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I'd like to learn more about the medical term 'Buried penis.' Can you provide some details?

Buried penis (also known as hidden penis or retractile penis) is a congenital or acquired condition in which the penis is partially or completely hidden below the surface of the skin. A buried penis can lead to urinary difficulties, poor hygiene, infection, and inhibition of normal sexual function.Buried penis is different than micropenis, which is an abnormally small, normally structured penis with a stretched penile length of less than 2.5 standard deviations below the mean for age or stage of sexual development of the patient. History Buried penis was first described by Edward Lawrence Keyes in 1919 as the apparent absence of the penis due to the penis being buried beneath the skin of the abdomen, thigh, or scrotum. Further research was done by Maurice Campbell in 1951, when he reported on the penis being buried beneath subcutaneous fat of the scrotum, perineum, hypogastrium, and thigh. Causes Congenital Congenital causes can include the maldevelopment of the penile shaft with a lack of attachments of the shaft skin to the penile shaft. While rare, it can include an abnormally large pubic fat pad and firm tissue that pulls the penis inward. Acquired Obesity While not every obese male has the buried penis condition, 87% of men that received surgical treatment for buried penis were reported to be obese. Significant overlying abdominal fat can also create an environment that encourages bacterial and fungal growth. Obesity can also increase the likelihood of the development of type II diabetes mellitus, which is characterized by increase susceptibility to infections, making it difficult to successfully and promptly manage the buried penis condition. Such recurring infections can also lead to scar contracture, which can cause the prepubic skin to shift over the shaft and glans, thus invaginating the shafts skin and leading to a buried penis. </ref> Penoscrotal lymphodema While an uncommon cause, penoscrotal lymphodema causes a deformity of the shaft and scrotum, resulting in a buried penis. Overly aggressive circumcision In some cases of circumcision, too much foreskin is removed or the suture line constricts, causing cicatricial scarring, which can trap the penis in the remaining foreskin or push the penis into the suprapubic area and lead to a buried penis. Balanitis xerotica obliterans (BXO) BXO is a chronic inflammatory dermatological process that causes sclerosis of the glans, shaft, prepuce, or urethra. This can result in a cicatrix of the distal penis and its entrapment. Dysgenic dartos Dysgenic dartos is a condition characterized by a lack of dorsal support together with the hypermobility of the ventral skin and the lack of proper attachment between the dartos and the penis. This can enable the penis to "telescope" into the scrotum, thus creating a buried penis. Treatment The condition may resolve itself without any intervention in very young children; however, patients may eventually need definitive reconstructive surgery. Urgent surgery may be necessary if infection is present. Congenitial buried penis can be corrected surgically in childhood by anchoring the corpora cavernosa to dartos bundles at the penile base. While weight loss may be of help to morbidly obese children and adults, it usually does not resolve the problem completely.Surgical options could include the detachment of the ligaments connecting the base of the penis to the pubic bone; the performance of skin grafts to cover areas of the penis requiring additional skin; liposuction using catheters to suck out fat cells under the skin from the area around the penis; an abdominoplasty in which excess fat and skin from the region are removed; an escutheonectomy in which the pad of fat just above the pubic area is removed; or a panniculectomy in which the panniculus, excess tissue, and skin that hangs over the genitals and thighs are removed. In a video demonstrating the use of a panniculectomy in the repair of adult buried penis, Dr. Bryan Voelzke and his colleagues emphasized the need to tack the suprapubic fat pad to the periosteum of the symphysis pubis as well as the importance of not pulling down the peno-scrotal junction and peno-abdominal junction just in order to further expose the penis.King IC, Tahir A, Ramanathan C, and Siddiqui H developed a modified treatment algorithm employing a single surgical technique consisting primarily of scar release and the mobilization of the skin of the penis.An article published in August 2019 by Dr. James J. Elist reported that a procedure involving the insertion of a subcutaneous soft silicone penile implant was successful in reversing the condition of adult acquired buried penis. See also Micropenis Phalloplasty Webbed penis References External links Examples

You are a medical knowledge base. Your task is to elucidate medical terminology, offering insights into their meanings, origins, and applications.

I'm not familiar with the medical term 'Combat stress reaction.' Could you provide some insights?

