direct negative feedback on the anterior pituitary to inhibit gonadotropin release (short-loop mechanism), leading to AAS-induced hypogonadism. Pharmacology Mechanism of action The pharmacodynamics of AAS are unlike peptide hormones. Water-soluble peptide hormones cannot penetrate the fatty cell membrane and only indirectly affect the nucleus of target cells through their interaction with the cells surface receptors. However, as fat-soluble hormones, AAS are membrane-permeable and influence the nucleus of cells by direct action. The pharmacodynamic action of AAS begin when the exogenous hormone penetrates the membrane of the target cell and binds to an androgen receptor (AR) located in the cytoplasm of that cell. From there, the compound hormone-receptor diffuses into the nucleus, where it either alters the expression of genes or activates processes that send signals to other parts of the cell. Different types of AAS bind to the AAR with different affinities, depending on their chemical structure.The effect of AAS on muscle mass is caused in at least two ways: first, they increase the production of proteins; second, they reduce recovery time by blocking the effects of stress hormone cortisol on muscle tissue, so that catabolism of muscle is greatly reduced. It has been hypothesized that this reduction in muscle breakdown may occur through AAS inhibiting the action of other steroid hormones called glucocorticoids that promote the breakdown of muscles. AAS also affect the number of cells that develop into fat-storage cells, by favouring cellular differentiation into muscle cells instead. Anabolic and androgenic effects As their name suggests, AAS have two different, but overlapping, types of effects: anabolic, meaning that they promote anabolism (cell growth), and androgenic (or virilizing), meaning that they affect the development and maintenance of masculine characteristics. Some examples of the anabolic effects of these hormones are increased protein synthesis from amino acids, increased appetite, increased bone remodeling and growth, and stimulation of bone marrow, which increases the production of red blood cells. Through a number of mechanisms AAS stimulate the formation of muscle cells and hence cause an increase in the size of skeletal muscles, leading to increased strength.The androgenic effects of AAS are numerous. Depending on the length of use, the side effects of the steroid can be irreversible. Processes affected include pubertal growth, sebaceous gland oil production, and sexuality (especially in fetal development). Some examples of virilizing effects are growth of the clitoris in females and the penis in male children (the adult penis size does not change due to steroids ), increased vocal cord size, increased libido, suppression of natural sex hormones, and impaired production of sperm. Effects on women include deepening of the voice, facial hair growth, and possibly a decrease in breast size. Men may develop an enlargement of breast tissue, known as gynecomastia, testicular atrophy, and a reduced sperm count. The androgenic:anabolic ratio of an AAS is an important factor when determining the clinical application of these compounds. Compounds with a high ratio of androgenic to an anabolic effects are the drug of choice in androgen-replacement therapy (e.g., treating hypogonadism in males), whereas compounds with a reduced androgenic:anabolic ratio are preferred for anemia and osteoporosis, and to reverse protein loss following trauma, surgery, or prolonged immobilization. Determination of androgenic:anabolic ratio is typically performed in animal studies, which has led to the marketing of some compounds claimed to have anabolic activity with weak androgenic effects. This disassociation is less marked in humans, where all AAS have significant androgenic effects.A commonly used protocol for determining the androgenic:anabolic ratio, dating back to the 1950s, uses the relative weights of ventral prostate (VP) and levator ani muscle (LA) of male rats. The VP weight is an indicator of the androgenic effect, while the LA weight is an indicator of the anabolic effect. Two or more batches of rats are castrated and given no treatment and respectively some AAS of interest. The LA/VP ratio for an AAS is calculated as the ratio of LA/VP weight gains produced by the treatment with that compound using castrated but untreated rats as baseline: (LAc,t–LAc)/(VPc,t–VPc). The LA/VP weight gain ratio from rat experiments is not unitary for testosterone (typically 0.3–0.4), but it is normalized for presentation purposes, and used as basis of comparison for other AAS, which have their androgenic:anabolic ratios scaled accordingly (as shown in the table above). In the early 2000s, this procedure was standardized and generalized throughout OECD in what is now known as the Hershberger assay. Body composition and strength improvements Body weight in men may increase by 2 to 5 kg as a result of short-term (<10 weeks) AAS use, which may be attributed mainly to an increase of lean mass. Animal studies also found that fat mass was reduced, but most studies in humans failed to elucidate significant fat mass decrements. The effects on lean body mass have been shown to be dose-dependent. Both muscle hypertrophy and the formation of new muscle fibers have been observed. The hydration of lean mass remains unaffected by AAS use, although small increments of blood volume cannot be ruled out.The upper region of the body (thorax, neck, shoulders, and upper arm) seems to be more susceptible for AAS than other body regions because of predominance of ARs in the upper body. The largest difference in muscle fiber size between AAS users and non-users was observed in type I muscle fibers of the vastus lateralis and the trapezius muscle as a result of long-term AAS self-administration. After drug withdrawal, the effects fade away slowly, but may persist for more than 6–12 weeks after cessation of AAS use.Strength improvements in the range of 5 to 20% of baseline strength, depending largely on the drugs and dose used as well as the administration period. Overall, the exercise where the most significant improvements were observed is the bench press. For almost two decades, it was assumed that AAS exerted significant effects only in experienced strength athletes. A randomized controlled trial demonstrated, however, that even in novice athletes a 10-week strength training program accompanied by testosterone enanthate at 600 mg/week may improve strength more than training alone does. This dose is sufficient to significantly improve lean muscle mass relative to placebo even in subjects that did not exercise at all. The anabolic effects of testosterone enanthate were highly dose dependent. Dissociation of effects Endogenous/natural AAS like testosterone and DHT and synthetic AAS mediate their effects by binding to and activating the AR. On the basis of animal bioassays, the effects of these agents have been divided into two partially dissociable types: anabolic (myotrophic) and androgenic. Dissociation between the ratios of these two types of effects relative to the ratio observed with testosterone is observed in rat bioassays with various AAS. Theories for the dissociation include differences between AAS in terms of their intracellular metabolism, functional selectivity (differential recruitment of coactivators), and non-genomic mechanisms (i.e., signaling through non-AR membrane androgen receptors, or mARs). Support for the latter two theories is limited and more hypothetical, but there is a good deal of support for the intracellular metabolism theory.The measurement of the dissociation between anabolic and androgenic effects among AAS is based largely on a simple but outdated and unsophisticated model using rat tissue bioassays. It has been referred to as the "myotrophic–androgenic index". In this model, myotrophic or anabolic activity is measured by change in the weight of the rat bulbocavernosus/levator ani muscle, and androgenic activity is measured by change in the weight of the rat ventral prostate (or, alternatively, the rat seminal vesicles), in response to exposure to the AAS. The measurements are then compared to form a ratio. Intracellular metabolism Testosterone is metabolized in various tissues by 5α-reductase into DHT, which is 3- to 10-fold more potent as an AR agonist, and by aromatase into estradiol, which is an estrogen and lacks significant AR affinity. In addition, DHT is metabolized by 3α-hydroxysteroid dehydrogenase (3α-HSD) and 3β-hydroxysteroid dehydrogenase (3β-HSD) into 3α-androstanediol and 3β-androstanediol, respectively, which are metabolites with little or no AR affinity. 5α-reductase is widely distributed throughout the body, and is concentrated to various extents in skin (particularly the scalp, face, and genital areas), prostate, seminal vesicles, liver, and the brain. In contrast, expression of 5α-reductase in skeletal muscle is undetectable. Aromatase is highly expressed in adipose tissue and the brain, and is also expressed significantly in skeletal muscle. 3α-HSD is highly expressed in skeletal muscle as well.Natural AAS like testosterone and DHT and synthetic AAS are analogues and are very similar structurally. For this reason, they have the capacity to bind to and be metabolized by the same steroid-metabolizing enzymes. According to the intracellular metabolism explanation, the androgenic-to-anabolic ratio of a given AR agonist is related to its capacity to be transformed by the aforementioned enzymes in conjunction with the AR activity of any resulting products. For instance, whereas the AR activity of testosterone is greatly potentiated by local conversion via 5α-reductase into DHT in tissues where 5α-reductase is expressed, an AAS that is not metabolized by 5α-reductase or is already 5α-reduced, such as DHT itself or a derivative (like mesterolone or drostanolone), would not undergo such potentiation in said tissues. Moreover, nandrolone is metabolized by 5α-reductase, but unlike the case of testosterone and DHT, the 5α-reduced metabolite of nandrolone has much lower affinity for the AR than does nandrolone itself, and this results in reduced AR activation in 5α-reductase-expressing tissues. As so-called "androgenic" tissues such as skin/hair follicles and male reproductive tissues are very high in 5α-reductase expression, while skeletal muscle is virtually devoid of 5α-reductase, this may primarily explain the high myotrophic–androgenic ratio and dissociation seen with nandrolone, as well as with various other AAS.Aside from 5α-reductase, aromatase may inactivate testosterone signaling in skeletal muscle and adipose tissue, so AAS that lack aromatase affinity, in addition to being free of the potential side effect of gynecomastia, might be expected to have a higher myotrophic–androgenic ratio in comparison. In addition, DHT is inactivated by high activity of 3α-HSD in skeletal muscle (and cardiac tissue), and AAS that lack affinity for 3α-HSD could similarly be expected to have a higher myotrophic–androgenic ratio (although perhaps also increased long-term cardiovascular risks). In accordance, DHT, mestanolone (17α-methyl-DHT), and mesterolone (1α-methyl-DHT) are all described as very poorly anabolic due to inactivation by 3α-HSD in skeletal muscle, whereas other DHT derivatives with other structural features like metenolone, oxandrolone, oxymetholone, drostanolone, and stanozolol are all poor substrates for 3α-HSD and are described as potent anabolics.The intracellular metabolism theory explains how and why remarkable dissociation between anabolic and androgenic effects might occur despite the fact that these effects are mediated through the same signaling receptor, and why this dissociation is invariably incomplete. In support of the model is the rare condition congenital 5α-reductase type 2 deficiency, in which the 5α-reductase type 2 enzyme is defective, production of DHT is impaired, and DHT levels are low while testosterone levels are normal. Males with this condition are born with ambiguous genitalia and a severely underdeveloped or even absent prostate gland. In addition, at the time of puberty, such males develop normal musculature, voice deepening, and libido, but have reduced facial hair, a female pattern of body hair (i.e., largely restricted to the pubic triangle and underarms), no incidence of male pattern hair loss, and no prostate enlargement or incidence of prostate cancer. They also notably do not develop gynecomastia as a consequence of their condition. Functional selectivity An animal study found that two different kinds of androgen response elements could differentially respond to testosterone and DHT upon activation of the AR. Whether this is involved in the differences in the ratios of anabolic-to-myotrophic effect of different AAS is unknown however. Non-genomic mechanisms Testosterone signals not only through the nuclear AR, but also through mARs, including ZIP9 and GPRC6A. It has been proposed that differential signaling through mARs may be involved in the dissociation of the anabolic and androgenic effects of AAS. Indeed, DHT has less than 1% of the affinity of testosterone for ZIP9, and the synthetic AAS metribolone and mibolerone are ineffective competitors for the receptor similarly. This indicates that AAS do show differential interactions with the AR and mARs. However, women with complete androgen insensitivity syndrome (CAIS), who have a 46,XY ("male") genotype and testes but a defect in the AR such that it is non-functional, are a challenge to this notion. They are completely insensitive to the AR-mediated effects of androgens like testosterone, and show a perfectly female phenotype despite having testosterone levels in the high end of the normal male range. These women have little or no sebum production, incidence of acne, or body hair growth (including in the pubic and axillary areas). Moreover, CAIS women have lean body mass that is normal for females but is of course greatly reduced relative to males. These observations suggest that the AR is mainly or exclusively responsible for masculinization and myotrophy caused by androgens. The mARs have however been found to be involved in some of the health-related effects of testosterone, like modulation of prostate cancer risk and progression. Antigonadotropic effects Changes in endogenous testosterone levels may also contribute to differences in myotrophic–androgenic ratio between testosterone and synthetic AAS. AR agonists are antigonadotropic – that is, they dose-dependently suppress gonadal testosterone production and hence reduce systemic testosterone concentrations. By suppressing endogenous testosterone levels and effectively replacing AR signaling in the body with that of the exogenous AAS, the myotrophic–androgenic ratio of a given AAS may be further, dose-dependently increased, and this hence may be an additional factor contributing to the differences in myotrophic–androgenic ratio among different AAS. In addition, some AAS, such as 19-nortestosterone derivatives like nandrolone, are also potent progestogens, and activation of the progesterone receptor (PR) is antigonadotropic similarly to activation of the AR. The combination of sufficient AR and PR activation can suppress circulating testosterone levels into the castrate range in men (i.e., complete suppression of gonadal testosterone production and circulating testosterone levels decreased by about 95%). As such, combined progestogenic activity may serve to further increase the myotrophic–androgenic ratio for a given AAS. GABAA receptor modulation Some AAS, such as testosterone, DHT, stanozolol, and methyltestosterone, have been found to modulate the GABAA receptor similarly to endogenous neurosteroids like allopregnanolone, 3α-androstanediol, dehydroepiandrosterone sulfate, and pregnenolone sulfate. It has been suggested that this may contribute as an alternative or additional mechanism to the neurological and behavioral effects of AAS. Comparison of AAS AAS differ in a variety of ways including in their capacities to be metabolized by steroidogenic enzymes such as 5α-reductase, 3-hydroxysteroid dehydrogenases, and aromatase, in whether their potency as AR agonists is potentiated or diminished by 5α-reduction, in their ratios of anabolic/myotrophic to androgenic effect, in their estrogenic, progestogenic, and neurosteroid activities, in their oral activity, and in their capacity to produce hepatotoxicity. 5α-Reductase and androgenicity Testosterone can be robustly converted by 5α-reductase into DHT in so-called androgenic tissues such as skin, scalp, prostate, and seminal vesicles, but not in muscle or bone, where 5α-reductase either is not expressed or is only minimally expressed. As DHT is 3- to 10-fold more potent as an agonist of the AR than is testosterone, the AR agonist activity of testosterone is thus markedly and selectively potentiated in such tissues. In contrast to testosterone, DHT and other 4,5α-dihydrogenated AAS are already 5α-reduced, and for this reason, cannot be potentiated in androgenic tissues. 19-Nortestosterone derivatives like nandrolone can be metabolized by 5α-reductase similarly to testosterone, but 5α-reduced metabolites of 19-nortestosterone derivatives (e.g., 5α-dihydronandrolone) tend to have reduced activity as AR agonists, resulting in reduced androgenic activity in tissues that express 5α-reductase. In addition, some 19-nortestosterone derivatives, including trestolone (7α-methyl-19-nortestosterone (MENT)), 11β-methyl-19-nortestosterone (11β-MNT), and dimethandrolone (7α,11β-dimethyl-19-nortestosterone), cannot be 5α-reduced. Conversely, certain 17α-alkylated AAS like methyltestosterone are 5α-reduced and potentiated in androgenic tissues similarly to testosterone. 17α-Alkylated DHT derivatives cannot be potentiated via 5α-reductase however, as they are already 4,5α-reduced.The capacity to be metabolized by 5α-reductase and the AR activity of the resultant metabolites appears to be one of the major, if not the most important determinant of the androgenic–myotrophic ratio for a given AAS. AAS that are not potentiated by 5α-reductase or that are weakened by 5α-reductase in androgenic tissues have a reduced risk of androgenic side effects such as acne, androgenic alopecia (male-pattern baldness), hirsutism (excessive male-pattern hair growth), benign prostatic hyperplasia (prostate enlargement), and prostate cancer, while incidence and magnitude of other effects such as muscle hypertrophy, bone changes, voice deepening, and changes in sex drive show no difference. Aromatase and estrogenicity Testosterone can be metabolized by aromatase into estradiol, and many other AAS can be metabolized into their corresponding estrogenic metabolites as well. As an example, the 17α-alkylated AAS methyltestosterone and metandienone are converted by aromatase into methylestradiol. 4,5α-Dihydrogenated derivatives of testosterone such as DHT cannot be aromatized, whereas 19-nortestosterone derivatives like nandrolone can be but to a greatly reduced extent. Some 19-nortestosterone derivatives, such as dimethandrolone and 11β-MNT, cannot be aromatized due to steric hindrance provided by their 11β-methyl group, whereas the closely related AAS trestolone (7α-methyl-19-nortestosterone), in relation to its lack of an 11β-methyl group, can be aromatized. AAS that are 17α-alkylated (and not also 4,5α-reduced or 19-demethylated) are also aromatized but to a lesser extent than is testosterone. However, it is notable that estrogens that are 17α-substituted (e.g., ethinylestradiol and methylestradiol) are of markedly increased estrogenic potency due to improved metabolic stability, and for this reason, 17α-alkylated AAS can actually have high estrogenicity and comparatively greater estrogenic effects than testosterone.The major effect of estrogenicity is gynecomastia (woman-like breasts). AAS that have a high potential for aromatization like testosterone and particularly methyltestosterone show a high risk of gynecomastia at sufficiently high dosages, while AAS that have a reduced potential for aromatization like nandrolone show a much lower risk (though still potentially significant at high dosages). In contrast, AAS that are 4,5α-reduced, and some other AAS (e.g., 11β-methylated 19-nortestosterone derivatives), have no risk of gynecomastia. In addition to gynecomastia, AAS with high estrogenicity have increased antigonadotropic activity, which results in increased potency in suppression of the hypothalamic-pituitary-gonadal axis and gonadal testosterone production. Progestogenic activity Many 19-nortestosterone derivatives, including nandrolone, trenbolone, ethylestrenol (ethylnandrol), metribolone (R-1881), trestolone, 11β-MNT, dimethandrolone, and others, are potent agonists of the progesterone receptor (AR) and hence are progestogens in addition to AAS. Similarly to the case of estrogenic activity, the progestogenic activity of these drugs serves to augment their antigonadotropic activity. This results in increased potency and effectiveness of these AAS as antispermatogenic agents and male contraceptives (or, put in another way, increased potency and effectiveness in producing azoospermia and reversible male infertility). Oral activity and hepatotoxicity Non-17α-alkylated testosterone derivatives such as testosterone itself, DHT, and nandrolone all have poor oral bioavailability due to extensive first-pass hepatic metabolism and hence are not orally active. A notable exception to this are AAS that are androgen precursors or prohormones, including dehydroepiandrosterone (DHEA), androstenediol, androstenedione, boldione (androstadienedione), bolandiol (norandrostenediol), bolandione (norandrostenedione), dienedione, mentabolan (MENT dione, trestione), and methoxydienone (methoxygonadiene) (although these are relatively weak AAS). AAS that are not orally active are used almost exclusively in the form of esters administered by intramuscular injection, which act as depots and function as long-acting prodrugs. Examples include testosterone, as testosterone cypionate, testosterone enanthate, and testosterone propionate, and nandrolone, as nandrolone phenylpropionate and nandrolone decanoate, among many others (see here for a full list of testosterone and nandrolone esters). An exception is the very long-chain ester testosterone undecanoate, which is orally active, albeit with only very low oral bioavailability (approximately 3%). In contrast to most other AAS, 17α-alkylated testosterone derivatives show resistance to metabolism due to steric hindrance and are orally active, though they may be esterified and administered via intramuscular injection as well.In addition to oral activity, 17α-alkylation also confers a high potential for hepatotoxicity, and all 17α-alkylated AAS have been associated, albeit uncommonly and only after prolonged use (different estimates between 1 and 17%), with hepatotoxicity. In contrast, testosterone esters have only extremely rarely or never been associated with hepatotoxicity, and other non-17α-alkylated AAS only rarely, although long-term use may reportedly still increase the risk of hepatic changes (but at a much lower rate than 17α-alkylated AAS and reportedly not at replacement dosages). In accordance, D-ring glucuronides of testosterone and DHT have been found to be cholestatic.Aside from prohormones and testosterone undecanoate, almost all orally active AAS are 17α-alkylated. A few AAS that are not 17α-alkylated are orally active. Some examples include the testosterone 17-ethers cloxotestosterone, quinbolone, and silandrone, which are prodrugs (to testosterone, boldenone (Δ1-testosterone), and testosterone, respectively), the DHT 17-ethers mepitiostane, mesabolone, and prostanozol (which are also prodrugs), the 1-methylated DHT derivatives mesterolone and metenolone (although these are relatively weak AAS), and the 19-nortestosterone derivatives dimethandrolone and 11β-MNT, which have improved resistance to first-pass hepatic metabolism due to their 11β-methyl groups (in contrast to them, the related AAS trestolone (7α-methyl-19-nortestosterone) is not orally active). As these AAS are not 17α-alkylated, they show minimal potential for hepatotoxicity. Neurosteroid activity DHT, via its metabolite 3α-androstanediol (produced by 3α-hydroxysteroid dehydrogenase (3α-HSD)), is a neurosteroid that acts via positive allosteric modulation of the GABAA receptor. Testosterone, via conversion into DHT, also produces 3α-androstanediol as a metabolite and hence has similar activity. Some AAS that are or can be 5α-reduced, including testosterone, DHT, stanozolol, and methyltestosterone, among many others, can or may modulate the GABAA receptor, and this may contribute as an alternative or additional mechanism to their central nervous system effects in terms of mood, anxiety, aggression, and sex drive. Chemistry AAS are androstane or estrane steroids. They include testosterone (androst-4-en-17β-ol-3-one) and derivatives with various structural modifications such as: 17α-Alkylation: methyltestosterone, metandienone, fluoxymesterone, oxandrolone, oxymetholone, stanozolol, norethandrolone, ethylestrenol 19-Demethylation: nandrolone, trenbolone, norethandrolone, ethylestrenol, trestolone, dimethandrolone 5α-Reduction: androstanolone, drostanolone, mestanolone, mesterolone, metenolone, oxandrolone, oxymetholone, stanozolol 3β- and/or 17β-esterification: testosterone enanthate, nandrolone decanoate, drostanolone propionate, boldenone undecylenate, trenbolone acetateAs well as others such as 1-dehydrogenation (e.g., metandienone, boldenone), 1-substitution (e.g., mesterolone, metenolone), 2-substitution (e.g., drostanolone, oxymetholone, stanozolol), 4-substitution (e.g., clostebol, oxabolone), and various other modifications. Detection in body fluids The most commonly employed human physiological specimen for detecting AAS usage is urine, although both blood and hair have been investigated for this purpose. The AAS, whether of endogenous or exogenous origin, are subject to extensive hepatic biotransformation by a variety of enzymatic pathways. The primary urinary metabolites may be detectable for up to 30 days after the last use, depending on the specific agent, dose and route of administration. A number of the drugs have common metabolic pathways, and their excretion profiles may overlap those of the endogenous steroids, making interpretation of testing results a very significant challenge to the analytical chemist. Methods for detection of the substances or their excretion products in urine specimens usually involve gas chromatography–mass spectrometry or liquid chromatography-mass spectrometry. History Discovery of androgens The use of gonadal steroids pre-dates their identification and isolation. Extraction of hormones from urines began in China c. 100 BCE. Medical use of testicle extract began in the late 19th century while its effects on strength were still being studied. The isolation of gonadal steroids can be traced back to 1931, when Adolf Butenandt, a chemist in Marburg, purified 15 milligrams of the male hormone androstenone from tens of thousands of litres of urine. This steroid was subsequently synthesized in 1934 by Leopold Ružička, a chemist in Zurich.In the 1930s, it was already known that the testes contain a more powerful androgen than androstenone, and three groups of scientists, funded by competing pharmaceutical companies in the Netherlands, Germany, and Switzerland, raced to isolate it. This hormone was first identified by Karoly Gyula David, E. Dingemanse, J. Freud and Ernst Laqueur in a May 1935 paper "On Crystalline Male Hormone from Testicles (Testosterone)." They named the hormone testosterone, from the stems of testicle and sterol, and the suffix of ketone. The chemical synthesis of testosterone was achieved in August that year, when Butenandt and G. Hanisch published a paper describing "A Method for Preparing Testosterone from Cholesterol." Only a week later, the third group, Ruzicka and A. Wettstein, announced a patent application in a paper "On the Artificial Preparation of the Testicular Hormone Testosterone (Androsten-3-one-17-ol)." Ruzicka and Butenandt were offered the 1939 Nobel Prize in Chemistry for their work, but the Nazi government forced Butenandt to decline the honor, although he accepted the prize after the end of World War II.Clinical trials on humans, involving either PO doses of methyltestosterone or injections of testosterone propionate, began as early as 1937. There are often reported rumors that German soldiers were administered AAS during the Second World War, the aim being to increase their aggression and stamina, but these are, as yet, unproven.: 6  Adolf Hitler himself, according to his physician, was injected with testosterone derivatives to treat various ailments. AAS were used in experiments conducted by the Nazis on concentration camp inmates, and later by the allies attempting to treat the malnourished victims that survived Nazi camps.: 6  President John F. Kennedy was administered steroids both before and during his presidency. Development of synthetic AAS The development of muscle-building properties of testosterone was pursued in the 1940s, in the Soviet Union and in Eastern Bloc countries such as East Germany, where steroid programs were used to enhance the performance of Olympic and other amateur weight lifters. In response to the success of Russian weightlifters, the U.S. Olympic Team physician John Ziegler worked with synthetic chemists to develop an AAS with reduced androgenic effects. Zieglers work resulted in the production of methandrostenolone, which Ciba Pharmaceuticals marketed as Dianabol. The new steroid was approved for use in the U.S. by the Food and Drug Administration (FDA) in 1958. It was most commonly administered to burn victims and the elderly. The drugs off-label users were mostly bodybuilders and weight lifters. Although Ziegler prescribed only small doses to athletes, he soon discovered that those having abused Dianabol developed enlarged prostates and atrophied testes. AAS were placed on the list of banned substances of the International Olympic Committee (IOC) in 1976, and a decade later the committee introduced out-of-competition doping tests because many athletes used AAS in their training period rather than during competition.Three major ideas governed modifications of testosterone into a multitude of AAS: Alkylation at C17α position with methyl or ethyl group created POly active compounds because it slows the degradation of the drug by the liver; esterification of testosterone and nortestosterone at the C17β position allows the substance to be administered parenterally and increases the duration of effectiveness because agents soluble in oily liquids may be present in the body for several months; and alterations of the ring structure were applied for both PO and parenteral agents to seeking to obtain different anabolic-to-androgenic effect ratios. Society and culture Etymology Androgens were discovered in the 1930s and were characterized as having effects described as androgenic (i.e., virilizing) and anabolic (e.g., myotrophic, renotrophic). The term anabolic steroid can be dated as far back as at least the mid-1940s, when it was used to describe the at-the-time hypothetical concept of a testosterone-derived steroid with anabolic effects but with minimal or no androgenic effects. This concept was formulated based on the observation that steroids had ratios of renotrophic to androgenic potency that differed significantly, which suggested that anabolic and androgenic effects might be dissociable.In 1953, a testosterone-derived steroid known as norethandrolone (17α-ethyl-19-nortestosterone) was synthesized at G. D. Searle & Company and was studied as a progestin, but was not marketed. Subsequently, in 1955, it was re-examined for testosterone-like activity in animals and was found to have similar anabolic activity to testosterone, but only one-sixteenth of its androgenic potency. It was the first steroid with a marked and favorable separation of anabolic and androgenic effect to be discovered, and has accordingly been described as the "first anabolic steroid". Norethandrolone was introduced for medical use in 1956, and was quickly followed by numerous similar steroids, for instance nandrolone phenylpropionate in 1959 and stanozolol in 1962. With these developments, anabolic steroid became the preferred term to refer to such steroids (over "androgen"), and entered widespread use. Although anabolic steroid was originally intended to specifically describe testosterone-derived steroids with a marked dissociation of anabolic and androgenic effect, it is applied today indiscriminately to all steroids with AR agonism-based anabolic effects regardless of their androgenic potency, including even non-synthetic steroids like testosterone. While many anabolic steroids have diminished androgenic potency in comparison to anabolic potency, there is no anabolic steroid that is exclusively anabolic, and hence all anabolic steroids retain at least some degree of androgenicity. (Likewise, all "androgens" are inherently anabolic.) Indeed, it is probably not possible to fully dissociate anabolic effects from androgenic effects, as both types of effects are mediated by the same signaling receptor, the AR. As such, the distinction between the terms anabolic steroid and androgen is questionable, and this is the basis for the revised and more recent term anabolic–androgenic steroid (AAS). Legal status The legal status of AAS varies from country to country: some have stricter controls on their use or prescription than others though in many countries they are not illegal. In the U.S., AAS are currently listed as Schedule III controlled substances under the Controlled Substances Act, which makes simple possession of such substances without a prescription a federal crime punishable by up to one year in prison for the first offense. Unlawful distribution or possession with intent to distribute AAS as a first offense is punished by up to ten years in prison. In Canada, AAS and their derivatives are part of the Controlled Drugs and Substances Act and are Schedule IV substances, meaning that it is illegal to obtain or sell them without a prescription; however, possession is not punishable, a consequence reserved for schedule I, II, or III substances. Those guilty of buying or selling AAS in Canada can be imprisoned for up to 18 months. Import and export also carry similar penalties. In Canada, researchers have concluded that steroid use among student athletes is extremely widespread. A study conducted in 1993 by the Canadian Centre for Drug-Free Sport found that nearly 83,000 Canadians between the ages of 11 and 18 use steroids. AAS are also illegal without prescription in Australia, Argentina, Brazil, and Portugal, and are listed as Class C Controlled Drugs in the United Kingdom. AAS are readily available without a prescription in some countries such as Mexico and Thailand. United States The history of the U.S. legislation on AAS goes back to the late 1980s, when the U.S. Congress considered placing AAS under the Controlled Substances Act following the controversy over Ben Johnsons victory at the 1988 Summer Olympics in Seoul. AAS were added to Schedule III of the Controlled Substances Act in the Anabolic Steroids Control Act of 1990.The same act also introduced more stringent controls with higher criminal penalties for offenses involving the illegal distribution of AAS and human growth hormone. By the early 1990s, after AAS were scheduled in the U.S., several pharmaceutical companies stopped manufacturing or marketing the products in the U.S., including Ciba, Searle, Syntex, and others. In the Controlled Substances Act, AAS are defined to be any drug or hormonal substance chemically and pharmacologically related to testosterone (other than estrogens, progestins, and corticosteroids) that promote muscle growth. The act was amended by the Anabolic Steroid Control Act of 2004, which added prohormones to the list of controlled substances, with effect from January 20, 2005.Even though they can still be prescribed by a medical doctor in the U.S, the use of anabolic steroids for injury recovery purposes has been a taboo subject, even amongst the majority of sports medicine doctors and endocrinologists. United Kingdom In the United Kingdom, AAS are classified as class C drugs for their illegal abuse potential, which puts them in the same class as benzodiazepines. AAS are in Schedule 4, which is divided in 2 parts; Part 1 contains most of the benzodiazepines and Part 2 contains the AAS. Part 1 drugs are subject to full import and export controls with possession being an offence without an appropriate prescription. There is no restriction on the possession when it is part of a medicinal product. Part 2 drugs require a Home Office licence for importation and export unless the substance is in the form of a medicinal product and is for self-administration by a person. Status in sports AAS are banned by all major sports bodies including Association of Tennis Professionals, Major League Baseball, Fédération Internationale de Football Association the Olympics, the National Basketball Association, the National Hockey League, World Wrestling Entertainment and the National Football League. The World Anti-Doping Agency (WADA) maintains the list of performance-enhancing substances used by many major sports bodies and includes all anabolic agents, which includes all AAS and precursors as well as all hormones and related substances. Spain has passed an anti-doping law creating a national anti-doping agency. Italy passed a law in 2000 where penalties range up to three years in prison if an athlete has tested positive for banned substances. In 2006, Russian President Vladimir Putin signed into law ratification of the International Convention Against Doping in Sport which would encourage cooperation with WADA. Many other countries have similar legislation prohibiting AAS in sports including Denmark, France, the Netherlands and Sweden. Usage Law enforcement United States federal law enforcement officials have expressed concern about AAS use by police officers. "Its a big problem, and from the number of cases, its something we shouldnt ignore. Its not that we set out to target cops, but when were in the middle of an active investigation into steroids, there have been quite a few cases that have led back to police officers," says Lawrence Payne, a spokesman for the United States Drug Enforcement Administration. The FBI Law Enforcement Bulletin stated that "Anabolic steroid abuse by police officers is a serious problem that merits greater awareness by departments across the country". It is also believed that police officers across the United Kingdom "are using criminals to buy steroids" which he claims to be a top risk factor for police corruption. Professional wrestling Following the murder-suicide of Chris Benoit in 2007, the Oversight and Government Reform Committee investigated steroid usage in the wrestling industry. The Committee investigated WWE and Total Nonstop Action Wrestling (now known as Impact Wrestling), asking for documentation of their companies drug policies. WWE CEO and chairman, Linda and Vince McMahon respectively, both testified. The documents stated that 75 wrestlers—roughly 40 percent—had tested positive for drug use since 2006, most commonly for steroids. Economics AAS are frequently produced in pharmaceutical laboratories, but, in nations where stricter laws are present, they are also produced in small home-made underground laboratories, usually from raw substances imported from abroad. In these countries, the majority of steroids are obtained illegally through black market trade. These steroids are usually manufactured in other countries, and therefore must be smuggled across international borders. As with most significant smuggling operations, organized crime is involved.In the late 2000s, the worldwide trade in illicit AAS increased significantly, and authorities announced record captures on three continents. In 2006, Finnish authorities announced a record seizure of 11.8 million AAS tablets. A year later, the DEA seized 11.4 million units of AAS in the largest U.S seizure ever. In the first three months of 2008, Australian customs reported a record 300 seizures of AAS shipments.In the U.S., Canada, and Europe, illegal steroids are sometimes purchased just as any other illegal drug, through dealers who are able to obtain the drugs from a number of sources. Illegal AAS are sometimes sold at gyms and competitions, and through the mail, but may also be obtained through pharmacists, veterinarians, and physicians. In addition, a significant number of counterfeit products are sold as AAS, in particular via mail order from websites posing as overseas pharmacies. In the U.S., black-market importation continues from Mexico, Thailand, and other countries where steroids are more easily available, as they are legal. Research AAS, alone and in combination with progestogens, have been studied as potential male hormonal contraceptives. Dual AAS and progestins such as trestolone and dimethandrolone undecanoate have also been studied as male contraceptives, with the latter under active investigation as of 2018.Topical androgens have been used and studied in the treatment of cellulite in women. Topical androstanolone on the abdomen has been found to significantly decrease subcutaneous abdominal fat in women, and hence may be useful for improving body silhouette. However, men and hyperandrogenic women have higher amounts of abdominal fat than healthy women, and androgens have been found to increase abdominal fat in postmenopausal women and transgender men as well. See also References Further reading External links Media related to Anabolic-androgenic steroids at Wikimedia Commons

Depersonalization

Depersonalization can consist of a detachment within the self, regarding ones mind or body, or being a detached observer of oneself. Subjects feel they have changed and that the world has become vague, dreamlike, less real, lacking in significance or being outside reality while looking in. It can be described as feeling like one is on “autopilot” and that the persons sense of individuality or selfhood has been hindered or suppressed.Chronic depersonalization refers to depersonalization/derealization disorder, which is classified by the DSM-5 as a dissociative disorder, based on the findings that depersonalization and derealization are prevalent in other dissociative disorders including dissociative identity disorder.Though degrees of depersonalization and derealization can happen to anyone who is subject to temporary anxiety or stress, chronic depersonalization is more related to individuals who have experienced a severe trauma or prolonged stress/anxiety. Depersonalization-derealization is the single most important symptom in the spectrum of dissociative disorders, including dissociative identity disorder and "dissociative disorder not otherwise specified" (DD-NOS). It is also a prominent symptom in some other non-dissociative disorders, such as anxiety disorders, clinical depression, bipolar disorder, schizophrenia, schizoid personality disorder, hypothyroidism or endocrine disorders, schizotypal personality disorder, borderline personality disorder, obsessive–compulsive disorder, migraines, and sleep deprivation; it can also be a symptom of some types of neurological seizure. In social psychology, and in particular self-categorization theory, the term depersonalization has a different meaning and refers to "the stereotypical perception of the self as an example of some defining social category". Description Individuals who experience depersonalization feel divorced from their own personal self by sensing their body sensations, feelings, emotions, behaviors etc. as not belonging to the same person or identity. Often a person who has experienced depersonalization claims that things seem unreal or hazy. Also, a recognition of a self breaks down (hence the name). Depersonalization can result in very high anxiety levels, which further increase these perceptions.Depersonalization is a subjective experience of unreality in ones self, while derealization is unreality of the outside world. Although most authors currently regard depersonalization (personal/self) and derealization (reality/surroundings) as independent constructs, many do not want to separate derealization from depersonalization. Prevalence Depersonalization is a symptom of anxiety disorders, such as panic disorder. It can also accompany sleep deprivation (often occurring when experiencing jet lag), migraine, epilepsy (especially temporal lobe epilepsy,complex-partial seizure, both as part of the aura and during the seizure), obsessive-compulsive disorder, severe stress or trauma, anxiety, the use of recreational drugs —especially cannabis, hallucinogens, ketamine, and MDMA, certain types of meditation, deep hypnosis, extended mirror or crystal gazing, sensory deprivation, and mild-to-moderate head injury with little or full loss of consciousness (less likely if unconscious for more than 30 minutes). Interoceptive exposure is a non-pharmacological method that can be used to induce depersonalization.In the general population, transient depersonalization/derealization are common, having a lifetime prevalence between 26 and 74%. A random community-based survey of 1,000 adults in the US rural south found a 1-year depersonalization prevalence rate at 19%. Several studies, but not all, found age to be a significant factor: adolescents and young adults in the normal population reported the highest rate. In a study, 46% of college students reported at least one significant episode in the previous year. In another study, 20% of patients with minor head injury experience significant depersonalization and derealization. Several studies found that up to 66% of individuals in life-threatening accidents report transient depersonalization at minimum during or immediately after the accidents. Depersonalization occurs 2-4 times more in women than in men.A similar and overlapping concept called ipseity disturbance (ipse is Latin for "self" or "itself") may be part of the core process of schizophrenia spectrum disorders. However, specific to the schizophrenia spectrum seems to be "a dislocation of first-person perspective such that self and other or self and world may seem to be non-distinguishable, or in which the individual self or field of consciousness takes on an inordinate significance in relation to the objective or intersubjective world" (emphasis in original).For the purposes of evaluation and measurement depersonalization can be conceived of as a construct and scales are now available to map its dimensions in time and space. A study of undergraduate students found that individuals high on the depersonalization/derealization subscale of the Dissociative Experiences Scale exhibited a more pronounced cortisol response in stress. Individuals high on the absorption subscale, which measures a subjects experiences of concentration to the exclusion of awareness of other events, showed weaker cortisol responses.In general infantry and special forces soldiers, measures of depersonalization and derealization increased significantly after training that includes experiences of uncontrollable stress, semi-starvation, sleep deprivation, as well as lack of control over hygiene, movement, communications, and social interactions. Pharmacological and situational causes Depersonalization has been described by some as a desirable state, particularly by those that have experienced it under the influence of mood-altering recreational drugs. It is an effect of dissociatives and psychedelics, as well as a possible side effect of caffeine, alcohol, amphetamine, cannabis, and antidepressants. It is a classic withdrawal symptom from many drugs.Benzodiazepine dependence, which can occur with long-term use of benzodiazepines, can induce chronic depersonalization symptomatology and perceptual disturbances in some people, even in those who are taking a stable daily dosage, and it can also become a protracted feature of the benzodiazepine withdrawal syndrome.Lieutenant Colonel Dave Grossman, in his book On Killing, suggests that military training artificially creates depersonalization in soldiers, suppressing empathy and making it easier for them to kill other human beings.Graham Reed (1974) claimed that depersonalization occurs in relation to the experience of falling in love. Depersonalization as a psychobiological mechanism Depersonalization is a classic response to acute trauma, and may be highly prevalent in individuals involved in different traumatic situations including motor vehicle accident, and imprisonment.Psychologically depersonalization can, just like dissociation in general, be considered a type of coping mechanism. Depersonalization is in that case unconsciously used to decrease the intensity of unpleasant experience, whether that is something as mild as stress or something as severe as chronically high anxiety and post-traumatic stress disorder. The decrease in anxiety and psychobiological hyperarousal helps preserving adaptive behaviors and resources under threat or danger. Depersonalization is an overgeneralized reaction in that it doesnt diminish just the unpleasant experience, but more or less all experience – leading to a feeling of being detached from the world and experiencing it in a more bland way. An important distinction must be made between depersonalization as a mild, short-term reaction to unpleasant experience and depersonalization as a chronic symptom stemming from a severe mental disorder such as PTSD or dissociative identity disorder. Chronic symptoms may represent persistence of depersonalization beyond the situations under threat. Treatment Treatment is dependent on the underlying cause, whether it is organic or psychological in origin. If depersonalization is a symptom of neurological disease, then diagnosis and treatment of the specific disease is the first approach. Depersonalization can be a cognitive symptom of such diseases as amyotrophic lateral sclerosis, Alzheimers disease, multiple sclerosis (MS), or any other neurological disease affecting the brain. For those with both depersonalization and migraine, tricyclic antidepressants are often prescribed. If depersonalization is a symptom of psychological causes such as developmental trauma, treatment depends on the diagnosis. In case of dissociative identity disorder or DD-NOS as a developmental disorder, in which extreme developmental trauma interferes with formation of a single cohesive identity, treatment requires proper psychotherapy, and—in the case of additional (co-morbid) disorders such as eating disorders—a team of specialists treating such an individual. It can also be a symptom of borderline personality disorder, which can be treated in the long term with proper psychotherapy and psychopharmacology.The treatment of chronic depersonalization is considered in depersonalization disorder. A 2001 Russian study showed that naloxone, a drug used to reverse the intoxicating effects of opioid drugs, can successfully treat depersonalization disorder. According to the study: "In three of 14 patients, depersonalization symptoms disappeared entirely and seven patients showed a marked improvement. The therapeutic effect of naloxone provides evidence for the role of the endogenous opioid system in the pathogenesis of depersonalization." The anti convulsion drug Lamotrigine has shown some success in treating symptoms of depersonalization, often in combination with a selective serotonin reuptake inhibitor and is the first drug of choice at the depersonalisation research unit at Kings College London. Research The Depersonalisation Research Unit at the Institute of Psychiatry in London conducts research into depersonalization disorder. Researchers there use the acronym DPAFU (Depersonalisation and Feelings of Unreality) as a shortened label for the disorder. In a 2020 article in the journal Nature, Vesuna, et al. describe experimental findings which show that layer 5 of the retrosplenial cortex is likely responsible for dissociative states of consciousness in mammals. See also References Other references Loewenstein, Richard J; Frewen, Paul; Lewis-Fernández, Roberto (2017). "20 Dissociative Disorders". In Sadock, Virginia A; Sadock, Benjamin J; Ruiz, Pedro (eds.). Kaplan & Sadocks Comprehensive Textbook of Psychiatry (10th ed.). Wolters Kluwer. ISBN 978-1-4511-0047-1.

Appendicitis

Appendicitis is inflammation of the appendix. Symptoms commonly include right lower abdominal pain, nausea, vomiting, and decreased appetite. However, approximately 40% of people do not have these typical symptoms. Severe complications of a ruptured appendix include widespread, painful inflammation of the inner lining of the abdominal wall and sepsis.Appendicitis is caused by a blockage of the hollow portion of the appendix. This is most commonly due to a calcified "stone" made of feces. Inflamed lymphoid tissue from a viral infection, parasites, gallstone, or tumors may also cause the blockage. This blockage leads to increased pressures in the appendix, decreased blood flow to the tissues of the appendix, and bacterial growth inside the appendix causing inflammation. The combination of inflammation, reduced blood flow to the appendix and distention of the appendix causes tissue injury and tissue death. If this process is left untreated, the appendix may burst, releasing bacteria into the abdominal cavity, leading to increased complications.The diagnosis of appendicitis is largely based on the persons signs and symptoms. In cases where the diagnosis is unclear, close observation, medical imaging, and laboratory tests can be helpful. The two most common imaging tests used are an ultrasound and computed tomography (CT scan). CT scan has been shown to be more accurate than ultrasound in detecting acute appendicitis. However, ultrasound may be preferred as the first imaging test in children and pregnant women because of the risks associated with radiation exposure from CT scans.The standard treatment for acute appendicitis is surgical removal of the appendix. This may be done by an open incision in the abdomen (laparotomy) or through a few smaller incisions with the help of cameras (laparoscopy). Surgery decreases the risk of side effects or death associated with rupture of the appendix. Antibiotics may be equally effective in certain cases of non-ruptured appendicitis. It is one of the most common and significant causes of abdominal pain that comes on quickly. In 2015 about 11.6 million cases of appendicitis occurred which resulted in about 50,100 deaths. In the United States, appendicitis is one of the most common cause of sudden abdominal pain requiring surgery. Each year in the United States, more than 300,000 people with appendicitis have their appendix surgically removed. Reginald Fitz is credited with being the first person to describe the condition in 1886. Signs and symptoms The presentation of acute appendicitis includes acute abdominal pain, nausea, vomiting, and fever. As the appendix becomes more swollen and inflamed, it begins to irritate the adjoining abdominal wall. This leads to the localization of the pain to the right lower quadrant. This classic migration of pain may not be seen in children under three years. This pain can be elicited through signs, which can feel sharp. Pain from appendicitis may begin as dull pain around the navel. After several hours, pain will usually transition towards the right lower quadrant, where it becomes localized. Symptoms include localized findings in the right iliac fossa. The abdominal wall becomes very sensitive to gentle pressure (palpation). There is pain in the sudden release of deep tension in the lower abdomen (Blumberg sign). If the appendix is retrocecal (localized behind the cecum), even deep pressure in the right lower quadrant may fail to elicit tenderness (silent appendix). This is because the cecum, distended with gas, protects the inflamed appendix from pressure. Similarly, if the appendix lies entirely within the pelvis, there is typically a complete absence of abdominal rigidity. In such cases, a digital rectal examination elicits tenderness in the rectovesical pouch. Coughing causes point tenderness in this area (McBurneys point), historically called Dunphys sign. Causes Acute appendicitis seems to be the result of a primary obstruction of the appendix. Once this obstruction occurs, the appendix becomes filled with mucus and swells. This continued production of mucus leads to increased pressures within the lumen and the walls of the appendix. The increased pressure results in thrombosis and occlusion of the small vessels, and stasis of lymphatic flow. At this point, spontaneous recovery rarely occurs. As the occlusion of blood vessels progresses, the appendix becomes ischemic and then necrotic. As bacteria begin to leak out through the dying walls, pus forms within and around the appendix (suppuration). The result is appendiceal rupture (a burst appendix) causing peritonitis, which may lead to sepsis and in rare cases, death. These events are responsible for the slowly evolving abdominal pain and other commonly associated symptoms.The causative agents include bezoars, foreign bodies, trauma, intestinal worms, lymphadenitis and, most commonly, calcified fecal deposits that are known as appendicoliths or fecaliths. The occurrence of obstructing fecaliths has attracted attention since their presence in people with appendicitis is higher in developed than in developing countries. In addition an appendiceal fecalith is commonly associated with complicated appendicitis. Fecal stasis and arrest may play a role, as demonstrated by people with acute appendicitis having fewer bowel movements per week compared with healthy controls.The occurrence of a fecalith in the appendix was thought to be attributed to a right-sided fecal retention reservoir in the colon and a prolonged transit time. However, a prolonged transit time was not observed in subsequent studies. Diverticular disease and adenomatous polyps was historically unknown and colon cancer was exceedingly rare in communities where appendicitis itself was rare or absent, such as various African communities. Studies have implicated a transition to a Western diet lower in fibre in rising frequencies of appendicitis as well as the other aforementioned colonic diseases in these communities. And acute appendicitis has been shown to occur antecedent to cancer in the colon and rectum. Several studies offer evidence that a low fiber intake is involved in the pathogenesis of appendicitis. This low intake of dietary fiber is in accordance with the occurrence of a right-sided fecal reservoir and the fact that dietary fiber reduces transit time. Diagnosis Diagnosis is based on a medical history (symptoms) and physical examination, which can be supported by an elevation of neutrophilic white blood cells and imaging studies if needed. Histories fall into two categories, typical and atypical. Typical appendicitis includes several hours of generalized abdominal pain that begins in the region of the umbilicus with associated anorexia, nausea, or vomiting. The pain then "localizes" into the right lower quadrant where the tenderness increases in intensity. It is possible the pain could localize to the left lower quadrant in people with situs inversus totalis. The combination of pain, anorexia, leukocytosis, and fever is classic. Atypical histories lack this typical progression and may include pain in the right lower quadrant as an initial symptom. Irritation of the peritoneum (inside lining of the abdominal wall) can lead to increased pain on movement, or jolting, for example going over speed bumps. Atypical histories often require imaging with ultrasound or CT scanning. Clinical Aure-Rozanovas sign: Increased pain on palpation with finger in right Petit triangle (can be a positive Shchetkin-Bloombergs). Bartomier-Michelsons sign: Increased pain on palpation at the right iliac region as the person being examined lies on their left side compared to when they lie on their back. Dunphys sign: Increased pain in the right lower quadrant with coughing. Hamburger sign: The patient refuses to eat (anorexia is 80% sensitive for appendicitis) Kochers (Koshers) sign: From the persons medical history, the start of pain in the umbilical region with a subsequent shift to the right iliac region. Massouh sign: Developed in and popular in southwest England, the examiner performs a firm swish with his or her index and middle finger across the abdomen from the xiphoid process to the left and the right iliac fossa. A positive Massouh sign is a grimace of the person being examined upon a right sided (and not left) sweep. Obturator sign: The person being evaluated lies on her or his back with the hip and knee both flexed at ninety degrees. The examiner holds the persons ankle with one hand and knee with the other hand. The examiner rotates the hip by moving the persons ankle away from his or her body while allowing the knee to move only inward. A positive test is pain with internal rotation of the hip. Psoas sign, also known as "Obraztsovas sign", is right lower-quadrant pain that is produced with either the passive extension of the right hip or by the active flexion of the persons right hip while supine. The pain that is elicited is due to inflammation of the peritoneum overlying the iliopsoas muscles and inflammation of the psoas muscles themselves. Straightening out the leg causes pain because it stretches these muscles, while flexing the hip activates the iliopsoas and causes pain. Rovsings sign: Pain in the lower right abdominal quadrant with continuous deep palpation starting from the left iliac fossa upwards (counterclockwise along the colon). The thought is there will be increased pressure around the appendix by pushing bowel contents and air toward the ileocaecal valve provoking right-sided abdominal pain. Sitkovskiy (Rosenstein)s sign: Increased pain in the right iliac region as the person is being examined lies on their left side. Permans sign: In acute appendicitis palpation in the left iliac fossa may produce pain in the right iliac fossa. Blood and urine test While there is no laboratory test specific for appendicitis, a complete blood count (CBC) is done to check for signs of infection. Although 70–90 percent of people with appendicitis may have an elevated white blood cell (WBC) count, there are many other abdominal and pelvic conditions that can cause the WBC count to be elevated. Due to its low sensitivity and specificity, on its own, WBC is not seen as a good indicator of appendicitis. The diagnostic performance of novel molecules such as Interleukin-6, calprotectin and NGAL has recently been studied in pediatric appendicitis and has shown moderate utility. Also, Interleukin-6 has shown has shown a moderate ability to discriminate between complicated and uncomplicated appendicitis in children. A urinalysis generally does not show infection, but it is important for determining pregnancy status, especially the possibility of an ectopic pregnancy in women of childbearing age. The urinalysis is also important for ruling out a urinary tract infection as the cause of abdominal pain. The presence of more than 20 WBC per high-power field in the urine is more suggestive of a urinary tract disorder. Imaging In children the clinical examination is important to determine which children with abdominal pain should receive immediate surgical consultation and which should receive diagnostic imaging. Because of the health risks of exposing children to radiation, ultrasound is the preferred first choice with CT scan being a legitimate follow-up if the ultrasound is inconclusive. CT scan is more accurate than ultrasound for the diagnosis of appendicitis in adults and adolescents. CT scan has a sensitivity of 94%, specificity of 95%. Ultrasonography had an overall sensitivity of 86%, a specificity of 81%. Ultrasound Abdominal ultrasonography, preferably with doppler sonography, is useful to detect appendicitis, especially in children. Ultrasound can show the free fluid collection in the right iliac fossa, along with a visible appendix with increased blood flow when using color Doppler, and noncompressibility of the appendix, as it is essentially walled-off abscess. Other secondary sonographic signs of acute appendicitis include the presence of echogenic mesenteric fat surrounding the appendix and the acoustic shadowing of an appendicolith. In some cases (approximately 5%), ultrasonography of the iliac fossa does not reveal any abnormalities despite the presence of appendicitis. This false-negative finding is especially true of early appendicitis before the appendix has become significantly distended. Also, false-negative findings are more common in adults where larger amounts of fat and bowel gas make visualizing the appendix technically difficult. Despite these limitations, sonographic imaging with experienced hands can often distinguish between appendicitis and other diseases with similar symptoms. Some of these conditions include inflammation of lymph nodes near the appendix or pain originating from other pelvic organs such as the ovaries or Fallopian tubes. Ultrasounds may be either done by the radiology department or by the emergency physician. Computed tomography Where it is readily available, computed tomography (CT) has become frequently used, especially in people whose diagnosis is not obvious on history and physical examination. Although some concerns about interpretation are identified, a 2019 Cochrane review found that sensitivity and specificity of CT for the diagnosis of acute appendicitis in adults was high. Concerns about radiation tend to limit use of CT in pregnant women and children, especially with the increasingly widespread usage of MRI.The accurate diagnosis of appendicitis is multi-tiered, with the size of the appendix having the strongest positive predictive value, while indirect features can either increase or decrease sensitivity and specificity. A size of over 6 mm is both 95% sensitive and specific for appendicitis.However, because the appendix can be filled with fecal material, causing intraluminal distention, this criterion has shown limited utility in more recent meta-analyses. This is as opposed to ultrasound, in which the wall of the appendix can be more easily distinguished from intraluminal feces. In such scenarios, ancillary features such as increased wall enhancement as compared to adjacent bowel and inflammation of the surrounding fat, or fat stranding, can be supportive of the diagnosis. However, their absence does not preclude it. In severe cases with perforation, an adjacent phlegmon or abscess can be seen. Dense fluid layering in the pelvis can also result, related to either pus or enteric spillage. When patients are thin or younger, the relative absence of fat can make the appendix and surrounding fat stranding difficult to see. Magnetic resonance imaging Magnetic resonance imaging (MRI) use has become increasingly common for diagnosis of appendicitis in children and pregnant patients due to the radiation dosage that, while of nearly negligible risk in healthy adults, can be harmful to children or the developing baby. In pregnancy, it is more useful during the second and third trimester, particularly as the enlargening uterus displaces the appendix, making it difficult to find by ultrasound. The periappendiceal stranding that is reflected on CT by fat stranding on MRI appears as an increased fluid signal on T2 weighted sequences. First trimester pregnancies are usually not candidates for MRI, as the fetus is still undergoing organogenesis, and there are no long-term studies to date regarding its potential risks or side effects. X-ray In general, plain abdominal radiography (PAR) is not useful in making the diagnosis of appendicitis and should not be routinely obtained from a person being evaluated for appendicitis. Plain abdominal films may be useful for the detection of ureteral calculi, small bowel obstruction, or perforated ulcer, but these conditions are rarely confused with appendicitis. An opaque fecalith can be identified in the right lower quadrant in fewer than 5% of people being evaluated for appendicitis. A barium enema has proven to be a poor diagnostic tool for appendicitis. While failure of the appendix to fill during a barium enema has been associated with appendicitis, up to 20% of normal appendices do not fill. Scoring systems Several scoring systems have been developed to try to identify people who are likely to have appendicitis. The performance of scores such as the Alvarado score and the Pediatric Appendicitis Score, however, are variable.The Alvarado score is the most known scoring system. A score below 5 suggests against a diagnosis of appendicitis, whereas a score of 7 or more is predictive of acute appendicitis. In a person with an equivocal score of 5 or 6, a CT scan or ultrasound exam may be used to reduce the rate of negative appendectomy. Pathology Even for clinically certain appendicitis, routine histopathology examination of appendectomy specimens is of value for identifying unsuspected pathologies requiring further postoperative management. Notably, appendix cancer is found incidentally in about 1% of appendectomy specimens.Pathology diagnosis of appendicitis can be made by detecting a neutrophilic infiltrate of the muscularis propria. Periappendicitis, inflammation of tissues around the appendix, is often found in conjunction with other abdominal pathology. Differential diagnosis Children: Gastroenteritis, mesenteric adenitis, Meckels diverticulitis, intussusception, Henoch–Schönlein purpura, lobar pneumonia, urinary tract infection (abdominal pain in the absence of other symptoms can occur in children with UTI), new-onset Crohns disease or ulcerative colitis, pancreatitis, and abdominal trauma from child abuse; distal intestinal obstruction syndrome in children with cystic fibrosis; typhlitis in children with leukemia. Women: A pregnancy test is important for all women of childbearing age since an ectopic pregnancy can have signs and symptoms similar to those of appendicitis. Other obstetrical/ gynecological causes of similar abdominal pain in women include pelvic inflammatory disease, ovarian torsion, menarche, dysmenorrhea, endometriosis, and Mittelschmerz (the passing of an egg in the ovaries approximately two weeks before menstruation).Men: testicular torsion Adults: new-onset Crohn disease, ulcerative colitis, regional enteritis, cholecystitis, renal colic, perforated peptic ulcer, pancreatitis, rectus sheath hematoma and epiploic appendagitis. Elderly: diverticulitis, intestinal obstruction, colonic carcinoma, mesenteric ischemia, leaking aortic aneurysm. The term "pseudoappendicitis" is used to describe a condition mimicking appendicitis. It can be associated with Yersinia enterocolitica. Management Acute appendicitis is typically managed by surgery. While antibiotics are safe and effective for treating uncomplicated appendicitis, 26% of people had a recurrence within a year and required an eventual appendectomy. Antibiotics are less effective if an appendicolith is present. Surgery is the standard management approach for acute appendicitis, however, the 2011 Cochrane review comparing appendectomy with antibiotics treatments has not been updated and has been withdrawn. The cost effectiveness of surgery versus antibiotics is unclear.Using antibiotics to prevent potential postoperative complications in emergency appendectomy procedures is recommended, and the antibiotics are effective when given to a person before, during, or after surgery. Pain Pain medications (such as morphine) do not appear to affect the accuracy of the clinical diagnosis of appendicitis and therefore should be given early in the patients care. Historically there were concerns among some general surgeons that analgesics would affect the clinical exam in children, and some recommended that they not be given until the surgeon was able to examine the person. Surgery The surgical procedure for the removal of the appendix is called an appendectomy. Appendectomy can be performed through open or laparoscopic surgery. Laparoscopic appendectomy has several advantages over open appendectomy as an intervention for acute appendicitis. Open appendectomy For over a century, laparotomy (open appendectomy) was the standard treatment for acute appendicitis. This procedure consists of the removal of the infected appendix through a single large incision in the lower right area of the abdomen. The incision in a laparotomy is usually 2 to 3 inches (51 to 76 mm) long. During an open appendectomy, the person with suspected appendicitis is placed under general anesthesia to keep the muscles completely relaxed and to keep the person unconscious. The incision is two to three inches (76 mm) long, and it is made in the right lower abdomen, several inches above the hip bone. Once the incision opens the abdomen cavity, and the appendix is identified, the surgeon removes the infected tissue and cuts the appendix from the surrounding tissue. After careful and close inspection of the infected area, and ensuring there are no signs that surrounding tissues are damaged or infected. In case of complicated appendicitis managed by an emergency open appendectomy, abdominal drainage (a temporary tube from the abdomen to the outside to avoid abscess formation) may be inserted, but this may increase the hospital stay. The surgeon will start closing the incision. This means sewing the muscles and using surgical staples or stitches to close the skin up. To prevent infections, the incision is covered with a sterile bandage or surgical adhesive. Laparoscopic appendectomy Laparoscopic appendectomy was introduced in 1983 and has become an increasingly prevalent intervention for acute appendicitis. This surgical procedure consists of making three to four incisions in the abdomen, each 0.25 to 0.5 inches (6.4 to 12.7 mm) long. This type of appendectomy is made by inserting a special surgical tool called a laparoscope into one of the incisions. The laparoscope is connected to a monitor outside the persons body, and it is designed to help the surgeon to inspect the infected area in the abdomen. The other two incisions are made for the specific removal of the appendix by using surgical instruments. Laparoscopic surgery requires general anesthesia, and it can last up to two hours. Laparoscopic appendectomy has several advantages over open appendectomy, including a shorter post-operative recovery, less post-operative pain, and lower superficial surgical site infection rate. However, the occurrence of an intra-abdominal abscess is almost three times more prevalent in laparoscopic appendectomy than open appendectomy. Laparoscopic-assisted transumbilical appendectomy In pediatric patients, the high mobility of the cecum allows externalization of the appendix through the umbilicus, and the entire procedure can be performed with a single incision. Laparoscopic-assisted transumbilical appendectomy is a relatively recent technique but with long published series and very good surgical and aesthetic results. Pre-surgery The treatment begins by keeping the person who will be having surgery from eating or drinking for a given period, usually overnight. An intravenous drip is used to hydrate the person who will be having surgery. Antibiotics given intravenously such as cefuroxime and metronidazole may be administered early to help kill bacteria and thus reduce the spread of infection in the abdomen and postoperative complications in the abdomen or wound. Equivocal cases may become more difficult to assess with antibiotic treatment and benefit from serial examinations. If the stomach is empty (no food in the past six hours), general anaesthesia is usually used. Otherwise, spinal anaesthesia may be used. Once the decision to perform an appendectomy has been made, the preparation procedure takes approximately one to two hours. Meanwhile, the surgeon will explain the surgery procedure and will present the risks that must be considered when performing an appendectomy. (With all surgeries there are risks that must be evaluated before performing the procedures.) The risks are different depending on the state of the appendix. If the appendix has not ruptured, the complication rate is only about 3% but if the appendix has ruptured, the complication rate rises to almost 59%. The most usual complications that can occur are pneumonia, hernia of the incision, thrombophlebitis, bleeding and adhesions. Evidence indicates that a delay in obtaining surgery after admission results in no measurable difference in outcomes to the person with appendicitis. The surgeon will explain how long the recovery process should take. Abdomen hair is usually removed to avoid complications that may appear regarding the incision. In most cases, patients going in for surgery experience nausea or vomiting that require medication before surgery. Antibiotics, along with pain medication, may be administered before appendectomies. After surgery Hospital lengths of stay typically range from a few hours to a few days but can be a few weeks if complications occur. The recovery process may vary depending on the severity of the condition: if the appendix had ruptured or not before surgery. Appendix surgery recovery is generally a lot faster if the appendix did not rupture. It is important that people undergoing surgery respect their doctors advice and limit their physical activity so the tissues can heal faster. Recovery after an appendectomy may not require diet changes or a lifestyle change. The length of hospital stays for appendicitis varies on the severity of the condition. A study from the United States found that in 2010, the average appendicitis hospital stay was 1.8 days. For stays where the persons appendix had ruptured, the average length of stay was 5.2 days.After surgery, the patient will be transferred to a postanesthesia care unit, so his or her vital signs can be closely monitored to detect anesthesia- or surgery-related complications. Pain medication may be administered if necessary. After patients are completely awake, they are moved to a hospital room to recover. Most individuals will be offered clear liquids the day after the surgery, then progress to a regular diet when the intestines start to function correctly. Patients are recommended to sit upon the edge of the bed and walk short distances several times a day. Moving is mandatory, and pain medication may be given if necessary. Full recovery from appendectomies takes about four to six weeks but can be prolonged to up to eight weeks if the appendix had ruptured. Prognosis Most people with appendicitis recover quickly after surgical treatment, but complications can occur if treatment is delayed or if peritonitis occurs. Recovery time depends on age, condition, complications, and other circumstances, including the amount of alcohol consumption, but usually is between 10 and 28 days. For young children (around ten years old), the recovery takes three weeks. The possibility of peritonitis is the reason why acute appendicitis warrants rapid evaluation and treatment. People with suspected appendicitis may have to undergo a medical evacuation. Appendectomies have occasionally been performed in emergency conditions (i.e., not in a proper hospital) when a timely medical evacuation was impossible. Typical acute appendicitis responds quickly to appendectomy and occasionally will resolve spontaneously. If appendicitis resolves spontaneously, it remains controversial whether an elective interval appendectomy should be performed to prevent a recurrent episode of appendicitis. Atypical appendicitis (associated with suppurative appendicitis) is more challenging to diagnose and is more apt to be complicated even when operated early. In either condition, prompt diagnosis and appendectomy yield the best results with full recovery in two to four weeks usually. Mortality and severe complications are unusual but do occur, especially if peritonitis persists and is untreated. Another entity known as the appendicular lump is talked about. It happens when the appendix is not removed early during infection, and omentum and intestine adhere to it, forming a palpable lump. During this period, surgery is risky unless there is pus formation evident by fever and toxicity or by USG. Medical management treats the condition. An unusual complication of an appendectomy is "stump appendicitis": inflammation occurs in the remnant appendiceal stump left after a prior incomplete appendectomy. Stump appendicitis can occur months to years after initial appendectomy and can be identified with imaging modalities such as ultrasound. Epidemiology Appendicitis is most common between the ages of 5 and 40. In 2013, it resulted in 72,000 deaths globally, down from 88,000 in 1990.In the United States, there were nearly 293,000 hospitalizations involving appendicitis in 2010. Appendicitis is one of the most frequent diagnoses for emergency department visits resulting in hospitalization among children ages 5–17 years in the United States. See also Deaths from appendicitis Evan ONeill Kane Leonid Rogozov References External links Appendicitis at Curlie CT of the abdomen showing acute appendicitis Appendicitis, history, diagnosis and treatment by Surgeons Net Education Appendicitis: Acute Abdomen and Surgical Gastroenterology from the Merck Manual Professional (content last modified September 2007) Appendicitis – Symptoms Causes and Treatment Archived 2021-02-27 at the Wayback Machine at Health N Surgery

Uterine sarcoma

The uterine sarcomas form a group of malignant tumors that arises from the smooth muscle or connective tissue of the uterus. Signs and symptoms Clinically, uterine sarcomas and leiomyomas (fibroids) both have similar symptoms such as increased uterine size, abdominal pain and vaginal bleeding so it can be difficult to tell them apart. Unusual or postmenopausal bleeding may be a sign of uterine sarcoma and needs to be investigated. Other signs include pelvic pain, pressure, and unusual discharge. A nonpregnant uterus that enlarges quickly is suspicious. However, none of the signs are specific. Specific screening test have not been developed; a Pap smear is a screening test for cervical cancer and not designed to detect uterine sarcoma. Histology Tumoral entities include leiomyosarcomas, endometrial stromal sarcomas, carcinosarcomas and "other" sarcomas. If the lesion originates from the stroma of the uterine lining it is an endometrial stromal sarcoma. If the uterine muscle cell is the originator the tumor is a uterine leiomyosarcoma. Carcinosarcomas comprise both malignant epithelial and malignant sarcomatous components. Diagnosis By using T2*-weighted imaging, MRI is able to differentiate distinguishing features of leiomyomas from uterine sarcomas. Investigations by the physician include imaging (ultrasound, CAT scan, MRI) and, if possible, obtaining a tissue diagnosis by biopsy, hysteroscopy, or D&C. Ultimately the diagnosis is established by the histologic examination of the specimen. Typically malignant lesions have >10 mitosis per high power field. In contrast, a uterine leiomyoma as a benign lesion would have < 5 mitoses per high power field. Classification Leiomyosarcomas are now staged using the 2009 FIGO staging system (previously they were staged like endometrial carcinomas) at the time of surgery. Stage I: tumor is limited to the uterusIA: ≤5 cm in greatest dimension IB: >5 cmStage II: tumor extends beyond the uterus, but within the pelvisIIA: involves adnexa of uterus IIB: involves other pelvic tissuesStage III: tumor infiltrates abdominal tissuesIIIA: 1 site IIIB: >1 site IIIC: regional lymph node metastasisStage IVA: invades bladder or rectum Stage IVB: distant metastasis (including intra-abdominal or inguinal lymph nodes; excluding adnexa, pelvic and abdominal tissues)Endometrial stromal sarcomas and uterine adenosarcomas are classified as above, with the exception of different classifications for Stage I tumors. Stage I: the tumor is limited to the uterusIA: limited to endometrium/endocervix IB: invades <½ myometrium IC: invades ≥½ myometriumFinally, malignant mixed Müllerian tumors, a type of carcinosarcoma, are staged similarly to endometrial carcinomas. Stage I: the tumor is limited to the uterusIA: invades <½ myometrium IB: invades ≥½ myometriumStage II: invades cervical stroma, but no extension beyond the uterus Stage III: local and/or regional spreadIIIA: invades uterine serosa and/or adnexa IIIB: vaginal and/or parametrial involvement IIIC: metastases to pelvic and/or paraaortic lymph nodes IIIC1: positive pelvic nodes IIIC2: positive para-aortic lymph nodesStage IVA: invades bladder and/or bowel mucosa Stage IVB: distant metastases (including intra-abdominal metastases and/or inguinal lymph nodes) Management Therapy is based on staging and patient condition and utilizes one or more of the following approaches. Surgery is the mainstay of therapy if feasible involving total abdominal hysterectomy with bilateral salpingo-oophorectomy. Other approaches include radiation therapy, chemotherapy, and hormonal therapy. Prognosis is relatively poor. Epidemiology Uterine sarcoma is rare, out of all malignancies of the uterine body only about 4% will be uterine sarcomas. Generally, the cause of the lesion is not known, however, patients with a history of pelvic radiation are at higher risk. Most tumors occur after menopause. Women who take long-term tamoxifen are at higher risk. See also Uterine fibroids Leiomyosarcoma References External links Leiomyosarcoma of the Uterus: A Review