Combat stress reaction (CSR) is acute behavioral disorganization as a direct result of the trauma of war. Also known as "combat fatigue", "battle fatigue", or "battle neurosis", it has some overlap with the diagnosis of acute stress reaction used in civilian psychiatry. It is historically linked to shell shock and can sometimes precurse post-traumatic stress disorder. Combat stress reaction is an acute reaction that includes a range of behaviors resulting from the stress of battle that decrease the combatants fighting efficiency. The most common symptoms are fatigue, slower reaction times, indecision, disconnection from ones surroundings, and the inability to prioritize. Combat stress reaction is generally short-term and should not be confused with acute stress disorder, post-traumatic stress disorder, or other long-term disorders attributable to combat stress, although any of these may commence as a combat stress reaction. The US Army uses the term/acronym COSR (Combat Stress Reaction) in official medical reports. This term can be applied to any stress reaction in the military unit environment. Many reactions look like symptoms of mental illness (such as panic, extreme anxiety, depression, and hallucinations), but they are only transient reactions to the traumatic stress of combat and the cumulative stresses of military operations.In World War I, shell shock was considered a psychiatric illness resulting from injury to the nerves during combat. The horrors of trench warfare meant that about 10% of the fighting soldiers were killed (compared to 4.5% during World War II) and the total proportion of troops who became casualties (killed or wounded) was about 57%. Whether a person with shell-shock was considered "wounded" or "sick" depended on the circumstances. When faced with the phenomenon of a minority of soldiers mentally breaking down, there was an expectation that the root of this problem lay in character of the individual soldier, not because of what they experienced on the front lines during the war. The large proportion of World War I veterans in the European population meant that the symptoms were common to the culture. Signs and symptoms Combat stress reaction symptoms align with the symptoms also found in psychological trauma, which is closely related to post-traumatic stress disorder (PTSD). CSR differs from PTSD (among other things) in that a PTSD diagnosis requires a duration of symptoms over one month, which CSR does not. Fatigue-related symptoms The most common stress reactions include: Autonomic nervous system – Autonomic arousal Battle casualty rates The ratio of stress casualties to battle casualties varies with the intensity of the fighting. With intense fighting, it can be as high as 1:1. In low-level conflicts, it can drop to 1:10 (or less). Modern warfare embodies the principles of continuous operations with an expectation of higher combat stress casualties.The World War II European Army rate of stress casualties of 1 in 10 (101:1,000) troops per annum is skewed downward from both its norm and peak by data by low rates during the last years of the war. Diagnosis The following PIE principles were in place for the "not yet diagnosed nervous" (NYDN) cases: Proximity – treat the casualties close to the front and within sound of the fighting. Immediacy – treat them without delay and not wait until the wounded were all dealt with. Expectancy – ensure that everyone had the expectation of their return to the front after a rest and replenishment.United States medical officer Thomas W. Salmon is often quoted as the originator of these PIE principles. However, his real strength came from going to Europe and learning from the Allies and then instituting the lessons. By the end of the war, Salmon had set up a complete system of units and procedures that was then the "worlds best practice". After the war, he maintained his efforts in educating society and the military. He was awarded the Distinguished Service Medal for his contributions.Effectiveness of the PIE approach has not been confirmed by studies of CSR, and there is some evidence that it is not effective in preventing PTSD.US services now use the more recently developed BICEPS principles: Brevity Immediacy Centrality or contact Expectancy Proximity Simplicity Between the wars The British government produced a Report of the War Office Committee of Inquiry into "Shell-Shock", which was published in 1922. Recommendations from this included: In forward areas No soldier should be allowed to think that loss of nervous or mental control provides an honorable avenue of escape from the battlefield, and every endeavor should be made to prevent slight cases leaving the battalion or divisional area, where treatment should be confined to provision of rest and comfort for those who need it and to heartening them for return to the front line. In neurological centers When cases are sufficiently severe to necessitate more scientific and elaborate treatment they should be sent to special Neurological Centers as near the front as possible, to be under the care of an expert in nervous disorders. No such case should, however, be so labelled on evacuation as to fix the idea of nervous breakdown in the patients mind. In base hospitals When evacuation to the base hospital is necessary, cases should be treated in a separate hospital or separate sections of a hospital, and not with the ordinary sick and wounded patients. Only in exceptional circumstances should cases be sent to the United Kingdom, as, for instance, men likely to be unfit for further service of any kind with the forces in the field. This policy should be widely known throughout the Force. Forms of treatment The establishment of an atmosphere of cure is the basis of all successful treatment, the personality of the physician is, therefore, of the greatest importance. While recognizing that each individual case of war neurosis must be treated on its merits, the Committee are of opinion that good results will be obtained in the majority by the simplest forms of psycho-therapy, i.e., explanation, persuasion and suggestion, aided by such physical methods as baths, electricity and massage. Rest of mind and body is essential in all cases.The committee are of opinion that the production of deep hypnotic sleep, while beneficial as a means of conveying suggestions or eliciting forgotten experiences are useful in selected cases, but in the majority they are unnecessary and may even aggravate the symptoms for a time. They do not recommend psycho-analysis in the Freudian sense.In the state of convalescence, re-education and suitable occupation of an interesting nature are of great importance. If the patient is unfit for further military service, it is considered that every endeavor should be made to obtain for him suitable employment on his return to active life. Return to the fighting line Soldiers should not be returned to the fighting line under the following conditions:(1) If the symptoms of neurosis are of such a character that the soldier cannot be treated overseas with a view to subsequent useful employment. (2) If the breakdown is of such severity as to necessitate a long period of rest and treatment in the United Kingdom. (3) If the disability is anxiety neurosis of a severe type. (4) If the disability is a mental breakdown or psychosis requiring treatment in a mental hospital. It is, however, considered that many of such cases could, after recovery, be usefully employed in some form of auxiliary military duty. Part of the concern was that many British veterans were receiving pensions and had long-term disabilities. By 1939, some 120,000 British ex-servicemen had received final awards for primary psychiatric disability or were still drawing pensions – about 15% of all pensioned disabilities – and another 44,000 or so were getting pensions for soldiers heart or Effort Syndrome. There is, though, much that statistics do not show, because in terms of psychiatric effects, pensioners were just the tip of a huge iceberg."War correspondent Philip Gibbs wrote: Something was wrong. They put on civilian clothes again and looked to their mothers and wives very much like the young men who had gone to business in the peaceful days before August 1914. But they had not come back the same men. Something had altered in them. They were subject to sudden moods, and queer tempers, fits of profound depression alternating with a restless desire for pleasure. Many were easily moved to passion where they lost control of themselves, many were bitter in their speech, violent in opinion, frightening. One British writer between the wars wrote: There should be no excuse given for the establishment of a belief that a functional nervous disability constitutes a right to compensation. This is hard saying. It may seem cruel that those whose sufferings are real, whose illness has been brought on by enemy action and very likely in the course of patriotic service, should be treated with such apparent callousness. But there can be no doubt that in an overwhelming proportion of cases, these patients succumb to shock because they get something out of it. To give them this reward is not ultimately a benefit to them because it encourages the weaker tendencies in their character. The nation cannot call on its citizens for courage and sacrifice and, at the same time, state by implication that an unconscious cowardice or an unconscious dishonesty will be rewarded. World War II American At the outbreak of World War II, most in the United States military had forgotten the treatment lessons of World War I. Screening of applicants was initially rigorous, but experience eventually showed it to lack great predictive power. The US entered the war in December 1941. Only in November 1943 was a psychiatrist added to the table of organization of each division, and this policy was not implemented in the Mediterranean Theater of Operations until March 1944. By 1943, the US Army was using the term "exhaustion" as the initial diagnosis of psychiatric cases, and the general principles of military psychiatry were being used. General Pattons slapping incident was in part the spur to institute forward treatment for the Italian invasion of September 1943. The importance of unit cohesion and membership of a group as a protective factor emerged. John Appel found that the average American infantryman in Italy was "worn out" in 200 to 240 days and concluded that the American soldier "fights for his buddies or because his self respect wont let him quit". After several months in combat, the soldier lacked reasons to continue to fight because he had proven his bravery in battle and was no longer with most of the fellow soldiers he trained with. Appel helped implement a 180-day limit for soldiers in active combat and suggested that the war be made more meaningful, emphasizing their enemies plans to conquer the United States, encouraging soldiers to fight to prevent what they had seen happen in other countries happen to their families. Other psychiatrists believed that letters from home discouraged soldiers by increasing nostalgia and needlessly mentioning problems soldiers could not solve. William Menninger said after the war, "It might have been wise to have had a nation-wide educational course in letter writing to soldiers", and Edward Strecker criticized "moms" (as opposed to mothers) who, after failing to "wean" their sons, damaged morale through letters.Airmen flew far more often in the Southwest Pacific than in Europe, and although rest time in Australia was scheduled, there was no fixed number of missions that would produce transfer out of combat, as was the case in Europe. Coupled with the monotonous, hot, sickly environment, the result was bad morale that jaded veterans quickly passed along to newcomers. After a few months, epidemics of combat fatigue would drastically reduce the efficiency of units. Flight surgeons reported that the men who had been at jungle airfields longest were in bad shape: Many have chronic dysentery or other disease, and almost all show chronic fatigue states. … They appear listless, unkempt, careless, and apathetic with almost mask-like facial expression. Speech is slow, thought content is poor, they complain of chronic headaches, insomnia, memory defect, feel forgotten, worry about themselves, are afraid of new assignments, have no sense of responsibility, and are hopeless about the future. British Unlike the Americans, the British leaders firmly held the lessons of World War I. It was estimated that aerial bombardment would kill up to 35,000 a day, but the Blitz killed only 40,000 in total. The expected torrent of civilian mental breakdown did not occur. The Government turned to World War I doctors for advice on those who did have problems. The PIE principles were generally used. However, in the British Army, since most of the World War I doctors were too old for the job, young, analytically trained psychiatrists were employed. Army doctors "appeared to have no conception of breakdown in war and its treatment, though many of them had served in the 1914–1918 war." The first Middle East Force psychiatric hospital was set up in 1942. With D-Day for the first month there was a policy of holding casualties for only 48 hours before they were sent back over the Channel. This went firmly against the expectancy principle of PIE.Appel believed that British soldiers were able to continue to fight almost twice as long as their American counterparts because the British had better rotation schedules and because they, unlike the Americans, "fight for survival" – for the British soldiers, the threat from the Axis powers was much more real, given Britains proximity to mainland Europe, and the fact that Germany was concurrently conducting air raids and bombarding British industrial cities. Like the Americans, British doctors believed that letters from home often needlessly damaged soldiers morale. Canadian The Canadian Army recognized combat stress reaction as "Battle Exhaustion" during the Second World War and classified it as a separate type of combat wound. Historian Terry Copp has written extensively on the subject. In Normandy, "The infantry units engaged in the battle also experienced a rapid rise in the number of battle exhaustion cases with several hundred men evacuated due to the stress of combat. Regimental Medical Officers were learning that neither elaborate selection methods nor extensive training could prevent a considerable number of combat soldiers from breaking down." Germans In his history of the pre-Nazi Freikorps paramilitary organizations, Vanguard of Nazism, historian Robert G. L. Waite describes some of the emotional effects of World War I on German troops, and refers to a phrase he attributes to Göring: men who could not become "de-brutalized".In an interview, Dr Rudolf Brickenstein stated that: ... he believed that there were no important problems due to stress breakdown since it was prevented by the high quality of leadership. But, he added, that if a soldier did break down and could not continue fighting, it was a leadership problem, not one for medical personnel or psychiatrists. Breakdown (he said) usually took the form of unwillingness to fight or cowardice. However, as World War II progressed there was a profound rise in stress casualties from 1% of hospitalizations in 1935 to 6% in 1942. Another German psychiatrist reported after the war that during the last two years, about a third of all hospitalizations at Ensen were due to war neurosis. It is probable that there was both less of a true problem and less perception of a problem. Finns The Finnish attitudes to "war neurosis" were especially tough. Psychiatrist Harry Federley, who was the head of the Military Medicine, considered shell shock as a sign of weak character and lack of moral fibre. His treatment for war neurosis was simple: the patients were to be bullied and harassed until they returned to front line service.Earlier, during the Winter War, several Finnish machine gun operators on the Karelian Isthmus theatre became mentally unstable after repelling several unsuccessful Soviet human wave assaults on fortified Finnish positions. Post-World War II developments Simplicity was added to the PIE principles by the Israelis: in their view, treatment should be brief, supportive, and could be provided by those without sophisticated training. Peacekeeping stresses Peacekeeping provides its own stresses because its emphasis on rules of engagement contains the roles for which soldiers are trained. Causes include witnessing or experiencing the following: Constant tension and threat of conflict. Threat of land mines and booby traps. Close contact with severely injured and dead people. Deliberate maltreatment and atrocities, possibly involving civilians. Cultural issues. Separation and home issues. Risk of disease including HIV. Threat of exposure to toxic agents. Mission problems. Return to service. Pathophysiology SNS activation Many of the symptoms initially experienced by people with CSR are effects of an extended activation of the human bodys fight-or-flight response. The fight-or-flight response involves a general sympathetic nervous system discharge in reaction to a perceived stressor and prepares the body to fight or run from the threat causing the stress. Catecholamine hormones, such as adrenaline or noradrenaline, facilitate immediate physical reactions associated with a preparation for violent muscular action. Although the flight-or-fight-response normally ends with the removal of the threat, the constant mortal danger in combat zones likewise constantly and acutely stresses soldiers. General adaptation syndrome The process whereby the human body responds to extended stress is known as general adaptation syndrome (GAS). After the initial fight-or-flight response, the body becomes more resistant to stress in an attempt to dampen the sympathetic nervous response and return to homeostasis. During this period of resistance, physical and mental symptoms of CSR may be drastically reduced as the body attempts to cope with the stress. Long combat involvement, however, may keep the body from homeostasis and thereby deplete its resources and render it unable to normally function, sending it into the third stage of GAS: exhaustion. Sympathetic nervous activation remains in the exhaustion phase and reactions to stress are markedly sensitized as fight-or-flight symptoms return. If the body remains in a state of stress, then such more severe symptoms of CSR as cardiovascular and digestive involvement may present themselves. Extended exhaustion can permanently damage the body. Treatment 7 Rs The British Army treated Operational Stress Reaction according to the 7 Rs: Recognition – identify that the individual has an Operational Stress Reaction Respite – provide a short period of relief from the front line Rest – allow rest and recovery Recall – give the individual the chance to recall and discuss the experiences that have led to the reaction Reassurance – inform them that their reaction is normal and they will recover Rehabilitation – improve the physical and mental health of the patient until they no longer show symptoms Return – allow the soldier to return to their unit BICEPS Modern front-line combat stress treatment techniques are designed to mimic the historically used PIE techniques with some modification. BICEPS is the current treatment route employed by the U.S. military and stresses differential treatment by the severity of CSR symptoms present in the service member. BICEPS is employed as a means to treat CSR symptoms and return soldiers quickly to combat. The following subsections on the BICEPS program are adapted from the USMC combat stress handbook: Brevity Critical Event Debriefing should take 2 to 3 hours. Initial rest and replenishment at medical CSC (Combat Stress Control) facilities should last no more than 3 or 4 days. Those requiring further treatment are moved to the next level of care. Since many require no further treatment, military commanders expect their service members to return to duty rapidly. Immediacy CSC should be done as soon as possible when operations permit. Intervention is provided as soon as symptoms appear. Centrality/Contact Service members requiring observation or care beyond the unit level are evacuated to facilities in close proximity to, but separate from the medical or surgical patients at the BAS, surgical support company in a central location (Marines) or forward support/division support or area support medical companies (Army) nearest the service members unit. It is best to send service members who cannot continue their mission and require more extensive respite to a central facility other than a hospital, unless no other alternative is possible. The service member must be encouraged to continue to think of themselves as a war fighter, rather than a patient or a sick person. The chain of command remains directly involved in the service members recovery and return to duty. The CSC team coordinates with the units leaders to learn whether the over-stressed individual was a good performer prior to the combat stress reaction, or whether they were always a marginal or problem performer whom the team would rather see replaced than returned. Whenever possible, representatives of the unit, or messages from the unit, tell the casualty that they are needed and wanted back. The CSC team coordinates with the unit leaders, through unit medical personnel or chaplains, any special advice on how to assure quick reintegration when the service member returns to their unit. Expectancy The individual is explicitly told that he is reacting normally to extreme stress and is expected to recover and return to full duty in a few hours or days. A military leader is extremely effective in this area of treatment. Of all the things said to a service member experiencing combat stress, the words of his small-unit leader have the greatest impact due to the positive bonding process that occurs during combat. Simple statements from the small-unit leader to the service member that he is reacting normally to combat stress and is expected back soon have positive impact. Small-unit leaders should tell service members that their comrades need and expect them to return. When they do return, the unit treats them as every other service member and expects them to perform well. Service members suffering and recovering from combat stress disorder are no more likely to become overloaded again than are those who have not yet been overloaded. In fact, they are less likely to become overloaded than inexperienced replacements. Proximity In mobile war requiring rapid and frequent movement, treatment of many combat stress cases takes place at various battalion or regimental headquarters or logistical units, on light duty, rather than in medical units, whenever possible. This is a key factor and another area where the small-unit leader helps in the treatment. CSC and follow-up care for combat stress casualties are held as close as possible to and maintain close association with the members unit, and are an integral part of the entire healing process. A visit from a member of the individuals unit during restoration is effective in keeping a bond with the organization. A service member experiencing combat stress reaction is having a crisis, and there are two basic elements to that crisis working in opposite directions. On the one hand, the service member is driven by a strong desire to seek safety and to get out of an intolerable environment. On the other hand, the service member does not want to let their comrades down. They want to return to their unit. If a service member starts to lose contact with their unit when he enters treatment, the impulse to get out of the war and return to safety takes over. They feel that theyve failed their comrades who have already rejected them as unworthy. The potential is for the service member to become more and more emotionally invested in keeping their symptoms so they can stay in a safe environment. Much of this is done outside the service members conscious awareness, but the result is the same. The more out of touch the service member is with their unit, the less likely they will recover. They are more likely to develop a chronic psychiatric illness and get evacuated from the war. Simplicity Treatment is kept simple. CSC is not therapy. Psychotherapy is not done. The goal is to rapidly restore the service members coping skills so that he functions and returns to duty again. Sleep, food, water, hygiene, encouragement, work details, and confidence-restoring talk are often all that is needed to restore a service member to full operational readiness. This can be done in units in reserve positions, logistical units or at medical companies. Every effort is made to reinforce service members identity. They are required to wear their uniforms and to keep their helmets, equipment, chemical protective gear, and flak jackets with them. When possible, they are allowed to keep their weapons after the weapons have been cleared. They may serve on guard duty or as members of a standby quick reaction force. Predeployment preparation Screening Historically, screening programs that have attempted to preclude soldiers exhibiting personality traits thought to predispose them to CSR have been a total failure. Part of this failure stems from the inability to base CSR morbidity on one or two personality traits. Full psychological work-ups are expensive and inconclusive, while pen and paper tests are ineffective and easily faked. In addition, studies conducted following WWII screening programs showed that psychological disorders present during military training did not accurately predict stress disorders during combat. Cohesion While it is difficult to measure the effectiveness of such a subjective term, soldiers who reported in a WWII study that they had a "higher than average" sense of camaraderie and pride in their unit were more likely to report themselves ready for combat and less likely to develop CSR or other stress disorders. Soldiers with a "lower than average" sense of cohesion with their unit were more susceptible to stress illness. Training Stress exposure training or SET is a common component of most modern military training. There are three steps to an effective stress exposure program. Providing knowledge of the stress environmentSoldiers with a knowledge of both the emotional and physical signs and symptoms of CSR are much less likely to have a critical event that reduces them below fighting capability. Instrumental information, such as breathing exercises that can reduce stress and suggestions not to look at the faces of enemy dead, is also effective at reducing the chance of a breakdown. Skills acquisitionCognitive control strategies can be taught to soldiers to help them recognize stressful and situationally detrimental thoughts and repress those thoughts in combat situations. Such skills have been shown to reduce anxiety and improve task performance. Confidence building through application and practiceSoldiers who feel confident in their own abilities and those of their squad are far less likely to develop combat stress reaction. Training in stressful conditions that mimic those of an actual combat situation builds confidence in the abilities of themselves and the squad. As this training can actually induce some of the stress symptoms it seeks to prevent, stress levels should be increased incrementally as to allow the soldiers time to adapt. Prognosis Figures from the 1982 Lebanon war showed that with proximal treatment, 90% of CSR casualties returned to their unit, usually within 72 hours. With rearward treatment, only 40% returned to their unit. It was also found that treatment efficacy went up with the application of a variety of front line treatment principles versus just one treatment. In Korea, similar statistics were seen, with 85% of US battle fatigue casualties returned to duty within three days and 10% returned to limited duties after several weeks.Though these numbers seem to promote the claims that proximal PIE or BICEPS treatment is generally effective at reducing the effects of combat stress reaction, other data suggests that long term PTSD effects may result from the hasty return of affected individuals to combat. Both PIE and BICEPS are meant to return as many soldiers as possible to combat, and may actually have adverse effects on the long-term health of service members who are rapidly returned to the front-line after combat stress control treatment. Although the PIE principles were used extensively in the Vietnam War, the post traumatic stress disorder lifetime rate for Vietnam veterans was 30% in a 1989 US study and 21% in a 1996 Australian study. In a study of Israeli Veterans of the 1973 Yom Kippur War, 37% of veterans diagnosed with CSR during combat were later diagnosed with PTSD, compared with 14% of control veterans. Controversy There is significant controversy with the PIE and BICEPS principles. Throughout a number of wars, but notably during the Vietnam War, there has been a conflict among doctors about sending distressed soldiers back to combat. During the Vietnam War this reached a peak with much discussion about the ethics of this process. Proponents of the PIE and BICEPS principles argue that it leads to a reduction of long-term disability but opponents argue that combat stress reactions lead to long-term problems such as post-traumatic stress disorder. The use of psychiatric drugs to treat people with CSR has also attracted criticism, as some military psychiatrists have come to question the efficacy of such drugs on the long-term health of veterans. Concerns have been expressed as to the effect of pharmaceutical treatment on an already elevated substance abuse rate among former people with CSR.Recent research has caused an increasing number of scientists to believe that there may be a physical (i.e., neurocerebral damage) rather than psychological basis for blast trauma. As traumatic brain injury and combat stress reaction have very different causes yet result in similar neurologic symptoms, researchers emphasize the need for greater diagnostic care. See also Acute stress disorder Eye movement desensitization and reprocessing (modern treatment) Lack of Moral Fibre Shell shock Social alienation – among returning war veterans References Further reading West, Rebecca (1918). The Return of the Soldier. Garden City, NY: Garden City Pub. Co. Woolf, Virginia (1925). Mrs Dalloway. Barker, Pat (1991). Regeneration. Dutton. ISBN 978-0525934271. Holden, Wendy (1998). Shell Shock. (Channel 4 Books). Grabenhorst, Georg (1928). Zero Hour. Roth, Joseph (1924). Die Rebellion. A Review on the Disarm Doctumentary Corns, Cathryn and Hughes-Wilson, John (2001) Blindfold and Alone – British Military Executions in the Great War (Cassell) Lamprecht, Friedhelm and Sack, Martin, "Posttraumatic Stress Disorder Revisited" Dispatches: Lessons learned for Soldiers; Stress Injury and Operational Deployments, The Army Lessons Learned Centre, Canadian Forces Base Kingston, Vol. 10, No. 1, February 2004. Tyquin, M. Madness and the Military: Australias Experience in the Great War. AMHP, Sydney, 2006. External links Glossary of Traumatology DCoE National Center for Telehealth and Technology Mortar attacks becoming routine for troops in Afghanistan A Matter of Duty: The Continuing War Against PTSD Documentary produced by the Maine Public Broadcasting Network

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I've come across the term 'Alcohol withdrawal syndrome' in a medical context, but I'm not sure what it means. Can you clarify?

Alcohol withdrawal syndrome (AWS) is a set of symptoms that can occur following a reduction in alcohol use after a period of excessive use. Symptoms typically include anxiety, shakiness, sweating, vomiting, fast heart rate, and a mild fever. More severe symptoms may include seizures, hallucinations, and delirium tremens (DTs). Symptoms typically begin around six hours following the last drink, are worst at 24 to 72 hours, and improve by seven days.Alcohol withdrawal may occur in those who are alcohol dependent. This may occur following a planned or unplanned decrease in alcohol intake. The underlying mechanism involves a decreased responsiveness of GABA receptors in the brain. The withdrawal process is typically followed using the Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-Ar).The typical treatment of alcohol withdrawal is with benzodiazepines such as chlordiazepoxide or diazepam. Often the amounts given are based on a persons symptoms. Thiamine is recommended routinely. Electrolyte problems and low blood sugar should also be treated. Early treatment improves outcomes.In the Western world about 15% of people have problems with alcoholism at some point in time. Alcohol depresses the central nervous system, slowing cerebral messaging and altering the way signals are sent and received. Progressively larger amounts of alcohol are needed to achieve the same physical and emotional results. The drinker eventually must consume alcohol just to avoid the physical cravings and withdrawal symptoms. About half of people with alcoholism will develop withdrawal symptoms upon reducing their use, with four percent developing severe symptoms. Among those with severe symptoms up to 15% die. Symptoms of alcohol withdrawal have been described at least as early as 400 BC by Hippocrates. It is not believed to have become a widespread problem until the 1700s. Signs and symptoms Signs and symptoms of alcohol withdrawal occur primarily in the central nervous system. The severity of withdrawal can vary from mild symptoms such as insomnia, trembling, and anxiety to severe and life-threatening symptoms such as alcoholic hallucinosis, delirium tremens, and autonomic instability.Withdrawal usually begins 6 to 24 hours after the last drink. It can last for up to one week. To be classified as alcohol withdrawal syndrome, patients must exhibit at least two of the following symptoms: increased hand tremor, insomnia, nausea or vomiting, transient hallucinations (auditory, visual or tactile), psychomotor agitation, anxiety, generalized tonic–clonic seizures, and autonomic instability.The severity of symptoms is dictated by a number of factors, the most important of which are degree of alcohol intake, length of time the individual has been using alcohol, and previous history of alcohol withdrawal. Symptoms are also grouped together and classified: Alcohol hallucinosis: patients have transient visual, auditory, or tactile hallucinations, but are otherwise clear. Withdrawal seizures: seizures occur within 48 hours of alcohol cessations and occur either as a single generalized tonic-clonic seizure or as a brief episode of multiple seizures. Delirium tremens: hyperadrenergic state, disorientation, tremors, diaphoresis, impaired attention/consciousness, and visual and auditory hallucinations. Progression Six to 12 hours after the ingestion of the last drink, withdrawal symptoms such as shaking, headache, sweating, anxiety, nausea or vomiting may occur. Twelve to 24 hours after cessation, the condition may progress to such major symptoms as confusion, hallucinations (with awareness of reality), while less severe symptoms may persist and develop including tremor, agitation, hyperactivity and insomnia.At 12 to 48 hours following the last ethanol ingestion, the possibility of generalized tonic–clonic seizures should be anticipated, occurring in 3-5% of cases. Meanwhile, none of the earlier withdrawal symptoms will typically have abated. Seizures carry the risk of major complications and death for the alcoholic.Although the persons condition usually begins to improve after 48 hours, withdrawal symptoms sometimes continue to increase in severity and advance to the most severe stage of withdrawal, delirium tremens. This occurs in 5 to 20% of patients experiencing detoxification and one third of untreated cases, which is characterized by hallucinations that are indistinguishable from reality, severe confusion, seizures, high blood pressure, and fever that can persist anywhere from 4 to 12 days. Protracted withdrawal A protracted alcohol withdrawal syndrome occurs in many alcoholics when withdrawal symptoms continue beyond the acute withdrawal stage but usually at a subacute level of intensity and gradually decreasing with severity over time. This syndrome is sometimes referred to as the post-acute-withdrawal syndrome. Some withdrawal symptoms can linger for at least a year after discontinuation of alcohol. Symptoms can include a craving for alcohol, inability to feel pleasure from normally pleasurable things (known as anhedonia), clouding of sensorium, disorientation, nausea and vomiting or headache.Insomnia is a common protracted withdrawal symptom that persists after the acute withdrawal phase of alcohol. Insomnia has also been found to influence relapse rate. Studies have found that magnesium or trazodone can help treat the persisting withdrawal symptom of insomnia in recovering alcoholics. Insomnia can be difficult to treat in these individuals because many of the traditional sleep aids (e.g., benzodiazepine receptor agonists and barbiturate receptor agonists) work via a GABAA receptor mechanism and are cross-tolerant with alcohol. However, trazodone is not cross-tolerant with alcohol. The acute phase of the alcohol withdrawal syndrome can occasionally be protracted. Protracted delirium tremens has been reported in the medical literature as a possible but unusual feature of alcohol withdrawal. Pathophysiology Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system. Various adaptations occur such as changes in gene expression and down regulation of GABAA receptors. During acute alcohol withdrawal, changes also occur such as upregulation of alpha4 containing GABAA receptors and downregulation of alpha1 and alpha3 containing GABAA receptors. Neurochemical changes occurring during alcohol withdrawal can be minimized with drugs which are used for acute detoxification. With abstinence from alcohol and cross-tolerant drugs these changes in neurochemistry may gradually return towards normal. Adaptations to the NMDA system also occur as a result of repeated alcohol intoxication and are involved in the hyper-excitability of the central nervous system during the alcohol withdrawal syndrome. Homocysteine levels, which are elevated during chronic drinking, increase even further during the withdrawal state, and may result in excitotoxicity. Alterations in ECG (in particular an increase in QT interval) and EEG abnormalities (including abnormal quantified EEG) may occur during early withdrawal. Dysfunction of the hypothalamic–pituitary–adrenal axis and increased release of corticotropin-releasing hormone occur during both acute as well as protracted abstinence from alcohol and contribute to both acute and protracted withdrawal symptoms. Anhedonia/dysphoria symptoms, which can persist as part of a protracted withdrawal, may be due to dopamine underactivity. Kindling Kindling is a phenomenon where repeated alcohol detoxifications leads to an increased severity of the withdrawal syndrome. For example, binge drinkers may initially experience no withdrawal symptoms, but with each period of alcohol use followed by cessation, their withdrawal symptoms intensify in severity and may eventually result in full-blown delirium tremens with convulsive seizures. Alcoholics who experience seizures during detoxification are more likely to have had previous episodes of alcohol detoxification than patients who did not have seizures during withdrawal. In addition, people with previous withdrawal syndromes are more likely to have more medically complicated alcohol withdrawal symptoms.Kindling can cause complications and may increase the risk of relapse, alcohol-related brain damage and cognitive deficits. Chronic alcohol misuse and kindling via multiple alcohol withdrawals may lead to permanent alterations in the GABAA receptors. The mechanism behind kindling is sensitization of some neuronal systems and desensitization of other neuronal systems which leads to increasingly gross neurochemical imbalances. This in turn leads to more profound withdrawal symptoms including anxiety, convulsions and neurotoxicity.Binge drinking is associated with increased impulsivity, impairments in spatial working memory and impaired emotional learning. These adverse effects are believed to be due to the neurotoxic effects of repeated withdrawal from alcohol on aberrant neuronal plasticity and cortical damage. Repeated periods of acute intoxication followed by acute detoxification has profound effects on the brain and is associated with an increased risk of seizures as well as cognitive deficits. The effects on the brain are similar to those seen in alcoholics who have detoxified repeatedly but not as severe as in alcoholics who have no history of prior detox. Thus, the acute withdrawal syndrome appears to be the most important factor in causing damage or impairment to brain function. The brain regions most sensitive to harm from binge drinking are the amygdala and prefrontal cortex.People in adolescence who experience repeated withdrawals from binge drinking show impairments of long-term nonverbal memory. Alcoholics who have had two or more alcohol withdrawals show more frontal lobe cognitive dysfunction than those who have experienced one or no prior withdrawals. Kindling of neurons is the proposed cause of withdrawal-related cognitive damage. Kindling from repeated withdrawals leads to accumulating neuroadaptive changes. Kindling may also be the reason for cognitive damage seen in binge drinkers. Diagnosis Many hospitals use the Clinical Institute Withdrawal Assessment for Alcohol (CIWA) protocol in order to assess the level of withdrawal present and therefore the amount of medication needed. When overuse of alcohol is suspected but drinking history is unclear, testing for elevated values of carbohydrate-deficient transferrin or gammaglutamyl transferase can help make the diagnosis of alcohol overuse and dependence more clear. The CIWA has also been shortened (now called the CIWA-Ar), while retaining its validity and reliability, to help assess patients more efficiently due to the life-threatening nature of alcohol withdrawal.Other conditions that may present similarly include benzodiazepine withdrawal syndrome (a condition also mainly caused by GABAA receptor adaptation). Treatment Benzodiazepines are effective for the management of symptoms as well as the prevention of seizures. Certain vitamins are also an important part of the management of alcohol withdrawal syndrome. In those with severe symptoms inpatient care is often required. In those with lesser symptoms treatment at home may be possible with daily visits with a health care provider. Benzodiazepines Benzodiazepines are the most commonly used medication for the treatment of alcohol withdrawal and are generally safe and effective in suppressing symptoms of alcohol withdrawal. This class of medication is generally effective in symptoms control, but need to be used carefully. Although benzodiazepines have a long history of successfully treating and preventing withdrawal, there is no consensus on the ideal one to use. The most commonly used agents are long-acting benzodiazepines, such as chlordiazepoxide and diazepam. These are believed to be superior to other benzodiazepines for treatment of delirium and allow for longer periods between doses. However, benzodiazepines with intermediate half-lives like lorazepam may be safer in people with liver problems. Benzodiazepines showed a protective benefit against alcohol withdrawal symptoms, in particular seizure, compared to other common methods of treatment.The primary debate between use of long-acting benzodiazepines and short-acting is that of ease of use. Longer-acting drugs, such as diazepam, can be administered less frequently. However, evidence does exist that "symptom-triggered regimens" such as those used when treating with lorazepam, are as safe and effective, but have decreased treatment duration and medication quantity used.Although benzodiazepines are very effective at treating alcohol withdrawal, they should be carefully used. Benzodiazepines should only be used for brief periods in alcoholics who are not already dependent on them, as they share cross tolerance with alcohol. There is a risk of replacing an alcohol addiction with benzodiazepine dependence or adding another addiction. Furthermore, disrupted GABA benzodiazepine receptor function is part of alcohol dependence and chronic benzodiazepines may prevent full recovery from alcohol induced mental effects. The combination of benzodiazepines and alcohol can amplify the adverse psychological effects of each other causing enhanced depressive effects on mood and increase suicidal actions and are generally contraindicated except for alcohol withdrawal. Vitamins Alcoholics are often deficient in various nutrients, which can cause severe complications during alcohol withdrawal, such as the development of Wernicke syndrome. To help to prevent Wernicke syndrome, these individuals should be administered a multivitamin preparation with sufficient quantities of thiamine and folic acid. During alcohol withdrawal, the prophylactic administration of thiamine, folic acid, and pyridoxine intravenously is recommended before starting any carbohydrate-containing fluids or food. These vitamins are often combined into a banana bag for intravenous administration. Anticonvulsants Very limited evidence indicates that topiramate or pregabalin may be useful in the treatment of alcohol withdrawal syndrome. Limited evidence supports the use of gabapentin or carbamazepine for the treatment of mild or moderate alcohol withdrawal as the sole treatment or as combination therapy with other medications; however, gabapentin does not appear to be effective for treatment of severe alcohol withdrawal and is therefore not recommended for use in this setting. A 2010 Cochrane review similarly reported that the evidence to support the role of anticonvulsants over benzodiazepines in the treatment of alcohol withdrawal is not supported. Paraldehyde combined with chloral hydrate showed superiority over chlordiazepoxide with regard to life-threatening side effects and carbamazepine may have advantages for certain symptoms. Long term anticonvulsant medications are not usually recommended in those who have had prior seizures due to withdrawal. Prevention of further drinking There are three medications used to help prevent a return to drinking: naltrexone, acamprosate, and disulfiram. They are used after withdrawal has occurred. Other Clonidine may be used in combination with benzodiazepines to help some of the symptoms. No conclusions can be drawn concerning the efficacy or safety of baclofen for alcohol withdrawal syndrome due to the insufficiency and low quality of the evidence.Antipsychotics, such as haloperidol, are sometimes used in addition to benzodiazepines to control agitation or psychosis. Antipsychotics may potentially worsen alcohol withdrawal as they lower the seizure threshold. Clozapine, olanzapine, or low-potency phenothiazines (such as chlorpromazine) are particularly risky; if used, extreme caution is required.While intravenous ethanol could theoretically be used, evidence to support this use, at least in those who are very sick, is insufficient. Prognosis Failure to manage the alcohol withdrawal syndrome appropriately can lead to permanent brain damage or death. It has been proposed that brain damage due to alcohol withdrawal may be prevented by the administration of NMDA antagonists, calcium antagonists, and glucocorticoid antagonists. Substances impairing recovery Continued use of benzodiazepines may impair recovery from psychomotor and cognitive impairments from alcohol. Cigarette smoking may slow down or interfere with recovery of brain pathways in recovering alcoholics. References External links CIWA-Ar for Alcohol Withdrawal Alcohol Detox Guidelines Example Archived 19 August 2019 at the Wayback Machine

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

Can you demystify the medical term 'Sinecatechins' for me?

Sinecatechins (USAN, trade names Veregen and Polyphenon E) is a specific water extract of green tea leaves from Camellia sinensis that is the active ingredient in an ointment approved by the FDA in 2006 as a botanical drug to treat genital warts. Sinecatechins are mostly catechins, 55% of which is epigallocatechin gallate. It was the first botanical drug approved by the US FDA. == References ==

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I'm seeking clarification on the medical term 'Netherton syndrome.' Could you explain it?