Cockayne syndrome

Cockayne syndrome (CS), also called Neill-Dingwall syndrome, is a rare and fatal autosomal recessive neurodegenerative disorder characterized by growth failure, impaired development of the nervous system, abnormal sensitivity to sunlight (photosensitivity), eye disorders and premature aging. Failure to thrive and neurological disorders are criteria for diagnosis, while photosensitivity, hearing loss, eye abnormalities, and cavities are other very common features. Problems with any or all of the internal organs are possible. It is associated with a group of disorders called leukodystrophies, which are conditions characterized by degradation of neurological white matter. The underlying disorder is a defect in a DNA repair mechanism. Unlike other defects of DNA repair, patients with CS are not predisposed to cancer or infection. Cockayne syndrome is a rare but destructive disease usually resulting in death within the first or second decade of life. The mutation of specific genes in Cockayne syndrome is known, but the widespread effects and its relationship with DNA repair is yet to be well understood.It is named after English physician Edward Alfred Cockayne (1880–1956) who first described it in 1936 and re-described in 1946. Neill-Dingwall syndrome was named after Mary M. Dingwall and Catherine A. Neill. These two scientists described the case of two brothers with Cockayne syndrome and asserted it was the same disease described by Cockayne. In their article, the two contributed to the signs of the disease through their discovery of calcifications in the brain. They also compared Cockayne syndrome to what is now known as Hutchinson–Gilford progeria syndrome (HGPS), then called progeria, due to the advanced aging that characterizes both disorders. Types CS Type I, the "classic" form, is characterized by normal fetal growth with the onset of abnormalities in the first two years of life. Vision and hearing gradually decline. The central and peripheral nervous systems progressively degenerate until death in the first or second decade of life as a result of serious neurological degradation. Cortical atrophy is less severe in CS Type I. CS Type II is present from birth (congenital) and is much more severe than CS Type 1. It involves very little neurological development after birth. Death usually occurs by age seven. This specific type has also been designated as cerebro-oculo-facio-skeletal (COFS) syndrome or Pena-Shokeir syndrome Type II. COFS syndrome is named so due to the effects it has on the brain, eyes, face, and skeletal system, as the disease frequently causes brain atrophy, cataracts, loss of fat in the face, and osteoporosis. COFS syndrome can be further subdivided into several conditions (COFS types 1, 2, 3 (associated with xeroderma pigmentosum) and 4). Typically patients with this early-onset form of the disorder show more severe brain damage, including reduced myelination of white matter, and more widespread calcifications, including in the cortex and basal ganglia. CS Type III, characterized by late-onset, is typically milder than Types I and II. Often patients with Type III will live into adulthood. Xeroderma pigmentosum-Cockayne syndrome (XP-CS) occurs when an individual also has xeroderma pigmentosum, another DNA repair disease. Some symptoms of each disease are expressed. For instance, freckling and pigment abnormalities characteristic of XP are present. The neurological disorder, spasticity, and underdevelopment of sexual organs characteristic of CS are seen. However, hypomyelination and the facial features of typical CS patients are not present. Causes If hyperoxia or excess oxygen occurs in the body, the cellular metabolism produces several highly reactive forms of oxygen called free radicals. This can cause oxidative damage to cellular components including the DNA. In normal cells, our body repairs the damaged sections. In the case of this disease, due to subtle defects in transcription, childrens genetic machinery for synthesizing proteins needed by the body does not operate at normal capacity. That is, scientists believed that these childrens genetic machinery for synthesizing proteins needed by the body does not operate at normal capacity. Over time, went this theory, results in developmental failure and death. Every minute, the body pumps 10 to 20 liters of oxygen through the blood, carrying it to billions of cells in our bodies. In its normal molecular form, oxygen is harmless. However, cellular metabolism involving oxygen can generate several highly reactive free radicals. These free radicals can cause oxidative damage to cellular components including the DNA. In an average human cell, several thousand lesions occur in the DNA every day. Many of these lesions result from oxidative damage. Each lesion—a damaged section of DNA—must be snipped out and the DNA repaired to preserve its normal function. Unrepaired DNA can lose its ability to code for proteins. Mutations also can result. These mutations can activate oncogenes or silence tumor suppressor genes. According to research, oxidative damage to active genes is not preferentially repaired, and in the most severe cases, the repair is slowed throughout the whole genome. The resulting accumulation of oxidative damage could impair the normal functions of the DNA and may even result in triggering a program of cell death (apoptosis). The children with this disease do not repair the active genes where oxidative damage occurs. Normally, oxidative damage repair is faster in the active genes (which make up less than five percent of the genome) than in inactive regions of the DNA. The resulting accumulation of oxidative damage could impair the normal functions of the DNA and may even result in triggering a program of cell death (apoptosis). Genetics Cockayne syndrome is classified genetically as follows: Mutations in the ERCC8 (also known as CSA) gene or the ERCC6 (also known as CSB) gene are the cause of Cockayne syndrome. Mutations in the ERCC6 gene mutation makes up ~70% of cases. The proteins made by these genes are involved in repairing damaged DNA via the transcription-coupled repair mechanism, particularly the DNA in active genes. DNA damage is caused by ultraviolet rays from sunlight, radiation, or free radicals in the body. A normal cell can repair DNA damage before it accumulates. If either the ERCC6 or the ERCC8 gene is altered (as in Cockayne Syndrome), DNA damage encountered during transcription isnt repaired, causing RNA polymerase to stall at that location, interfering with gene expression. As the unrepaired DNA damage accumulates, progressively more active gene expression is impeded, leading to malfunctioning cells or cell death, which likely contributes to the signs of Cockayne Syndrome such as premature aging and neuronal hypomyelination. Mechanism In contrast to cells with normal repair capability, CSA and CSB deficient cells are unable to preferentially repair cyclobutane pyrimidine dimers induced by the action of ultraviolet (UV) light on the template strand of actively transcribed genes. This deficiency reflects the loss of ability to perform the DNA repair process known as transcription coupled nucleotide excision repair (TC-NER).Within the damaged cell, the CSA protein normally localizes to sites of DNA damage, particularly inter-strand cross-links, double-strand breaks and some monoadducts. CSB protein is also normally recruited to DNA damaged sites, and its recruitment is most rapid and robust as follows: interstrand crosslinks > double-strand breaks > monoadducts > oxidative damage. CSB protein forms a complex with another DNA repair protein, SNM1A (DCLRE1A), a 5 – 3 exonuclease, that localizes to inter-strand cross-links in a transcription dependent manner. The accumulation of CSB protein at sites of DNA double-strand breaks occurs in a transcription dependent manner and facilitates homologous recombinational repair of the breaks. During the G0/G1 phase of the cell cycle, DNA damage can trigger a CSB-dependent recombinational repair process that uses an RNA (rather than DNA) template.The premature aging features of CS are likely due, at least in part, to the deficiencies in DNA repair (see DNA damage theory of aging). Diagnosis People with this syndrome have smaller than normal head sizes (microcephaly), are of short stature (dwarfism), their eyes appear sunken, and they have an "aged" look. They often have long limbs with joint contractures (inability to relax the muscle at a joint), a hunched back (kyphosis), and they may be very thin (cachetic), due to a loss of subcutaneous fat. Their small chin, large ears, and pointy, thin nose often give an aged appearance. The skin of those with Cockayne syndrome is also frequently affected: hyperpigmentation, varicose or spider veins (telangiectasia), and serious sensitivity to sunlight are common, even in individuals without XP-CS. Often patients with Cockayne Syndrome will severely burn or blister with very little heat exposure. The eyes of patients can be affected in various ways and eye abnormalities are common in CS. Cataracts and cloudiness of the cornea (corneal opacity) are common. The loss of and damage to the nerves of the optic nerve, causing optic atrophy, can occur. Nystagmus, or involuntary eye movement, and pupils that fail to dilate demonstrate a loss of control of voluntary and involuntary muscle movement. A salt and pepper retinal pigmentation is also a typical sign. Diagnosis is determined by a specific test for DNA repair, which measures the recovery of RNA after exposure to UV radiation. Despite being associated with genes involved in nucleotide excision repair (NER), unlike xeroderma pigmentosum, CS is not associated with an increased risk of cancer. Laboratory Studies In Cockayne syndrome patients, UV-irradiated cells show decreased DNA and RNA synthesis. https://emedicine.medscape.com/article/1115866-workup#c5 Laboratory studies are mainly useful to eliminate other disorders. For example, skeletal radiography, endocrinologic tests, and chromosomal breakage studies can help in excluding disorders included in the differential diagnosis. Imaging Studies Brain CT scanning in Cockayne syndrome patients may reveal calcifications and cortical atrophy. Other Tests Prenatal evaluation is possible. Amniotic fluid cell culturing is used to demonstrate that fetal cells are deficient in RNA synthesis after UV irradiation. Neurology Imaging studies reveal a widespread absence of the myelin sheaths of the neurons in the white matter of the brain and general atrophy of the cortex. Calcifications have also been found in the putamen, an area of the forebrain that regulates movements and aids in some forms of learning, along with the cortex. Additionally, atrophy of the central area of the cerebellum found in patients with Cockayne syndrome could also result in the lack of muscle control, particularly involuntary, and poor posture typically seen. Treatment There is no permanent cure for this syndrome, although patients can be symptomatically treated. Treatment usually involves physical therapy and minor surgeries to the affected organs, such as cataract removal. Also wearing high-factor sunscreen and protective clothing is recommended because Cockayne Syndrome patients are very sensitive to UV radiation. Optimal nutrition can also help. Genetic counseling for the parents is recommended, as the disorder has a 25% chance of being passed to any future children, and prenatal testing is also a possibility. Another important aspect is the prevention of recurrence of CS in other siblings. Identification of gene defects involved makes it possible to offer genetic counseling and antenatal diagnostic testing to the parents who already have one affected child. Prognosis The prognosis for those with Cockayne syndrome is poor, as death typically occurs by the age of 12. The prognosis for Cockayne syndrome varies by disease type. There are three types of Cockayne syndrome according to the severity and onset of the symptoms. However, the differences between the types are not always clear-cut, and some researchers believe the signs and symptoms reflect a spectrum instead of distinct types: Cockayne syndrome Type A (CSA) is marked by normal development until a child is 1 or 2 years old, at which point growth slows and developmental delays are noticed. Symptoms are not apparent until they are 1 year. Life expectancy for type A is approximately 10 to 20 years. These symptoms are seen in CS type 1 children. Cockayne syndrome type B (CSB), also known as "cerebro-oculo-facio-skeletal (COFS) syndrome" (or "Pena-Shokeir syndrome type B"), is the most severe subtype. Symptoms are present at birth and normal brain development stops after birth. The average lifespan for children with type B is up to 7 years of age. These symptoms are seen in CS type 2 children. Cockayne syndrome type C (CSC) appears later in childhood with milder symptoms than the other types and a slower progression of the disorder. People with this type of Cockayne syndrome live into adulthood, with an average lifespan of 40 to 50 years. These symptoms are seen in CS type 3. Epidemiology Cockayne syndrome is rare worldwide. No racial predilection is reported for Cockayne syndrome. No sexual predilection is described for Cockayne syndrome; the male-to-female ratio is equal. Cockayne syndrome I (CS-A) manifests in childhood. Cockayne syndrome II (CS-B) manifests at birth or in infancy, and it has a worse prognosis. Recent research The recent research on Jan 2018 mentions different CS features that are seen globally with similarities and differences: CS has an incidence of 1 in 250,000 live births, and a prevalence of approximately 1 per 2.5 million, which is remarkably consistent across various regions globally: See also Accelerated aging disease Biogerontology Degenerative disease Genetic disorder CAMFAK syndrome — thought to be a form (or subset) of Cockayne syndrome References External links This article incorporates some public domain text from The U.S. National Library of Medicine

Craniosynostosis

Craniosynostosis is a condition in which one or more of the fibrous sutures in a young infants skull prematurely fuses by turning into bone (ossification), thereby changing the growth pattern of the skull. Because the skull cannot expand perpendicular to the fused suture, it compensates by growing more in the direction parallel to the closed sutures. Sometimes the resulting growth pattern provides the necessary space for the growing brain, but results in an abnormal head shape and abnormal facial features. In cases in which the compensation does not effectively provide enough space for the growing brain, craniosynostosis results in increased intracranial pressure leading possibly to visual impairment, sleeping impairment, eating difficulties, or an impairment of mental development combined with a significant reduction in IQ.Craniosynostosis occurs in one in 2000 births. Craniosynostosis is part of a syndrome in 15% to 40% of affected patients, but it usually occurs as an isolated condition. The term is from cranio, cranium; + syn, together; + ost, relating to bone; + osis, denoting a condition. Signs and symptoms Children born with craniosynostosis have a distinct phenotype, i.e., appearance—observable traits caused by the expression of a conditions genes. The features of craniosynostosis particular phenotype are determined by which suture is closed. The fusion of this suture causes a certain change in the shape of the skull; a deformity of the skull.Virchows law dictates that, when premature suture closure occurs, growth of the skull typically is restricted perpendicularly to the fused suture and enhanced in a plane parallel to it, thus trying to provide space for the fast-growing brain. Using this law, the pattern of skull deformity in craniosynostosis often may be predicted. Scaphocephaly An illustrative example of this phenomenon is scaphocephaly; the name providing a direct hint regarding the deformity of the skull. The literal meaning of the Greek derived word scaphocephaly is boat-head. A synonymous term is dolichocephaly (the prefix dolicho- means elongated).Premature sagittal suture closure restricts growth in a perpendicular plane, thus the head will not grow sideways and will remain narrow. This is best seen in a view standing above the child looking downward at the top of the head. Compensatory growth occurs forward at the coronal suture and backward at the lambdoid suture giving respectively a prominent forehead, called frontal bossing, and a prominent back portion of the head, called coning. This is the most common form of craniosynostosis. Trigonocephaly Trigonocephaly is a result from the premature closure of the metopic suture. Using Virchows law again to predict the resulting deformity, this fusion will result in a narrow forehead, which is even further emphasized by ridging of the suture. Compensatory growth occurs at both the coronal sutures, thereby pushing the forehead forwards. The resulting shape can best be assessed from a top view again, which will reveal a somewhat triangular form of the head. Trigonocephaly is also a Greek-derived word, which can be translated as triangular-shaped head. A facial feature of metopic synostosis is hypotelorism; in the frontal view, it can be seen that the width between the eyes is smaller than usual. Plagiocephaly The Greek word πλάγιος plágios means "skew". Plagiocephaly can be subclassified as anterior plagiocephaly or posterior plagiocephaly. Anterior plagiocephaly Anterior plagiocephaly is a clinical description of unilateral coronal synostosis. Children born with unilateral coronal synostosis develop due to compensatory mechanisms a skew head; a plagiocephaly.The sagittal suture divides the coronal suture in two halves; unilateral meaning that either the right side or the left side to the sagittal suture is fused. This fact immediately raises an important point. Unlike closure of the sagittal or the metopic suture, right and left are not the same in unilateral coronal synostosis. This asymmetry shows in the skull deformity, as well as in the facial deformity and the complications.This time, the skull deformity can only partly be predicted using Virchows law. Growth is arrested in the plane perpendicular to the fused suture and the forehead is flattened, but only at the ipsilateral side of the head. Ipsilateral indicates the same side of the head as where the suture is closed. Compensatory growth occurs in a parallel plane, as well as in a perpendicular plane. An increase in growth at the metopic and the sagittal suture accounts for the parallel plane and will result in bulging at the temporal fossa. Compensatory growth in the perpendicular plane occurs on the side of the head with the patent coronal suture, the contralateral side. Half of the forehead will bulge forwards. Assessment of the skull from a top view shows asymmetry of the frontal bones, an increased width of the skull and a forward displacement of the ear at the ipsilateral side of the head. Assessment of the skull from a frontal view will show asymmetrical features of the face, including a displacement of the chin point of the jaw and a deviation of the tip of the nose. The chin point is located more to the contralateral side of the head, due to the ipsilateral forward displacement of the temporomandibular joint together with the ear. The tip of the nose will also point towards the contralateral side. Complications based on the skull deformation include malocclusion of the jaw, in as many as 90%; a subtle form of strabismus, caused by the asymmetrical placement of the orbits; and refractive error, particularly astigmatism, due to asymmetrical development of the orbits. Posterior plagiocephaly Unilateral lambdoid synostosis is also called posterior plagiocephaly, indicating that this gives, just like unilateral coronal synostosis, a skew head. The difference is that this time, the deformity mostly shows at the occiput.By Virchows law, restriction of growth will occur at the ipsilateral side of the head; compensatory growth will occur at the contralateral side of the head. This growth pattern exerts an effect at the base of the skull, which is not even when the child is assessed from a point of view standing behind the child, as well as on the cervical spine, which shows a curvature. In addition, from a point of view standing behind the child, a bulging of the mastoid can be seen. Minimal forehead asymmetries are typically seen. Brachycephaly Brachycephaly, or a short head, is the result of a closure of both the coronal sutures. Following Virchows law, this will result in a childs head with a restriction of growth in the forward direction and in the backward direction: recessed frontal bones and a flattened occiput. Compensatory growth will occur sideways, due to the sagittal suture, and upwards, due to the lambdoid sutures. Oxycephaly Oxycephaly, also known as turricephaly and high-head syndrome, is a type of cephalic disorder. This is a term sometimes used to describe the premature closure of the coronal suture plus any other suture, like the lambdoid suture, Pansynostosis The word pansynostosis is also Greek-derived and can be translated as "all one bone", indicating that all of the sutures are closed. In general practice, the term is used to describe the children with three or more cranial sutures closed.Pansynostosis can present in several ways. The appearance can be the same as that seen with primary microcephaly: a markedly small head, but with normal proportions. However, pansynostosis can also appear as a Kleeblattschädel (cloverleaf skull), which presents with bulging of the different bones of the cranial vault.The condition is associated with syndromes caused by mutations in fibroblast growth factor receptor genes (FGFR), including thanatophoric dwarfism type 2 (FGFR3) and Pfeiffer syndrome type 2 (FGFR2). Other craniosynostosis types and their signs Apert syndrome: an abnormal skull shape, small upper jaw, and fusion of the fingers and toes. Crouzon syndrome: Craniofacial abnormalities with bilateral coronal suture fusion; anterior and posterior of skull shortness, flat cheek bones and a flat nose are their features. Muenke syndrome: Coronal craniosynostosis (plagiocephaly and brachycephaly), short feet and palms, hearing impairment, hypertelorism, and proptosis Pfeiffer syndrome: abnormalities of the skull, hands, and feet; wide-set, bulging eyes, an underdeveloped upper jaw, beaked nose. Saethre–Chotzen syndrome: short or broad head; the eyes may be spaced wide apart and have palpebral ptosis (droopy eyelids), and fingers maybe abnormally short and webbed. Complications Not all cranial abnormalities seen in children with craniosynostosis are solely a consequence of the premature fusion of a cranial suture. This is especially true in the cases with syndromic craniosynostosis. Findings include elevation of the intracranial pressure; obstructive sleep apnea (OSA); abnormalities in the skull base and neurobehavioral impairment. Elevated intracranial pressure When the ICP is elevated the following symptomes may occur: vomiting, visual disturbance, bulging of the anterior fontanel, altered mental status, papilledema and headache.The main risks of prolonged elevated intracranial pressure may include cognitive impairment and impaired vision through prolonged papilledema and subsequent optic atrophy. These are the main reasons why fundoscopy should be performed during the physical examination of children with craniosynostosis.The causes of an elevation of the intracranial pressure are best understood using the Monro-Kellie doctrine. The Monro-Kellie doctrine reduces the cranial vault to a box with rigid walls. This box contains three elements: brain, intracranial blood and cerebrospinal fluid. The sum of volumes of these three elements is constant. An increase in one should cause a decrease in one or both of the remaining two, thereby preventing an elevation of the intracranial pressure.A compensatory mechanism involves the movement of cerebrospinal fluid from the cranial vault towards the spinal cord. The volume of blood in the cranial vault is auto-regulated by the brain, and will therefore not decrease that easily.Intracranial pressure will rise as a result of continued brain growth within the rigid skull. It appears that in children with craniosynostosis, the expected decrease of intracranial blood is probably not occurring as it should according to the Monro-Kellie hypothesis. This is shown when the brain expands in the fixed skull, which gives a faster rise in intracranial pressure than would be expected. Obstructive sleep apnea The short stops in breathing during the sleep are the mainstay of OSA. Other symptoms can be difficulty in breathing, snoring, day-time sleepiness and perspiration. The main causative agent of OSA is the [midface hypoplasia], which also poses a risk to the eyes that can be seen bulging out of the eye sockets. Other factors, such as a micrognathism and adenoid hypertrophy, are likely to contribute in causing OSA. The most common syndromic forms of craniosynostosis; i.e. Apert, Crouzon and Pfeiffer, have an increased risk of developing OSA. The children have nearly 50% chance of developing this condition.A theory regarding the involvement of OSA as a causative agent for elevated intracranial pressure suggests an association with the auto-regulation of blood flow in the brain. Certain cells in the brain respond specifically to an increase of CO2 in the blood. The response involves vasodilatation of the cranial vault blood vessels, increasing the volume of one of the elements in the Monro-Kellie doctrine. The increase of CO2 concentration in the blood is a consequence of impaired breathing, especially seen when the child with OSA is sleeping. It is well documented that the highest spikes in intracranial pressure often occur during sleep. Abnormalities in the skull base Impaired venous outflow is often caused by a hypoplastic jugular foramen. This causes an increase in the intracranial blood volume, thereby causing an increase in intracranial pressure.This can be further complicated with a possible Arnold–Chiari malformation, which can partially obstruct the flow of cerebro-spinal fluid from the neurocranium to the spinal cord. The Chiari malformation may be asymptomatic or present with ataxia, spasticity or abnormalities in breathing, swallowing or sleeping.Due to the impaired venous outflow, which may be further complicated with an Arnold–Chiari malformation, there is often a clinical image of hydrocephalus present. Hydrocephalus is seen in 6.5 to 8% of patients with Aperts syndrome, 25.6% in patients with Crouzons syndrome and 27.8% of those with Pfeifers syndrome.Ventriculomegaly is a usual finding in children with the Apert syndrome. Neurobehavioural impairment Neurobehavioural impairment includes problems with attention and planning, processing speed, visual spatial skills, language, reading and spelling. A decreased IQ may also be part of the problems.It has been suggested that these problems are caused by a primary malformation of the brain, rather than being a consequence of the growth restriction of the skull and elevated intracranial pressure. Some evidence for this statement has been provided by studies using computed tomographic (CT) scans and magnetic resonance imaging (MRI) to identify differences between the structures of the brains of healthy children and those affected with craniosynostosis. It has been found that corrective surgery of the cranial vault alters the morphology of the brain compared with the situation before surgical intervention. However the structure was still abnormal in comparison to children without craniosynostosis. Causes Advances in the fields of molecular biology and genetics, as well as the use of animal models have been of great importance in expanding our knowledge of suture fusion. Research in animal models has led to the idea that the dura mater plays an important role in determining closure or patency of the suture. In contrast to the dura mater it appears that the periosteum is not essential in causing closure or patency. Instead of describing the abnormalities in structure and form, research focuses nowadays at decoding the molecular interactions that underlie them. Based on data from quantitative real-time PCR on samples of suture junctions during development, cranial suture fusion in mammals is a tightly orchestrated expression of genes in specific temporal order, leading to endochondral ossification. Despite the progress that has been made, many things are still not understood about the suture biology and the exact causative pathways remain yet to be completely understood.Multiple potential causes of premature suture closure have been identified, such as the several genetic mutations that are associated with syndromic craniosynostosis. The cause of nonsyndromic craniosynostosis however, is still greatly unknown. Most likely, a role is played by biomechanical factors, as well as environmental, hormonal and genetical factors.New insights have given fuel to a debate whether there might be an intrinsic factor causing the premature fusion of the sutures. Brain structures of children with craniosynostosis were evaluated using magnetic resonance imaging. Differences were seen compared with the brain structures of normal children. The question now is whether these differences are caused by the craniosynostosis, or are the cause of craniosynostosis. Biomechanical factors Biomechanical factors include fetal head constraint during pregnancy. It has been found by Jacob et al. that constraint inside the womb is associated with decreased expression of Indian hedgehog protein and noggin. These last two are both important factors influencing bone development. Environmental factors Environmental factors refer for example to maternal smoking and the maternal exposure to amine-containing drugs. Several research groups have found evidence that these environmental factors are responsible for an increase in the risk of craniosynostosis, likely through effects on fibroblast growth factor receptor genes.On the other hand, a recent evaluation of valproic acid (an anti-epilepticum), which has been implicated as a causative agent, has shown no association with craniosynostosis.Certain medication (like amine-containing drugs) can increase the risk of craniosynostosis when taken during pregnancy, these are so-called teratogenic factors. Hormonal factors Hyperthyroid induced craniosynostosis is a hormone mediated premature closure. It is thought that the bone matures faster due to high levels of thyroid hormone. Genetic factors In 6 to 11% of the children born with coronal synostosis, more often involving the bilateral cases than unilateral, other members of the family have been reported that were also born with the same condition. This finding is highly suggestive of a genetic cause, which has possibly been found in the fibroblast growth factor receptor 3 (FGFR3) and TWIST genes.Fibroblast growth factor and fibroblast growth factor receptors regulate fetal bone growth and are expressed in cranial sutures during pregnancy. The transcription factor gene TWIST is thought to decrease the function of FGFR, thus also indirectly regulating fetal bone growth. A relation between the mutations in these genes and craniosynostosis is therefore possible. Moloney et al. observed a FGFR3 mutation in as many as 31% of the cases with nonsyndromic coronal synostosis, thus showing that FGFR abnormalities play an important role in nonsyndromic craniosynostosis.In terms of syndromic craniosynostosis not only do FGFR3 and TWIST genes feature, but also FGFR1 and in particular FGFR2, which has been reported in 90% of the syndromic craniosynostoses such as Apert, Crouzon, Peiffer and Jackson–Weiss. The mutations can be divided into mutations that lead to gain of function (in FGFR genes) and mutations that lead to loss of function (in TWIST genes). Craniosynostosis is therefore likely the result of a disturbance in the fine balance that regulates the multiplication and maturation of the precursor bone cells in the cranial sutures.The familial rate, which is different for nonsyndromic and syndromic cases, provides an important clue. In the nonsyndromic cases, a positive family history is found in 2% of the cases with sagittal suture closure and in 6% to 11% of the cases with coronal suture closure. Cranial sutures The mesenchyme above the meninges undergoes intramembranous ossification forming the neurocranium. The neurocranium consists of several bones, which are united and at the same time separated by fibrous sutures. This allows movement of the separate bones in relation to one another; the infant skull is still malleable. The fibrous sutures specifically allow the deformation of the skull during birth and absorb mechanical forces during childhood They also allow the necessary expansion during brain growth.In the very first years of life the sutures serve as the most important centers of growth in the skull. The growth of the brain and the patency of the sutures depend on each other. Brain growth pushes the two sides of the patent sutures away from each other, thereby enabling growth of the neurocranium. This means that the neurocranium can only grow if the sutures remain open. The neurocranium will not grow when the forces induced by brain growth are not there. This will occur for example when the intracranial pressure drops; the sutures do not experience stretching anymore causing them to fuse. Diagnosis The evaluation of a child suspected to have craniosynostosis is preferentially performed in a craniofacial center. The three main elements of analysis include medical history, physical examination and radiographic analysis.Medical history should in any case include questions about risk factors during pregnancy, the familial rate and the presence of symptoms of elevated intracranial pressure (ICP). Elevated ICP Symptoms of increased intracranial pressure – such as headache and vomiting – should be questioned after. An elevation of ICP can be present in 4 to 20% of the children where only a single suture is affected. The incidence of ICP in children with more than one suture involved can be as high as 62%. However, even though the children are affected, symptoms are not always present. Physical examination Fundoscopy should always be performed in children with craniosynostosis. It is used to find papilledema which is sometimes the only symptom of elevated intracranial pressure shown in these children.Other parts of the physical examination include the measurement of the head circumference, the assessment of the skull deformity and the search for deformities affecting other parts of the body. The head circumference and the growth curve of the head provide important clues into making a differentiation between craniosynostosis, primary microcephaly and hydrocephalus. This differentiation has an important influence on the further treatment of the child.In a recent article Cunningham et al. described several steps in which a pediatrician should observe the patient to assess skull deformity: The first is looking with a birds eye view at the patient while the patient preferably faces the parent while sitting on the parents lap. The goal is to assess the shape of the forehead, the skull length, the width of the skull, position of the ears and the symmetry of the frontal bones and [occiput]. The second is looking at the patient from behind while preferably the child is in the same position as described above. It is important to look at the skull base (to determine whether it is level or not), the position of the ears and to the mastoid (to spot the possible presence of a bulge). The third point of view is the frontal view. The points to look at are: eye position, eye symmetry and twisting of the nasal tip.The implications of the deformities that are seen are extensively discussed under phenotype. Syndromal craniosynostosis presents with a skull deformity as well as deformities affecting other parts of the body. Clinical examination should in any case include evaluation of the neck, spine, digits and toes. Medical imaging Radiographic analysis by performing a computed axial tomographic scan is the gold standard for diagnosing craniosynostosis.Plain radiography of the skull may be sufficient for diagnosing a single suture craniosynostosis and should therefore be performed, but the diagnostic value is outweighed by that of the CT-scan. Not only can the sutures be identified more accurately, thus objectively demonstrating a fused suture, but also evaluation of the brain for structural abnormalities and excluding other causes of asymmetric growth are possible at the same time. In addition to this, CT-scanning can visualize the extent of skull deformity, thereby enabling the surgeon to start planning surgical reconstruction. Classification There are several ways to classify craniosynostosis. For example, one can consider the number of closed sutures. If only one of the four sutures is prematurely closed (single suture craniosynostosis), the craniosynostosis is referred to as simple (or isolated). Whereas when two or more sutures are no longer open, the craniosynostosis is complex. A second classification scheme gives a clinical description of the resulting shape of the skull. This will be further discussed under phenotype. A third classification involves the presence or absence of an identified craniofacial syndrome. Craniosynostosis where no extracranial deformations are present, is called non-syndromic or isolated craniosynostosis. When there are extracranial deformations present, for instance involving the limbs, heart, central nervous system or the respiratory tract, you may speak of a syndromic form of craniosynostosis. More than 180 identified syndromes show deformations due to craniosynostosis. The following syndromes are associated with fibroblast growth factor receptors:In addition, the following syndromes have been identified: Differential diagnosis Deformational plagiocephaly The main difference between plagiocephaly based on craniosynostosis and deformational plagiocephaly is that there is no suture fusion in the latter one. The malleability of the neonatal skull allows the skull to change shape due to extrinsic forces.With the tests a pediatrician should perform, as explained above, the difference is quite easy to make. In deformational plagiocephaly the skull does not show a bulging of the mastoid and in these patients the skull base and position of the ears is level, all in contrary with plagiocephaly due to craniosynostosis. Displacement of one ear to the front is characteristic for deformational plagiocephaly. Primary microcephaly Primary microcephaly shows a clinical image of craniosynostosis, but due to a different cause. The primary failure is the absence of growth of the brain, rendering the sutures of the cranial vault useless. As a consequence, the sutures close, presenting a pansynostosis like image. A differentiation between these two conditions can be made with a computed tomography (CT) scan. The subarachnoid spaces are typically enlarged with primary microcephaly, whereas they are reduced or absent in true pansynostosis. Treatment The primary goal of surgical intervention is to allow normal cranial vault development to occur. This can be achieved by excision of the prematurely fused suture and correction of the associated skull deformities. If the synostosis goes uncorrected, the deformity will progressively worsen not only threatening the aesthetic aspect, but also the functional aspect. This is especially prevalent with asymmetric conditions, such as unilateral coronal synostosis, with compromised function of the eyes and the jaw. In addition, signs of compromised neurodevelopment have been seen amongst all the synostoses, although this may also be caused by primary maldevelopment of the brain and can thus not be prevented by surgical intervention.There are a few basic elements involved in surgical intervention which is aimed at normalization of the cranial vault: Surgery for craniosynostosis is often associated with significant perioperative hemorrhage so multiple strategies are often used to minimize blood loss. One such method involves the injection of vasoconstrictive agents (i.e. epinephrine) seven to ten minutes before scalp incision. Additionally, the initiation of surgery should be delayed until blood products are physically present in the operating room. Another general agreement is the avoidance of the use of titanium plates in the fixation of the skull. One potential complication following this procedure involves the gradual movement of the titanium plates towards the brain, induced by resorption of the innermost bone layer of the skull with deposition of new bone on the outermost layer, thereby integrating the titanium plates. In some cases, the plates have been observed to come into direct contact with the brain. Absorbable plates are now used instead. Timing of surgery The prevention of post-surgical complications, including those mentioned above, plays an important role in discussions over the timing of potential surgery. The general consensus is to perform surgery in late infancy, i.e. between six and twelve months. Within this time frame the efficacy of surgery will be enhanced for several reasons: The bone is still more malleable and can be remodelled relatively simply by greenstick fractures of the bone. At approximately one year of age the bone has become more mineralized and brittle and needs to be attached to the surrounding bone with sutures or an absorbable plate. Reshaping of the cranial vault most commonly means excision of the bones to allow shape adjustment. Replacement of cranial bones can leave gaps which are readily re-ossified before the age of one year, but will need bony filling thereafter.Most surgeons will not intervene until after the age of six months due to the heightened risk which blood loss poses before this age. It is generally preferable to wait until after three months of age when anaesthetic risks will also be decreased.Surgery is not performed in early childhood in every country; in some countries surgical intervention can take place in the late teens.It is important that families seek out a Pediatric Craniofacial Physician who has experience with craniosynostosis for proper diagnosis, surgical care, and followup. Specific sutures Sagittal craniosynostosis/scaphocephaly There are two surgical procedures which are commonly used to treat sagittal synostosis. The matter of which procedure is superior is still heavily debated amongst the surgeons treating this condition, however it is generally agreed upon that the cephalic index should be used to assess the efficacy of the preferred surgical intervention. Firstly, the extended strip craniectomy will be discussed, which is a further developed form of the traditional craniectomy. The traditional procedure involved only the excision of the closed suture, with the intent that the compensatory skull deformations would automatically be corrected by the fast growth of the brain during the first year of life.This did not quite result in a true normalization of the cranial vault, causing the development of numerous modifications. One of those is the extended strip craniectomy. This procedure can be performed by using an endoscope, becoming more popular due to the resultant rapid recovery of the child and reduced need for blood transfusion. The patient is afterwards placed in a custom made molding helmet to correct the resting deformities of the skull. In the other widely used surgical procedure, total cranial vault remodelling, the compensatory deformities are corrected during the operation, with excision of the fused suture. Most of the bones that collectively form the cranial vault – i.e. the frontal, the parietal and the occipital bones – are removed and reshaped to normalize the contours. The bones are then replaced and fixated to form a cranial vault with a normalized shape.Retrospective analysis has given an indication that the use of total cranial vault remodelling provides children with a better cephalic index than does the extended strip craniectomy.An approach that is currently being evaluated involves the use of springs. This intervention is likely most effective when used in the time frame between three and six months of age. Metopic synostosis/trigonocephaly The main elements of metopic suture closure involve a low volume of the anterior cranial fossa, the metopic ridging and hypotelorism. These problems are all addressed during the surgical intervention.The volume is increased by placing the frontal bones and the supraorbital rim further forward. This is done by excision of the bones after which they are reshaped with greenstick fracturing. Replacement of the bones provides a possibility for the correction of the hypotelorism at the same time. A bone graft is placed in between the two halves of the supraorbital bars, thereby increasing the width between the orbits. The metopic ridge can then be corrected with a (simple) burring. Unilateral coronal synostosis/anterior plagiocephaly The treatment of unilateral coronal synostosis is typically performed in two parts: the forward advancement of the supraorbital bar and the correction of the orbital asymmetry.The supraorbital bar is the rim just above the eye socket; as discussed under phenotype, the supraorbital and the frontal bone are typically recessed at the ipsilateral side of the head. The goal of treatment is to position this bar together with the frontal bone in a plane three millimetres further forwards than the vertical plane of the cornea. A two-dimensional sagittal image is used to pre-operatively determine the extent of movement, which can vary between seven and fifteen millimetres depending on the severity of the deformity.The orbital asymmetry exists typically of a narrower and taller orbit at the ipsilateral side of the head. The contralateral orbit, however, is wider than usual. Symmetry is restored by extracting a small piece of bone from the supraorbital bar at the contralateral side, thereby reducing the width. This bone fragment is then introduced into the supraorbital bar on the ipsilateral side, thereby increasing width. The height of the orbit is altered at the ipsilateral side only, by extracting a piece of bone. Any correction of the nasal tip, which points towards the contralateral side, will not be performed during childhood. Unilateral lambdoid synostosis/posterior plagiocephaly An excision of the flattened occipital bone with release of the fused suture tends to correct the cranial vault deformity. Bilateral coronal synostosis/brachycephaly The treatment of bilateral coronal synostosis shows a high degree of overlap with treatment of unilateral coronal synostosis; in both surgical interventions is the forward advancement of the supraorbital rim together with the frontal bones is an important part of the procedure. Again, the plane three millimetres further forwards than the vertical plane of the [cornea] is the appropriate position to place the bone. The increased height of the skull is addressed in the same procedure. Parts of the flattened occiput are extracted and given a rounder shape by greenstick fracturing them. Pansynostosis/kleeblattschädel The treatment of pansynostosis comprises the expansion of the anterior cranial vault, as well as the posterior cranial vault. Whilst this may be accomplished in one procedure it is generally performed in two stages. Complications The most common complications of uncorrected craniosynostosis include increased intracranial pressure, asymmetry of the face, and malocclusion. Asymmetry of the orbits often leads to strabismus. Epidemiology It is estimated that craniosynostosis affects 1 in 1,800 to 3,000 live births worldwide. three out of every four cases affect males. Sagittal synostosis is the most common phenotype, representing 40% to 55% of nonsyndromic cases, whilst coronal synostosis represents between 20% to 25% of cases. Metopic synostosis is a factor in 5% to 15% of cases, and lambdoid synostosis is seen in 0% to 5% of nonsyndromic cases.Five to 15% of the time more than one suture is involved; this is referred to as "complex craniosynostosis" and is typically part of a syndrome. References External links GeneReview/NIH/UW entry on FGFR-Related Craniosynostosis Syndromes Ebenezer, Roy (1960). "Craniostenosis or oxycephaly". Indian Journal of Ophthalmology. 8 (3): 77–80. ISSN 0301-4738. PMID 13819157.

Arthropathy

An arthropathy is a disease of a joint. Types Arthritis is a form of arthropathy that involves inflammation of one or more joints, while the term arthropathy may be used regardless of whether there is inflammation or not. Joint diseases can be classified as follows: ArthritisInfectious arthritisSeptic arthritis (infectious) Tuberculosis arthritis Reactive arthritis (indirectly)Noninfectious arthritisSeronegative spondyloarthropathy:Psoriatic arthritis Ankylosing spondylitisRheumatoid arthritis:Feltys syndromeJuvenile idiopathic arthritis Adult-onset Stills disease Crystal arthropathyGout ChondrocalcinosisOsteoarthritisHemarthrosis (joint bleeding) Synovitis is the medical term for inflammation of the synovial membrane. Joint dislocation With arthropathy in the name Reactive arthropathy (M02-M03) is caused by an infection, but not a direct infection of the synovial space. (See also Reactive arthritis) Enteropathic arthropathy (M07) is caused by colitis and related conditions. Crystal arthropathy (also known as crystal arthritis) (M10-M11) involves the deposition of crystals in the joint. In gout, the crystal is uric acid. In pseudogout/chondrocalcinosis/calcium pyrophosphate deposition disease, the crystal is calcium pyrophosphate. Diabetic arthropathy (M14.2, E10-E14) is caused by diabetes. Neuropathic arthropathy (M14.6) is associated with a loss of sensation.Spondylarthropathy is any form of arthropathy of the vertebral column. Signs and symptoms Joint pain is a common but non-specific sign of joint disease. Signs will depend on the specific disease, and may even then vary. Common signs may include: Decreased range of motion Stiffness Effusion Pneumarthrosis, air in a joint (which is also a common normal finding). Bone erosion Systemic signs of arthritis such as fatigue Diagnosis Diagnosis may be a combination of medical history, physical examination, blood tests and medical imaging (generally X-ray initially). Treatment References == External links ==

Abscess

An abscess is a collection of pus that has built up within the tissue of the body. Signs and symptoms of abscesses include redness, pain, warmth, and swelling. The swelling may feel fluid-filled when pressed. The area of redness often extends beyond the swelling. Carbuncles and boils are types of abscess that often involve hair follicles, with carbuncles being larger.They are usually caused by a bacterial infection. Often many different types of bacteria are involved in a single infection. In many areas of the world, the most common bacteria present is methicillin-resistant Staphylococcus aureus. Rarely, parasites can cause abscesses; this is more common in the developing world. Diagnosis of a skin abscess is usually made based on what it looks like and is confirmed by cutting it open. Ultrasound imaging may be useful in cases in which the diagnosis is not clear. In abscesses around the anus, computer tomography (CT) may be important to look for deeper infection.Standard treatment for most skin or soft tissue abscesses is cutting it open and drainage. There appears to be some benefit from also using antibiotics. A small amount of evidence supports not packing the cavity that remains with gauze after drainage. Closing this cavity right after draining it rather than leaving it open may speed healing without increasing the risk of the abscess returning. Sucking out the pus with a needle is often not sufficient.Skin abscesses are common and have become more common in recent years. Risk factors include intravenous drug use, with rates reported as high as 65% among users. In 2005, in the United States, 3.2 million people went to the emergency department for an abscess. In Australia, around 13,000 people were hospitalized in 2008 with the condition. Signs and symptoms Abscesses may occur in any kind of tissue but most frequently within the skin surface (where they may be superficial pustules known as boils or deep skin abscesses), in the lungs, brain, teeth, kidneys, and tonsils. Major complications may include spreading of the abscess material to adjacent or remote tissues, and extensive regional tissue death (gangrene). The main symptoms and signs of a skin abscess are redness, heat, swelling, pain, and loss of function. There may also be high temperature (fever) and chills. If superficial, abscesses may be fluctuant when palpated; this wave-like motion is caused by movement of the pus inside the abscess.An internal abscess is more difficult to identify, but signs include pain in the affected area, a high temperature, and generally feeling unwell. Internal abscesses rarely heal themselves, so prompt medical attention is indicated if such an abscess is suspected. An abscess can potentially be fatal depending on where it is located. Causes Risk factors for abscess formation include intravenous drug use. Another possible risk factor is a prior history of disc herniation or other spinal abnormality, though this has not been proven. Abscesses are caused by bacterial infection, parasites, or foreign substances. Bacterial infection is the most common cause, particularly Staphylococcus aureus. The more invasive methicillin-resistant Staphylococcus aureus (MRSA) may also be a source of infection, though is much rarer. Among spinal subdural abscesses, methicillin-sensitive Staphylococcus aureus is the most common organism involved.Rarely parasites can cause abscesses and this is more common in the developing world. Specific parasites known to do this include dracunculiasis and myiasis. Perianal abscess Surgery of the anal fistula to drain an abscess treats the fistula and reduces likelihood of its recurrence and the need for repeated surgery. There is no evidence that fecal incontinence is a consequence of this surgery for abscess drainage.Perianal abscesses can be seen in people with, for example, inflammatory bowel disease (such as Crohns disease) or diabetes. Often the abscess will start as an internal wound caused by ulceration, hard stool, or penetrative objects with insufficient lubrication. This wound typically becomes infected as a result of the normal presence of feces in the rectal area, and then develops into an abscess. This often presents itself as a lump of tissue near the anus which grows larger and more painful with time. Like other abscesses, perianal abscesses may require prompt medical treatment, such as an incision and debridement or lancing. Incisional abscess An incisional abscess is one that develops as a complication secondary to a surgical incision. It presents as redness and warmth at the margins of the incision with purulent drainage from it. If the diagnosis is uncertain, the wound should be aspirated with a needle, with aspiration of pus confirming the diagnosis and availing for Gram stain and bacterial culture. Pathophysiology An abscess is a defensive reaction of the tissue to prevent the spread of infectious materials to other parts of the body. The organisms or foreign materials kill the local cells, resulting in the release of cytokines. The cytokines trigger an inflammatory response, which draws large numbers of white blood cells to the area and increases the regional blood flow. The final structure of the abscess is an abscess wall, or capsule, that is formed by the adjacent healthy cells in an attempt to keep the pus from infecting neighboring structures. However, such encapsulation tends to prevent immune cells from attacking bacteria in the pus, or from reaching the causative organism or foreign object. Diagnosis An abscess is a localized collection of pus (purulent inflammatory tissue) caused by suppuration buried in a tissue, an organ, or a confined space, lined by the pyogenic membrane. Ultrasound imaging can help in a diagnosis. Classification Abscesses may be classified as either skin abscesses or internal abscesses. Skin abscesses are common; internal abscesses tend to be harder to diagnose, and more serious. Skin abscesses are also called cutaneous or subcutaneous abscesses. IV drug use For those with a history of intravenous drug use, an X-ray is recommended before treatment to verify that no needle fragments are present. If there is also a fever present in this population, infectious endocarditis should be considered. Differential Abscesses should be differentiated from empyemas, which are accumulations of pus in a preexisting, rather than a newly formed, anatomical cavity. Other conditions that can cause similar symptoms include: cellulitis, a sebaceous cyst, and necrotising fasciitis. Cellulitis typically also has an erythematous reaction, but does not confer any purulent drainage. Treatment The standard treatment for an uncomplicated skin or soft tissue abscess is the act of opening and draining. There does not appear to be any benefit from also using antibiotics in most cases. A small amount of evidence did not find a benefit from packing the abscess with gauze. Incision and drainage The abscess should be inspected to identify if foreign objects are a cause, which may require their removal. If foreign objects are not the cause, incising and draining the abscess is standard treatment.In critical areas where surgery presents a high risk, it may be delayed or used as a last resort. The drainage of a lung abscess may be performed by positioning the affected individual in a way that enables the contents to be discharged via the respiratory tract. Warm compresses and elevation of the limb may be beneficial for a skin abscess. Antibiotics Most people who have an uncomplicated skin abscess should not use antibiotics. Antibiotics in addition to standard incision and drainage is recommended in persons with severe abscesses, many sites of infection, rapid disease progression, the presence of cellulitis, symptoms indicating bacterial illness throughout the body, or a health condition causing immunosuppression. People who are very young or very old may also need antibiotics. If the abscess does not heal only with incision and drainage, or if the abscess is in a place that is difficult to drain such as the face, hands, or genitals, then antibiotics may be indicated.In those cases of abscess which do require antibiotic treatment, Staphylococcus aureus bacteria is a common cause and an anti-staphylococcus antibiotic such as flucloxacillin or dicloxacillin is used. The Infectious Diseases Society of America advises that the draining of an abscess is not enough to address community-acquired methicillin-resistant Staphylococcus aureus (MRSA), and in those cases, traditional antibiotics may be ineffective. Alternative antibiotics effective against community-acquired MRSA often include clindamycin, doxycycline, minocycline, and trimethoprim-sulfamethoxazole. The American College of Emergency Physicians advises that typical cases of abscess from MRSA get no benefit from having antibiotic treatment in addition to the standard treatment. If the condition is thought to be cellulitis rather than an abscess, consideration should be given to the possibility of the strep species as a cause, that are still sensitive to traditional anti-staphylococcus agents such as dicloxacillin or cephalexin. This would be in the case of people that are able to tolerate penicillin. Antibiotic therapy alone without surgical drainage of the abscess is seldom effective due to antibiotics often being unable to get into the abscess and their ineffectiveness at low pH levels. Culturing the wound is not needed if standard follow-up care can be provided after the incision and drainage. Performing a wound culture is unnecessary because it rarely gives information which can be used to guide treatment. Packing In North America, after drainage, an abscess cavity is usually packed, often with special iodoform-treated cloth. This is done to absorb and neutralize any remaining exudate as well as to promote draining and prevent premature closure. Prolonged draining is thought to promote healing. The hypothesis is that though the hearts pumping action can deliver immune and regenerative cells to the edge of an injury, an abscess is by definition a void in which no blood vessels are present. Packing is thought to provide a wicking action that continuously draws beneficial factors and cells from the body into the void that must be healed. Discharge is then absorbed by cutaneous bandages and further wicking promoted by changing these bandages regularly. However, evidence from emergency medicine literature reports that packing wounds after draining, especially smaller wounds, causes pain to the person and does not decrease the rate of recurrence, nor bring faster healing, or fewer physician visits. Loop drainage More recently, several North American hospitals have opted for less-invasive loop drainage over standard drainage and wound packing. In one study of 143 pediatric outcomes, a failure rate of 1.4% was reported in the loop group versus 10.5% in the packing group (P<.030), while a separate study reported a 5.5% failure rate among the loop group. Primary closure Closing an abscess immediately after draining it appears to speed healing without increasing the risk of recurrence. This may not apply to anorectal abscesses as while they may heal faster, there may be a higher rate of recurrence than those left open. Prognosis Even without treatment, skin abscesses rarely result in death, as they will naturally break through the skin. Other types of abscess are more dangerous. Brain abscesses are fatal if untreated. When treated, the mortality rate reduces to 5–10%, but is higher if the abscess ruptures. Epidemiology Skin abscesses are common and have become more common in recent years. Risk factors include intravenous drug use, with rates reported as high as 65% among users. In 2005, in the United States 3.2 million people went to the emergency department for an abscess. In Australia around 13,000 people were hospitalized in 2008 for the disease. Society and culture The Latin medical aphorism "ubi pus, ibi evacua" expresses "where there is pus, there evacuate it" and is classical advice in the culture of Western medicine. Needle exchange programmes often administer or provide referrals for abscess treatment to injection drug users as part of a harm reduction public health strategy. Etymology An abscess is so called "abscess" because there is an abscessus (a going away or departure) of portions of the animal tissue from each other to make room for the suppurated matter lodged between them.The word carbuncle is believed to have originated from the Latin: carbunculus, originally a small coal; diminutive of carbon-, carbo: charcoal or ember, but also a carbuncle stone, "precious stones of a red or fiery colour", usually garnets. Other types The following types of abscess are listed in the medical dictionary: References External links MedlinePlus Encyclopedia: Abscess MedlinePlus Encyclopedia: Skin Abscess "Abscess" . Colliers New Encyclopedia. 1921. "Abscess" . Encyclopædia Britannica (11th ed.). 1911. "Abscess". MedlinePlus. U.S. National Library of Medicine.

Black eye

A periorbital hematoma, commonly called a black eye or "a shiner" (associated with boxing or stick sports such as hockey), is bruising around the eye commonly due to an injury to the face rather than to the eye. The name refers to the dark-colored bruising which is the result of accumulated blood and fluid in the loose areolar tissue following a blow to the head. This blood tracks freely under the scalp producing a generalised swelling over the dome of the skull but cannot pass into either occipital or the temple regions because of the bony attachments of the occipitofrontalis muscle. But this fluid can, however, track forward into the eyelid because the occipitofrontalis muscle has no bony attachment anteriorly. This leads to formation of hematoma a few hours after the head injury or cranial operation. If injury is more extensive, potentially even a skull fracture, an apparent black eye can sometimes worsen and may require professional medical treatment before it will resolve. This is more likely if the area around both eyes has been injured (raccoon eyes) or if there is a history of prior head injury or fracture around the eye. Though disfiguring, the vast majority of black eyes are not serious, require little or no treatment, and will resolve spontaneously within a week or two. Bleeding within the eye, a condition called a hyphema, is more serious: it can permanently reduce vision and can damage the cornea. In some cases, abnormally high pressure inside the eyeball (ocular hypertension) can also result. Signs and symptoms Despite the name, the eye itself is not affected. Blunt force or trauma to the eye socket results in burst capillaries and subsequent haemorrhaging (hematoma). The fatty tissue along with the lack of muscle around the eye socket allows a potential space for blood accumulation. As this blood decomposes and is resorbed, various pigments are released lending itself to the extreme outward appearance.The appearance (discoloration in purple and blue along with swelling) does not usually indicate a serious injury, and most black eyes resolve within a week. The tissues around the eye are soft and thus bruise easily when compressed against margins of bone which surround and protect the eye socket. The treatment is the same as that for bruises in other parts of the body – cold compresses during the first twenty-four hours. During the process of healing, and so long as there no breaks in the skin, a black eye can be made less conspicuous by using cosmetics designed to obscure discolorations of the skin. In a severe contusion, blowout of the floor of the orbit may occur, leading to double vision. Such an injury may require surgical correction. Treatment Unless there is actual trauma to the eye itself (see below), extensive medical attention is generally not needed.Applying an ice pack will keep down swelling and reduce internal bleeding by constricting the capillaries. Analgesic drugs (painkillers) can be administered to relieve pain.An anecdotal remedy for a black eye consists of applying raw meat to the eye area. Research has yet to find any evidence of this treatment being effective. Likely the raw meat was used when ice packs were not yet commercially available and meat was stored in iceboxes instead of in a protective gas. While cold but not freezing, meat is more gentle to the skin than ice and will not damage the surface of the skin as the skin temperature cannot go below freezing even in extreme cases. Meat is also soft and comes easier into contact with the skin than blocks of ice that were available. Associated conditions Eye injury and head trauma may also coincide with a black eye. Some common signs of a more serious injury may include: Double vision Loss of sight and/or fuzzy vision could occur Loss of consciousness Inability to move the eye or large swelling around the eye Blood or clear fluid from the nose or the ears Blood on the surface of the eye itself or cuts on the eye itself Persistent headache or migraine References == External links ==

Hypoactive sexual desire disorder

Hypoactive sexual desire disorder (HSDD), hyposexuality or inhibited sexual desire (ISD) is sometimes considered a sexual dysfunction, and is characterized as a lack or absence of sexual fantasies and desire for sexual activity, as judged by a clinician. For this to be regarded as a disorder, it must cause marked distress or interpersonal difficulties and not be better accounted for by another mental disorder, a drug (legal or illegal), or some other medical condition. A person with ISD will not start, or respond to their partners desire for, sexual activity. HSDD affects approximately 10% of all pre-menopausal women in the United States, or about 6 million women.There are various subtypes. HSDD can be general (general lack of sexual desire) or situational (still has sexual desire, but lacks sexual desire for current partner), and it can be acquired (HSDD started after a period of normal sexual functioning) or lifelong (the person has always had no/low sexual desire.) In the DSM-5, HSDD was split into male hypoactive sexual desire disorder and female sexual interest/arousal disorder. It was first included in the DSM-III under the name inhibited sexual desire disorder, but the name was changed in the DSM-III-R. Other terms used to describe the phenomenon include sexual aversion and sexual apathy. More informal or colloquial terms are frigidity and frigidness. Causes Low sexual desire alone is not equivalent to HSDD because of the requirement in HSDD that the low sexual desire causes marked distress and interpersonal difficulty and because of the requirement that the low desire is not better accounted for by another disorder in the DSM or by a general medical problem. It is therefore difficult to say exactly what causes HSDD. It is easier to describe, instead, some of the causes of low sexual desire.In men, though there are theoretically more types of HSDD/low sexual desire, typically men are only diagnosed with one of three subtypes. Lifelong/generalised: The man has little or no desire for sexual stimulation (with a partner or alone) and never had. Acquired/generalised: The man previously had sexual interest in his present partner, but lacks interest in sexual activity, partnered or solitary. Acquired/situational: The man was previously sexually interested in his present partner but now lacks sexual interest in this partner but has desire for sexual stimulation (i.e. alone or with someone other than his present partner.)Though it can sometimes be difficult to distinguish between these types, they do not necessarily have the same cause. The cause of lifelong/generalized HSDD is unknown. In the case of acquired/generalized low sexual desire, possible causes include various medical/health problems, psychiatric problems, low levels of testosterone or high levels of prolactin. One theory suggests that sexual desire is controlled by a balance between inhibitory and excitatory factors. This is thought to be expressed via neurotransmitters in selective brain areas. A decrease in sexual desire may therefore be due to an imbalance between neurotransmitters with excitatory activity like dopamine and norepinephrine and neurotransmitters with inhibitory activity, like serotonin. Low sexual desire can also be a side effect of various medications. In the case of acquired/situational HSDD, possible causes include intimacy difficulty, relationship problems, sexual addiction, and chronic illness of the mans partner. The evidence for these is somewhat in question. Some claimed causes of low sexual desire are based on empirical evidence. However, some are based merely on clinical observation. In many cases, the cause of HSDD is simply unknown.Some factors are believed to be possible causes of HSDD in women. As with men, various medical problems, psychiatric problems (such as mood disorders), or increased amounts of prolactin can cause HSDD. Other hormones are believed to be involved as well. Additionally, factors such as relationship problems or stress are believed to be possible causes of reduced sexual desire in women. According to one recent study examining the affective responses and attentional capture of sexual stimuli in women with and without HSDD, women with HSDD do not appear to have a negative association to sexual stimuli, but rather a weaker positive association than women without HSDD. Diagnosis In the DSM-5, male hypoactive sexual desire disorder is characterized by "persistently or recurrently deficient (or absent) sexual/erotic thoughts or fantasies and desire for sexual activity", as judged by a clinician with consideration for the patients age and cultural context. Female sexual interest/arousal disorder is defined as a "lack of, or significantly reduced, sexual interest/arousal", manifesting as at least three of the following symptoms: no or little interest in sexual activity, no or few sexual thoughts, no or few attempts to initiate sexual activity or respond to partners initiation, no or little sexual pleasure/excitement in 75–100% of sexual experiences, no or little sexual interest in internal or external erotic stimuli, and no or few genital/nongenital sensations in 75–100% of sexual experiences.For both diagnoses, symptoms must persist for at least six months, cause clinically significant distress, and not be better explained by another condition. Simply having lower desire than ones partner is not sufficient for a diagnosis. Self-identification of a lifelong lack of sexual desire as asexuality precludes diagnosis. Treatment Counseling HSDD, like many sexual dysfunctions, is something that people are treated for in the context of a relationship. Theoretically, one could be diagnosed with and treated for HSDD without being in a relationship. However, relationship status is the most predictive factor accounting for distress in women with low desire and distress is required for a diagnosis of HSDD. Therefore, it is common for both partners to be involved in therapy. Typically, the therapist tries to find a psychological or biological cause of the HSDD. If the HSDD is organically caused, the clinician may try to treat it. If the clinician believes it is rooted in a psychological problem, he or she may recommend therapy. If not, treatment generally focuses more on relationship and communication issues, improved communication (verbal and nonverbal), working on non-sexual intimacy, or education about sexuality may all be possible parts of treatment. Sometimes problems occur because people have unrealistic perceptions about what normal sexuality is and are concerned that they do not compare well to that, and this is one reason why education can be important. If the clinician thinks that part of the problem is a result of stress, techniques may be recommended to more effectively deal with that. Also, it can be important to understand why the low level of sexual desire is a problem for the relationship because the two partners may associate different meanings with sex but not know it.In the case of men, the therapy may depend on the subtype of HSDD. Increasing the level of sexual desire of a man with lifelong/generalized HSDD is unlikely. Instead, the focus may be on helping the couple to adapt. In the case of acquired/generalized, it is likely that there is some biological reason the clinician can address. In the case of acquired/situational, some form of psychotherapy may be used, possibly with the man alone and possibly together with his partner. Medication Approved Flibanserin was the first medication approved by FDA for the treatment of HSDD in pre-menopausal women. Its approval was controversial and a systematic review found its benefits to be marginal. The only other medication approved in the US for HSDD in pre-menopausal women is bremelanotide, in 2019. Off-label A few studies suggest that the antidepressant, bupropion, can improve sexual function in women who are not depressed, if they have HSDD. The same is true for the anxiolytic, buspirone, which is a 5-HT1A receptor agonist similarly to flibanserin.Testosterone supplementation is effective in the short term. However, its long-term safety is unclear. History The term "frigid" to describe sexual dysfunction derives from medieval and early modern canonical texts about witchcraft. It was thought that witches could put spells on men to make them incapable of erections. Only in the early nineteenth century were women first described as "frigid", and a vast literature exists on what was considered a serious problem if a woman did not desire sex with her husband. Many medical texts between 1800 and 1930 focused on womens frigidity, considering it a sexual pathology.The French psychoanalyst Princess Marie Bonaparte theorized about frigidity and considered herself to have it. In the early versions of the DSM, there were only two sexual dysfunctions listed: frigidity (for women) and impotence (for men). In 1970, Masters and Johnson published their book Human Sexual Inadequacy describing sexual dysfunctions, though these included only dysfunctions dealing with the function of genitals such as premature ejaculation and impotence for men, and anorgasmia and vaginismus for women. Prior to Masters and Johnsons research, female orgasm was assumed by some to originate primarily from vaginal, rather than clitoral, stimulation. Consequently, feminists have argued that "frigidity" was "defined by men as the failure of women to have vaginal orgasms".Following this book, sex therapy increased throughout the 1970s. Reports from sex-therapists about people with low sexual desire are reported from at least 1972, but labeling this as a specific disorder did not occur until 1977. In that year, sex therapists Helen Singer Kaplan and Harold Lief independently of each other proposed creating a specific category for people with low or no sexual desire. Lief named it "inhibited sexual desire", and Kaplan named it "hypoactive sexual desire". The primary motivation for this was that previous models for sex therapy assumed certain levels of sexual interest in ones partner and that problems were only caused by abnormal functioning/non-functioning of the genitals or performance anxiety but that therapies based on those problems were ineffective for people who did not sexually desire their partner. The following year, 1978, Lief and Kaplan together made a proposal to the APAs taskforce for sexual disorders for the DSM III, of which Kaplan and Lief were both members. The diagnosis of Inhibited Sexual Desire (ISD) was added to the DSM when the 3rd edition was published in 1980.For understanding this diagnosis, it is important to recognize the social context in which it was created. In some cultures, low sexual desire may be considered normal, and high sexual desire conversely problematic. For example, sexual desire may be lower in East Asian populations than Euro-Canadian/American populations. In other cultures, this may be reversed. Some cultures try hard to restrain sexual desire. Others try to excite it. Concepts of "normal" levels of sexual desire are culturally dependent and rarely value-neutral. In the 1970s, there were strong cultural messages that sex is good for you and "the more the better". Within this context, people who were habitually uninterested in sex, who in previous times may not have seen this as a problem, were more likely to feel that this was a situation that needed to be fixed. They may have felt alienated by dominant messages about sexuality and increasingly people went to sex-therapists complaining of low sexual desire. It was within this context that the diagnosis of ISD was created.In the revision of the DSM-III, published in 1987 (DSM-III-R), ISD was subdivided into two categories: Hypoactive Sexual Desire Disorder and Sexual Aversion Disorder (SAD). The former is a lack of interest in sex and the latter is a phobic aversion to sex. In addition to this subdivision, one reason for the change is that the committee involved in revising the psychosexual disorders for the DSM-III-R thought that the term "inhibited" suggests psychodynamic cause (i.e., that the conditions for sexual desire are present, but the person is, for some reason, inhibiting their own sexual interest). The term "hypoactive sexual desire" is more awkward, but more neutral with respect to the cause. The DSM-III-R estimated that about 20% of the population had HSDD. In the DSM-IV (1994), the criterion that the diagnosis requires "marked distress or interpersonal difficulty" was added.The DSM-5, published in 2013, split HSDD into male hypoactive sexual desire disorder and female sexual interest/arousal disorder. The distinction was made because men report more intense and frequent sexual desire than women. According to Lori Brotto, this classification is desirable compared to the DSM-IV classification system because: (1) it reflects the finding that desire and arousal tend to overlap (2) it differentiates between women who lack desire before the onset of activity, but who are receptive to initiation and or initiate sexual activity for reasons other than desire, and women who never experience sexual arousal (3) it takes the variability in sexual desire into account. Furthermore, the criterion that 6 symptoms be present for a diagnosis helps safeguard against pathologizing adaptive decreases in desire. Criticism General HSDD, as currently defined by the DSM, has come under criticism of the social function of the diagnosis. HSDD could be seen as part of a history of the medicalization of sexuality by the medical profession to define normal sexuality. It has also been examined within a "broader frame of historical interest in the problematization of sexual appetite". HSDD has been criticized over pathologizing normal variations in sexuality because the parameters of normality are unclear. This lack of clarity is partly due to the fact that the terms "persistent" and "recurrent" do not have clear operational definitions. HSDD may function to pathologize asexuals, though their lack of sexual desire may not be maladaptive. Because of this, some members of the asexual community lobbied the mental health community working on the DSM-5 to regard asexuality as a legitimate sexual orientation rather than a mental disorder.Other criticisms focus more on scientific and clinical issues. HSDD is such a diverse group of conditions with many causes that it functions as little more than a starting place for clinicians to assess people. The requirement that low sexual desire causes distress or interpersonal difficulty has been criticized. It has been claimed that it is not clinically useful because if it is not causing any problems, the person will not seek out a clinician. One could claim that this criterion (for all of the sexual dysfunctions, including HSDD) decreases the scientific validity of the diagnoses or is a cover-up for a lack of data on what constitutes normal sexual function. The distress requirement is also criticized because the term "distress" lacks a clear definition. NICE (UK) assessment Hypoactive sexual desire disorder is not recognized as a disorder by the National Institute for Health and Care Excellence for the British National Health Service, with the judgement based on an article in the Journal of Medical Ethics that "Hypoactive sexual desire disorder is a typical example of a condition that was sponsored by industry to prepare the market for a specific treatment". DSM-IV criteria Prior to the publication of the DSM-5, the DSM-IV criteria were criticized on several grounds. It was suggested that a duration criterion should be added because lack of interest in sex over the past month is significantly more common than lack of interest lasting six months. Similarly, a frequency criterion (i.e., the symptoms of low desire be present in 75% or more of sexual encounters) has been suggested.The current framework for HSDD is based on a linear model of human sexual response, developed by Masters and Johnson and modified by Kaplan consisting of desire, arousal, orgasm. The sexual dysfunctions in the DSM are based around problems at any one or more of these stages. Many of the criticisms of the DSM-IV framework for sexual dysfunction in general, and HSDD in particular, claimed that this model ignored the differences between male and female sexuality. Several criticisms were based on the inadequacy of the DSM-IV framework for dealing with females sexual problems. Increasingly, evidence shows that there are significant differences between male and female sexuality. Level of desire is highly variable from female to female and there are some females who are considered sexually functional who have no active desire for sex, but they can erotically respond well in contexts they find acceptable. This has been termed "responsive desire" as opposed to spontaneous desire. The focus on merely the physiological ignores the social, economic and political factors including sexual violence and lack of access to sexual medicine or education throughout the world affecting females and their sexual health. The focus on the physiological ignores the relationship context of sexuality despite the fact that this is often the cause of sexual problems. The focus on discrepancy in desire between two partners may result in the partner with the lower level of desire being labeled as "dysfunctional," but the problem really sits with the difference between the two partners. However, within couples the assessment of desire tends to be relative. That is, individuals make judgments by comparing their levels of desire to that of their partner. The sexual problems that females complain of often do not fit well into the DSM-IV framework for sexual dysfunctions. The DSM-IV system of sub-typing may be more applicable to one sex than the other. Research indicates a high degree of comorbidity between HSDD and female sexual arousal disorder. Therefore, a diagnosis combining the two (as the DSM-5 eventually did) might be more appropriate. See also Drugs and sexual desire HypersexualityAsexuality Sexual anhedonia Sexual anorexia Sexual arousal disorder References Further reading Cryle, Peter; Moore, Alison (2011). Frigidity: An Intellectual History. Basingstoke: Palgrave Macmillan. ISBN 978-0-230-30345-4. Cryle, Peter; Moore, Alison (May 2010). "Frigidity at the Fin-de-Siècle, a Slippery and Capacious Concept". Journal of the History of Sexuality. 19 (2): 243–61. doi:10.1353/sex.0.0096. PMID 20617591. S2CID 40019141. Moore, Alison (November 2009). "Frigidity, Gender and Power in French Cultural History – From Jean Fauconney to Marie Bonaparte". French Cultural Studies. 20 (4): 331–49. doi:10.1177/0957155809344155. S2CID 145773398. Moore, Alison (2009). "The Invention of the Unsexual: Situating Frigidity in the History of Sexuality and in Feminist Thought". French History and Civilization. 2: 181–92. Montgomery, KA (Jun 2008). "Sexual Desire Disorders". Psychiatry (Edgmont). 5 (6): 50–55. PMC 2695750. PMID 19727285. Basson, R; Leiblum, S; Brotto, L; et al. (December 2003). "Definitions of womens sexual dysfunction reconsidered: advocating expansion and revision". Journal of Psychosomatic Obstetrics and Gynaecology. 24 (4): 221–9. doi:10.3109/01674820309074686. PMID 14702882. S2CID 4780569. Warnock, JJ (2002). "Female hypoactive sexual desire disorder: epidemiology, diagnosis and treatment". CNS Drugs. 16 (11): 745–53. doi:10.2165/00023210-200216110-00003. PMID 12383030. S2CID 24669452. Basson, R (10 May 2005). "Womens sexual dysfunction: revised and expanded definitions". Canadian Medical Association Journal. Canadian Medical Association. 172 (10): 1327–1333. doi:10.1503/cmaj.1020174. PMC 557105. PMID 15883409. Nappi, RE; Wawra, K; Schmitt, S (Jun 2006). "Hypoactive sexual desire disorder in postmenopausal women". Gynecological Endocrinology. 22 (6): 318–23. doi:10.1080/09513590600762265. PMID 16785156. S2CID 24526712. == External links ==

Ileitis

Ileitis is an inflammation of the ileum, a portion of the small intestine. Crohns ileitis is a type of Crohns disease affecting the ileum. Ileitis is caused by the bacterium Lawsonia intracellularis. Inflammatory bowel disease does not associate with Lawsonia intracellularis infection. References == External links ==

Shake

Shake may refer to: Handshake Milkshake Tremor Shakes (wood), cracks in timber Shake (shingle), a wooden shingle made from split logsShake, The Shakes, Shaking, or Shakin may refer to: Geography Shake, Zimbabwe Shake, another name for Sake language, used in parts of Gabon People Shakin Stevens, Welsh rock and roll singer Anthony "Shake" Shakir, Detroit techno producer Master Shake, a character in Aqua Teen Hunger Force Shake (singer) (Sheikh Abdullah Ahmad), Malaysian singer Shaking, a stage name of Xie Keyin, Chinese singer, rapper and songwriter Malik "Shake" Milton, American basketball player Music Shake (music) (more commonly known as a trill), a musical ornament The Shake (dance), a fad dance of the 1960s The Shake (American rock band) Albums Shake (The Thing album) (2015) Shake (John Schlitt album) (1995) Shake! (album) (1968), by the Siegel–Schwall Band Shake (2001), by Zucchero Fornaciari Shakin (album), 1986 work by country music group Sawyer Brown The Shake (Laurie Johnson), an LP by Laurie Johnson, the base of what is now known as "The Avengers Theme" Songs "Shake" (Sam Cooke song) (1964), notably covered by Otis Redding "Shake!" (The Time song) (1990) "Shake" (EliZe song) (2004) "Shake" (Ying Yang Twins song) (2005) "Shake" (Jesse McCartney song) (2010) "Shake" (Little Boots song) (2011) "Shake" (Flavour Nabania song) (2012) "Shake" (CNBLUE song) (2017) "Shake" (1981), by GQ "Shake" (1993), from the album Concentration by Machines of Loving Grace "Shake" (1999), by Double "Shake" (2009), by Chae Yeon "Shake" (2009), from The Alesha Show: The Encore by Alesha Dixon "Shake" (2013), by Victoria Justice "Shake" (2013), from Lets Be Still by The Head and the Heart Shakin (Eddie Money song) Shakin (Sawyer Brown song) "Shakin", a song on the 2000 album Thirteen Tales from Urban Bohemia by The Dandy Warhols "The Shake" (Kisschasy song) "The Shake" (Neal McCoy song) Other Camera shake, an effect fixed with image stabilization Shake (company), a legal document startup Shake (software), an image-compositing package produced by Apple Inc Shake (unit), an informal unit of time equal to ten nanoseconds SHAKE algorithm, a time integration algorithm for molecular dynamics simulation See also Earthquake The Shake (disambiguation) Shake It (disambiguation) Shaked (surname) Shaken (disambiguation) Shaker (disambiguation) Shakes (disambiguation) Shock (disambiguation) Shook (disambiguation) All pages with titles beginning with Shake All pages with titles containing Shake