Netherton syndrome is a severe, autosomal recessive form of ichthyosis associated with mutations in the SPINK5 gene. It is named after Earl W. Netherton (1910–1985), an American dermatologist who discovered it in 1958. Signs and symptoms Netherton syndrome is characterized by chronic skin inflammation, universal pruritus (itch), severe dehydration, and stunted growth. Patients with this disorder tend to have a hair shaft defect (trichorrhexis invaginata), also known as "bamboo hair". The disrupted skin barrier function in affected individuals also presents a high susceptibility to infection and allergy, leading to the development of scaly, reddish skin similar to atopic dermatitis. In severe cases, these atopic manifestations persist throughout the individuals life, and consequently post-natal mortality rates are high. In less severe cases, this develops into the milder ichthyosis linearis circumflexa.Netherton syndrome has recently been characterised as a primary immunodeficiency, which straddles the innate and acquired immune system, much as does Wiskott–Aldrich syndrome. A group of Netherton patients have been demonstrated to have altered immunoglobulin levels (typically high IgE and low to normal IgG) and immature natural killer cells. These Natural Killer cells have a reduced lytic function; which can be improved with regular infusions of immunoglobulin (see Treatment); although the mechanism for this is not clear.Patients are more prone than healthy people to infections of all types, especially recurrent skin infections with staphylococcus. They may have more severe infections; but are not as vulnerable to opportunistic pathogens as patients with true Natural Killer cell deficiency-type SCID. Cause Netherton syndrome is an autosomal recessive disorder associated with mutations in the SPINK5 gene, which encodes the serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI). These mutations result in a dysfunctional protein that has a reduced capacity to inhibit serine proteases expressed in the skin. Potential endogenous targets of LEKTI include KLK5, KLK7 and KLK14. These enzymes are involved in various aspects of epidermal remodelling, including desquamation, PAR-2 activation and degradation of lipid hydrolases, suggesting a potential mechanism for the development of atopic manifestations characteristic of Netherton syndrome.Disease severity is determined by the level of LEKTI expression and, consequently, serine protease activity. Complete SPINK5 gene deletions have been linked to severe cases, while mutations which induce alternate splicing or create premature stop codons may lead to varying levels of severity. Furthermore, LEKTI-knockout mice exhibit a phenotype similar to Netherton syndrome in humans. Diagnosis Treatment There is no known cure at the moment but there are several things that can be done to relieve the symptoms. Moisturising products are very helpful to minimize the scaling/cracking, and anti-infective treatments are useful when appropriate because the skin is very susceptible to infection. Extra protein in the diet during childhood is also beneficial, to replace that which is lost through the previously mentioned "leaky" skin.Steroid and retinoid products have been proven ineffective against Netherton syndrome, and may in fact make things worse for the affected individual.Intravenous immunoglobulin has become established as the treatment of choice in Nethertons syndrome. This therapy reduces infection; enables improvement and even resolution of the skin and hair abnormalities, and dramatically improves quality of life of the patients; although exactly how it achieves this is not known. Given this; it is possible that the reason Nethertons usually is not very severe at or shortly after birth is due to a protective effect of maternal antibodies; which cross the placenta but wane by four to six months. See also List of skin conditions References Yang T, Liang D, Koch PJ, Hohl D, Kheradmand F, Overbeek PA (October 2004). "Epidermal detachment, desmosomal dissociation, and destabilization of corneodesmosin in Spink5-/- mice". Genes Dev. 18 (19): 2354–8. doi:10.1101/gad.1232104. PMC 522985. PMID 15466487.{{cite journal}}: CS1 maint: multiple names: authors list (link) External links DermAtlas 1194463137

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I'm encountering the term 'Hyperglycinemia' in medical literature. What's its definition?

Hyperglycinemia may refer to one of two related inborn amino acid disorders that are characterized by elevated levels of glycine in the blood. Propionic acidemia, also known as "ketotic glycinemia" Glycine encephalopathy, also known as "non-ketotic hyperglycinemia"

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Please help me grasp the concept behind the medical term 'Pneumatosis intestinalis.'

Pneumatosis intestinalis (also called intestinal pneumatosis, pneumatosis cystoides intestinalis, pneumatosis coli, or intramural bowel gas) is pneumatosis of an intestine, that is, gas cysts in the bowel wall. As a radiological sign it is highly suggestive for necrotizing enterocolitis. This is in contrast to gas in the intestinal lumen (which is relieved by flatulence). In newborns, pneumatosis intestinalis is considered diagnostic for necrotizing enterocolitis, and the gas is produced by bacteria in the bowel wall. The pathogenesis of pneumatosis intestinalis is poorly understood and is likely multifactorial. PI itself is not a disease, but rather a clinical sign. In some cases, PI is an incidental finding, whereas in others, it portends a life-threatening intra-abdominal condition. Additional images References == External links ==

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I'd like to learn more about the medical term 'Barbiturate overdose.' Can you provide some details?

Barbiturate overdose is poisoning due to excessive doses of barbiturates. Symptoms typically include difficulty thinking, poor coordination, decreased level of consciousness, and a decreased effort to breathe (respiratory depression). Complications of overdose can include noncardiogenic pulmonary edema. If death occurs this is typically due to a lack of breathing.Barbiturate overdose may occur by accident or purposefully in an attempt to cause death. The toxic effects are additive to those of alcohol and benzodiazepines. The lethal dose varies with a persons tolerance and how the drug is taken. The effects of barbiturates occur via the GABA neurotransmitter. Exposure may be verified by testing the urine or blood.Treatment involves supporting a persons breathing and blood pressure. While there is no antidote, activated charcoal may be useful. Multiple doses of charcoal may be required. Hemodialysis may occasionally be considered. Urine alkalinisation has not been found to be useful. While once a common cause of overdose, barbiturates are now a rare cause. Mechanism Barbiturates increase the time that the chloride pore of the GABAA receptor is opened, thereby increasing the efficacy of GABA. In contrast, benzodiazepines increase the frequency with which the chloride pore is opened, thereby increasing GABAs potency. Treatment Treatment involves supporting a persons breathing and blood pressure. While there is no antidote, activated charcoal may be useful. Multiple doses of charcoal may be required. Hemodialysis may occasionally be considered. Urine alkalinisation has not been found to be useful.If a person is drowsy but awake and can swallow and breathe without difficulty, the treatment can be as simple as monitoring the person closely. If the person is not breathing, it may involve mechanical ventilation until the drug has worn off. Psychiatric consult is generally recommended. Notable cases People who are known to have died by suicide from barbiturate overdose include, Gillian Bennett, Charles Boyer, Ruan Lingyu, Victor Folke Nelson, Dalida, Jeannine "The Singing Nun" Deckers, Felix Hausdorff, Abbie Hoffman, Phyllis Hyman, Marilyn Monroe, C. P. Ramanujam, George Sanders, Jean Seberg, Lupe Vélez and the members of Heavens Gate cult. Others who have died as a result of barbiturate overdose include Pier Angeli, Brian Epstein, Judy Garland, Jimi Hendrix, Inger Stevens, Dinah Washington, Ellen Wilkinson, and Alan Wilson; in some cases these have been speculated to be suicides as well. Those who died of a combination of barbiturates and other drugs include Rainer Werner Fassbinder, Dorothy Kilgallen, Malcolm Lowry, Edie Sedgwick and Kenneth Williams. Dorothy Dandridge died of either an overdose or an unrelated embolism. Ingeborg Bachmann may have died of the consequences of barbiturate withdrawal (she was hospitalized with burns, the doctors treating her not being aware of her barbiturate addiction). Maurice Chevalier attempted suicide in March 1971 by swallowing a large amount of barbiturates and slitting his wrists. While he lived, he suffered severe organ damage as a result and died from multiple organ failure nine months later. Differential diagnosis The differential diagnosis should include intoxication by other substances with sedative effects, such as benzodiazepines, anticonvulsants (carbamazepine), alcohols (ethanol, ethylene glycol, methanol), opioids, carbon monoxide, sleep aids, and gamma-Hydroxybutyric acid (GHB – a known date rape drug). Natural disease that can result in disorientation may be in the differential, including hypoglycemia and myxedema coma. In the right setting, hypothermia should be ruled out. References == External links ==

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Can you demystify the medical term 'Sixth nerve palsy' for me?

Sixth nerve palsy, or abducens nerve palsy, is a disorder associated with dysfunction of cranial nerve VI (the abducens nerve), which is responsible for causing contraction of the lateral rectus muscle to abduct (i.e., turn out) the eye. The inability of an eye to turn outward, results in a convergent strabismus or esotropia of which the primary symptom is diplopia (commonly known as double vision) in which the two images appear side-by-side. Thus, the diplopia is horizontal and worse in the distance. Diplopia is also increased on looking to the affected side and is partly caused by overaction of the medial rectus on the unaffected side as it tries to provide the extra innervation to the affected lateral rectus. These two muscles are synergists or "yoke muscles" as both attempt to move the eye over to the left or right. The condition is commonly unilateral but can also occur bilaterally.The unilateral abducens nerve palsy is the most common of the isolated ocular motor nerve palsies. Signs and symptoms The nerve dysfunction induces esotropia, a convergent squint on distance fixation. On near fixation the affected individual may have only a latent deviation and be able to maintain binocularity or have an esotropia of a smaller size. Patients sometimes adopt a face turned towards the side of the affected eye, moving the eye away from the field of action of the affected lateral rectus muscle, with the aim of controlling diplopia and maintaining binocular vision. Diplopia is typically experienced by adults with VI nerve palsies, but children with the condition may not experience diplopia due to suppression. The neuroplasticity present in childhood allows the child to switch off the information coming from one eye (in this case the esotropic eye), thus relieving any diplopic symptoms. Whilst this is a positive adaptation in the short term, in the long term it can lead to a lack of appropriate development of the visual cortex giving rise to permanent visual loss in the suppressed eye; a condition known as amblyopia or Lazy eye. Cause Because the nerve emerges near the bottom of the brain, it is often the first nerve compressed when there is any rise in intracranial pressure. Different presentations of the condition, or associations with other conditions, can help to localize the site of the lesion along the VIth cranial nerve pathway. The most common causes of VIth nerve palsy in adults are: More common: Vasculopathic (diabetes, hypertension, atherosclerosis), trauma, idiopathic. Less common: Increased intracranial pressure, giant cell arteritis, cavernous sinus mass (e.g. meningioma, Brain stem Glioblastoma aneurysm, metastasis), multiple sclerosis, sarcoidosis/vasculitis, postmyelography, lumbar puncture, stroke (usually not isolated), Chiari Malformation, hydrocephalus, intracranial hypertension, tuberculosis meningitis.In children, Harley reports typical causes as traumatic, neoplastic (most commonly brainstem glioma), as well as idiopathic. Sixth nerve palsy causes the eyes to deviate inward (see: Pathophysiology of strabismus). Vallee et al. report that benign and rapidly recovering isolated VIth nerve palsy can occur in childhood, sometimes precipitated by ear, nose and throat infections. Pathophysiology The pathophysiological mechanism of sixth nerve palsy with increased intracranial pressure has traditionally been said to be stretching of the nerve in its long intracranial course, or compression against the petrous ligament or the ridge of the petrous temporal bone. Collier, however, was "unable to accept this explanation", his view being that since the sixth nerve emerges straight forward from the brain stem, whereas other cranial nerves emerge obliquely or transversely, it is more liable to the mechanical effects of backward brain stem displacement by intracranial space occupying lesions. Brainstem Isolated lesions of the VI nerve nucleus will not give rise to an isolated VIth nerve palsy because paramedian pontine reticular formation fibers pass through the nucleus to the opposite IIIrd nerve nucleus. Thus, a nuclear lesion will give rise to an ipsilateral gaze palsy. In addition, fibers of the seventh cranial nerve wrap around the VIth nerve nucleus, and, if this is also affected, a VIth nerve palsy with ipsilateral facial palsy will result. In Millard–Gubler syndrome, a unilateral softening of the brain tissue arising from obstruction of the blood vessels of the pons involving sixth and seventh cranial nerves and the corticospinal tract, the VIth nerve palsy and ipsilateral facial paresis occur with a contralateral hemiparesis. Fovilles syndrome can also arise as a result of brainstem lesions which affect Vth, VIth and VIIth cranial nerves. Subarachnoid space As the VIth nerve passes through the subarachnoid space it lies adjacent to anterior inferior and posterior inferior cerebellar and basilar arteries and is therefore vulnerable to compression against the clivus. Typically palsies caused in this way will be associated with signs and symptoms of headache and/or a rise in ICP. Petrous apex The nerve passes adjacent to the mastoid sinus and is vulnerable to mastoiditis, leading to inflammation of the meninges, which can give rise to Gradenigos syndrome. This condition results in a VIth nerve palsy with an associated reduction in hearing ipsilaterally, plus facial pain and paralysis, and photophobia. Similar symptoms can also occur secondary to petrous fractures or to nasopharyngeal tumours. Cavernous sinus/Superior orbital fissure The nerve runs in the sinus body adjacent to the internal carotid artery and oculo-sympathetic fibres responsible for pupil control, thus, lesions here might be associated with pupillary dysfunctions such as Horners syndrome. In addition, III, IV, V1, and V2 involvement might also indicate a sinus lesion as all run toward the orbit in the sinus wall. Lesions in this area can arise as a result of vascular problems, inflammation, metastatic carcinomas and primary meningiomas. Orbit The VIth nerves course is short and lesions in the orbit rarely give rise to isolated VIth nerve palsies, but more typically involve one or more of the other extraocular muscle groups. Diagnosis Differential diagnoses Differential diagnosis is rarely difficult in adults. Onset is typically sudden with symptoms of horizontal diplopia. Limitations of eye movements are confined to abduction of the affected eye (or abduction of both eyes if bilateral) and the size of the resulting convergent squint or esotropia is always larger on distance fixation - where the lateral recti are more active - than on near fixation - where the medial recti are dominant. Abduction limitations that mimic VIth nerve palsy may result secondary to surgery, to trauma or as a result of other conditions such as myasthenia gravis or thyroid eye disease. In children, differential diagnosis is more difficult because of the problems inherent in getting infants to cooperate with a full eye movement investigation. Possible alternative diagnosis for an abduction deficit would include: 1. Mobius syndrome - a rare congenital disorder in which both VIth and VIIth nerves are bilaterally affected giving rise to a typically expressionless face. 2. Duane syndrome - A condition in which both abduction and adduction are affected arising as a result of partial innervation of the lateral rectus by branches from the IIIrd oculomotor cranial nerve. 3. Cross fixation which develops in the presence of infantile esotropia or nystagmus blockage syndrome and results in habitual weakness of lateral recti. 4. Iatrogenic injury. Abducens nerve palsy is also known to occur with halo orthosis placement. The resultant palsy is identified through loss of lateral gaze after application of the orthosis and is the most common cranial nerve injury associated with this device. Management The first aims of management should be to identify and treat the cause of the condition, where this is possible, and to relieve the patients symptoms, where present. In children, who rarely appreciate diplopia, the aim will be to maintain binocular vision and, thus, promote proper visual development.Thereafter, a period of observation of around 6 months is appropriate before any further intervention, as some palsies will recover without the need for surgery. Symptom relief and/or binocular vision maintenance This is most commonly achieved through the use of fresnel prisms. These slim flexible plastic prisms can be attached to the patients glasses, or to plano glasses if the patient has no refractive error, and serve to compensate for the inward misalignment of the affected eye. Unfortunately, the prism only correct for a fixed degree of misalignment and, because the affected individuals degree of misalignment will vary depending upon their direction of gaze, they may still experience diplopia when looking to the affected side. The prisms are available in different strengths and the most appropriate one can be selected for each patient. However, in patients with large deviations, the thickness of the prism required may reduce vision so much that binocularity is not achievable. In such cases it may be more appropriate simply to occlude one eye temporarily. Occlusion would never be used in infants though both because of the risk of inducing stimulus deprivation amblyopia and because they do not experience diplopia.Other management options at this initial stage include the use of botulinum toxin, which is injected into the ipsilateral medial rectus (botulinum toxin therapy of strabismus). The use of BT serves a number of purposes. Firstly, it helps to prevent the contracture of the medial rectus which might result from its acting unopposed for a long period. Secondly, by reducing the size of the deviation temporarily it might allow prismatic correction to be used where this was not previously possible, and, thirdly, by removing the pull of the medial rectus it may serve to reveal whether the palsy is partial or complete by allowing any residual movement capability of the lateral rectus to operate. Thus, the toxin works both therapeutically, by helping to reduce symptoms and enhancing the prospects for fuller ocular movements post-operatively, and diagnostically, by helping to determine the type of operation most appropriate for each patient.A Cochrane Review on interventions for eye movement disorders due to acquired brain injury, last updated June 2017, identified one study of botulinum toxin for acute sixth nerve palsy. The Cochrane review authors judged this to be low-certainty evidence; the study was not masked and the estimate of effect was imprecise. Longer term management If adequate recovery has not occurred after the 6-month period (during which observation, prism management, occlusion, or botulinum toxin may be considered), surgical treatment is often recommended.If the residual esotropia is small, or if the patient is unfit or unwilling to have surgery, prisms can be incorporated into their glasses to provide more permanent symptom relief. When the deviation is too large for prismatic correction to be effective, permanent occlusion may be the only option for those unfit or unwilling to have surgery. Surgery The procedure chosen will depend upon the degree to which any function remains in the affected lateral rectus. Where there is complete paralysis, the preferred option is to perform vertical muscle transposition procedures such as Jensens, Hummelheims or whole muscle transposition, with the aim of using the functioning inferior and superior recti to gain some degree of abduction. An alternative approach is to operate on both the lateral and medial recti of the affected eye, with the aim of stabilising it at the midline, thus giving single vision straight ahead but potentially diplopia on both far left and right gaze. This procedure is often most appropriate for those with total paralysis who, because of other health problems, are at increased risk of the anterior segment ischaemia associated with complex multi-muscle transposition procedures. Where some function remains in the affected eye, the preferred procedure depends upon the degree of development of muscle sequelae. In a sixth nerve palsy one would expect that, over the 6 month observation period, most patients would show the following pattern of changes to their ocular muscle actions: firstly, an overaction of the medial rectus of the affected eye, then an overaction of the medial rectus of the contraletral eye and, finally, an underaction of the lateral rectus of the unaffected eye - something known as an inhibitional palsy. These changes serve to reduce the variation in the misalignment of the two eyes in different gaze positions (incomitance). Where this process has fully developed, the preferred option is a simple recession, or weakening, of the medial rectus of the affected eye, combined with a resection, or strengthening, of the lateral rectus of the same eye. However, where the inhibitional palsy of the contralateral lateral rectus has not developed, there will still be gross incomitance, with the disparity between the eye positions being markedly greater in the field of action of the affected muscle. In such cases recession of the medial rectus of the affected eye is accompanied by recession and/or posterior fixation (Fadenoperation) of the contraleral medial rectus.The same approaches are adopted bilaterally where both eyes have been affected. See also Congenital fourth nerve palsy References Further reading == External links ==

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I'm looking for a concise explanation of the medical term 'Rotavirus vaccine.'

Rotavirus vaccine is a vaccine used to protect against rotavirus infections, which are the leading cause of severe diarrhea among young children. The vaccines prevent 15–34% of severe diarrhea in the developing world and 37–96% of severe diarrhea in the developed world. The vaccines decrease the risk of death among young children due to diarrhea. Immunizing babies decreases rates of disease among older people and those who have not been immunized.The World Health Organization (WHO) recommends that rotavirus vaccine be included in national routine vaccinations programs, especially in areas where the disease is common. This should be done along with promoting breastfeeding, handwashing, clean water, and good sanitation. It is given by mouth and requires two or three doses. It should be given starting around six weeks of age.The vaccines are safe. This includes their use in people with HIV/AIDS. The vaccines are made from weakened rotavirus.The vaccine first became available in the United States in 2006. It is on the World Health Organizations List of Essential Medicines. As of 2013, there are two types of vaccine available globally, Rotarix and RotaTeq. Others are used in some countries. Medical uses Effectiveness A 2009 review estimated that vaccination against rotavirus would prevent about 45% of deaths due to rotavirus gastroenteritis, or about 228,000 deaths annually worldwide. At US$5 per dose, the estimated cost per life saved was $3,015, $9,951 and $11,296 in low-, lower-middle-, and upper-middle-income countries, respectively.Safety and efficacy trials in Africa and Asia found that the vaccines dramatically reduced severe disease among infants in developing countries, where a majority of rotavirus-related deaths occur. A 2019 Cochrane review concluded that RV1, RV5, and Rotavac vaccines are safe and are effective at preventing diarrhea.Rotavirus vaccines are licensed in more than 100 countries, and more than 80 countries have introduced routine rotavirus vaccination. The incidence and severity of rotavirus infections has declined significantly in countries that have acted on the recommendation to introduce the rotavirus vaccine. In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, the diarrheal disease death rates from rotavirus dropped by more than 65% among children age two and under during the 2009 rotavirus season. In Nicaragua, which in 2006 became the first developing country to introduce the rotavirus vaccine, investigators recorded a substantial impact, with rotavirus vaccine preventing 60% of cases against severe rotavirus and cutting emergency room visits in half. In the United States, vaccination has reduced rotavirus-related hospitalizations by as much as 86% since 2006. In April 2016, the World Health Organization released statistics for the period of 2000–2013, which showed developing countries that have introduced rotavirus vaccines experienced significant decreases in deaths and hospitalizations from rotavirus diarrhea after introduction.Additionally, the vaccines may also prevent illness in non-vaccinated children by limiting exposure through the number of circulating infections. A 2014 review of available clinical trial data from countries routinely using rotavirus vaccines in their national immunization programs found that rotavirus vaccines have reduced rotavirus hospitalizations by 49–92% and all-cause diarrhea hospitalizations by 17–55%. Schedule The World Health Organization recommends the first dose of vaccine be given right after six weeks of age. Types Rotarix Rotarix is a monovalent, human, live attenuated rotavirus vaccine containing one rotavirus strain of G1P[8] specificity. Rotarix is indicated for the prevention of rotavirus gastroenteritis caused by G1 and non-G1 types (G3, G4, and G9) when administered as a 2-dose series in infants and children. It was approved in Europe in 2006 and by the U.S. FDA in April 2008. It is administered by mouth. RotaTeq RotaTeq is a live, oral pentavalent vaccine that contains five rotavirus strains produced by reassortment. The rotavirus A parent strains of the reassortants were isolated from human and bovine hosts. Four reassortant rotaviruses express one of the outer capsid, VP7, proteins (serotypes G1, G2, G3, or G4) from the human rotavirus parent strain and the attachment protein VP4 (type P7) from the bovine rotavirus parent strain. The fifth reassortant virus expresses the attachment protein VP4, (type P1A), from the human rotavirus parent strain and the outer capsid protein VP7 (serotype G6) from the bovine rotavirus parent strain. In February 2006, the U.S. Food and Drug Administration approved RotaTeq for use in the United States. In August 2006, Health Canada approved RotaTeq for use in Canada. Merck worked with a range of partners including governmental and non-governmental organisations to develop and implement mechanisms for providing access to this vaccine in the developing world, an effort which was slated to come to an end in 2020. Rotavac Rotavac was licensed for use in India in 2014, and is manufactured by Bharat Biotech International Limited. It is a live attenuated, monovalent vaccine containing a G9P[11] human strain isolated from an Indian child. It is given by mouth in a three-dose series, four weeks apart, beginning at six weeks of age up until eight months of age. Rotavin-M1 Rotavin-M1 was licensed for use in Vietnam in 2007, and is manufactured by the Center for Research and Production of Vaccines. The vaccine contains a G1P[8] human rotavirus strain. Lanzhou lamb Lanzhou lamb rotavirus vaccine was licensed for use in China in 2000, and is manufactured by the Lanzhou Institute of Biological Products. It contains a G10P[12] lamb rotavirus strain. Rotasiil Rotasiil is a lyophilized pentavalent vaccine licensed for use in India in 2018. It contain human bovine reassortant strains of rotavirus serotypes G1, G2, G3, G4 and G9. This is worlds first thermostable vaccine which can be stored without refrigeration at or below 25 °C. Rotasiil is manufactured by the Serum Institute of India. History In 1998, a rotavirus vaccine (RotaShield, by Wyeth) was licensed for use in the United States. Clinical trials in the United States, Finland, and Venezuela had found it to be 80 to 100% effective at preventing severe diarrhea caused by rotavirus A, and researchers had detected no statistically significant serious adverse effects. The manufacturer of the vaccine, however, withdrew it from the market in 1999, after it was discovered that the vaccine may have contributed to an increased risk for intussusception, or bowel obstruction, in one of every 12,000 vaccinated infants. There then followed eight years of delay until rival manufacturers were able to introduce new vaccines that were shown to be more safe and effective in children: Rotarix by GlaxoSmithKline and RotaTeq by Merck. Both are taken orally and contain disabled live virus.The World Health Organization recommends that rotavirus vaccine be included in all national immunization schedules because the risk of intussusception following rotavirus vaccination remains very low compared with the benefits of preventing the impact of severe and deadly diarrhea. Society and culture More than 80 countries have introduced routine rotavirus vaccination, almost half with the support of Gavi, the Vaccine Alliance. In order to make rotavirus vaccines available, accessible, and affordable in all countries—particularly low- and middle-income countries in Africa and Asia where the majority of rotavirus deaths occur—international non-governmental organization PATH, the WHO, the U.S. Centers for Disease Control and Prevention (CDC), and Gavi have partnered with research institutions and governments to generate and disseminate evidence, lower prices, and accelerate introduction. These and other organizations continue to work to improve coverage and public health impact of rotavirus vaccination today. Temporary suspension in the US On March 22, 2010, the detection of DNA from porcine circovirus types 1 and 2 within RotaTeq and Rotarix prompted the FDA to suspend the use of rotavirus vaccines while conducting an investigation the finding of DNA from porcine circovirus-1 (PCV1) in the vaccine in collaboration with the 12 members of the Vaccines and Related Biological Products Advisory Committee (VRBPAC). On May 6, 2010, the FDA announced its decision to revoke the suspension, stating that porcine circovirus types 1 and 2 pose no safety risks in humans and concluded that health risks involved did not offset the benefits of the vaccination. In May 2010 the suspension of the Rotarix vaccine was lifted. Research Doctors Without Borders (MSF) developed a heat-stable version named BRV-PV. Phase 3 of the clinical trials were completed in Niger on December 31, 2020.The vaccine has been associated with lower rates of type 1 diabetes. References Further reading Cortese MM, Parashar UD (February 2009). "Prevention of rotavirus gastroenteritis among infants and children: recommendations of the Advisory Committee on Immunization Practices (ACIP)" (PDF). MMWR Recomm Rep. 58 (RR-2): 1–25. PMID 19194371. External links "Rotavirus Vaccine Information Statement". U.S. Centers for Disease Control and Prevention (CDC). 2019-10-25. Rotavirus, Vaccine Resource Library Rotavirus ROTA Council Rotavirus Vaccines at the US National Library of Medicine Medical Subject Headings (MeSH)

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Molybdenum deficiency'?

Molybdenum deficiency refers to the clinical consequences of inadequate supplies of molybdenum in the diet. The amount of molybdenum required is relatively small, and molybdenum deficiency usually does not occur in natural settings. However, it can occur in individuals receiving parenteral nutrition. Signs and symptoms Descriptions of human molybdenum deficiency are few. A patient receiving prolonged parenteral nutrition acquired a syndrome described as ‘acquired molybdenum deficiency.’ This syndrome, exacerbated by methionine administration, was characterized by high blood methionine, low blood uric acid, and low urinary uric acid and sulfate concentrations. The patient suffered mental disturbances that progressed to a coma. Pathological changes occurring in individuals with a genetic disease that results in a sulfite oxidase (a molybdoenzyme) deficiency include increased plasma and urine sulfite, sulfate, thiosulfate, S-sulfocysteine and taurine; seizures, and brain atrophy/lesions; dislocated lenses; and death at an early age.. Diagnosis Treatment 300 mcg Ammonium Molybdate per day can bring about recovery of “acquired molybdenum deficiency” [3] See also Molybdenum cofactor deficiency References Further reading == External links ==

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Could you provide a brief overview of 'Urticarial vasculitis' in a medical context?