Postpartum bleeding

Postpartum bleeding or postpartum hemorrhage (PPH) is often defined as the loss of more than 500 ml or 1,000 ml of blood following childbirth. Some have added the requirement that there also be signs or symptoms of low blood volume for the condition to exist. Signs and symptoms may initially include: an increased heart rate, feeling faint upon standing, and an increased breathing rate. As more blood is lost, the patient may feel cold, blood pressure may drop, and they may become restless or unconscious. The condition can occur up to six weeks following delivery.The most common cause is poor contraction of the uterus following childbirth. Not all of the placenta being delivered, a tear of the uterus, or poor blood clotting are other possible causes. It occurs more commonly in those who: already have a low amount of red blood, are Asian, with bigger or more than one baby, are obese or are older than 40 years of age. It also occurs more commonly following caesarean sections, those in whom medications are used to start labor, those requiring the use of a vacuum or forceps, and those who have an episiotomy.Prevention involves decreasing known risk factors including procedures associated with the condition, if possible, and giving the medication oxytocin to stimulate the uterus to contract shortly after the baby is born. Misoprostol may be used instead of oxytocin in resource-poor settings. Treatments may include: intravenous fluids, blood transfusions, and the medication ergotamine to cause further uterine contraction. Efforts to compress the uterus using the hands may be effective if other treatments do not work. The aorta may also be compressed by pressing on the abdomen. The World Health Organization has recommended the non-pneumatic anti-shock garment to help until other measures such as surgery can be carried out. Tranexamic acid has also been shown to reduce the risk of death, and has been recommended within three hours of delivery.In the developing world about 1.2% of deliveries are associated with PPH and when PPH occurred about 3% of women died. Globally it occurs about 8.7 million times and results in 44,000 to 86,000 deaths per year making it the leading cause of death during pregnancy. About 0.4 women per 100,000 deliveries die from PPH in the United Kingdom while about 150 women per 100,000 deliveries die in sub-Saharan Africa. Rates of death have decreased substantially since at least the late 1800s in the United Kingdom. Definition Depending on the source, primary postpartum bleeding is defined as blood loss in excess of 500 ml following vaginal delivery or 1000 ml following caesarean section in the first 24 hours following birth. Secondary postpartum bleeding is that which occurs after the first day and up to six weeks after childbirth. Signs and symptoms Symptoms generally include heavy bleeding from the vagina that doesnt slow or stop over time. Initially there may be an increased heart rate, feeling faint upon standing, and an increased respiratory rate. As more blood is lost, the patient may feel cold, blood pressure may drop, and they may become unconscious.Signs and symptoms of circulatory shock may also include blurry vision, cold and clammy skin, confusion, and feeling sleepy or weak. Causes Causes of postpartum hemorrhage are uterine atony, trauma, retained placenta or placental abnormalities, and coagulopathy, commonly referred to as the "four Ts": Tone: uterine atony is the inability of the uterus to contract and may lead to continuous bleeding. Retained placental tissue and infection may contribute to uterine atony. Uterine atony is the most common cause of postpartum hemorrhage. Trauma: Injury to the birth canal which includes the uterus, cervix, vagina and the perineum which can happen even if the delivery is monitored properly. The bleeding is substantial as all these organs become more vascular during pregnancy. Tissue: retention of tissue from the placenta or fetus as well as placental abnormalities such as placenta accreta and percreta may lead to bleeding. Thrombin: a bleeding disorder occurs when there is a failure of clotting, such as with diseases known as coagulopathies.Other risk factors include obesity, fever during pregnancy, bleeding before delivery, and heart disease. Prevention Oxytocin is typically used right after the delivery of the baby to prevent PPH. Misoprostol may be used in areas where oxytocin is not available. Early clamping of the umbilical cord does not decrease risks and may cause anemia in the baby, and thus is usually not recommended.Active management of the third stage is a method of shortening the stage between when the baby is born and when the placenta is delivered. This stage is when the mother is at risk of having a PPH. Active management involves giving a drug which helps the uterus contract before delivering the placenta by a gentle but sustained pull on the umbilical cord whilst exerting upward pressure on the lower abdomen to support the uterus (controlled cord traction).Another method of active management which is not recommended now is fundal pressure during the delivery of the placenta. A review into this method found no research and advises controlled cord traction because fundal pressure can cause the mother unnecessary pain. Allowing the cord to drain appears to shorten the third stage and reduce blood loss but evidence around this subject is not strong enough to draw solid conclusions.Nipple stimulation and breastfeeding triggers the release of natural oxytocin in the body, therefore it is thought that encouraging the baby to suckle soon after birth may reduce the risk of PPH for the mother. A review looking into this did not find enough good research to say whether or not nipple stimulation did reduce PPH. More research is needed to answer this question. Management Uterine massage is a simple first line treatment as it helps the uterus to contract to reduce bleeding. Although the evidence around the effectiveness of uterine massage is inconclusive, it is common practice after the delivery of the placenta. Medication Intravenous oxytocin is the drug of choice for postpartum hemorrhage. Ergotamine may also be used.Oxytocin helps the uterus to contract quickly and the contractions to last for longer. It is the first line treatment for PPH when its cause is the uterus not contracting well. A combination of syntocinon and ergometrine is commonly used as part of active management of the third stage of labour. This is called syntometrine. Syntocinon alone lowers the risk of PPH. Based on limited research available it is unclear whether syntocinon or syntometrine is most effective in preventing PPH but adverse effects are worse with syntometrine making syntocinon a more attractive option. Ergometrine also has to be kept cool and in a dark place so that it is safe to use. It may reduce the risk of PPH by improving the tone of the uterus when compared with no treatment, however it must be used with caution due to its effects of raising blood pressure and worsening pain. More research would be useful in determining the best doses of ergometrine and syntocinon.Oxytocin requires refrigeration, which may not always be available, particularly in low-resourced settings. When oxytocin is not available, misoprostol can be used. Misoprostol does not need to be kept at a certain temperature and research into its effectiveness in reducing blood loss appears promising when compared with a placebo in a setting where it is not appropriate to use oxytocin. Misoprostol can cause unpleasant side effects such as very high body temperatures and shivering. Lower doses of misoprostol appear to be safer and cause less side effects.Giving oxytocin in a solution of saline into the umbilical vein is a method of administering the drug directly to the placental bed and uterus. However quality of evidence around this technique is poor and it is not recommended for routine use in the management of the third stage. More research is needed to ascertain whether this is an effective way of administering uterotonic drugs. As a way of treating a retained placenta, this method is not harmful and has shown low certainty evidence of effectiveness.Carbetocin compared with oxytocin produced a reduction in women who needed uterine massage and further uterotonic drugs for women having caesarean sections. There was no difference in rates of PPH in women having caesarean sections or women having vaginal deliveries when given carbetocin. Carbetocin appears to cause less adverse effects. More research is needed to find the cost effectiveness of using carbetocin.Tranexamic acid, a clot stabilizing medication, may also be used to reduce bleeding and blood transfusions in low-risk patients, however evidence as of 2015 was not strong. A 2017 trial found that it decreased the risk of death from bleeding from 1.9% to 1.5% in women with postpartum bleeding. The benefit was greater when the medication was given within three hours.In some countries, such as Japan, methylergometrine and other herbal remedies are given following the delivery of the placenta to prevent severe bleeding more than a day after the birth. However, there is not enough evidence to suggest that these methods are effective. Surgery Surgery may be used if medical management fails or in case of cervical lacerations or tear or uterine rupture. Methods used may include uterine artery ligation, ovarian artery ligation, internal iliac artery ligation, selective arterial embolization, B-lynch suture, and hysterectomy. Bleeding caused by traumatic causes should be managed by surgical repair. When there is bleeding due to uterine rupture a repair can be performed but most of the time a hysterectomy is needed.There is currently no reliable evidence from randomised clinical trials about the effectiveness or risks of mechanical and surgical methods of treating postpartum bleeding. Medical devices The World Health Organization recommends the use of a device called the non-pneumatic anti-shock garment (NASG) for use in delivery activities outside of a hospital setting, the aim being to improve shock in a mother with obstetrical bleeding long enough to reach a hospital. External aortic compression devices (EACD) may also be used.Uterine balloon tamponade (UBT) can improve postpartum bleeding. Inflating a Sengstaken–Blakemore tube in the uterus successfully treats atonic postpartum hemorrhage refractory to medical management in approximately 80% of cases. Such procedure is relatively simple, inexpensive and has low surgical morbidity. A Bakri balloon is a balloon tamponade specifically constructed for uterine postpartum hemorrhage. While effective, commercially available devices may be expensive for settings in which postpartum hemorrhage is most common. Low-cost devices, such as the ESM-UBT, have been shown to be effective without the need for operative intervention. Protocol Protocols to manage postpartum bleeding are recommended to ensure the rapid giving of blood products when needed. A detailed stepwise management protocol has been introduced by the California Maternity Quality Care Collaborative. It describes four stages of obstetrical hemorrhage after childbirth and its application reduces maternal mortality. Stage 0: normal - treated with fundal massage and oxytocin. Stage 1: more than normal bleeding - establish large-bore intravenous access, assemble personnel, increase oxytocin, consider use of methergine, perform fundal massage, prepare 2 units of packed red blood cells. Stage 2: bleeding continues - check coagulation status, assemble response team, move to operating room, place intrauterine balloon, administer additional uterotonics (misoprostol, carboprost tromethamine), consider: uterine artery embolization, dilatation and curettage, and laparotomy with uterine compression stitches or hysterectomy. Stage 3: bleeding continues - activate massive transfusion protocol, mobilize additional personnel, recheck laboratory tests, perform laparotomy, consider hysterectomy.A Cochrane review suggests that active management (use of uterotonic drugs, cord clamping and controlled cord traction) during the third stage of labour may reduce severe bleeding and anemia. However, the review also found that active management increased the patients blood pressure, nausea, vomiting, and pain. In the active management group more patients returned to hospital with bleeding after discharge, and there was also a reduction in birthweight due to infants having a lower blood volume. The effects on the baby of early cord clamping was discussed in another review which found that delayed cord clamping improved iron stores longer term in the infants. Although they were more likely to need phototherapy (light therapy) to treat jaundice, the improved iron stores are expected to be worth increasing the practice of delayed cord clamping in healthy term babies.For preterm babies (babies born before 37 weeks) a review of the research found that delaying cord clamping may lead to fewer babies with bleeding in the brain, compared to early cord clamping.Another Cochrane review looking at the timing of the giving oxytocin as part of the active management found similar benefits with giving it before or after the expulsion of the placenta.There is no good quality evidence on how best to treat a secondary PPH (PPH occurring 24 hrs or more after the birth). Epidemiology Methods of measuring blood loss associated with childbirth vary, complicating comparison of prevalence rates. A systematic review reported the highest rates of PPH in Africa (27.5%), and the lowest in Oceania (7.2%), with an overall rate globally of 10.8%. The rate in both Europe and North America was around 13%. The rate is higher for multiple pregnancies (32.4% compared with 10.6% for singletons), and for first-time mothers (12.9% compared with 10.0% for women in subsequent pregnancies). The overall rate of severe PPH (>1000 ml) was much lower at an overall rate of 2.8%, again with the highest rate in Africa (5.1%). References External links WHO recommendations for the prevention and treatment of postpartum haemorrhage. Geneva: World Health Organization. 2012. ISBN 9789241548502. Postpartum hemorrhage and the B-Lynch technique

Autonomic dysreflexia

Autonomic dysreflexia (AD) is a potential medical emergency classically characterized by uncontrolled hypertension and bradycardia, although tachycardia is known to commonly occur. AD occurs most often in individuals with spinal cord injuries with lesions at or above the T6 spinal cord level, although it has been reported in patients with lesions as low as T10. Guillain–Barré syndrome may also cause autonomic dysreflexia.The uncontrolled hypertension in AD may result in mild symptoms, such as sweating above the lesion level, goosebumps, blurred vision, or headache; However, severe hypertension may result in potentially life-threatening complications including seizure, intracranial bleed, or retinal detachment.AD is triggered by either noxious or non-noxious stimuli, resulting in sympathetic stimulation and hyperactivity. The most common causes include bladder or bowel over-distension, from urinary retention and fecal compaction, respectively. The resulting sympathetic surge transmits through intact peripheral nerves, resulting in systemic vasoconstriction below the level of the spinal cord lesion. The peripheral arterial vasoconstriction and hypertension activates the baroreceptors, resulting in a parasympathetic surge originating in the central nervous system to inhibit the sympathetic outflow; however, the parasympathetic signal is unable to transmit below the level of the spinal cord lesion. This results in bradycardia, vasodilation, flushing, pupillary constriction and nasal stuffiness above the spinal lesion, while there is piloerection, pale and cool skin below the lesion due to the prevailing sympathetic outflow.Initial treatment involves sitting the patient upright, removing any constrictive clothing (including abdominal binders and support stockings), rechecking blood pressure frequently, and then checking for and removing the inciting issue, which may require urinary catheterization or bowel disimpaction. If systolic blood pressure remains elevated (over 150 mm Hg) after initial steps, fast-acting short-duration antihypertensives are considered, while other inciting causes must be investigated for the symptoms to resolve.Prevention of AD involves educating the patient, family and caregivers of the precipitating cause, if known, and how to avoid it, as well as other triggers. Since bladder and bowel are common causes, prevention involves routine bladder and bowel programs and urological follow-up for cystoscopy/urodynamic studies. Signs and symptoms This condition is distinct and usually episodic, with the people potentially experiencing remarkably high blood pressure, intense headaches, profuse sweating, facial erythema, goosebumps, nasal stuffiness, a "feeling of doom" or apprehension, and blurred vision. An elevation of 20 mm Hg over baseline systolic blood pressure, with a potential source below the neurological level of injury, meets the current definition of dysreflexia. Complications Autonomic dysreflexia can become chronic and recurrent, often in response to longstanding medical problems like soft tissue pressure injuries or hemorrhoids. Long term therapy may include alpha blockers or calcium channel blockers.Complications of severe acute hypertension can include seizures, pulmonary edema, myocardial infarction, or cerebral hemorrhage. Additional organs that may be affected include the kidneys and retinas of the eyes. Causes The first episode of autonomic dysreflexia may occur weeks to years after spinal cord injury takes place, but most people at risk (80%) develop their first episode within the first year after injury. Early AD tends to be associated with less severe increases in blood pressure.One common causative factor may be an undetected urinary tract infection. The difficulty in assessing this may be complicated with the usage of indwelling or suprapubic catheters. Other causes include medication side effects and various disease processes. The use of stimulants such as cocaine and amphetamines which can result in urinary retention, and the use of CNS depressants and other psychoactive drugs can also lead to urinary retention and constipation thus leading to autonomic dysreflexia when in use over an extended period of time. Pain Current scientific literature suggests that noxious (painful) stimuli are the primary initiators of AD. (Note: Not all noxious stimuli will cause AD. Some otherwise severe noxious stimuli in unaffected people, e.g. broken bones, may not result in AD, and may in fact even go unnoticed.) However, different studies have found that activation of pain receptors in muscle and skin below the lesion in spinal cord injured individuals did not trigger AD. These studies suggests that not all noxious stimuli are reliable triggers of AD, and because non-noxious stimuli can also trigger AD, attribution of an episode of AD to noxious stimuli may cause clinicians to overlook underlying non-noxious triggers. As a result, non-noxious trigger factors remain undetected, prolonging an episode of AD. They concluded that when deducing the potential causes of AD it is important to consider non-noxious sources of stimulation in addition to noxious triggers. Current assessment of autonomic dysreflexia in patients with known causative factors include palpation of the bladder and bowel and can also include bladder scan. Mechanism Supraspinal vasomotor neurons send projections to the intermediolateral cell column, which is composed of sympathetic preganglionic neurons (SPN) through the T1-L2 segments. The supraspinal neurons act on the SPN and its tonic firing, modulating its action on the peripheral sympathetic chain ganglia and the adrenal medulla. The sympathetic ganglia act directly on the blood vessels they innervate throughout the body, controlling vessel diameter and resistance, while the adrenal medulla indirectly controls the same action through the release of epinephrine and norepinephrine. The descending autonomic pathways, which are responsible for the supraspinal communication with the SPN, are interrupted resulting in decreased sympathetic outflow below the level of the injury. In this circumstance, the SPN is controlled only by spinal influences. The first couple of weeks after a spinal injury, the decreased sympathetic outflow causes reduced blood pressure and sympathetic reflex. Eventually, synaptic reorganization and plasticity of SPN develops into an overly sensitive state, which results in abnormal reflex activation of SPN due to afferent stimuli, such as bowel or bladder distension. Reflex activation results in systemic vasoconstriction below the spinal cord disruption. The peripheral arterial vasoconstriction and hypertension activates the baroreceptors, resulting in a parasympathetic surge originating in the central nervous system, which inhibits the sympathetic outflow; however, the parasympathetic signal is unable to transmit below the level of the spinal cord lesion. This results in vasodilation, flushing, pupillary constriction and nasal stuffiness above the spinal lesion, while theres piloerection, pale and cool skin below the lesion due to the prevailing sympathetic outflow. The reason this issue is much more prominent for lesions at or above the T6 level is because the Splanchnic nerves emerge from the T5 level and below. Loss of brains control over T6 and below causes splanchnic arteries to reflexively vasoconstrict and since the Splanchnic arteries are the bodys largest reservoir for circulating blood, their vasocontriction dramatically affects the blood pressure of the body. Diagnosis The symptoms are usually not subtle, although asymptomatic events have been documented. Autonomic dysreflexia differs from autonomic instability, the various modest cardiac and neurological changes that accompany a spinal cord injury, including bradycardia, orthostatic hypotension, and ambient temperature intolerance. In autonomic dysreflexia, patients will experience hypertension, sweating, spasms (sometimes severe spasms) and erythema (more likely in upper extremities) and may experience headaches and blurred vision. Mortality is rare with AD, but morbidity such as stroke, retinal hemorrhage and pulmonary edema if left untreated can be quite severe. Older patients with very incomplete spinal cord injuries and systolic hypertension without symptoms are usually experiencing essential hypertension, not autonomic dysreflexia. Aggressive treatment of these elderly patients with rapidly acting antihypertensive medications can have disastrous results. Treatment Proper treatment of autonomic dysreflexia involves administration of anti-hypertensives along with immediate determination and removal of the triggering stimuli. Often, sitting the patient up and dangling legs over the bedside can reduce blood pressures below dangerous levels and provide partial symptom relief. Tight clothing and stockings should be removed. Straight catheterization of the bladder or relief of a blocked urinary catheter tube may resolve the problem. The rectum should be cleared of stool impaction, using anaesthetic lubricating jelly. If the noxious precipitating trigger cannot be identified, drug treatment is needed to decrease elevating intracranial pressure until further studies can identify the cause.Drug treatment includes the rapidly acting vasodilators, including sublingual or topical nitrates or oral hydralazine or clonidine. Ganglionic blockers are also used to control sympathetic nervous system outflow. Topical nitroglycerin ointment is a convenient and safe treatment—an inch or two can be applied to the chest wall or forehead, and wiped off when blood pressures begin to normalize. Autonomic dysreflexia is abolished temporarily by spinal or general anaesthesia. These treatments are used during obstetric delivery of women with autonomic dysreflexia. Prognosis The cause of autonomic dysreflexia itself can be life-threatening, and must also be completely investigated and treated appropriately to prevent unnecessary morbidity and mortality.The Consortium for Spinal Cord Medicine has developed evidence-based clinical practice guidelines for the management of autonomic dysreflexia in adults, children, and pregnant women. There is also a consumer version of this guideline. References Further reading == External links ==

Coronary vasospasm

Coronary vasospasm refers to when a coronary artery suddenly undergoes either complete or sub-total temporary occlusion.In 1959, Prinzmetal et al. described a type of chest pain resulting from coronary vasospasm, referring to it as a variant form of classical angina pectoris. Consequently, this angina has come to be reported and referred to in the literature as Prinzmetal angina. A subsequent study distinguished this type of angina from classical angina pectoris further by showing normal coronary arteries on cardiac catheterization. This finding is unlike the typical findings in classical angina pectoris, which usually shows atherosclerotic plaques on cardiac catheterization.When coronary vasospasm occurs, the occlusion temporarily produces ischemia. A wide array of symptoms or presentations can follow: ranging from asymptomatic myocardial ischemia, sometimes referred to as silent ischemia, to myocardial infarction and even sudden cardiac death. Signs and symptoms Coronary vasospasm classically produces chest pain at rest, also known as vasospastic angina. Chest pain is more common at certain times of the day, usually from late night to early morning. These episodes can be accompanied by nausea, vomiting, cold sweating, and even syncope. Coronary vasospasm is also associated with symptoms of fatigue and tiredness, dyspnea, and palpitations. These can sometimes be the primary presenting symptoms, but they can also occur in conjunction with chest pain.There are cases of coronary vasospasm that occur without any symptoms at all, leading to episodes of silent or asymptomatic myocardial ischemia. Complications Depending on how long the occlusion lasts, a spectrum of different myocardial ischemic syndromes can occur. Shorter episodes of occlusion can lead to what is referred to as silent myocardial ischemia due to its asymptomatic nature. These episodes can also be accompanied by arrhythmias. Longer episodes of occlusion can lead to stable or unstable angina, myocardial infarction, and sudden cardiac death. Risk factors Unlike classical angina pectoris, traditional cardiovascular risk factors are not thought to be significantly associated with coronary vasospasm. The exception to this is with smoking, which is known to be a modifiable risk factor for vasospastic angina.There are several risk factors that are thought to precipitate, or trigger, episodes of coronary vasospasm. Many of these factors work by exerting effects on the autonomic nervous system. One of the mechanisms through which this occurs is via increasing sympathetic nervous system activity. The resulting increased sympathetic outflow leads to vasoconstrictive effects on blood vessels. For example, cocaine use can trigger vasospasm in coronary arteries through its actions on adrenergic receptors causing vasoconstriction. Exercise, cold weather, physical activity or exertion, mental stress, hyperventilation are additional precipitating factors. Pathophysiology The exact pathophysiology behind coronary vasospasm has not been elucidated. Instead, a combination of different factors has been proposed to contribute to coronary vasospasm. In general, it is thought that an abnormality within a coronary artery causes it to become hyperreactive to vasoconstrictor stimuli. This abnormality can be located in one segment of the coronary artery, or it may be diffuse and present throughout the entire artery. If and when vasoconstrictor stimuli act upon the hyperreactive segment of the artery, then vasospasm can result. Ultimately, when large coronary arteries undergo vasospasm, this can lead to either complete or transient occlusion of blood flow within the artery. As a result, ischemia to the tissues served by the artery can occur. Symptoms due to ischemia can follow.Some of the factors that have been proposed to contribute to coronary vasospasm include the following: Endothelial dysfunction Certain vasodilatory agents exert their effects by working via the endothelium, the cells that make up the lining of blood vessels. Specifically, these agents work by enhancing the production of nitric oxide from endothelial nitric oxide synthase. Normally, nitric oxide then works to promote vasodilation in a blood vessel through its own mechanisms such as inhibiting the release of agents that cause vasoconstriction. Endothelial dysfunction wherein there is a deficiency in the production of nitric oxide has been found to be associated with coronary vasospasm in some but not all cases. Vasodilatory agents with mechanisms dependent on a functional endothelial nitric oxide synthase can cause vasoconstriction instead in the setting of endothelial dysfunction, leading to coronary vasospasm. Chronic inflammation Various markers of low-grade chronic inflammation have been found in cases of coronary vasospasm. In addition to this, one of the risk factors for coronary vasospasm is smoking. Chronic inflammation due to smoking has been shown to be damaging to endothelial cell function. Oxidative Stress Oxygen free radicals contribute to the pathogenesis of coronary vasospasm through their damaging effects on vascular endothelial cells and degrading nitric oxide, an important vasodilatory agent. Smooth Muscle Hypercontractility At a cellular level, pathways that lead to enhanced myosin light chain phosphorylation promote vasoconstriction. Increased activity of Rho-kinase leading to enhanced myosin light chain phosphorylation has been implicated in the pathogenesis of coronary vasospasm. Diagnosis There are no set criteria to diagnose coronary vasospasm. Thorough history taking by a clinician can assist in the diagnosis of coronary vasospasm. In cases where symptoms of chest pain are present, identifying features that distinguish episodes of vasospastic angina from traditional angina can aid in the diagnosis. Features such as chest pain at rest, a diurnal variation in tolerance for exercise with a reduction in tolerance for exercise in the morning, and responsiveness of chest pain to calcium channel blockers as opposed to beta blockers can be important clues.EKG can occasionally be used to diagnose episodes of coronary vasospasm. However, relying on EKG is not always possible due to the transient nature of coronary vasospasm episodes. Due to the challenge of capturing episodes of coronary vasospasm spontaneously, provocative testing to induce coronary vasospasm during coronary catheterization can be used to make the diagnosis. Provocative testing relies upon the use of pharmacological agents that promote or trigger episodes of vasospasm. Agents commonly administered include ergonovine and acetylcholine. Both pharmacological agents have vasoconstrictive effects on coronary arteries. However, in the clinical setting, provocative testing is not routinely performed. The reason for this is due to the adverse effects of these pharmacological agents. EKG findings When coronary vasospasm causes an artery to undergo complete occlusion, an EKG might show evidence of ST-segment elevation in the leads indicative of that arterys territory. Transient ST-segment depression can also occur, usually in the setting of sub-total occlusion of an artery.Additional EKG findings in coronary vasospasm include evidence of arrhythmias that might be induced by ischemia: ventricular premature contractions, ventricular tachycardia, ventricular fibrillation, and more. History Chest pain due to coronary vasospasm was described in the medical literature by Prinzmetal et al. in 1959. This discovery led to this type of angina being referred to in the literature as Prinzmetal angina. A following study further distinguished this angina from classical angina pectoris due to the fact that the results showed that the patients with chest pain due to coronary vasospasm lacked evidence of atherosclerosis on cardiac catheterization. Angina due to coronary vasospasm is also known as variant angina. References Further reading == External links ==

Encephalomyelitis

Encephalomyelitis is inflammation of the brain and spinal cord. Various types of encephalomyelitis include: Acute disseminated encephalomyelitis or postinfectious encephalomyelitis, a demyelinating disease of the brain and spinal cord, possibly triggered by viral infection. Encephalomyelitis disseminata, a synonym for multiple sclerosis. AntiMOG associated encephalomyelitis, one of the underlying conditions for the phenotype neuromyelitis optica and in general all the spectrum of MOG autoantibody-associated demyelinating diseases. Eastern equine encephalitis, Japanese encephalitis, Venezuelan equine encephalitis, and Western equine encephalitis: a group of viral illnesses that can affect horses and humans; collectively termed Equine encephalitis. Experimental autoimmune encephalomyelitis (EAE), an animal model of brain inflammation. Progressive encephalomyelitis with rigidity and myoclonus (PERM) – A kind of stiff person syndrome. AIDS-related encephalomyelitis, caused by opportunistic Human T-lymphotropic virus type III (HTLV-III) infection. See also Chronic fatigue syndrome, sometimes called myalgic encephalomyelitis. References == External links ==

Pemphigus foliaceus

Pemphigus foliaceus is an autoimmune blistering disease (bullous disorder) of the skin. Pemphigus foliaceus causes a characteristic inflammatory attack at the subcorneal layer of epidermis, which results in skin lesions that are scaly or crusted erosions with an erythematous (red) base. Mucosal involvement is absent even with widespread disease.If there is an autoimmune IgG buildup in the epidermis, then nearly all of the antibodies are aimed against desmoglein 1. The effect of the antibodies and the immunological pathway is most likely one of three mechanisms: Steric hindrance of the desmoglein 1: The antibody caps off the site for intracellular binding to another keratinocyte. Activation of an endocytic pathway: The antibody activates a pathway which causes an internalization of desmogleïn 1, which in turn causes a loss of adhesion. Disruption of function: In this case, the antibody blocks the desmoglein 1 from being formed into a desmosome. This in turn causes a loss of adhesion with acantholysis as a result. Cause The National Institute of Arthritis and Musculoskeletal and Skin Diseases describes it like this: Normally, our immune system produces antibodies that attack viruses and harmful bacteria to keep us healthy. In people with pemphigus, however, the immune system mistakenly attacks the cells in the epidermis, or top layer of the skin, and the mucous membranes. The immune system produces antibodies against proteins in the skin known as desmogleins. These proteins form the glue that keeps skin cells attached and the skin intact. When desmogleins are attacked, skin cells separate from each other and fluid can collect between the layers of skin, forming blisters that do not heal. In some cases, these blisters can cover a large area of skin. Diagnosis Pemphigus foliaceus is diagnosed base on history, biopsy of the affected skin, and testing either a blood sample or a skin sample for the antibodies that cause pemphigus. Treatment Epidemiology Pemphigus is endemic in the rural areas of Brazil, especially along inland riverbeds. History Pierre Louis Alphée Cazenave first described the disease in 1844. See also List of cutaneous conditions Pemphigus References == External links ==

Eosinophilic pneumonia

Eosinophilic pneumonia is a disease in which an eosinophil, a type of white blood cell, accumulates in the lungs. These cells cause disruption of the normal air spaces (alveoli) where oxygen is extracted from the atmosphere. Several different kinds of eosinophilic pneumonia exist and can occur in any age group. The most common symptoms include cough, fever, difficulty breathing, and sweating at night. Eosinophilic pneumonia is diagnosed by a combination of characteristic symptoms, findings on a physical examination by a health provider, and the results of blood tests and X-rays. Prognosis is excellent once most eosinophilic pneumonia is recognized and treatment with corticosteroids is begun. Classification Eosinophilic pneumonia is divided into different categories depending upon whether its cause can be determined or not. Known causes include certain medications or environmental triggers, parasitic infections, and cancer. Eosinophilic pneumonia can also occur when the immune system attacks the lungs, a disease called eosinophilic granulomatosis with polyangiitis. When a cause cannot be found, the eosinophilic pneumonia is termed "idiopathic". Idiopathic eosinophilic pneumonia can also be divided into acute and chronic forms, depending on the symptoms a person is experiencing. Signs and symptoms Most types of eosinophilic pneumonia have similar signs and symptoms. Prominent and nearly universal signs and symptoms include cough, fever, difficulty breathing, and night sweats. Acute eosinophilic pneumonia typically follows a rapid course. Fever and cough may develop only one or two weeks before breathing difficulties progress to the point of respiratory failure requiring mechanical ventilation. Chronic eosinophilic pneumonia usually follows a slower course. Symptoms accumulate over several months and include fever, cough, difficulty breathing, wheezing, and weight loss. Individuals with chronic eosinophilic pneumonia are often misdiagnosed with asthma before the correct diagnosis is made. Eosinophilic pneumonia due to medications or environmental exposures is similar and occurs after an exposure to a known offending agent. Eosinophilic pneumonia due to parasitic infections has a similar prodrome in addition to a host of different symptoms related to the variety of underlying parasites. Eosinophilic pneumonia in the setting of cancer often develops in the context of a known diagnosis of lung cancer, cervical cancer, or other certain types of cancer. Pathophysiology Eosinophilic pneumonia can develop in several different ways depending on the underlying cause of the disease. Eosinophils play a central role in defending the body against infection by parasites. Many diseases, such as asthma and eczema, are caused when eosinophils overreact to environmental triggers and release an excess of chemicals, e.g., cytokines and histamine. The common characteristic among different causes of eosinophilic pneumonia is eosinophil overreaction or dysfunction in the lungs. Medications and environmental exposures Medications, substance abuse, and environmental exposures may all trigger eosinophil dysfunction. Medications such as nonsteroidal anti-inflammatory drugs (e.g., ibuprofen), nitrofurantoin, phenytoin, L-tryptophan, daptomycin and ampicillin, and drugs of abuse such as inhaled heroin and cocaine may trigger an allergic response which results in eosinophilic pneumonia. Chemicals such as sulfites, aluminum silicate, and cigarette smoke can cause eosinophilic pneumonia when inhaled. A New York City firefighter developed eosinophilic pneumonia after inhalation of dust from the World Trade Center on September 11, 2001. Parasitic infections Parasites cause eosinophilic pneumonia in three different ways. Parasites can either invade the lungs, live in the lungs as part of their life cycle, or be spread to the lungs by the bloodstream. Eosinophils then migrate to the lungs in order to fight the parasites, and cause eosinophilic pneumonia when they release their contents. Important parasites that invade the lungs include Paragonimus lung flukes and the tapeworms Echinococcus and Taenia solium. Important parasites which inhabit the lungs as part of their normal life cycle include the worms (helminths) Ascaris lumbricoides, Strongyloides stercoralis and the hookworms Ancylostoma duodenale and Necator americanus. When eosinophilic pneumonia is caused by helminths, it is often called "Löfflers syndrome". The final group of parasites cause eosinophilic pneumonia when their eggs are carried into the lungs by the bloodstream. This can include Trichinella spiralis, Strongyloides stercoralis, Ascaris lumbricoides, the hookworms, and the schistosomes. Acute and Chronic Eosinophilic Pneumonia The causes for both acute and chronic eosinophilic pneumonia are unknown as of 2005. There is some suspicion that at least the acute form is the result of the bodys response to some unidentified environmental agent. Diagnosis Eosinophilic pneumonia is diagnosed in one of three circumstances: when a complete blood count reveals increased eosinophils and a chest X-ray or computed tomography identifies abnormalities in the lungs, when a biopsy identifies increased eosinophils in lung tissue, or when increased eosinophils are found in fluid obtained by a bronchoscopy (bronchoalveolar lavage fluid). Association with medication or cancer is usually apparent after review of a persons medical history. Specific parasitic infections are diagnosed after examining a persons exposure to common parasites and performing laboratory tests to look for likely causes. If no underlying cause is found, a diagnosis of acute or chronic eosinophilic pneumonia is made based upon the following criteria. Acute eosinophilic pneumonia is most likely with respiratory failure after an acute febrile illness of usually less than one week, changes in multiple areas and fluid in the area surrounding the lungs on a chest X-ray, and eosinophils comprising more than 25% of white blood cells in fluid obtained by bronchoalveolar lavage. Other typical laboratory abnormalities include an elevated white blood cell count, erythrocyte sedimentation rate, and immunoglobulin G level. Pulmonary function testing usually reveals a restrictive process with reduced diffusion capacity for carbon monoxide. Chronic eosinophilic pneumonia is most likely when the symptoms have been present for more than a month. Laboratory tests typical of chronic eosinophilic pneumonia include increased levels of eosinophils in the blood, a high erythrocyte sedimentation rate, iron deficiency anemia, and increased platelets. A chest X-ray can show abnormalities anywhere, but the most specific finding is increased shadow in the periphery of the lungs, away from the heart. Differential diagnosis This includes: Asthma Environmental allergic reaction Granulomatosis with polyangiitis Allergic bronchopulmonary aspergillosis Churg–Strauss syndrome Loefflers syndrome Acute eosinophilic pneumonia Chronic eosinophilic pneumonia (Carringtons disease) Polyarteritis nodosa Parasitic infections Tropical pulmonary eosinophilia Tuberculosis Fungal infection Sarcoidosis Drug reaction with eosinophilia and systemic symptoms Mastocytosis Lymphoproliferative hypereosinophilic syndrome Myeloproliferative hypereosinophilic syndrome Treatment When eosinophilic pneumonia is related to an illness such as cancer or parasitic infection, treatment of the underlying cause is effective in resolving the lung disease. When due to acute or chronic eosinophilic pneumonia, however, treatment with corticosteroids results in a rapid, dramatic resolution of symptoms over the course of one or two days. Either intravenous methylprednisolone or oral prednisone are most commonly used. In acute eosinophilic pneumonia, treatment is usually continued for a month after symptoms disappear and the X-ray returns to normal (usually four weeks total). In chronic eosinophilic pneumonia, treatment is usually continued for three months after symptoms disappear and the X-ray returns to normal (usually four months total). Inhaled steroids such as fluticasone have been used effectively when discontinuation of oral prednisone has resulted in relapse. Because eosinophilic pneumonia affects the lungs, individuals develop difficulty breathing. If enough of the lungs are involved, it may not be possible for a person to breathe without support. Non-invasive machines such as a bilevel positive airway pressure machine may be used. Otherwise, placement of a breathing tube into the mouth may be necessary and a ventilator may be used to help the person breathe. Prognosis Eosinophilic pneumonia due to cancer or parasitic infection carries a prognosis related to the underlying illness. Acute and chronic eosinophilic pneumonia, however, have very little associated mortality as long as intensive care is available and treatment with corticosteroids is given. Chronic eosinophilic pneumonia often relapses when prednisone is stopped; therefore, some people require lifelong therapy. Long-term use of prednisone has many side effects, including increased infections, osteoporosis, stomach ulcers, Cushings syndrome, and changes in appearance. Epidemiology Eosinophilic pneumonia is a rare disease. Parasitic causes are most common in geographic areas where each parasite is endemic. Acute eosinophilic pneumonia can occur at any age, even in previously healthy children, though most patients are between 20 and 40 years of age. Men are affected approximately twice as frequently as women. Acute eosinophilic pneumonia has been associated with smoking. Chronic eosinophilic pneumonia occurs more frequently in women than men and does not appear to be related to smoking. An association with radiation for breast cancer has been described. History Chronic eosinophilic pneumonia was first described by Carrington in 1969, and it is also known as Carrington syndrome. Prior to that, eosinophilic pneumonia was a well-described pathologic entity usually associated with medication or parasite exposures. Acute eosinophilic pneumonia was first described in 1989. See also Asthma Parasitic pneumonia Pneumonia References == External links ==

Glycosuria

Glycosuria is the excretion of glucose into the urine. Ordinarily, urine contains no glucose because the kidneys are able to reabsorb all of the filtered glucose from the tubular fluid back into the bloodstream. Glycosuria is nearly always caused by elevated blood glucose levels, most commonly due to untreated diabetes mellitus. Rarely, glycosuria is due to an intrinsic problem with glucose reabsorption within the kidneys (such as Fanconi syndrome), producing a condition termed renal glycosuria. Glycosuria leads to excessive water loss into the urine with resultant dehydration, a process called osmotic diuresis. Alimentary glycosuria is a temporary condition, when a high amount of carbohydrate is taken, it is rapidly absorbed in some cases where a part of the stomach is surgically removed, the excessive glucose appears in urine producing glycosuria. Follow-up In a patient with glucosuria, diabetes is confirmed by measuring fasting or random plasma glucose and glycated hemoglobin(HbA1c). Pathophysiology Blood is filtered by millions of nephrons, the functional units that comprise the kidneys. In each nephron, blood flows from the arteriole into the glomerulus, a tuft of leaky capillaries. The Bowmans capsule surrounds each glomerulus, and collects the filtrate that the glomerulus forms. The filtrate contains waste products (e.g. urea), electrolytes (e.g. sodium, potassium, chloride), amino acids, and glucose. The filtrate passes into the renal tubules of the kidney. In the first part of the renal tubule, the proximal tubule, glucose is reabsorbed from the filtrate, across the tubular epithelium and into the bloodstream. The proximal tubule can only reabsorb a limited amount of glucose (~375 mg/min), known as the transport maximum. When the blood glucose level exceeds about 160–180 mg/dL (8.9-10 mmol/L), the proximal tubule becomes overwhelmed and begins to excrete glucose in the urine. This point is called the renal threshold for glucose (RTG). Some people, especially children and pregnant women, may have a low RTG (less than ~7 mmol/L glucose in blood to have glucosuria). If the RTG is so low that even normal blood glucose levels produce the condition, it is referred to as renal glycosuria. Glucose in urine can be identified by Benedicts qualitative test. If yeast is present in the bladder, the sugar in the urine may begin to ferment, producing a rare condition known as urinary auto-brewery syndrome. References == External links ==

Hyperventilation

Hyperventilation is irregular breathing that occurs when the rate or tidal volume of breathing eliminates more carbon dioxide than the body can produce. This leads to hypocapnia, a reduced concentration of carbon dioxide dissolved in the blood. The body normally attempts to compensate for this homeostatically, but if this fails or is overridden, the blood pH will rise, leading to respiratory alkalosis. The symptoms of respiratory alkalosis include: dizziness, tingling in the lips, hands or feet, headache, weakness, fainting, and seizures. In extreme cases it may cause carpopedal spasms, a flapping and contraction of the hands and feet.Factors that may induce or sustain hyperventilation include: physiological stress, anxiety or panic disorder, high altitude, head injury, stroke, respiratory disorders such as asthma, pneumonia, or hyperventilation syndrome, cardiovascular problems such as pulmonary embolisms, anemia, an incorrectly calibrated medical respirator, and adverse reactions to certain drugs. Hyperventilation can also be induced intentionally to achieve an altered state of consciousness such as in the choking game, during breathwork, or in an attempt to extend a breath-hold dive. See also List of terms of lung size and activity Control of respiration Choking game a game which may involve hyperventilation in order to induce temporary syncope and euphoria Respiratory alkalosis Kussmaul breathing Shallow water blackout, the role of hyperventilation in some drowning incidents References == External links ==

Hypokinesia

Hypokinesia is one of the classifications of movement disorders, and refers to decreased bodily movement. Hypokinesia is characterized by a partial or complete loss of muscle movement due to a disruption in the basal ganglia. Hypokinesia is a symptom of Parkinsons disease shown as muscle rigidity and an inability to produce movement. It is also associated with mental health disorders and prolonged inactivity due to illness, amongst other diseases. The other category of movement disorder is hyperkinesia that features an exaggeration of unwanted movement, such as twitching or writhing in Huntingtons disease or Tourette syndrome. Spectrum of disorders Hypokinesia describes a variety of more specific disorders: Causes The most common cause of Hypokinesia is Parkinsons disease, and conditions related to Parkinsons disease. Other conditions may also cause slowness of movements. These include hypothyroidism and severe depression. These conditions need to be carefully ruled out, before a diagnosis of Parkinsonism is made. The remainder of this article describes Hypokinesia associated with Parkinsons disease, and conditions related to Parkinsons disease. Pathophysiology Associated neurotransmitters Dopamine The main neurotransmitter thought to be involved in hypokinesia is dopamine. Essential to the basal ganglionic-thalamocortical loop, which processes motor function, dopamine depletion is common in these areas of hypokinesic patients. Bradykinesia is correlated with lateralized dopaminergic depletion in the substantia nigra. The dopamine pathway in the substantia nigra is essential to motor function, and commonly a lesion in this area correlates with displayed hypokinesia. Tremor and rigidity, however, seem to be only partially due to dopamine deficits in the substantia nigra, suggesting other processes are involved in motor control. Treatments for hypokinesia often either attempt to prevent dopamine degradation by MAO-B or increase the amount of neurotransmitter present in the system.GABA and glutamate The inhibitory neurotransmitter GABA and the excitatory glutamate are found in many parts of the central nervous system, including in the motor pathways that involve hypokinesia. In one pathway, glutamate in the substantia nigra excites the release of GABA into the thalamus, which then inhibits the release of glutamate in the cortex and thereby reduces motor activity. If too much glutamate is initially in the substantia nigra, then through interaction with GABA in the thalamus and glutamate in the cortex, movements will be reduced or will not occur at all.Another direct pathway from the basal ganglia sends GABA inhibitory messages to the globus pallidus and substantia nigra, which then send GABA to the thalamus. In the indirect pathway, the basal ganglia send GABA to the globus pallidus which then sends it to the subthalamic nucleus, which then disinhibited sends glutamate to the output structures of the basal ganglia. Inhibition of GABA release could disrupt the feedback loop to the basal ganglia and produce hypokinesic movements.GABA and glutamate often interact with each other and with dopamine directly. In the basal ganglia, the nigrostriatal pathway is where GABA and dopamine are housed in the same neurons and released together. Neurobiology Hypokinetic symptoms arise from damage to the basal ganglia, which plays a role in producing force and computing the effort necessary to make a movement. Two possible neural pathways enable the basal ganglia to produce movement. When activated, the direct pathway sends sensory and motor information from the cerebral cortex to the first structure of the basal ganglia, the putamen. That information directly inhibits the globus pallidus internal and allows free movement. The indirect pathway, traveling through the putamen, globus pallidus external, and subthalamic nucleus, activates the globus pallidus internal threshold and inhibits the thalamus from communicating with the motor cortex, producing hypokinetic symptoms. When levels of dopamine decrease, the normal wave-firing pattern of basal ganglia neural oscillations changes and the tendency for oscillations increases, particularly in the beta wave of the basal ganglia. Recent research indicates, when oscillations fire simultaneously, processing is disrupted at the thalamus and cortex, affecting activities such as motor planning and sequence learning, as well as causing hypokinetic tremors. Treatments Dopaminergic drugs Dopaminergic drugs are commonly used in the early stages of the hypokinesia to treat patients. With increased intake, though, they can become ineffective because of the development of noradrenergic lesions. While initially the dopaminergic drugs may be effective, these noradrenergic lesions are associated with hypokinesic gait disorder development later on.Some Parkinsons patients are unable to move during sleep, prompting the diagnosis of "nocturnal hypokinesia". Physicians have experienced success treating this sleep disorder with slow-release or night-time dopaminergic drugs, and in some cases, continuous stimulation by the dopamine agonist rotigotine. Despite improved mobility during sleep, many Parkinsons patients report an extremely uncomfortable sleeping experience even after dopaminergic treatments. Deep brain stimulation Once the reaction to dopaminergic drugs begins to fluctuate in Parkinsons patients, deep brain stimulation (DBS) of the subthalamic nucleus and internal globus pallidus is often used to treat hypokinesia. DBS, like dopaminergic drugs, initially provides relief, but chronic use causes worse hypokinesia and freezing of gait. Lower-frequency DBS in irregular patterns has been shown to be more effective and less detrimental in treatment. Posteroventral pallidotomy (PVP) is a specific kind of DBS that destroys a small part of the globus pallidus by scarring the neural tissue, reducing brain activity and therefore tremors and rigidity. PVP is suspected to recalibrate basal ganglia activity in the thalamocortical pathway. PVP in the dominant hemisphere has been reported to disrupt executive function verbal processing abilities, and bilateral PVP may disturb processes of focused attention.Many akinesia patients also form a linguistic akinesia in which their ability to produce verbal movements mirrors their physical akinesia symptoms, especially after unsuccessful PVP. Patients are usually able to maintain normal levels of fluency, but often stop midsentence, unable to remember or produce a desired word. According to a study of Parkinsons patients with articulatory hypokinesia, subjects with faster rates of speech experienced more problems trying to produce conversational language than those who normally spoke at slower rates. Methylphenidate Methylphenidate, commonly used to treat ADHD, has been used in conjunction with levodopa to treat hypokinesia in the short term. The two work together to increase dopamine levels in the striatum and prefrontal cortex. Methylphenidate mainly inhibits dopamine and noradrenaline reuptake by blocking presynaptic transporters, and levodopa increases the amount of dopamine, generally improving hypokinesic gait. Some patients, however, have adverse reactions of nausea and headache to the treatment and the long-term effects of the drug treatment still need to be assessed. Stem cells New treatments include increasing the number of dopamine cells by transplanting stem cells into the basal ganglia or stimulating endogenous stem cell production and movement to the basal ganglia. The successful integration of stem cells can relieve hypokinetic symptoms and decrease the necessary dose of dopaminergic drugs. However, a variety of complications, including possible tumor formation, inappropriate cell migration, rejection of cells by the immune system, and cerebral hemorrhage are possible, causing many physicians to believe the risks outweigh the possible benefits. NOP receptor antagonists Another treatment, still in an experimental stage, is the administration of nociception FQ peptide (NOP) receptor antagonists. This treatment has been shown to reduce hypokinesia in animal studies when increasing nociception FQ in the substantia nigra and subthalamic nucleus. Low doses can be taken with dopaminergic treatment to decrease the amount of L-dopa needed, which can reduce its long-term side effects and improve motor performance. Dance therapy Dance therapy has also been shown to reduce hypokinesic movements and rigidity, though targeted more at the muscular aspects of the disorder than the neural activity. Associations Cognitive impairment Bradykinesia has been shown to precede impairment of executive functions, working memory, and attention. These cognitive deficiencies can be tied to nonfunction of the basal ganglia and prefrontal cortex, which is also linked to the motor-dysfunction of hypokinesia. Tremor and rigidity have not had observable connections to cognitive impairments, supporting the idea that they are not as involved in the dopamine pathway in the basal ganglionic-thalamocortical loop. Dopaminergic treatments have shown improvement in cognitive functions associated with hypokinesia, suggesting they are also dependent on dopamine levels in the system. Motor motivation Often debated is whether the efficiency, vigor, and speed of movements in patients with hypokinesia are tied to motivation for rewarding and against punishing stimuli. The basal ganglia have been tied to the incentives behind movement, therefore suggesting a cost/benefit analysis of planned movement could be affected in hypokinesia. Rewards have not been shown to change the aspects of a hypokinesic individuals movement. In fact, the motor planning and control of a patient with hypokinesia is already as efficient as possible (as shown by slightly faster, but generally the same movement after deep brain stimulation of the subthalamic nucleus). This suggests that hypokinetic individuals simply have a narrower range of movement that does not increase relative to motivation.Other studies have come to the same conclusion about rewards and hypokinesia, but have shown that aversive stimuli can, in fact, reduce hypokinesic movement. Dopamine is either less involved or has a more complex role in the response to punishment than it does to rewards, as the hypodopaminergic striatum allows more movement in response to aversive stimuli. Demographic differentiation Gender More men than women typically develop hypokinesia, which is reflected in young and middle-aged populations where females have displayed higher levels of nigrostriatal dopamine than males. In the elderly, however, this differentiation is not present. Typically, women exhibit more tremor in the beginning development of hypokinesia. In the disorder, men tend to display more rigidity and women more bradykinesic motor behavior.Age of onset Hypokinesia is displayed in the brain and outwardly slightly different depending on when an individual is first affected. In young-onset hypokinesia (younger than 45 years of age), typically slightly more cell loss occurs in the substantia nigra with more displayed dystonia and muscle stiffness. In old-onset hypokinesia (older than 70 years of age), typically more of a hypokinesic gait and difficulty walking and no dystonia are seen. Both onsets can display resting tremor, although more generally found in old-onset cases. Symptoms Stress causes alterations of cerebral circulation, increasing blood flow in the supramarginal gyrus and angular gyrus of the parietal lobe, the frontal lobe, and the superior temporal gyrus of the left hemisphere. Also, an increase in cardiac activity and change in the tonus of the heart vessels occurs, which is an elementary indication of stress development. In patients with normal stress, an adaptive fight-or-flight response is usually triggered by sympathetic nervous system activation. Hypokinesia patients experience these typical stress symptoms on a regular basis because of damage to the basal ganglia system. Therefore, when a hypokinesia victim is under stress, he or she does not display a typical fight-or-flight response, placing the patient under greater danger from potentially harmful stimuli. Low-impact exercise, elimination of drug and alcohol use, and regular meditation can help to restore normal stress responses in hypokinesia patients. Connections to other medical conditions Though it is often most associated with Parkinsons disease, hypokinesia can be present in a wide variety of other conditions. See also Akinetic mutism Hyperkinesia == References ==

Ataxia

Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in eye movements. Ataxia is a clinical manifestation indicating dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum. Ataxia can be limited to one side of the body, which is referred to as hemiataxia. Several possible causes exist for these patterns of neurological dysfunction. Dystaxia is a mild degree of ataxia. Friedreichs ataxia has gait abnormality as the most commonly presented symptom. The word is from Greek α- [a negative prefix] + -τάξις [order] = "lack of order". Types Cerebellar The term cerebellar ataxia is used to indicate ataxia due to dysfunction of the cerebellum. The cerebellum is responsible for integrating a significant amount of neural information that is used to coordinate smoothly ongoing movements and to participate in motor planning. Although ataxia is not present with all cerebellar lesions, many conditions affecting the cerebellum do produce ataxia. People with cerebellar ataxia may have trouble regulating the force, range, direction, velocity, and rhythm of muscle contractions. This results in a characteristic type of irregular, uncoordinated movement that can manifest itself in many possible ways, such as asthenia, asynergy, delayed reaction time, and dyschronometria. Individuals with cerebellar ataxia could also display instability of gait, difficulty with eye movements, dysarthria, dysphagia, hypotonia, dysmetria, and dysdiadochokinesia. These deficits can vary depending on which cerebellar structures have been damaged, and whether the lesion is bi- or unilateral.People with cerebellar ataxia may initially present with poor balance, which could be demonstrated as an inability to stand on one leg or perform tandem gait. As the condition progresses, walking is characterized by a widened base and high stepping, as well as staggering and lurching from side to side. Turning is also problematic and could result in falls. As cerebellar ataxia becomes severe, great assistance and effort are needed to stand and walk. Dysarthria, an impairment with articulation, may also be present and is characterized by "scanning" speech that consists of slower rate, irregular rhythm, and variable volume. Also, slurring of speech, tremor of the voice, and ataxic respiration may occur. Cerebellar ataxia could result with incoordination of movement, particularly in the extremities. Overshooting (or hypermetria) occurs with finger-to-nose testing and heel to shin testing; thus, dysmetria is evident. Impairments with alternating movements (dysdiadochokinesia), as well as dysrhythmia, may also be displayed. Tremor of the head and trunk (titubation) may be seen in individuals with cerebellar ataxia.Dysmetria is thought to be caused by a deficit in the control of interaction torques in multijoint motion. Interaction torques are created at an associated joint when the primary joint is moved. For example, if a movement required reaching to touch a target in front of the body, flexion at the shoulder would create a torque at the elbow, while extension of the elbow would create a torque at the wrist. These torques increase as the speed of movement increases and must be compensated and adjusted for to create coordinated movement. This may, therefore, explain decreased coordination at higher movement velocities and accelerations. Dysfunction of the vestibulocerebellum (flocculonodular lobe) impairs balance and the control of eye movements. This presents itself with postural instability, in which the person tends to separate his/her feet upon standing, to gain a wider base and to avoid titubation (bodily oscillations tending to be forward-backward ones). The instability is, therefore, worsened when standing with the feet together, regardless of whether the eyes are open or closed. This is a negative Rombergs test, or more accurately, it denotes the individuals inability to carry out the test, because the individual feels unstable even with open eyes. Dysfunction of the spinocerebellum (vermis and associated areas near the midline) presents itself with a wide-based "drunken sailor" gait (called truncal ataxia), characterised by uncertain starts and stops, lateral deviations, and unequal steps. As a result of this gait impairment, falling is a concern in patients with ataxia. Studies examining falls in this population show that 74–93% of patients have fallen at least once in the past year and up to 60% admit to fear of falling. Dysfunction of the cerebrocerebellum (lateral hemispheres) presents as disturbances in carrying out voluntary, planned movements by the extremities (called appendicular ataxia). These include: Intention tremor (coarse trembling, accentuated over the execution of voluntary movements, possibly involving the head and eyes, as well as the limbs and torso) Peculiar writing abnormalities (large, unequal letters, irregular underlining) A peculiar pattern of dysarthria (slurred speech, sometimes characterised by explosive variations in voice intensity despite a regular rhythm) Inability to perform rapidly alternating movements, known as dysdiadochokinesia, occurs, and could involve rapidly switching from pronation to supination of the forearm. Movements become more irregular with increases of speed. Inability to judge distances or ranges of movement happens. This dysmetria is often seen as undershooting, hypometria, or overshooting, hypermetria, the required distance or range to reach a target. This is sometimes seen when a patient is asked to reach out and touch someones finger or touch his or her own nose. The rebound phenomenon, also known as the loss of the check reflex, is also sometimes seen in patients with cerebellar ataxia, for example, when patients are flexing their elbows isometrically against a resistance. When the resistance is suddenly removed without warning, the patients arms may swing up and even strike themselves. With an intact check reflex, the patients check and activate the opposing triceps to slow and stop the movement. Patients may exhibit a constellation of subtle to overt cognitive symptoms, which are gathered under the terminology of Schmahmanns syndrome. Sensory The term sensory ataxia is used to indicate ataxia due to loss of proprioception, the loss of sensitivity to the positions of joint and body parts. This is generally caused by dysfunction of the dorsal columns of the spinal cord, because they carry proprioceptive information up to the brain. In some cases, the cause of sensory ataxia may instead be dysfunction of the various parts of the brain that receive positional information, including the cerebellum, thalamus, and parietal lobes.Sensory ataxia presents itself with an unsteady "stomping" gait with heavy heel strikes, as well as a postural instability that is usually worsened when the lack of proprioceptive input cannot be compensated for by visual input, such as in poorly lit environments.Physicians can find evidence of sensory ataxia during physical examination by having patients stand with their feet together and eyes shut. In affected patients, this will cause the instability to worsen markedly, producing wide oscillations and possibly a fall; this is called a positive Rombergs test. Worsening of the finger-pointing test with the eyes closed is another feature of sensory ataxia. Also, when patients are standing with arms and hands extended toward the physician, if the eyes are closed, the patients fingers tend to "fall down" and then be restored to the horizontal extended position by sudden muscular contractions (the "ataxic hand"). Vestibular The term vestibular ataxia is used to indicate ataxia due to dysfunction of the vestibular system, which in acute and unilateral cases is associated with prominent vertigo, nausea, and vomiting. In slow-onset, chronic bilateral cases of vestibular dysfunction, these characteristic manifestations may be absent, and dysequilibrium may be the sole presentation. Causes The three types of ataxia have overlapping causes, so can either coexist or occur in isolation. Cerebellar ataxia can have many causes despite normal neuroimaging. Focal lesions Any type of focal lesion of the central nervous system (such as stroke, brain tumor, multiple sclerosis, inflammatory [such as sarcoidosis], and "chronic lymphocytyc inflammation with pontine perivascular enhancement responsive to steroids syndrome" [CLIPPERS]) will cause the type of ataxia corresponding to the site of the lesion: cerebellar if in the cerebellum; sensory if in the dorsal spinal cord...to include cord compression by thickened ligamentum flavum or stenosis of the boney spinal canal...(and rarely in the thalamus or parietal lobe); or vestibular if in the vestibular system (including the vestibular areas of the cerebral cortex). Exogenous substances (metabolic ataxia) Exogenous substances that cause ataxia mainly do so because they have a depressant effect on central nervous system function. The most common example is ethanol (alcohol), which is capable of causing reversible cerebellar and vestibular ataxia. Chronic intake of ethanol causes atrophy of the cerebellum by oxidative and endoplasmic reticulum stresses induced by thiamine deficiency. Other examples include various prescription drugs (e.g. most antiepileptic drugs have cerebellar ataxia as a possible adverse effect), Lithium level over 1.5mEq/L, synthetic cannabinoid HU-211 ingestion and various other medical and recreational drugs (e.g. ketamine, PCP or dextromethorphan, all of which are NMDA receptor antagonists that produce a dissociative state at high doses). A further class of pharmaceuticals which can cause short term ataxia, especially in high doses, are benzodiazepines. Exposure to high levels of methylmercury, through consumption of fish with high mercury concentrations, is also a known cause of ataxia and other neurological disorders. Radiation poisoning Ataxia can be induced as a result of severe acute radiation poisoning with an absorbed dose of more than 30 grays. Vitamin B12 deficiency Vitamin B12 deficiency may cause, among several neurological abnormalities, overlapping cerebellar and sensory ataxia. Neuropsychological symptoms may include sense loss, difficulty in proprioception, poor balance, loss of sensation in the feet, changes in reflexs, dementia, and psychosis, can be reversible with treatment. Complications may include a neurological complex known as subacute combined degeneration of spinal cord, and other neurological disorders. Hypothyroidism Symptoms of neurological dysfunction may be the presenting feature in some patients with hypothyroidism. These include reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Most of the neurological complications improve completely after thyroid hormone replacement therapy. Causes of isolated sensory ataxia Peripheral neuropathies may cause generalised or localised sensory ataxia (e.g. a limb only) depending on the extent of the neuropathic involvement. Spinal disorders of various types may cause sensory ataxia from the lesioned level below, when they involve the dorsal columns. Non-hereditary cerebellar degeneration Non-hereditary causes of cerebellar degeneration include chronic alcohol use disorder, head injury, paraneoplastic and non-paraneoplastic autoimmune ataxia, high altitude cerebral oedema, coeliac disease, normal pressure hydrocephalus and infectious or post-infectious cerebellitis. Hereditary ataxias Ataxia may depend on hereditary disorders consisting of degeneration of the cerebellum or of the spine; most cases feature both to some extent, and therefore present with overlapping cerebellar and sensory ataxia, even though one is often more evident than the other. Hereditary disorders causing ataxia include autosomal dominant ones such as spinocerebellar ataxia, episodic ataxia, and dentatorubropallidoluysian atrophy, as well as autosomal recessive disorders such as Friedreichs ataxia (sensory and cerebellar, with the former predominating) and Niemann Pick disease, ataxia-telangiectasia (sensory and cerebellar, with the latter predominating),autosomal recessive spinocerebellar ataxia-14 and abetalipoproteinaemia. An example of X-linked ataxic condition is the rare fragile X-associated tremor/ataxia syndrome or FXTAS. Arnold–Chiari malformation (congenital ataxia) Arnold–Chiari malformation is a malformation of the brain. It consists of a downward displacement of the cerebellar tonsils and the medulla through the foramen magnum, sometimes causing hydrocephalus as a result of obstruction of cerebrospinal fluid outflow. Succinic semialdehyde dehydrogenase deficiency Succinic semialdehyde dehydrogenase deficiency is an autosomal-recessive gene disorder where mutations in the ALDH5A1 gene results in the accumulation of gamma-Hydroxybutyric acid (GHB) in the body. GHB accumulates in the nervous system and can cause ataxia as well as other neurological dysfunction. Wilsons disease Wilsons disease is an autosomal-recessive gene disorder whereby an alteration of the ATP7B gene results in an inability to properly excrete copper from the body. Copper accumulates in the nervous system and liver and can cause ataxia as well as other neurological and organ impairments. Gluten ataxia Gluten ataxia is an autoimmune disease triggered by the ingestion of gluten. Early diagnosis and treatment with a gluten-free diet can improve ataxia and prevent its progression. The effectiveness of the treatment depends on the elapsed time from the onset of the ataxia until diagnosis, because the death of neurons in the cerebellum as a result of gluten exposure is irreversible. It accounts for 40% of ataxias of unknown origin and 15% of all ataxias. Less than 10% of people with gluten ataxia present any gastrointestinal symptom and only about 40% have intestinal damage. This entity is classified into primary auto-immune cerebellar ataxias (PACA). Potassium pump Malfunction of the sodium-potassium pump may be a factor in some ataxias. The Na+-K+ pump has been shown to control and set the intrinsic activity mode of cerebellar Purkinje neurons. This suggests that the pump might not simply be a homeostatic, "housekeeping" molecule for ionic gradients; but could be a computational element in the cerebellum and the brain. Indeed, an ouabain block of Na+-K+ pumps in the cerebellum of a live mouse results in it displaying ataxia and dystonia. Ataxia is observed for lower ouabain concentrations, dystonia is observed at higher ouabain concentrations. Cerebellar ataxia associated with anti-GAD antibodies Antibodies against the enzyme glutamic acid decarboxylase (GAD: enzyme changing glutamate into GABA) cause cerebellar deficits. The antibodies impair motor learning and cause behavioral deficits. GAD antibodies related ataxia is part of the group called immune-mediated cerebellar ataxias. The antibodies induce a synaptopathy. The cerebellum is particularly vulnerable to autoimmune disorders. Cerebellar circuitry has capacities to compensate and restore function thanks to cerebellar reserve, gathering multiple forms of plasticity. LTDpathies gather immune disorders targeting long-term depression (LTD), a form of plasticity. Diagnosis Imaging studies - A CT scan or MRI of the brain might help determine potential causes. An MRI can sometimes show shrinkage of the cerebellum and other brain structures in people with ataxia. It may also show other treatable findings, such as a blood clot or benign tumour, that could be pressing on the cerebellum. Lumbar puncture (spinal tap) - A needle is inserted into the lower back (lumbar region) between two lumbar vertebrae to obtain a sample of cerebrospinal fluid for testing. Genetic testing - Determines whether the mutation that causes one of the hereditary ataxic conditions is present. Tests are available for many but not all of the hereditary ataxias. Treatment The treatment of ataxia and its effectiveness depend on the underlying cause. Treatment may limit or reduce the effects of ataxia, but it is unlikely to eliminate them entirely. Recovery tends to be better in individuals with a single focal injury (such as stroke or a benign tumour), compared to those who have a neurological degenerative condition. A review of the management of degenerative ataxia was published in 2009. A small number of rare conditions presenting with prominent cerebellar ataxia are amenable to specific treatment and recognition of these disorders is critical. Diseases include vitamin E deficiency, abetalipoproteinemia, cerebrotendinous xanthomatosis, Niemann–Pick type C disease, Refsums disease, glucose transporter type 1 deficiency, episodic ataxia type 2, gluten ataxia, glutamic acid decarboxylase ataxia. Novel therapies target the RNA defects associated with cerebellar disorders, using in particular anti-sense oligonucleotides.The movement disorders associated with ataxia can be managed by pharmacological treatments and through physical therapy and occupational therapy to reduce disability. Some drug treatments that have been used to control ataxia include: 5-hydroxytryptophan (5-HTP), idebenone, amantadine, physostigmine, L-carnitine or derivatives, trimethoprim/sulfamethoxazole, vigabatrin, phosphatidylcholine, acetazolamide, 4-aminopyridine, buspirone, and a combination of coenzyme Q10 and vitamin E.Physical therapy requires a focus on adapting activity and facilitating motor learning for retraining specific functional motor patterns. A recent systematic review suggested that physical therapy is effective, but there is only moderate evidence to support this conclusion. The most commonly used physical therapy interventions for cerebellar ataxia are vestibular habituation, Frenkel exercises, proprioceptive neuromuscular facilitation (PNF), and balance training; however, therapy is often highly individualized and gait and coordination training are large components of therapy.Current research suggests that, if a person is able to walk with or without a mobility aid, physical therapy should include an exercise program addressing five components: static balance, dynamic balance, trunk-limb coordination, stairs, and contracture prevention. Once the physical therapist determines that the individual is able to safely perform parts of the program independently, it is important that the individual be prescribed and regularly engage in a supplementary home exercise program that incorporates these components to further improve long term outcomes. These outcomes include balance tasks, gait, and individual activities of daily living. While the improvements are attributed primarily to changes in the brain and not just the hip or ankle joints, it is still unknown whether the improvements are due to adaptations in the cerebellum or compensation by other areas of the brain.Decomposition, simplification, or slowing of multijoint movement may also be an effective strategy that therapists may use to improve function in patients with ataxia. Training likely needs to be intense and focused—as indicated by one study performed with stroke patients experiencing limb ataxia who underwent intensive upper limb retraining. Their therapy consisted of constraint-induced movement therapy which resulted in improvements of their arm function. Treatment should likely include strategies to manage difficulties with everyday activities such as walking. Gait aids (such as a cane or walker) can be provided to decrease the risk of falls associated with impairment of balance or poor coordination. Severe ataxia may eventually lead to the need for a wheelchair. To obtain better results, possible coexisting motor deficits need to be addressed in addition to those induced by ataxia. For example, muscle weakness and decreased endurance could lead to increasing fatigue and poorer movement patterns.There are several assessment tools available to therapists and health care professionals working with patients with ataxia. The International Cooperative Ataxia Rating Scale (ICARS) is one of the most widely used and has been proven to have very high reliability and validity. Other tools that assess motor function, balance and coordination are also highly valuable to help the therapist track the progress of their patient, as well as to quantify the patients functionality. These tests include, but are not limited to: The Berg Balance Scale Tandem Walking (to test for Tandem gaitability) Scale for the Assessment and Rating of Ataxia (SARA) tapping tests – The person must quickly and repeatedly tap their arm or leg while the therapist monitors the amount of dysdiadochokinesia. finger-nose testing – This test has several variations including finger-to-therapists finger, finger-to-finger, and alternate nose-to-finger. Other uses The term "ataxia" is sometimes used in a broader sense to indicate lack of coordination in some physiological process. Examples include optic ataxia (lack of coordination between visual inputs and hand movements, resulting in inability to reach and grab objects) and ataxic respiration (lack of coordination in respiratory movements, usually due to dysfunction of the respiratory centres in the medulla oblongata). Optic ataxia may be caused by lesions to the posterior parietal cortex, which is responsible for combining and expressing positional information and relating it to movement. Outputs of the posterior parietal cortex include the spinal cord, brain stem motor pathways, pre-motor and pre-frontal cortex, basal ganglia and the cerebellum. Some neurons in the posterior parietal cortex are modulated by intention. Optic ataxia is usually part of Balints syndrome, but can be seen in isolation with injuries to the superior parietal lobule, as it represents a disconnection between visual-association cortex and the frontal premotor and motor cortex. See also Ataxic cerebral palsy Locomotor ataxia Bruns apraxia References Further reading == External links ==

Paleness

Paleness may refer to: Pallor, a medical condition Paleness (color) See also Pale (disambiguation)

Rectal tenesmus

Rectal tenesmus is a feeling of incomplete defecation. It is the sensation of inability or difficulty to empty the bowel at defecation, even if the bowel contents have already been evacuated. Tenesmus indicates the feeling of a residue, and is not always correlated with the actual presence of residual fecal matter in the rectum. It is frequently painful and may be accompanied by involuntary straining and other gastrointestinal symptoms. Tenesmus has both a nociceptive and a neuropathic component. Often, rectal tenesmus is simply called tenesmus. The term rectal tenesmus is a retronym to distinguish defecation-related tenesmus from vesical tenesmus. Vesical tenesmus is a similar condition, experienced as a feeling of incomplete voiding despite the bladder being empty. Tenesmus is a closely related topic to obstructed defecation. The term is from Latin: tēnesmus, from Greek τεινεσμός teinesmos, from τείνω teínō to stretch, strain. Considerations Tenesmus is characterized by a sensation of needing to pass stool, accompanied by pain, cramping, and straining. Despite straining, little stool is passed. Tenesmus is generally associated with inflammatory diseases of the bowel, which may be caused by either infectious or noninfectious conditions. Conditions associated with tenesmus include: Tenesmus (rectal) is also associated with the installation of either a reversible or non reversible stoma where rectal disease may or may not be present. Patients who experience tenesmus as a result of stoma installation can experience the symptoms of tenesmus for the duration of the stoma presence. Long term pain management may need to be considered as a result. Treatment Pain relief is administered concomitantly to the treatment of the primary disease causing tenesmus. See also Encopresis Constipation Fecal incontinence References External links MedlinePlus Encyclopedia: 003131