Urticarial vasculitis (also known as "chronic urticaria as a manifestation of venulitis", "hypocomplementemic urticarial vasculitis syndrome", "hypocomplementemic vasculitis" and "unusual lupus-like syndrome") is a skin condition characterized by fixed urticarial lesions that appear histologically as a vasculitis.: 834 Mechanism Antibodies are usually raised against foreign proteins, such as those made by a replicating virus or invading bacterium. Virus or bacteria with antibodies opsonized or "stuck" to them highlight them to other cells of the immune system for clearance. Antibodies against self proteins are known as autoantibodies, and are not found in healthy individuals. These autoantibodies can be used to detect certain diseases. C1q C1q is an integral component within the complement pathway – a complicated cascade of protein interactions, culminating in an immune response against a broad variety of pathogens. The anti-C1q antibodies found in patients with hypocomplementemic urticarial vasculitis activate C1q, which instigates activation of the entire complement pathway. Consequently, levels of all complement proteins become low. Impaired classical complement pathway The complement pathway is composed of several subset pathways: the lectin/mannose pathway, alternative pathway and the classical pathway. All pathways culminate in the production of a C3 convertase, which catalyses C3 into its constitutive parts (better detailed here – classical complement pathway).In brief, the crucial role of C1q in the pathway is its importance as the first protein to start the complement cascade (which ends in the destruction of the invading bacteria or virus), and its ability to link the two important arms of the immune system – the innate immune system: a broad defence system; and the adaptive immune system: the strong immune response capable of remembering previous infections, allowing fast response against recurrent infections, meaning that people with a normal immune system dont continually catch the same cold or same strain of flu repeatedly.Case studies of individuals with HUV have also highlighted other potential complicating factors which it seems the anti-C1q antibodies play a role in. This can mean in some cases the deposition of large immune complexes in the kidney which cannot be cleared by the usual cells of the immune system (e.g. macrophages which are unable to bind the Fc portion of the C1q antibody), leading to further complications. This seems to be rare, but can occur when a pre-existing renal condition is apparent. Also, there has been some speculation as to an additional autoantibody against an inhibitor protein (in the complement pathway) named C1-inhibitor. The inhibition of C1-inhibitor leads to over-activation of the complement pathway and one protein that builds up controls angioedema (vessel – swelling), resulting in excess water building up under the skin (the weal appearance). Diagnosis A rare autoimmune disease characterized by recurrent urticaria (nettle rash), first described in the 1970s. There is no defined paradigm for the syndrome aetiology and severity in progression. Diagnosis is confirmed with the identification of at least two conditions from: venulitis on skin biopsy, arthritis, ocular inflammation, abdominal pain or positive C1q antibodies to immune complexes. It is this last category, anti-C1q antibodies, that all HUV patients test positive for. In vitro experiments and mouse models of the disease have not thoroughly determined the link between these antibodies and the disease, even though the link is so pronounced. Treatment Unfortunately there are no known specific therapies for HUV. The regime of prescription steroids and other immunosuppressive drugs aims to dampen the bodys production of anti-C1q antibodies. However, this again renders the individual immunocompromised. Popular culture Urticarial vasculitis is featured prominently in the 2010 documentary film Fat, Sick and Nearly Dead. The main character and narrator has the disease. See also Cutaneous small-vessel vasculitis List of cutaneous conditions References == External links ==

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I'm trying to understand 'Aztreonam' within a medical context. Could you shed some light on it?

Aztreonam, sold under the brand name Azactam among others, is an antibiotic used primarily to treat infections caused by gram-negative bacteria such as Pseudomonas aeruginosa. This may include bone infections, endometritis, intra abdominal infections, pneumonia, urinary tract infections, and sepsis. It is given by intravenous or intramuscular injection or by inhalation.Common side effects when given by injection include pain at the site of injection, vomiting, and rash. Common side effects when inhaled include wheezing, cough, and vomiting. Serious side effects include Clostridium difficile infection and allergic reactions including anaphylaxis. Those who are allergic to other β-lactam have a low rate of allergy to aztreonam. Use in pregnancy appears to be safe. It is in the monobactam family of medications. Aztreonam inhibits cell wall synthesis by blocking peptidoglycan crosslinking to cause bacterial death.Aztreonam was approved for medical use in the United States in 1986. It was removed from the World Health Organizations List of Essential Medicines in 2019. It is available as a generic medication. It is a manufactured version of a chemical from the bacterium Chromobacterium violaceum. Medical uses Nebulized forms of aztreonam are used to treat infections that are complications of cystic fibrosis and are approved for such use in Europe and the US; they are also used off-label for non-CF bronchiectasis, ventilator-associated pneumonia, chronic obstructive pulmonary disease, mycobacterial disease, and to treat infections in people who have received lung transplants.Aztreonam has strong activity against susceptible Gram-negative bacteria, including Pseudomonas aeruginosa. It is resistant to some beta-lactamases, but is inactivated by extended-spectrum beta-lactamases. It has no useful activity against Gram-positive bacteria or anaerobes. It is known to be effective against a wide range of bacteria including Citrobacter, Enterobacter, E. coli, Haemophilus, Klebsiella, Proteus, and Serratia species. The following represents minimum inhibitory concentration (MIC) susceptibility data for a few medically significant microorganisms. Staphylococcus aureus 8 - >128 μg/ml Staphylococcus epidermidis 8 - 32 μg/ml Streptococcus pyogenes 8 - ≥128 μg/mlSynergism between aztreonam and arbekacin or tobramycin against P. aeruginosa has been suggested. Spectrum of activity Acinetobacter anitratus, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis are generally susceptible to aztreonam, while some staphylococci, Staphylococcus aureus, Staphylococcus haemolyticus and Xanthomonas maltophilia are resistant to it. Furthermore, Aeromonas hydrophila, Citrobacter koseri (Citrobacter diversus), Pantoea agglomerans (Enterobacter agglomerans), Haemophilus spp. and Streptococcus pyogenes have developed resistance to aztreonam to varying degrees.Aztreonam can be safely used in patients with a penicillin or cephalosporin allergy (except for patients with a ceftazidime allergy as ceftazidime and aztreonam share a similar side chain). It is also frequently used as an alternative to aminoglycosides because is not ototoxic or nephrotoxic.Aztreonam use has been recently reconsidered for human infections sustained by metallo-beta-lactamase (MBL)-producing Gram-negative bacteria. In these circumstances aztreonam is combined with avibactam (ceftazidime/avibactam). The combination of aztreonam and avibactam has demonstrated to be active against 80% of MBL isolates reaching a clinical infection resolution in 80% of MBL-infected patients. Administration Aztreonam is poorly absorbed when given orally, so it must be administered as an intravenous or intramuscular injection (trade name Azactam), or inhaled (trade name Cayston) using an ultrasonic nebulizer. In the United States, the Food and Drug Administration (FDA) approved the inhalation form on 22 February 2010, for the suppression of P. aeruginosa infections in patients with cystic fibrosis. It received conditional approval for administration in Canada and the European Union in September 2009, and has been fully approved in Australia. Side effects Reported side effects include injection site reactions, rash, and rarely toxic epidermal necrolysis. Gastrointestinal side effects generally include diarrhea and nausea and vomiting. There may be drug-induced eosinophilia. Because of the unfused beta-lactam ring there is somewhat lower cross-reactivity between aztreonam and many other beta-lactam antibiotics, and it may be safe to administer aztreonam to many patients with hypersensitivity (allergies) to penicillins and nearly all cephalosporins. There is a much lower risk of cross-sensitivity between aztreonam and other beta-lactam antibiotics than within other beta-lactam antibiotics. However, there is a higher chance of cross-sensitivity if a person is specifically allergic to ceftazidime, a cephalosporin. Aztreonam exhibits cross-sensitivity with ceftazidime due to a similar side chain. Mechanism of action Aztreonam is similar in action to penicillin. It inhibits synthesis of the bacterial cell wall, by blocking peptidoglycan crosslinking. It has a very high affinity for penicillin-binding protein-3 and mild affinity for penicillin-binding protein-1a. Aztreonam binds the penicillin-binding proteins of Gram-positive and anaerobic bacteria very poorly and is largely ineffective against them. Aztreonam is bactericidal, but less so than some of the cephalosporins. References External links "Aztreonam". Drug Information Portal. U.S. National Library of Medicine.

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What is the significance of the term 'Trichotillomania' in the medical field?