Acute pancreatitis

Acute pancreatitis (AP) is a sudden inflammation of the pancreas. Causes in order of frequency include: 1) a gallstone impacted in the common bile duct beyond the point where the pancreatic duct joins it; 2) heavy alcohol use; 3) systemic disease; 4) trauma; 5) and, in minors, mumps. Acute pancreatitis may be a single event; it may be recurrent; or it may progress to chronic pancreatitis. Mild cases are usually successfully treated with conservative measures: hospitalization, pain control, nothing by mouth, intravenous nutritional support, and intravenous fluid rehydration. Severe cases often require admission to an intensive care unit to monitor and manage complications of the disease. Complications are associated with a high mortality, even with optimal management. Signs and symptoms Common severe epigastric pain (upper abdominal pain) radiating to the back in 50% of cases nausea vomiting loss of appetite fever chills (shivering) hemodynamic instability, including shock tachycardia (rapid heartbeat) respiratory distress peritonitis hiccupAlthough these are common symptoms, frequently they are not all present; and epigastric pain may be the only symptom. Uncommon The following are associated with severe disease: Grey-Turners sign (hemorrhagic discoloration of the flanks) Cullens sign (hemorrhagic discoloration of the umbilicus) Pleural effusions (fluid in the bases of the pleural cavity) Grünwald sign (appearance of ecchymosis, large bruise, around the umbilicus due to local toxic lesion of the vessels) Körtes sign (pain or resistance in the zone where the head of pancreas is located (in epigastrium, 6–7 cm above the umbilicus)) Kamenchiks sign (pain with pressure under the xiphoid process) Mayo-Robsons sign (pain while pressing at the top of the angle lateral to the erector spinae muscles and below the left 12th rib (left costovertebral angle (CVA)) Mayo-Robsons point – a point on border of inner 2/3 with the external 1/3 of the line that represents the bisection of the left upper abdominal quadrant, where tenderness on pressure exists in disease of the pancreas. At this point the tail of pancreas is projected on the abdominal wall. Complications Locoregional complications include pancreatic pseudocyst (most common, occurring in up to 25% of all cases, typically after 4–6 weeks) and phlegmon/abscess formation, splenic artery pseudoaneurysms, hemorrhage from erosions into splenic artery and vein, thrombosis of the splenic vein, superior mesenteric vein and portal veins (in descending order of frequency), duodenal obstruction, common bile duct obstruction, progression to chronic pancreatitis, pancreatic ascites, pleural effusion, sterile/infected pancreatic necrosis.Systemic complications include ARDS, multiple organ dysfunction syndrome, DIC, hypocalcemia (from fat saponification), hyperglycemia and insulin dependent diabetes mellitus (from pancreatic insulin-producing beta cell damage), malabsorption due to exocrine failure MetabolicHypocalcemia, hyperglycemia, hypertriglyceridemiaRespiratoryHypoxemia, atelectasis, Effusion, pneumonitis, Acute respiratory distress syndrome (ARDS)Renal Renal artery or vein thrombosis Kidney failure Circulatory Arrhythmias Hypovolemia and shock myocardial infarction Pericardial effusion vascular thrombosis Gastrointestinal Gastrointestinal hemorrhage from stress ulceration; gastric varices (secondary to splenic vein thrombosis) Gastrointestinal obstruction Hepatobiliary Jaundice Portal vein thrombosis Neurologic Psychosis or encephalopathy (confusion, delusion and coma) Cerebral Embolism Blindness (angiopathic retinopathy with hemorrhage) Hematologic Anemia DIC Leucocytosis Dermatologic Painful subcutaneous fat necrosis Miscellaneous Subcutaneous fat necrosis Arthalgia Causes Most common Biliary pancreatitis due to gallstones or constriction of ampulla of Vater in 40% of cases Alcohol in 30% of cases Idiopathic in 15-25% of cases Metabolic disorders: hereditary pancreatitis, hypercalcemia, elevated triglycerides, malnutrition Post-ERCP Abdominal trauma Penetrating ulcers Carcinoma of the head of pancreas, and other cancer Drugs: diuretics (e.g., thiazides, furosemide), gliptins (e.g., vildagliptin, sitagliptin, saxagliptin, linagliptin), tetracycline, sulfonamides, estrogens, azathioprine and mercaptopurine, pentamidine, salicylates, steroids, Depakote Infections: mumps, viral hepatitis, coxsackie B virus, cytomegalovirus, Mycoplasma pneumoniae, Ascaris Structural abnormalities: choledochocele, pancreas divisum Radiotherapy Autoimmune pancreatitis Severe hypertriglyceridemia Less common Scorpion venom Chinese liver fluke Ischemia from bypass surgery Heart valve surgery Fat necrosis Pregnancy Infections other than mumps, including varicella zoster Hyperparathyroidism Valproic acid Cystic fibrosis Anorexia or bulimia Codeine phosphate reaction Pathology Pathogenesis Acute pancreatitis occurs when there is abnormal activation of digestive enzymes within the pancreas. This occurs through inappropriate activation of inactive enzyme precursors called zymogens (or proenzymes) inside the pancreas, most notably trypsinogen. Normally, trypsinogen is converted to its active form (trypsin) in the first part of the small intestine (duodenum), where the enzyme assists in the digestion of proteins. During an episode of acute pancreatitis, trypsinogen comes into contact with lysosomal enzymes (specifically cathepsin), which activate trypsinogen to trypsin. The active form trypsin then leads to further activation of other molecules of trypsinogen. The activation of these digestive enzymes lead to inflammation, edema, vascular injury, and even cellular death. The death of pancreatic cells occurs via two main mechanisms: necrosis, which is less organized and more damaging, or apoptosis, which is more controlled. The balance between these two mechanisms of cellular death is mediated by caspases which regulate apoptosis and have important anti-necrosis functions during pancreatitis: preventing trypsinogen activation, preventing ATP depletion through inhibiting polyADP-ribose polymerase, and by inhibiting the inhibitors of apoptosis (IAPs). If, however, the caspases are depleted due to either chronic ethanol exposure or through a severe insult then necrosis can predominate. Pathophysiology The two types of acute pancreatitis are mild and severe, which are defined based on whether the predominant response to cell injury is inflammation (mild) or necrosis (severe). In mild pancreatitis, there is inflammation and edema of the pancreas. In severe pancreatitis, there is necrosis of the pancreas, and nearby organs may become injured. As part of the initial injury there is an extensive inflammatory response due to pancreatic cells synthesizing and secreting inflammatory mediators: primarily TNF-alpha and IL-1. A hallmark of acute pancreatitis is a manifestation of the inflammatory response, namely the recruitment of neutrophils to the pancreas. The inflammatory response leads to the secondary manifestations of pancreatitis: hypovolemia from capillary permeability, acute respiratory distress syndrome, disseminated intravascular coagulations, renal failure, cardiovascular failure, and gastrointestinal hemorrhage. Histopathology The acute pancreatitis (acute hemorrhagic pancreatic necrosis) is characterized by acute inflammation and necrosis of pancreas parenchyma, focal enzymic necrosis of pancreatic fat and vessel necrosis (hemorrhage). These are produced by intrapancreatic activation of pancreatic enzymes. Lipase activation produces the necrosis of fat tissue in pancreatic interstitium and peripancreatic spaces as well as vessel damage. Necrotic fat cells appear as shadows, contours of cells, lacking the nucleus, pink, finely granular cytoplasm. It is possible to find calcium precipitates (hematoxylinophilic). Digestion of vascular walls results in thrombosis and hemorrhage. Inflammatory infiltrate is rich in neutrophils. Due to the pancreas lacking a capsule, the inflammation and necrosis can extend to include fascial layers in the immediate vicinity of the pancreas. Diagnosis Acute pancreatitis is diagnosed using clinical history and physical examination, based on the presence of at least 2 of 3 criteria: abdominal pain, elevated serum lipase or amylase, and abdominal imaging findings consistent with acute pancreatitis. Additional blood studies are used to identify organ failure, offer prognostic information, and determine if fluid resuscitation is adequate and whether ERCP is necessary. Blood investigations – complete blood count, kidney function tests, liver function, serum calcium, serum amylase and lipase Imaging – A triple phase abdominal CT and abdominal ultrasound are together considered the gold standard for the evaluation of acute pancreatitis. Other modalities including the abdominal x-ray lack sensitivity and are not recommended. An important caveat is that imaging during the first 12 hours may be falsely reassuring as the inflammatory and necrotic process usually requires 48 hours to fully manifest. Differential diagnosis The differential diagnosis includes: Perforated peptic ulcer Biliary colic Acute cholecystitis Pneumonia Pleuritic pain Myocardial infarction Biochemical Elevated serum amylase and lipase levels, in combination with severe abdominal pain, often trigger the initial diagnosis of acute pancreatitis. However, they have no role in assessing disease severity. Serum lipase rises 4 to 8 hours from the onset of symptoms and normalizes within 7 to 14 days after treatment. Serum amylase may be normal (in 10% of cases) for cases of acute or chronic pancreatitis (depleted acinar cell mass) and hypertriglyceridemia. Reasons for false positive elevated serum amylase include salivary gland disease (elevated salivary amylase), bowel obstruction, infarction, cholecystitis, and a perforated ulcer. If the lipase level is about 2.5 to 3 times that of amylase, it is an indication of pancreatitis due to alcohol.Decreased serum calcium GlycosuriaRegarding selection on these tests, two practice guidelines state: "It is usually not necessary to measure both serum amylase and lipase. Serum lipase may be preferable because it remains normal in some nonpancreatic conditions that increase serum amylase including macroamylasemia, parotitis, and some carcinomas. In general, serum lipase is thought to be more sensitive and specific than serum amylase in the diagnosis of acute pancreatitis""Although amylase is widely available and provides acceptable accuracy of diagnosis, where lipase is available it is preferred for the diagnosis of acute pancreatitis (recommendation grade A)"Most, but not all individual studies support the superiority of the lipase. In one large study, there were no patients with pancreatitis who had an elevated amylase with a normal lipase. Another study found that the amylase could add diagnostic value to the lipase, but only if the results of the two tests were combined with a discriminant function equation.While often quoted lipase levels of 3 or more times the upper-limit of normal is diagnostic of pancreatitis, there are also other differential diagnosis to be considered relating to this rise. Computed tomography Regarding the need for computed tomography, practice guidelines state: CT is an important common initial assessment tool for acute pancreatitis. Imaging is indicated during the initial presentation if: the diagnosis of acute pancreatitis is uncertain there is abdominal distension and tenderness, fever >102 F (38,9 C), or leukocytosis there is a Ranson score > 3 or APACHE score > 8 there is no improvement after 72 hours of conservative medical therapy there has been an acute change in status: fever, pain, or shockCT is recommended as a delayed assessment tool in the following situations: acute change in status to determine therapeutic response after surgery or interventional radiologic procedure before discharge in patients with severe acute pancreatitisAbdominal CT should not be performed before the first 12 hours of onset of symptoms as early CT (<12 hours) may result in equivocal or normal findings. CT findings can be classified into the following categories for easy recall: Intrapancreatic – diffuse or segmental enlargement, edema, gas bubbles, pancreatic pseudocysts and phlegmons/abscesses (which present 4 to 6 wks after initial onset) Peripancreatic / extrapancreatic – irregular pancreatic outline, obliterated peripancreatic fat, retroperitoneal edema, fluid in the lessar sac, fluid in the left anterior pararenal space Locoregional – Gerotas fascia sign (thickening of inflamed Gerotas fascia, which becomes visible), pancreatic ascites, pleural effusion (seen on basal cuts of the pleural cavity), adynamic ileus, etc.The principal value of CT imaging to the treating clinician is the capacity to identify devitalised areas of the pancreas which have become necrotic due to ischaemia. Pancreatic necrosis can be reliably identified by intravenous contrast-enhanced CT imaging, and is of value if infection occurs and surgical or percutaneous debridement is indicated. Magnetic resonance imaging While computed tomography is considered the gold standard in diagnostic imaging for acute pancreatitis, magnetic resonance imaging (MRI) has become increasingly valuable as a tool for the visualization of the pancreas, particularly of pancreatic fluid collections and necrotized debris. Additional utility of MRI includes its indication for imaging of patients with an allergy to CTs contrast material, and an overall greater sensitivity to hemorrhage, vascular complications, pseudoaneurysms, and venous thrombosis.Another advantage of MRI is its utilization of magnetic resonance cholangiopancreatography (MRCP) sequences. MRCP provides useful information regarding the etiology of acute pancreatitis, i.e., the presence of tiny biliary stones (choledocholithiasis or cholelithiasis) and duct anomalies. Clinical trials indicate that MRCP can be as effective a diagnostic tool for acute pancreatitis with biliary etiology as endoscopic retrograde cholangiopancreatography, but with the benefits of being less invasive and causing fewer complications. Ultrasound On abdominal ultrasonography, the finding of a hypoechoic and bulky pancreas is regarded as diagnostic of acute pancreatitis. Treatment Initial management of a patient with acute pancreatitis consists of supportive care with fluid resuscitation, pain control, nothing by mouth, and nutritional support. Fluid replacement Aggressive hydration at a rate of 5 to 10 mL/kg per hour of isotonic crystalloid solution (e.g., normal saline or lactated Ringers solution) to all patients with acute pancreatitis, unless cardiovascular, renal, or other related comorbid factors preclude aggressive fluid replacement. In patients with severe volume depletion that manifests as hypotension and tachycardia, more rapid repletion with 20 mL/kg of intravenous fluid given over 30 minutes followed by 3 mL/kg/hour for 8 to 12 hours.Fluid requirements should be reassessed at frequent intervals in the first six hours of admission and for the next 24 to 48 hours. The rate of fluid resuscitation should be adjusted based on clinical assessment, hematocrit and blood urea nitrogen (BUN) values. In the initial stages (within the first 12 to 24 hours) of acute pancreatitis, fluid replacement has been associated with a reduction in morbidity and mortality. Pain control Abdominal pain is often the predominant symptom in patients with acute pancreatitis and should be treated with analgesics. Opioids are safe and effective at providing pain control in patients with acute pancreatitis. Adequate pain control requires the use of intravenous opiates, usually in the form of a patient-controlled analgesia pump. Hydromorphone or fentanyl (intravenous) may be used for pain relief in acute pancreatitis. Fentanyl is being increasingly used due to its better safety profile, especially in renal impairment. As with other opiates, fentanyl can depress respiratory function. It can be given both as a bolus as well as constant infusion. Meperidine has been historically favored over morphine because of the belief that morphine caused an increase in sphincter of Oddi pressure. However, no clinical studies suggest that morphine can aggravate or cause pancreatitis or cholecystitis. In addition, meperidine has a short half-life and repeated doses can lead to accumulation of the metabolite normeperidine, which causes neuromuscular side effects and, rarely, seizures. Bowel rest In the management of acute pancreatitis, the treatment is to stop feeding the patient, giving them nothing by mouth, giving intravenous fluids to prevent dehydration, and sufficient pain control. As the pancreas is stimulated to secrete enzymes by the presence of food in the stomach, having no food pass through the system allows the pancreas to rest. Approximately 20% of patients have a relapse of pain during acute pancreatitis. Approximately 75% of relapses occur within 48 hours of oral refeeding.The incidence of relapse after oral refeeding may be reduced by post-pyloric enteral rather than parenteral feeding prior to oral refeeding. IMRIE scoring is also useful. Nutritional support Recently, there has been a shift in the management paradigm from total parenteral nutrition (TPN) to early, post-pyloric enteral feeding (in which a feeding tube is endoscopically or radiographically introduced to the third portion of the duodenum). The advantage of enteral feeding is that it is more physiological, prevents gut mucosal atrophy, and is free from the side effects of TPN (such as fungemia). The additional advantages of post-pyloric feeding are the inverse relationship of pancreatic exocrine secretions and distance of nutrient delivery from the pylorus, as well as reduced risk of aspiration. Disadvantages of a naso-enteric feeding tube include increased risk of sinusitis (especially if the tube remains in place greater than two weeks) and a still-present risk of accidentally intubating the trachea even in intubated patients (contrary to popular belief, the endotracheal tube cuff alone is not always sufficient to prevent NG tube entry into the trachea). Oxygen Oxygen may be provided in some patients (about 30%) if Pao2 levels fall below 70mm of Hg. Antibiotics Up to 20 percent of people with acute pancreatitis develop an infection outside the pancreas such as bloodstream infections, pneumonia, or urinary tract infections. These infections are associated with an increase in mortality. When an infection is suspected, antibiotics should be started while the source of the infection is being determined. However, if cultures are negative and no source of infection is identified, antibiotics should be discontinued. Preventative antibiotics are not recommended in people with acute pancreatitis, regardless of the type (interstitial or necrotizing) or disease severity (mild, moderately severe, or severe) ERCP In 30% of those with acute pancreatitis, no cause is identified. ERCP with empirical biliary sphincterotomy has an equal chance of causing complications and treating the underlying cause, therefore, is not recommended for treating acute pancreatitis. If a gallstone is detected, Endoscopic retrograde cholangiopancreatography (ERCP), performed within 24 to 72 hours of presentation with successful removal of the stone, is known to reduce morbidity and mortality. The indications for early ERCP are: Clinical deterioration or lack of improvement after 24 hours Detection of common bile duct stones or dilated intrahepatic or extrahepatic ducts on abdominal CTThe risks of ERCP are that it may worsen pancreatitis, it may introduce an infection to otherwise sterile pancreatitis, and bleeding. Surgery Surgery is indicated for (i) infected pancreatic necrosis and (ii) diagnostic uncertainty and (iii) complications. The most common cause of death in acute pancreatitis is secondary infection. Infection is diagnosed based on 2 criteria Gas bubbles on CT scan (present in 20 to 50% of infected necrosis) Positive bacterial culture on FNA (fine needle aspiration, usually CT or US guided) of the pancreas.Surgical options for infected necrosis include: Minimally invasive management – necrosectomy through small incision in skin (left flank) or abdomen Conventional management – necrosectomy with simple drainage Closed management – necrosectomy with closed continuous postoperative lavage Open management – necrosectomy with planned staged reoperations at definite intervals (up to 20+ reoperations in some cases) Other measures Pancreatic enzyme inhibitors are proven not to work. The use of octreotide has been shown not to improve outcomes. Classification by severity: prognostic scoring systems Acute pancreatitis patients recover in majority of cases. Some may develop abscess, pseudocyst or duodenal obstruction. In 5 percent cases, it may result in ARDS (acute respiratory distress syndrome), DIC (disseminated intravascular coagulation) Acute pancreatitis can be further divided into mild and severe pancreatitis. Mostly the Ranson Criteria are used to determine severity of acute pancreatitis. In severe pancreatitis serious amounts of necrosis determine the further clinical outcome. About 20% of the acute pancreatitis are severe with a mortality of about 20%. This is an important classification as severe pancreatitis will need intensive care therapy whereas mild pancreatitis can be treated on the common ward. Necrosis will be followed by a systemic inflammatory response syndrome (SIRS) and will determine the immediate clinical course. The further clinical course is then determined by bacterial infection. SIRS is the cause of bacterial (Gram negative) translocation from the patients colon. There are several ways to help distinguish between these two forms. One is the above-mentioned Ranson Score. In predicting the prognosis, there are several scoring indices that have been used as predictors of survival. Two such scoring systems are the Ranson criteria and APACHE II (Acute Physiology and Chronic Health Evaluation) indices. Most, but not all studies report that the Apache score may be more accurate. In the negative study of the APACHE-II, the APACHE-II 24-hour score was used rather than the 48-hour score. In addition, all patients in the study received an ultrasound twice which may have influenced allocation of co-interventions. Regardless, only the APACHE-II can be fully calculated upon admission. As the APACHE-II is more cumbersome to calculate, presumably patients whose only laboratory abnormality is an elevated lipase or amylase do not need assessment with the APACHE-II; however, this approach is not studied. The APACHE-II score can be calculated at www.sfar.org. Practice guidelines state: 2006: "The two tests that are most helpful at admission in distinguishing mild from severe acute pancreatitis are APACHE-II score and serum hematocrit. It is recommended that APACHE-II scores be generated during the first 3 days of hospitalization and thereafter as needed to help in this distinction. It is also recommended that serum hematocrit be obtained at admission, 12 h after admission, and 24 h after admission to help gauge adequacy of fluid resuscitation."2005: "Immediate assessment should include clinical evaluation, particularly of any cardiovascular, respiratory, and renal compromise, body mass index, chest x ray, and APACHE II score" Ranson score The Ranson score is used to predict the severity of acute pancreatitis. They were introduced in 1974. At admission age in years > 55 years white blood cell count > 16000 cells/mm3 blood glucose > 11.1 mmol/L (> 200 mg/dL) serum AST > 250 IU/L serum LDH > 350 IU/L At 48 hours Calcium (serum calcium < 2.0 mmol/L (< 8.0 mg/dL) Hematocrit fall >10% Oxygen (hypoxemia PO2 < 60 mmHg) BUN increased by 1.8 or more mmol/L (5 or more mg/dL) after IV fluid hydration Base deficit (negative base excess) > 4 mEq/L Sequestration of fluids > 6 LThe criteria for point assignment is that a certain breakpoint be met at any time during that 48 hour period, so that in some situations it can be calculated shortly after admission. It is applicable to both gallstone and alcoholic pancreatitis. Alternatively, pancreatitis can be diagnosed by meeting any of the following:[2] Alternative Ranson score Ransons score of ≥ 8 Organ failure Substantial pancreatic necrosis (at least 30% glandular necrosis according to contrast-enhanced CT) Interpretation If the score ≥ 3, severe pancreatitis likely. If the score < 3, severe pancreatitis is unlikely Or Score 0 to 2 : 2% mortality Score 3 to 4 : 15% mortality Score 5 to 6 : 40% mortality Score 7 to 8 : 100% mortality APACHE II score "Acute Physiology And Chronic Health Evaluation" (APACHE II) score > 8 points predicts 11% to 18% mortality Hemorrhagic peritoneal fluid Obesity Indicators of organ failure Hypotension (SBP <90 mmHG) or tachycardia > 130 beat/min PO2 <60 mmHg Oliguria (<50 mL/h) or increasing BUN and creatinine Serum calcium < 1.90 mmol/L (<8.0 mg/dL) or serum albumin <33 g/L (<3.2.g/dL)> Balthazar score Developed in the early 1990s by Emil J. Balthazar et al., the Computed Tomography Severity Index (CTSI) is a grading system used to determine the severity of acute pancreatitis. The numerical CTSI has a maximum of ten points, and is the sum of the Balthazar grade points and pancreatic necrosis grade points: Balthazar grade Necrosis score CTSIs staging of acute pancreatitis severity has been shown by a number of studies to provide more accurate assessment than APACHE II, Ranson, and C-reactive protein (CRP) level. However, a few studies indicate that CTSI is not significantly associated with the prognosis of hospitalization in patients with pancreatic necrosis, nor is it an accurate predictor of AP severity. Glasgow score The Glasgow score is valid for both gallstone and alcohol induced pancreatitis, whereas the Ranson score is only for alcohol induced pancreatitis. If a patient scores 3 or more it indicates severe pancreatitis and the patient should be considered for transfer to ITU. It is scored through the mnemonic, PANCREAS: P - PaO2 <8kPa A - Age >55-years-old N - Neutrophilia: WCC >15x10(9)/L C - Calcium <2 mmol/L R - Renal function: Urea >16 mmol/L E - Enzymes: LDH >600iu/L; AST >200iu/L A - Albumin <32g/L (serum) S - Sugar: blood glucose >10 mmol/L BISAP score Predicts mortality risk in pancreatitis with fewer variables than Ransons criteria. Data should be taken from the first 24 hours of the patients evaluation. BUN >25 mg/dL (8.9 mmol/L) Abnormal mental status with a Glasgow coma score <15 Evidence of SIRS (systemic inflammatory response syndrome) Patient age >60 years old Imaging study reveals pleural effusionPatients with a score of zero had a mortality of less than one percent, whereas patients with a score of five had a mortality rate of 22 percent. In the validation cohort, the BISAP score had similar test performance characteristics for predicting mortality as the APACHE II score. As is a problem with many of the other scoring systems, the BISAP has not been validated for predicting outcomes such as length of hospital stay, need for ICU care, or need for intervention. Epidemiology In the United States, the annual incidence is 18 cases of acute pancreatitis per 100,000 population, and it accounts for 220,000 hospitalizations in the US. In a European cross-sectional study, incidence of acute pancreatitis increased from 12.4 to 15.9 per 100,000 annually from 1985 to 1995; however, mortality remained stable as a result of better outcomes. Another study showed a lower incidence of 9.8 per 100,000 but a similar worsening trend (increasing from 4.9 in 1963–74) over time.In Western countries, the most common cause is alcohol, accounting for 65 percent of acute pancreatitis cases in the US, 20 percent of cases in Sweden, and 5 percent of those in the United Kingdom. In Eastern countries, gallstones are the most common cause of acute pancreatitis. The causes of acute pancreatitis also varies across age groups, with trauma and systemic disease (such as infection) being more common in children. Mumps is a more common cause in adolescents and young adults than in other age groups. See also Canine pancreatitis Chronic pancreatitis References External links Banks et al. Modified Marshall scoring system online calculator Pathology Atlas image. Parikh RP, Upadhyay KJ. Cullens sign for acute haemorrhagic pancreatitis. Indian J Med Res [serial online] 2013 [cited 2013 Jul 4];137:1210 http://www.ijmr.org.in/text.asp?2013/137/6/1210/114397

Cyanide poisoning

Cyanide poisoning is poisoning that results from exposure to any of a number of forms of cyanide. Early symptoms include headache, dizziness, fast heart rate, shortness of breath, and vomiting. This phase may then be followed by seizures, slow heart rate, low blood pressure, loss of consciousness, and cardiac arrest. Onset of symptoms usually occurs within a few minutes. Some survivors have long-term neurological problems.Toxic cyanide-containing compounds include hydrogen cyanide gas and a number of cyanide salts. Poisoning is relatively common following breathing in smoke from a house fire. Other potential routes of exposure include workplaces involved in metal polishing, certain insecticides, the medication sodium nitroprusside, and certain seeds such as those of apples and apricots. Liquid forms of cyanide can be absorbed through the skin. Cyanide ions interfere with cellular respiration, resulting in the bodys tissues being unable to use oxygen.Diagnosis is often difficult. It may be suspected in a person following a house fire who has a decreased level of consciousness, low blood pressure, or high lactic acid. Blood levels of cyanide can be measured but take time. Levels of 0.5–1 mg/L are mild, 1–2 mg/L are moderate, 2–3 mg/L are severe, and greater than 3 mg/L generally result in death.If exposure is suspected, the person should be removed from the source of exposure and decontaminated. Treatment involves supportive care and giving the person 100% oxygen. Hydroxocobalamin (vitamin B12a) appears to be useful as an antidote and is generally first-line. Sodium thiosulphate may also be given. Historically cyanide has been used for mass suicide and by the Nazis for genocide. Signs and symptoms Acute exposure If hydrogen cyanide is inhaled it can cause a coma with seizures, apnea, and cardiac arrest, with death following in a matter of seconds. At lower doses, loss of consciousness may be preceded by general weakness, dizziness, headaches, vertigo, confusion, and perceived difficulty in breathing. At the first stages of unconsciousness, breathing is often sufficient or even rapid, although the state of the person progresses towards a deep coma, sometimes accompanied by pulmonary edema, and finally cardiac arrest. A cherry red skin color that darkens may be present as the result of increased venous hemoglobin oxygen saturation. Despite the similar name, cyanide does not directly cause cyanosis. A fatal dose for humans can be as low as 1.5 mg/kg body weight. Other sources claim a lethal dose is 1–3 mg per kg body weight for vertebrates. Chronic exposure Exposure to lower levels of cyanide over a long period (e.g., after use of improperly processed cassava roots, which are a primary food source in tropical Africa) results in increased blood cyanide levels, which can result in weakness and a variety of symptoms, including permanent paralysis, nervous lesions, hypothyroidism, and miscarriages. Other effects include mild liver and kidney damage. Causes Cyanide poisoning can result from the ingestion of cyanide salts; imbibing pure liquid prussic acid; skin absorption of prussic acid; intravenous infusion of nitroprusside for hypertensive crisis; or the inhalation of hydrogen cyanide gas. The last typically occurs through one of three mechanisms: The gas is directly released from canisters (e.g. as part of a pesticide, insecticide, or Zyklon B). It is generated on site by reacting potassium cyanide or sodium cyanide with sulfuric acid (e.g. in a modern American gas chamber). Fumes arise during a building fire or any similar scenario involving the burning of polyurethane, vinyl or other polymer products that required nitriles in their production.As potential contributing factors, cyanide is present in: Tobacco smoke. Many seeds or kernels such as those of almonds, apricots, apples, oranges, and flaxseed. Foods including cassava (also known as tapioca, yuca or manioc) and bamboo shoots.As a potential harm-reduction factor, Vitamin B12, in the form of hydroxocobalamin (also spelled hydroxycobalamin), might reduce the negative effects of chronic exposure; whereas, a deficiency might worsen negative health effects following exposure to cyanide. Mechanism Cyanide is a potent cytochrome c oxidase (COX, a.k.a Complex IV) inhibitor. As such, cyanide poisoning is a form of histotoxic hypoxia, because it interferes with oxidative phosphorylation.: 1475 Specifically, cyanide binds to the heme a3-CuB binuclear center of COX (and thus is a non-competitive inhibitor of it). This prevents electrons passing through COX from being transferred to O2, which not only blocks the mitochondrial electron transport chain but also interferes with the pumping of a proton out of the mitochondrial matrix which would otherwise occur at this stage. Therefore, cyanide interferes not only with aerobic respiration but also with the ATP synthesis pathway it facilitates, owing to the close relationship between those two processes.: 705 One antidote for cyanide poisoning, nitrite (i.e. via amyl nitrite), works by converting ferrohemoglobin to ferrihemoglobin, which can then compete with COX for free cyanide (as the cyanide will bind to the iron in its heme groups instead). Ferrihemoglobin cannot carry oxygen, but the amount of ferrihemoglobin that can be formed without impairing oxygen transport is much greater than the amount of COX in the body.: 1475 Cyanide is a broad-spectrum poison because the reaction it inhibits is essential to aerobic metabolism; COX is found in many forms of life. However, susceptibility to cyanide is far from uniform across affected species; for instance, plants have an alternative electron transfer pathway available that passes electrons directly from ubiquinone to O2, which confers cyanide resistance by bypassing COX.: 704 Diagnosis Lactate is produced by anaerobic glycolysis when oxygen concentration becomes too low for the normal aerobic respiration pathway. Cyanide poisoning inhibits aerobic respiration and therefore increases anaerobic glycolysis which causes a rise of lactate in the plasma. A lactate concentration above 10 mmol per liter is an indicator of cyanide poisoning, as defined by the presence of a blood cyanide concentration above 40 µmol per liter. Lactate levels greater than 6 mmol/L after reported or strongly suspected pure cyanide poisoning, such as cyanide-containing smoke exposure, suggests significant cyanide exposure.Methods of detection include colorimetric assays such as the Prussian blue test, the pyridine-barbiturate assay, also known as the "Conway diffusion method" and the taurine fluorescence-HPLC but like all colorimetric assays these are prone to false positives. Lipid peroxidation resulting in "TBARS," an artifact of heart attack produces dialdehydes that cross-react with the pyridine-barbiturate assay. Meanwhile, the taurine-fluorescence-HPLC assay used for cyanide detection is identical to the assay used to detect glutathione in spinal fluid. Cyanide and thiocyanate assays have been run with mass spectrometry (LC/MS/MS), which are considered specific tests. Since cyanide has a short half-life, the main metabolite, thiocyanate is typically measured to determine exposure. Other methods of detection include the identification of plasma lactate. Treatment Decontamination Decontamination of people exposed to hydrogen cyanide gas only requires removal of the outer clothing and the washing of their hair. Those exposed to liquids or powders generally require full decontamination. Antidote The International Programme on Chemical Safety issued a survey (IPCS/CEC Evaluation of Antidotes Series) that lists the following antidotal agents and their effects: oxygen, sodium thiosulfate, amyl nitrite, sodium nitrite, 4-dimethylaminophenol, hydroxocobalamin, and dicobalt edetate (Kelocyanor), as well as several others. Other commonly-recommended antidotes are solutions A and B (a solution of ferrous sulfate in aqueous citric acid, and aqueous sodium carbonate, respectively) and amyl nitrite. The United States standard cyanide antidote kit first uses a small inhaled dose of amyl nitrite, followed by intravenous sodium nitrite, followed by intravenous sodium thiosulfate. Hydroxocobalamin was approved for use in the US in late 2006 and is available in Cyanokit antidote kits. Sulfanegen TEA, which could be delivered to the body through an intra-muscular (IM) injection, detoxifies cyanide and converts the cyanide into thiocyanate, a less toxic substance. Alternative methods of treating cyanide intoxication are used in other countries. The Irish Health and Safety Executive (HSE) has recommended against the use of solutions A and B because of their limited shelf life, potential to cause iron poisoning, and limited applicability (effective only in cases of cyanide ingestion, whereas the main modes of poisoning are inhalation and skin contact). The HSE has also questioned the usefulness of amyl nitrite due to storage/availability problems, risk of abuse, and lack of evidence of significant benefits. It also states that the availability of kelocyanor at the workplace may mislead doctors into treating a patient for cyanide poisoning when this is an erroneous diagnosis. The HSE no longer recommends a particular cyanide antidote. History Fires The República Cromañón nightclub fire broke out in Buenos Aires, Argentina on 30 December 2004, killing 194 people and leaving at least 1,492 injured. Most of the victims died from inhaling poisonous gases, and carbon monoxide. After the fire, the technical institution INTI found that the level of toxicity due to the materials and volume of the building was 225 ppm of cyanide in the air. A lethal dose for rats is between 150 ppm and 220 ppm, meaning the air in the building was highly toxic. On 5 December 2009, a fire in the night club Lame Horse (Khromaya Loshad) in the Russian city of Perm took the lives of 156 people. Fatalities consisted of 111 people at the site and 45 later in hospitals. One of the main causes of death was poisoning from cyanide and other toxic gases released by the burning of plastic and polyurethane foam used in the construction of club interiors. Taking into account the number of deaths, this was the largest fire in post-Soviet Russia.On 27 January 2013, a fire at the Kiss nightclub in the city of Santa Maria, in the south of Brazil, caused the poisoning of hundreds of young people by cyanide released by the combustion of soundproofing foam made with polyurethane. By March 2013, 245 fatalities were confirmed. Gas chambers In early 1942, Zyklon B, which contains hydrogen cyanide, emerged as the preferred killing tool of Nazi Germany for use in extermination camps during the Holocaust. The chemical was used to murder roughly one million people in gas chambers installed in extermination camps at Auschwitz-Birkenau, Majdanek, and elsewhere. Most of the people who were murdered were Jews, and by far the majority of these murders took place at Auschwitz. Zyklon B was supplied to concentration camps at Mauthausen, Dachau, and Buchenwald by the distributor Heli, and to Auschwitz and Majdanek by Testa. Camps also occasionally bought Zyklon B directly from the manufacturers. Of the 729 tonnes of Zyklon B sold in Germany in 1942–44, 56 tonnes (about eight percent of domestic sales) were sold to concentration camps. Auschwitz received 23.8 tonnes, of which six tonnes were used for fumigation. The remainder was used in the gas chambers or lost to spoilage (the product had a stated shelf life of only three months). Testa conducted fumigations for the Wehrmacht and supplied them with Zyklon B. They also offered courses to the SS in the safe handling and use of the material for fumigation purposes. In April 1941, the German agriculture and interior ministries designated the SS as an authorized applier of the chemical, and thus they were able to use it without any further training or governmental oversight.Hydrogen cyanide gas has been used for judicial execution in some states of the United States, where cyanide was generated by reaction between potassium cyanide (or sodium cyanide) dropped into a compartment containing sulfuric acid, directly below the chair in the gas chamber. Suicide Cyanide salts are sometimes used as fast-acting suicide devices. Cyanide reacts at a higher level with high stomach acidity. On 26 January 1904, company promoter and swindler Whitaker Wright committed suicide by ingesting cyanide in a court anteroom immediately after being convicted of fraud. In February 1937, the Uruguayan short story writer Horacio Quiroga committed suicide by drinking cyanide in a hospital at Buenos Aires. In 1937, polymer chemist Wallace Carothers committed suicide by cyanide. In the 1943 Operation Gunnerside to destroy the Vemork Heavy Water Plant in World War II (an attempt to stop or slow German atomic bomb progress), the commandos were given cyanide tablets (cyanide enclosed in rubber) kept in the mouth and were instructed to bite into them in case of German capture. The tablets ensured death within three minutes. Cyanide, in the form of pure liquid prussic acid (a historical name for hydrogen cyanide), was the favored suicide agent of Nazi Germany. Erwin Rommel (1944), Adolf Hitlers wife, Eva Braun (1945), and Nazi leaders Heinrich Himmler (1945), possibly Martin Bormann (1945), and Hermann Göring (1946) all committed suicide by ingesting it. It is speculated that, in 1954, Alan Turing used an apple that had been injected with a solution of cyanide to commit suicide after being convicted of having a homosexual relationship, which was illegal at the time in the United Kingdom, and forced to undergo hormonal castration to avoid prison. An inquest determined that Turings death from cyanide poisoning was a suicide, although this has been disputed. Members of the Sri Lankan LTTE (Liberation Tigers of Tamil Eelam, whose insurgency lasted from 1983 to 2009), used to wear cyanide vials around their necks with the intention of committing suicide if captured by the government forces. On 22 June 1977, Moscow, Aleksandr Dmitrievich Ogorodnik, a Soviet diplomat accused of spying on behalf of the Colombian Intelligence Agency and the US Central Intelligence Agency, was arrested. During the interrogations, Ogorodnik offered to write a full confession and asked for his pen. Inside the pen cap was a cleverly hidden cyanide pill, which when bitten on, caused Ogorodnik to die before he hit the floor, according to the Soviets. On 18 November 1978, Jonestown. A total of 909 individuals died in Jonestown, many from apparent cyanide poisoning, in an event termed "revolutionary suicide" by Jones and some members on an audio tape of the event and in prior discussions. The poisonings in Jonestown followed the murder of five others by Temple members at Port Kaituma, including United States Congressman Leo Ryan, an act that Jones ordered. Four other Temple members committed murder-suicide in Georgetown at Jones command. On 6 June 1985, serial killer Leonard Lake died in custody after having ingested cyanide pills he had sewn into his clothes. On 28 June 2012, Wall Street trader Michael Marin ingested a cyanide pill seconds after a guilty verdict was read in his arson trial in Phoenix, AZ; he died minutes after. On 22 June 2015, John B. McLemore, a horologist and the central figure of the podcast S-Town, died after ingesting cyanide. On 29 November 2017, Slobodan Praljak died from drinking potassium cyanide, after being convicted of war crimes by the International Criminal Tribunal for the former Yugoslavia. Mining and industrial In 1993, an illegal spill resulted in the death of seven people in Avellaneda, Argentina. In their memory, the National Environmental Conscious Day (Día Nacional de la Conciencia Ambiental) was established. In 2000, a spill at Baia Mare, Romania, resulted in the worst environmental disaster in Europe since Chernobyl. In 2000, Allen Elias, CEO of Evergreen Resources was convicted of knowing endangerment for his role in the cyanide poisoning of employee Scott Dominguez. This was one of the first successful criminal prosecutions of a corporate executive by the Environmental Protection Agency. Murder John Tawell, a murderer who in 1845 became the first person to be arrested as the result of telecommunications technology. Grigori Rasputin (1916; attempted, later killed by gunshot) The Goebbels children (1945) Stepan Bandera (1959) Jonestown, Guyana, was the site of a large mass murder–suicide, in which over 900 members of the Peoples Temple drank potassium cyanide–laced Flavor Aid in 1978. Chicago Tylenol murders (1982) Timothy Marc OBryan (1966–1974) died on October 31, 1974 by ingesting potassium cyanide placed into a giant Pixy Stix. His father, Ronald Clark OBryan, was convicted of Tims murder plus four counts of attempted murder. OBryan put potassium cyanide into five giant Pixy Stix that he gave to his son and daughter along with three other children. Only Timothy ate the poisoned candy and died. Bruce Nickell (5 June 1986) Murdered by his wife who poisoned a bottle of Excedrin. Richard Kuklinski (1935–2006) Janet Overton (1942–1988) Her husband, Richard Overton was convicted of poisoning her, but Janets symptoms did not match those of classic cyanide poisoning, the timeline was inconsistent with cyanide poisoning, and the amount found was just a trace. The diagnostic method used was prone to false positives. Richard Overton died in prison in 2009. Urooj Khan (1966–2012), won the lottery and was found dead a few days later. A blood diagnostic reported a lethal level of cyanide in his blood, but the body did not display any classic symptoms of cyanide poisoning, and no link to cyanide could be found in Uroojs social circle. The diagnostic method used was the Conway diffusion method, prone to false positives with artifacts of heart attack and kidney failure. Autumn Marie Klein (20 April 2013), a prominent 41-year-old neuroscientist and physician, died from cyanide poisoning. Kleins husband, Robert J. Ferrante, also a prominent neuroscientist who used cyanide in his research, was convicted of murder and sentenced to life in prison for her death. Robert Ferrante is appealing his conviction. Mirna Salihin died in hospital on 6 January 2016, after drinking a Vietnamese iced coffee at a cafe in a shopping mall in Jakarta. Police reports claim that cyanide poisoning was the most likely cause of her death. Jolly Thomas of Kozhikode, Kerala, India, was arrested in 2019 for the murder of 6 family members. Murders took place over 14-year period and each victim ate a meal prepared by the killer. The murders were allegedly motivated by wanting control of the family finances and property. Mei Xiang Li of Brooklyn, NY, collapsed and died in April 2017, with cyanide later reported to be in her blood. However, Mei never exhibited symptoms of cyanide poisoning and no link to cyanide could be found in her life. Warfare or terrorism In 1988, between 3,200 and 5,000 people died in the Halabja massacre owing to unknown chemical nerve agents. Hydrogen cyanide gas was strongly suspected. In 1995, a device was discovered in a restroom in the Kayabacho Tokyo subway station, consisting of bags of sodium cyanide and sulfuric acid with a remote controlled motor to rupture them in what was believed to be an attempt by the Aum Shinrikyo cult to produce toxic amounts of hydrogen cyanide gas. In 2003, Al Qaeda reportedly planned to release cyanide gas into the New York City Subway system. The attack was supposedly aborted because there would not be enough casualties. Research Cobinamide is the final compound in the biosynthesis of cobalamin. It has greater affinity for the cyanide than cobalamin itself, which suggests that it could be a better option for emergency treatment. See also Anaerobic glycolysis Lactic acidosis List of poisonings Konzo References Explanatory notes Citations Sources Longerich, Peter (2010). Holocaust: The Nazi Persecution and Murder of the Jews. Oxford; New York: Oxford University Press. ISBN 978-0-19-280436-5. Hayes, Peter (2004). From Cooperation to Complicity: Degussa in the Third Reich. Cambridge; New York; Melbourne: Cambridge University Press. ISBN 978-0-521-78227-2. Piper, Franciszek (1994). "Gas Chambers and Crematoria". In Gutman, Yisrael; Berenbaum, Michael (eds.). Anatomy of the Auschwitz Death Camp. Bloomington, Indiana: Indiana University Press. pp. 157–182. ISBN 978-0-253-32684-3.

Lactation suppression

Lactation suppression refers to the act of suppressing lactation by medication or other non pharmaceutical means. The breasts may become painful when engorged with milk if breastfeeding is ceased abruptly, or if never started. This may occur if a woman never initiates breastfeeding, or if she is weaning from breastfeeding abruptly. Historically women who did not plan to breastfeed were given diethylstilbestrol and other medications after birth to suppress lactation. However, its use was discontinued, and there are no medications currently approved for lactation suppression in the US and the UK. Dopamine agonists are routinely prescribed to women following a stillbirth in the UK under the NHS. Reasons After birth, some women may desire to stop the production of breast milk, for example when the mother decides to bottle feed from birth, or in the case when the infant dies or is surrendered at birth. Additionally, women who are breastfeeding may need to stop breastfeeding abruptly, for instance if she is taking medication contraindicated for breastfeeding or undergoes surgery. The abrupt weaning process may lead to severe engorgement, extremely painful breasts, and possibly mastitis. Up to one third of women who do not breast-feed and who use a brassiere or binder, ice packs, or analgesics may experience severe breast pain. Specific studies of nonpharmacologic methods of lactation suppression were limited and inconclusive. Available data suggest that many women using currently recommended strategies for treatment of symptoms may nevertheless experience engorgement or pain for most of the first postpartum week. Methods Medication Dopamine agonists are currently the preferred medication for suppressing lactation, which work by suppressing prolactin production. Cabergoline (Dostinex™) is currently most effective option currently available, as it is available as a single dose (as opposed to bromocriptine which must be taken twice daily for 2 weeks.) It may be prescribed in the case of breast abscess. Although the preferred method of treatment for breast abscess and mastitis is actually to continue breastfeeding, if the decision is made to stop breastfeeding, then chemical lactation suppression is indicated, particularly for severe cases. Carbergoline is not indicated for treatment of discomfort caused by engorgement. In the UK dopamine agonists are routinely prescribed following a stillbirth. Pre-eclampsia is a contraindication for prescribing dopamine agonists.In the past, hormonal therapies such as diethylstilbestrol were routinely used in the postpartum period, but these are no longer recommended due to side effects such as nausea and vomiting, and severe potential side effects such as thromboembolism, cerebral accident, and myocardial infarction. Estrogen containing birth control pills may have the same side effect, but like diethylstilbestrol is inappropriate for use in the postpartum period due to the risk of side effects. Pseudoephedrine may also suppress lactation, as it is known to cause low supply.In the US. Spitz et al. in a 100-year review of all available information concluded that there was nothing new or helpful to assist with the mammary involution or milk suppression process or to treat the pain or discomfort of severely engorged breasts. Other methods By simply not stimulating the breasts after birth, after a few days the production of milk will decease. If breastfeeding has already been established, the production of milk typically takes longer to decrease and may take several weeks. Women may experience pain and discomfort from engorgement. This discomfort is may be relieved by hand-expressing milk or the use of a pump to reduce engorgement and prevent mastitis. The discomfort can also be treated with analgesics. However, as much as one third of all women will experience severe pain in this process.Historically, binding the breasts by use of tight-fitting bras or ace bandages was used, but this is now discouraged as this may cause blocked milk ducts and mastitis. Fluid restriction is also not recommended as it is likely ineffective and unnecessary.Cabbage leaves are a common recommendation to reduce discomfort from engorgement. However, a Cochrane review of three studies on this subject concluded that there was no statistically significant evidence that interventions were associated with a more rapid resolution of symptoms; in these studies women tended to have improvements in pain and other symptoms over time whether or not they received active treatment.According to the Cochrane review other interventions such as hot/cold packs, Gua-Sha (scraping therapy), acupuncture, and proteolytic enzymes may be promising for the treatment of breast engorgement, but there is insufficient evidence to justify widespread implementation. See also Hypothalamic–pituitary–prolactin axis Prolactin modulator == References ==

Epithelial dysplasia

Epithelial dysplasia, a term becoming increasingly referred to as intraepithelial neoplasia, is the sum of various disturbances of epithelial proliferation and differentiation as seen microscopically. Individual cellular features of dysplasia are called epithelial atypia.Examples of epithelial dysplasia include cervical intraepithelial neoplasia – a disorder commonly detected by an abnormal pap smear) consisting of an increased population of immature (basal-like) cells which are restricted to the mucosal surface, and have not invaded through the basement membrane to the deeper soft tissues. Analogous conditions include vaginal intraepithelial neoplasia and vulvar intraepithelial neoplasia. Metanephric dysplastic hematoma of the sacral region is a dysplastic overgrowth observed in infants. Screening Some tests which detect cancer could be called "screening for epithelial dysplasia". The principle behind these tests is that physicians expect dysplasia to occur at the same rate in a typical individual as it would in many other people. Because of this, researchers design screening recommendations which assume that if a physician can find no dysplasia at certain time, then doing testing before waiting until new dysplasia could potentially develop would be a waste of medical resources for the patient and the healthcare provider because the chances of detecting anything is extremely low. Some examples of this in practice are that if a patient whose endoscopy did not detect dysplasia on biopsy during screening for Barretts esophagus, then research shows that there is little chance of any test detecting dysplasia for that patient within three years.Individuals at average-risk for colorectal cancer should have another screening after ten years if they get a normal result and after five years if they have only one or two adenomatous polyps removed. Microscopic changes Dysplasia is characterised by four major pathological microscopic changes: Anisocytosis (cells of unequal size) Poikilocytosis (abnormally shaped cells) Hyperchromatism (excessive pigmentation) Presence of mitotic figures (an unusual number of cells which are currently dividing).Other changes that occur in epithelial dysplasia include: Drop-shaped rete processes Basal cell hyperplasia Irregular epithelial stratification Increased nuclear-cytoplasmic ratio Increased normal and abnormal mitosis Enlarged nucleoli Individual cell keratinization Loss or reduction of cellular cohesion Cellular pleomorphism Loss of basal cell polarity KoilocytosisEpithelial cell dysplasia is divided into three categories of severity: mild, moderate, and severe. Epithelial dysplasia becomes microinvasive squamous cell carcinoma once the tumor begins to invade nearby tissue. Dysplasia vs. carcinoma in situ vs. invasive carcinoma These terms are related since they represent three stages in the progression of many malignant tumors of the epithelium. The likelihood of the development to cancer is related to the degree of dysplasia. Dysplasia is the earliest form of precancerous lesion which pathologists can recognize in a pap smear or in a biopsy. Dysplasia can be low grade or high grade. The risk of low-grade dysplasia transforming into high-grade dysplasia, and eventually cancer, is low. Treatment is usually straightforward. High-grade dysplasia represents a more advanced progression towards malignant transformation. Carcinoma in situ, meaning "cancer in place", represents the transformation of a neoplastic lesion to one in which cells undergo essentially no maturation, thus may be considered cancer-like. In this state, epithelial cells have lost their tissue identity and have reverted to a primitive cell form that grows rapidly and with abnormal regulation for the tissue type. However, this form of cancer remains localized, and has not invaded past the basement membrane into tissues below the surface. Invasive carcinoma is the final step in this sequence. It is a cancer which has invaded beyond the basement membrane and has potential to spread to other parts of the body. Invasive carcinoma can usually be treated, but not always successfully. However, if it is left untreated, it is almost always fatal. See also Dysplasia == References ==

Purple glove syndrome

Purple glove syndrome (PGS) is a poorly understood skin disease in which the extremities become swollen, discoloured and painful. PGS is potentially serious, and may require amputation. PGS is most common among elderly patients and those receiving multiple large intravenous doses of the epilepsy drug phenytoin. Compartment syndrome is a complication of PGS. Cause Purple glove syndrome is caused by the intravenous anticonvulsant phenytoin. This medication has many already established neurological side effects, however glove syndrome is a rare, but very serious adverse effect that may lead to limb amputations. This may occur due to the administration of phenytoin with or without extravasation. The defining characteristic is a purplish to black discoloration of the extremity followed by peripheral edema and pain distal to the site of infusion. Onset is generally seen within the first few hours of administration. The true pathology of purple glove syndrome is not fully elucidated, however it is believed to be due to the crystallization of phenytoin within the blood and extravasates into the surrounding interstitium. Another mechanism may be due to the disruption of endothelial transcellular junctions followed by leaking of phenytoin into the surround soft tissues. Diagnosis Treatment Doctors recommend discontinuing the use of phenytoin. The application of heat can help to relieve pain. Oral phenytoin can also result in development of purple glove syndrome. References External links FDA: Potential Signals of Serious Risks/New Safety Information Identified by the Adverse Event Reporting System (AERS) -- January - March 2008

Preadolescence

Preadolescence is a stage of human development following early childhood and preceding adolescence. It commonly ends with the beginning of puberty but may also be defined as ending with the start of the teenage years. Preadolescence is commonly defined as ages 9-12 ending with the major onset of puberty. It may also be defined as simply the 2-year period before the major onset of puberty. Preadolescence can bring its own challenges and anxieties. Terminology Other slang and terminology used to refer to the preadolescent stage include tween or tweener, as a combination of the words "teen" and "between."While known as preadolescent in psychology, the terms preteen, preteenager, or tween are common in everyday use. A preteen or preteenager is a person 12 and under. Generally, the term is restricted to those close to reaching age 13, especially ages 9 to 12. Tween is an American neologism and marketing term for preteen, which is a blend of between and teen. People within this age range are variously described as tweens, preadolescents, tweenies, preteens, pubescents, junior highschoolers, middle schoolers, or tweenagers. Prepubescence, puberty, and age range Being prepubescent is not the same thing as being preadolescent. Instead, prepubescent (and sometimes child) is a term for boys and girls who have not developed secondary sex characteristics, while preadolescent is generally defined as those ranging from age 9 to 12 years. Preadolescence may also be defined as the period from 10 to 13 years.The point at which a child becomes an adolescent is defined by the onset of puberty or the beginning of the teenage stage. However, in some individuals (particularly females), puberty begins in the preadolescence years. Studies indicate that the onset of puberty has been one year earlier with each generation since the 1950s.One can also distinguish middle childhood and preadolescence – middle childhood from approximately 5–8 years, as opposed to the time children are generally considered to reach preadolescence. There is no exact agreement as to when preadolescence starts and ends. Hormonal development and the development of secondary sex characteristics Early puberty begins as the result of the initiation of the pulsatile gonadotropin-releasing hormone (GnRH) secretion by the hypothalamus; the exact mechanism of this initiation is currently unknown and remains under investigation. Pulsatile GnRH secretion results in the pulsatile secretions of gonadotropins Luteinizing Hormone (LH) and Follicle Stimulating Hormone (FSH), which act on the gonads (ovaries in females or testicles in males) to cause increase secretion of sex steroids. In females, the predominant sex steroid released is estrogen and in individuals with testicles, the predominant sex steroid released is testosterone. These sex hormones then lead to the development of secondary sex characteristics. The stages of puberty can be described with the Tanner scale, also known as the Sexual Maturity Rating, which incorporates measurements and characteristics of primary and secondary sex characteristics. For example, genital and breast development, as well as pubic hair growth. Pubertal development is regulated by the hypothalamic-pituitary-gonadal (HPG) axis. Tanner staging ranges from 1 through 5 (with 5 being the most developed).With regards to pubic hair development, the scale goes as follows: Stage 1-no hair; 2-downy hair; 3-scant terminal hair; 4-terminal hair overlying the pubic triangle; 5-terminal hair extending to the thigh. With regards to male genitalia development, the scale goes as follows: 1-testes at the same size and proportion of early childhood; 2-enlargement of the scrotum/change in texture of scrotal skin; 3-growth of the penis length-wise; 4-growth of the penis in terms of length and circumference; 5-adult-sized genitalia. With regards to female breast development, the scale is as follows: 1-no palpable gland tissue; 2-palpable breast bud under areola; 3-breast tissue palpable outside of areola; 4-areola elevated above breast contour; 5-areolar mound recedes into single breast contour. The average age in which both males and females reach Tanner stage 5 of pubertal development is around 15–16. Neurological development There are significant neurological changes that are expressed during preadolescence. White matter refers to the region of the nervous system corresponding to neuronal axons, which form fibers that convey information across different regions of the brain. In contrast, grey matter refers to the region of the nervous system corresponding to neuronal cell bodies, which process and relay neuronal signals. White matter volume increases at a relatively linear rate of about 12% from ages 4 through 22, specifically focused in the frontal, parietal, and occipital lobes. Increases in white matter volume may be correlated to improvements of fine motor performance, auditory processing, as well as sensory information transfer between language areas of the brain. In contrast, cortical gray matter increases in early life, peaks in preadolescence, and declines through adulthood, with the exception of occipital lobe gray matter. For example, parietal lobe gray matter peaks at age 10 in girls and 12 in boys, while frontal lobe gray matter peaks at age 11 in girls and 12 in boys. Such changes might reflect overproduction of synapses in the preadolescent years; in subsequent years, there seems to be pruning dependent on environmental context, corresponding to increased synchronicity of neuron firing. A key caveat from these imaging studies, however, is that there exists significant variability in the timing and characteristics of neurological change in preadolescents. Neurological changes, particularly in the prefrontal cortex, appear to be highly dependent on environmental input. Toxins, hormones, and lifestyle factors including stress and nutrition impact neurological maturation, demonstrating the importance of early lifestyle health interventions in preadolescence with regards to neurological and psychological development. Psychological and social development Of the two major socializing agents in childrens lives: the family environment...and formal educational institutions, it is the family in its function a primary socializer of the child that predominates in the first five years of life: middle childhood by contrast is characterized by a childs readiness for school...being self-assured and interested; knowing what kind of behavior is expected...being able to wait, to follow directions, and getting along with other children.Preadolescent children have a different view of the world from younger children in many significant ways. Typically, theirs is a more realistic view of life than the intense, fantasy-oriented world of earliest childhood. Preadolescents have more mature, sensible, realistic thoughts and actions: the most "sensible" stage of development...the child is a much less emotional being now. They will often have developed a sense of intentionality. The wish and capacity to have an impact, and to act upon that with persistence; and will have a more developed sense of looking into the future and seeing effects of their actions (as opposed to early childhood where children often do not worry about their future). This can include more realistic job expectations ("I want to be an engineer when I grow up", as opposed to "I want to be a wizard"). Middle children generally show more investment in control over external reality through the acquisition of knowledge and competence: where they do have worries, these may be more a fear of kidnappings, rapes, and scary media events, as opposed to fantasy things (e.g., witches, monsters, ghosts). Preadolescents may well view human relationships differently (e.g. they may notice the flawed, human side of authority figures). Alongside that, they may begin to develop a sense of self-identity, and to have increased feelings of independence: may feel an individual, no longer "just one of the family." A different view on morality can emerge; and the middle child will also show more cooperativeness. The ability to balance ones own needs with those of others in group activities. Many preadolescents will often start to question their home life and surroundings around this time and they may also start to form opinions that may differ from their upbringing in regards to issues such as politics, religion, sexuality, and gender roles. Greater responsibility within the family can also appear, as middle children become responsible for younger siblings and relatives, as with babysitting; while preadolescents may start caring about what they look like and what they are wearing. Prior to adolescence, children may have a dependence on their family as their main agent of socialization. This helps the child establish their attitudes, viewpoints, social norms, and societal roles.Among these changes is the shift from elementary to middle (or junior high) school. In this unfamiliar environment, the child may find the pressure to rapidly adapt and fit in. Children start to spend less time with family and more time with friends. At this time, socialization by the school and peer environment can become more predominant, as the preadolescent starts to learn more about how they would wish to hold themselves during interpersonal relationships.While children find this need to fit in, preadolescents have a conflicting desire to establish their own individualism. As the child grows into the transitionary period of preadolescence, the child often starts to develop a sense of autonomy as the child is exposed to a larger world around them full of sudden and unfamiliar changes. Compounded with a sense of self-consciousness, the preadolescent starts to explore their own self-identity and their role in society further. Development of sexual orientation During preadolescence (early adolescence), individuals may become more preoccupied with body image and privacy, corresponding to physical changes seen during adrenarche and puberty. Early adolescents may become aware of their sexuality for the first time, and experience attraction towards others. Homosexual and heterosexual experimentation is not uncommon, although it is important to note that many teens who eventually identify as LGBT do not always do so during adolescence. On average, gay, lesbian, and bisexual individuals report experiencing same-sex attraction in early adolescence, at age 12. About 4 in 10 gay men, and 2 in 10 lesbian women report experiencing same-sex attraction before age 10. For individuals who begin to experience same-sex attraction, familial support and acceptance consistently predicts positive outcomes. Parents and guardians can support preadolescents, regardless of sexual orientation, by having honest conversations about sex. Specifically, parents can talk and listen in a way that invites preadolescents to have an open discussion about sexual orientation. Home from home Where development has been optimal, preadolescents come to school for something to be added to their lives; they want to learn lessons...which can lead to their eventually working in a job like their parents. When earlier developmental stages have gone astray, however, then, on the principle that if you miss a stage, you can always go through it later, some middle children come to school for another purpose...[not] to learn but to find a home from home...a stable emotional situation in which they can exercise their own emotional liability, a group of which they can gradually become a part. Divorce Children at the threshold of adolescence in the nine-to-twelve-year-old group would seem to have particular vulnerabilities to parental separation. Among such problems were the very "eagerness of these youngsters to be co-opted into the parental battling; their willingness to take sides...and the intense, compassionate, caretaking relations which led these youngsters to attempt to rescue a distressed parent often to their own detriment". Media Preadolescents may well be more exposed to popular culture than younger children and have interests based on internet trends, television shows and movies (no longer just cartoons), fashion, technology, music and social media. Preadolescents generally prefer certain brands, and are a heavily targeted market of many advertisers. Their tendency to buy brand-name items may be due to a desire to fit in, although the desire is not as strong as it is with teenagers. Some scholars suggest that pre-adolescents ... reported frequent encounters with sexual material in the media, valued the information received from it, and used it as a learning resource ... and evaluated such content through what they perceived to be sexual morality. However, other research has suggested that sexual media influences on preadolescent and adolescent sexual behavior is minimal. Freud Freud called this stage the latency period to indicate that sexual feelings and interest went underground. Erik H. Erikson noted that latency period children in middle childhood can then direct more of their energy into asexual pursuits such as school, athletics, and same-sex friendships. Nevertheless, recent research contradicts these notions—suggesting that sexual development, interest, and behavior among latent period children does not cease. Instead, the apparent lack of sexual interest is due to children not sharing their sexual interests/emotions with adults. See also Precocious puberty References Further reading The dictionary definition of Wikisaurus:preteen at Wiktionary Myers, James. "Tweens and cool", Admap, March 2004. G. Berry Brazelton, Heart Start: The Emotional Foundations of School Readiness (Arlington 1992)

Dilated cardiomyopathy

Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood effectively. Symptoms vary from none to feeling tired, leg swelling, and shortness of breath. It may also result in chest pain or fainting. Complications can include heart failure, heart valve disease, or an irregular heartbeat.Causes include genetics, alcohol, cocaine, certain toxins, complications of pregnancy, and certain infections. Coronary artery disease and high blood pressure may play a role, but are not the primary cause. In many cases the cause remains unclear. It is a type of cardiomyopathy, a group of diseases that primarily affects the heart muscle. The diagnosis may be supported by an electrocardiogram, chest X-ray, or echocardiogram.In those with heart failure, treatment may include medications in the ACE inhibitor, beta blocker, and diuretic families. A low salt diet may also be helpful. In those with certain types of irregular heartbeat, blood thinners or an implantable cardioverter defibrillator may be recommended. Cardiac resynchronization therapy (CRT) may be necessary. If other measures are not effective a heart transplant may be an option in some.About 1 per 2,500 people is affected. It occurs more frequently in men than women. Onset is most often in middle age. Five-year survival rate is about 50%. It can also occur in children and is the most common type of cardiomyopathy in this age group. Signs and symptoms Dilated cardiomyopathy develops insidiously, and may not initially cause symptoms significant enough to impact on quality of life. Nevertheless, many people experience significant symptoms. These might include: Shortness of breath Syncope (fainting) Angina, but only in the presence of ischemic heart diseaseA person who has dilated cardiomyopathy may have an enlarged heart, with pulmonary edema and an elevated jugular venous pressure and a low pulse pressure. Signs of mitral and tricuspid regurgitation may be present. Causes Although in many cases no cause is apparent, dilated cardiomyopathy is probably the result of damage to the myocardium produced by a variety of toxic, metabolic, or infectious agents. In many cases the cause remains unclear. It may be due to fibrous change of the myocardium from a previous myocardial infarction. Or, it may be the late sequelae of acute viral myocarditis, such as with Coxsackie B virus and other enteroviruses possibly mediated through an immunologic mechanism. Specific autoantibodies are detectable in some cases.Other causes include: Chagas disease, due to Trypanosoma cruzi. This is the most common infectious cause of dilated cardiomyopathy in Latin America Pregnancy: Dilated cardiomyopathy occurs late in gestation or several weeks to months postpartum as a peripartum cardiomyopathy. It is reversible in half of cases. Alcohol use disorder (alcoholic cardiomyopathy) Non-alcoholic toxic insults include administration of certain chemotherapeutic agents, in particular doxorubicin (Adriamycin), and cobalt. Thyroid disease Inflammatory diseases such as sarcoidosis and connective tissue diseases Tachycardia-induced cardiomyopathy Muscular dystrophy Tuberculosis: 1 to 2% of TB cases. Autoimmune mechanisms Thiamine deficiencyRecent studies have shown that those subjects with an extremely high occurrence (several thousands a day) of premature ventricular contractions (extrasystole) can develop dilated cardiomyopathy. In these cases, if the extrasystole are reduced or removed (for example, via ablation therapy) the cardiomyopathy usually regresses. Genetics About 25–35% of affected individuals have familial forms of the disease, with most mutations affecting genes encoding cytoskeletal proteins, while some affect other proteins involved in contraction. The disease is genetically heterogeneous, but the most common form of its transmission is an autosomal dominant pattern.Autosomal recessive (as found, for example, in Alström syndrome), X-linked (as in Duchenne muscular dystrophy), and mitochondrial inheritance of the disease is also found. Some relatives of those affected by dilated cardiomyopathy have preclinical, asymptomatic heart-muscle changes.Other cytoskeletal proteins involved in DCM include α-cardiac actin, desmin, and the nuclear lamins A and C. Mitochondrial deletions and mutations presumably cause DCM by altering myocardial ATP generation.Kayvanpour et al. performed 2016 a meta-analysis with the largest dataset available on genotype-phenotype associations in DCM and mutations in lamin (LMNA), phospholamban (PLN), RNA Binding Motif Protein 20 (RBM20), Cardiac Myosin Binding Protein C (MYBPC3), Myosin Heavy Chain 7 (MYH7), Cardiac Troponin T 2 (TNNT2), and Cardiac Troponin I (TNNI3). They also reviewed recent studies investigating genotype-phenotype associations in DCM patients with titin (TTN) mutations. LMNA and PLN mutation carriers showed a high prevalence of cardiac transplantation and ventricular arrhythmia. Dysrhythmias and sudden cardiac death (SCD) was shown to occur even before the manifestation of DCM and heart failure symptoms in LMNA mutation carriers. Pathophysiology The progression of heart failure is associated with left ventricular remodeling, which manifests as gradual increases in left ventricular end-diastolic and end-systolic volumes, wall thinning, and a change in chamber geometry to a more spherical, less elongated shape. This process is usually associated with a continuous decline in ejection fraction. The concept of cardiac remodeling was initially developed to describe changes that occur in the days and months following myocardial infarction. Compensation effects As DCM progresses, two compensatory mechanisms are activated in response to impaired myocyte contractility and reduced stroke volume: Frank-Starling law Neurohormonal feedback, via activation of the sympathetic nervous system and the renin-angiotensin system.These responses initially compensate for decreased cardiac output and maintain those with DCM as asymptomatic. Eventually, however, these mechanisms become detrimental, intravascular volume becomes too great, and progressive dilatation leads to heart failure symptoms. Computational models Cardiac dilatation is a transversely isotropic, irreversible process resulting from excess strains on the myocardium. A computation model of volumetric, isotropic, and cardiac wall growth predicts the relationship between cardiac strains (e.g. volume overload after myocardial infarction) and dilation using the following governing equations: F = F e ⋅ F g {\displaystyle F=F^{e}\cdot F^{g}\,} where F e {\displaystyle F^{e}} is elastic volume stretch that is reversible and F g {\displaystyle F^{g}} is irreversible, isotropic volume growth described by: F g = I + [ λ g − 1 ] f 0 ⊗ f 0 {\displaystyle F^{g}=\mathbb {I} +[\lambda ^{g}-1]f_{0}\otimes f_{0}\,} where f 0 {\displaystyle f_{0}} is a vector, which points along a cardiomyocytes long axis and λ g {\displaystyle \lambda ^{g}} is the cardiomyocyte stretch due to growth. The total cardiomyocyte growth is given by: λ = λ e ⋅ F λ g {\displaystyle \lambda =\lambda ^{e}\cdot F\lambda ^{g}\,} The above model reveals a gradual dilation of the myocardium, especially the ventricular myocardium, to support the blood volume overload in the chambers. Dilation manifests itself in an increase in total cardiac mass and cardiac diameter. Cardiomyocytes reach their maximum length of 150 μ {\displaystyle \mu } m in the endocardium and 130 μ {\displaystyle \mu } m in the epicardium by the addition of sarcomeres. Due to the increase in diameter, the dilated heart appears spherical in shape, as opposed the elliptical shape of a healthy human heart. In addition, the ventricular walls maintain the same thickness, characteristic of pathophysiological cardiac dilation. Valvular effects As the ventricles enlarge, both the mitral and tricuspid valves may lose their ability to come together properly. This loss of coaptation may lead to mitral and tricuspid regurgitation. As a result, those with DCM are at increased risk of atrial fibrillation. Furthermore, stroke volume is decreased and a greater volume load is placed on the ventricle, thus increasing heart failure symptoms. Diagnosis Generalized enlargement of the heart is seen upon normal chest X-ray. Pleural effusion may also be noticed, which is due to pulmonary venous hypertension.The electrocardiogram often shows sinus tachycardia or atrial fibrillation, ventricular arrhythmias, left atrial enlargement, and sometimes intraventricular conduction defects and low voltage. When left bundle-branch block (LBBB) is accompanied by right axis deviation (RAD), the rare combination is considered to be highly suggestive of dilated or congestive cardiomyopathy. Echocardiogram shows left ventricular dilatation with normal or thinned walls and reduced ejection fraction. Cardiac catheterization and coronary angiography are often performed to exclude ischemic heart disease.Genetic testing can be important, since one study has shown that gene mutations in the TTN gene (which codes for a protein called titin) are responsible for "approximately 25% of familial cases of idiopathic dilated cardiomyopathy and 18% of sporadic cases." The results of the genetic testing can help the doctors and patients understand the underlying cause of the dilated cardiomyopathy. Genetic test results can also help guide decisions on whether a patients relatives should undergo genetic testing (to see if they have the same genetic mutation) and cardiac testing to screen for early findings of dilated cardiomyopathy.Cardiac magnetic resonance imaging (cardiac MRI) may also provide helpful diagnostic information in patients with dilated cardiomyopathy. Treatment Medical therapy Drug therapy can slow down progression and in some cases even improve the heart condition. Standard therapy may include salt restriction, ACE inhibitors, diuretics, and beta blockers. Anticoagulants may also be used for antithrombotic therapy. There is some evidence for the benefits of coenzyme Q10 in treating heart failure. Electrical treatment Artificial pacemakers may be used in patients with intraventricular conduction delay, and implantable cardioverter-defibrillators in those at risk of arrhythmia. These forms of treatment have been shown to prevent sudden cardiac death, improve symptoms, and reduce hospitalization in patients with systolic heart failure. In addition, an implantable cardioverter-defibrillator should be considered as a therapeutic option for the primary prevention of sudden cardiac death in patients with a confirmed LMNA mutation responsible for dilated cardiomyopathy disease phenotype and clinical risk factors. A novel risk score calculator has been developed that allows calculation of risk of sustained ventricular arrhythmia in the next 5 years in patients with DCM https://www.ikard.pl/SVA/ Surgical treatment In patients with advanced disease who are refractory to medical therapy, heart transplantation may be considered. For these people, 1-year survival approaches 90% and over 50% survive greater than 20 years. Epidemiology Although the disease is more common in African-Americans than in Caucasians, it may occur in any patient population. Research directions Therapies that support reverse remodeling have been investigated, and this may suggests a new approach to the prognosis of cardiomyopathies (see ventricular remodeling). Animals In some types of animals, both a hereditary and acquired version of dilated cardiomyopathy has been documented. Dogs Dilated cardiomyopathy is a heritable disease in some dog breeds, including the Boxer, Dobermann, Great Dane, Irish Wolfhound, and St Bernard. Treatment is based on medication, including ACE inhibitors, loop diuretics, and phosphodiesterase inhibitors.An acquired variation of dilated cardiomyopathy describing a link between certain diets was discovered in 2019 by researchers at University of California, Davis School of Veterinary Medicine who published a report on the development of dilated cardiomyopathy in dog breeds lacking the genetic predisposition, particularly in Golden Retrievers. The diets associated with DCM were described as "BEG" (boutique, exotic-ingredient, and/or grain-free) dog foods, as well as legume-rich diets. For treating diet-related DCM, food changes, taurine and carnitine supplementation may be indicated even if the dog does not have a documented taurine or carnitine deficiency although the cost of carnitine supplementation may be viewed as prohibitive by some Cats Dilated cardiomyopathy is also a disease affecting some cat breeds, including the Oriental Shorthair, Burmese, Persian, and Abyssinian. In cats, taurine deficiency is the most common cause of dilated cardiomyopathy. As opposed to these hereditary forms, non-hereditary DCM used to be common in the overall cat population before the addition of taurine to commercial cat food. Other animals There is also a high incidence of heritable dilated cardiomyopathy in captive Golden Hamsters (Mesocricetus auratus), due in no small part to their being highly inbred. The incidence is high enough that several strains of Golden Hamster have been developed to serve as animal models in clinical testing for human forms of the disease. References External links Dilated cardiomyopathy information for parents.