Trichotillomania (TTM), also known as hair-pulling disorder or compulsive hair pulling, is a mental disorder characterized by a long-term urge that results in the pulling out of ones own hair. A brief positive feeling may occur as hair is removed. Efforts to stop pulling hair typically fail. Hair removal may occur anywhere; however, the head and around the eyes are most common. The hair pulling is to such a degree that it results in distress and hair loss can be seen.The disorder may run in families. It occurs more commonly in those with obsessive compulsive disorder. Episodes of pulling may be triggered by anxiety. People usually acknowledge that they pull their hair, and broken hairs may be seen on examination. Other conditions that may present similarly include body dysmorphic disorder; however, in that condition people remove hair to try to improve what they see as a problem in how they look.Treatment is typically with cognitive behavioral therapy. The medication clomipramine may also be helpful, as will keeping fingernails clipped. Trichotillomania is estimated to affect one to four percent of people. Trichotillomania most commonly begins in childhood or adolescence. Women are affected about 10 times more often than men. The name was created by François Henri Hallopeau in 1889, from the Greek θριξ/τριχ; thrix (meaning hair), along with τίλλειν; tíllein (meaning to pull), and μανία; mania (meaning madness). Signs and symptoms Trichotillomania is usually confined to one or two sites, but can involve multiple sites. The scalp is the most common pulling site, followed by the eyebrows, eyelashes, face, arms, and legs. Some less common areas include the pubic area, underarms, beard, and chest. The classic presentation is the "Friar Tuck" form of vertex and crown alopecia. Children are less likely to pull from areas other than the scalp.People with trichotillomania often pull only one hair at a time and these hair-pulling episodes can last for hours at a time. Trichotillomania can go into remission-like states where the individual may not experience the urge to "pull" for days, weeks, months, or even years.Individuals with trichotillomania exhibit hair of differing lengths; some are broken hairs with blunt ends, some new growth with tapered ends, some broken mid-shaft, or some uneven stubble. Scaling on the scalp is not present, overall hair density is normal, and a hair pull test is negative (the hair does not pull out easily). Hair is often pulled out leaving an unusual shape. Individuals with trichotillomania may be secretive or shameful of the hair pulling behavior.An additional psychological effect can be low self-esteem, often associated with being shunned by peers and the fear of socializing, due to appearance and negative attention they may receive. Some people with trichotillomania wear hats, wigs, false eyelashes, eyebrow pencil, or style their hair in an effort to avoid such attention. There seems to be a strong stress-related component. In low-stress environments, some exhibit no symptoms (known as "pulling") whatsoever. This "pulling" often resumes upon leaving this environment. Some individuals with trichotillomania may feel they are the only person with this problem due to low rates of reporting.For some people, trichotillomania is a mild problem, merely a frustration. But for many, embarrassment about hair pulling causes isolation and results in a great deal of emotional distress, placing them at risk for a co-occurring psychiatric disorder, such as a mood or anxiety disorder. Hair pulling can lead to tension and strained relationships with family members and friends. Family members may need professional help in coping with this problem.Other medical complications include infection, permanent loss of hair, repetitive stress injury, carpal tunnel syndrome, and gastrointestinal obstruction as a result of trichophagia. In trichophagia, people with trichotillomania also ingest the hair that they pull; in extreme (and rare) cases this can lead to a hair ball (trichobezoar). Rapunzel syndrome, an extreme form of trichobezoar in which the "tail" of the hair ball extends into the intestines, can be fatal if misdiagnosed.Environment is a large factor which affects hair pulling. Sedentary activities such as being in a relaxed environment are conducive to hair pulling. A common example of a sedentary activity promoting hair pulling is lying in a bed while trying to rest or fall asleep. An extreme example of automatic trichotillomania is found when some patients have been observed to pull their hair out while asleep. This is called sleep-isolated trichotillomania. Causes Anxiety, depression and obsessive–compulsive disorder are more frequently encountered in people with trichotillomania. Trichotillomania has a high overlap with post traumatic stress disorder, and some cases of trichotillomania may be triggered by stress. Another school of thought emphasizes hair pulling as addictive or negatively reinforcing, as it is associated with rising tension beforehand and relief afterward. A neurocognitive model — the notion that the basal ganglia play a role in habit formation and that the frontal lobes are critical for normally suppressing or inhibiting such habits — sees trichotillomania as a habit disorder.Abnormalities in the caudate nucleus are noted in OCD, but there is no evidence to support that these abnormalities can also be linked to trichotillomania. One study has shown that individuals with trichotillomania have decreased cerebellar volume. These findings suggest some differences between OCD and trichotillomania. There is a lack of structural MRI studies on trichotillomania. In several MRI studies that have been conducted, it has been found that people with trichotillomania have more gray matter in their brains than those who do not have the disorder.It is likely that multiple genes confer vulnerability to trichotillomania. One study identified mutations in the SLITRK1 gene. Diagnosis Patients may be ashamed or actively attempt to disguise their symptoms. This can make diagnosis difficult as symptoms are not always immediately obvious, or have been deliberately hidden to avoid disclosure. If the patient admits to hair pulling, diagnosis is not difficult; if patients deny hair pulling, a differential diagnosis must be pursued. The differential diagnosis will include evaluation for alopecia areata, iron deficiency, hypothyroidism, tinea capitis, traction alopecia, alopecia mucinosa, thallium poisoning, and loose anagen syndrome. In trichotillomania, a hair pull test is negative.A biopsy can be performed and may be helpful; it reveals traumatized hair follicles with perifollicular hemorrhage, fragmented hair in the dermis, empty follicles, and deformed hair shafts. Multiple catagen hairs are typically seen. An alternative technique to biopsy, particularly for children, is to shave a part of the involved area and observe for regrowth of normal hairs. Classification Trichotillomania is defined as a self-induced and recurrent loss of hair. It includes the criterion of an increasing sense of tension before pulling the hair and gratification or relief when pulling the hair. However, some people with trichotillomania do not endorse the inclusion of "rising tension and subsequent pleasure, gratification, or relief" as part of the criteria because many individuals with trichotillomania may not realize they are pulling their hair, and patients presenting for diagnosis may deny the criteria for tension prior to hair pulling or a sense of gratification after hair is pulled.Trichotillomania may lie on the obsessive-compulsive spectrum, also encompassing obsessive-compulsive disorder (OCD), body dysmorphic disorder (BDD), nail biting (onychophagia) and skin picking (dermatillomania), tic disorders and eating disorders. These conditions may share clinical features, genetic contributions, and possibly treatment response; however, differences between trichotillomania and OCD are present in symptoms, neural function and cognitive profile. In the sense that it is associated with irresistible urges to perform unwanted repetitive behavior, trichotillomania is akin to some of these conditions, and rates of trichotillomania among relatives of OCD patients is higher than expected by chance. However, differences between the disorder and OCD have been noted, including: differing peak ages at onset, rates of comorbidity, gender differences, and neural dysfunction and cognitive profile. When it occurs in early childhood, it can be regarded as a distinct clinical entity.Because trichotillomania can be present in multiple age groups, it is helpful in terms of prognosis and treatment to approach three distinct subgroups by age: preschool age children, preadolescents to young adults, and adults.In preschool age children, trichotillomania is considered benign. For these children, hair-pulling is considered either a means of exploration or something done subconsciously, similar to nail-biting and thumb-sucking, and almost never continues into further ages.The most common age of onset of trichotillomania is between ages 9 and 13. In this age range, trichotillomania is usually chronic, and continues into adulthood. Trichiotillomania that begins in adulthood most commonly arises from underlying psychiatric causes.Trichotillomania is often not a focused act, but rather hair pulling occurs in a "trance-like" state; hence, trichotillomania is subdivided into "automatic" versus "focused" hair pulling. Children are more often in the automatic, or unconscious, subtype and may not consciously remember pulling their hair. Other individuals may have focused, or conscious, rituals associated with hair pulling, including seeking specific types of hairs to pull, pulling until the hair feels "just right", or pulling in response to a specific sensation. Knowledge of the subtype is helpful in determining treatment strategies. Treatment Treatment is based on a persons age. Most pre-school age children outgrow the condition if it is managed conservatively. In young adults, establishing the diagnosis and raising awareness of the condition is an important reassurance for the family and patient. Non-pharmacological interventions, including behavior modification programs, may be considered; referrals to psychologists or psychiatrists may be considered when other interventions fail. When trichotillomania begins in adulthood, it is often associated with other mental disorders, and referral to a psychologist or psychiatrist for evaluation or treatment is considered best. The hair pulling may resolve when other conditions are treated. Psychotherapy Habit reversal training (HRT) has the highest rate of success in treating trichotillomania. HRT has also been shown to be a successful adjunct to medication as a way to treat trichotillomania. With HRT, the individual is trained to learn to recognize their impulse to pull and also teach them to redirect this impulse. In comparisons of behavioral versus pharmacologic treatment, cognitive behavioral therapy (including HRT) have shown significant improvement over medication alone. It has also proven effective in treating children. Biofeedback, cognitive-behavioral methods, and hypnosis may improve symptoms. Acceptance and commitment therapy (ACT) is also demonstrating promise in trichotillomania treatment. A systematic review from 2012 found tentative evidence for "movement decoupling". Medication The United States Food and Drug Administration (FDA) has not approved any medications for trichotillomania treatment.However, some medications have been used to treat trichotillomania, with mixed results. Treatment with clomipramine, a tricyclic antidepressant, was shown in a small double-blind study to improve symptoms, but results of other studies on clomipramine for treating trichotillomania have been inconsistent. Naltrexone may be a viable treatment. Fluoxetine and other selective serotonin reuptake inhibitors (SSRIs) have limited usefulness in treating trichotillomania, and can often have significant side effects. Behavioral therapy has proven more effective when compared to fluoxetine. There is little research on the effectiveness of behavioral therapy combined with medication, and robust evidence from high-quality studies is lacking. Acetylcysteine treatment stemmed from an understanding of glutamates role in regulation of impulse control.Different medications, depending on the individual, may increase hair pulling. Devices Technology can be used to augment habit reversal training or behavioral therapy. Several mobile apps exist to help log behavior and focus on treatment strategies. There are also wearable devices that track the position of a users hands. They produce sound or vibrating notifications so that users can track rates of these events over time. Prognosis When it occurs in early childhood (before five years of age), the condition is typically self-limiting and intervention is not required. In adults, the onset of trichotillomania may be secondary to underlying psychiatric disturbances, and symptoms are generally more long-term.Secondary infections may occur due to picking and scratching, but other complications are rare. Individuals with trichotillomania often find that support groups are helpful in living with and overcoming the disorder. Epidemiology Although no broad-based population epidemiologic studies had been conducted as of 2009, the lifetime prevalence of trichotillomania is estimated to be between 0.6% and 4.0% of the overall population. With a 1% prevalence rate, 2.5 million people in the U.S. may have trichotillomania at some time during their lifetimes.Trichotillomania is diagnosed in all age groups; onset is more common during preadolescence and young adulthood, with mean age of onset between 9 and 13 years of age, and a notable peak at 12–13. Among preschool children the genders are equally represented; there appears to be a female predominance among preadolescents to young adults, with between 70% and 93% of patients being female. Among adults, females typically outnumber males by 3 to 1."Automatic" pulling occurs in approximately three-quarters of adult patients with trichotillomania. History Hair pulling was first mentioned by Aristotle in the fourth century B.C., was first described in modern literature in 1885, and the term trichotillomania was coined by the French dermatologist François Henri Hallopeau in 1889.In 1987, trichotillomania was recognized in the Diagnostic and Statistical Manual of the American Psychiatric Association, third edition-revised (DSM-III-R). Society and culture Support groups and internet sites can provide recommended educational material and help persons with trichotillomania in maintaining a positive attitude and overcoming the fear of being alone with the disorder. Media A documentary film exploring trichotillomania, Bad Hair Life, was the 2003 winner of the International Health & Medical Media Award for best film in psychiatry and the winner of the 2004 Superfest Film Festival Merit Award.Trichster is a 2016 documentary that follows seven individuals living with trichotillomania, as they navigate the complicated emotions surrounding the disorder, and the effect it has on their daily lives. Fiction The trichotillomania of a prominent character is a key plot element in the 1999 novel Whatever Love Means by David Baddiel.In the superhero fiction series The Boys character Ashley Barret, portrayed by Colby Minifie is shown suffering from it. Music On the 2017 album, 20s a Difficult Age by Marcus Orelias, there is a song called "Trichotillomania". See also Feather-plucking Noncicatricial alopecia Psychogenic alopecia, a form of baldness that is caused by excessive grooming in cats Self-harm == References ==

You function as a medical dictionary. Offer comprehensive and accurate descriptions of medical terms, ensuring clarity and depth in your explanations.

Could you please explain the term 'Ventilator-associated pneumonia' in simple language?

Ventilator-associated pneumonia (VAP) is a type of lung infection that occurs in people who are on mechanical ventilation breathing machines in hospitals. As such, VAP typically affects critically ill persons that are in an intensive care unit (ICU) and have been on a mechanical ventilator for at least 48 hours. VAP is a major source of increased illness and death. Persons with VAP have increased lengths of ICU hospitalization and have up to a 20–30% death rate. The diagnosis of VAP varies among hospitals and providers but usually requires a new infiltrate on chest x-ray plus two or more other factors. These factors include temperatures of >38 °C or <36 °C, a white blood cell count of >12 × 109/ml, purulent secretions from the airways in the lung, and/or reduction in gas exchange.A different less studied infection found in mechanically ventilated people is ventilator-associated tracheobronchitis (VAT). As with VAP, tracheobronchial infection can colonise the trachea and travel to the bronchi. VAT may be a risk factor for VAP. Signs and symptoms People who are on mechanical ventilation are often sedated and are rarely able to communicate. As such, many of the typical symptoms of pneumonia will either be absent or unable to be obtained. The most important signs are fever or low body temperature, new purulent sputum, and hypoxemia (decreasing amounts of oxygen in the blood). However, these symptoms may be similar for tracheobronchitis. Cause Risk factors Risk factors for VAP include underlying heart or lung disease, neurologic disease, and trauma, as well as modifiable risk factors such as whether the head of the bed is flat (increased risk) or raised, whether the patient had an aspiration event before intubation, and prior antibiotic exposure. As a result of intubation many of the bodys defenses against infections are reduced or impaired; this can result in an ability for microorganisms to enter and cause infection. Patients who are in the ICU for head trauma or other severe neurologic illness, as well as patients who are in the ICU for blunt or penetrating trauma, are at especially high risk of developing VAP. Further, patients hospitalized for blunt trauma are at a higher risk of developing VAP compared to patients with penetrating trauma.Ventilator-associated tracheobronchitis may be a risk factor for VAP, though not all cases of VAT progress to VAP.Recent studies have also linked the overall oral health of a patient to the potential development of VAP; suggesting that bacteria found in plaque can "migrate to the respiratory system." Microbiology The microbiologic flora responsible for VAP is different from that of the more common community-acquired pneumonia (CAP). In particular, viruses and fungi are uncommon causes in people who do not have underlying immune deficiencies. Though any microorganism that causes CAP can cause VAP, there are several bacteria which are particularly important causes of VAP because of their resistance to commonly used antibiotics. These bacteria are referred to as multidrug resistant (MDR). Pseudomonas aeruginosa is the most common MDR Gram-negative bacterium causing VAP. Pseudomonas has natural resistance to many antibiotics and has been known to acquire resistance to every antibiotic except for polymyxin B. Resistance is typically acquired through upregulation or mutation of a variety of efflux pumps which pump antibiotics out of the cell. Resistance may also occur through loss of an outer membrane porin channel (OprD) Klebsiella pneumoniae has natural resistance to some beta-lactam antibiotics such as ampicillin. Resistance to cephalosporins and aztreonam may arise through induction of a plasmid-based extended spectrum beta-lactamase (ESBL) or plasmid-based ampC-type enzyme Serratia marcescens has an ampC gene which can be induced by exposure to antibiotics such as cephalosporins. Thus, culture sensitivities may initially indicate appropriate treatment which fails due to bacterial response. Enterobacter as a group also have an inducible ampC gene. Enterobacter may also develop resistance by acquiring plasmids. Citrobacter also has an inducible ampC gene. Stenotrophomonas maltophilia often colonizes people who have tracheal tubes but can also cause pneumonia. It is often resistant to a wide array of antibiotics but is usually sensitive to co-trimoxazole Acinetobacter are becoming more common and may be resistant to carbapenems such as imipenem and meropenem Burkholderia cepacia is an important organism in people with cystic fibrosis and is often resistant to multiple antibiotics Methicillin-resistant Staphylococcus aureus is an increasing cause of VAP. As many as fifty percent of Staphylococcus aureus isolates in the intensive care setting are resistant to methicillin. Resistance is conferred by the mecA gene. The development of molecular diagnostic techniques is changing the understanding of the microbiology of VAP, with an increasing appreciation of the role of hard to culture bacteria and the change in the lung microbiome. A recent finding has highlighted the presence of Mycoplasma in the lavage of patients with VAP, a finding which was largely absent from ventilated patients without VAP and healthy controls. The Mycoplasma species most commonly identified, Mycoplasma salivarium, was able to impair the antibacterial functions of monocytes and macrophages. Pathophysiology It is thought by many, that VAP primarily occurs because the endotracheal or tracheostomy tube allows free passage of bacteria into the lower segments of the lung in a person who often has underlying lung or immune problems. Bacteria travel in small droplets both through the endotracheal tube and around the cuff. Often, bacteria colonize the endotracheal or tracheostomy tube and are embolized into the lungs with each breath. Bacteria may also be brought down into the lungs with procedures such as deep suctioning or bronchoscopy. Another possibility is that the bacteria already exist in the mucus lining the bronchial tree, and are just kept in check by the bodys first line of defenses. Ciliary action of the cells lining the trachea drive the mucus superiorly, leading to a build-up of fluids around the inflated cuff where there is little to no airway clearance. The bacteria can then colonize easily without disturbance and then rise in numbers enough to become infective. The droplets that are driven into the airstream and into the lung fields are lofted by way of Bernoullis principle. There is also a condition called oxidative damage that occurs when concentrations of pure oxygen come into prolonged contact with cells and this damages the cilia of the cells, thus inhibiting their action as part of the bodys first line of defense. Whether bacteria also travel from the sinuses or the stomach into the lungs is, as of 2005, controversial. However, spread to the lungs from the blood stream or the gut is uncommon. Once inside the lungs, bacteria then take advantage of any deficiencies in the immune system (such as due to malnutrition or chemotherapy) and multiply. Patients with VAP demonstrate impaired function of key immune cells, including the neutrophil, both in the blood and in the alveolar space, with this impairment being driven by pro-inflammatory molecules such as C5a. These defects in immune function appear to be causally linked to the development of VAP, as they are seen before clinical infection develops. A combination of bacterial damage and consequences of the immune response lead to disruption of gas exchange with resulting symptoms. Diagnosis Diagnosis of ventilator-associated pneumonia is difficult and is not standardized. The criteria used for diagnosis of VAP varies by institution, but tends to be a combination of several of the following radiographic, clinical sign, and laboratory evidence: Temperature greater than 38 °C or less than 36 °C White blood cell count greater than 12,000/mm3 or less than 4,000/mm3 Purulent secretions, increased secretions, or change in secretions Positive tracheal cultures or bronchoalveolar lavage cultures Some sign of respiratory distress, such as shortness of breath, rapid breathing, abnormal breathing sounds when listening with stethoscope Increased need for oxygen on the ventilator Chest X-rays: at least two serial x-rays showing sustained or worsening shadowing (infiltrates or consolidations) Positive cultures that were obtained directly from the lung environment, such as from the trachea or bronchiolesAs an example, some institutions may require one clinical symptoms such as shortness of breath, one clinical sign such as fever, plus evidence on chest xray and in tracheal cultures.There is no gold standard for getting cultures to identify the bacteria, virus, or fungus that is causing the pneumonia, and there are invasive and non-invasive strategies for obtaining the culture sample. One non-invasive strategy collects cultures from the trachea of people with symptoms of VAP. Another is more invasive and advocates a bronchoscopy plus bronchoalveolar lavage (BAL) for people with symptoms of VAP. Both strategies also require a new or enlarging infiltrate on chest x-ray as well as clinical signs/symptoms such as fever and shortness of breath. There is no strong evidence to suggest that an invasive method to collect cultures is more effective than a non-invasive method. In addition, a quantitative approach to assessing the culture (performing a bacterial count of the pathogen that is causing the pneumonia) does not appear to be superior to a qualitative approach (determining the presence of the pathogen). In recent years there has been a focus on rapid diagnostics, allowing for detection of significant levels of pathogens before this becomes apparent on microbial cultures. Several approaches have been used, including using host biomarkers such as IL-1β and IL-8. Alternatively, molecular detection of bacteria has been undertaken, with reports that amplifying the pan-bacterial 16S gene can provide a measure of bacterial load. A trial of biomarker-based exclusion of VAP (VAP-RAPID2) has recently finished recruitment, and results are awaited (https://clinicaltrials.gov/ct2/show/NCT01972425). Blood cultures may reveal the microorganisms causing VAP, but are often not helpful as they are positive in only 25% of clinical VAP cases. Even in cases with positive blood cultures, the bacteremia may be from a source other than the lung infection. Prevention Prevention of VAP involves limiting exposure to resistant bacteria, discontinuing mechanical ventilation as soon as possible, and a variety of strategies to limit infection while intubated. Resistant bacteria are spread in much the same ways as any communicable disease. Proper hand washing, sterile technique for invasive procedures, and isolation of individuals with known resistant organisms are all mandatory for effective infection control. A variety of aggressive weaning protocols to limit the amount of time a person spends intubated have been proposed. One important aspect is limiting the amount of sedation that a ventilated person receives. Weak evidence suggests that raising the head of the bed to at least 30 degrees may help prevent VAP, however further research is required to understand the risks associated with this. Antiseptic mouthwashes (in particular associated with toothbrushing) such as chlorhexidine may also reduce the risk of VAP, although the evidence is mainly restricted to those who have undergone cardiac surgery.American and Canadian guidelines strongly recommend the use of subglottic secretion drainage (SSD). Special tracheal tubes with an incorporated suction lumen as the EVAC tracheal tube form Covidien / Mallinckrodt can be used for that reason. New cuff technology based on polyurethane material in combination with subglottic drainage (SealGuard Evac tracheal tube from Covidien / Mallinckrodt) showed significant delay in early and late onset of VAP.There is little evidence that the use of silver-coated endotracheal tubes reduces the incidence of VAP in the first ten days of ventilation. There is tentative evidence that the use of probiotics may reduced the likelihood of getting VAP, however it is unclear if probiotics affect ICU or in-hospital death. Treatment Treatment of VAP should be matched to known causative bacteria. However, when VAP is first suspected, the bacteria causing infection is typically not known and broad-spectrum antibiotics are given (empiric therapy) until the particular bacterium and its sensitivities are determined. Empiric antibiotics should take into account both the risk factors a particular individual has for resistant bacteria as well as the local prevalence of resistant microorganisms. If a person has previously had episodes of pneumonia, information may be available about prior causative bacteria. The choice of initial therapy is therefore entirely dependent on knowledge of local flora and will vary from hospital to hospital. Treatment of VAP with a single antibiotic has been reported to result in similar outcomes as with a combination of more than one antibiotics, in terms of cure rates, duration of ICU stay, mortality and adverse effects.Risk factors for infection with an MDR strain include ventilation for more than five days, recent hospitalization (last 90 days), residence in a nursing home, treatment in a hemodialysis clinic, and prior antibiotic use (last 90 days). Possible empirical therapy combinations include (but are not limited to): vancomycin/linezolid and ciprofloxacin, cefepime and gentamicin/amikacin/tobramycin vancomycin/linezolid and ceftazidime Ureidopenicillin plus β-lactamase inhibitor such as piperacillin/tazobactam or ticarcillin/clavulanate a carbapenem (e.g., imipenem or meropenem)Therapy is typically changed once the causative bacteria are known and continued until symptoms resolve (often 7 to 14 days). For patients with VAP not caused by nonfermenting Gram-negative bacilli (like Acinetobacter, Pseudomonas aeruginosa) the available evidence seems to support the use of short-course antimicrobial treatments (< or =10 days).People who do not have risk factors for MDR organisms may be treated differently depending on local knowledge of prevalent bacteria. Appropriate antibiotics may include ceftriaxone, ciprofloxacin, levofloxacin, or ampicillin/sulbactam. As of 2005, there is ongoing research into inhaled antibiotics as an adjunct to conventional therapy. Tobramycin and polymyxin B are commonly used in certain centres but there is no clinical evidence to support their use. Prognosis VAP occurring early after intubation typically involves fewer resistant organisms and is thus associated with a more favorable outcome. Because respiratory failure requiring mechanical ventilation is itself associated with a high mortality, determination of the exact contribution of VAP to mortality has been difficult. As of 2006, estimates range from 33% to 50% death in patients who develop VAP. Mortality is more likely when VAP is associated with certain microorganisms (Pseudomonas, Acinetobacter), blood stream infections, and ineffective initial antibiotics. VAP is especially common in people who have acute respiratory distress syndrome (ARDS). Epidemiology Between 8 and 28% of patients receiving mechanical ventilation are affected by VAP. VAP can develop at any time during ventilation, but occurs most often in the first week of mechanical ventilation. There is some evidence for gender differences in the course of VAP: men have been found to get VAP more often, but women are more likely to die after contracting VAP. Recent reports indicate that patients with Coronavirus disease 2019 who require mechanical ventilation in an Intensive care unit are at increased risk of ventilator-associated pneumonia, compared to patients without COVID-19 ventilated in the same unit and patients who had viral pneumonitis arising from viruses other than SARS-CoV-2. Why this increased susceptibility should be present remains uncertain, as the noted reports adjusted for duration of ventilation, it is likely that the increased susceptibility relates impaired innate immunity in the lungs. However several observational studies have identified the use of glucocorticoids as a factor associated with increased risk of VAP and other Hospital-acquired infections. References Further reading == External links ==