Neutropenic enterocolitis

Neutropenic enterocolitis is inflammation of the cecum (part of the large intestine) that may be associated with infection. It is particularly associated with neutropenia, a low level of neutrophil granulocytes (the most common form of white blood cells) in the blood. Signs and symptoms Signs and symptoms of typhlitis may include diarrhea, a distended abdomen, fever, chills, nausea, vomiting, and abdominal pain or tenderness. Cause The condition is usually caused by Gram-positive enteric commensal bacteria of the gut (gut flora). Clostridium difficile is a species of Gram-positive bacteria that commonly causes severe diarrhea and other intestinal diseases when competing bacteria are wiped out by antibiotics, causing pseudomembranous colitis, whereas Clostridium septicum is responsible for most cases of neutropenic enterocolitis.Typhlitis most commonly occurs in immunocompromised patients, such as those undergoing chemotherapy, patients with AIDS, kidney transplant patients, or the elderly. Diagnosis Typhlitis is diagnosed with a radiograph CT scan showing thickening of the cecum and "fat stranding". Treatment Typhlitis is a medical emergency and requires prompt management. Untreated typhlitis has a poor prognosis, particularly if associated with pneumatosis intestinalis (air in the bowel wall) and/or bowel perforation, and has significant morbidity unless promptly recognized and aggressively treated.Successful treatment hinges on: Early diagnosis provided by a high index of suspicion and the use of CT scanning Nonoperative treatment for uncomplicated cases Empiric antibiotics, particularly if the patient is neutropenic or at other risk of infection.In rare cases of prolonged neutropenia and complications such as bowel perforation, neutrophil transfusions can be considered but have not been studied in a randomized control trial. Elective right hemicolectomy may be used to prevent recurrence but is generally not recommended"...The authors have found nonoperative treatment highly effective in patients who do not manifest signs of peritonitis, perforation, gastrointestinal hemorrhage, or clinical deterioration. Recurrent typhlitis was frequent after conservative therapy (recurrence rate, 67 percent), however," as based on studies from the 1980s Prognosis Inflammation can spread to other parts of the gut in patients with typhlitis. The condition can also cause the cecum to become distended and can cut off its blood supply. This and other factors can result in necrosis and perforation of the bowel, which can cause peritonitis and sepsis.Historically, the mortality rate for typhlitis was as high as 50%, mostly because it is frequently associated with bowel perforation. More recent studies have demonstrated better outcomes with prompt medical management, generally with resolution of symptoms with neutrophil recovery without death . See also Colitis References == External links ==

Hypertonia

Hypertonia is a term sometimes used synonymously with spasticity and rigidity in the literature surrounding damage to the central nervous system, namely upper motor neuron lesions. Impaired ability of damaged motor neurons to regulate descending pathways gives rise to disordered spinal reflexes, increased excitability of muscle spindles, and decreased synaptic inhibition. These consequences result in abnormally increased muscle tone of symptomatic muscles. Some authors suggest that the current definition for spasticity, the velocity-dependent over-activity of the stretch reflex, is not sufficient as it fails to take into account patients exhibiting increased muscle tone in the absence of stretch reflex over-activity. They instead suggest that "reversible hypertonia" is more appropriate and represents a treatable condition that is responsive to various therapy modalities like drug and/or physical therapy. Presentation Symptoms associated with central nervous systems disorders are classified into positive and negative categories. Positive symptoms include those that increase muscle activity through hyper-excitability of the stretch reflex (i.e., rigidity and spasticity) where negative symptoms include those of insufficient muscle activity (i.e. weakness) and reduced motor function. Often the two classifications are thought to be separate entities of a disorder; however, some authors propose that they may be closely related. Pathophysiology Hypertonia is caused by upper motor neuron lesions which may result from injury, disease, or conditions that involve damage to the central nervous system. The lack of or decrease in upper motor neuron function leads to loss of inhibition with resultant hyperactivity of lower motor neurons. Different patterns of muscle weakness or hyperactivity can occur based on the location of the lesion, causing a multitude of neurological symptoms, including spasticity, rigidity, or dystonia.Spastic hypertonia involves uncontrollable muscle spasms, stiffening or straightening out of muscles, shock-like contractions of all or part of a group of muscles, and abnormal muscle tone. It is seen in disorders such as cerebral palsy, stroke, and spinal cord injury. Rigidity is a severe state of hypertonia where muscle resistance occurs throughout the entire range of motion of the affected joint independent of velocity. It is frequently associated with lesions of the basal ganglia. Individuals with rigidity present with stiffness, decreased range of motion and loss of motor control. Dystonic hypertonia refers to muscle resistance to passive stretching (in which a therapist gently stretches the inactive contracted muscle to a comfortable length at very low speeds of movement) and a tendency of a limb to return to a fixed involuntary (and sometimes abnormal) posture following movement. Management Therapeutic interventions are best individualized to particular patients.Basic principles of treatment for hypertonia are to avoid noxious stimuli and provide frequent range of motion exercise. Physical interventions Physiotherapy has been shown to be effective in controlling hypertonia through the use of stretching aimed to reduce motor neuron excitability. The aim of a physical therapy session could be to inhibit excessive tone as far as possible, give the patient a sensation of normal position and movement, and to facilitate normal movement patterns. While static stretch has been the classical means to increase range of motion, PNF stretching has been used in many clinical settings to effectively reduce muscle spasticity.Icing and other topical anesthetics may decrease the reflexive activity for short period of time in order to facilitate motor function. Inhibitory pressure (applying firm pressure over muscle tendon) and promoting body heat retention and rhythmic rotation (slow repeated rotation of affected body part to stimulate relaxation) have also been proposed as potential methods to decrease hypertonia. Aside from static stretch casting, splinting techniques are extremely valuable to extend joint range of motion lost to hypertonicity. A more unconventional method for limiting tone is to deploy quick repeated passive movements to an involved joint in cyclical fashion; this has also been demonstrated to show results on persons without physical disabilities. For a more permanent state of improvement, exercise and patient education is imperative. Isokinetic, aerobic, and strength training exercises should be performed as prescribed by a physiotherapist, and stressful situations that may cause increased tone should be minimized or avoided. Pharmaceutical interventions Baclofen, diazepam and dantrolene remain the three most commonly used pharmacologic agents in the treatment of spastic hypertonia. Baclofen is generally the drug of choice for spinal cord types of spasticity, while sodium dantrolene is the only agent which acts directly on muscle tissue. Tizanidine is also available. Phenytoin with chlorpromazine may be potentially useful if sedation does not limit their use. Ketazolam, not yet available in the United States, may be a significant addition to the pharmacologic set of options. Intrathecal administration of antispastic medications allows for high concentrations of drug near the site of action, which limits side effects. See also Dystonia Hypotonia Spasticity Clasp-knife response References == External links ==

Blister

A blister is a small pocket of body fluid (lymph, serum, plasma, blood, or pus) within the upper layers of the skin, usually caused by forceful rubbing (friction), burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid, either serum or plasma. However, blisters can be filled with blood (known as "blood blisters") or with pus (for instance, if they become infected). The word "blister" entered English in the 14th century. It came from the Middle Dutch bluyster and was a modification of the Old French blostre, which meant a leprous nodule—a rise in the skin due to leprosy. In dermatology today, the words vesicle and bulla refer to blisters of smaller or greater size, respectively. To heal properly, a blister should not be popped unless medically necessary. If popped, the excess skin should not be removed because the skin underneath needs the top layer to heal properly. Causes A blister may form when the skin has been damaged by friction or rubbing, heat, cold or chemical exposure. Fluid collects between the upper layers of skin (the epidermis) and the layers below (the dermis). This fluid cushions the tissue underneath, protecting it from further damage and allowing it to heal. Friction Intense rubbing can cause a blister, as can any friction on the skin if continued long enough. This kind of blister is most common after walking long distances or by wearing old or poorly fitting shoes. Blisters are most common on the hands and feet, as these extremities are susceptible while walking, running, or performing repetitive motions, such as joystick manipulation whilst playing certain video games, certain sports (e.g., baseball pitching), digging with a shovel, playing guitar or bass, etc. Blisters form more easily on damp skin than on dry or soaked skin, and are more common in warm conditions. Less-aggressive rubbing over long periods of time may cause calluses to form rather than a blister. Both blisters and calluses can lead to more serious complications, such as foot ulceration and infection, particularly when sensation or circulation is impaired, as in the case of diabetes, neuropathy or peripheral artery disease (PAD). Burning This type of blistering is one of the tools used to determine the degree of burns sustained. First and second degree burns may result in blistered skin; however, it is characteristic of second degree burns to blister immediately, whereas first degree burns can have blisters after a couple of days. Sunburn can also result in blisters. Blisters can also form on the hands and feet as a result of tissue damage incurred by frostbite. Chemical exposure Sometimes, the skin will blister when it comes into contact with a cosmetic, detergent, solvent, or other chemical such as nickel sulfate, Balsam of Peru, or urushiol (poison ivy, poison oak, poison sumac). This is known as contact dermatitis. Blisters can also develop as a result of an allergic reaction to an insect bite or sting. Some chemical warfare agents, known as blister agents or vesicants, cause large, painful blisters wherever they contact skin; an example is mustard gas. Blood blister A blood blister usually forms when a minute blood vessel close to the surface of the skin ruptures (breaks), and blood leaks into a tear between the layers of skin. This can happen if the skin is crushed, pinched or aggressively squeezed. Medical conditions There are also a number of medical conditions that cause blisters. The most common are chickenpox, herpes, impetigo, and a form of eczema called dyshidrosis. Other, much rarer conditions that cause blisters include: Bullous pemphigoid: a skin disease that causes large, tightly filled blisters to develop, usually affecting people over the age of 60. Pemphigus: a serious skin disease in which blisters develop if pressure is applied to the skin; the blisters burst easily, leaving raw areas that can become infected. Dermatitis herpetiformis: a skin disease that causes intensely itchy blisters, usually on the elbows, knees, back and buttocks. The blisters usually develop in patches of the same shape and size on both sides of the body. Chronic bullous dermatosis: a disease that causes clusters of blisters on the face, mouth or genitals. Cutaneous radiation syndrome Epidermolysis bullosa Pathophysiology Friction blisters Friction blisters are caused by excess shear stress between the bottom and surface of the skin and the body. The strata of skin around the stratum spinosum are most susceptible to shear. As the stratum spinosum tears away from the connecting tissues below, plasma from the cells diffuses out. This plasma solution helps new cells divide and grow into new connective tissues and epidermal layers. The clear fluid will be reabsorbed as new cells develop and the swollen appearance will subside. Painful blisters located on hands (palmar surface) and feet (plantar surface) are due to tissue shearing deeper in the epidermis, near nerve endings. Lower tissues are more susceptible to infection. Prevention Friction blisters Friction blisters, caused by rubbing against the skin, can be prevented by reducing the friction to a level where blisters will not form. This can be accomplished in a variety of ways. Blisters on the feet can be prevented by wearing comfortable, well-fitting shoes and clean socks. Inherently ill-fitting or stiffer shoes, such as high heels and dress shoes, present a larger risk of blistering. Blisters are more likely to develop on skin that is moist, so socks that manage moisture or frequent sock changes will aid those with particularly sweaty feet. While exercising or playing sports, special sports socks can help keep feet drier and reduce the chance of blisters. Before going for a long walk, it is also important to ensure that shoes or hiking boots have been properly broken in. Even before a "hot" or irritated area on the foot is felt, taping a protective layer of padding or a friction-reducing interface between the affected area and the footwear can prevent the formation of a blister. Bandages, moleskin and tapes generally must be applied to the foot daily, and most have a very high coefficient of friction (COF), but a friction-management patch applied to the shoe will remain in place much longer, throughout many changes of socks and insoles. This type of intervention may be used with footwear that is worn daily, with specialty shoes and boots like hockey skates, ice skates, inline skates, ski boots and cleats, or even with orthotic braces and splints. For periods of sustained use such as hiking and trail running, especially where water ingress or moisture build up in the shoe or boot can occur, moisture wicking liner socks can provide the required friction protection. To avoid friction blisters on the hands, gloves should be worn when using tools such as a shovel or pickaxe, doing manual work such as gardening, or using sports equipment like golf clubs or baseball bats. Oars used for competitive rowing are known for causing frequent blisters on the hands of oarsmen. Weightlifters are also prone to blisters as are gymnasts from the friction developed by the rubbing against the bars. To further reduce the occurrence one can tape the hands, and there are also a number of products on the market that claim to reduce the occurrence of blisters. These are all intended to be worn as a liner underneath a glove. The majority of these offerings simply add padding, and create a layer that reduces the coefficient of friction between the skin and the glove. A lubricant, typically talcum powder, can be used to reduce friction between skin and apparel in the short term. People put talcum powder inside gloves or shoes for this purpose, although this type of lubricant can actually increase the friction in the long term as it absorbs moisture. Increased friction makes blisters more likely. Other Sunscreen and protective clothing should also be used during the hottest part of the day to avoid blisters from sunburn. Avoiding sunlight during midday is the best way to avoid blisters from sunburn. Protective gloves should be worn when handling detergents, cleaning products, solvents and other chemicals. References External links Media related to blisters at Wikimedia Commons The dictionary definition of blister at Wiktionary

Livedoid dermatitis

Livedoid dermatitis is a iatrogenic cutaneous reaction that occurs immediately after a drug injection. It presents as an immediate, extreme pain around the injection site, with overlying skin rapidly becoming erythematous, violaceous, or blanched ("ischemic pallor"): 124  and sometimes with reticular pattern. The reaction eventually leads to variable degrees of necrosis to the skin and underlying tissue. The wound eventually heals, but can lead to atrophic, disfiguring scarring. The reaction is associated with a range of both injection sites and drugs. It was first reported by Freudenthal in 1924 following an injection of bismuth salts for syphilis. Although initial reports were following intramuscular injections, the reaction has since also been reported following subcutaneous, intravenous, and intraarticular injections. Livedoid dermatitis has been reported to occur with many different drug injections, including: penicillins, local anesthetics (e.g. lidocaine), vaccines (e.g. Dtap), corticosteroids, NSAIDs, and more. Presentation Pathogenesis The cause of this condition is poorly understood. Microscopic examination of affected tissue shows ischemic necrosis, and so various hypotheses exist to explain this ischemia, including vasospasm from needle prick, the injected drug, or cold compresses applied to the wound. Diagnosis The diagnosis is mainly clinical. Skin biopsies of the site show necrosis caused by ischemia. Radiographic imaging may help to delineate the extent of the wound. Treatment Depending on the extent and state of infection of the wound, the condition may require antibiotics, wound debridement in early stages, and corrective plastic surgery in late stages. See also Injection site reactions List of cutaneous conditions == References ==

Empyema

An empyema () is a collection or gathering of pus within a naturally existing anatomical cavity. For example, pleural empyema is empyema of the pleural cavity. It must be differentiated from an abscess, which is a collection of pus in a newly formed cavity. The term is from Greek ἐμπύημα, "abscess". Classification Empyema occurs in: the pleural cavity (pleural empyema also known as pyothorax) the thoracic cavity the uterus (pyometra) the appendix (appendicitis) the meninges (subdural empyema) the joints (septic arthritis) the gallbladder External links Shen, K. Robert; Bribriesco, Alejandro; Crabtree, Traves; Denlinger, Chad; Eby, Joshua; Eiken, Patrick; Jones, David R.; Keshavjee, Shaf; Maldonado, Fabien; Paul, Subroto; Kozower, Benjamin (February 2017). "The American Association for Thoracic Surgery consensus guidelines for the management of empyema". The Journal of Thoracic and Cardiovascular Surgery. 153 (6): e129–e146. doi:10.1016/j.jtcvs.2017.01.030. PMID 28274565.

Irritant diaper dermatitis

Irritant diaper dermatitis (IDD, also called a diaper/nappy rash) is a generic term applied to skin rash in the diaper nappy area that are caused by various skin disorders and/or irritants. Generic irritant diaper/nappy dermatitis is characterized by joined patches of erythema and scaling mainly seen on the convex surfaces, with the skin folds spared. Diaper/nappy dermatitis with secondary bacterial or fungal involvement tends to spread to concave surfaces (i.e. skin folds), as well as convex surfaces, and often exhibits a central red, beefy erythema with satellite pustules around the border. It is usually considered a form of irritant contact dermatitis. The word "diaper" is in the name not because the diaper/nappy itself causes the rash but rather because the rash is associated with diaper use, being caused by the materials trapped by the diaper (usually feces). Allergic contact dermatitis has also been suggested, but there is little evidence for this cause. In adults with incontinence (fecal, urinary, or both), the rash is sometimes called incontinence-associated dermatitis (IAD).The term diaper candidiasis is used when a fungal origin is identified. The distinction is critical because the treatment (antifungals) is completely different. Causes Irritant diaper dermatitis develops when skin is exposed to prolonged wetness, increased skin pH caused by the combination, and subsequent reactions, of urine and feces, and resulting breakdown of the stratum corneum, or outermost layer of the skin. This may be due to diarrhea, frequent stools, tight diapers, overexposure to ammonia, or allergic reactions. In adults, the stratum corneum is composed of 25 to 30 layers of flattened dead keratinocytes, which are continuously shed and replaced from below. These dead cells are interlaid with lipids secreted by the stratum granulosum just underneath, which help to make this layer of the skin a waterproof barrier. The stratum corneums function is to reduce water loss, repel water, protect deeper layers of the skin from injury, and to repel microbial invasion of the skin. In infants, this layer of the skin is much thinner and more easily disrupted. Urine Although wetness alone has the effect of macerating the skin, softening the stratum corneum, and greatly increasing susceptibility to friction injury, urine has an additional impact on skin integrity because of its effect on skin pH. While studies show that ammonia alone is only a mild skin irritant, when urea breaks down in the presence of fecal urease it increases pH because ammonia is released, which in turn promotes the activity of fecal enzymes such as protease and lipase. These fecal enzymes increase the skins hydration and permeability to bile salts which also act as skin irritants. There is no detectable difference in rates of diaper rash in conventional disposable diaper wearers and reusable cloth diaper wearers. "Babies wearing superabsorbent disposable diapers with a central gelling material have fewer episodes of diaper dermatitis compared with their counterparts wearing cloth diapers. However, keep in mind that superabsorbent diapers contain dyes that were suspected to cause allergic contact dermatitis (ACD)." Whether wearing cloth or disposable diapers they should be changed frequently to prevent diaper rash, even if they dont feel wet. To reduce the incidence of diaper rash, disposable diapers have been engineered to pull moisture away from the babys skin using synthetic non-biodegradable gel. Today, cloth diapers use newly available superabsorbent microfiber cloth placed in a pocket with a layer of light permeable material that contacts the skin. This design serves to pull moisture away from the skin in to the microfiber cloth. This technology is used in most major pocket cloth diapers brands today. Diet The interaction between fecal enzyme activity and IDD explains the observation that infant diet and diaper rash are linked because fecal enzymes are in turn affected by diet. Breast-fed babies, for example, have a lower incidence of diaper rash, possibly because their stools have higher pH and lower enzymatic activity. Diaper rash is also most likely to be diagnosed in infants 8–12 months old, perhaps in response to an increase in eating solid foods and dietary changes around that age that affect fecal composition. Any time an infants diet undergoes a significant change (i.e. from breast milk to formula or from milk to solids) there appears to be an increased likelihood of diaper rash.The link between feces and IDD is also apparent in the observation that infants are more susceptible to developing diaper rash after treating with antibiotics, which affect the intestinal microflora. Also, there is an increased incidence of diaper rash in infants who have had diarrhea in the previous 48 hours, which may be because fecal enzymes such as lipase and protease are more active in feces which have passed rapidly through the gastrointestinal tract. Secondary infections The significance of secondary infection in IDD remains controversial. There seems to be no link between presence or absence of IDD and microbial counts. Although apparently healthy infants sometimes culture positive for Candida and other organisms without exhibiting any symptoms, there does seem to be a positive correlation between the severity of the diaper rash noted and the likelihood of secondary involvement. A wide variety of infections has been reported, including Staphylococcus aureus, Streptococcus pyogenes, Proteus mirabilis, enterococci and Pseudomonas aeruginosa, but it appears that Candida is the most common opportunistic invader in diaper areas. Diagnosis The diagnosis of IDD is made clinically, by observing the limitation of an erythematous eruption to the convex surfaces of the genital area and buttocks. If the diaper dermatitis occurs for greater than 3 days it may be colonized with Candida albicans, giving it the beefy red, sharply marginated, appearance of diaper candidiasis. Differential diagnosis Other rashes that occur in the diaper area include seborrhoeic dermatitis and atopic dermatitis. Both Seborrheic and Atopic dermatitis require individualized treatment; they are not the subject of this article. Seborrheic dermatitis, typified by oily, thick yellowish scales, is most commonly seen on the scalp (cradle cap) but can also appear in the inguinal folds. Atopic dermatitis, or eczema, is associated with allergic reaction, often hereditary. This class of rashes may appear anywhere on the body and is characterized by intense itchiness. Treatments Possible treatments include minimizing diaper use, barrier creams, mild topical cortisones, and antifungal agents. A variety of other inflammatory and infectious processes can occur in the diaper area and an awareness of these secondary types of diaper dermatitis aids in the accurate diagnosis and treatment of patients.Overall, there is sparse evidence of sufficient quality to be certain of the effectiveness of the various treatments. Washcloths with cleansing, moisturising and protective properties may be better than soap and water, and skin cleansers may also be better than soap and water, but the certainty of evidence with regard other treatments is very low. Diaper changing The most effective treatment, although not the most practical one, is to discontinue use of diapers, allowing the affected skin to air out. Another option is simply to increase the frequency of diaper changing. Thorough drying of the skin before diapering is a good preventive measure because it is the excess moisture, either from urine and feces or from sweating, that sets the conditions for a diaper rash to occur. Diaper type Some sources claim that diaper rash is more common with cloth diapers. Others claim the material of the diaper is relevant insofar as it can wick and keep moisture away from the babys skin, and preventing secondary Candida infection. However, there may not be enough data from good-quality, randomized controlled trials to support or refute disposable diaper use thus far. Furthermore, the effect of non-biodegradable diapers on the environment is a concerning matter for public policy. Creams, ointments Another approach is to block moisture from reaching the skin, and commonly recommended remedies using this approach include oil-based protectants or barrier cream, various over-the-counter "diaper creams", petroleum jelly, dimethicone and other oils. Such sealants sometimes accomplish the opposite if the skin is not thoroughly dry, in which case they serve to seal the moisture inside the skin rather than outside. Zinc oxide-based ointments such as Pinxav can be quite effective, especially in prevention, because they have both a drying and an astringent effect on the skin, being mildly antiseptic without causing irritation.A 2005 meta-analysis found no evidence to support the use of topical vitamin A to treat the condition. Dangers of using powders Various moisture-absorbing powders, such as talcum or starch, reduce moisture but may introduce other complications. Airborne powders of any sort can irritate lung tissue, and powders made from starchy plants (corn, arrowroot) provide food for fungi and are not recommended by the American Academy of Dermatology. Antifungals In persistent or especially bad rashes, an antifungal cream often has to be used. In cases that the rash is more of an irritation, a mild topical corticosteroid preparation, e.g. hydrocortisone cream, is used. As it is often difficult to tell a fungal infection apart from a mere skin irritation, many physicians prefer an corticosteroid-and-antifungal combination cream such as hydrocortisone/miconazole. References == External links ==

Gait abnormality

Gait abnormality is a deviation from normal walking (gait). Watching a patient walk is the most important part of the neurological examination. Normal gait requires that many systems, including strength, sensation and coordination, function in an integrated fashion. Many common problems in the nervous system and musculoskeletal system will show up in the way a person walks. Presentation and causes Patients with musculoskeletal pain, weakness or limited range of motion often present conditions such as Trendelenburgs sign, limping, myopathic gait and antalgic gait.Patients who have peripheral neuropathy also experience numbness and tingling in their hands and feet. This can cause ambulation impairment, such as trouble climbing stairs or maintaining balance. Gait abnormality is also common in persons with nervous system problems such as cauda equina syndrome, multiple sclerosis, parkinsons disease, alzheimers disease, vitamin B12 deficiency, myasthenia gravis, normal pressure hydrocephalus, and Charcot–Marie–Tooth disease. Research has shown that neurological gait abnormalities are associated with an increased risk of falls in older adults.Orthopedic corrective treatments may also manifest into gait abnormality, such as lower extremity amputation, healed fractures, and arthroplasty (joint replacement). Difficulty in ambulation that results from chemotherapy is generally temporary in nature, though recovery times of six months to a year are common. Likewise, difficulty in walking due to arthritis or joint pains (antalgic gait) sometimes resolves spontaneously once the pain is gone. Hemiplegic persons have circumduction gait, where the affected limb moves through an arc away from the body, and those with cerebral palsy often have scissoring gait. See also Ataxia Foot drop Gait Abnormality Rating Scale Limp References External links Videos of various abnormal gaits Foot Abnormality

Eczema herpeticum

Eczema herpeticum is a rare but severe disseminated infection that generally occurs at sites of skin damage produced by, for example, atopic dermatitis, burns, long-term usage of topical steroids or eczema. It is also known as Kaposi varicelliform eruption, Pustulosis varioliformis acute and Kaposi-Juliusberg dermatitis. Some sources reserve the term "eczema herpeticum" when the cause is due to human herpes simplex virus, and the term "Kaposi varicelliform eruption" to describe the general presentation without specifying the virus.This condition is most commonly caused by herpes simplex virus type 1 or 2, but may also be caused by coxsackievirus A16, or vaccinia virus. It appears as numerous umbilicated vesicles superimposed on healing atopic dermatitis. it is often accompanied by fever and lymphadenopathy. Eczema herpeticum can be life-threatening in babies. Presentation In addition to the skin, this infection affects multiple organs, including the eyes, brain, lung, and liver, and can be fatal. Treatment It can be treated with systemic antiviral drugs, such as aciclovir or valganciclovir. Foscarnet may also be used for immunocompromised host with Herpes simplex and acyclovir-resistant Herpes simplex. Epidemiology Even though the disease may develop at any age it is mostly present in childhood. Those who are affected typically had pre-existing cutaneous condition like atopic dermatitis. History Eczema herpeticum was first described by Hungarian dermatologist Moriz Kaposi in 1887. Fritz Juliusberg coined the term Pustulosis varioliformis acute in 1898. Eczema herpeticum is caused by Herpes simplex virus HV1, the virus that causes cold sores; it can also be caused by other related viruses. See also Herpes simplex List of cutaneous conditions References External links Eczema Herpeticum photo library at Dermnet

Pulmonary embolism

Pulmonary embolism (PE) is a blockage of an artery in the lungs by a substance that has moved from elsewhere in the body through the bloodstream (embolism). Symptoms of a PE may include shortness of breath, chest pain particularly upon breathing in, and coughing up blood. Symptoms of a blood clot in the leg may also be present, such as a red, warm, swollen, and painful leg. Signs of a PE include low blood oxygen levels, rapid breathing, rapid heart rate, and sometimes a mild fever. Severe cases can lead to passing out, abnormally low blood pressure, obstructive shock, and sudden death.PE usually results from a blood clot in the leg that travels to the lung. The risk of blood clots is increased by cancer, prolonged bed rest, smoking, stroke, certain genetic conditions, estrogen-based medication, pregnancy, obesity, and after some types of surgery. A small proportion of cases are due to the embolization of air, fat, or amniotic fluid. Diagnosis is based on signs and symptoms in combination with test results. If the risk is low, a blood test known as a D-dimer may rule out the condition. Otherwise, a CT pulmonary angiography, lung ventilation/perfusion scan, or ultrasound of the legs may confirm the diagnosis. Together, deep vein thrombosis and PE are known as venous thromboembolism (VTE).Efforts to prevent PE include beginning to move as soon as possible after surgery, lower leg exercises during periods of sitting, and the use of blood thinners after some types of surgery. Treatment is with anticoagulants such as heparin, warfarin or one of the direct-acting oral anticoagulants (DOACs). These are recommended for at least three months. Severe cases may require thrombolysis using medication such as tissue plasminogen activator (tPA) given intravenously or through a catheter, and some may require surgery (a pulmonary thrombectomy). If blood thinners are not appropriate, a temporary vena cava filter may be used.Pulmonary emboli affect about 430,000 people each year in Europe. In the United States, between 300,000 and 600,000 cases occur each year, which contribute to at least 40,000 deaths. Rates are similar in males and females. They become more common as people get older. Signs and symptoms Symptoms of pulmonary embolism are typically sudden in onset and may include one or many of the following: dyspnea (shortness of breath), tachypnea (rapid breathing), chest pain of a "pleuritic" nature (worsened by breathing), cough and hemoptysis (coughing up blood). More severe cases can include signs such as cyanosis (blue discoloration, usually of the lips and fingers), collapse, and circulatory instability because of decreased blood flow through the lungs and into the left side of the heart. About 15% of all cases of sudden death are attributable to PE. While PE may present with syncope, less than 1% of syncope cases are due to PE.On physical examination, the lungs are usually normal. Occasionally, a pleural friction rub may be audible over the affected area of the lung (mostly in PE with infarct). A pleural effusion is sometimes present that is exudative, detectable by decreased percussion note, audible breath sounds, and vocal resonance. Strain on the right ventricle may be detected as a left parasternal heave, a loud pulmonary component of the second heart sound, and/or raised jugular venous pressure. A low-grade fever may be present, particularly if there is associated pulmonary hemorrhage or infarction.As smaller pulmonary emboli tend to lodge in more peripheral areas without collateral circulation, they are more likely to cause lung infarction and small effusions (both of which are painful), but not hypoxia, dyspnea, or hemodynamic instability such as tachycardia. Larger PEs, which tend to lodge centrally, typically cause dyspnea, hypoxia, low blood pressure, fast heart rate and fainting, but are often painless because there is no lung infarction due to collateral circulation. The classic presentation for PE with pleuritic pain, dyspnea, and tachycardia is likely caused by a large fragmented embolism causing both large and small PEs. Thus, small PEs are often missed because they cause pleuritic pain alone without any other findings and large PEs are often missed because they are painless and mimic other conditions often causing ECG changes and small rises in troponin and brain natriuretic peptide levels.PEs are sometimes described as massive, submassive, and nonmassive depending on the clinical signs and symptoms. Although the exact definitions of these are unclear, an accepted definition of massive PE is one in which there is hemodynamic instability. This is a cause of obstructive shock, which presents as sustained low blood pressure, slowed heart rate, or pulselessness. Risk factors About 90% of emboli are from proximal leg deep vein thrombosis (DVTs) or pelvic vein thromboses. The rare venous thoracic outlet syndrome can also be a cause of DVTs, especially in young men without significant risk factors. DVTs are at risk for dislodging and migrating to the lung circulation. The conditions are generally regarded as a continuum termed venous thromboembolism (VTE).VTE is much more common in immunocompromised individuals as well as individuals with comorbidities including: Those that undergo orthopedic surgery at or below the hip without prophylaxis.This is due to immobility during or after the surgery, as well as venous damage during the surgery. Pancreatic and colon cancer patients (other forms of cancer also can be factors, but these are the most common)This is due to the release of procoagulants.Risk of VTE is at its greatest during diagnosis and treatment, but lowers in remission. Patients with high-grade tumors Pregnant individualsAs the body puts itself into what is known as a "hypercoagulable state" the risk of a hemorrhage during childbirth is decreased and is regulated by increased expression of factors VII, VIII, X, Von Willebrand, and fibrinogen. Those on estrogen medicationThe development of thrombosis is classically due to a group of causes named Virchows triad (alterations in blood flow, factors in the vessel wall, and factors affecting the properties of the blood). Often, more than one risk factor is present. Alterations in blood flow: immobilization (after surgery, long-haul flight), injury, pregnancy (also procoagulant), obesity (also procoagulant), cancer (also procoagulant) Factors in the vessel wall: surgery, catheterizations causing direct injury ("endothelial injury") Factors affecting the properties of the blood (procoagulant state): Estrogen-containing medication (transgender hormone therapy, menopausal hormone therapy and hormonal contraceptives) Genetic thrombophilia (factor V Leiden, prothrombin mutation G20210A, protein C deficiency, protein S deficiency, antithrombin deficiency, hyperhomocysteinemia and plasminogen/fibrinolysis disorders) Acquired thrombophilia (antiphospholipid syndrome, nephrotic syndrome, paroxysmal nocturnal hemoglobinuria) Cancer (due to secretion of pro-coagulants)Although most pulmonary embolisms are the result of proximal leg deep vein thrombosis (DVTs), there are still many other risk factors that can also result in a pulmonary embolism. Risk factors include: Varicose veins caused by vascular damage Pulmonary hypertension Diabetes Traumatic hip fractures that immobilize the patient Joint fixation (primarily in the legs) Underlying causes After a first PE, the search for secondary causes is usually brief. Only when a second PE occurs, and especially when this happens while still under anticoagulant therapy, a further search for underlying conditions is undertaken. This will include testing ("thrombophilia screen") for Factor V Leiden mutation, antiphospholipid antibodies, protein C and S and antithrombin levels, and later prothrombin mutation, MTHFR mutation, Factor VIII concentration and rarer inherited coagulation abnormalities. Diagnosis To diagnose a pulmonary embolism, a review of clinical criteria to determine the need for testing is recommended. In those who have low risk, age less than 50, heart rate less than 100 beats per minute, oxygen level more than 94% on room air, and no leg swelling, coughing up of blood, surgery or trauma in the last four weeks, previous blood clots, or estrogen use, further testing is not typically needed.In situations with more high risk individuals, further testing is needed. A CT pulmonary angiogram (CTPA) is the preferred method for diagnosis of a pulmonary embolism due to its easy administration and accuracy. Although a CTPA is preferred, there are also other tests that can be done. For example, a proximal lower limb compression ultrasound (CUS) can be used. This is a test which is primarily used as a confirmatory test, meaning it confirms a previous analysis showing the presence or suspected presence of a pulmonary embolism. According to a cross-sectional study, CUS tests have a sensitivity of 41% and specificity of 96%.If there are concerns this is followed by testing to determine a likelihood of being able to confirm a diagnosis by imaging, followed by imaging if other tests have shown that there is a likelihood of a PE diagnosis.The diagnosis of PE is based primarily on validated clinical criteria combined with selective testing because the typical clinical presentation (shortness of breath, chest pain) cannot be definitively differentiated from other causes of chest pain and shortness of breath. The decision to perform medical imaging is based on clinical reasoning, that is, the medical history, symptoms, and findings on physical examination, followed by an assessment of clinical probability. Probability testing The most commonly used method to predict clinical probability, the Wells score, is a clinical prediction rule, whose use is complicated by multiple versions being available. In 1995, Philip Steven Wells, initially developed a prediction rule (based on a literature search) to predict the likelihood of PE, based on clinical criteria. The prediction rule was revised in 1998 This prediction rule was further revised when simplified during a validation by Wells et al. in 2000. In the 2000 publication, Wells proposed two different scoring systems using cutoffs of 2 or 4 with the same prediction rule. In 2001, Wells published results using the more conservative cutoff of 2 to create three categories. An additional version, the "modified extended version", using the more recent cutoff of 2 but including findings from Wellss initial studies were proposed. Most recently, a further study reverted to Wellss earlier use of a cutoff of 4 points to create only two categories.There are additional prediction rules for PE, such as the Geneva rule. More importantly, the use of any rule is associated with reduction in recurrent thromboembolism.The Wells score: clinically suspected DVT – 3.0 points alternative diagnosis is less likely than PE – 3.0 points tachycardia (heart rate > 100) – 1.5 points immobilization (≥ 3d)/surgery in previous four weeks – 1.5 points history of DVT or PE – 1.5 points hemoptysis – 1.0 points malignancy (with treatment within six months) or palliative – 1.0 pointsTraditional interpretation Score >6.0 – High (probability 59% based on pooled data) Score 2.0 to 6.0 – Moderate (probability 29% based on pooled data) Score <2.0 – Low (probability 15% based on pooled data)Alternative interpretation Score > 4 – PE likely. Consider diagnostic imaging. Score 4 or less – PE unlikely. Consider D-dimer to rule out PE.Recommendations for a diagnostic algorithm were published by the PIOPED investigators; however, these recommendations do not reflect research using 64 slice MDCT. These investigators recommended: Low clinical probability. If negative D-dimer, PE is excluded. If positive D-dimer, obtain MDCT and base treatment on results. Moderate clinical probability. If negative D-dimer, PE is excluded. However, the authors were not concerned that a negative MDCT with negative D-dimer in this setting has a 5% probability of being false. Presumably, the 5% error rate will fall as 64 slice MDCT is more commonly used. If positive D-dimer, obtain MDCT and base treatment on results. High clinical probability. Proceed to MDCT. If positive, treat, if negative, more tests are needed to exclude PE. A D-dimer of less than 750 ug/L does not rule out PE in those who are at high risk. Pulmonary embolism rule-out criteria The pulmonary embolism rule-out criteria (PERC) helps assess people in whom pulmonary embolism is suspected, but unlikely. Unlike the Wells score and Geneva score, which are clinical prediction rules intended to risk stratify people with suspected PE, the PERC rule is designed to rule out the risk of PE in people when the physician has already stratified them into a low-risk category.People in this low risk category without any of these criteria may undergo no further testing for PE: low oxygen saturations – SaO2 <95%, unilateral leg swelling, coughing up blood, prior DVT or PE, recent surgery or trauma, age >50, hormone use, fast heart rate. The rationale behind this decision is that further testing (specifically CT angiogram of the chest) may cause more harm (from radiation exposure and contrast dye) than the risk of PE. The PERC rule has a sensitivity of 97.4% and specificity of 21.9% with a false negative rate of 1.0% (16/1666). Blood tests In people with a low or moderate suspicion of PE, a normal D-dimer level (shown in a blood test) is enough to exclude the possibility of thrombotic PE, with a three-month risk of thromboembolic events being 0.14%. D-dimer is highly sensitive but not specific (specificity around 50%). In other words, a positive D-dimer is not synonymous with PE, but a negative D-dimer is, with a good degree of certainty, an indication of absence of a PE. A low pretest probability is also valuable in ruling out PE. The typical cut off is 500 μg/L, although this varies based on the assay. However, in those over the age of 50, changing the cut-off value to the persons age multiplied by 10 μg/L (accounting for assay which has been used) is recommended as it decreases the number of falsely positive tests without missing any additional cases of PE.When a PE is being suspected, several blood tests are done in order to exclude important secondary causes of PE. This includes a full blood count, clotting status (PT, aPTT, TT), and some screening tests (erythrocyte sedimentation rate, kidney function, liver enzymes, electrolytes). If one of these is abnormal, further investigations might be warranted to the issue.Troponin levels are increased in between 16 and 47% with pulmonary embolism. Imaging In typical people who are not known to be at high risk of PE, imaging is helpful to confirm or exclude a diagnosis of PE after simpler first-line tests are used. Medical societies recommend tests such as the D-dimer to first provide supporting evidence for the need for imaging, and imaging would be done if other tests confirmed a moderate or high probability of finding evidence to support a diagnosis of PE.CT pulmonary angiography is the recommended first line diagnostic imaging test in most people.Ultrasound of the legs can confirm the presence of a PE but cannot rule it out. CT pulmonary angiography CT pulmonary angiography (CTPA) is a pulmonary angiogram obtained using computed tomography (CT) with radiocontrast rather than right heart catheterization. Its advantages are that it is accurate, it is non-invasive, it is more often available, and it may identifying other lung disorders in case there is no pulmonary embolism. The accuracy and non-invasive nature of CTPA also make it advantageous for people who are pregnant. Assessing the accuracy of CT pulmonary angiography is hindered by the rapid changes in the number of rows of detectors available in multidetector CT (MDCT) machines. According to a cohort study, single-slice spiral CT may help diagnose detection among people with suspected pulmonary embolism. In this study, the sensitivity was 69% and specificity was 84%. In this study which had a prevalence of detection was 32%, the positive predictive value of 67.0% and negative predictive value of 85.2%. However, this studys results may be biased due to possible incorporation bias, since the CT scan was the final diagnostic tool in people with pulmonary embolism. The authors noted that a negative single slice CT scan is insufficient to rule out pulmonary embolism on its own. A separate study with a mixture of 4 slice and 16 slice scanners reported a sensitivity of 83% and a specificity of 96%, which means that it is a good test for ruling out a pulmonary embolism if it is not seen on imaging and that it is very good at confirming a pulmonary embolism is present if it is seen. This study noted that additional testing is necessary when the clinical probability is inconsistent with the imaging results. CTPA is non-inferior to VQ scanning, and identifies more emboli (without necessarily improving the outcome) compared to VQ scanning. Ventilation/perfusion scan A ventilation/perfusion scan (or V/Q scan or lung scintigraphy) shows that some areas of the lung are being ventilated but not perfused with blood (due to obstruction by a clot). This type of examination is as accurate as multislice CT, but is less used, due to the greater availability of CT technology. It is particularly useful in people who have an allergy to iodinated contrast, impaired kidney function, or are pregnant (due to its lower radiation exposure as compared to CT). The test can be performed with planar two-dimensional imaging, or single photon emission computed tomography (SPECT) which enables three-dimensional imaging. Hybrid devices combining SPECT and CT (SPECT/CT) further enable anatomic characterization of any abnormality. Low probability diagnostic tests/non-diagnostic tests Tests that are frequently done that are not sensitive for PE, but can be diagnostic. Chest X-rays are often done on people with shortness of breath to help rule-out other causes, such as congestive heart failure and rib fracture. Chest X-rays in PE are rarely normal, but usually lack signs that suggest the diagnosis of PE (for example, Westermark sign, Hamptons hump). Ultrasonography of the legs, also known as leg doppler, in search of deep venous thrombosis (DVT). The presence of DVT, as shown on ultrasonography of the legs, is in itself enough to warrant anticoagulation, without requiring the V/Q or spiral CT scans (because of the strong association between DVT and PE). This may be a valid approach in pregnancy, in which the other modalities would increase the risk of birth defects in the unborn child. However, a negative scan does not rule out PE, and low-radiation dose scanning may be required if the mother is deemed at high risk of having a pulmonary embolism. The main use of ultrasonography of the legs is therefore in those with clinical symptoms suggestive of deep vein thrombosis. Fluoroscopic pulmonary angiography Historically, the gold standard for diagnosis was pulmonary angiography by fluoroscopy, but this has fallen into disuse with the increased availability of non-invasive techniques that offer similar diagnostic accuracy. Electrocardiogram The primary use of the ECG is to rule out other causes of chest pain. An electrocardiogram (ECG) is routinely done on people with chest pain to quickly diagnose myocardial infarctions (heart attacks), an important differential diagnosis in an individual with chest pain. While certain ECG changes may occur with PE, none are specific enough to confirm or sensitive enough to rule out the diagnosis. An ECG may show signs of right heart strain or acute cor pulmonale in cases of large PEs – the classic signs are a large S wave in lead I, a large Q wave in lead III, and an inverted T wave in lead III (S1Q3T3), which occurs in 12–50% of people with the diagnosis, yet also occurs in 12% without the diagnosis.This is occasionally present (occurring in up to 20% of people), but may also occur in other acute lung conditions, and, therefore, has limited diagnostic value. The most commonly seen signs in the ECG are sinus tachycardia, right axis deviation, and right bundle branch block. Sinus tachycardia, however, is still only found in 8–69% of people with PE.ECG findings associated with pulmonary emboli may suggest worse prognosis since the six findings identified with RV strain on ECG (heart rate > 100 beats per minute, S1Q3T3, inverted T waves in leads V1-V4, ST elevation in aVR, complete right bundle branch block, and atrial fibrillation) are associated with increased risk of circulatory shock and death.Cases with inverted T in leads V1-3 are suspected with PE or inferior myocardial infarction. PE cases show inverted T waves in leads II and aVF, but inferior myocardial infarction cases do not show inverted T waves in II and aVF. Echocardiography In massive and submassive PE, dysfunction of the right side of the heart may be seen on echocardiography, an indication that the pulmonary artery is severely obstructed and the right ventricle, a low-pressure pump, is unable to match the pressure. Some studies (see below) suggest that this finding may be an indication for thrombolysis. Not every person with a (suspected) pulmonary embolism requires an echocardiogram, but elevations in cardiac troponins or brain natriuretic peptide may indicate heart strain and warrant an echocardiogram, and be important in prognosis.The specific appearance of the right ventricle on echocardiography is referred to as the McConnells sign. This is the finding of akinesia of the mid-free wall but a normal motion of the apex. This phenomenon has a 77% sensitivity and a 94% specificity for the diagnosis of acute pulmonary embolism in the setting of right ventricular dysfunction. Prevention Pulmonary embolism may be preventable in those with risk factors. People admitted to hospital may receive preventative medication, including unfractionated heparin, low molecular weight heparin (LMWH), or fondaparinux, and anti-thrombosis stockings to reduce the risk of a DVT in the leg that could dislodge and migrate to the lungs.Following the completion of anticoagulation in those with prior PE, long-term aspirin is useful to prevent recurrence. Treatment Anticoagulant therapy is the mainstay of treatment. Acutely, supportive treatments, such as oxygen or analgesia, may be required. People are often admitted to hospital in the early stages of treatment, and tend to remain under inpatient care until the INR has reached therapeutic levels (if warfarin is used). Increasingly, however, low-risk cases are managed at home in a fashion already common in the treatment of DVT. Evidence to support one approach versus the other is weak. Anticoagulation Anticoagulant therapy is the mainstay of treatment. For many years, vitamin K antagonists (warfarin or less commonly acenocoumarol or phenprocoumon) have been the cornerstone. As vitamin K antagonists do not act immediately, initial treatment is with rapidly acting injectable anticoagulants: unfractionated heparin (UFH), low molecular weight heparin (LMWH), or fondaparinux, while oral vitamin K antagonists are initiated and titrated (usually as part of inpatient hospital care) to the international normalized ratio, a test that determines the dose. In terms of injectable treatments, LMWH may reduce bleeding among people with pulmonary embolism as compared to UFH. According to the same review, LMWH reduced the incidence of recurrent thrombotic complications and reduced thrombus size when compared to heparin. There was no difference in overall mortality between participants treated with LMWH and those treated with unfractionated heparin. Vitamin K antagonists require frequent dose adjustment and monitoring of the international normalized ratio (INR). In PE, INRs between 2.0 and 3.0 are generally considered ideal. If another episode of PE occurs under warfarin treatment, the INR window may be increased to e.g. 2.5–3.5 (unless there are contraindications) or anticoagulation may be changed to a different anticoagulant e.g. LMWH.In recent years, many anticoagulants have been introduced that offer similar to warfarin but without a need for titration to the INR. Known as the directly acting oral anticoagulants, these treatments are now preferred over vitamin K antagonists by American professional guidelines. Two of these (rivaroxaban and apixaban) do not require initial heparin or fondaparinux treatment, whereas dabigatran and edoxaban do. A Cochrane review found that there is no evidence of a difference between oral DTIs (dabigatran, rivaroxaban, edoxaban, apixaban) and standard anticoagulation in the prevention of recurrent pulmonary embolism.In people with cancer who develop pulmonary embolism, therapy with a course of LMWH is favored over warfarin or other oral anticoagulants. Similarly, pregnant women are treated with low molecular weight heparin until after delivery to avoid the known teratogenic effects of warfarin, especially in the early stages of pregnancy, but it can be used while breastfeeding.Anticoagulation therapy is usually continued for 3–6 months, or "lifelong" if there have been previous DVTs or PEs, or none of the usual transient risk factors is present. In those without a known cause that can be reversed 2 years of treatment may be better than 6 months. For those with small PEs (known as subsegmental PEs) the effects of anticoagulation is unknown as it has not been properly studied as of 2020. Thrombolysis Massive PE causing hemodynamic instability (shock and/or low blood pressure, defined as a systolic blood pressure <90 mmHg or a pressure drop of 40 mmHg for >15 min if not caused by new-onset arrhythmia, hypovolemia or sepsis) is an indication for thrombolysis, the enzymatic destruction of the clot with medication. In this situation, it is the best available treatment in those without contraindications and is supported by clinical guidelines. It is also recommended in those in cardiac arrest with a known PE. Catheter-directed thrombolysis (CDT) is a new technique found to be relatively safe and effective for massive PEs. This involves accessing the venous system by placing a catheter into a vein in the groin and guiding it through the veins by using fluoroscopic imaging until it is located next to the PE in the lung circulation. Medication that breaks up blood clots is released through the catheter so that its highest concentration is directly next to the pulmonary embolus. CDT is performed by interventional radiologists or vascular surgeons, and in medical centers that offer CDT, it may be offered as a first-line treatment. Catheter-based ultrasound-assisted thrombolysis is being investigated.The use of thrombolysis in non-massive PEs is still debated. Some have found that the treatment decreases the risk of death and increases the risk of bleeding including intracranial hemorrhage. Others have found no decrease in the risk of death. Inferior vena cava filter There are two situations when an inferior vena cava filter is considered advantageous, and those are if anticoagulant therapy is contraindicated (e.g. shortly after a major operation), or a person has a pulmonary embolus in spite of being anticoagulated. In these instances, it may be implanted to prevent new or existing DVTs from entering the pulmonary artery and combining with an existing blockage. In spite of the devices theoretical advantage of preventing pulmonary emboli, there is a lack of evidence supporting its effectiveness.Inferior vena cava filters should be removed as soon as it becomes safe to start using anticoagulation. Although modern filters are meant to be retrievable, complications may prevent some from being removed. The long-term safety profile of permanently leaving a filter inside the body is not known. Surgery Surgical management of acute pulmonary embolism (pulmonary thrombectomy) is uncommon and has largely been abandoned because of poor long-term outcomes. However, recently, it has gone through a resurgence with the revision of the surgical technique and is thought to benefit certain people. Chronic pulmonary embolism leading to pulmonary hypertension (known as chronic thromboembolic hypertension) is treated with a surgical procedure known as a pulmonary thromboendarterectomy. Epidemiology There are roughly 10 million cases of pulmonary embolisms per year. In the United States, pulmonary embolisms are the primary cause of at least 10,000 to 12,000 deaths per year and a contributing cause in at least 30,000 to 40,000 deaths per year. True incidence involving pulmonary embolisms is unknown because they often go undiagnosed or unnoticed until autopsy. From 1993 to 2012, there have been an increased number of admissions in hospitals due to pulmonary embolisms, jumping from 23 cases per 100,000 people to 65 cases per 100,000 people. Despite this increase, there has been a decrease in mortality during that same time period due to medical advances that have occurred.Venous thromboembolism (VTE), a common risk factor, is present at much higher rates in those over the age of 70 (three times higher compared to those aged 45 to 69). This is likely due to there being a generally lower level of activity among the elderly, resulting in higher rates of immobility and obesity. VTE has a large, and continuously rising, case fatality rate. This rate is roughly 10% after 30 days, 15% after three months and up to 20% after one year. Pulmonary embolisms alone (when resulting in hospitalizations) have a case fatality rate of about 5% to 10% so VTE can play a large factor in the severity of the embolisms.When looking at all cases, the rate of fatal pulmonary emboli has declined from 6% to 2% over the last 25 years in the United States. In Europe, an average of approximately 40,000 deaths per year with pulmonary embolism as the primary cause were reported between 2013 and 2015, a conservative estimate because of potential underdiagnosis. Prognosis Less than 5 to 10% of symptomatic PEs are fatal within the first hour of symptoms.There are several markers used for risk stratification and these are also independent predictors of adverse outcomes. These include hypotension, cardiogenic shock, syncope, evidence of right heart dysfunction, and elevated cardiac enzymes. Some ECG changes including S1Q3T3 also correlate with a worse short-term prognosis. There have been other patient-related factors such as COPD and chronic heart failure thought to also play a role in prognosis.Prognosis depends on the amount of lung that is affected and on the co-existence of other medical conditions; chronic embolisation to the lung can lead to pulmonary hypertension. After a massive PE, the embolus must be resolved somehow if the patient is to survive. In thrombotic PE, the blood clot may be broken down by fibrinolysis, or it may be organized and recanalized so that a new channel forms through the clot. Blood flow is restored most rapidly in the first day or two after a PE. Improvement slows thereafter and some deficits may be permanent. There is controversy over whether small subsegmental PEs need treatment at all and some evidence exists that patients with subsegmental PEs may do well without treatment.Once anticoagulation is stopped, the risk of a fatal pulmonary embolism is 0.5% per year.Mortality from untreated PEs was said to be 26%. This figure comes from a trial published in 1960 by Barrit and Jordan, which compared anticoagulation against placebo for the management of PE. Barritt and Jordan performed their study in the Bristol Royal Infirmary in 1957. This study is the only placebo-controlled trial ever to examine the place of anticoagulants in the treatment of PE, the results of which were so convincing that the trial has never been repeated as to do so would be considered unethical. That said, the reported mortality rate of 26% in the placebo group is probably an overstatement, given that the technology of the day may have detected only severe PEs. Predicting mortality The PESI and sPESI (= simplified Pulmonary Embolism Severity Index) scoring tools can estimate mortality of patients. The Geneva prediction rules and Wells criteria are used to calculate a pre-test probability of patients to predict who has a pulmonary embolism. These scores are tools to be used with clinical judgment in deciding diagnostic testing and types of therapy. The PESI algorithm comprises 11 routinely available clinical variables. It puts the subjects into one of five classes (I–V), with 30-day mortality ranging from 1.1% to 24.5%. Those in classes I and II are low-risk and those in classes III–V are high-risk. References External links Pulmonary embolism at Curlie Wells criteria for pulmonary embolism online calculator Archived 2016-11-21 at the Wayback Machine Clinical prediction website – Wells criteria for pulmonary embolism Media related to Pulmonary embolism at Wikimedia Commons "Pulmonary Embolism". MedlinePlus. U.S. National Library of Medicine.

Metabolic alkalosis

Metabolic alkalosis is a metabolic condition in which the pH of tissue is elevated beyond the normal range (7.35–7.45). This is the result of decreased hydrogen ion concentration, leading to increased bicarbonate, or alternatively a direct result of increased bicarbonate concentrations. The condition typically cannot last long if the kidneys are functioning properly. Signs and symptoms Mild cases of metabolic alkalosis often cause no symptoms. Typical manifestations of moderate to severe metabolic alkalosis include abnormal sensations, neuromuscular irritability, tetany, abnormal heart rhythms (usually due to accompanying electrolyte abnormalities such as low levels of potassium in the blood), coma, seizures, and temporary waxing and waning confusion. Causes The causes of metabolic alkalosis can be divided into two categories, depending upon urine chloride levels. Chloride-responsive (Urine chloride < 25 mEq/L) Loss of hydrogen ions – Most often occurs via two mechanisms, either vomiting or via the kidney. Vomiting results in the loss of hydrochloric acid (hydrogen and chloride ions) with the stomach contents. In the hospital setting this can commonly occur from nasogastric suction tubes. Severe vomiting also causes loss of potassium (hypokalemia) and sodium (hyponatremia). The kidneys compensate for these losses by retaining sodium in the collecting ducts at the expense of hydrogen ions (sparing sodium/potassium pumps to prevent further loss of potassium), leading to metabolic alkalosis. Congenital chloride diarrhea – rare for being a diarrhea that causes alkalosis instead of acidosis. Contraction alkalosis – This results from a loss of water in the extracellular space, such as from dehydration. Decreased extracellular volume triggers the renin-angiotensin-aldosterone system, and aldosterone subsequently stimulates reabsorption of sodium (and thus water) within the nephron of the kidney. However, a second action of aldosterone is to stimulate renal excretion of hydrogen ions (while retaining bicarbonate), and it is this loss of hydrogen ions that raises the pH of the blood. Diuretic therapy – loop diuretics and thiazides can both initially cause increase in chloride, but once stores are depleted, urine excretion will be below < 25 mEq/L. The loss of fluid from sodium excretion causes a contraction alkalosis. Diuretic abuse among athletes and people with eating disorders may present with metabolic alkalosis. Posthypercapnia – Hypoventilation (decreased respiratory rate) causes hypercapnia (increased levels of CO2), which results in respiratory acidosis. Renal compensation with excess bicarbonate retention occurs to lessen the effect of the acidosis. Once carbon dioxide levels return to base line, the higher bicarbonate levels reveal themselves putting the patient into metabolic alkalosis. Cystic fibrosis – excessive loss of sodium chloride in the sweat leads to contraction of the extracellular volume in the same way as contraction alkalosis, as well chloride depletion. Alkalotic agents – Alkalotic agents, such as bicarbonate (administrated in cases of peptic ulcer or hyperacidity) or antacids, administered in excess can lead to an alkalosis. Chloride-indeterminate alkalosis Milk alkali syndrome Blood product administration since this contains sodium citrate which is then metabolized into sodium bicarbonate. Typically, this is seen with large volume transfusions such as more than 8 units. Decreases in albumin and phosphate will cause metabolic alkalosis. Chloride-resistant (Urine chloride > 40 mEq/L) Retention of bicarbonate – Retention of bicarbonate would lead to alkalosis. Shift of hydrogen ions into intracellular space – Seen in hypokalemia. Due to a low extracellular potassium concentration, potassium shifts out of the cells. In order to maintain electrical neutrality, hydrogen shifts into the cells, raising blood pH. Hyperaldosteronism – Loss of hydrogen ions in the urine occurs when excess aldosterone (Conns syndrome) increases the activity of a sodium-hydrogen exchange protein in the kidney. This increases the retention of sodium ions whilst pumping hydrogen ions into the renal tubule. Excess sodium increases extracellular volume and the loss of hydrogen ions creates a metabolic alkalosis. Later, the kidney responds through the aldosterone escape to excrete sodium and chloride in urine. Excess glycyrrhizin consumption Low levels of magnesium in the blood Severely high levels of calcium in the blood Bartter syndrome and Gitelman syndrome – syndromes with presentations analogous to taking diuretics characterized with normotensive patients Liddle syndrome – a gain of function mutation in the genes encoding the epithelial sodium channel (ENaC) which is characterized by hypertension and hypoaldosteronism. 11β-hydroxylase deficiency and 17α-hydroxylase deficiency – both characterized by hypertension Aminoglycoside toxicity can induce a hypokalemic metabolic alkalosis via activating the calcium sensing receptor in the thick ascending limb of the nephron, inactivating the NKCC2 cotransporter, creating a Bartters syndrome like effect. Compensation Compensation for metabolic alkalosis occurs mainly in the lungs, which retain carbon dioxide (CO2) through slower breathing, or hypoventilation (respiratory compensation). CO2 is then consumed toward the formation of the carbonic acid intermediate, thus decreasing pH. Respiratory compensation, though, is incomplete. The decrease in [H+] suppresses the peripheral chemoreceptors, which are sensitive to pH. But, because respiration slows, there is an increase in pCO2 which would cause an offset of the depression because of the action of the central chemoreceptors which are sensitive to the partial pressure of CO2 in the cerebral spinal fluid. So, because of the central chemoreceptors, respiration rate would be increased. Renal compensation for metabolic alkalosis, less effective than respiratory compensation, consists of increased excretion of HCO3− (bicarbonate), as the filtered load of HCO3− exceeds the ability of the renal tubule to reabsorb it. To calculate the expected pCO2 in the setting of metabolic alkalosis, the following equations are used: pCO2 = 0.7 [HCO3] + 20 mmHg ± 5 pCO2 = 0.7 [HCO3] + 21 mmHg Treatment To effectively treat metabolic alkalosis, the underlying cause(s) must be corrected. A trial of intravenous chloride-rich fluid is warranted if there is a high index of suspicion for chloride-responsive metabolic alkalosis caused by loss of gastrointestinal fluid (e.g., due to vomiting). Terminology Alkalosis refers to a process by which the pH is increased. Alkalemia refers to a pH which is higher than normal, specifically in the blood. See also Hypokalemia Metabolic acidosis Respiratory acidosis Respiratory alkalosis References == External links ==

Hyperproteinemia

Hyperproteinemia is the state of having overly high levels of protein in the blood. This can occur due to monoclonal gammopathies such as multiple myeloma and after intravenous immunoglobulin has been given. It can result in a falsely low appearing sodium level (hyponatremia). References == External links ==

Alcohol intolerance

Alcohol intolerance is due to a genetic polymorphism of the enzyme alcohol dehydrogenase, the enzyme that metabolises ingested alcohol. This polymorphism is most often reported in Asian patients. It can also be an effect or side effect associated with certain drugs such as disulfiram, metronidazole, or nilutamide. Stuffy nose and skin flushing are the most common symptoms when ingesting alcohol. It may also be characterized as intolerance causing hangover symptoms similar to the "disulfiram-like reaction" of aldehyde dehydrogenase deficiency or chronic fatigue syndrome. Severe pain after drinking alcohol may indicate a more serious condition.If people are intolerant, some non-alcoholic beverages may be a problem, similar to alcohol-containing medications, vinegar, inhalation of alcohol or the vapour of alcohol-containing cleaning agents.Drinking alcohol first or afterwards together with calcium cyanamide, an inorganic compound used as a fertilizer, can cause permanent or long lasting intolerance (nitrolime disease), contributing together with other substances to the accumulation of harmful acetaldehyde by inhibiting the enzyme acetaldehyde dehydrogenase. See also Disulfiram-like drug Alcohol flush reaction == References ==

Hypotonic-hyporesponsive episode

A hypotonic-hyporesponsive episode (HHE) is defined as sudden onset of poor muscle tone, reduced consciousness, and pale or bluish skin occurring within 48 hours after vaccination, most commonly pertussis vaccination. An HHE is estimated to occur after 1 in 4,762 to 1 in 1,408 doses of whole cell pertussis vaccine, and after 1 in 14,286 to 1 in 2,778 doses of acellular pertussis vaccine. == References ==

Esophageal rupture

Esophageal rupture is a rupture of the esophageal wall. Iatrogenic causes account for approximately 56% of esophageal perforations, usually due to medical instrumentation such as an endoscopy or paraesophageal surgery. In contrast, the term Boerhaave syndrome is reserved for the 10% of esophageal perforations which occur due to vomiting.Spontaneous perforation of the esophagus most commonly results from a full-thickness tear in the esophageal wall due to a sudden increase in intraesophageal pressure combined with relatively negative intrathoracic pressure caused by straining or vomiting (effort rupture of the esophagus or Boerhaaves syndrome). Other causes of spontaneous perforation include caustic ingestion, pill esophagitis, Barretts esophagus, infectious ulcers in patients with AIDS, and following dilation of esophageal strictures.In most cases of Boerhaaves syndrome, the tear occurs at the left postero-lateral aspect of the distal esophagus and extends for several centimeters. The condition is associated with high morbidity and mortality and is fatal without treatment. The occasionally nonspecific nature of the symptoms may contribute to a delay in diagnosis and a poor outcome. Spontaneous effort rupture of the cervical esophagus, leading to localized cervical perforation, may be more common than previously recognized and has a generally benign course. Preexisting esophageal disease is not a prerequisite for esophageal perforation but it contributes to increased mortality.This condition was first documented by the 18th-century physician Herman Boerhaave, after whom it is named. A related condition is Mallory-Weiss syndrome which is only a mucosal tear. In case of iatrogenic perforation common site is cervical esophagus just above the upper sphincter whereas spontaneous rupture as seen in Boerhaaves syndrome perforation commonly occurs in the lower one-third of esophagus. Signs and symptoms The classic history of esophageal rupture is one of severe retching and vomiting followed by excruciating retrosternal chest and upper abdominal pain. Odynophagia, tachypnea, dyspnea, cyanosis, fever, and shock develop rapidly thereafter.Physical examination is usually not helpful, particularly early in the course. Subcutaneous emphysema (crepitation) is an important diagnostic finding but is not very sensitive, being present in only 9 of 34 patients (27 percent) in one series. A pleural effusion may be detected.Macklers triad includes chest pain, vomiting, and subcutaneous emphysema, and while it is a classical presentation, it is only present in 14% of people.Pain can occasionally radiate to the left shoulder, causing physicians to confuse an esophageal perforation with a myocardial infarction.It may also be audibly recognized as Hammans sign. Pathophysiology Esophageal rupture, in Boerhaave syndrome, is thought to be the result of a sudden rise in internal esophageal pressure produced during vomiting, as a result of neuromuscular incoordination causing failure of the cricopharyngeus muscle (a sphincter within the pharynx) to relax. As the intra-oesophageal pressure increases, the bolus within the oesophagus has nowhere to go superiorly (as the cricopharyngeus fails to relax) which causes the oesophagus to rupture. The syndrome is commonly associated with the consumption of excessive food and/or alcohol as well as eating disorders such as bulimia.The most common anatomical location of the tear in Boerhaave syndrome is at left posterolateral wall of the lower third of the esophagus, 2–3 cm before the stomach.Currently, the most common cause of esophageal perforation is iatrogenic. However, iatrogenic perforations, while still constituting a serious medical condition, are easier to treat and less prone to complications, particularly mediastinitis and sepsis. This is because they usually do not involve contamination of the mediastinum with gastric contents. Diagnosis The diagnosis of Boerhaaves syndrome is suggested on the plain chest radiography and confirmed by chest CT scan. The initial plain chest radiograph is almost always abnormal in patients with Boerhaaves syndrome and usually reveals mediastinal or free peritoneal air as the initial radiologic manifestation. With cervical esophageal perforations, plain films of the neck show air in the soft tissues of the prevertebral space.Hours to days later, pleural effusion(s) with or without pneumothorax, widened mediastinum, and subcutaneous emphysema is typically seen. CT scan may show esophageal wall edema and thickening, extraesophageal air, periesophageal fluid with or without gas bubbles, mediastinal widening, and air and fluid in the pleural spaces, retroperitoneum or lesser sac.The diagnosis of esophageal perforation could also be confirmed by water-soluble contrast esophagram (Gastrografin), which reveals the location and extent of extravasation of contrast material. Although barium is superior in demonstrating small perforations, the spillage of barium sulfate into the mediastinal and pleural cavities can cause an inflammatory response and subsequent fibrosis and is therefore not used as the primary diagnostic study. If, however, the water-soluble study is negative, a barium study should be performed for better definition.Endoscopy has no role in the diagnosis of spontaneous esophageal perforation. Both the endoscope and insufflation of air can extend the perforation and introduce air into the mediastinum.Patients may also have a pleural effusion high in amylase (from saliva), low pH, and may contain particles of food. Differential diagnosis Common misdiagnoses include myocardial infarction, pancreatitis, lung abscess, pericarditis, and spontaneous pneumothorax. If esophageal perforation is suspected, even in the absence of physical findings, chest xray, water soluble contrast radiographic studies of the esophagus and a CT scan should be promptly obtained. In most cases, non-operative management is administered based on radiological evidence contained in mediastinal collection. Treatment With the exception of a few case reports describing survival without surgery, the mortality of untreated Boerhaave syndrome is 100%. Its treatment includes immediate antibiotic therapy to prevent mediastinitis and sepsis, surgical repair of the perforation, and if there is significant fluid loss it should be replaced with IV fluid therapy since oral rehydration is not possible. Even with early surgical intervention (within 24 hours) the risk of death is 25%. References Further reading Radiology Esophageal rupture Arens, Ann; Ben-Youssef, Leila; Hayashi, Sandra; Smollin, Craig (2016). "Esophageal Rupture After Ghost Pepper Ingestion". The Journal of Emergency Medicine. 51 (6): e141–e143. doi:10.1016/j.jemermed.2016.05.061. PMID 27693067. Henderson, John A.M.; Péloquin, AndréJ.M. (1989). "Boerhaave revisited: Spontaneous esophageal perforation as a diagnostic masquerader". The American Journal of Medicine. 86 (5): 559–67. doi:10.1016/0002-9343(89)90385-9. PMID 2653030. Larrieu, AJ; Kieffer, R (1975). "Boerhaave syndrome: report of a case treated non-operatively". Annals of Surgery. 181 (4): 452–4. doi:10.1097/00000658-197504000-00015. PMC 1343787. PMID 1130863. Patton, Anthony S.; Lawson, Dexter W.; Shannon, James M.; Risley, Thomas S.; Bixby, Frank E. (1979). "Reevaluation of the Boerhaave syndrome". The American Journal of Surgery. 137 (4): 560–5. doi:10.1016/0002-9610(79)90131-4. PMID 426207. Ivey, Tom D.; Simonowitz, David A.; Dillard, David H.; Miller, Donald W. (1981). "Boerhaave syndrome". The American Journal of Surgery. 141 (5): 531–3. doi:10.1016/0002-9610(81)90040-4. PMID 6784584. == External links ==

Leukorrhea

Leukorrhea or (leucorrhoea British English), also known as fluor albus, is a thick, whitish, yellowish or greenish vaginal discharge. It has also been referred to as "the whites". There are many causes of leukorrhea, the usual one being estrogen imbalance. The amount of discharge may increase due to vaginal infection, and it may disappear and reappear from time to time. This discharge can keep occurring for years, in which case it becomes more yellow and strong-smelling. It is usually a non-pathological symptom secondary to inflammatory conditions of the vagina or cervix.Leukorrhea can be confirmed by finding >10 WBC per high-power field under a microscope when examining vaginal fluid.Vaginal discharge is normal, and causes of change in discharge include infection, malignancy, and hormonal changes. It sometimes occurs before an adolescent female has her first period, and is considered a sign of puberty. Etymology The word leukorrhea comes from Greek λευκός (leukós, “white”) + ῥοία (rhoía, “flow, flux”). In Latin leukorrhea is fluor albus (fluor, "flow" & albus, "white"). Types Physiologic leukorrhea It is not a major issue but is to be resolved as soon as possible. It can be a natural defense mechanism that the vagina uses to maintain its chemical balance, as well as to preserve the flexibility of the vaginal tissue. The term "physiologic leukorrhea" is used to refer to leukorrhea due to estrogen stimulation.Leukorrhea may occur normally during pregnancy. This is caused by increased bloodflow to the vagina due to increased estrogen. Female infants may have leukorrhea for a short time after birth due to their in-uterine exposure to estrogen. Inflammatory leukorrhea It may also result from inflammation or congestion of the vaginal mucosa. In cases where it is yellowish or gives off an odor, a doctor should be consulted since it could be a sign of several disease processes, including an organic bacterial infection (aerobic vaginitis) or STD.After delivery, leukorrhea accompanied by backache and foul-smelling lochia (post-partum vaginal discharge, containing blood, mucus, and placental tissue) may suggest the failure of involution (the uterus returning to pre-pregnancy size) due to infection. A number of investigation such as wet smear, Gram stain, culture, pap smear and biopsy are suggested to diagnose the condition. Parasitic leukorrhea Leukorrhea is also caused by trichomonads, a group of parasitic protozoan, specifically Trichomonas vaginalis. Common symptoms of this disease are burning sensation, itching and discharge of frothy substance, thick, white or yellow mucous. Treatment Leukorrhea may be caused by sexually transmitted diseases; therefore, treating the STD will help treat the leukorrhea. Treatment may include antibiotics, such as metronidazole. Other antibiotics common for the treatment of STIs include clindamycin or tinidazole. References == External links ==

Crackles

Crackles are the clicking, rattling, or crackling noises that may be made by one or both lungs of a human with a respiratory disease during inhalation. They are usually heard only with a stethoscope ("on auscultation"). Pulmonary crackles are abnormal breath sounds that were formerly referred to as rales.Bilateral crackles refers to the presence of crackles in both lungs. Basal crackles are crackles apparently originating in or near the base of the lung. Bibasal crackles refer to crackles at the bases of both the left and right lungs. Bilateral basal crackles also refers to the presence of basal crackles in both lungs. Crackles are caused by the "popping open" of small airways and alveoli collapsed by fluid, exudate, or lack of aeration during expiration. Crackles can be heard in patients with pneumonia, atelectasis, pulmonary fibrosis, acute bronchitis, bronchiectasis, acute respiratory distress syndrome (ARDS), interstitial lung disease or post thoracotomy or metastasis ablation. Pulmonary edema secondary to left-sided congestive heart failure can also cause crackles. Terminology René Laennec adopted the existing word râles (which has been translated as "rattles", groans" and otherwise) to describe the added breath sounds that are now referred to as "crackles". He described them using unusual daily examples, such as "whistling of little birds", "crackling of salt on a heated dish", "cooing of the woodpidgeon", etc., but he soon realized that he was unable to use the term in front of his patients because it conjured the association of le râle de la mort, which translates to " the death rattle", the noise that people who are about to die make when they can no longer clear secretions. Therefore, at the bedside, he used the Latin word rhonchus, which originally meant a snore. That was not clearly understood by his translator, John Forbes, and the terminology became very confusing after the publication in the 1830s of Forbess English translation of Laennecs De LAuscultation Mediate. The difficulty of translating râle itself had been remarked upon in a British review of Laennecs work in 1820.The terminology of "rales" and "rhonchi" in English remained variable until 1977, when a standardization was established by the American Thoracic Society and American College of Chest Physicians. As a result, the term râles was abandoned, and "crackles" became its recommended substitute. The term "rales" is still common in English-language medical literature, but cognizance of the ATS/CHEST guidelines calls for "crackles". In 2016, the European Respiratory Society reported on a study of various physicians listening to audiovisual recordings of auscultation findings and interobserver variation was analyzed. The study found that broad descriptions agreed better than detailed descriptions. Sound Crackles are caused by explosive opening of small airways and are discontinuous, nonmusical, and brief. Crackles are much more common during the inspiratory than the expiratory phase of breathing, but they may be heard during the expiratory phase. Crackles are often associated with inflammation or infection of the small bronchi, bronchioles, and alveoli. Crackles that do not clear after a cough may indicate pulmonary edema or fluid in the alveoli due to heart failure, pulmonary fibrosis, or acute respiratory distress syndrome. Crackles that partially clear or change after coughing may indicate bronchiectasis. Crackles are often described as fine, medium, and coarse. They can also be characterized as to their timing: fine crackles are usually late-inspiratory, whereas coarse crackles are early inspiratory. Fine crackles are soft, high-pitched, and very brief. This sound can be simulated by rolling a strand of hair between ones fingers near the ears, or by moistening ones thumb and index finger and separating them near the ears. Their presence usually indicates an interstitial process, such as pulmonary fibrosis or congestive heart failure. The sounds from interstitial pulmonary fibrosis have been described as sounding like opening a Velcro fastener. Coarse crackles are somewhat louder, lower in pitch, and last longer than fine crackles. Their presence usually indicates an airway disease, such as bronchiectasis.They can also be described as unilateral or bilateral, as well as dry or moist/wet. See also Bronchophony Egophony Consumption Whooping cough Croup Pertussis toxin Allergic asthma Respiratory sounds References External links Audio Breath Sounds - Multiple case studies with audio files of lung sounds. R.A.L.E. Repository - sound files of breath sounds

Intermenstrual bleeding

Intermenstrual bleeding, previously known as metrorrhagia, is uterine bleeding at irregular intervals, particularly between the expected menstrual periods. It is a cause of vaginal bleeding. In some women, menstrual spotting between periods occurs as a normal and harmless part of ovulation. Some women experience acute mid-cycle abdominal pain around the time of ovulation (sometimes referred to by the German term for this phenomenon, mittelschmerz). This may also occur at the same time as menstrual spotting. The term breakthrough bleeding or breakthrough spotting is usually used for women using hormonal contraceptives, such as IUDs or oral contraceptives, in which it refers to bleeding or spotting between any expected withdrawal bleedings, or bleeding or spotting at any time if none is expected. If spotting continues beyond the first 3-4 cycles of oral contraceptive use, a woman should have her prescription adjusted to a pill containing higher estrogen:progesterone ratio by either increasing the estrogen dose or decreasing the relative progestin dose.Besides the aforementioned physiologic forms, metrorrhagia may also represent abnormal uterine bleeding and be a sign of an underlying disorder, such as hormone imbalance, endometriosis, uterine fibroids, uterine cancer, or vaginal cancer. If the bleeding is repeated and heavy, it can cause significant iron-deficiency anemia. Cause Intermittent spotting between periods can result from any of numerous reproductive system disorders: Breakthrough bleeding Breakthrough bleeding (BTB) is any of various forms of vaginal bleeding, usually referring to mid-cycle bleeding in users of combined oral contraceptives, as attributed to insufficient estrogens. It may also occur with other hormonal contraceptives. Sometimes, breakthrough bleeding is classified as abnormal and thereby as a form of metrorrhagia, and sometimes it is classified as not abnormal.In the context of hemophilia, the term describes a bleeding that occurs while a patient is on prophylaxis. Presentation The bleeding is usually light, often referred to as "spotting," though a few people may experience heavier bleeding.It is estimated that breakthrough bleeding affects around 25 % of combined oral contraceptive pill (COCP) users during the initial 3 to 4 months of use, it then usually resolves on its own. Mechanism Breakthrough bleeding is commonly due to 4 factors: physiologic effects of OCs on the endometrium, OC-related parameters, (dose, formulation, and regimen), patient behavior, (compliance, using concomitant medications, and smoking) and benign or malignant pathology. Treatment Breakthrough bleeding that does not resolve on its own is a common reason for women to switch to different pill formulations, or to switch to a non-hormonal method of birth control. Terminology Metrorrhagia is from metro = measure, -rrhagia = abnormal flow. The term is no longer recommended. See also Menometrorrhagia Istihadha Menstruation Menstruation in Islam Postcoital bleeding Vaginal bleeding Withdrawal bleeding Culture and menstruation References == External links ==

Sciatica

Sciatica is pain going down the leg from the lower back. This pain may go down the back, outside, or front of the leg. Onset is often sudden following activities like heavy lifting, though gradual onset may also occur. The pain is often described as shooting. Typically, symptoms are only on one side of the body. Certain causes, however, may result in pain on both sides. Lower back pain is sometimes present. Weakness or numbness may occur in various parts of the affected leg and foot.About 90% of sciatica is due to a spinal disc herniation pressing on one of the lumbar or sacral nerve roots. Spondylolisthesis, spinal stenosis, piriformis syndrome, pelvic tumors, and pregnancy are other possible causes of sciatica. The straight-leg-raising test is often helpful in diagnosis. The test is positive if, when the leg is raised while a person is lying on their back, pain shoots below the knee. In most cases medical imaging is not needed. However, imaging may be obtained if bowel or bladder function is affected, there is significant loss of feeling or weakness, symptoms are long standing, or there is a concern for tumor or infection. Conditions that may present similarly are diseases of the hip and infections such as early shingles (prior to rash formation).Initial treatment typically involves pain medications. However, evidence for pain medication and muscle relaxants is lacking. It is generally recommended that people continue with normal activity to the best of their abilities. Often all that is required for sciatica resolution is time; in about 90% of people symptoms resolve in less than six weeks. If the pain is severe and lasts for more than six weeks, surgery may be an option. While surgery often speeds pain improvement, its long term benefits are unclear. Surgery may be required if complications occur, such as loss of normal bowel or bladder function. Many treatments, including corticosteroids, gabapentin, pregabalin, acupuncture, heat or ice, and spinal manipulation, have limited or poor evidence for their use.Depending on how it is defined, less than 1% to 40% of people have sciatica at some point in time. Sciatica is most common between the ages of 40 and 59, and men are more frequently affected than women. The condition has been known since ancient times. The first known use of the word sciatica dates from 1451. Definition The term "sciatica" usually describes a symptom—pain along the sciatic nerve pathway—rather than a specific condition, illness, or disease. Some use it to mean any pain starting in the lower back and going down the leg. The pain is characteristically described as shooting or shock-like, quickly traveling along the course of the affected nerves. Others use the term as a diagnosis (i.e. an indication of cause and effect) for nerve dysfunction caused by compression of one or more lumbar or sacral nerve roots from a spinal disc herniation. Pain typically occurs in the distribution of a dermatome and goes below the knee to the foot. It may be associated with neurological dysfunction, such as weakness and numbness. Causes Risk factors Modifiable risk factors for sciatica include smoking, obesity, occupation, and physical sports where back muscles and heavy weights are involved. Non-modifiable risk factors include increasing age, being male, and having a personal history of low back pain. Spinal disc herniation Spinal disc herniation pressing on one of the lumbar or sacral nerve roots is the most frequent cause of sciatica, being present in about 90% of cases. This is particularly true in those under age 50. Disc herniation most often occurs during heavy lifting. Pain typically increases when bending forward or sitting, and reduces when lying down or walking. Spinal stenosis Other compressive spinal causes include lumbar spinal stenosis, a condition in which the spinal canal, the space the spinal cord runs through, narrows and compresses the spinal cord, cauda equina, or sciatic nerve roots. This narrowing can be caused by bone spurs, spondylolisthesis, inflammation, or a herniated disc, which decreases available space for the spinal cord, thus pinching and irritating nerves from the spinal cord that become the sciatic nerve. This is the most frequent cause after age 50. Sciatic pain due to spinal stenosis is most commonly brought on by standing, walking, or sitting for extended periods of time, and reduces when bending forward. However, pain can arise with any position or activity in severe cases. The pain is most commonly relieved by rest. Piriformis syndrome Piriformis syndrome is a condition that, depending on the analysis, varies from a "very rare" cause to contributing up to 8% of low back or buttock pain. In 17% of people, the sciatic nerve runs through the piriformis muscle rather than beneath it. When the piriformis shortens or spasms due to trauma or overuse, it is posited that this causes compression of the sciatic nerve. Piriformis syndrome has colloquially been referred to as "wallet sciatica" since a wallet carried in a rear hip pocket compresses the buttock muscles and sciatic nerve when the bearer sits down. Piriformis syndrome may be suspected as a cause of sciatica when the spinal nerve roots contributing to the sciatic nerve are normal and no herniation of a spinal disc is apparent. Endometriosis Sciatic endometriosis, also called catamenial or cyclical sciatica, is a sciatica whose cause is endometriosis. Its incidence is unknown. Diagnosis is usually made by an MRI or CT-myelography. Pregnancy Sciatica may also occur during pregnancy, especially during later stages, as a result of the weight of the fetus pressing on the sciatic nerve during sitting or during leg spasms. While most cases do not directly harm the woman or the fetus, indirect harm may come from the numbing effect on the legs, which can cause loss of balance and falls. There is no standard treatment for pregnancy-induced sciatica. Other Pain that does not improve when lying down suggests a nonmechanical cause, such as cancer, inflammation, or infection. Sciatica can be caused by tumors impinging on the spinal cord or the nerve roots. Severe back pain extending to the hips and feet, loss of bladder or bowel control, or muscle weakness may result from spinal tumors or cauda equina syndrome. Trauma to the spine, such as from a car accident or hard fall onto the heel or buttocks, may also lead to sciatica. A relationship has been proposed with a latent Cutibacterium acnes infection in the intervertebral discs, but the role it plays is not yet clear. Pathophysiology Sciatica is generally caused by the compression of lumbar nerves L4 or L5 or sacral nerve S1. Less commonly, sacral nerves S2 or S3 or compression of the sciatic nerve itself may cause sciatica. In 90% of sciatica cases, this can occur as a result of a spinal disc bulge or herniation. Intervertebral spinal discs consist of an outer anulus fibrosus and an inner nucleus pulposus. The anulus fibrosus forms a rigid ring around the nucleus pulposus early in human development, and the gelatinous contents of the nucleus pulposus are thus contained within the disc. Discs separate the spinal vertebrae, thereby increasing spinal stability and allowing nerve roots to properly exit through the spaces between the vertebrae from the spinal cord. As an individual ages, the anulus fibrosus weakens and becomes less rigid, making it at greater risk for tear. When there is a tear in the anulus fibrosus, the nucleus pulposus may extrude through the tear and press against spinal nerves within the spinal cord, cauda equina, or exiting nerve roots, causing inflammation, numbness, or excruciating pain. Inflammation of spinal tissue can then spread to adjacent facet joints and cause facet syndrome, which is characterized by lower back pain and referred pain in the posterior thigh.Other causes of sciatica secondary to spinal nerve entrapment include the roughening, enlarging, or misalignment (spondylolisthesis) of vertebrae, or disc degeneration that reduces the diameter of the lateral foramen through which nerve roots exit the spine. When sciatica is caused by compression of a dorsal nerve root, it is considered a lumbar radiculopathy or radiculitis when accompanied by an inflammatory response. Sciatica-like pain prominently focused in the buttocks can also be caused by compression of peripheral sections of the sciatic nerve usually from soft tissue tension in the piriformis or related muscles. Diagnosis Sciatica is typically diagnosed by physical examination, and the history of the symptoms. Physical tests Generally, if a person reports the typical radiating pain in one leg, as well as one or more neurological indications of nerve root tension or neurological deficit, sciatica can be diagnosed.The most frequently used diagnostic test is the straight leg raise to produce Lasègues sign, which is considered positive if pain in the distribution of the sciatic nerve is reproduced with passive flexion of the straight leg between 30 and 70 degrees. While this test is positive in about 90% of people with sciatica, approximately 75% of people with a positive test do not have sciatica. Straight leg raising of the leg unaffected by sciatica may produce sciatica in the leg on the affected side; this is known as the Fajersztajn sign. The presence of the Fajersztajn sign is a more specific finding for a herniated disc than Lasègues sign. Maneuvers that increase intraspinal pressure, such as coughing, flexion of the neck, and bilateral compression of the jugular veins, may transiently worsen sciatica pain. Medical imaging Imaging modalities such as computerised tomography or magnetic resonance imaging can help with the diagnosis of lumbar disc herniation. The utility of MR neurography in the diagnosis of piriformis syndrome is controversial.Discography could be considered to determine a specific discs role in an individuals pain. Discography involves the insertion of a needle into a disc to determine the pressure of disc space. Radiocontrast is then injected into the disc space to assess for visual changes that may indicate an anatomic abnormality of the disc. The reproduction of an individuals pain during discography is also diagnostic. Differential diagnosis Cancer should be suspected if there is previous history of it, unexplained weight loss, or unremitting pain. Spinal epidural abscess is more common among those who have diabetes mellitus or immunodeficiency, or who have had spinal surgery, injection or catheter; it typically causes fever, leukocytosis and increased erythrocyte sedimentation rate. If cancer or spinal epidural abscess is suspected, urgent magnetic resonance imaging is recommended for confirmation. Proximal diabetic neuropathy typically affects middle aged and older people with well-controlled type-2 diabetes mellitus; onset is sudden, causing pain, usually in multiple dermatomes, quickly followed by weakness. Diagnosis typically involves electromyography and lumbar puncture. Shingles is more common among the elderly and immunocompromised; typically, pain is followed by the appearance of a rash with small blisters along a single dermatome. Acute Lyme radiculopathy may follow a history of outdoor activities during warmer months in likely tick habitats in the previous 1–12 weeks. In the U.S., Lyme is most common in New England and Mid-Atlantic states and parts of Wisconsin and Minnesota, but it is expanding to other areas. The first manifestation is usually an expanding rash possibly accompanied by flu-like symptoms. Lyme can also cause a milder, chronic radiculopathy an average of 8 months after the acute illness. Management Sciatica can be managed with a number of different treatments with the goal of restoring a persons normal functional status and quality of life. When the cause of sciatica is lumbar disc herniation (90% of cases), most cases resolve spontaneously over weeks to months. Initially treatment in the first 6–8 weeks should be conservative. More than 75% of sciatica cases are managed without surgery. In persons that smoke who also have sciatica, smoking cessation should be strongly considered, in order to promote healing. Treatment of the underlying cause of nerve compression is needed in cases of epidural abscess, epidural tumors, and cauda equina syndrome. Physical activity Physical activity is often recommended for the conservative management of sciatica for persons who are physically able. However, the difference in outcomes between physical activity compared to bed rest have not been fully elucidated. The evidence for physical therapy in sciatica is unclear though such programs appear safe. Physical therapy is commonly used. Nerve mobilization techniques for sciatic nerve is supported by tentative evidence. Medication There is no one medication regimen used to treat sciatica. Evidence supporting the use of opioids and muscle relaxants is poor. Low-quality evidence indicates that NSAIDs do not appear to improve immediate pain, and all NSAIDs appear to be nearly equivalent in their ability to relieve sciatica. Nevertheless, NSAIDs are commonly recommended as a first-line treatment for sciatica. In those with sciatica due to piriformis syndrome, botulinum toxin injections may improve pain and function. While there is little evidence supporting the use of epidural or systemic steroids, systemic steroids may be offered to individuals with confirmed disc herniation if there is a contraindication to NSAID use. Low-quality evidence supports the use of gabapentin for acute pain relief in those with chronic sciatica. Anticonvulsants and biologics have not been shown to improve acute or chronic sciatica. Antidepressants have demonstrated some efficacy in treating chronic sciatica, and may be offered to individuals who are not amenable to NSAIDs or who have failed NSAID therapy. Surgery If sciatica is caused by a herniated disc, the discs partial or complete removal, known as a discectomy, has tentative evidence of benefit in the short term. If the cause is spondylolisthesis or spinal stenosis, surgery appears to provide pain relief for up to two years. Alternative medicine Low to moderate-quality evidence suggests that spinal manipulation is an effective treatment for acute sciatica. For chronic sciatica, the evidence supporting spinal manipulation as treatment is poor. Spinal manipulation has been found generally safe for the treatment of disc-related pain; however, case reports have found an association with cauda equina syndrome, and it is contraindicated when there are progressive neurological deficits. Prognosis About 39% to 50% of people with sciatica still have symptoms after one to four years. In one study, around 20% were unable to work at their one-year followup, and 10% had had surgery for the condition. Epidemiology Depending on how it is defined, less than 1% to 40% of people have sciatica at some point in time. Sciatica is most common between the ages of 40 and 59, and men are more frequently affected than women. References External links "Sciatica". MedlinePlus. U.S. National Library of Medicine.

Casting defect

A casting defect is an undesired irregularity in a metal casting process. Some defects can be tolerated while others can be repaired, otherwise they must be eliminated. They are broken down into five main categories: gas porosity, shrinkage defects, mould material defects, pouring metal defects, and metallurgical defects. Terminology The terms "defect" and "discontinuity" refer to two specific and separate things in castings. Defects are defined as conditions in a casting that must be corrected or removed, or the casting must be rejected. Discontinuities, also known as "imperfections", are defined as "interruptions in the physical continuity of the casting". Therefore, if the casting is less than perfect, but still useful and in tolerance, the imperfections should be deemed "discontinuities". Types There are many types of defects which result from many different causes. Some of the solutions to certain defects can be the cause for another type of defect.The following defects can occur in sand castings. Most of these also occur in other casting processes. Shrinkage defects Shrinkage defects can occur when standard feed metal is not available to compensate for shrinkage as the thick metal solidifies. Shrinkage defects will have jagged or linear appearance. Shrinkage defects usually occur in either the cope or drag portion of the casting. Shrinkage defects can be split into two different types: open shrinkage defects and closed shrinkage defects. Open shrinkage defects are open to the atmosphere, therefore as the shrinkage cavity forms, air compensates. There are two types of open air defects: pipes and caved surfaces. Pipes form at the surface of the casting and burrow into the casting, while caved surfaces are shallow cavities that form across the surface of the casting.Closed shrinkage defects, also known as shrinkage porosity, are defects that form within the casting. Isolated pools of liquid form inside solidified metal, which are called hot spots. The shrinkage defect usually forms at the top of the hot spots. They require a nucleation point, so impurities and dissolved gas can induce closed shrinkage defects. The defects are broken up into macroporosity and microporosity (or micro shrinkage), where macroporosity can be seen by the naked eye and microporosity cannot. Gas porosity Gas porosity is the formation of bubbles within the casting after it has cooled. This occurs because most liquid materials can hold a large amount of dissolved gas, but the solid form of the same material cannot, so the gas forms bubbles within the material as it cools. Gas porosity may present itself on the surface of the casting as porosity or the pore may be trapped inside the metal, which reduces strength in that vicinity. Nitrogen, oxygen and hydrogen are the most encountered gases in cases of gas porosity. In aluminium castings, hydrogen is the only gas that dissolves in significant quantity, which can result in hydrogen gas porosity. For casting that are a few kilograms in weight the pores are usually 0.01 to 0.5 mm (0.00039 to 0.01969 in) in size. In larger casting, they can be up to a millimetre (0.040 in) in diameter.To prevent gas porosity the material may be melted in a vacuum, in an environment of low-solubility gases, such as argon or carbon dioxide, or under a flux that prevents contact with the air. To minimize gas solubility the superheat temperatures can be kept low. Turbulence from pouring the liquid metal into the mould can introduce gases, so the moulds are often streamlined to minimize such turbulence. Other methods include vacuum degassing, gas flushing, or precipitation. Precipitation involves reacting the gas with another element to form a compound that will form a dross that floats to the top. For instance, oxygen can be removed from copper by adding phosphorus; aluminium or silicon can be added to steel to remove oxygen. A third source consists of reactions of the molten metal with grease or other residues in the mould. Hydrogen is produced by the reaction of the metal with humidity or residual moisture in the mould. Drying the mould can eliminate this source of hydrogen formation.Gas porosity can sometimes be difficult to distinguish from micro shrinkage because microshrinkage cavities can contain gases as well. In general, microporosities will form if the casting is not properly risered or if a material with a wide solidification range is cast. If neither of these are the case then most likely the porosity is due to gas formation. Tiny gas bubbles are called porosities, but larger gas bubbles are called blowholes or blisters. Such defects can be caused by air entrained in the melt, steam or smoke from the casting sand, or other gasses from the melt or mould. (Vacuum holes caused by metal shrinkage (see above) may also be loosely referred to as blowholes). Proper foundry practices, including melt preparation and mould design, can reduce the occurrence of these defects. Because they are often surrounded by a skin of sound metal, blowholes may be difficult to detect, requiring harmonic, ultrasonic, magnetic, or X-ray (e.g., industrial CT scanning) analysis. Pouring metal defects Pouring metal defects include misruns, cold shuts, and inclusions. A misrun occurs when the liquid metal does not completely fill the mould cavity, leaving an unfilled portion. Cold shuts occur when two fronts of liquid metal do not fuse properly in the mould cavity, leaving a weak spot. Both are caused by either a lack of fluidity in the molten metal or cross-sections that are too narrow. The fluidity can be increased by changing the chemical composition of the metal or by increasing the pouring temperature. Another possible cause is back pressure from improperly vented mould cavities.Misruns and cold shuts are closely related and both involve the material freezing before it completely fills the mould cavity. These types of defects are serious because the area surrounding the defect is significantly weaker than intended. The castability and viscosity of the material can be important factors with these problems. Fluidity affects the minimum section thickness that can be cast, the maximum length of thin sections, fineness of feasibly cast details, and the accuracy of filling mould extremities. There are various ways of measuring the fluidity of a material, although it usually involves using a standard mould shape and measuring the distance the material flows. Fluidity is affected by the composition of the material, freezing temperature or range, surface tension of oxide films, and, most importantly, the pouring temperature. The higher the pouring temperature, the greater the fluidity; however, excessive temperatures can be detrimental, leading to a reaction between the material and the mould; in casting processes that use a porous mould material the material may even penetrate the mould material.The point at which the material cannot flow is called the coherency point. The point is difficult to predict in mould design because it is dependent on the solid fraction, the structure of the solidified particles, and the local shear strain rate of the fluid. Usually this value ranges from 0.4 to 0.8.An inclusion is a metal contamination of dross, if solid, or slag, if liquid. These usually are impurities in the pour metal (generally oxides, less frequently nitrides, carbides, or sulfides), material that is eroded from furnace or ladle linings, or contaminates from the mould. In the specific case of aluminium alloys, it is important to control the concentration of inclusions by measuring them in the liquid aluminium and taking actions to keep them to the required level. There are a number of ways to reduce the concentration of inclusions. In order to reduce oxide formation the metal can be melted with a flux, in a vacuum, or in an inert atmosphere. Other ingredients can be added to the mixture to cause the dross to float to the top where it can be skimmed off before the metal is poured into the mould. If this is not practical, then a special ladle that pours the metal from the bottom can be used. Another option is to install ceramic filters into the gating system. Otherwise swirl gates can be formed which swirl the liquid metal as it is poured in, forcing the lighter inclusions to the center and keeping them out of the casting. If some of the dross or slag is folded into the molten metal then it becomes an entrainment defect. Metallurgical defects There are two defects in this category: hot tears and hot spots. Hot tears, also known as hot cracking, are failures in the casting that occur as the casting cools. This happens because the metal is weak when it is hot and the residual stresses in the material can cause the casting to fail as it cools. Proper mould design prevents this type of defect.Hot spots are sections of casting which have cooled down more slowly than the surrounding material due to higher volume than its surrounding. This causes abnormal shrinkage in this region, which can lead to porosity and cracks. This type of defect can be avoided by proper cooling practices or by changing the chemical composition of the metal. Additional methods of minimising hot tears are not overheating the casting material and increasing the temperature of the mould. Process specific defects Die casting In die casting the most common defects are misruns and cold shuts. These defects can be caused by cold dies, low metal temperature, dirty metal, lack of venting, or too much lubricant. Other possible defects are gas porosity, shrinkage porosity, hot tears, and flow marks. Flow marks are marks left on the surface of the casting due to poor gating, sharp corners, or excessive lubricant. Continuous casting A longitudinal facial crack is a specialized type of defect that only occurs in continuous casting processes. This defect is caused by uneven cooling, both primary cooling and secondary cooling, and includes molten steel qualities, such as the chemical composition being out of specification, cleanliness of the material, and homogeneity. Sand casting Sand casting has many defects that can occur due to the mould failing. The mould usually fails because of one of two reasons: the wrong material is used or it is improperly rammed.The first type is mould erosion, which is the wearing away of the mould as the liquid metal fills the mould. This type of defect usually only occurs in sand castings because most other casting processes have more robust moulds. The castings produced have rough spots and excess material. The moulding sand becomes incorporated into the casting metal and decreases the ductility, fatigue strength, and fracture toughness of the casting. This can be caused by a sand with too little strength or a pouring velocity that is too fast. The pouring velocity can be reduced by redesigning the gating system to use larger runners or multiple gates. A related source of defects are drops, in which part of the moulding sand from the cope drops into the casting while it is still a liquid. This also occurs when the mould is not properly rammed.The second type of defect is metal penetration, which occurs when the liquid metal penetrates into the moulding sand. This causes a rough surface finish. This is caused by sand particles which are too coarse, lack of mould wash, or pouring temperatures that are too high. An alternative form of metal penetration into the mould known as veining is caused by cracking of the sand. If the pouring temperature is too high or a sand of low melting point is used then the sand can fuse to the casting. When this happens the surface of the casting produced has a brittle, glassy appearance.A run out occurs when the liquid metal leaks out of the mould because of a faulty mould or flask.Scabs are a thin layer of metal that sits proud of the casting. They are easy to remove and always reveal a buckle underneath, which is an indentation in the casting surface. Rattails are similar to buckles, except they are thin line indentations and not associated with scabs. Another similar defect is pulldowns, which are buckles that occur in the cope of sand castings. All of these defects are visual in nature and are no reason to scrap the workpiece. These defects are caused by overly high pouring temperatures or deficiencies of carbonaceous material.A swell occurs when the mould wall gives way across a whole face, and is caused by an improperly rammed mould.Burn-on occurs when metallic oxides interact with impurities in silica sands. The result is sand particles embedded in the surface of the finished casting. This defect can be avoided by reducing the temperature of the liquid metal, by using a mould wash, and by using various additives in the sand mixture. See also Hydrogen gas porosity Inclusions in aluminium alloys Non-metallic inclusions for inclusions in steel Porosity sealing References Bibliography Avedesian, M. M.; Baker, Hugh; ASM International (1999). Magnesium and magnesium alloys (2nd ed.). ASM International. ISBN 978-0-87170-657-7.. Campbell, John (2003). Castings. Butterworth-Heinemann. ISBN 978-0-7506-4790-8.. Degarmo, E. Paul; Black, J T.; Kohser, Ronald A. (2003). Materials and Processes in Manufacturing (9th ed.). Wiley. ISBN 0-471-65653-4.. Rao, Posinasetti Nageswara (1999). Manufacturing technology: foundry, forming and welding (2nd ed.). Tata McGraw-Hill. ISBN 978-0-07-463180-5.. Stefanescu, Doru Michael (2008). Science and Engineering of Casting Solidification (2nd ed.). Springer. ISBN 978-0-387-74609-8.. Yu, Kuang-Oscar (2002). Modeling for casting and solidification processing. CRC Press. ISBN 978-0-8247-8881-0..

Libido

Libido (; colloquial: sex drive) is a persons overall sexual drive or desire for sexual activity. Libido is influenced by biological, psychological, and social factors. Biologically, the sex hormones and associated neurotransmitters that act upon the nucleus accumbens (primarily testosterone and dopamine, respectively) regulate libido in humans. Social factors, such as work and family, and internal psychological factors, such as personality and stress, can affect libido. Libido can also be affected by medical conditions, medications, lifestyle and relationship issues, and age (e.g., puberty). A person who has extremely frequent sexual urges, or a suddenly increased sex drive may be experiencing hypersexuality, while the opposite condition is hyposexuality. In psychoanalytic theory, libido is psychic drive or energy, particularly associated with sexual instinct, but also present in other instinctive desires and drives.A person may have a desire for sex, but not have the opportunity to act on that desire, or may on personal, moral or religious reasons refrain from acting on the urge. Psychologically, a persons urge can be repressed or sublimated. Conversely, a person can engage in sexual activity without an actual desire for it. Multiple factors affect human sex drive, including stress, illness, pregnancy, and others. A 2001 review found that, on average, men have a higher desire for sex than women.Sexual desires are often an important factor in the formation and maintenance of intimate relationships in humans. A lack or loss of sexual desire can adversely affect relationships. Changes in the sexual desires of any partner in a sexual relationship, if sustained and unresolved, may cause problems in the relationship. The infidelity of a partner may be an indication that a partners changing sexual desires can no longer be satisfied within the current relationship. Problems can arise from disparity of sexual desires between partners, or poor communication between partners of sexual needs and preferences.There is no widely accepted measure of what is a healthy level for sex desire. Some people want to have sex every day, or more than once a day; others once a year or not at all. However, a person who lacks a desire for sexual activity for some period of time may be experiencing a hypoactive sexual desire disorder or may be asexual. Psychological perspectives Psychoanalysis Sigmund Freud, who is considered the originator of the modern use of the term, defined libido as "the energy, regarded as a quantitative magnitude... of those instincts which have to do with all that may be comprised under the word love." It is the instinctual energy or force, contained in what Freud called the id, the strictly unconscious structure of the psyche. He also explained that it is analogous to hunger, the will to power, and so on insisting that it is a fundamental instinct that is innate in all humans.Freud developed the idea of a series of developmental phases in which the libido fixates on different erogenous zones—first in the oral stage (exemplified by an infants pleasure in nursing), then in the anal stage (exemplified by a toddlers pleasure in controlling his or her bowels), then in the phallic stage, through a latency stage in which the libido is dormant, to its reemergence at puberty in the genital stage. (Karl Abraham would later add subdivisions in both oral and anal stages.)Freud pointed out that these libidinal drives can conflict with the conventions of civilised behavior, represented in the psyche by the superego. It is this need to conform to society and control the libido that leads to tension and disturbance in the individual, prompting the use of ego defenses to dissipate the psychic energy of these unmet and mostly unconscious needs into other forms. Excessive use of ego defenses results in neurosis. A primary goal of psychoanalysis is to bring the drives of the id into consciousness, allowing them to be met directly and thus reducing the patients reliance on ego defenses.Freud viewed libido as passing through a series of developmental stages within the individual. Failure to adequately adapt to the demands of these different stages could result in libidinal energy becoming dammed up or fixated in these stages, producing certain pathological character traits in adulthood. Thus the psychopathologized individual for Freud was an immature individual, and the goal of psychoanalysis was to bring these fixations to conscious awareness so that the libido energy would be freed up and available for conscious use in some sort of constructive sublimation. Analytical psychology According to Swiss psychiatrist Carl Gustav Jung, the libido is identified as the totality of psychic energy, not limited to sexual desire. As Jung states in "The Concept of Libido," "[libido] denotes a desire or impulse which is unchecked by any kind of authority, moral or otherwise. Libido is appetite in its natural state. From the genetic point of view it is bodily needs like hunger, thirst, sleep, and sex, and emotional states or affects, which constitute the essence of libido." The Duality (opposition) creates the energy (or libido) of the psyche, which Jung asserts expresses itself only through symbols: "It is the energy that manifests itself in the life process and is perceived subjectively as striving and desire." (Ellenberger, 697) These symbols may manifest as "fantasy-images" in the process of psychoanalysis which embody the contents of the libido, otherwise lacking in any definite form. Desire, conceived generally as a psychic longing, movement, displacement and structuring, manifests itself in definable forms which are apprehended through analysis. Defined more narrowly, libido also refers to an individuals urge to engage in sexual activity, and its antonym is the force of destruction termed mortido or destrudo. Factors that affect libido Endogenous compounds Libido is governed primarily by activity in the mesolimbic dopamine pathway (ventral tegmental area and nucleus accumbens). Consequently, dopamine and related trace amines (primarily phenethylamine) that modulate dopamine neurotransmission play a critical role in regulating libido.Other neurotransmitters, neuropeptides, and sex hormones that affect sex drive by modulating activity in or acting upon this pathway include: Testosterone (directly correlated) – and other androgens Estrogen (directly correlated) – and related female sex hormones Progesterone (inversely correlated) Oxytocin (directly correlated) Serotonin (inversely correlated) Norepinephrine (directly correlated) Acetylcholine Sex hormone levels and the menstrual cycle A womans desire for sex is correlated to her menstrual cycle, with many women experiencing a heightened sexual desire in the several days immediately before ovulation, which is her peak fertility period, which normally occurs two days before and until two days after the ovulation. This cycle has been associated with changes in a womans testosterone levels during the menstrual cycle. According to Gabrielle Lichterman, testosterone levels have a direct impact on a womans interest in sex. According to her, testosterone levels rise gradually from about the 24th day of a womans menstrual cycle until ovulation on about the 14th day of the next cycle, and during this period the womans desire for sex increases consistently. The 13th day is generally the day with the highest testosterone levels. In the week following ovulation, the testosterone level is the lowest and as a result women will experience less interest in sex.Also, during the week following ovulation, progesterone levels increase, resulting in a woman experiencing difficulty achieving orgasm. Although the last days of the menstrual cycle are marked by a constant testosterone level, womens libido may get a boost as a result of the thickening of the uterine lining which stimulates nerve endings and makes a woman feel aroused. Also, during these days, estrogen levels decline, resulting in a decrease of natural lubrication. Although some specialists disagree with this theory, menopause is still considered by the majority a factor that can cause decreased sexual desire in women. The levels of estrogen decrease at menopause and this usually causes a lower interest in sex and vaginal dryness which makes sex painful. However, the levels of testosterone increase at menopause and this may be why some women may experience a contrary effect of an increased libido. Psychological and social factors Certain psychological or social factors can reduce the desire for sex. These factors can include lack of privacy or intimacy, stress or fatigue, distraction, or depression. Environmental stress, such as prolonged exposure to elevated sound levels or bright light, can also affect libido. Other causes include experience of sexual abuse, assault, trauma, or neglect, body image issues, and anxiety about engaging in sexual activity.Individuals with PTSD may find themselves with reduced sexual desire. Struggling to find pleasure, as well as having trust issues, many with PTSD experience feelings of vulnerability, rage and anger, and emotional shutdowns, which have been shown to inhibit sexual desire in those with PTSD. Reduced sex drive may also be present in trauma victims due to issues arising in sexual function. For women, it has been found that treatment can improve sexual function, thus helping restore sexual desire. Depression and libido decline often coincide, with reduced sex drive being one of the symptoms of depression. Those with depression often report the decline in libido to be far reaching and more noticeable than other symptoms. In addition, those with depression often are reluctant to report their reduced sex drive, often normalizing it with cultural/social values, or by the failure of the physician to inquire about it. Physical factors Physical factors that can affect libido include endocrine issues such as hypothyroidism, the effect of certain prescription medications (for example flutamide), and the attractiveness and biological fitness of ones partner, among various other lifestyle factors.Anemia is a cause of lack of libido in women due to the loss of iron during the period.Smoking, alcohol use disorder, and the use of certain drugs can also lead to a decreased libido. Moreover, specialists suggest that several lifestyle changes such as exercising, quitting smoking, lowering consumption of alcohol or using prescription drugs may help increase ones sexual desire. Medications Some people purposefully attempt to decrease their libido through the usage of anaphrodisiacs. Aphrodisiacs, such as dopaminergic psychostimulants, are a class of drugs which can increase libido. On the other hand, a reduced libido is also often iatrogenic and can be caused by many medications, such as hormonal contraception, SSRIs and other antidepressants, antipsychotics, opioids, beta blockers and Isotretinoin. Isotretinoin and many SSRIs can cause a long-term decrease in libido and other sexual functions, even after users of those drugs have shown improvement in their depression and have stopped usage. Multiple studies have shown that with the exception of bupropion (Wellbutrin), trazodone (Desyrel) and nefazodone (Serzone), antidepressants generally will lead to lowered libido. SSRIs that typically lead to decreased libido are fluoxetine (Prozac), paroxetine (Paxil), fluvoxamine (Luvox), citalopram (Celexa) and sertraline (Zoloft). Some antidepressant users have tried decreasing their dosage in the hopes of maintaining an adequate sex drive. Other users try enrolling in psychotherapy to solve depression-related issues of libido. However, the effectiveness of this therapy is mixed, with many reporting that it had no or little effect on sexual drive.Testosterone is one of the hormones controlling libido in human beings. Emerging research is showing that hormonal contraception methods like oral contraceptive pills (which rely on estrogen and progesterone together) are causing low libido in females by elevating levels of sex hormone-binding globulin (SHBG). SHBG binds to sex hormones, including testosterone, rendering them unavailable. Research is showing that even after ending a hormonal contraceptive method, SHBG levels remain elevated and no reliable data exists to predict when this phenomenon will diminish.Oral contraceptives lower androgen levels in users, and lowered androgen levels generally lead to a decrease in sexual desire. However, usage of oral contraceptives has shown to typically not have a connection with lowered libido in women. Multiple studies have shown that usage of oral contraceptives is associated with either a small increase or decrease in libido, with most users reporting a stable sex drive. Effects of age Males reach the peak of their sex drive in their teenage years, while females reach it in their thirties. The surge in testosterone hits the male at puberty resulting in a sudden and extreme sex drive which reaches its peak at age 15–16, then drops slowly over his lifetime. In contrast, a females libido increases slowly during adolescence and peaks in her mid-thirties. Actual testosterone and estrogen levels that affect a persons sex drive vary considerably. Some boys and girls will start expressing romantic or sexual interest by age 10–12. The romantic feelings are not necessarily sexual, but are more associated with attraction and desire for another. For boys and girls in their preteen years (ages 11–12), at least 25% report "thinking a lot about sex". By the early teenage years (ages 13–14), however, boys are much more likely to have sexual fantasies than girls. In addition, boys are much more likely to report an interest in sexual intercourse at this age than girls. Masturbation among youth is common, with prevalence among the population generally increasing until the late 20s and early 30s. Boys generally start masturbating earlier, with less than 10% boys masturbating around age 10, around half participating by age 11–12, and over a substantial majority by age 13–14. This is in sharp contrast to girls where virtually none are engaging in masturbation before age 13, and only around 20% by age 13–14.People in their 60s and early 70s generally retain a healthy sex drive, but this may start to decline in the early to mid-70s. Older adults generally develop a reduced libido due to declining health and environmental or social factors. In contrast to common belief, postmenopausal women often report an increase in sexual desire and an increased willingness to satisfy their partner. Women often report family responsibilities, health, relationship problems, and well-being as inhibitors to their sexual desires. Aging adults often have more positive attitudes towards sex in older age due to being more relaxed about it, freedom from other responsibilities, and increased self-confidence. Those exhibiting negative attitudes generally cite health as one of the main reasons. Stereotypes about aging adults and sexuality often regard seniors as asexual beings, doing them no favors when they try to talk about sexual interest with caregivers and medical professionals. Non-western cultures often follow a narrative of older women having a much lower libido, thus not encouraging any sort of sexual behavior for women. Residence in retirement homes has affects on residents libidos. In these homes, sex occurs, but it is not encouraged by the staff or other residents. Lack of privacy and resident gender imbalance are the main factors lowering desire. Generally, for older adults, being excited about sex, good health, sexual self-esteem and having a sexually talented partner can be factors. Sexual desire disorders A sexual desire disorder is more common in women than in men, and women tend to exhibit less frequent and less intense sexual desires than men. Erectile dysfunction may happen to the penis because of lack of sexual desire, but these two should not be confused. For example, large recreational doses of amphetamine or methamphetamine can simultaneously cause erectile dysfunction and significantly increase libido. However, men can also experience a decrease in their libido as they age. The American Medical Association has estimated that several million US women have a female sexual arousal disorder, though arousal is not at all synonymous with desire, so this finding is of limited relevance to the discussion of libido. Some specialists claim that women may experience low libido due to some hormonal abnormalities such as lack of luteinising hormone or androgenic hormones, although these theories are still controversial. See also References Further reading Ellenberger, Henri (1970). The Discovery of the Unconscious: The History and Evolution of Dynamic Psychiatry. New York: Basic Books. Hardcover ISBN 0-465-01672-3, softcover ISBN 0-465-01672-3. Froböse, Gabriele, and Froböse, Rolf. Lust and Love: Is It More than Chemistry? Michael Gross (trans. and ed.). Royal Society of Chemistry, ISBN 0-85404-867-7 (2006) Giles, James, The Nature of Sexual Desire, Lanham, Maryland: University Press of America, 2008.

Embolic and thrombotic events after COVID-19 vaccination

Post-vaccination embolic and thrombotic events, termed vaccine-induced immune thrombotic thrombocytopenia (VITT), vaccine-induced prothrombotic immune thrombocytopenia (VIPIT), thrombosis with thrombocytopenia syndrome (TTS), vaccine-induced immune thrombocytopenia and thrombosis (VITT), or vaccine-associated thrombotic thrombocytopenia (VATT), are rare types of blood clotting syndromes that were initially observed in a number of people who had previously received the Oxford–AstraZeneca COVID‑19 vaccine (AZD1222) during the COVID‑19 pandemic. It was subsequently also described in the Janssen COVID‑19 vaccine (Johnson & Johnson) leading to suspension of its use until its safety had been reassessed. On 5 May 2022 the FDA posted a bulletin limiting the use of the Janssen Vaccine to very specific cases due to further reassesment of the risks of TTS, although the FDA also stated in the same bulletin that the benefits of the vaccine outweigh the risks.In April 2021, AstraZeneca and the European Medicines Agency (EMA) updated their information for healthcare professionals about AZD1222, saying it is "considered plausible" that there is a causal relationship between the vaccination and the occurrence of thrombosis in combination with thrombocytopenia and that, "although such adverse reactions are very rare, they exceeded what would be expected in the general population". Signs and symptoms The thrombosis events associated with the COVID‑19 vaccine may occur 4–28 days after its administration and mainly affects women under 55. Several relatively unusual types of thrombosis were specifically reported to be occurring in those with the reaction: cerebral venous sinus thrombosis and thrombosis of the splanchnic veins. Cerebral venous sinus thrombosis may cause severe headache, stroke-like symptoms (weakness of a limb and/or facial muscles), seizures and coma. Splanchnic vein thrombosis may cause abdominal pain, accumulation of fluid in the abdominal cavity, and gastrointestinal bleeding.Other forms of thrombosis, such as the more common pulmonary embolism, may also occur. Arterial thrombosis has also been reported. The low platelet count may manifest as petechia (tiny blood spots under the skin) beyond the site of the injection.Disseminated intravascular coagulation (DIC), diffuse formation of blood clots throughout the blood vessels of the body, has been reported as part of the syndrome. DIC may cause a range of symptoms, including abnormal bleeding, breathlessness, chest pain, neurological symptoms, low blood pressure, or swelling.COVID‑19 vaccines have some adverse effects that are listed as common in the two or three days following vaccination which are usually mild and temporary. Causes The rare simultaneous occurrence of thrombocytopenia (low blood platelets) with blood clots after vaccination raised the original concern about this condition. In many cases where acute thrombosis and thrombocytopenia have been found together after COVID‑19 vaccination, an antibody against platelet factor 4 has been identified. This phenomenon is mostly encountered in some people who have been administered heparin, but none of the reported cases had received heparin. More rarely, this phenomenon had previously been described as an autoimmune phenomenon in people who had not been exposed to heparin. One striking feature of thrombocytopenia in the presence of anti-PF4 antibodies is the propensity of some to develop thrombosis, a phenomenon called heparin-induced thrombocytopenia if heparin is involved.Thrombocytopenia is generally a common symptom after or during many viral infections, and it "has been consistently reported" after intravenous administration of adenoviral gene transfer vectors, although its mechanisms are not yet clear. There is no confirmed causal link to the syndrome and any COVID‑19 vaccination, however EMA is conducting investigations into AZD1222 and the Janssen COVID‑19 vaccine (Johnson & Johnson) for possible causal links.On 7 April 2021, the EMA noted one "plausible explanation" for the combination of blood clots and low blood platelets is "an immune response, leading to a condition similar to one seen sometimes in people treated with heparin", that is heparin induced thrombocytopenia (HIT). Diagnosis In the United Kingdom, professional societies led by the Royal College of Emergency Medicine have issued a guideline for suspected cases. Someone presenting with concerning symptoms between five and 28 days after administration of the vaccine is assessed for a possible thrombotic complication, with a full blood count (which includes a platelet count) as the initial investigation. If the platelet count is decreased, determination of the D-dimer and fibrinogen levels may be performed, with hematology expert advice recommended if these are elevated above specific cut offs. Management Guidelines from professional societies recommend treatment with alternative anticoagulants instead of heparin, as there is a possibility that it may aggravate the phenomenon. Alternative options as the directly acting oral anticoagulants (DOACs), argatroban, fondaparinux or danaparoid depending on the circumstances. Platelet transfusion is discouraged, as this too may aggravate thrombosis. UK guidelines by the British Society for Haematology recommend the administration of intravenous immunoglobulin (IVIG) to reduce levels of the pathogenic antibody. Low fibrinogen levels may require correction with fibrinogen concentrate or cryoprecipitate. Epidemiology The Paul Ehrlich Institute has recorded 31 cerebral venous sinus thromboses (CVST) and nine deaths out of 2.7 million vaccinated in Germany with the AZD1222. On 2 April 2021, the UKs Medicines and Healthcare products Regulatory Agency reported 22 cases of CVST and a further eight cases of clotting problems both associated with a low level of blood platelets following a "rigorous review" of its Yellow Card reporting. The institute also reported finding no events of this type which occurred after vaccination with the Pfizer–BioNTech COVID‑19 vaccine. The EMA had earlier said that a link between certain very rare blood clots and the AstraZeneca vaccine is "not proven, but is possible".Observations in Germany of these rare events seemed to relate mostly women aged under 55. However, because Germany had previously restricted AZD1222 to under 65s, the population vaccinated there with AZD1222 is comparatively younger, and consequently contained a higher proportion of women taking the contraceptive pill. As CVSTs are more likely in women using hormonal contraceptives, this inherent risk factor may be an influence on the reported preponderance of women experiencing these events following vaccination. The UK, in contrast, has applied its Pfizer and AZD1222 vaccines generally to older groups first, then by decreasing age.The UK Medicines and Healthcare products Regulatory Agency (MHRA) reporting regards AZD1222 to 3 November 2021, recording 73 deaths out of 425 cases (17%) in the context of 24.9 million first doses administered. Regulatory status According to the European Medicines Agency (EMA), as of 28 March 2021, the reported number of cases of embolic and thrombotic events after vaccination is lower than the rate of such events in the general population overall. However, the specific syndrome - of embolic and thrombotic events in combination with low levels of blood platelets - presenting in post-vaccination cases raised the possibility of an association between the vaccine and the relatively rare syndrome. The EMA also said that there is no proof that these events are caused by the vaccines, but that the possibility could not yet be ruled out completely. Accordingly, the EMA advised that people who received the vaccine and experienced symptoms suggestive of thrombosis, including shortness of breath, blurred vision and severe or persistent headache, should seek medical attention.In a press briefing on 7 April 2021, Emer Cooke, the executive director of the European Medicines Agency (EMA) began by stating "Our safety committee, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency, has confirmed that the benefits of the AstraZeneca vaccine in preventing COVID‑19 overall outweigh the risks of side effects. COVID‑19 is a very serious disease with high hospitalization and death rates and every day COVID is still causing thousands of deaths across the EU. This vaccine has proven to be highly effective, it prevents severe disease and hospitalization, and it is saving lives. Vaccination is extremely important in helping us in the fight against COVID‑19 and we need to use the vaccines we have to protect us from the devastating effects". She went on to say "The PRAC after a very in-depth analysis has concluded that the reported cases of unusual blood clotting following vaccination with the AstraZeneca vaccine should be listed as possible side effects of the vaccine". At the same briefing Dr. Samina Strauss of PRAC confirmed "our conclusion is that these clotting disorders are very rare side effects of the vaccine".The UK Medicines and Healthcare products Regulatory Agency (MHRA) held a news conference on 7 April 2021, and while there is no proof that the AZD1222 vaccination caused the rare blood clots, they indicated the possibility of a link is getting stronger. The UK is to offer under 30s alternative vaccines. The reasoning is because in the 20-29 age range the benefits to individual of vaccination were less as their likelihood of harm from COVID‑19 is less and closer to the potential risk of harm from the vaccine (at a medium exposure risk with COVID‑19 infection cases running at a rate of 60 per 100,000). For higher age groups the benefit to risk ratio increased.Also on 7 April 2021, an interim statement from the WHO said its advisory body, GACVS, found any "causal relationship" between the rare blood clot cases and AZD1222 to be "plausible but is not confirmed".On 20 April 2021, the safety committee of the EMA (PRAC) found a "possible link to very rare cases of unusual blood clots with low blood platelets" for the Johnson & Johnson Janssen vaccine; and required that these rare events, similar to those noted for AZD1222, should be listed as a very rare side effect. The EMA states the overall risk-benefit for the Janssen vaccine remains positive.On 16 December 2021, the US Centers for Disease Control and Prevention (CDC) recommended the Moderna and Pfizer­­-BioNTech vaccines should be preferred over the Janssen vaccine, following growing concerns about rare blood clots. Janssen should still be offered to people who specifically request it. History Organizations Global vaccine safety comes under the remit of the World Health Organization (WHO), and in particular its Global Advisory Committee on Vaccine Safety (GAVCS). Other drug regulatory agencies significantly involved include: European Medicines Agency (EMA), the regional regulatory authority for the EU. Medicines and Healthcare products Regulatory Agency (MHRA), the medical authority for the United Kingdom. Paul Ehrlich Institute (PEI), a German federal agency supervised by the Federal Ministry of Health with expertise in vaccines and biomedicines. It is a WHO collaborating centre. Syndrome identification A number of COVID‑19 vaccines began to become approved and available at scale in December 2020, with vaccinations beginning to ramp up at scale from the beginning of 2021, among them the Oxford–AstraZeneca COVID‑19 vaccine, based on an adenovirus vector and internally termed AZD1222.On 11 March 2021, the EMA issued a statement noting Denmark had suspended AZD1222 vaccinations due to a vaccinated patient dying with blood clots. While noting there had been reports of other vaccinated people having blood clots and that its safety committee is already reviewing such cases, the number of thromboembolic events in vaccinated people is no higher than in the general population.The World Health Organization (WHO) Global Advisory Committee on Vaccine Safety on 19 March 2021, issued a statement relating to safety signals related to AZD1222 relating to thromboembolic events and thrombocytopenia following review of available data and conclusions included that AZD1222 "a positive benefit-risk profile, with tremendous potential to prevent infections and reduce deaths across the world".In its safety update of 29 March 2021, the EMA indicated it had initiated investigations into the very rare cases of specific embolic and thrombotic events in combination with thrombocytopenia (low levels of blood platelets) and related bleeding including disseminated intravascular coagulation and cerebral venous sinus thrombosis (CVST), noting any link with AZD1222 is not proven but could not be excluded. The EMA also initiated an assessment for all COVID‑19 vaccines used in the EU for immune thrombocytopenia (ITP), described as low blood platelet levels that could lead to bruising and bleeding, as a possible side effect, whilst also stating that up to this point no link with any COVID‑19 had been established.On 7 April 2021, the EMA determined that unusual blood clots with low blood platelets should be listed as very rare side effects of AZD1222, with WHO and UK EHRA issuing generally similar statements on the same day. None of the agencies found a confirmed causal link between the vaccine and these incidents at the time, but were listing them out of an abundance of caution.A highlight of minutes of the EMAs Pharmacovigilance Risk Assessment Committee (PRAC) concluding 9 April 2021, indicating they also were investigating four cases of unusual blood clots with low blood platelets, including one death, amongst people who had taken the Janssen COVID‑19 vaccine. The Janssen vaccine is approved but not yet deployed in the EU, though vaccinations are in progress in the US. PRAC has determined that it is not clear if there is a causal association. Should regulatory action prove necessary, PRAC have indicated the likely outcome would be an update to product information characteristics. Vaccination campaign responses Early reports of the events of concern seemed to indicate the presentation rate for the specific blood clots of concern might be higher for women of younger ages, UK Medicines and Healthcare products Regulatory Agency (MHRA) found examples across all genders and ages, their data skewing towards these specific blood clots being more prevalent in AZD1222 vaccinated persons of younger ages.The WHO has continued to stress the administration of vaccines is based on risk versus benefit analysis. Some variables that may be factored into such analysis include risk of an individual from catching COVID‑19, which relate to the infection rate in that area, and the benefits to that individual if vaccinated and exposed to COVID‑19 which varies with age, versus whatever the risks of vaccination are to that individual. Regional and national responses The advisory panel for the government of Ontario, Canada has recommended against the use of heparin for management of thrombosis after vaccination until more is known.In response to the concerns over the adverse effects relating to rare blood clotting types Germany has suspended use of the AZD1222 in those under 60 years of age; in contrast to a period previously having suspended use of AZD1222 to over–65s due to limited data of the efficacy of the vaccine to this age group at that time.Following a few days of suspended use of AZD1222, the Ministry of Health, Welfare and Sport of the Netherlands decided to continue administering the vaccine only to persons above the age of 60.On 8 April 2021, the Australian Technical Advisory Group on Immunisation (ATAGI) advised the Australian Government that the Pfizer COVID‑19 vaccine is recommended over AZD1222 for adults aged under 50 years. The advice is "based on the increasing risk of severe outcomes from COVID‑19 in older adults (and hence a higher benefit from vaccination) and a potentially increased risk of thrombosis with thrombocytopenia following AstraZeneca vaccination in those under 50 years." AZD1222 is still recommended by ATAGI for people over 50, and those under 50 who have already had their first dose with no ill effects. In the state of Victoria, there were reports of some, aged under 50, being turned away from vaccination centres, despite having confirmed appointments. It is understood a special consent process will be developed by the Australian Government for people under 50 who choose to receive the AZD1222 vaccine. Studies A study convened by a group of British hematologists on 19 March 2021, just two days after the acknowledgement of the condition, published its finding in The New England Journal of Medicine, establishing case definition criteria. The study included 294 participants who presented with symptoms of thrombocytopenia and thrombosis after receipt of the first dose of the Oxford–AstraZeneca COVID‑19 vaccine, showing an independent association between baseline platelet count and the presence of intracranial hemorrhage. The study established that 85% of the participants effected by the condition were aged younger than 60 years, and that those participants with a history of thrombosis or prothrombotic disorders did not appear to be at increased risk. The study showed an overall mortality rate of 22% and set out plans for additional research to determine the genetic factors that may increase risk of the condition and identify potential therapeutic agents. References Notes Footnotes Further reading Aleem A, Nadeem AJ (July 2021). "Coronavirus (COVID-19) Vaccine-Induced Immune Thrombotic Thrombocytopenia (VITT)". StatPearls. PMID 34033367. Arepally GM, Ortel TL (July 2021). "Vaccine-induced immune thrombotic thrombocytopenia: what we know and do not know". Blood. 138 (4): 293–8. doi:10.1182/blood.2021012152. PMC 8172307. PMID 34323940. Iba T, Levy JH, Warkentin TE (January 2022). "Recognizing Vaccine-Induced Immune Thrombotic Thrombocytopenia". Crit Care Med. 50 (1): e80–e86. doi:10.1097/CCM.0000000000005211. PMC 8670081. PMID 34259661. Schultz NH, Sørvoll IH, Michelsen AE, Munthe LA, Lund-Johansen F, Ahlen MT, et al. (June 2021). "Thrombosis and Thrombocytopenia after ChAdOx1 nCoV-19 Vaccination". N Engl J Med. 384 (22): 2124–30. doi:10.1056/NEJMoa2104882. PMC 8112568. PMID 33835768. Scully M, Singh D, Lown R, Poles A, Solomon T, Levi M, et al. (June 2021). "Pathologic Antibodies to Platelet Factor 4 after ChAdOx1 nCoV-19 Vaccination". N Engl J Med. 384 (23): 2202–11. doi:10.1056/NEJMoa2105385. PMC 8112532. PMID 33861525. External links EMA press conference 7th April on YouTube

Vasospasm

Vasospasm refers to a condition in which an arterial spasm leads to vasoconstriction. This can lead to tissue ischemia and tissue death (necrosis). Cerebral vasospasm may arise in the context of subarachnoid hemorrhage. Symptomatic vasospasm or delayed cerebral ischemia is a major contributor to post-operative stroke and death especially after aneurysmal subarachnoid hemorrhage. Vasospasm typically appears 4 to 10 days after subarachnoid hemorrhage. Along with physical resistance, vasospasm is a main cause of ischemia. Like physical resistance, vasospasms can occur due to atherosclerosis. Vasospasm is the major cause of Prinzmetals angina. Pathophysiology Normally endothelial cells release prostacyclin and nitric oxide (NO) which induce relaxation of the smooth muscle cells, and reduce aggregation of platelets. Aggregating platelets stimulate ADP to act on endothelial cells and help them induce relaxation of the smooth muscle cells. However, aggregating platelets also stimulate thromboxane A2 and serotonin which can induce contraction of the smooth muscle cells. In general, the relaxations outweighs the contractions. In atherosclerosis, a dysfunctional endothelium is observed on examination. It does not stimulate as much prostacyclin and NO to induce relaxation on smooth muscle cells. Also there is not as much inhibition of aggregation of platelets. In this case, the greater aggregation of platelets produce ADP, serotonin, and thromboxane A2. However the serotonin and the thromboxane A2 cause more contraction of the smooth muscle cells and as a result contractions outweigh the relaxations. Complications Vasospasm can occur in a wide variety of peripheral vascular beds under poorly understood mechanisms. Prinzmetal angina, Buergers disease, contrast mediated selective renal vasospasm, hypercoagulability and cryoglobulinemia likely represent just a few of the known pieces of this puzzling phenomena. Ischemia in the heart due to prolonged coronary vasospasm can lead to angina, myocardial infarction and even death. Vasospasm in the hands and fingers due to prolonged exposure to vibration (30 – 300 Hz) and triggered by cold can lead to Hand-arm vibration syndrome in which feeling and manual dexterity are lost. Angiography In angiography, vascular access through femoral and axillary arteries are preferred because they are less prone to vasospasm. Meanwhile, brachial artery is more prone to vasospasm during instrumental access. Hypothermia Rewarming In a case study in 2000, following surgery for head trauma, a patient developed mild hypothermia, a typical defense mechanism the brain uses to protect itself after injury. After the hypothermia rewarming period, the patient died from increased intracranial pressure and anisocoria. A sample of the cerebrospinal fluid and autopsy results indicated cerebral vasospasm. Treatment The occurrence of vasospasm can be reduced by preventing the occurrence of atherosclerosis. This can be done in several ways, the most important being lifestyle modifications—decreasing low-density lipoprotein (LDL), quitting smoking, physical activity, and control for other risk factors including diabetes, obesity, and hypertension. Pharmacological therapies include hypolipidemic agents, thrombolytics and anticoagulants. Pharmacological options for reducing the severity and occurrence of ischemic episodes include the organic nitrates, which are rapidly metabolized to release nitric oxide in many tissues, and are classified as having either long-acting (i.e. isosorbide dinitrate) or short-acting (i.e. nitroglycerin) durations of action. These drugs work by increasing nitric oxide levels in the blood and inducing coronary vasodilation which will allow for more coronary blood flow due to a decreased coronary resistance, allowing for increased oxygen supply to the vital organs (myocardium). The nitric oxide increase in the blood resulting from these drugs also causes dilation of systemic veins which in turn causes a reduction in venous return, ventricular work load and ventricular radius. All of these reductions contribute to the decrease in ventricular wall stress which is significant because this causes the demand of oxygen to decrease. In general organic nitrates decrease oxygen demand and increase oxygen supply. It is this favourable change to the body that can decrease the severity of ischemic symptoms, particularly angina. Other medications used to reduce the occurrence and severity of vasospasm and ultimately ischemia include L-type calcium channel blockers (notably nimodipine, as well as verapamil, diltiazem, nifedipine) and beta-receptor antagonists (more commonly known as beta blockers or β-blockers) such as propranolol. L-type calcium channel blockers can induce dilation of the coronary arteries while also decreasing the hearts demand for oxygen by reducing contractility, heart rate, and wall stress. The reduction of these latter three factors decreases the contractile force that the myocardium must exert in order to achieve the same level of cardiac output. Beta-receptor antagonists do not cause vasodilation, but like L-type calcium channel blockers, they do reduce the hearts demand for oxygen. This reduction similarly results from a decrease in heart rate, afterload, and wall stress. Adverse effects Like most pharmacological therapeutic options, there are risks that should be considered. For these drugs in particular, vasodilation can be associated with some adverse effects which might include orthostatic hypotension, reflex tachycardia, headaches and palpitations. Tolerance may also develop over time due compensatory response of the body, as well as depletion of -SH groups of glutathione which are essential for the metabolism of the drugs to their active forms. Potential side effects: Verapamil: hypotension, bradycardia, constipation Diltiazem: hypotension, bradycardia, risk of heart block Nifedipine: hypotension Propranolol: asystole, asthma attacks Contraindications Organic nitrates should not be taken with PDE5 inhibitors (i.e. sildenafil) since both NO and PDE5 inhibitors increase cyclic GMP levels and the sum of their pharmacodynamic effects will greatly exceed the optimal therapeutic levels. What you could see upon taking both medications at the same time, as caused by the much higher induction of relaxation of smooth muscle cells, include a severe drop in blood pressure. Beta-receptor antagonists should be avoided in patients with reactive pulmonary disease to avoid asthma attacks. Also Beta-receptor antagonists should be avoided in patients with AV node dysfunction and/or patients on other medications which might cause bradycardia (i.e. calcium channel blockers). The potential for these contraindications and drug-drug interaction could lead to asystole and cardiac arrest. Certain calcium channel blocker should be avoided with some beta-receptor blockers since they may cause severe bradycardia and other potential side effects. Corrective therapy Since vasospasms can be caused by atherosclerosis and contribute to the severity of ischemia there are some surgical options which can restore circulation to these ischemic areas. Regarding coronary vasospasm, one surgical intervention, referred to as percutaneous coronary intervention or angioplasty, involves placing a stent at the site of stenosis in an artery and inflating the stent using a balloon catheter. Another surgical intervention is coronary artery bypass. See also Coronary artery vasospasm Raynauds phenomenon, a vasospastic disorder Reversible cerebral vasoconstriction syndrome References == 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

Hydronephrosis

Hydronephrosis describes hydrostatic dilation of the renal pelvis and calyces as a result of obstruction to urine flow downstream. Alternatively, hydroureter describes the dilation of the ureter, and hydronephroureter describes the dilation of the entire upper urinary tract (both the renal pelvicalyceal system and the ureter). Signs and symptoms The signs and symptoms of hydronephrosis depend upon whether the obstruction is acute or chronic, partial or complete, unilateral or bilateral. Hydronephrosis that occurs acutely with sudden onset (as caused by a kidney stone) can cause intense pain in the flank area (between the hips and ribs) known as a renal colic. Historically, this type of pain has been described as "Dietls crisis". Conversely, hydronephrosis that develops gradually over time will generally cause either a dull discomfort or no pain. Nausea and vomiting may also occur. An obstruction that occurs at the urethra or bladder outlet can cause pain and pressure resulting from distension of the bladder. Blocking the flow of urine will commonly be prone to urinary tract infections which can lead to further development of stones, fever, and blood or pus in the urine. If complete obstruction occurs, a postrenal kidney failure (obstructive nephropathy) may follow.Blood tests may show impaired kidney function (elevated urea or creatinine) or electrolyte imbalances such as hyponatremia or hyperchloremic metabolic acidosis. Urinalysis may indicate an elevated pH due to the secondary destruction of nephrons within the affected kidney, which impairs acid excretion. Physical examination in a thin patient may detect a palpable abdominal or flank mass caused by the enlarged kidney. Causes Hydronephrosis is the result of any of several abnormal pathophysiological occurrences. Structural abnormalities of the junctions between the kidney, ureter and bladder that lead to hydronephrosis can occur during fetal development. Some of these congenital defects have been identified as inherited conditions, however, the benefits of linking genetic testing to early diagnosis have not been determined. Other structural abnormalities could be caused by injury, surgery, or radiation therapy.The most common causes of hydronephrosis in children are anatomical abnormalities. These include vesicoureteral reflux, urethral stricture, and stenosis. The most common cause of hydronephrosis in young adults is kidney stones. In older adults, the most common cause of hydronephrosis is benign prostate hyperplasia (BPH), or intrapelvic neoplasms such as prostate cancer. Compression of one or both ureters can also be caused by other developmental defects not completely occurring during the fetal stage such as an abnormally placed vein, artery, or tumor. Bilateral compression of the ureters can occur during pregnancy due to enlargement of the uterus. Changes in hormone levels during this time may also affect the muscle contractions of the bladder, further complicating this condition.Sources of obstruction that can arise from other various causes include kidney stones, blood clots or retroperitoneal fibrosis.The obstruction may be either partial or complete, and can occur anywhere from the urethral meatus to the renal calyces. Hydronephrosis can also result from the retrograde flow of urine from the bladder back into the kidneys (vesicoureteral reflux), which can be caused by some of the factors listed above as well as compression of the bladder outlet into the urethra by prostate enlargement or fecal impaction in the rectum (which sits immediately behind the prostate), as well as abnormal contractions of bladder detrusor muscles resulting from neurological dysfunction (neurogenic bladder) or other muscular disorders. Pathophysiology Hydronephrosis is caused by obstruction of urine before the renal pelvis. The obstruction causes dilation of the nephron tubules and flattening of the lining of the tubules within the kidneys which in turn causes swelling of the renal calyces. Hydronephrosis can either be acute or chronic. In acute hydronephrosis full recovery of kidney function is seen. However, with chronic hydronephrosis, permanent loss of kidney function is seen even once obstruction is removed. Obstruction that occurs anywhere along the upper urinary tract will lead to increased pressure within the structures of the kidney due to the inability to pass urine from the kidney to the bladder. Common causes of upper tract obstruction include obstructing stones and ureteropelvic junction (UPJ) obstruction caused by intrinsic narrowing of the ureters or an overlying vessel. Obstruction occurring in the lower urinary tract can also cause this increased pressure through the reflux of urine into the kidney. Common causes include bladder dysfunction (such as neurogenic bladder) and urethral obstruction (such as posterior urethral valves in male infants) or compression (such as from prostatic hypertrophy in older male adults). In pregnancy, dextrorotation (rotation to the right) of the uterus can cause compression on the right ureter, thus making hydronephrosis more common in right kidney than left kidney. Besides, hormones such as oestrogen, progestrerone, and prostaglandin can cause ureter dilatation, thus causing hydronephrosis despite the absence of visible obstruction along the urinary tract. Diagnosis Prenatal diagnosis is possible, and in fact, most cases in pediatric patients are incidentally detected by routine screening ultrasounds obtained during pregnancy. However, approximately half of all prenatally identified hydronephrosis is transient, and resolves by the time the infant is born, and in another 15%, the hydronephrosis persists but is not associated with urinary tract obstruction (so-called non-refluxing, non-obstructive hydronephrosis). For these children, regression of the hydronephrosis occurs spontaneously, usually by age 3. However, in the remaining 35% of cases of prenatal hydronephrosis, a pathological condition can be identified postnatally.Diagnostic workup depends on the age of the patient, as well as whether the hydronephrosis was detected incidentally or prenatally or is associated with other symptoms. Blood tests (such measurement of creatinine) are typically indicated, though they must be interpreted cautiously. Even in cases of severe unilateral hydronephrosis, the overall kidney function may remain normal since the unaffected kidney will compensate for the obstructed kidney.Urinalysis is usually performed to determine the presence of blood (which is typical for kidney stones) or signs of infection (such as a positive leukocyte esterase or nitrite). Impaired concentrating ability or elevated urine pH (distal renal tubular acidosis) are also commonly found due to tubular stress and injury. Imaging studies Imaging studies, such as an intravenous urogram (IVU), renal ultrasonography, CT, or MRI, are also important investigations in determining the presence and/ or cause of hydronephrosis. Whilst ultrasound allows for visualisation of the ureters and kidneys (and determine the presence of hydronephrosis and / or hydroureter), an IVU is useful for assessing the anatomical location of the obstruction. Antegrade or retrograde pyelography will show similar findings to an IVU but offer a therapeutic option as well. Real-time ultrasounds and Doppler ultrasound tests in association with vascular resistance testing helps determine how a given obstruction is effecting urinary functionality in hydronephrotic patients.In determining the cause of hydronephrosis, the location of obstruction can be determined with a Whittaker (or pressure perfusion) test, wherein the collecting system of the kidney is accessed percutaneously, and the liquid is introduced at high pressure and constant rate of 10ml/min while measuring the pressure within the renal pelvis. A rise in pressure above 22 cm H2O suggests that the urinary collection system is obstructed. When arriving at this pressure measurement, bladder pressure is subtracted from the initial reading of internal pressure. (The test was first described by Whittaker in 1973 to test the hypothesis that patients whose hydronephrosis persists after the posterior urethral valves have been ablated usually have ureters that are not obstructed, even though they may be dilated.)Kay recommends that a neonate born with untreated in utero hydronephrosis receive a renal ultrasound within two days of birth. A renal pelvis greater than 12mm in a neonate is considered abnormal and suggests significant dilation and possible abnormalities such as obstruction or morphological abnormalities in the urinary tract.The choice of imaging depends on the clinical presentation (history, symptoms and examination findings). In the case of renal colic (one sided loin pain usually accompanied by a trace of blood in the urine) the initial investigation is usually a spiral or helical CT scan. This has the advantage of showing whether there is any obstruction of flow of urine causing hydronephrosis as well as demonstrating the function of the other kidney. Many stones are not visible on plain X-ray or IVU but 99% of stones are visible on CT and therefore CT is becoming a common choice of initial investigation. CT is not used, however, when there is a reason to avoid radiation exposure, e.g. in pregnancy.For incidentally detected prenatal hydronephrosis, the first study to obtain is a postnatal renal ultrasound, since as noted, many cases of prenatal hydronephrosis resolve spontaneously. This is generally done within the first few days after birth, although there is some risk that obtaining an imaging study this early may miss some cases of mild hydronephrosis due to the relative oliguria of a newborn. Thus, some experts recommend obtaining a follow-up ultrasound at 4–6 weeks to reduce the false-negative rate of the initial ultrasound. A voiding cystourethrogram (VCUG) is also typically obtained to exclude the possibility of vesicoureteral reflux or anatomical abnormalities such as posterior urethral valves. Finally, if hydronephrosis is significant and obstruction is suspected, such as a ureteropelvic junction (UPJ) or ureterovesical junction (UVJ) obstruction, a nuclear imaging study such as a MAG-3 scan is warranted. Grading The Society of Fetal Ultrasound (SFU) has developed a grading system for hydronephrosis, initially intended for use in neonatal and infant hydronephrosis, but it is now used for grading hydronephrosis in adults as well: Grade 0 – No renal pelvis dilation. This means an anteroposterior diameter of less than 4 mm in fetuses up to 32 weeks of gestational age and 7 mm afterwards. In adults, cutoff values for renal pelvic dilation have been defined differently by different sources, with anteroposterior diameters ranging between 10 and 20 mm. About 13% of normal healthy adults have a transverse pelvic diameter of over 10 mm. Grade 1 (mild) – Mild renal pelvis dilation (anteroposterior diameter less than 10 mm in fetuses) without dilation of the calyces nor parenchymal atrophy Grade 2 (mild) – Moderate renal pelvis dilation (between 10 and 15 mm in fetuses), including a few calyces Grade 3 (moderate) – Renal pelvis dilation with all calyces uniformly dilated. Normal renal parenchyma Grade 4 (severe) – As grade 3 but with thinning of the renal parenchyma Treatment Treatment of hydronephrosis focuses upon the removal of the obstruction and drainage of the urine that has accumulated behind the obstruction. Therefore, the specific treatment depends upon where the obstruction lies.Acute obstruction of the upper urinary tract is usually treated by the insertion of a nephrostomy tube. Chronic upper urinary tract obstruction is treated by the insertion of a ureteric stent or a pyeloplasty.Lower urinary tract obstruction (such as that caused by bladder outflow obstruction secondary to prostatic hypertrophy) is usually treated by insertion of a urinary catheter or a suprapubic catheter. Surgery is not required in all prenatally detected cases. Prognosis The prognosis of hydronephrosis is extremely variable and depends on the condition leading to hydronephrosis, whether one (unilateral) or both (bilateral) kidneys are affected, the pre-existing kidney function, the duration of hydronephrosis (acute or chronic), and whether hydronephrosis occurred in developing or mature kidneys.Permanent kidney damage can occur from prolonged hydronephrosis secondary to compression of kidney tissue and ischemia.For example, unilateral hydronephrosis caused by an obstructing stone will likely resolve when the stone passes, and the likelihood of recovery is excellent. Alternately, severe bilateral prenatal hydronephrosis (such as occurs with posterior urethral valves) will likely carry a poor long-term prognosis, because obstruction while the kidneys are developing causes permanent kidney damage even if the obstruction is relieved postnatal.Hydronephrosis can be a cause of pyonephrosis, which is a urological emergency. == References ==

Penile pain

Penile pain refers to pain in the penis, human or otherwise. Common causes Penile injury Circumcision Penile fracture Priapism Phimosis Peyronies disease Sexually transmitted infections Chronic prostatitis/chronic pelvic pain syndrome Cultural references Priapus, a minor Greek god of fertility, is marked by his oversized, permanent erection, which gave rise to the medical term priapism. Some researchers believe the depiction of Priapus penis referred to a penile disease, and that paintings of Priapus were used to ward off the disease. See also Genital pain Vaginal pain Testicular pain List of the causes of genital pain == References ==

Tracheoesophageal fistula

A tracheoesophageal fistula (TEF, or TOF; see spelling differences) is an abnormal connection (fistula) between the esophagus and the trachea. TEF is a common congenital abnormality, but when occurring late in life is usually the sequela of surgical procedures such as a laryngectomy. Presentation Tracheoesophageal fistula is suggested in a newborn by copious salivation associated with choking, coughing, vomiting, and cyanosis coincident with the onset of feeding. Esophageal atresia and the subsequent inability to swallow typically cause polyhydramnios in utero. Rarely it may present in an adult. Complications Surgical repair can sometimes result in complications, including: Stricture, due to gastric acid erosion of the shortened esophagus Leak of contents at the point of anastomosis Recurrence of fistula Gastro-esophageal reflux disease Dysphagia Asthma-like symptoms, such as persistent coughing/wheezing Recurrent chest infections Tracheomalacia Associations Neonates with TEF or esophageal atresia are unable to feed properly. Once diagnosed, prompt surgery is required to allow the food intake. Some children experience problems following TEF surgery; they can develop dysphagia and thoracic problems. Children with TEF can also be born with other abnormalities, most commonly those described in VACTERL association - a group of anomalies which often occur together, including heart, kidney and limb deformities. 6% of babies with TEF also have a laryngeal cleft. Cause Congenital TEF can arise due to failed fusion of the tracheoesophageal ridges after the fourth week of embryological development.A fistula, from the Latin meaning a pipe, is an abnormal connection running either between two tubes or between a tube and a surface. In tracheo-esophageal fistula it runs between the trachea and the esophagus. This connection may or may not have a central cavity; if it does, then food within the esophagus may pass into the trachea (and on to the lungs) or alternatively, air in the trachea may cross into the esophagus.TEF can also occur due to pressure necrosis by a tracheostomy tube in apposition to a nasogastric tube (NGT). Diagnosis TEF should be suspected once the baby fails to swallow after their first feeding during the first day of life. Esophageal atresia can be diagnosed by Ryle nasogastric tube; if the Ryle fails to pass into the stomach, then this indicates esophageal atresia and loss of communication between stomach and esophagus. TEF may be diagnosed by MRI which clarifies the atretic esophagus (if presents) and TEF, as well as its location and anatomy. Gastrograffin contrast swallow should not be used if TEF is suspected, due to its high risk of allergy and severe intractable chest infection. Classification Fistulae between the trachea and esophagus in the newborn can be of diverse morphology and anatomical location. However, various pediatric surgical publications have attempted a classification system based on the below specified types.Not all types include both esophageal agenesis and tracheoesophageal fistula, but the most common types do. The letter codes are usually associated with the system used by Gross, while number codes are usually associated with Vogt.An additional type, "blind upper segment only" has been described, but this type is not usually included in most classifications. (For the purposes of this discussion, proximal esophagus indicates normal esophageal tissue arising normally from the pharynx, and distal esophagus indicates normal esophageal tissue emptying into the proximal stomach.) Treatment It is surgically corrected, with resection of any fistula and anastomosis of any discontinuous segments. Babies often need to spend time in a neonatal intensive care unit for feeding with a stomach feeding tube. Antibiotics, pain relief, a chest drain, oxygen, and ventilation may all be needed. References == External links ==

Hemoperitoneum

Hemoperitoneum (also haemoperitoneum, sometimes also hematoperitoneum) is the presence of blood in the peritoneal cavity. The blood accumulates in the space between the inner lining of the abdominal wall and the internal abdominal organs. Hemoperitoneum is generally classified as a surgical emergency; in most cases, urgent laparotomy is needed to identify and control the source of the bleeding. In selected cases, careful observation may be permissible. The abdominal cavity is highly distensible and may easily hold greater than five liters of blood, or more than the entire circulating blood volume for an average-sized individual. Therefore, large-scale or rapid blood loss into the abdomen will reliably induce hemorrhagic shock and, if untreated, may rapidly lead to death. Causes Causes of hemoperitoneum include: Penetrating trauma Blunt trauma, most commonly injuries to solid organs such as the liver and spleen. Vascular accidents, such as rupture of an abdominal aortic aneurysm, iliac aneurysm, or splenic aneurysm. Bleeding due to a ruptured ectopic pregnancy or uterine rupture. Rupture of corpus luteum in some cases. Less commonly, bleeding due to a perforated gastric ulcer. Bleeding due to rupture of an intra-abdominal neoplasm, (e.g., Hepatoblastoma) Disseminated intravascular coagulation People on high dose of anticoagulants (blood thinners) Perforation of the colon Diagnosis Hemoperitoneum can be reliably diagnosed with the following examinations: Focused assessment with sonography for trauma (FAST) Paracentesis or diagnostic peritoneal lavage Computed tomography Diagnostic laparoscopy or exploratory laparotomy Treatment Initial management consists of immediate blood transfusion if the patient is in hemorrhagic shock. Classically, hemoperitoneum was an indication for emergency surgery to locate the source of bleeding and also to recover spilled blood from the peritoneal cavity and to use it for auto-transfusion if it has not been contaminated by ruptured bowel contents. The method of control depends on the source of blood loss. Vascular bleeding, i.e. from a blood vessel, would be treated by clamping and ligation of the offending vessel, or repair of the vessel in the case of major arteries such as the aorta or mesenteric arteries. Bleeding from the spleen most often requires splenectomy, or removal of the spleen, usually but not always in the form of a total splenectomy. Bleeding from the liver might be controlled by application of hemostatic sponges, thrombin, or more recently, argon beam cauterization.With modern diagnostic aids such as computed tomography (CT) scans, certain injuries such as low-grade lacerations of the spleen may be diagnosed early and observed, with surgical options deferred unless clinical deterioration obligates them. In rare occasions, rupture of an Abdominal Aortic Aneurysm may be repaired via an endovascular technique, though this is generally not performed in the setting of acute rupture. References == External links ==

Orthostatic hypotension

Orthostatic hypotension, also known as postural hypotension, is a medical condition wherein a persons blood pressure drops when standing up or sitting down. Primary orthostatic hypertension is also often referred to as neurogenic orthostatic hypotension. The drop in blood pressure may be sudden (vasovagal orthostatic hypotension), within 3 minutes (classic orthostatic hypotension) or gradual (delayed orthostatic hypotension). It is defined as a fall in systolic blood pressure of at least 20 mmHg or diastolic blood pressure of at least 10 mmHg when a person assumes a standing position. It occurs predominantly by delayed (or absent) constriction of the lower body blood vessels, which is normally required to maintain adequate blood pressure when changing the position to standing. As a result, blood pools in the blood vessels of the legs for a longer period, and less is returned to the heart, thereby leading to a reduced cardiac output and inadequate blood flow to the brain. Very mild occasional orthostatic hypotension is common and can occur briefly in anyone, although it is prevalent in particular among the elderly and those with known low blood pressure. Severe drops in blood pressure can lead to fainting, with a possibility of injury. Moderate drops in blood pressure can cause confusion/inattention, delirium, and episodes of ataxia. Chronic orthostatic hypotension is associated with cerebral hypoperfusion that may accelerate the pathophysiology of dementia. Whether it is a causative factor in dementia is unclear.The numerous possible causes for orthostatic hypotension include certain medications (e.g. alpha blockers), autonomic neuropathy, decreased blood volume, multiple system atrophy, and age-related blood-vessel stiffness. Apart from addressing the underlying cause, orthostatic hypotension may be treated with a recommendation to increase salt and water intake (to increase the blood volume), wearing compression stockings, and sometimes medication (fludrocortisone, midodrine, or others). Salt loading (dramatic increases in salt intake) must be supervised by a doctor, as this can cause severe neurological problems if done too aggressively. Signs and symptoms Orthostatic hypotension is characterized by symptoms that occur after standing (from lying or sitting), particularly when done rapidly. Many report lightheadedness (a feeling that one might be about to faint), sometimes severe, or even actual fainting with associated fall risk. With chronic orthostatic hypotension, the condition and its effects may worsen even as fainting and many other symptoms become less frequent. Generalized weakness or tiredness may also occur. Some also report difficulty concentrating, blurred vision, tremulousness, vertigo, anxiety, palpitations (awareness of the heartbeat), unsteadiness, feeling sweaty or clammy, and sometimes nausea. A person may look pale. Some people may experience severe orthostatic hypotension with the only symptoms being confusion or extreme fatigue. Chronic severe orthostatic hypotension may present as fluctuating cognition/delirium. Women who are pregnant are also susceptible to orthostatic hypotension. Associated diseases The disorder may be associated with Addisons disease, atherosclerosis (build-up of fatty deposits in the arteries), diabetes, pheochromocytoma, porphyria, and certain neurological disorders, including autoimmune autonomic ganglionopathy, multiple system atrophy, and other forms of dysautonomia. It is also associated with Ehlers–Danlos syndrome and anorexia nervosa. It is also present in many patients with Parkinsons disease or Lewy body dementia resulting from sympathetic denervation of the heart or as a side effect of dopaminomimetic therapy. This rarely leads to fainting unless the person has developed true autonomic failure or has an unrelated heart problem.Another disease, dopamine beta hydroxylase deficiency, also thought to be underdiagnosed, causes loss of sympathetic noradrenergic function and is characterized by low or extremely low levels of norepinephrine, but an excess of dopamine.Quadriplegics and paraplegics also might experience these symptoms due to multiple systems inability to maintain normal blood pressure and blood flow to the upper part of the body. Causes Some causes of orthostatic hypotension include neurodegenerative disorders, low blood volume (e.g. caused by dehydration, bleeding, or the use of diuretics), drugs that cause vasodilation, other types of drugs (notably, narcotics and marijuana), discontinuation of vasoconstrictors, prolonged bed rest (immobility), significant recent weight loss, anemia, vitamin B12 deficiency, or recent bariatric surgery. Medication Orthostatic hypotension can be a side effect of certain antidepressants, such as tricyclics or monoamine oxidase inhibitors (MAOIs). Marijuana and tetrahydrocannabinol can on occasion produce marked orthostatic hypotension. Alcohol can potentiate orthostatic hypotension to the point of syncope. Orthostatic hypotension can also be a side effect of alpha-1 blockers (alpha1 adrenergic blocking agents). Alpha1 blockers inhibit vasoconstriction normally initiated by the baroreceptor reflex upon postural change and the subsequent drop in pressure. Other factors Patients prone to orthostatic hypotension are the elderly, post partum mothers, and those having been on bed rest. People with anorexia nervosa and bulimia nervosa often develop orthostatic hypotension as a common side effect. Consuming alcohol may also lead to orthostatic hypotension due to its dehydrating effects. Mechanism Orthostatic hypotension happens when gravity causes blood to pool in the lower extremities, which in turn compromises venous return, resulting in decreased cardiac output and subsequent lowering of arterial pressure. For example, changing from a lying position to standing loses about 700 ml of blood from the thorax, with a decrease in systolic and diastolic blood pressures. The overall effect is insufficient blood perfusion in the upper part of the body.Normally, a series of cardiac, vascular, neurologic, muscular, and neurohumoral responses occurs quickly so the blood pressure does not fall very much. One response is a vasoconstriction (baroreceptor reflex), pressing the blood up into the body again. (Often, this mechanism is exaggerated and is why diastolic blood pressure is a bit higher when a person is standing up, compared to a person in the horizontal position.) Therefore, some factor that inhibits one of these responses and causes a greater than normal fall in blood pressure is required. Such factors include low blood volume, diseases, and medications. Diagnosis Orthostatic hypotension can be confirmed by measuring a persons blood pressure after lying flat for 5 minutes, then 1 minute after standing, and 3 minutes after standing. Orthostatic hypotension is defined as a fall in systolic blood pressure of at least 20 mmHg or the diastolic blood pressure of at least 10 mmHg between the supine reading and the upright reading. Also, the heart rate should be measured for both positions. A significant increase in heart rate from supine to standing may indicate a compensatory effort by the heart to maintain cardiac output. A related syndrome, postural orthostatic tachycardia syndrome (POTS), is diagnosed when at least a 30 bpm increase in heart rate occurs with little or no change in blood pressure. A tilt table test may also be performed. Definition Orthostatic hypotension (or postural hypotension) is a drop in blood pressure upon standing. One definition (AAFP) calls for a systolic blood pressure decrease of at least 20 mm Hg or a diastolic blood pressure decrease of at least 10 mm Hg within 3 minutes of standing. A common first symptom is lightheadedness upon standing, possibly followed by more severe symptoms: narrowing or loss of vision, dizziness, weakness, and even syncope (fainting). Subcategories Orthostatic hypotension can be subcategorized into three groups – initial, classic, and delayed.Initial orthostatic hypotension is frequently characterized by a systolic blood pressure decrease of ≥40 mmHg or diastolic blood pressure decrease of ≥20 mmHg within 15 seconds of standing. Blood pressure then spontaneously and rapidly returns to normal, so the period of hypotension and symptoms is short (<30 s). Only continuous beat-to-beat BP measurement during an active standing-up maneuver can document this condition.Classic orthostatic hypotension is frequently characterized by a systolic blood pressure decrease of ≥20 mmHg or diastolic blood pressure decrease of ≥10 mmHg between 30 seconds and 3 min of standing.Delayed orthostatic hypotension is frequently characterized by a sustained systolic blood pressure decrease of ≥20 mm Hg or a sustained diastolic blood pressure decrease ≥of 10 mm Hg beyond 3 minutes of standing or upright tilt table testing. Management Lifestyle changes Apart from treating underlying reversible causes (e.g., stopping or reducing certain medications, treating autoimmune causes), several measures can improve the symptoms of orthostatic hypotension and prevent episodes of syncope (fainting). Even small increases in the blood pressure may be sufficient to maintain blood flow to the brain on standing.In dysautonomic patients who do not have a diagnosis of high blood pressure, drinking 2–3 liters of fluid a day and taking 10 g of salt can improve symptoms, by maximizing the amount of fluid in the bloodstream. Another strategy is keeping the head of the bed slightly elevated. This reduces the return of fluid from the limbs to the kidneys at night, thereby reducing nighttime urine production and maintaining fluid in the circulation. Various measures can be used to improve the return of blood to the heart; the wearing of compression stockings and exercises ("physical counterpressure maneuvers" or PCMs) can be undertaken just before standing up (e.g., leg crossing and squatting). Medications The medication midodrine can benefit people with orthostatic hypotension, The main side effect is piloerection ("goose bumps"). Fludrocortisone is also used, although based on more limited evidence.Droxidopa has been shown to be effective as well, with few, mostly mild side effects reported.A number of other measures have slight evidence to support their use – indomethacin, fluoxetine, dopamine antagonists, metoclopramide, domperidone, monoamine oxidase inhibitors with tyramine (can produce severe hypertension), oxilofrine, potassium chloride, and yohimbine. Other Robotic devices, such as the ERIGO machine, has been proven to help orthostatic hypotension in some patients. These machines adjust a patients position from 0 degrees to 90 degrees in progressive increments, allowing the blood pressure to adjust more slowly. Prognosis Orthostatic hypotension may cause accidental falls. It is also linked to an increased risk of cardiovascular disease, heart failure, and stroke. Also, observational data suggest that orthostatic hypotension in middle age increases the risk of eventual dementia and reduced cognitive function. See also Orthostatic hypertension Orthostatic intolerance Vasovagal response References External links Orthostatic hypotension at Curlie Postural hypotension : what it is and how to manage it – Centers for Disease Control and Prevention

Hyposmia

Hyposmia, or microsmia, is a reduced ability to smell and to detect odors. A related condition is anosmia, in which no odors can be detected. Some of the causes of olfaction problems are allergies, nasal polyps, viral infections and head trauma. In 2012 an estimated 9.8 million people aged 40 and older in the United States had hyposmia and an additional 3.4 million had anosmia/severe hyposmia.Hyposmia might be a very early sign of Parkinsons disease. Hyposmia is also an early and almost universal finding in Alzheimers disease and dementia with Lewy bodies. Lifelong hyposmia could be caused by Kallmann syndrome or Autism Spectrum Disorder. Along with other chemosensory disturbances, hyposmia can be a key indicator of COVID-19. Epidemiology The National Health and Nutrition Examination Survey (NHANES) collected data on chemosensory function (taste and smell) in a nationally-representative sample of US civilian, non-institutionalized persons in 2012. Olfactory function was assessed on persons aged 40 years and older with an 8-item, odor identification test (Pocket Smell Tests™, Sensonics, Inc., Haddon Heights, NJ). Odors included food odors (strawberry, chocolate, onion, grape), warning odors (natural gas, smoke) and household odors (leather, soap). Olfactory function score was based on the number of correct identifications. Prevalence (%) of anosmia/severe hyposmia (scores 0 to 3) was 0.3 at age 40-49 rising to 14.1 at age 80+. Prevalence of hyposmia (scores 4 to 5) was much higher: 3.7% at age 40-49 and 25.9% at 80+. Both were more prevalent in individuals of African descent than in those of Caucasian descent. Chemosensory data were also collected in a larger NHANES sample in 2013-2014. The prevalence of smell disorder (scores 0-5 out of 8 correct) was 13.5% in persons aged 40 years and over. If the same prevalence occurred in 2016, an estimated 20.5 million persons 40 and over had hyposmia or anosmia. In addition multiple demographic socioeconomic, and lifestyle characteristics were assessed as risk factors for diminished smell. In statistical analyses, greater age and male sex, coupled with either Black and/or non-Hispanic ethnicity, low family income, low educational attainment, high alcohol consumption (more than 4 drinks per day), and a history of asthma or cancer were independently associated with a greater prevalence of smell impairment. See also Hyperosmia Dysosmia Anosmia == References ==

Birth defect

A birth defect, also known as a congenital disorder, is an abnormal condition that is present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth defects are divided into two main types: structural disorders in which problems are seen with the shape of a body part and functional disorders in which problems exist with how a body part works. Functional disorders include metabolic and degenerative disorders. Some birth defects include both structural and functional disorders.Birth defects may result from genetic or chromosomal disorders, exposure to certain medications or chemicals, or certain infections during pregnancy. Risk factors include folate deficiency, drinking alcohol or smoking during pregnancy, poorly controlled diabetes, and a mother over the age of 35 years old. Many are believed to involve multiple factors. Birth defects may be visible at birth or diagnosed by screening tests. A number of defects can be detected before birth by different prenatal tests.Treatment varies depending on the defect in question. This may include therapy, medication, surgery, or assistive technology. Birth defects affected about 96 million people as of 2015. In the United States, they occur in about 3% of newborns. They resulted in about 628,000 deaths in 2015, down from 751,000 in 1990. The types with the greatest numbers of deaths are congenital heart disease (303,000), followed by neural tube defects (65,000). Classification Much of the language used for describing congenital conditions antedates genome mapping, and structural conditions are often considered separately from other congenital conditions. Many metabolic conditions are now known to have subtle structural expression, and structural conditions often have genetic links. Still, congenital conditions are often classified on a structural basis, organized when possible by primary organ system affected. Primarily structural Several terms are used to describe congenital abnormalities. (Some of these are also used to describe noncongenital conditions, and more than one term may apply in an individual condition.) Terminology A congenital physical anomaly is an abnormality of the structure of a body part. It may or may not be perceived as a problem condition. Many, if not most, people have one or more minor physical anomalies if examined carefully. Examples of minor anomalies can include curvature of the fifth finger (clinodactyly), a third nipple, tiny indentations of the skin near the ears (preauricular pits), shortness of the fourth metacarpal or metatarsal bones, or dimples over the lower spine (sacral dimples). Some minor anomalies may be clues to more significant internal abnormalities. Birth defect is a widely used term for a congenital malformation, i.e. a congenital, physical anomaly that is recognizable at birth, and which is significant enough to be considered a problem. According to the Centers for Disease Control and Prevention (CDC), most birth defects are believed to be caused by a complex mix of factors including genetics, environment, and behaviors, though many birth defects have no known cause. An example of a birth defect is cleft palate, which occurs during the fourth through seventh weeks of gestation. Body tissue and special cells from each side of the head grow toward the center of the face. They join to make the face. A cleft means a split or separation; the "roof" of the mouth is called the palate. A congenital malformation is a physical anomaly that is deleterious, i.e. a structural defect perceived as a problem. A typical combination of malformations affecting more than one body part is referred to as a malformation syndrome. Some conditions are due to abnormal tissue development: A malformation is associated with a disorder of tissue development. Malformations often occur in the first trimester. A dysplasia is a disorder at the organ level that is due to problems with tissue development. Conditions also can arise after tissue is formed: A deformation is a condition arising from mechanical stress to normal tissue. Deformations often occur in the second or third trimester, and can be due to oligohydramnios. A disruption involves breakdown of normal tissues. When multiple effects occur in a specified order, they are known as a sequence. When the order is not known, it is a syndrome. Examples of primarily structural congenital disorders A limb anomaly is called a dysmelia. These include all forms of limbs anomalies, such as amelia, ectrodactyly, phocomelia, polymelia, polydactyly, syndactyly, polysyndactyly, oligodactyly, brachydactyly, achondroplasia, congenital aplasia or hypoplasia, amniotic band syndrome, and cleidocranial dysostosis. Congenital heart defects include patent ductus arteriosus, atrial septal defect, ventricular septal defect, and tetralogy of Fallot. Congenital anomalies of the nervous system include neural tube defects such as spina bifida, encephalocele, and anencephaly. Other congenital anomalies of the nervous system include the Arnold–Chiari malformation, the Dandy–Walker malformation, hydrocephalus, microencephaly, megalencephaly, lissencephaly, polymicrogyria, holoprosencephaly, and agenesis of the corpus callosum. Congenital anomalies of the gastrointestinal system include numerous forms of stenosis and atresia, and perforation, such as gastroschisis. Congenital anomalies of the kidney and urinary tract include renal parenchyma, kidneys, and urinary collecting system.Defects can be bilateral or unilateral, and different defects often coexist in an individual child. Primarily metabolic A congenital metabolic disease is also referred to as an inborn error of metabolism. Most of these are single-gene defects, usually heritable. Many affect the structure of body parts, but some simply affect the function. Other Other well-defined genetic conditions may affect the production of hormones, receptors, structural proteins, and ion channels. Causes Alcohol exposure The mothers consumption of alcohol during pregnancy can cause a continuum of various permanent birth defects: craniofacial abnormalities, brain damage, intellectual disability, heart disease, kidney abnormality, skeletal anomalies, ocular abnormalities.The prevalence of children affected is estimated at least 1% in U.S. as well in Canada. Very few studies have investigated the links between paternal alcohol use and offspring health.However, recent animal research has shown a correlation between paternal alcohol exposure and decreased offspring birth weight. Behavioral and cognitive disorders, including difficulties with learning and memory, hyperactivity, and lowered stress tolerance have been linked to paternal alcohol ingestion. The compromised stress management skills of animals whose male parent was exposed to alcohol are similar to the exaggerated responses to stress that children with fetal alcohol syndrome display because of maternal alcohol use. These birth defects and behavioral disorders were found in cases of both long- and short-term paternal alcohol ingestion. In the same animal study, paternal alcohol exposure was correlated with a significant difference in organ size and the increased risk of the offspring displaying ventricular septal defects at birth. Toxic substances Substances whose toxicity can cause congenital disorders are called teratogens, and include certain pharmaceutical and recreational drugs in pregnancy, as well as many environmental toxins in pregnancy.A review published in 2010 identified six main teratogenic mechanisms associated with medication use: folate antagonism, neural crest cell disruption, endocrine disruption, oxidative stress, vascular disruption, and specific receptor- or enzyme-mediated teratogenesis.An estimated 10% of all birth defects are caused by prenatal exposure to a teratogenic agent. These exposures include medication or drug exposures, maternal infections and diseases, and environmental and occupational exposures. Paternal smoking has also been linked to an increased risk of birth defects and childhood cancer for the offspring, where the paternal germline undergoes oxidative damage due to cigarette use. Teratogen-caused birth defects are potentially preventable. Nearly 50% of pregnant women have been exposed to at least one medication during gestation. During pregnancy, a woman can also be exposed to teratogens from contaminated clothing or toxins within the seminal fluid of a partner. An additional study found that of 200 individuals referred for genetic counseling for a teratogenic exposure, 52% were exposed to more than one potential teratogen.The United States Environmental Protection Agency studied 1,065 chemical and drug substances in their ToxCast program (part of the CompTox Chemicals Dashboard) using in silico modeling and a human pluripotent stem cell-based assay to predict in vivo developmental intoxicants based on changes in cellular metabolism following chemical exposure. Findings of the study published in 2020 were that 19% of the 1065 chemicals yielded a prediction of developmental toxicity. Medications and supplements Probably, the most well-known teratogenic drug is thalidomide. It was developed near the end of the 1950s by Chemie Grünenthal as a sleep-inducing aid and antiemetic. Because of its ability to prevent nausea, it was prescribed for pregnant women in almost 50 countries worldwide between 1956 and 1962. Until William McBride published the study leading to its withdrawal from the market in 1961, about 8,000 to 10,000 severely malformed children were born. The most typical disorders induced by thalidomide were reductional deformities of the long bones of the extremities. Phocomelia, otherwise a rare deformity, therefore helped to recognise the teratogenic effect of the new drug. Among other malformations caused by thalidomide were those of ears, eyes, brain, kidney, heart, and digestive and respiratory tracts; 40% of the prenatally affected children died soon after birth. As thalidomide is used today as a treatment for multiple myeloma and leprosy, several births of affected children were described in spite of the strictly required use of contraception among female patients treated by it. Vitamin A is the sole vitamin that is embryotoxic even in a therapeutic dose, for example in multivitamins, because its metabolite, retinoic acid, plays an important role as a signal molecule in the development of several tissues and organs. Its natural precursor, β-carotene, is considered safe, whereas the consumption of animal liver can lead to malformation, as the liver stores lipophilic vitamins, including retinol. Isotretinoin (13-cis-retinoic-acid; brand name Roaccutane), vitamin A analog, which is often used to treat severe acne, is such a strong teratogen that just a single dose taken by a pregnant woman (even transdermally) may result in serious birth defects. Because of this effect, most countries have systems in place to ensure that it is not given to pregnant women and that the patient is aware of how important it is to prevent pregnancy during and at least one month after treatment. Medical guidelines also suggest that pregnant women should limit vitamin A intake to about 700 μg/day, as it has teratogenic potential when consumed in excess. Vitamin A and similar substances can induce spontaneous abortions, premature births, defects of eyes (microphthalmia), ears, thymus, face deformities, and neurological (hydrocephalus, microcephalia) and cardiovascular defects, as well as intellectual disability.Tetracycline, an antibiotic, should never be prescribed to women of reproductive age or to children, because of its negative impact on bone mineralization and teeth mineralization. The "tetracycline teeth" have brown or grey colour as a result of a defective development of both the dentine and the enamel of teeth.Several anticonvulsants are known to be highly teratogenic. Phenytoin, also known as diphenylhydantoin, along with carbamazepine, is responsible for the fetal hydantoin syndrome, which may typically include broad nose base, cleft lip and/or palate, microcephalia, nails and fingers hypoplasia, intrauterine growth restriction, and intellectual disability. Trimethadione taken during pregnancy is responsible for the fetal trimethadione syndrome, characterized by craniofacial, cardiovascular, renal, and spine malformations, along with a delay in mental and physical development. Valproate has antifolate effects, leading to neural tube closure-related defects such as spina bifida. Lower IQ and autism have recently also been reported as a result of intrauterine valproate exposure.Hormonal contraception is considered harmless for the embryo. Peterka and Novotná do, however, state that synthetic progestins used to prevent miscarriage in the past frequently caused masculinization of the outer reproductive organs of female newborns due to their androgenic activity. Diethylstilbestrol is a synthetic estrogen used from the 1940s to 1971, when the prenatal exposition has been linked to the clear-cell adenocarcinoma of the vagina. Following studies showed elevated risks for other tumors and congenital malformations of the sex organs for both sexes. All cytostatics are strong teratogens; abortion is usually recommended when pregnancy is discovered during or before chemotherapy. Aminopterin, a cytostatic drug with antifolate effect, was used during the 1950s and 1960s to induce therapeutic abortions. In some cases, the abortion did not happen, but the newborns had a fetal aminopterin syndrome consisting of growth retardation, craniosynostosis, hydrocephalus, facial dismorphities, intellectual disability, or leg deformities Toxic substances Drinking water is often a medium through which harmful toxins travel. Heavy metals, elements, nitrates, nitrites, and fluoride can be carried through water and cause congenital disorders. Nitrate, which is found mostly in drinking water from ground sources, is a powerful teratogen. A case-control study in rural Australia that was conducted following frequent reports of prenatal mortality and congenital malformations found that those who drank the nitrate-containing groundwater, as opposed to rain water, ran the risk of giving birth to children with central nervous system disorders, muscoskeletal defects, and cardiac defects.Chlorinated and aromatic solvents such as benzene and trichloroethylene sometimes enter the water supply due to oversights in waste disposal. A case-control study on the area found that by 1986, leukemia was occurring in the children of Woburn, Massachusetts, at a rate that was four times the expected rate of incidence. Further investigation revealed a connection between the high occurrence of leukemia and an error in water distribution that delivered water to the town with significant contamination with manufacturing waste containing trichloroethylene. As an endocrine disruptor, DDT was shown to induce miscarriages, interfere with the development of the female reproductive system, cause the congenital hypothyroidism, and suspectably childhood obesity.Fluoride, when transmitted through water at high levels, can also act as a teratogen. Two reports on fluoride exposure from China, which were controlled to account for the education level of parents, found that children born to parents who were exposed to 4.12 ppm fluoride grew to have IQs that were, on average, seven points lower than their counterparts whose parents consumed water that contained 0.91 ppm fluoride. In studies conducted on rats, higher fluoride in drinking water led to increased acetylcholinesterase levels, which can alter prenatal brain development. The most significant effects were noted at a level of 5 ppm.The fetus is even more susceptible to damage from carbon monoxide intake, which can be harmful when inhaled during pregnancy, usually through first- or second-hand tobacco smoke. The concentration of carbon monoxide in the infant born to a nonsmoking mother is around 2%, and this concentration drastically increases to a range of 6%–9% if the mother smoked tobacco. Other possible sources of prenatal carbon monoxide intoxication are exhaust gas from combustion motors, use of dichloromethane (paint thinner, varnish removers) in enclosed areas, defective gas water heaters, indoor barbeques, open flames in poorly ventilated areas, and atmospheric exposure in highly polluted areas. Exposure to carbon monoxide at toxic levels during the first two trimesters of pregnancy can lead to intrauterine growth restriction, leading to a baby who has stunted growth and is born smaller than 90% of other babies at the same gestational age. The effect of chronic exposure to carbon monoxide can depend on the stage of pregnancy in which the mother is exposed. Exposure during the embryonic stage can have neurological consequences, such as telencephalic dysgenesis, behavioral difficulties during infancy, and reduction of cerebellum volume. Also, possible skeletal defects could result from exposure to carbon monoxide during the embryonic stage, such as hand and foot malformations, hip dysplasia, hip subluxation, agenesis of a limb, and inferior maxillary atresia with glossoptosis. Also, carbon monoxide exposure between days 35 and 40 of embryonic development can lead to an increased risk of the child developing a cleft palate. Exposure to carbon monoxide or polluted ozone exposure can also lead to cardiac defects of the ventrical septal, pulmonary artery, and heart valves. The effects of carbon monoxide exposure are decreased later in fetal development during the fetal stage, but they may still lead to anoxic encephalopathy.Industrial pollution can also lead to congenital defects. Over a period of 37 years, the Chisso Corporation, a petrochemical and plastics company, contaminated the waters of Minamata Bay with an estimated 27 tons of methylmercury, contaminating the local water supply. This led many people in the area to develop what became known as the "Minamata disease". Because methylmercury is a teratogen, the mercury poisoning of those residing by the bay resulted in neurological defects in the offspring. Infants exposed to mercury poisoning in utero showed predispositions to cerebral palsy, ataxia, inhibited psychomotor development, and intellectual disability.Landfill sites have been shown to have adverse effects on fetal development. Extensive research has shown that landfills have several negative effects on babies born to mothers living near landfill sites: low birth weight, birth defects, spontaneous abortion, and fetal and infant mortality. Studies done around the Love Canal site near Niagara Falls and the Lipari Landfill in New Jersey have shown a higher proportion of low birth-weight babies than communities farther away from landfills. A study done in California showed a positive correlation between time and quantity of dumping and low birth weights and neonatal deaths. A study in the United Kingdom showed a correlation between pregnant women living near landfill sites and an increased risk of congenital disorders, such as neural tube defects, hypospadias, epispadia, and abdominal wall defects, such as gastroschisis and exomphalos. A study conducted on a Welsh community also showed an increased incidence of gastroschisis. Another study on 21 European hazardous-waste sites showed that those living within 3 km had an increased risk of giving birth to infants with birth defects and that as distance from the land increased, the risk decreased. These birth defects included neural tube defects, malformations of the cardiac septa, anomalies of arteries and veins, and chromosomal anomalies. Looking at communities that live near landfill sites brings up environmental justice. A vast majority of sites are located near poor, mostly black, communities. For example, between the early 1920s and 1978, about 25% of Houstons population was black. However, over 80% of landfills and incinerators during this time were located in these black communities.Another issue regarding environmental justice is lead poisoning. A fetus exposed to lead during the pregnancy can result in learning difficulties and slowed growth. Some paints (before 1978) and pipes contain lead. Therefore, pregnant women who live in homes with lead paint inhale the dust containing lead, leading to lead exposure in the fetus. When lead pipes are used for drinking water and cooking water, this water is ingested, along with the lead, exposing the fetus to this toxin. This issue is more prevalent in poorer communities because more well-off families are able to afford to have their homes repainted and pipes renovated. Smoking Paternal smoking prior to conception has been linked with the increased risk of congenital abnormalities in offspring.Smoking causes DNA mutations in the germline of the father, which can be inherited by the offspring. Cigarette smoke acts as a chemical mutagen on germ cell DNA. The germ cells suffer oxidative damage, and the effects can be seen in altered mRNA production, infertility issues, and side effects in the embryonic and fetal stages of development. This oxidative damage may result in epigenetic or genetic modifications of the fathers germline. Fetal lymphocytes have been damaged as a result of a fathers smoking habits prior to conception.Correlations between paternal smoking and the increased risk of offspring developing childhood cancers (including acute leukemia, brain tumors, and lymphoma) before age five have been established. Little is currently known about how paternal smoking damages the fetus, and what window of time in which the father smokes is most harmful to offspring. Infections A vertically transmitted infection is an infection caused by bacteria, viruses, or in rare cases, parasites transmitted directly from the mother to an embryo, fetus, or baby during pregnancy or childbirth. Congenital disorders were initially believed to be the result of only hereditary factors. However, in the early 1940s, Australian pediatric ophthalmologist Norman Gregg began recognizing a pattern in which the infants arriving at his surgery were developing congenital cataracts at a higher rate than those who developed it from hereditary factors. On October 15, 1941, Gregg delivered a paper that explained his findings-68 out of the 78 children with congenital cataracts had been exposed in utero to rubella due to an outbreak in Australian army camps. These findings confirmed, to Gregg, that, in fact, environmental causes for congenital disorders could exist. Rubella is known to cause abnormalities of the eye, internal ear, heart, and sometimes the teeth. More specifically, fetal exposure to rubella during weeks five to ten of development (the sixth week particularly) can cause cataracts and microphthalmia in the eyes. If the mother is infected with rubella during the ninth week, a crucial week for internal ear development, destruction of the organ of Corti can occur, causing deafness. In the heart, the ductus arteriosus can remain after birth, leading to hypertension. Rubella can also lead to atrial and ventricular septal defects in the heart. If exposed to rubella in the second trimester, the fetus can develop central nervous system malformations. However, because infections of rubella may remain undetected, misdiagnosed, or unrecognized in the mother, and/or some abnormalities are not evident until later in the childs life, precise incidence of birth defects due to rubella are not entirely known. The timing of the mothers infection during fetal development determines the risk and type of birth defect. As the embryo develops, the risk of abnormalities decreases. If exposed to the rubella virus during the first four weeks, the risk of malformations is 47%. Exposure during weeks five through eight creates a 22% chance, while weeks 9–12, a 7% chance exists, followed by 6% if the exposure is during the 13th-16th weeks. Exposure during the first eight weeks of development can also lead to premature birth and fetal death. These numbers are calculated from immediate inspection of the infant after birth. Therefore, mental defects are not accounted for in the percentages because they are not evident until later in the childs life. If they were to be included, these numbers would be much higher.Other infectious agents include cytomegalovirus, the herpes simplex virus, hyperthermia, toxoplasmosis, and syphilis. Maternal exposure to cytomegalovirus can cause microcephaly, cerebral calcifications, blindness, chorioretinitis (which can cause blindness), hepatosplenomegaly, and meningoencephalitis in fetuses. Microcephaly is a disorder in which the fetus has an atypically small head, cerebral calcifications means certain areas of the brain have atypical calcium deposits, and meningoencephalitis is the enlargement of the brain. All three disorders cause abnormal brain function or intellectual disability. Hepatosplenomegaly is the enlargement of the liver and spleen which causes digestive problems. It can also cause some kernicterus and petechiae. Kernicterus causes yellow pigmentation of the skin, brain damage, and deafness. Petechaie is when the capillaries bleed resulting in red/purple spots on the skin. However, cytomegalovirus is often fatal in the embryo. The Zika virus can also be transmitted from the pregnant mother to her baby and cause microcephaly. The herpes simplex virus can cause microcephaly, microphthalmus (abnormally small eyeballs), retinal dysplasia, hepatosplenomegaly, and intellectual disability. Both microphthalmus and retinal dysplasia can cause blindness. However, the most common symptom in infants is an inflammatory response that develops during the first three weeks of life. Hyperthermia causes anencephaly, which is when part of the brain and skull are absent in the infant. Mother exposure to toxoplasmosis can cause cerebral calcification, hydrocephalus (causes mental disabilities), and intellectual disability in infants. Other birth abnormalities have been reported as well, such as chorioretinitis, microphthalmus, and ocular defects. Syphilis causes congenital deafness, intellectual disability, and diffuse fibrosis in organs, such as the liver and lungs, if the embryo is exposed. Malnutrition For example, a lack of folic acid, a B vitamin, in the diet of a mother can cause cellular neural tube deformities that result in spina bifida. Congenital disorders such as a neural tube deformity can be prevented by 72% if the mother consumes 4 mg of folic acid before the conception and after twelve weeks of pregnancy. Folic acid, or vitamin B9, aids the development of the foetal nervous system.Studies with mice have found that food deprivation of the male mouse prior to conception leads to the offspring displaying significantly lower blood glucose levels. Physical restraint External physical shocks or constraints due to growth in a restricted space may result in unintended deformation or separation of cellular structures resulting in an abnormal final shape or damaged structures unable to function as expected. An example is Potter syndrome due to oligohydramnios. This finding is important for future understanding of how genetics may predispose individuals for diseases such as obesity, diabetes, and cancer. For multicellular organisms that develop in a womb, the physical interference or presence of other similarly developing organisms such as twins can result in the two cellular masses being integrated into a larger whole, with the combined cells attempting to continue to develop in a manner that satisfies the intended growth patterns of both cell masses. The two cellular masses can compete with each other, and may either duplicate or merge various structures. This results in conditions such as conjoined twins, and the resulting merged organism may die at birth when it must leave the life-sustaining environment of the womb and must attempt to sustain its biological processes independently. Genetics Genetic causes of birth defects include inheritance of abnormal genes from the mother or the father, as well as new mutations in one of the germ cells that gave rise to the fetus. Male germ cells mutate at a much faster rate than female germ cells, and as the father ages, the DNA of the germ cells mutates quickly. If an egg is fertilized with sperm that has damaged DNA, a possibility exists that the fetus could develop abnormally.Genetic disorders are all congenital (present at birth), though they may not be expressed or recognized until later in life. Genetic disorders may be grouped into single-gene defects, multiple-gene disorders, or chromosomal defects. Single-gene defects may arise from abnormalities of both copies of an autosomal gene (a recessive disorder) or of only one of the two copies (a dominant disorder). Some conditions result from deletions or abnormalities of a few genes located contiguously on a chromosome. Chromosomal disorders involve the loss or duplication of larger portions of a chromosome (or an entire chromosome) containing hundreds of genes. Large chromosomal abnormalities always produce effects on many different body parts and organ systems. Socioeconomics A low socioeconomic status in a deprived neighborhood may include exposure to "environmental stressors and risk factors". Socioeconomic inequalities are commonly measured by the Cartairs-Morris score, Index of Multiple Deprivation, Townsend deprivation index, and the Jarman score. The Jarman score, for example, considers "unemployment, overcrowding, single parents, under-fives, elderly living alone, ethnicity, low social class and residential mobility". In Vos meta-analysis these indices are used to view the effect of low SES neighborhoods on maternal health. In the meta-analysis, data from individual studies were collected from 1985 up until 2008. Vos concludes that a correlation exists between prenatal adversities and deprived neighborhoods. Other studies have shown that low SES is closely associated with the development of the fetus in utero and growth retardation. Studies also suggest that children born in low SES families are "likely to be born prematurely, at low birth weight, or with asphyxia, a birth defect, a disability, fetal alcohol syndrome, or AIDS". Bradley and Corwyn also suggest that congenital disorders arise from the mothers lack of nutrition, a poor lifestyle, maternal substance abuse and "living in a neighborhood that contains hazards affecting fetal development (toxic waste dumps)". In a meta-analysis that viewed how inequalities influenced maternal health, it was suggested that deprived neighborhoods often promoted behaviors such as smoking, drug and alcohol use. After controlling for socioeconomic factors and ethnicity, several individual studies demonstrated an association with outcomes such as perinatal mortality and preterm birth. Radiation For the survivors of the atomic bombing of Hiroshima and Nagasaki, who are known as the Hibakusha, no statistically demonstrable increase of birth defects/congenital malformations was found among their later conceived children, or found in the later conceived children of cancer survivors who had previously received radiotherapy. The surviving women of Hiroshima and Nagasaki who were able to conceive, though exposed to substantial amounts of radiation, later had children with no higher incidence of abnormalities/birth defects than in the Japanese population as a whole.Relatively few studies have researched the effects of paternal radiation exposure on offspring. Following the Chernobyl disaster, it was assumed in the 1990s that the germ line of irradiated fathers suffered minisatellite mutations in the DNA, which was inherited by descendants. More recently, however, the World Health Organization states, "children conceived before or after their fathers exposure showed no statistically significant differences in mutation frequencies". This statistically insignificant increase was also seen by independent researchers analyzing the children of the liquidators. Animal studies have shown that incomparably massive doses of X-ray irradiation of male mice resulted in birth defects of the offspring.In the 1980s, a relatively high prevalence of pediatric leukemia cases in children living near a nuclear processing plant in West Cumbria, UK, led researchers to investigate whether the cancer was a result of paternal radiation exposure. A significant association between paternal irradiation and offspring cancer was found, but further research areas close to other nuclear processing plants did not produce the same results. Later this was determined to be the Seascale cluster in which the leading hypothesis is the influx of foreign workers, who have a different rate of leukemia within their race than the British average, resulted in the observed cluster of 6 children more than expected around Cumbria. Parents age Certain birth complications can occur more often in advanced maternal age (greater than 35 years). Complications include fetal growth restriction, preeclampsia, placental abruption, pre-mature births, and stillbirth. These complications not only may put the child at risk, but also the mother.The effects of the fathers age on offspring are not yet well understood and are studied far less extensively than the effects of the mothers age. Fathers contribute proportionally more DNA mutations to their offspring via their germ cells than the mother, with the paternal age governing how many mutations are passed on. This is because, as humans age, male germ cells acquire mutations at a much faster rate than female germ cells.Around a 5% increase in the incidence of ventricular septal defects, atrial septal defects, and patent ductus arteriosus in offspring has been found to be correlated with advanced paternal age. Advanced paternal age has also been linked to increased risk of achondroplasia and Apert syndrome. Offspring born to fathers under the age of 20 show increased risk of being affected by patent ductus arteriosus, ventricular septal defects, and the tetralogy of Fallot. It is hypothesized that this may be due to environmental exposures or lifestyle choices.Research has found that there is a correlation between advanced paternal age and risk of birth defects such as limb anomalies, syndromes involving multiple systems, and Down syndrome. Recent studies have concluded that 5-9% of Down syndrome cases are due to paternal effects, but these findings are controversial.There is concrete evidence that advanced paternal age is associated with the increased likelihood that a mother will have a miscarriage or that fetal death will occur. Unknown Although significant progress has been made in identifying the etiology of some birth defects, approximately 65% have no known or identifiable cause. These are referred to as sporadic, a term that implies an unknown cause, random occurrence regardless of maternal living conditions, and a low recurrence risk for future children. For 20-25% of anomalies there seems to be a "multifactorial" cause, meaning a complex interaction of multiple minor genetic anomalies with environmental risk factors. Another 10–13% of anomalies have a purely environmental cause (e.g. infections, illness, or drug abuse in the mother). Only 12–25% of anomalies have a purely genetic cause. Of these, the majority are chromosomal anomalies. Prevention Folate supplements decrease the risk of neural tube defects. Tentative evidence supports the role of L-arginine in decreasing the risk of intrauterine growth restriction. Screening Newborn screening tests were introduced in the early 1960s and initially dealt with just two disorders. Since then tandem mass spectrometry, gas chromatography–mass spectrometry, and DNA analysis has made it possible for a much larger range of disorders to be screened. Newborn screening mostly measures metabolite and enzyme activity using a dried blood spot sample. Screening tests are carried out in order to detect serious disorders that may be treatable to some extent. Early diagnosis makes possible the readiness of therapeutic dietary information, enzyme replacement therapy and organ transplants. Different countries support the screening for a number of metabolic disorders (inborn errors of metabolism (IEM)), and genetic disorders including cystic fibrosis and Duchenne muscular dystrophy. Tandem mass spectroscopy can also be used for IEM, and investigation of sudden infant death, and shaken baby syndrome.Screening can also be carried out prenatally and can include obstetric ultrasonography to give scans such as the nuchal scan. 3D ultrasound scans can give detailed information of structural anomalies. Epidemiology Congenital anomalies resulted in about 632,000 deaths per year in 2013 down from 751,000 in 1990. The types with the greatest death are congenital heart defects (323,000), followed by neural tube defects (69,000).Many studies have found that the frequency of occurrence of certain congenital malformations depends on the sex of the child (table). For example, pyloric stenosis occurs more often in males while congenital hip dislocation is four to five times more likely to occur in females. Among children with one kidney, there are approximately twice as many males, whereas among children with three kidneys there are approximately 2.5 times more females. The same pattern is observed among infants with excessive number of ribs, vertebrae, teeth and other organs which in a process of evolution have undergone reduction—among them there are more females. Contrarily, among the infants with their scarcity, there are more males. Anencephaly is shown to occur approximately twice as frequently in females. The number of boys born with 6 fingers is two times higher than the number of girls. Now various techniques are available to detect congenital anomalies in fetus before birth.About 3% of newborns have a "major physical anomaly", meaning a physical anomaly that has cosmetic or functional significance. Physical congenital abnormalities are the leading cause of infant mortality in the United States, accounting for more than 20% of all infant deaths. Seven to ten percent of all children will require extensive medical care to diagnose or treat a birth defect. Data obtained on opposite-sex twins. ** — Data were obtained in the period 1983–1994.P. M. Rajewski and A. L. Sherman (1976) have analyzed the frequency of congenital anomalies in relation to the system of the organism. Prevalence of men was recorded for the anomalies of phylogenetically younger organs and systems.In respect of an etiology, sexual distinctions can be divided on appearing before and after differentiation of males gonads during embryonic development, which begins from the eighteenth week. The testosterone level in male embryos thus raises considerably. The subsequent hormonal and physiological distinctions of male and female embryos can explain some sexual differences in frequency of congenital defects. It is difficult to explain the observed differences in the frequency of birth defects between the sexes by the details of the reproductive functions or the influence of environmental and social factors. United States The CDC and National Birth Defect Project studied the incidence of birth defects in the US. Key findings include: Down syndrome was the most common condition with an estimated prevalence of 14.47 per 10,000 live births, implying about 6,000 diagnoses each year. About 7,000 babies are born with a cleft palate, cleft lip or both. See also Idiopathic List of congenital disorders List of ICD-9 codes 740-759: Congenital anomalies Malformative syndrome March of Dimes Mitochondrial disease National Birth Defects Prevention Network, founded 1997 Supernumerary body part References External links CDCs National Center on Birth Defects and Developmental Disabilities

Pyoderma gangrenosum

Pyoderma gangrenosum is a rare, inflammatory skin disease where painful pustules or nodules become ulcers that progressively grow. Pyoderma gangrenosum is not infectious.Treatments may include corticosteroids, ciclosporin, infliximab, or canakinumab.The disease was identified in 1930. It affects approximately 1 person in 100,000 in the population. Though it can affect people of any age, it mostly affects people in their 40s and 50s. Types There are two main types of pyoderma gangrenosum: the typical ulcerative form, which occurs in the legs an atypical form that is more superficial and occurs in the hands and other parts of the bodyOther variations are: Peristomal pyoderma gangrenosum comprises 15% of all cases of pyoderma Bullous pyoderma gangrenosum Pustular pyoderma gangrenosum Vegetative pyoderma gangrenosum Presentation Associations The following are conditions commonly associated with pyoderma gangrenosum: Inflammatory bowel disease: Ulcerative colitis Crohns disease Arthritides: Rheumatoid arthritis Seronegative arthritis Hematological disease: Myelocytic leukemia Hairy cell leukemia Myelofibrosis Myeloid metaplasia Monoclonal gammopathy Autoinflammatory disease: Pyogenic sterile arthritis, and acne syndrome (PAPA syndrome) Causes Though the cause is not well understood, the disease is thought to be due to immune system dysfunction, and particularly improper functioning of neutrophils. In support of an immune cause, a variety of immune mediators such as interleukin (IL)-8, IL-1β, IL-6, interferon (IFN)-γ, granulocyte colony-stimulating factor, tumor necrosis factor alpha, matrix metalloproteinase (MMP)-9, MMP10, and elafin have all been reported to be elevated in patients with pyoderma gangrenosum.Also in support of an immune cause is the finding that at least half of all pyoderma gangrenosum patients suffer from immune-mediated diseases. For instance, ulcerative colitis, rheumatoid arthritis, and multiple myeloma (MM) have all been associated with pyoderma gangrenosum. It can also be part of a syndromes such as PAPA syndrome.One hallmark of pyoderma gangrenosum is pathergy, which is the appearance of new lesions at sites of trauma, including surgical wounds. Diagnosis Diagnosis of PG is challenging owing to its variable presentation, clinical overlap with other conditions, association with several systemic diseases, and absence of defining histopathologic or laboratory findings. Misdiagnosis and delayed diagnosis are common. It has been shown that up to 39% of patients who initially received a diagnosis of PG have an alternative diagnosis. In light of this, validated diagnostic criteria have recently been developed for ulcerative pyoderma gangrenosum. Diagnostic criteria In addition to a biopsy demonstrating a neutrophilic infiltrate, patients must have at least 4 minor criteria to meet diagnostic criteria. These criteria are based on histology, history, clinical examination and treatment. Histology: Exclusion of infection (including histologically indicated stains and tissue cultures) Pathergy (ulcer occurring at sites of trauma, with ulcer extending past area of trauma) Personal history of inflammatory bowel disease or inflammatory arthritis History of papule, pustule, or vesicle that rapidly ulcerated Clinical examination (or photographic evidence) of peripheral erythema, undermining border, and tenderness at site of ulceration Multiple ulcerations (at least 1 occurring on an anterior lower leg) Cribriform or “wrinkled paper” scars at sites of healed ulcers Decrease in ulcer size within 1 month of initiating immunosuppressive medications Treatment First-line therapy for disseminated or localized instances of pyoderma gangrenosum is systemic treatment with corticosteroids and ciclosporin. Topical application of clobetasol, mupirocin, and gentamicin alternated with tacrolimus can be effective. Pyoderma gangrenosum ulcers demonstrate pathergy, that is, a worsening in response to minor trauma or surgical debridement. Significant care should be taken with dressing changes to prevent potentially rapid wound growth. Many patients respond differently to different types of treatment, for example some benefit from a moist environment, so treatment should be carefully evaluated at each stage.Papules that begin as small "spouts" can be treated with Dakins solution to prevent infection and wound clusters also benefit from this disinfectant. Wet to dry applications of Dakins can defeat spread of interior infection. Heavy drainage can be offset with Coban dressings. Grafting is not recommended due to tissue necrosis.If ineffective, alternative therapeutic procedures include systemic treatment with corticosteroids and mycophenolate mofetil; mycophenolate mofetil and ciclosporin; tacrolimus; thalidomide; infliximab; or plasmapheresis. See also Superficial granulomatous pyoderma Brown recluse spider bite References == External links ==

Lactic acidosis

Lactic acidosis is a medical condition characterized by a build-up of lactate (especially L-lactate) in the body, with formation of an excessively low pH in the bloodstream. It is a form of metabolic acidosis, in which excessive acid accumulates due to a problem with the bodys oxidative metabolism. Lactic acidosis is typically the result of an underlying acute or chronic medical condition, medication, or poisoning. The symptoms are generally attributable to these underlying causes, but may include nausea, vomiting, Kussmaul breathing (laboured and deep), and generalised weakness. The diagnosis is made on biochemical analysis of blood (often initially on arterial blood gas samples), and once confirmed, generally prompts an investigation to establish the underlying cause to treat the acidosis. In some situations, hemofiltration (purification of the blood) is temporarily required. In rare chronic forms of lactic acidosis caused by mitochondrial disease, a specific diet or dichloroacetate may be used. The prognosis of lactic acidosis depends largely on the underlying cause; in some situations (such as severe infections), it indicates an increased risk of death. Classification The Cohen–Woods classification categorizes causes of lactic acidosis as: Type A: Decreased tissue oxygenation (e.g., from decreased blood flow) Type B B1: Underlying diseases (sometimes causing type A) B2: Medication or intoxication B3: Inborn error of metabolism Signs and symptoms Lactic acidosis is commonly found in people who are unwell, such as those with severe heart and/or lung disease, a severe infection with sepsis, the systemic inflammatory response syndrome due to another cause, severe physical trauma, or severe depletion of body fluids. Symptoms in humans include all those of typical metabolic acidosis (nausea, vomiting, generalized muscle weakness, and laboured and deep breathing). Causes The several different causes of lactic acidosis include: Genetic conditions Biotinidase deficiency, multiple carboxylase deficiency, or nongenetic deficiencies of biotin Diabetes mellitus and deafness Fructose 1,6-bisphosphatase deficiency Glucose-6-phosphatase deficiency GRACILE syndrome Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes Pyruvate dehydrogenase deficiency Pyruvate carboxylase deficiency Leigh syndrome Drugs Linezolid Paracetamol/acetaminophen poisoning Metformin: this risk is low (less than 10 cases for 100,000 patient years), but the risk of metformin-induced lactic acidosis (MALA) increases in certain situations where both the plasma levels of metformin are increased and lactate clearance is impaired. The older related and now withdrawn drug phenformin carried a much higher risk of lactic acidosis. Isoniazid toxicity Propofol Epinephrine Propylene glycol (D-lactic acidosis) Nucleoside reverse-transcriptase inhibitors Abacavir/dolutegravir/lamivudine Emtricitabine/tenofovir Potassium cyanide (cyanide poisoning) Fialuridine Other Thiamine deficiency (especially during TPN) Impaired delivery of oxygen to cells in the tissues (e.g., from impaired blood flow (hypoperfusion)) Bleeding Polymyositis Ethanol toxicity Sepsis Shock Advanced liver disease Diabetic ketoacidosis Excessive exercise (overtraining) Regional hypoperfusion (e.g., bowel ischemia or marked cellulitis) Cancers such as Non-Hodgkins and Burkitt lymphomas Pheochromocytoma Tumor lysis syndrome D-lactic acidosis due to intestinal bacterial flora production in short gut syndrome Pathophysiology Glucose metabolism begins with glycolysis, in which the molecule is broken down into pyruvate in ten enzymatic steps. A significant proportion of pyruvate is converted into lactate (usually 10:1). The human metabolism produces about 20 mmol/kg of lactic acid every 24 hours. This happens predominantly in tissues (especially muscle) that have high levels of the "A" isoform of the enzyme lactate dehydrogenase (LDHA), which predominantly converts pyruvate into lactate. The lactate is carried by the bloodstream to other tissues where it is converted at the expense of ATP back to pyruvate by the "B" isoform of LDH (LDHB). Firstly there is gluconeogenesis in the liver (as well as the kidney and some other tissues), where pyruvate is converted into glucose; this is known as the Cori cycle. In addition, lactate moved to other tissues enters the citric acid cycle and eventually oxidative phosphorylation, a process that yields ATP.Elevations in lactate are either a consequence of increased production or of decreased metabolism. With regards to metabolism, this predominantly takes place in the liver (70%), which explains that lactate levels may be elevated in the setting of liver disease.In "type A" lactic acidosis, the production of lactate is attributable to insufficient oxygen for aerobic metabolism. If there is no oxygen available for the parts of the glucose metabolism that require oxygen (citric acid cycle and oxidative phosphorylation), excess pyruvate will be converted in excess lactate. In "type B" lactic acidosis the lactate accumulates because there is a mismatch between glycolysis activity and the remainder of glucose metabolism. Examples are situations where the sympathetic nervous system is highly active (e.g. severe asthma). There is controversy as to whether elevated lactate in acute illness can be attributed to tissue hypoxia; there is limited empirical support for this theoretical notion. Diagnosis Acid-base disturbances such as lactic acidosis are typically first assessed using arterial blood gas tests. Testing of venous blood is also available as an alternative as they are effectively interchangeable. Normally resulting lactate concentrations are in the range indicated below: Lactic acidosis is classically defined as an elevated lactate together with pH < 7.35 and bicarbonate below 20 mmol/L, but this is not required as lactic acidosis may exist together with other acid-base abnormalities that may affect these two parameters. Treatment If elevated lactate is present in acute illness, supporting the oxygen supply and blood flow are key initial steps. Some vasopressors (drugs that augment the blood pressure) are less effective when lactate levels are high, and some agents that stimulate the beta-2 adrenergic receptor can elevate the lactate further.Direct removal of lactate from the body (e.g. with hemofiltration or dialysis) is difficult, with limited evidence for benefit; it may not be possible to keep up with the lactate production.Limited evidence supports the use of sodium bicarbonate solutions to improve the pH (which is associated with increased carbon dioxide generation and may reduce the calcium levels).Lactic acidosis caused by inherited mitochondrial disorders (type B3) may be treated with a ketogenic diet and possibly with dichloroacetate (DCA), although this may be complicated by peripheral neuropathy and has a weak evidence base. Prognosis Mild and transient elevations in lactate have limited impact on mortality, whereas sustained and severe lactate elevations are associated with a high mortality.The mortality of lactic acidosis in people taking metformin was previously reported to be 50%, but in more recent reports this was closer to 25%. Other animals Reptiles Reptiles, which rely primarily on anaerobic energy metabolism (glycolysis) for intense movements, can be particularly susceptible to lactic acidosis. In particular, during the capture of large crocodiles, the animals use of their glycolytic muscles often alter the bloods pH to a point where they are unable to respond to stimuli or move. Cases are recorded in which particularly large crocodiles which put up extreme resistance to capture later died of the resulting pH imbalance.Certain turtle species have been found to be capable of tolerating high levels of lactic acid without experiencing the effects of lactic acidosis. Painted turtles hibernate buried in mud or underwater and do not resurface for the entire winter. As a result, they rely on anaerobic respiration to provide the majority of their energy needs. Adaptations in particular in the turtles blood composition and shell allow it to tolerate high levels of lactic acid accumulation. In the anoxic conditions where anaerobic respiration is dominant, calcium levels in the blood plasma increase. This calcium serves as a buffer, reacting with the excess lactate to form the precipitate calcium lactate. This precipitate is suggested to be reabsorbed by the shell and skeleton, thereby removing it from the bloodstream; studies examining turtles that have been subjected to prolonged anoxic conditions have up to 45% of their lactate stored within their skeletal structure. Ruminants In ruminant livestock, the cause of clinically serious lactic acidosis is different from the causes described above. In domesticated ruminants, lactic acidosis may occur as a consequence of ingesting large amounts of grain, especially when the rumen population is poorly adapted to deal with grain. Activity of various rumen organisms results in accumulation of various volatile fatty acids (normally, mostly acetic, propionic, and butyric acids), which are partially dissociated. Although some lactate is normally produced in the rumen, it is normally metabolized by such organisms as Megasphaera elsdenii and, to a lesser extent, Selenomonas ruminantium and some other organisms. With high grain consumption, the concentration of dissociated organic acids can become quite high, resulting in rumen pH dropping below 6. Within this lower pH range, Lactobacillus spp. (producing lactate and hydrogen ions) are favored, and M. elsdenii and S. ruminantium are inhibited, tending to result in a considerable rise of lactate and hydrogen ion concentrations in the rumen fluid. The pKa of lactic acid is low, about 3.9, versus, for example, 4.8 for acetic acid; this contributes to the considerable drop in rumen pH which can occur.Because of the high solute concentration of the rumen fluid under such conditions, considerable water is translocated from the blood to the rumen along the osmotic potential gradient, resulting in dehydration which cannot be relieved by drinking, and which can ultimately lead to hypovolemic shock. As more lactate accumulates and rumen pH drops, the ruminal concentration of undissociated lactic acid increases. Undissociated lactic acid can cross the rumen wall to the blood, where it dissociates, lowering blood pH. Both L and D isomers of lactic acid are produced in the rumen; these isomers are metabolized by different metabolic pathways, and activity of the principal enzyme involved in metabolism of the D isomer declines greatly with lower pH, tending to result in an increased ratio of D:L isomers as acidosis progresses.Measures for preventing lactic acidosis in ruminants include avoidance of excessive amounts of grain in the diet, and gradual introduction of grain over a period of several days, to develop a rumen population capable of safely dealing with a relatively high grain intake. Administration of lasalocid or monensin in feed can reduce risk of lactic acidosis in ruminants, inhibiting most of the lactate-producing bacterial species without inhibiting the major lactate fermenters. Also, using a higher feeding frequency to provide the daily grain ration can allow higher grain intake without reducing the pH of the rumen fluid.Treatment of lactic acidosis in ruminants may involve intravenous administration of dilute sodium bicarbonate, oral administration of magnesium hydroxide, and/or repeated removal of rumen fluids and replacement with water (followed by reinoculation with rumen organisms, if necessary). References == External links ==

Pulmonary hemorrhage

Pulmonary hemorrhage (or pulmonary haemorrhage) is an acute bleeding from the lung, from the upper respiratory tract and the trachea, and the pulmonary alveoli. When evident clinically, the condition is usually massive. The onset of pulmonary hemorrhage is characterized by a cough productive of blood (hemoptysis) and worsening of oxygenation leading to cyanosis. Treatment should be immediate and should include tracheal suction, oxygen, positive pressure ventilation, and correction of underlying abnormalities such as disorders of coagulation. A blood transfusion may be necessary. Causes Infant prematurity is the factor most commonly associated with pulmonary hemorrhage. Other associated factors are those that predisposed to perinatal asphyxia or bleeding disorders, including toxemia of pregnancy, maternal cocaine use, erythroblastosis fetalis, breech delivery, hypothermia, infection (like pulmonary tuberculosis), Infant respiratory distress syndrome (IRDS), administration of exogenous surfactants (in some studies) and extracorporeal membrane oxygenation (ECMO). Pathophysiology Although the pathogenesis is uncertain, it is probable that the symptoms are a consequence of hemorrhagic pulmonary edema, as the hematocrit is lower than normal blood (usually 15-20% less) and the concentration of small proteins is higher than in plasma. It is postulated that the infant suffers from asphyxia with resultant heart attack; this increases pulmonary microvascular pressure, resulting in pulmonary edema. Contributing factors include factors that favor increased filtration of fluid from pulmonary capillaries (e.g., low concentration of plasma proteins, high alveolar surface tension, lung damage, hypervolemia). Diffuse alveolar hemorrhage Diffuse alveolar hemorrhage is bleeding from many alveoli throughout the lungs. Common causes include autoimmune diseases and connective tissue diseases. Diagnosis of DAH is often given following observation of a patient presenting with hemoptysis, anemia, and cough, along with a chest X-ray showing alveolar infiltrates in the lungs, which are areas of air space in the lungs that are opacified and of higher density that normal, usually indicating that they are filled with a substance such as pus, blood, or another fluid. Incidence The outcome of treatment is dependent on causality. Pulmonary Hemorrhage is present in 7 to 10% of neonatal autopsies, but up to 80% of autopsies of very preterm infants. The incidence is 1 in 1,000 live births. Pulmonary hemorrhage has a high mortality rate of 30% to 40%. See also Hemoptysis References == External links ==

Circulatory collapse

A circulatory collapse is defined as a general or specific failure of the circulation, either cardiac or peripheral in nature. Although the mechanisms, causes and clinical syndromes are different, the pathogenesis is the same—the circulatory system fails to maintain the supply of oxygen and other nutrients to the tissues and to remove the carbon dioxide and other metabolites from them. The failure may be hypovolemic or distributive. A common cause of this could be shock or trauma from injury or surgery. Types A general failure is one that occurs across a wide range of locations in the body, such as systemic shock after the loss of a large amount of blood collapsing all the circulatory systems in the legs. A specific failure can be traced to a particular point, such as a clot. Cardiac circulatory collapse affects the vessels of the heart such as the aorta and is almost always fatal. It is sometimes referred to as "acute" circulatory failure. Peripheral circulatory collapse involves outlying arteries and veins in the body and can result in gangrene, organ failure or other serious complications. This form is sometimes called peripheral vascular failure, shock or peripheral vascular shutdown. A milder or preliminary form of circulatory collapse is circulatory insufficiency. Causes A very large range of medical conditions can cause circulatory collapse. These include, but are not limited to: Hypovolemic shock Trauma, especially those with massive hemorrhage Surgery, particularly on patients who have lost blood Hemorrhagic conditions, e.g. upper gastrointestinal bleeding (esophageal varices, Mallory–Weiss syndrome, aortoenteric fistula, etc.), ruptured aortic aneurysm, superior mesenteric artery syndrome, etc. Severe dehydration Third spacing, e.g. malignant pleural effusion, ascites, severe peripheral oedema due to kidney failure Rapid fluid shift due to dialysis Cardiogenic shock Myocardial infarction Severe cardiac arrhythmia, e.g. ventricular fibrillation, sea water poisoning Failed heart transplant or artificial heart; in those with cardiovascular disease who are just being treated with medical therapy or oxygen, pacing, cardioversion, or defibrillation using an implantable cardioverter-defibrillator, or else implantation of an intra-aortic balloon pump, or a unilateral or bilateral ventricular assist device, may help matters, as could the use of stenting and/or coronary artery bypass surgery and/or the removal of atherosclerotic plaques. Eventually, a heart transplant or artificial heart may be needed, and these can be replaced when they are no longer performing as well as they did. If necessary, while waiting for a transplant or device, extracorporeal membrane oxygenation (ECMO) or mechanical ventilation using a ventilator, or other less invasive methods, can be used to help compensate. If other systems get impaired, renal dialysis, liver dialysis, and artificial nutrition and hydration (including total or partial parenteral nutrition) can also be used. Congenital heart defects Obstructive shock Pulmonary embolism Cardiac tamponade Aortic dissection Tension pneumothorax Hypertrophic cardiomyopathy Constrictive pericarditis Distributive shock Septic shock Anaphylactic shock Acute pancreatitis Hypotension due to medications Intoxicative inhalants Combined Dengue fever Effects The effects of a circulatory collapse vary based on the type of collapse it is. Peripheral collapses usually involve abnormally low blood pressure and result in collapsed arteries and/or veins, leading to oxygen deprivation to tissues, organs, and limbs.Acute collapse can result from heart failure causing the primary vessels of the heart to collapse, perhaps combined with cardiac arrest. Diagnosis Treatment References == External links ==

Dysthymia

Dysthymia ( dihs-THIY-mee-uh), also known as persistent depressive disorder (PDD), is a mental and behavioral disorder, specifically a disorder primarily of mood, consisting of similar cognitive and physical problems as major depressive disorder, but with longer-lasting symptoms. The concept was used by Robert Spitzer as a replacement for the term "depressive personality" in the late 1970s.In the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV), dysthymia is a serious state of chronic depression, which persists for at least two years (one year for children and adolescents). Dysthymia is not a minor form of major depressive disorder, and for some may be more disabling.As dysthymia is a chronic disorder, those with the condition may experience symptoms for many years before it is diagnosed, if diagnosis occurs at all. As a result, they may believe that depression is a part of their character, so they may not even discuss their symptoms with doctors, family members or friends. In the DSM-5, dysthymia is replaced by persistent depressive disorder. This new condition includes both chronic major depressive disorder and the previous dysthymic disorder. The reason for this change is that there was no evidence for meaningful differences between these two conditions. Signs and symptoms Dysthymia characteristics include an extended period of depressed mood combined with at least two other symptoms which may include insomnia or hypersomnia, fatigue or low energy, eating changes (more or less), low self-esteem, or feelings of hopelessness. Poor concentration or difficulty making decisions are treated as another possible symptom. Irritability is one of the more common symptoms in children and adolescents.Mild degrees of dysthymia may result in people withdrawing from stress and avoiding opportunities for failure. In more severe cases of dysthymia, people may withdraw from daily activities. They will usually find little pleasure in usual activities and pastimes. Diagnosis of dysthymia can be difficult because of the subtle nature of the symptoms and patients can often hide them in social situations, making it challenging for others to detect symptoms. Additionally, dysthymia often occurs at the same time as other psychological disorders, which adds a level of complexity in determining the presence of dysthymia, particularly because there is often an overlap in the symptoms of disorders.There is a high incidence of comorbid illness in those with dysthymia. Suicidal behavior is also a particular problem with those with dysthymia. It is vital to look for signs of major depression, panic disorder, generalised anxiety disorder, alcohol and substance use disorders, and personality disorder. Causes There are no known biological causes that apply consistently to all cases of dysthymia, which suggests diverse origin of the disorder. However, there are some indications that there is a genetic predisposition to dysthymia: "The rate of depression in the families of people with dysthymia is as high as fifty percent for the early-onset form of the disorder". Other factors linked with dysthymia include stress, social isolation, and lack of social support.In a study using identical and fraternal twins, results indicated that there is a stronger likelihood of identical twins both having depression than fraternal twins. This provides support for the idea that dysthymia is in part caused by heredity means. Co-occurring conditions Dysthymia often co-occurs with other mental disorders. A "double depression" is the occurrence of episodes of major depression in addition to dysthymia. Switching between periods of dysthymic moods and periods of hypomanic moods is indicative of cyclothymia, which is a mild variant of bipolar disorder. "At least three-quarters of patients with dysthymia also have a chronic physical illness or another psychiatric disorder such as one of the anxiety disorders, cyclothymia, drug addiction, or alcoholism". Common co-occurring conditions include major depression (up to 75%), anxiety disorders (up to 50%), personality disorders (up to 40%), somatoform disorders (up to 45%) and substance use disorders (up to 50%). People with dysthymia have a higher-than-average chance of developing major depression. A 10-year follow-up study found that 95% of dysthymia patients had an episode of major depression. When an intense episode of depression occurs on top of dysthymia, the state is called "double depression." Double depression Double depression occurs when a person experiences a major depressive episode on top of the already-existing condition of dysthymia. It is difficult to treat, as patients accept these major depressive symptoms as a natural part of their personality or as a part of their life that is outside of their control. The fact that people with dysthymia may accept these worsening symptoms as inevitable can delay treatment. When and if such people seek out treatment, the treatment may not be very effective if only the symptoms of the major depression are addressed, but not the dysthymic symptoms. Patients with double depression tend to report significantly higher levels of hopelessness than is normal. This can be a useful symptom for mental health services providers to focus on when working with patients to treat the condition. Additionally, cognitive therapies can be effective for working with people with double depression in order to help change negative thinking patterns and give individuals a new way of seeing themselves and their environment.It has been suggested that the best way to prevent double depression is by treating the dysthymia. A combination of antidepressants and cognitive therapies can be helpful in preventing major depressive symptoms from occurring. Additionally, exercise and good sleep hygiene (e.g., improving sleep patterns) are thought to have an additive effect on treating dysthymic symptoms and preventing them from worsening. Pathophysiology There is evidence that there may be neurological indicators of early onset dysthymia. There are several brain structures (corpus callosum and frontal lobe) that are different in women with dysthymia than in those without dysthymia. This may indicate that there is a developmental difference between these two groups.Another study, which used fMRI techniques to assess the differences between individuals with dysthymia and other people, found additional support for neurological indicators of the disorder. This study found several areas of the brain that function differently. The amygdala (associated with processing emotions such as fear) was more activated in dysthymia patients. The study also observed increased activity in the insula (which is associated with sad emotions). Finally, there was increased activity in the cingulate gyrus (which serves as the bridge between attention and emotion).A study comparing healthy individuals to people with dysthymia indicates there are other biological indicators of the disorder. An anticipated result appeared as healthy individuals expected fewer negative adjectives to apply to them, whereas people with dysthymia expected fewer positive adjectives to apply to them in the future. Biologically these groups are also differentiated in that healthy individuals showed greater neurological anticipation for all types of events (positive, neutral, or negative) than those with dysthymia. This provides neurological evidence of the dulling of emotion that individuals with dysthymia have learned to use to protect themselves from overly strong negative feelings, compared to healthy people.There is some evidence of a genetic basis for all types of depression, including dysthymia. A study using identical and fraternal twins indicated that there is a stronger likelihood of identical twins both having depression than fraternal twins. This provides support for the idea that dysthymia is caused in part by heredity.A new model has recently surfaced in the literature regarding the HPA axis (structures in the brain that get activated in response to stress) and its involvement with dysthymia (e.g. phenotypic variations of corticotropin releasing hormone (CRH) and arginine vasopressin (AVP), and down-regulation of adrenal functioning) as well as forebrain serotonergic mechanisms. Since this model is highly provisional, further research is still needed. Diagnosis The Diagnostic and Statistical Manual of Mental Disorders IV (DSM-IV), published by the American Psychiatric Association, characterizes dysthymic disorder. The essential symptom involves the individual feeling depressed for the majority of days, and parts of the day, for at least two years. Low energy, disturbances in sleep or in appetite, and low self-esteem typically contribute to the clinical picture as well. Those with the condition have often experienced dysthymia for many years before it is diagnosed. People around them often describe them in words similar to "just a moody person". The following are the diagnostic criteria: During a majority of days for two years or more, the adult patient reports depressed mood, or appears depressed to others for most of the day. When depressed, the patient has two or more of: decreased or increased appetite; decreased or increased sleep (insomnia or hypersomnia); fatigue or low energy; reduced self-esteem; decreased concentration or problems making decisions; feelings of hopelessness or pessimism. During this two-year period, the above symptoms are never absent longer than two consecutive months. During the duration of the two-year period, the patient may have had a perpetual major depressive episode. The patient has not had any manic, hypomanic, or mixed episodes. The patient has never fulfilled criteria for cyclothymic disorder. The depression does not exist only as part of a chronic psychosis (such as schizophrenia or delusional disorder). The symptoms are often not directly caused by a medical illness or by substances, including substance use or other medications. The symptoms may cause significant problems or distress in social, work, academic, or other major areas of life functioning.In children and adolescents, mood can be irritable, and duration must be at least one year, in contrast to two years needed for diagnosis in adults. Early onset (diagnosis before age 21) is associated with more frequent relapses, psychiatric hospitalizations, and more co-occurring conditions. For younger adults with dysthymia, there is a higher co-occurrence in personality abnormalities and the symptoms are likely chronic. However, in older adults with dysthymia, the psychological symptoms are associated with medical conditions and/or stressful life events and losses.Dysthymia can be contrasted with major depressive disorder by assessing the acute nature of the symptoms. Dysthymia is far more chronic (long lasting) than major depressive disorder, in which symptoms may be present for as little as two weeks. Also dysthymia often presents itself at an earlier age than major depressive disorder. Prevention Though there is no clear-cut way to prevent dysthymia from occurring, some suggestions have been made. Since dysthymia will often first occur in childhood, it is important to identify children who may be at risk. It may be beneficial to work with children in helping to control their stress, increase resilience, boost self-esteem, and provide strong networks of social support. These tactics may be helpful in warding off or delaying dysthymic symptoms. Treatments Persistent depressive disorder can be treated with psychotherapy and pharmacotherapy. The overall rate and degree of treatment success is somewhat lower than for non-chronic depression, and a combination of psychotherapy and pharmacotherapy shows best results. Therapy Psychotherapy can be effective in treating dysthymia. In a meta-analytic study from 2010, psychotherapy had a small but significant effect when compared to control groups. However, psychotherapy is significantly less effective than pharmacotherapy in direct comparisons.There are many different types of therapy, and some are more effective than others. The empirically most studied type of treatment is cognitive-behavioral therapy. This type of therapy is very effective for non-chronic depression, and it appears to be also effective for chronic depression. Cognitive behavioral analysis system of psychotherapy (CBASP) has been designed specifically to treat PDD. Empirical results on this form of therapy are inconclusive: While one study showed remarkably high treatment success rates, a later, even larger study showed no significant benefit of adding CBASP to treatment with antidepressants. Schema therapy and psychodynamic psychotherapy have been used for PDD, though good empirical results are lacking. Interpersonal psychotherapy has also been said to be effective in treating the disorder, though it only shows marginal benefit when added to treatment with antidepressants. Medications In a 2010 meta-analysis, the benefit of pharmacotherapy was limited to selective serotonin reuptake inhibitors (SSRIs) rather than tricyclic antidepressants (TCA). According to a 2014 meta-analysis, antidepressants are at least as effective for persistent depressive disorder as for major depressive disorder. The first line of pharmacotherapy is usually SSRIs due to their purported more tolerable nature and reduced side effects compared to the irreversible monoamine oxidase inhibitors or tricyclic antidepressants. Studies have found that the mean response to antidepressant medications for people with dysthymia is 55%, compared with a 31% response rate to a placebo. The most commonly prescribed antidepressants/SSRIs for dysthymia are escitalopram, citalopram, sertraline, fluoxetine, paroxetine, and fluvoxamine. It often takes an average of 6–8 weeks before the patient begins to feel these medications therapeutic effects. Additionally, STAR*D, a multi-clinic governmental study, found that people with overall depression will generally need to try different brands of medication before finding one that works specifically for them. Research shows that 1 in 4 of those who switch medications get better results regardless of whether the second medication is an SSRI or some other type of antidepressant.In a meta-analytic study from 2005, it was found that SSRIs and TCAs are equally effective in treating dysthymia. They also found that MAOIs have a slight advantage over the use of other medication in treating this disorder. However, the author of this study cautions that MAOIs should not necessarily be the first line of defense in the treatment of dysthymia, as they are often less tolerable than their counterparts, such as SSRIs.Tentative evidence supports the use of amisulpride to treat dysthymia but with increased side effects. Combination treatment When pharmacotherapy alone is compared with combined treatment with pharmacotherapy plus psychotherapy, there is a strong trend in favour of combined treatment. Working with a psychotherapist to address the causes and effects of the disorder, in addition to taking antidepressants to help eliminate the symptoms, can be extremely beneficial. This combination is often the preferred method of treatment for those who have dysthymia. Looking at various studies involving treatment for dysthymia, 75% of people responded positively to a combination of cognitive behavioral therapy (CBT) and pharmacotherapy, whereas only 48% of people responded positively to just CBT or medication alone.A 2019 Cochrane review of 10 studies involving 840 participants could not conclude with certainty that continued pharmacotherapy with antidepressants (those used in the studies) was effective in preventing relapse or recurrence of persistent depressive disorder. The body of evidence was too small for any greater certainty although the study acknowledges that continued psychotherapy may be beneficial when compared to no treatment. Resistance Because of dysthymias chronic nature, treatment resistance is somewhat common. In such a case, augmentation is often recommended. Such treatment augmentations can include lithium pharmacology, thyroid hormone augmentation, amisulpride, buspirone, bupropion, stimulants, and mirtazapine. Additionally, if the person also has seasonal affective disorder, light therapy can be useful in helping augment therapeutic effects. Epidemiology Globally dysthymia occurs in about 105 million people a year (1.5% of the population). It is 38% more common in women (1.8% of women) than in men (1.3% of men). The lifetime prevalence rate of dysthymia in community settings appears to range from 3 to 6% in the United States. However, in primary care settings the rate is higher ranging from 5 to 15 percent. United States prevalence rates tend to be somewhat higher than rates in other countries. See also Anhedonia, a symptom of dysthymia characterized by a decreased or absent ability to enjoy a sense of pleasure Atypical depression Blunted affect, a symptom of PTSD, schizophrenia, and ASPD involving decreased or absent emotional response Dysphoria, a state of feeling unwell or unhappy Epigenetics of depression List of medications used to treat major depressive disorder or dysthymia References External links NIMH Depression Page

Gastric outlet obstruction

Gastric outlet obstruction (GOO) is a medical condition where there is an obstruction at the level of the pylorus, which is the outlet of the stomach. Individuals with gastric outlet obstruction will often have recurrent vomiting of food that has accumulated in the stomach, but which cannot pass into the small intestine due to the obstruction. The stomach often dilates to accommodate food intake and secretions. Causes of gastric outlet obstruction include both benign causes (such as peptic ulcer disease affecting the area around the pylorus), as well as malignant causes, such as gastric cancer. Causation related to ulcers may involve severe pain which the patient may interpret as a heart condition/attack.Treatment of the condition depends upon the underlying cause; it can involve antibiotic treatment when Helicobacter pylori is related to an ulcer, endoscopic therapies (such as dilation of the obstruction with balloons or the placement of self expandable metallic stents), other medical therapies, or surgery to resolve the obstruction. Signs and symptoms The main symptom is vomiting, which typically occurs after meals, of undigested food devoid of any bile. A history of previous peptic ulcers and loss of weight is not uncommon. In advanced cases, signs to look for on physical examination are wasting and dehydration. Visible peristalsis from left to right may be present. Succussion splash is a splash-like sound heard over the stomach in the left upper quadrant of the abdomen on shaking the patient, with or without the stethoscope. Bowel sound may be increased (borborygmi) due to excessive peristaltic action of the stomach. Fullness in the left hypochondrium may also be present. Causes The causes are divided into benign or malignant. Benign Peptic ulcer disease Infections, such as tuberculosis; and infiltrative diseases, such as amyloidosis. A rare cause of gastric outlet obstruction is blockage with a gallstone, also termed "Bouveret syndrome" or "Bouverets syndrome". In children congenital pyloric stenosis / congenital hypertrophic pyloric stenosis may be a cause. A pancreatic pseudocyst can cause gastric compression. Pyloric mucosal diaphragm could be a rare cause. Malignant Tumours of the stomach, including adenocarcinoma (and its linitis plastica variant), lymphoma, and gastrointestinal stromal tumours Pathophysiology In a peptic ulcer it is believed to be a result of edema and scarring of the ulcer, followed by healing and fibrosis, which leads to obstruction of the gastroduodenal junction (usually an ulcer in the first part of the duodenum). Diagnosis The most confirmatory investigation is endoscopy of upper gastrointestinal tract. Laboratory often find hypochloremic, hypokalemic, and alkalotic due to loss of hydrogen chloride and potassium. High urea and creatinine levels may also be observed if the patient is dehydrated. Abdominal X-ray may show a gastric fluid level which would support the diagnosis. Barium meal and follow through may show an enlarged stomach and pyloroduodenal stenosis.Gastroscopy may help with cause and can be used therapeutically. Differential diagnosis The differential diagnosis of gastric outlet obstruction may include: early gastric carcinoma, hiatal hernia, gastroesophageal reflux, adrenal insufficiency, and inborn errors of metabolism. Treatment Treatment of gastric outlet obstruction depends on the cause, but is usually either surgical or medical. Medication In most people with peptic ulcer disease, the oedema will usually settle with conservative management with nasogastric suction, replacement of fluids and electrolytes and proton pump inhibitors. Surgery Surgery is indicated in cases of gastric outlet obstruction in which there is significant obstruction and in cases where medical therapy has failed. Endoscopic balloon therapy may be attempted as an alternative to surgery, with balloon dilation reporting success rates of 76% after repeat dilatons. The operation usually performed is an antrectomy, the removal of the antral portion of the stomach. Other surgical approaches include: vagotomy, the severing of the vagus nerve, the Billroth I, a procedure which involves anastomosing the duodenum to the distal stomach, or a bilateral truncal vagotomy with gastrojejunostomy. References External links Gastric outlet obstruction due to duodenal tuberculosis

Anal fissure

An anal fissure is a break or tear in the skin of the anal canal. Anal fissures may be noticed by bright red anal bleeding on toilet paper and undergarments, or sometimes in the toilet. If acute they are painful after defecation, but with chronic fissures, pain intensity often reduces. Anal fissures usually extend from the anal opening and are usually located posteriorly in the midline, probably because of the relatively unsupported nature and poor perfusion of the anal wall in that location. Fissure depth may be superficial or sometimes down to the underlying sphincter muscle. Untreated fissures develop a hood-like skin tag (sentinel piles) which cover the fissure and cause discomfort and pain. Causes Most anal fissures are caused by stretching of the anal mucous membrane beyond its capability.Superficial or shallow anal fissures look much like a paper cut, and may be hard to detect upon visual inspection; they will generally self-heal within a couple of weeks. However, some anal fissures become chronic and deep and will not heal. The most common cause of non-healing is spasming of the internal anal sphincter muscle which results in impaired blood supply to the anal mucosa. The result is a non-healing ulcer, which may become infected by fecal bacteria. In adults, fissures may be caused by constipation, the passing of large, hard stools, or by prolonged diarrhea. In older adults, anal fissures may be caused by decreased blood flow to the area. When fissures are found laterally, tuberculosis, occult abscesses, leukemic infiltrates, carcinoma, acquired immunodeficiency syndrome (AIDS) or inflammatory bowel disease should be considered as causes. Some sexually transmitted infections can promote the breakdown of tissue resulting in a fissure. Examples of sexually transmitted infections that may affect the anorectal area are syphilis, herpes, chlamydia and human papilloma virus.Other common causes of anal fissures include: childbirth trauma in women anal sex Crohns disease ulcerative colitis poor toileting in young children. Diagnosing External anal fissures on the anal verge can be diagnosed by visual inspection.Internal anal fissures in adults on anterior side, posterior side or within any part of the inner circumference of the anal sphincter muscle can be diagnosed with beak proctoscope 23mm diameter, Chelsea Eaton anal speculum 23mm diameter, Park anal retractor or by digital rectal examination with a finger inside the anal sphincter muscle. Narrow anal fissures might not be felt by finger during rectal examination due to the glove.Note that colonoscopy, sigmoidoscopy, or normal proctoscopy is for diagnosing internal hemorrhoids and other internal rectal diseases and not for diagnosing anal fissures. Prevention For adults, the following may help prevent anal fissures: Avoiding straining when defecating. This includes treating and preventing constipation by eating food rich in dietary fiber, drinking enough water, occasional use of a stool softener, and avoiding constipating agents. Similarly, prompt treatment of diarrhea may reduce anal strain. Careful anal hygiene after defecation, including using soft toilet paper and cleaning with water, plus the use of sanitary wipes. In cases of pre-existing or suspected fissure, use of a lubricating ointment (It is important to note that hemorrhoid ointment is contraindicated because it constricts small blood vessels, thus causes a decrease in blood flow, which prevents healing).In infants, frequent diaper change can prevent anal fissure. As constipation can be a cause, making sure the infant is drinking enough fluids (i.e. breastmilk, proper ratios when mixing formulas) is beneficial. In infants, once an anal fissure has occurred, addressing underlying causes is usually enough to ensure healing occurs. Treatment Non-surgical treatments are recommended initially for acute and chronic anal fissures. These include topical nitroglycerin or calcium channel blockers (e.g. diltiazem), or injection of botulinum toxin into the anal sphincter.Other measures include warm sitz baths, topical anesthetics, high-fiber diet and stool softeners. Medication Local application of medication to relax the sphincter muscle, thus allowing the healing to proceed, was first proposed in 1994 with nitroglycerine ointment, and then calcium channel blockers in 1999 with nifedipine ointment, and the following year with topical diltiazem. Branded preparations are now available of topical nitroglycerine ointment (Rectogesic (Rectiv) as 0.2% in Australia and 0.4% in UK and US), topical nifedipine 0.3% with lidocaine 1.5% ointment (Antrolin in Italy since April 2004) and diltiazem 2% (Anoheal in UK, although still in Phase III development). A common side effect drawback of nitroglycerine ointment is headache, caused by systemic absorption of the drug, which limits patient acceptability. A combined surgical and pharmacological treatment, administered by colorectal surgeons, is the direct injection of botulinum toxin (Botox) into the anal sphincter to relax it. This treatment was first investigated in 1993. However, in many cases involving Botox injections, the patients eventually had to choose another cure as the injections proved less and less potent, spending thousands of dollars in the meantime for a partial cure. Lateral sphincterotomy is the Gold Standard for curing this condition. Combination of medical therapies may offer up to 98% cure rates. Surgery Surgical procedures are generally reserved for people with anal fissure who have tried medical therapy for at least one to three months and have not healed. It is not the first option in treatment. The main concern with surgery is the development of anal incontinence. Anal incontinence can include the inability to control gas, mild fecal soiling, or loss of solid stool. Some degree of incontinence can occur in up to 45 percent of patients in the immediate surgical recovery period. However, incontinence is rarely permanent and is usually mild. The risk should be discussed with ones surgeon. Surgical treatment, under general anaesthesia, was either anal stretch (Lords operation) or lateral sphincterotomy where the internal anal sphincter muscle is incised. Both operations aim to decrease sphincter spasming and thereby restore normal blood supply to the anal mucosa. Surgical operations involve a general or regional anaesthetia. Anal stretch is also associated with anal incontinence in a small proportion of cases and thus sphincterotomy is the operation of choice. Lateral internal sphincterotomy Lateral internal sphincterotomy (LIS) is the surgical procedure of choice for anal fissures due to its simplicity and its high success rate (~95%). In this procedure the internal anal sphincter is partially divided in order to reduce spasming and thus improve the blood supply to the perianal area. This improvement in the blood supply helps to heal the fissure, and the weakening of the sphincter is also believed to reduce the potential for recurrence. The procedure is generally performed as a day surgery after the patient is given general anesthesia. The pain from the sphincterotomy is usually mild and is often less than the pain of the fissure itself. Patients often return to normal activity within one week. LIS does, however, have a number of potential side effects including problems with incision site healing and incontinence to flatus and faeces (some surveys of surgical results suggest incontinence rates of up to 36%).Though lateral internal sphincterotomy (LIS) is considered safe on a short-term basis, there are concerns about its long-term safety. Pankaj Garg et al. published a systematic review and meta-analysis in which they analyzed the long-term continence disturbance two years after the LIS procedure. They found the incidence of long-term continence disturbance to be 14%, so caution and careful patient selection are needed before undergoing LIS. Anal dilation Anal dilation, or stretching of the anal canal (Lords operation), has fallen out of favour in recent years, primarily due to the unacceptably high incidence of fecal incontinence. In addition, anal stretching can increase the rate of flatus incontinence. The incidence of incontinence is thought to be due to a lack of standardization and that proper technique results in little chance that it will occur.In the early 1990s, however, a repeatable method of anal dilation proved to be very effective and showed a very low incidence of side effects. Since then, at least one other controlled, randomized study has shown there to be little difference in healing rates and complications between controlled anal dilation and LIS, while another has again shown high success rates with anal dilation coupled with low incidence of side effects. Fissurectomy Fissurectomy involves excision of the skin on and around the anal fissure and excision of the sentinel pile if one is present. The surgical wound can be left open. New skin tissue grows and it heals. Epidemiology The incidence of anal fissures is around 1 in 350 adults. They occur equally common in men and women and most often occur in adults aged 15 to 40. See also Anal fistula Hemorrhoid Pruritus ani References == External links ==

Hypertrichosis

Hypertrichosis is an abnormal amount of hair growth over the body. The two distinct types of hypertrichosis are generalized hypertrichosis, which occurs over the entire body, and localized hypertrichosis, which is restricted to a certain area. Hypertrichosis can be either congenital (present at birth) or acquired later in life. The excess growth of hair occurs in areas of the skin with the exception of androgen-dependent hair of the pubic area, face, and axillary regions.Several circus sideshow performers in the 19th and early 20th centuries, such as Julia Pastrana, had hypertrichosis. Many of them worked as freaks and were promoted as having distinct human and animal traits. Classification Two methods of classification are used for hypertrichosis. One divides them into either generalized versus localized hypertrichosis, while the other divides them into congenital versus acquired. Congenital Congenital forms of hypertrichosis are caused by genetic mutations, and are extremely rare, unlike acquired forms. Congenital hypertrichosis is always present at birth. Hypertrichosis lanuginosa Congenital hypertrichosis lanuginosa can be noticed at birth, with the infant completely covered in thin lanugo hair. In normal circumstances, lanugo hair is shed before birth and replaced by vellus hair; however, in a person with congenital hypertrichosis lanuginosa, the lanugo hair remains after birth. The palms of the hands, soles of the feet, and mucous membranes are not affected. As the person ages, the lanugo hair may thin, leaving only limited areas of hypertrichosis. Generalized hypertrichosis Congenital generalized hypertrichosis causes males to exhibit excessive facial and upper body hair, whereas women exhibit less severe asymmetrical hair distribution. The palms, soles, and mucous membranes are not affected. Terminal hypertrichosis Congenital terminal hypertrichosis is characterized by the presence of fully pigmented terminal hair that covers the entire body. This condition is usually accompanied by gingival hyperplasia. This form is most responsible for the term "werewolf syndrome" because of the thick, dark hair that appears. People with this condition are sometimes performers at circuses because of their unusual appearance. Circumscribed hypertrichosis Congenital circumscribed hypertrichosis is associated with the presence of thick vellus hair on the upper extremities. Circumscribed signifies this type of hypertrichosis is restricted to certain parts of the body, in this case, the extensor surfaces of the upper extremities. Hairy elbow syndrome, a type of congenital circumscribed hypertrichosis, shows excessive growth on and around the elbows. This type of hypertrichosis is present at birth, becomes more prominent during aging, and regresses at puberty. Localized hypertrichosis Congenital localized hypertrichosis is a localized increase in hair density and length. Nevoid hypertrichosis Nevoid hypertrichosis may be present at birth or appear later in life. It features an isolated area of excessive terminal hair and is usually not related to any other diseases. Acquired Acquired hypertrichosis appears after birth. The multiple causes include the side effects of drugs, associations with cancer, and possible links with eating disorders. Acquired forms can usually be reduced with various treatments. Hypertrichosis lanuginosa Acquired hypertrichosis lanuginosa is characterized by rapid growth of lanugo hair, particularly on the face. Hair also appears on the trunk and armpits, while palms and soles are unaffected. The excess hair is commonly referred to as malignant down. This hair is very fine and unpigmented. Generalized hypertrichosis Acquired generalized hypertrichosis commonly affects the cheeks, upper lip, and chin. This form also affects the forearms and legs, but is less common in these areas. Another deformity associated with acquired generalized hypertrichosis is multiple hairs occupying the same follicle. It may also include abnormal hair growth patterns as what happens to the eyelashes in a condition known as trichiasis. Oral minoxidil treatments for hypertension are known to cause this condition. Topical minoxidil used for alopecia causes hair growth in the areas where it is applied; however, this hair disappears shortly after discontinuing the use of topical minoxidil. Patterned hypertrichosis Acquired patterned hypertrichosis is an increase in hair growth in a pattern formation. It is similar to acquired generalized hypertrichosis and is a sign of internal malignancy. Localized hypertrichosis Acquired localized hypertrichosis is an increase in hair density and length often secondary to irritation or trauma. This form is restricted to certain areas of the body. Hirsutism Hypertrichosis is often mistakenly classified as hirsutism. Hirsutism is a type of hypertrichosis exclusive to women and children, resulting from an excess of androgen-sensitive hair growth. Patients with hirsutism exhibit patterns of adult male hair growth. Chest and back hair are often present on women with hirsutism.Hirsutism is both congenital and acquired. It is linked to excessive male hormones in women, thus symptoms may include acne, deepening of the voice, irregular menstrual periods, and the formation of a more masculine body shape. Increases in androgen (male hormone) levels are the primary cause of most hirsutism cases. If caused by increased levels of androgens, it can be treated with medications that reduce androgen levels. Some birth control pills and spironolactone reduce androgen levels. Signs and symptoms The primary characteristic of all forms of hypertrichosis is excessive hair. Hair in hypertrichosis is usually longer than expected and may consist of any hair type (lanugo, vellus, or terminal). Patterned forms of hypertrichosis cause hair growth in patterns. Generalized forms of hypertrichosis result in hair growth over the entire body. Circumscribed and localized forms lead to hair growth restricted to a certain area. Cause Genetic Hypertrichosis lanuginosa Congenital hypertrichosis lanuginosa may be caused by a paracentric inversion mutation of the q22 band of chromosome 8; however, it could also possibly be the result of a spontaneous genetic mutation rather than inheritance. This form is an autosomal (not located on the sex chromosomes) dominant cutaneous disorder, that affects the skin. Generalized hypertrichosis Congenital generalized hypertrichosis has a dominant pattern of inheritance and has been linked to chromosome Xq24-27.1. An affected female (carrying the hypertrichosis gene) has a 50% chance of passing it to her offspring. An affected male will pass this form of hypertrichosis to his daughters, but never the sons. Generalized hypertrichosis terminalis Congenital generalized hypertrichosis terminalis is thought to be caused by genetic changes on chromosome 17 resulting in the addition or removal of millions of nucleotides. The gene MAP2K6 may be a factor contributing to this condition. This condition may also be due to the change in the chromosome affecting the transcription of genes. Other hypertrichosis patterns Porphyria cutanea tarda may manifest in some patients as hypertrichosis on the face (mainly on top of the cheeks). Medical conditions Acquired hypertrichosis lanuginosa is commonly present with cancer. This condition is also linked to metabolic disorders, such as anorexia, hormone imbalances, such as hyperthyroidism, or as a side effect of certain drugs.Acquired generalized hypertrichosis may be caused by cancer. The resulting hair growth is known as malignant down. The mechanism behind cancer induced hypertrichosis is unknown. Oral and topical minoxidil treatments are also known to cause acquired generalized hypertrichosis. Medications Several medications can cause generalized or localized acquired hypertrichosis including: Anticonvulsants: phenytoin Immunosuppressants: cyclosporine Vasodilators: diazoxide and minoxidil Antibiotics: streptomycin Diuretics: acetazolamide Photosensitizers: PsoralenThe acquired hypertrichosis is usually reversible once these medications are discontinued. Other Unknown causes The exact genetic mutation that causes congenital circumscribed, localized, and nevoid hypertrichosis is unknown. Pathophysiology A number of mechanisms can lead to hypertrichosis. One cause involves areas of the skin that are transforming from the small vellus type to the larger terminal type. This change normally occurs during adolescence, when vellus hair follicles in the underarms and groin grow into terminal hair follicles. Hypertrichosis involves this same type of switching, but in areas that do not normally produce terminal hair. The mechanisms for this switch are poorly understood.Another mechanism involves a change in the hair cycle. There are three stages of the hair cycle: the anagen phase (hair growth), the catagen phase (hair follicle death), and the telogen phase (hair shedding). If the anagen phase increases beyond what is normal, that region of the body will experience excessive hair growth. Diagnosis Hypertrichosis is diagnosed clinically by the occurrence of hair in excess of what is expected for age, sex, and ethnicity in areas that are not androgen-sensitive. The excess can be in the form of excessive length or density and may consist of any hair type (lanugo, vellus, or terminal). Management There is no cure for any congenital forms of hypertrichosis. The treatment for acquired hypertrichosis is based on attempting to address the underlying cause. Acquired forms of hypertrichosis have a variety of sources, and are usually treated by removing the factor causing hypertrichosis, e.g. a medication with undesired side-effects. All hypertrichosis, congenital or acquired, can be reduced through hair removal. Hair removal treatments are categorized into two principal subdivisions: temporary removal and permanent removal. Treatment may have adverse effects by causing scarring, dermatitis, or hypersensitivity.Temporary hair removal may last from several hours to several weeks, depending on the method used. These procedures are purely cosmetic. Depilation methods, such as trimming, shaving, and depilatories, remove hair to the level of the skin and produce results that last several hours to several days. Epilation methods, such as plucking, electrology, waxing, sugaring, threading remove the entire hair from the root, the results lasting several days to several weeks.Permanent hair removal uses chemicals, energy of various types, or a combination to target the cells that cause hair growth. Laser hair removal is an effective method of hair removal on hairs that have color. Laser cannot treat white hair. The laser targets the melanin color in the lower third of the hair follicle, which is the target zone. Electrolysis (electrology) uses electrical current, and/or localized heating. The U.S. Food and Drug Administration (FDA) allows only electrology to use the term "permanent hair removal" because it has been shown to be able to treat all colors of hair.Medication to reduce production of hair is currently under testing. One medicinal option suppresses testosterone by increasing the sex hormone-binding globulin. Another controls the overproduction of hair through the regulation of a luteinizing hormone. Epidemiology Congenital forms of hypertrichosis are rare. Only 50 cases of congenital hypertrichosis lanuginosa have been recorded since the Middle Ages, and fewer than 100 cases of congenital generalized hypertrichosis have been documented in scientific publications and by the media. Congenital generalized hypertrichosis is isolated to one family in Mexico. Acquired hypertrichosis and hirsutism are more common. For example, hirsutism occurs in about 10% of women between ages 18 and 45. Society and culture People with hair often found jobs as circus performers, making the best of their unusual appearance. Fedor Jeftichew ("Jo-Jo the Dog-faced Man"), Stephan Bibrowski ("Lionel the Lion-faced Man"), Jesús "Chuy" Aceves ("Wolfman"), Annie Jones ("the bearded woman") and Alice Elizabeth Doherty ("The Minnesota Woolly Girl") all had hypertrichosis. Extensive hypertrichosis carries an emotional burden and can cause cosmetic embarrassment; however, some people attempt no treatments because they say it defines who they are. The Gonsalvus family Petrus Gonsalvus (1537–1618) was referred to by Italian naturalist Ulisse Aldrovandi as "the man of the woods". Four of his seven children were also afflicted with hypertrichosis and painted. Barbara van Beck Barbara van Beck (1629–1668?) is one of the first people to be depicted with Ambras syndrome. She was the only member of her family with the condition. She travelled around Europe, living in court and appearing before the nobility in cities such as London and Paris. The hairy family of Burma One record in history concerning congenital hypertrichosis lanuginosa is the hairy family of Burma, a four-generational pedigree of the disease. In 1826, John Crawford was leading a mission for the Governor-General of India through Burma. He tells of meeting a hairy man, Shwe-Maong. Shwe-Maong lived in the court of King Ava and acted as an entertainer. Shwe-Maong had four children: three unaffected children, and one child with congenital hypertrichosis, named Maphoon. On a second mission to Ava, Maphoon was described as a thirty-year-old woman with two sons, one of which had hypertrichosis. The affected son was named Maong-Phoset. He had an affected daughter named Mah-Me. Whereas all affected members of the family had dental problems, the unaffected members had perfect teeth. Julia Pastrana Julia Pastrana (1834–1860) travelled throughout the United States in a freak show as the bearded lady, capturing the attention of many artists. She is portrayed as having dark extensive hairs distributed equally throughout the surface of her body, even on the palms of her hands. Originally, she was believed to have congenital hypertrichosis lanuginosa; however, the generalized form of the syndrome coupled with her gingival hyperplasia indicated that her condition was congenital terminal hypertrichosis. This was not confirmed until after her death, when it became clear that her X-linked syndrome resulted in terminal hairs. Supattra Sasupan In 2011, Supattra Sasupan (Thai: สุพัตรา สะสุพันธ์; born August 5, 2000), an 11-year-old girl from Thailand with hypertrichosis was named the worlds hairiest girl by the Guinness Book of World Records (as Supatra Sasuphan). Etymology Origin of the word hypertrichosis is in Greek roots (hyper-, ʽexcessʼ; trikhos, hair and -osis, ʽformationʼ) and means a disorder that causes excessive hair growth over the body. Medieval sources do not use this term, however prefer hairy men and women instead. These men and women are often mistaken for savages, who similarly have excessive hair, but hairy and savage individuals belong to different categories, since savagery is associated with social or religious isolation. Having exceptional strength, they are deemed closer to the animal than to the human plane. On the contrary, hairy men and women with hypertrichosis are not necessarily isolated and they often live in courts as entertainers, together with other monster-like subjects. History The first recorded case of hypertrichosis was Petrus Gonsalvus of the Canary Islands. This was documented by Ulisse Aldrovandi and published in his posthumous Monstrorum Historia cum Paralipomenis historiae omnium animalium in 1642. He noted that two daughters, a son, and a grandchild in Gonsalvus family all had hypertrichosis. Altrovandus dubbed them the Ambras family, after Ambras Castle near Innsbruck, where portraits of the family were found. During the next 300 years, about 50 cases were observed. The scientist Rudolf Virchow described a form of hypertrichosis accompanied by gingival hyperplasia in 1873.In summer 2019, at least 17 Spanish children have developed so-called “werewolf syndrome”, Spains health ministry has said. Instead of being treated with omeprazole, a drug that helps with gastric reflux, they had received a treatment of minoxidil, a medication against hair loss. How the laboratory FarmaQuimica Sur, based in Malaga, made the mistake, is not yet clear. The lab has been closed as a precaution. In animals The condition is also sometimes found in cats. A male Persian with the condition named Atchoum achieved a certain level of notice due to the unusual appearance his hypertrichosis gave him, and has been nicknamed "The Werewolf Cat".In 1955, a female Müllers Bornean gibbon was obtained from Sarawak that exhibited abnormal hair growth in the facial region. It has been hypothesized that this could be due to facial hypertrichosis.Hypertrichosis (often mistakenly classified as hirsutism) is a well documented condition in horses with a hormonal disorder of the hypothalamus, called Cushings disease. It is the most common endocrine disease of the middle-aged to older horse, often resulting in fatal laminitis. It can be successfully controlled by medications if diagnosed early. See also Jesús Aceves, the first person with hypertrichosis to perform in the UK in thirty years. Stephan Bibrowski (1890–1932), known as Lionel the Lion-faced Man. Krao Farini (1876–1926), known as The Missing Link. Fedor Jeftichew (1868–1904), known as Jo-Jo the Dog-Faced Boy. Human Nature, a 2001 American-French film where one of the main characters has hypertrichosis. Fur: An Imaginary Portrait of Diane Arbus, a 2006 American film where one of the main characters has hypertrichosis. Milo, a 2012 (Netherlands) movie about a 10-year-old boy with hypersensitive skin. Moon of Desire, a 2014 Filipino TV drama with a girl that has hypertrichosis as the main protagonist. The True Adventures of Wolfboy, a 2019 Drama Movie about a 13-year-old boy that has hypertrichosis. References External links The Hairy Family of Burma

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

Seborrhoeic dermatitis

Seborrhoeic dermatitis, sometimes inaccurately referred to as seborrhoea, is a long-term skin disorder. Symptoms include red, scaly, greasy, itchy, and inflamed skin. Areas of the skin rich in oil-producing glands are often affected including the scalp, face, and chest. It can result in social or self-esteem problems. In babies, when the scalp is primarily involved, it is called cradle cap. Dandruff is a milder form of the condition without inflammation.The cause is unclear but believed to involve a number of genetic and environmental factors. Risk factors include poor immune function, Parkinsons disease, and alcoholic pancreatitis. The condition may worsen with stress or during the winter. The Malassezia yeast is believed to play a role. It is not a result of poor hygiene. Diagnosis is typically based on the symptoms. The condition is not contagious.The typical treatment is antifungal cream and anti-inflammatory agents. Specifically, ketoconazole or ciclopirox are effective. It is unclear if other antifungals, such as miconazole, are equally effective as they have been poorly studied. Other options may include salicylic acid, coal tar, benzoyl peroxide, and phototherapy.The condition is most common in infants within the first 3 months or in adults aged 30 to 70 years. In adults between 1% and 10% of people are affected. Males are more often affected than females. Up to 70% of babies may be affected at some point in time. Signs and symptoms Seborrhoeic dermatitis symptoms appear gradually, and usually the first signs are flaky skin and scalp. Symptoms occur most commonly anywhere on the skin of the scalp, behind the ears, on the face, and in areas where the skin folds. Flakes may be yellow, white or grayish. Redness and flaking may also occur on the skin near the eyelashes, on the forehead, around the sides of the nose, on the chest, and on the upper back. In more severe cases, yellowish to reddish scaly pimples appear along the hairline, behind the ears, in the ear canal, on the eyebrows, on the bridge of the nose, around the nose, on the chest, and on the upper back.Commonly, patients experience mild redness, scaly skin lesions and in some cases hair loss. Other symptoms include patchy scaling or thick crusts on the scalp, red, greasy skin covered with flaky white or yellow scales, itching, soreness and yellow or white scales that may attach to the hair shaft.Seborrhoeic dermatitis can occur in infants younger than three months and it causes a thick, oily, yellowish crust around the hairline and on the scalp. Itching is not common among infants. Frequently, a stubborn diaper rash accompanies the scalp rash. Causes The cause of seborrhoeic dermatitis has not been fully clarified.In addition to the presence of Malassezia, genetic, environmental, hormonal, and immune-system factors are necessary for and/or modulate the expression of seborrhoeic dermatitis. The condition may be aggravated by illness, psychological stress, fatigue, sleep deprivation, change of season, and reduced general health. In children and babies, excessive vitamin A intake or issues with Δ6-desaturase enzymes have been correlated with increased risk. Seborrhoeic dermatitis-like eruptions are also associated with vitamin B6 deficiency. Those with immunodeficiency (especially infection with HIV) and with neurological disorders such as Parkinsons disease (for which the condition is an autonomic sign) and stroke are particularly prone to it. Climate Low humidity and low temperature are responsible for high frequency of seborrheic dermatitis. Fungi The condition is thought to be due to a local inflammatory response to over-colonization by Malassezia fungi species in sebum-producing skin areas including the scalp, face, chest, back, underarms, and groin. This is based on observations of high counts of Malassezia species in skin affected by seborrhoeic dermatitis and on the effectiveness of antifungals in treating the condition. Such species of Malassezia include M. furfur (formerly Pityrosporum ovale), M. globosa, M. restricta, M. sympodialis, and M. slooffiae. Although Malassezia appears to be the central predisposing factor in seborrhoeic dermatitis, it is thought that other factors are necessary for the presence of Malassezia to result in the pathology characteristic of the condition. This is based on the fact that summer growth of Malassezia in the skin alone does not result in seborrhoeic dermatitis. Besides antifungals, the effectiveness of anti-inflammatory drugs, which reduce inflammation, and antiandrogens, which reduce sebum production, provide further insights into the pathophysiology of seborrhoeic dermatitis. Eunuchs, owing to their low androgen levels and small sebaceous glands, do not develop seborrheic dermatitis. Management Humidity A humidifier can be used to prevent low indoor humidity during winter (especially with indoor heating), and dry season. And a dehumidifier can be used during seasons with excessive humidity. Medications A variety of different types of medications are able to reduce symptoms of seborrhoeic dermatitis. These include certain antifungals, anti-inflammatory agents like corticosteroids and nonsteroidal anti-inflammatory drugs, antiandrogens, and antihistamines, among others. Antifungals Regular use of an over-the-counter or prescription antifungal shampoo or cream may help those with recurrent episodes. The topical antifungal medications ketoconazole and ciclopirox have the best evidence. It is unclear if other antifungals are equally effective as this has not been sufficiently studied. Antifungals that have been studied and found to be effective in the treatment of seborrhoeic dermatitis include ketoconazole, fluconazole, miconazole, bifonazole, sertaconazole, clotrimazole, flutrimazole, ciclopirox, terbinafine, butenafine, selenium sulfide, and lithium salts such as lithium gluconate and lithium succinate. Topical climbazole appears to have little effectiveness in the treatment of seborrhoeic dermatitis. Systemic therapy with oral antifungals including itraconazole, fluconazole, ketoconazole, and terbinafine is effective. Anti-inflammatory treatments Topical corticosteroids have been shown to be effective in short-term treatment of seborrhoeic dermatitis and are as effective or more effective than antifungal treatment with azoles. There is also evidence for the effectiveness of calcineurin inhibitors like tacrolimus and pimecrolimus as well as lithium salt therapy.Oral immunosuppressive treatment, such as with prednisone, has been used in short courses as a last resort in seborrhoeic dermatitis due to its potential side effects. Antiandrogens Seborrhoea, which is sometimes associated with seborrhoeic dermatitis, is recognized as an androgen-sensitive condition – that is, it is caused or aggravated by androgen sex hormones such as testosterone and dihydrotestosterone – and is a common symptom of hyperandrogenism (e.g., that seen in polycystic ovary syndrome). In addition, seborrhoea, as well as acne, are commonly associated with puberty due to the steep increase of androgen levels at that time.In accordance with the involvement of androgens in seborrhoea, antiandrogens, such as cyproterone acetate, spironolactone, flutamide, and nilutamide, are highly effective in alleviating the condition. As such, they are used in the treatment of seborrhoea, particularly severe cases. While beneficial in seborrhoea, effectiveness may vary with different antiandrogens; for instance, spironolactone (which is regarded as a relatively weak antiandrogen) has been found to produce a 50% improvement after three months of treatment, whereas flutamide has been found to result in an 80% improvement within three months. Cyproterone acetate, similarly more potent and effective than spironolactone, results in considerable improvement or disappearance of acne and seborrhoea in 90% of patients within three months.Systemic antiandrogen therapy is generally used to treat seborrhoea only in women, not in men, as these medications can result in feminization (e.g., gynecomastia), sexual dysfunction, and infertility in males. In addition, antiandrogens theoretically have the potential to feminize male fetuses in pregnant women and, for this reason, are usually combined with effective birth control in sexually active women who can or may become pregnant. Antihistamines Antihistamines are used primarily to reduce itching, if present. However, research studies suggest that some antihistamines have anti-inflammatory properties. Other treatments Coal tar can be effective. Although no significant increased risk of cancer in human treatment with coal tar shampoos has been found, caution is advised since coal tar is carcinogenic in animals, and heavy human occupational exposures do increase cancer risks. Isotretinoin, a sebosuppressive agent, may be used to reduce sebaceous gland activity as a last resort in refractory disease. However, isotretinoin has potentially serious side effects, and few patients with seborrhoeic dermatitis are appropriate candidates for therapy. Keratolytics like topical urea Metronidazole Topical 4% nicotinamide Phototherapy Another potential option is natural and artificial UV radiation since it can curb the growth of Malassezia yeast. Some recommend photodynamic therapy using UV-A and UV-B laser or red and blue LED light to inhibit the growth of Malassezia fungus and reduce seborrhoeic inflammation. Epidemiology Seborrhoeic dermatitis affects 1 to 5% of the general population. It is slightly more common in men, but affected women tend to have more severe symptoms. The condition usually recurs throughout a persons lifetime. Seborrhoeic dermatitis can occur in any age group but usually starts at puberty and peaks in incidence at around 40 years of age. It can reportedly affect as many as 31% of older people. Severity is worse in dry climates. Seborrhoeic dermatitis is common in this with alcoholism, between 7 and 11 percent, which is twice the normal expected occurrence. See also Seborrheic keratosis Eczema herpeticum, condition that primarily manifests in childhood References External links American Academy of Dermatology: Seborrheic dermatitis

Tachyphylaxis

Tachyphylaxis (Greek ταχύς, tachys, "rapid", and φύλαξις, phylaxis, "protection") is a medical term describing an acute, sudden decrease in response to a drug after its administration; i.e. a rapid and short-term onset of drug tolerance. It can occur after an initial dose or after a series of small doses. Increasing the dose of the drug may be able to restore the original response. Characteristics Tachyphylaxis is characterized by the rate sensitivity: the response of the system depends on the rate with which a stimulus is presented. To be specific, a high-intensity prolonged stimulus or often-repeated stimulus may bring about a diminished response also known as desensitization. Molecular interaction In biological sciences, molecular interactions are the physical bases of the operation of the system. The control of the operation, in general, involves interaction of a stimulus molecule with a receptor/enzyme subsystem by, typically, binding to the macromolecule A and causing an activation or an inhibition of the subsystem by forming an activated form of the macromolecule B. The following schematic represents the activity: A → p B {\displaystyle A{\xrightarrow {\ \ p\ \ }}B} where p is the activation rate coefficient. It is customary that p is called a rate constant, but, since the p stands for measure of the intensity of the stimulus causing the activation, p may be variable (non-constant). More complete is an open system, namely, in its simplest form, R → A → p ( S ) B → q , {\displaystyle R{\xrightarrow {}}A{\xrightarrow {\ \ p(S)\ \ }}B{\xrightarrow {\ \ q\ \ }},} where R stands for the rate of production of A, p(S) is the activation rate coefficient explicitly expressing its dependence on the stimulus intensity S and q represents the rate coefficient of removal from the state B. In this elementally open system the steady state of B always equal to R/q. The above scheme is only the necessary condition for the rate sensitivity phenomenon, and other pathways of deactivation of B may be considered, with the subsequent return to the inactive form of the receptor/enzyme A. Examples offer particular use of such (mathematical) models in endocrinology, physiology and pharmacology. Examples Psychedelics Psychedelics such as LSD-25 and psilocybin-containing mushrooms demonstrate very rapid tachyphylaxis. Opioids In a patient fully withdrawn from opioids, going back to an intermittent schedule or maintenance dosing protocol, a fraction of the old tolerance level will rapidly develop, usually starting two days after therapy is resumed and, in general, leveling off after day 7. Whether this is caused directly by opioid receptors modified in the past or affecting a change in some metabolic set-point is unclear. Increasing the dose will usually restore efficacy; relatively rapid opioid rotation may also be of use if the increase in tolerance continues. Beta-2 agonists Inhalation of an agonist for the beta-2 adrenergic receptor, such as salbutamol (albuterol in the US), is the most common treatment for asthma. Polymorphisms of the beta-2 receptor play a role in tachyphylaxis. Expression of the Gly-16 allele (glycine at position 16) results in greater receptor downregulation by endogenous catecholamines at baseline compared to Arg-16. This results in a greater single-use bronchodilator response in individuals homozygous for Arg-16 compared to Gly-16 homozygotes. However, with regular beta-2 agonist use, asthmatic Arg-16 individuals experience a significant decline in bronchodilator response. This decline does not occur in Gly-16 individuals. It has been proposed that the tachyphylactic effect of regular exposure to exogenous beta-2 agonists is more apparent in Arg-16 individuals because their receptors have not been downregulated prior to agonist administration. Nicotine Nicotine may also show tachyphylaxis over the course of a day, although the mechanism of this action is unclear. Other examples Nitroglycerine (or glyceryl trinitrate) and other nitrovasodilators of the nitrate type demonstrates tachyphylaxis, requiring drug-free intervals of 6 to 8 hours. Hydralazine displays tachyphylaxis if given as a monotherapy for antihypertensive treatment. It is administered with a beta-blocker with or without a diuretic. Metoclopramide Dobutamine, a direct-acting beta agonist used in congestive heart failure, also demonstrates tachyphylaxis. Desmopressin used in the treatment of type 1 von Willebrand disease is, in general, given every 12–24 hours in limited numbers due to its tachyphylactic properties. Ranitidine, used for acid reflux treatment, can display rapid tachyphylaxis within six weeks of treatment initiation, limiting its long-term use potential. Hormone replacement, when used in menopausal women in the form of estrogen and progesterone implants, is cited as having potential to lead to tachyphylaxis, but that citation is based on a single study done in 1990 and no follow-up research is available to support this interpretation. Intervention and reversal Intranasal decongestants Use of intranasal decongestants (such as oxymetazoline) for more than three days leads to tachyphylaxis of response and rebound congestion, caused by alpha-adrenoceptor downregulation and desensitization. The mechanism may specifically include receptor internalisation and resistance to endogenous vasoconstrictors causing worsening in symptoms post use of medication. Oxymetazoline-induced tachyphylaxis and rebound congestion are reversed by intranasal fluticasone. See also References External links Tachyphylaxis and Tolerance: Biomathematics of Rate Sensitivity Tachyphylaxis at the US National Library of Medicine Medical Subject Headings (MeSH)

Nerve injury

Nerve injury is an injury to nervous tissue. There is no single classification system that can describe all the many variations of nerve injuries. In 1941, Seddon introduced a classification of nerve injuries based on three main types of nerve fiber injury and whether there is continuity of the nerve. Usually, however, peripheral nerve injuries are classified in five stages, based on the extent of damage to both the nerve and the surrounding connective tissue, since supporting glial cells may be involved.Unlike in the central nervous system, neuroregeneration in the peripheral nervous system is possible. The processes that occur in peripheral regeneration can be divided into the following major events: Wallerian degeneration, axon regeneration/growth, and reinnervation of nervous tissue. The events that occur in peripheral regeneration occur with respect to the axis of the nerve injury. The proximal stump refers to the end of the injured neuron that is still attached to the neuron cell body; it is the part that regenerates. The distal stump refers to the end of the injured neuron that is still attached to the end of the axon; it is the part of the neuron that will degenerate, but the stump remains capable of regenerating its axons. The study of peripheral nerve injury began during the American Civil War and greatly expanded during modern medicine with such advances as use of growth-promoting molecules. Types To assess the location and severity of a peripheral nerve injury, clinical assessment is commonly combined with electrodiagnostic tests. Injuries to the myelin are usually the least severe (neuropraxia), while injuries to the axons and supporting structures are more severe (axonotmesis is moderate injury, while neurotmesis is severe injury). It may be difficult to differentiate the severity by clinical findings due to common neurological impairments, including motor and sensory impairments distal to the lesion. Neurapraxia Neurapraxia is the least severe form of nerve injury, with complete recovery. In this case, the axon remains intact, but there is myelin damage causing an interruption in conduction of the impulse down the nerve fiber. Most commonly, this involves compression of the nerve or disruption to the blood supply (ischemia). There is a temporary loss of function which is reversible within hours to months of the injury (the average is 6–8 weeks). Wallerian degeneration does not occur, so recovery does not involve actual regeneration. There is frequently greater involvement of motor than sensory function with autonomic function being retained. In electrodiagnostic testing with nerve conduction studies, there is a normal compound motor action potential amplitude distal to the lesion at day 10, and this indicates a diagnosis of mild neurapraxia instead of axonotmesis or neurotmesis. Axonotmesis This is a more severe nerve injury with disruption of the neuronal axon, but with maintenance of the epineurium. This type of nerve damage may cause paralysis of the motor, sensory, and autonomic, and is mainly seen in crush injury.If the force creating the nerve damage is removed in a timely fashion, the axon may regenerate, leading to recovery. Electrically, the nerve shows rapid and complete degeneration, with loss of voluntary motor units. Regeneration of the motor end plates will occur, as long as the endoneural tubules are intact.Axonotmesis involves the interruption of the axon and its covering of myelin, but with preservation of the connective tissue framework of the nerve (the encapsulating tissue, the epineurium and perineurium, are preserved). Because axonal continuity is lost, Wallerian degeneration occurs. Electromyography (EMG) performed 2 to 4 weeks later shows fibrillations and denervation potentials in musculature distal to the injury site. Loss in both motor and sensory spines is more complete with axonotmesis than with neurapraxia, and recovery occurs only through regenerations of the axons, a process requiring time. Axonotmesis is usually the result of a more severe crush or contusion than neurapraxia, but can also occur when the nerve is stretched (without damage to the epineurium). There is usually an element of retrograde proximal degeneration of the axon, and for regeneration to occur, this loss must first be overcome. The regeneration fibers must cross the injury site and regeneration through the proximal or retrograde area of degeneration may require several weeks. Then the neuritis tip progresses down the distal site, such as the wrist or hand. Proximal lesion may grow distally as fast as 2 to 3 mm per day and distal lesion as slowly as 1.5 mm per day. Regeneration occurs over weeks to years. Neurotmesis Neurotmesis is the most severe lesion with no potential of full recovery. It occurs on severe contusion, stretch, or laceration. The axon and encapsulating connective tissue lose their continuity. The last (extreme) degree of neurotmesis is transsection, but most neurotmetic injuries do not produce gross loss of continuity of the nerve but rather internal disruption of nerve structures sufficient to involve perineurium and endoneurium as well as axons and their covering. Denervation changes recorded by EMG are the same as those seen with axonotmetic injury. There is a complete loss of motor, sensory and autonomic function. If the nerve has been completely divided, axonal regeneration causes a neuroma to form in the proximal stump. For neurotmesis, it is better to use a new more complete classification called the Sunderland System. Overview of peripheral regeneration Wallerian degeneration is a process that occurs before nerve regeneration and can be described as a cleaning or clearing process that essentially prepares the distal stump for reinnervation. Schwann cells are glial cells in the peripheral nervous system that support neurons by forming myelin that encases nerves. During Wallerian degeneration Schwann cells and macrophages interact to remove debris, specifically myelin and the damaged axon, from the distal injury site. Calcium has a role in the degeneration of the damage axon. Bands of Büngner are formed when uninnervated Schwann cells proliferate and the remaining connective tissue basement membrane forms endoneurial tubes. Bands of Büngner are important for guiding the regrowing axon.At the neuronal cell body, a process called chromatolysis occurs in which the nucleus migrates to the periphery of the cell body and the endoplasmic reticulum breaks up and disperses. Nerve damage causes the metabolic function of the cell to change from that of producing molecules for synaptic transmission to that of producing molecules for growth and repair. These factors include GAP-43, tubulin and actin. Chromatolysis is reversed when the cell is prepared for axon regeneration.Axon regeneration is characterized by the formation of a growth cone, which has the ability to produce a protease that digests any material or debris that remains in its path of regeneration toward the distal site. The growth cone responds to molecules produced by Schwann cells such as laminin and fibronectin. Neuron-intrinsic changes Immediately following injury, neurons undergo a large number of transcriptional and proteomic changes which switch the cell from a mature, synaptically active neuron to a synaptically silent, growth state. This process is dependent on new transcription, as blocking the ability of cells to transcribe new mRNA severely impairs regeneration. A number of signaling pathways have been shown to be turned on by axon injury and help to enable long distance regeneration including BMP, TGFβ, and MAPKs. Similarly, a growing number of transcription factors also boost the regenerative capacity of peripheral neurons including ASCL1, ATF3, CREB1, HIF1α, JUN, KLF6, KLF7, MYC, SMAD1, SMAD2, SMAD3, SOX11, SRF, STAT3, TP53, and XBP1. Several of these can also boost the regenerative capacity of CNS neurons, making them potential therapeutic targets for treating spinal cord injury and stroke. Role of Schwann cells Schwann cells are active in Wallerian degeneration. They not only have a role in phagocytosis of myelin, but they also have a role in recruitment of macrophages to continue the phagocytosis of myelin. The phagocytic role of Schwann cells has been investigated by studying the expression of molecules in Schwann cells that are typically specific to inflammatory macrophages. Expression of one such molecule MAC-2, a galactose-specific lectin, is observed in not only degenerating nerves that are macrophage-rich but also degenerating nerves that are macrophage-scarce and Schwann cell-rich. Furthermore, the effects of MAC-2 in degenerating nerves are associated with myelin phagocytosis. There was a positive correlation between the amount of MAC-2 expression and the extent of myelin phagocytosis. A deficiency in MAC-2 expression can even cause inhibition of myelin removal from injury sites.Schwann cells are active in demyelination of injured nerves before macrophages are even present at the site of nerve injury. Electron microscopy and immunohistochemical staining analysis of teased nerve fibers shows that before macrophages arrive at the injury site, myelin is fragmented and myelin debris and lipid droplets are found in the cytoplasm of Schwann cells, indicating phagocytic activity before macrophages arrive.Schwann cell activity includes recruitment of macrophages to the injury site. Monocyte chemoattractant protein (MCP-1) plays a role in recruiting monocytes/macrophages. In tellurium-induced demylenation with no axon degeneration, nerve crush with axon degeneration, and nerve transection with axon degeneration an increase in MCP-1 mRNA expression followed by an increase in macrophage recruitment occurred. In addition varying levels of MCP-1 mRNA expression also had an effect. Increased MCP-1 mRNA levels correlated positively with an increase in macrophage recruitment. Furthermore, in situ hybridation determined that the cellular source of MCP-1 was Schwann cells.Schwann cells play an important role in not only producing neurotrophic factors such as nerve growth factor (NGF) and ciliary neurotrophic factor (CNTF), which promote growth, of both the damaged nerve and supporting Schwann cells, but also producing neurite promoting factors, which guide the growing axon, both of which are discussed below. Role of macrophages The primary role of macrophages in peripheral regeneration is demylenation during Wallerian degeneration. Immunohistochemical analysis showed that in tellurium demylenated, crushed, and cut nerves, expression of lysozyme, which is a marker for myelin phagocytosis, and of ED1, which is a marker for macrophages, occurred in the same region. Lysozyme was also investigated with respect to the temporal progression of myelin phagocytosis by macrophages in nerve injury. Northern blotting showed that peak lysozyme mRNA expression occurred at an appropriate time with respect to temporal models of myelin phagocytosis. Macrophages do not phagocytose all cellular debris at the nerve injury site; they are selective and will salvage certain factors. Macrophages produce apolipoprotein E which is involved in rescuing cholesterol in damaged nerves. In the same investigation, temporal levels of apolipoprotein E mRNA expression in the three models for demylenation and nerve damage were consistent with respect to models for cholesterol salvage in nerve injury. Macrophages play a role in salvaging cholesterol during nerve injury.Macrophages also play a role in inducing the proliferation of Schwann cells that occurs during Wallerian degeneration. Supernatant has been collected from medium in which macrophages are active in myelin phagocytosis where lysosomal processing of the myelin occurs within the macrophage. The supernatant contains a mitogenic factor, a mitosis promoting factor, that is characterized heat and trypsin sensitivity, both of which characterize it as a peptide. Treatment of Schwann cells with the collected supernatant shows that it is a mitogenic factor and thus plays an important role in the proliferation of Schwann cells.Macrophages are also involved in the secretion factors that promote nerve regeneration. Macrophages secrete not only interleukin-1, a cytokine that induces expression of nerve growth factor (NGF) in Schwann cells but also an interleukin-1 receptor antagonist (IL-1ra). Expression of IL-1ra in mice with transected sciatic nerves via implantation of a tube releasing IL-1ra showed the regrowth of fewer myelinated and unmyelinated axons. Macrophage secretion of interleukin-1 is involved in stimulation of nerve regeneration. Role of neurotrophic factors Neurotrophic factors are those that promote survival and growth of neurons. A trophic factor can be described as a factor that is associated with providing nourishment to allow for growth. In general they are protein ligands for tyrosine kinase receptors; binding to the specific receptor yields autophosphorylation and subsequent phosphorylation of tyrosine residues on proteins that participate in further downstream signaling to activate proteins and genes involved in growth and proliferation. Neurotrophic factors act through retrograde transport in neurons, in which they are taken up by the growth cone of the injured neuron and transported back to the cell body. These neurotrophic factors have both autocrine and paracrine effects, as they promote growth of the damaged neurons as well as the adjacent Schwann cells. Nerve growth factor (NGF) typically has a low level of expression in nerves that are healthy and not growing or developing, but in response to nerve injury NGF expression increases in Schwann cells. This is a mechanism to increase growth and proliferation of Schwann cells at the distal stump in order to prepare for reception of the regenerating axon. NGF has not only a trophic role but also a tropic or guiding role. The Schwann cells that form the bands of Bungner at the distal injury site express NGF receptors as a guiding factor for the regenerating axon of the injured neuron. NGF bound to the receptors on Schwann cells provides the growing neurons that are contacted with a trophic factor to promote further growth and regenerationCiliary neurotrophic factor (CNTF) typically has a high level of expression in Schwann cells associated with nerves that are healthy, but in response to nerve injury CNTF expression decreases in Schwann cells distal to the injury site and remains relatively low unless the injured axon begins to regrow. CNTF has numerous trophic roles in motor neurons in the peripheral nervous system including the prevention of atrophy of dennervated tissue and the prevention of degeneration and death of motor neurons after nerve injury. (frostick) In sciatic motor neurons both CNTF receptor mRNA expression and CNTF receptor is increased after injury for a prolonged time frame compared to the short time frame in the central nervous system suggesting a role for CNTF in nerve regeneration.Insulin-like growth factors (IGFs) have been shown to increase the rate of peripheral nervous system axon regeneration. IGF-I and IGF-II mRNA levels are significantly increased distal to the site of crush injury in rat sciatic nerves. At the site of nerve repair, locally delivered IGF-I can significantly increase the rate of axon regeneration within a nerve graft and help expedite functional recovery of a paralyzed muscle. Role of neurite-promoting factors Neurite promoting factors include many extracellular matrix proteins produced by Schwann cells at the distal stump including fibronectin and laminin. Fibronectin are components of the basal lamina and promote neurite growth and adhesion of the growth cone to the basal lamina. In regenerating neural cells, neurite promoting factors play a role in adhesion of the axon and include neural cell adhesion molecule (N-CAM) and N-cadherin. Treatment Unless otherwise demonstrated, nerve injuries are commonly irreversible, and therefore complete treatment is rather difficult, though still possible and hence lifelong management of disabilities arising due to nerve injuries is necessary. Nerve regeneration therapies Electrical stimulation can promote nerve regeneration. The positive effect of electrical stimulation on nerve regeneration is due to its molecular influence on the damaged neuron and Schwann cells. Electrical stimulation can directly accelerate the expression of cyclic adenosine monophosphate (cAMP) both in neurons and Schwann cells. cAMP is a molecule that stimulates multiple signaling pathways that aid nerve regeneration by enhancing the expression of several neurotrophic factors. Electrical stimulation also results in the influx of calcium ions, which further triggers multiple regeneration pathways.The frequency of stimulation is an important factor in the success of both quality and quantity of axon regeneration as well as growth of the surrounding myelin and blood vessels that support the axon. Histological analysis and measurement of regeneration showed that low frequency stimulation had a more successful outcome than high frequency stimulation on regeneration of damaged sciatic nerves.Other studies have used both oscillating current (AC) and non-oscillating direct current (DC) stimulation to regenerate mammalian peripheral nerves. Mammalian neurons preferentially orient and grow towards the cathode in DC electric fields.Surgery can be done in case a nerve has become cut or otherwise divided. Recovery of a nerve after surgical repair depends mainly on the age of patients. Younger the patients, better the prognosis, because of better healing capacity of young tissues. Young children can recover almost normal nerve function. In contrast, a patient over 60 years old with a cut nerve in the hand would expect to recover only protective sensory function, that is, the ability to distinguish hot/cold or sharp/dull; recovery of motor function would be likely incomplete. Many other factors also affect nerve recovery. The use of autologous nerve grafting procedures that involve redirection of regenerative donor nerve fibers into the graft conduit has been successful in restoring target muscle function. Localized delivery of soluble neurotrophic factors may help promote the rate of axon regeneration observed within these graft conduits.An expanding area of nerve regeneration research deals with the development of scaffolding and bio-conduits. Scaffolding developed from bio-compatible material would be useful in nerve regeneration if they successfully exhibit essentially the same role as the endoneurial tubes and Schwann cells do in guiding regrowing axons. Prevention of nerve injuries Methods to help prevent peripheral nerve injuries include injection pressure monitoring. The presence of a high opening injection pressure (> 20 PSI) is a sensitive sign of intrafascicular/intraneural needle tip placement. Extrafascicular needle tip placement is associated with low pressures (< 20 PSI). Also, high pressure injection was associated with neurologic deficits and severe axonal damage after the block. Other methods of preventing peripheral nerve injury include electrical nerve stimulation and ultrasonography. Electrical stimulation with a motor response at < 0.2 mA only can occur with an intraneural/intrafasciular needle tip location. See also Brain injury References == External links ==

Rectal pain

Rectal pain is the symptom of pain in the area of the rectum. A number of different causes (68) have been documented. Differential diagnosis Anal fissures One of the most common causes of rectal pain is an anal fissure. It involves a tear in the anal canal probably due to trauma from defecation and are usually treated effectively with sitz baths, stool softeners, and analgesics. LAS and proctalgia fugax Two more highly common causes of functional anorectal pain are levator ani syndrome (LAS) and proctalgia fugax. Both of these conditions are thought to be caused by muscle spasms of the either the levator ani muscle or the anal sphincter muscle respectively, and may overlap symptomatically with a third less-common condition called coccygodynia which is the result of previous trauma to the coccyx bone. Stress, prolonged sitting, and constipation all seem to be associated with LAS. The majority (90%) of those reporting chronic episodes of such pain are women. Some researchers group these conditions under the medical category of "tension myalgia of the pelvic floor". Less than a third of those experiencing these conditions seek medical treatment for them. Treatment can involve the use of antispasmodic medications as well as the down-training (conscious involvement and relaxation of previously unconscious muscle movements) so that spasms occur less frequently or not at all. Anorectal abscess An anorectal abscess is an infection that forms a pocket of pus within the tissues around the anus. It is treated surgically by incision and drainage. Infections Bacterial, viral, and protozoal infections may occur in the area surround the rectum. These may be the result of a sexually transmitted disease. Other Hemorrhoids or rectal foreign body. References == External links ==

Intestinal ischemia

Intestinal ischemia is a medical condition in which injury to the large or small intestine occurs due to not enough blood supply. It can come on suddenly, known as acute intestinal ischemia, or gradually, known as chronic intestinal ischemia. The acute form of the disease often presents with sudden severe abdominal pain and is associated with a high risk of death. The chronic form typically presents more gradually with abdominal pain after eating, unintentional weight loss, vomiting, and fear of eating.Risk factors for acute intestinal ischemia include atrial fibrillation, heart failure, chronic kidney failure, being prone to forming blood clots, and previous myocardial infarction. There are four mechanisms by which poor blood flow occurs: a blood clot from elsewhere getting lodged in an artery, a new blood clot forming in an artery, a blood clot forming in the superior mesenteric vein, and insufficient blood flow due to low blood pressure or spasms of arteries. Chronic disease is a risk factor for acute disease. The best method of diagnosis is angiography, with computed tomography (CT) being used when that is not available.Treatment of acute ischemia may include stenting or medications to break down the clot provided at the site of obstruction by interventional radiology. Open surgery may also be used to remove or bypass the obstruction and may be required to remove any intestines that may have died. If not rapidly treated outcomes are often poor. Among those affected even with treatment the risk of death is 70% to 90%. In those with chronic disease bypass surgery is the treatment of choice. Those who have thrombosis of the vein may be treated with anticoagulation such as heparin and warfarin, with surgery used if they do not improve.Acute intestinal ischemia affects about five per hundred thousand people per year in the developed world. Chronic intestinal ischemia affects about one per hundred thousand people. Most people affected are over 60 years old. Rates are about equal in males and females of the same age. Intestinal ischemia was first described in 1895. Signs and symptoms While not always present and often overlapping, three progressive phases of intestinal ischemia have been described: A hyper active stage occurs first, in which the primary symptoms are severe abdominal pain and the passage of bloody stools. Many patients get better and do not progress beyond this phase. A paralytic phase can follow if ischemia continues; in this phase, the abdominal pain becomes more widespread, the belly becomes more tender to the touch, and bowel motility decreases, resulting in abdominal bloating, no further bloody stools, and absent bowel sounds on exam. Finally, a shock phase can develop as fluids start to leak through the damaged colon lining. This can result in shock and metabolic acidosis with dehydration, low blood pressure, rapid heart rate, and confusion. Patients who progress to this phase are often critically ill and require intensive care. Clinical findings Symptoms of intestinal ischemia vary and can be acute (especially if embolic), subacute, or chronic.Case series report prevalence of clinical findings and provide the best available, yet biased, estimate of the sensitivity of clinical findings. In a series of 58 patients with intestinal ischemia due to mixed causes: abdominal pain was present in 95% (median of 24 hours duration). The other three patients presented with shock and metabolic acidosis. nausea in 44% vomiting in 35% diarrhea in 35% heart rate > 100 in 33% rectal bleeding in 16% (not stated if this number also included occult blood – presumably not) constipation in 7% Diagnostic heuristics In the absence of adequate quantitative studies to guide diagnosis, various heuristics help guide diagnosis: Intestinal ischemia" should be suspected when individuals, especially those at high risk for acute intestinal ischemia, develop severe and persisting abdominal pain that is disproportionate to their abdominal findings"., or simply, pain out of proportion to exam. Regarding intestinal arterial thrombosis or embolism: "early symptoms are present and are relative mild in 50% of cases for three to four days before medical attention is sought". Regarding intestinal arterial thrombosis or embolism: "Any patient with an arrhythmia such as atrial fibrillation who complains of abdominal pain is highly suspected of having embolization to the superior mesenteric artery until proved otherwise." Regarding nonocclusive intestinal ischemia: "Any patient who takes digitalis and diuretics and who complains of abdominal pain must be considered to have nonocclusive ischemia until proved otherwise." Diagnosis It is difficult to diagnose intestinal ischemia early. Blood tests In a series of 58 patients with intestinal ischemia due to mixed causes: White blood cell count >10.5 in 98% (probably an overestimate as only tested in 81% of patients) Lactic acid elevated 91% (probably an overestimate as only tested in 57% of patients)In very early or very extensive acute intestinal ischemia, elevated lactate and white blood cell count may not yet be present. In extensive mesenteric ischemia, bowel may be ischemic but separated from the blood flow such that the byproducts of ischemia are not yet circulating. During endoscopy A number of devices have been used to assess the sufficiency of oxygen delivery to the colon. The earliest devices were based on tonometry, and required time to equilibrate and estimate the pHi, roughly an estimate of local CO2 levels. The first device approved by the U.S. FDA (in 2004) used visible light spectroscopy to analyze capillary oxygen levels. Use during aortic aneurysm repair detected when colon oxygen levels fell below sustainable levels, allowing real-time repair. In several studies, specificity has been 83% for chronic intestinal ischemia and 90% or higher for acute colonic ischemia, with a sensitivity of 71%-92%. This device must be placed using endoscopy, however.Findings on gastroscopy may include edematous gastric mucosa, and hyperperistalsis.Finding on colonoscopy may include: fragile mucosa, segmental erythema, longitudinal ulcer, and loss of haustrations Plain X-ray Plain X-rays are often normal or show non-specific findings. Computed tomography Computed tomography (CT scan) is often used. The accuracy of the CT scan depends on whether a small bowel obstruction (SBO) is present.SBO absent prevalence of intestinal ischemia 23% sensitivity 64% specificity 92% positive predictive value (at prevalence of 23%) 79% negative predictive value (at prevalence of 23%) 95%SBO present prevalence of intestinal ischemia 62% sensitivity 83% specificity 93% positive predictive value (at prevalence of 62%) 93% negative predictive value (at prevalence of 62%) 61%Early findings on CT scan include: Intestinal mesenteric edema Bowel dilatation Bowel wall thickening Intestinal mesenteric stranding Evidence of adjacent solid organ infarctions to the kidney or spleen, consistent with a cardiac embolic shower phenomenonIn embolic acute intestinal ischemia, CT-Angiography can be of great value for diagnosis and treatment. It may reveal the emboli itself lodged in the superior mesenteric artery, as well as the presence or absence of distal mesenteric branches.Late findings, which indicate dead bowel, include: Intramural bowel gas Portal venous gas Free abdominal air Angiography As the cause of the ischemia can be due to embolic or thrombotic occlusion of the mesenteric vessels or nonocclusive ischemia, the best way to differentiate between the etiologies is through the use of mesenteric angiography. Though it has serious risks, angiography provides the possibility of direct infusion of vasodilators in the setting of nonocclusive ischemia. Treatment The treatment of intestinal ischemia depends on the cause and can be medical or surgical. However, if bowel has become necrotic, the only treatment is surgical removal of the dead segments of bowel.In non-occlusive disease, where there is no blockage of the arteries supplying the bowel, the treatment is medical rather than surgical. People are admitted to the hospital for resuscitation with intravenous fluids, careful monitoring of laboratory tests, and optimization of their cardiovascular function. NG tube decompression and heparin anticoagulation may also be used to limit stress on the bowel and optimize perfusion, respectively.Surgical revascularisation remains the treatment of choice for intestinal ischaemia related to an occlusion of the vessels supplying the bowel, but thrombolytic medical treatment and vascular interventional radiological techniques have a growing role.If the ischemia has progressed to the point that the affected intestinal segments are gangrenous, a bowel resection of those segments is called for. Often, obviously dead segments are removed at the first operation, and a second-look operation is planned to assess segments that are borderline that may be savable after revascularization. Methods for revascularization Open surgical thrombectomy Intestinal bypass Trans-femoral antegrade intestinal angioplasty and stenting Open retrograde intestinal angioplasty stenting Trans-catheter thrombolysis Prognosis The prognosis depends on prompt diagnosis (less than 12–24 hours and before gangrene) and the underlying cause: venous thrombosis: 32% mortality arterial embolism: 54% mortality arterial thrombosis: 77% mortality non-occlusive ischemia: 73% mortality.In the case of prompt diagnosis and therapy, acute intestinal ischemia can be reversible. History Acute intestinal ischemia was first described in 1895 while chronic disease was first described in the 1940s. Chronic disease was initially known as angina abdominis. Terminology The related term mesenteric ischemia generally defined as ischemia of the small bowel specifically. It has also been defined as poor circulation in the vessels supplying blood flow to any or several of the mesenteric organs, including the stomach, liver, colon and intestine. In the large intestine Ischemia of the large intestine (colon) is termed ischemic colitis. Although uncommon in the general population, ischemic colitis occurs with greater frequency in the elderly, and is the most common form of bowel ischemia. Causes of the reduced blood flow can include changes in the systemic circulation (e.g. low blood pressure) or local factors such as constriction of blood vessels or a blood clot. In most cases, no specific cause can be identified.Ischemic colitis is usually suspected on the basis of the clinical setting, physical examination, and laboratory test results; the diagnosis can be confirmed by endoscopy or by using sigmoid or endoscopic placement of a visible light spectroscopic catheter (see Diagnosis). Ischemic colitis can span a wide spectrum of severity; most patients are treated supportively and recover fully, while a minority with very severe ischemia may develop sepsis and become critically, sometimes fatally, ill.Patients with mild to moderate ischemic colitis are usually treated with IV fluids, analgesia, and bowel rest (that is, no food or water by mouth) until the symptoms resolve. Those with severe ischemia who develop complications such as sepsis, intestinal gangrene, or bowel perforation may require more aggressive interventions such as surgery and intensive care. Most patients make a full recovery; occasionally, after severe ischemia, patients may develop long-term complications such as a stricture or chronic colitis. References == External links ==

Gastric distension

Gastric distention is the enlargement of the stomach, and can be due to a number of causes.Physiologic (normal) gastric distension occurs when eating. Distension of the upper stomach stimulates the secretion of stomach acid, while distension of the lower stomach stimulates gastrin secretion. Distension of the stomach also stimulates the secretion of ghrelin.Other causes include: binge eating associated with bulimia nervosa tumors causing obstruction diabetic neuropathy scarring due to pyloric gastritis delayed gastric emptyingTo identify the cause of gastric distention, an upper endoscopy or barium upper GI imaging should be done. == References ==