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What is the significance of the term 'Uveitis' in the medical field?

Uveitis () is the inflammation of the uvea, the pigmented layer that lies between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Uveitis is described anatomically, by the part of the eye affected, as anterior, intermediate or posterior, from front to back. In the panuveitic form, all parts are involved. The most common form is the anterior one. Symptoms include pain, floaters and blurred vision, and clinical examination may show redness and an irregular pupil, while ophthalmic examination shows dilated ciliary blood vessels and the presence of cells in the anterior chamber. Uveitis may arise spontaneously and associated with some genetic factors, or be associated with a wide range of conditions including autoimmune disease and infections. While the eye is a relatively protected environment, its immune mechanisms may be overcome resulting in inflammation and tissue destruction associated with T-cell activation. The incidence is approximately 1:4500, most commonly between the ages of 20–60. Uveitis is an ophthalmic emergency and requires a thorough examination by an ophthalmologist or optometrist, including dilation of the pupil to allow better visualisation. Urgent treatment is required to control the inflammation. Further procedures may be required to identify any underlying disease. Treatment usually involves the use of steroids, most commonly as eye drops. Any underlying disease, for instance herpes zoster (shingles) will also require treatment. While initial treatment is usually successful, complications include other ocular disorders, such as uveitic glaucoma, retinal detachment, optic nerve damage, cataracts, and in some cases, a permanent loss of vision. In the United States uveitis accounts for about 10%-20% of cases of blindness. Signs and symptoms The signs and symptoms of uveitis include the following; Anterior uveitis (Iritis) Pain in the eye(s) Redness of the eye(s) Blurred vision Photophobia Irregular pupil Signs of anterior uveitis include dilated ciliary vessels, presence of cells and flare in the anterior chamber, and keratic precipitates ("KP") on the posterior surface of the cornea. In severe inflammation there may be evidence of a hypopyon. Old episodes of uveitis are identified by pigment deposits on lens, KPs, and festooned pupil on dilation of pupil. Busacca nodules, inflammatory nodules located on the surface of the iris in granulomatous forms of anterior uveitis such as Fuchs heterochromic iridocyclitis (FHI). Synechia Intermediate uveitis Most common: Floaters, which are dark spots that float in the visual field Blurred visionIntermediate uveitis usually affects one eye. Less common is the presence of pain and photophobia. Posterior uveitis Inflammation in the back of the eye is commonly characterized by: Floaters Blurred vision Causes Uveitis is usually an isolated illness, but can be associated with many other medical conditions. In anterior uveitis, no associated condition or syndrome is found in approximately one-half of cases. However, anterior uveitis is often one of the syndromes associated with HLA-B27. Presence of this type of HLA allele has a relative risk of evolving this disease by approximately 15%.The most common form of uveitis is acute anterior uveitis (AAU). It is most commonly associated with HLA-B27, which has important features: HLA-B27 AAU can be associated with ocular inflammation alone or in association with systemic disease. HLA-B27 AAU has characteristic clinical features including male preponderance, unilateral alternating acute onset, a non-granulomatous appearance, and frequent recurrences, whereas HLA-B27 negative AAU has an equivalent male to female onset, bilateral chronic course, and more frequent granulomatous appearance. Rheumatoid arthritis is not uncommon in Asian countries as a significant association of uveitis. Noninfectious or autoimmune causes Sympathetic ophthalmia Behçet disease Crohns disease Fuchs heterochromic iridocyclitis Granulomatosis with polyangiitis HLA-B27 related uveitis Spondyloarthritis (especially seen in ankylosing spondylitis) Juvenile idiopathic arthritis Sarcoidosis Tubulointerstitial nephritis and uveitis syndrome Infectious causes Uveitis may be an immune response to fight an infection inside the eye. While representing the minority of patients with uveitis, such possible infections include: brucellosis herpesviruses (herpes zoster ophthalmicus - shingles of the eye) leptospirosis Lyme disease presumed ocular histoplasmosis syndrome syphilis toxocariasis toxoplasmic chorioretinitis tuberculosis Zika fever Associated with systemic diseases Systemic disorders that can be associated with uveitis include: Enthesitis Ankylosing spondylitis Juvenile rheumatoid arthritis psoriatic arthritis reactive arthritis Behçets disease inflammatory bowel disease Whipples disease systemic lupus erythematosus polyarteritis nodosa Kawasakis disease chronic granulomatous disease sarcoidosis multiple sclerosis Vogt–Koyanagi–Harada disease Drug related side effects Rifabutin, a derivative of Rifampin, has been shown to cause uveitis. Several reports suggest the use of quinolones, especially Moxifloxacin, may lead to uveitis. White Dot syndromes Occasionally, uveitis is not associated with a systemic condition: the inflammation is confined to the eye and has unknown cause. In some of these cases, the presentation in the eye is characteristic of a described syndrome, which are called white dot syndromes, and include the following diagnoses: acute posterior multifocal placoid pigment epitheliopathy birdshot chorioretinopathy multifocal choroiditis and panuveitis multiple evanescent white dot syndrome punctate inner choroiditis serpiginous choroiditis acute zonal occult outer retinopathy Masquerade syndromes Masquerade syndromes are those conditions that include the presence of intraocular cells but are not due to immune-mediated uveitis entities. These may be divided into neoplastic and non-neoplastic conditions. Non-neoplastic:retinitis pigmentosa intraocular foreign body juvenile xanthogranuloma retinal detachmentNeoplastic:retinoblastoma lymphoma malignant melanoma leukemia reticulum cell sarcoma Pathophysiology Immunologic factors Onset of uveitis can broadly be described as a failure of the ocular immune system and the disease results from inflammation and tissue destruction. Uveitis is driven by the Th17 T cell sub-population that bear T-cell receptors specific for proteins found in the eye. These are often not deleted centrally whether due to ocular antigen not being presented in the thymus (therefore not negatively selected) or a state of anergy is induced to prevent self targeting.Autoreactive T cells must normally be held in check by the suppressive environment produced by microglia and dendritic cells in the eye. These cells produce large amounts of TGF beta and other suppressive cytokines, including IL-10, to prevent damage to the eye by reducing inflammation and causing T cells to differentiate to inducible T reg cells. Innate immune stimulation by bacteria and cellular stress is normally suppressed by myeloid suppression while inducible Treg cells prevent activation and clonal expansion of the autoreactive Th1 and Th17 cells that possess potential to cause damage to the eye. Whether through infection or other causes, this balance can be upset and autoreactive T cells allowed to proliferate and migrate to the eye. Upon entry to the eye, these cells may be returned to an inducible Treg state by the presence of IL-10 and TGF-beta from microglia. Failure of this mechanism leads to neutrophil and other leukocyte recruitment from the peripheral blood through IL-17 secretion. Tissue destruction is mediated by non-specific macrophage activation and the resulting cytokine cascades. Serum TNF-α is significantly elevated in cases while IL-6 and IL-8 are present in significantly higher quantities in the aqueous humour in patients with both quiescent and active uveitis. These are inflammatory markers that non-specifically activate local macrophages causing tissue damage. Genetic factors The cause of non-infectious uveitis is unknown but there are some strong genetic factors that predispose disease onset including HLA-B27 and the PTPN22 genotype. Infectious agents Recent evidence has pointed to reactivation of herpes simplex, varicella zoster and other viruses as important causes of developing what was previously described as idiopathic anterior uveitis. Bacterial infection is another significant contributing factor in developing uveitis. Diagnosis Diagnosis includes dilated fundus examination to rule out posterior uveitis, which presents with white spots across the retina along with retinitis and vasculitis. Laboratory testing is usually used to diagnose specific underlying diseases, including rheumatologic tests (e.g. antinuclear antibody, rheumatoid factor) and serology for infectious diseases (Syphilis, Toxoplasmosis, Tuberculosis). Major histocompatibility antigen testing may be performed to investigate genetic susceptibility to uveitis. The most common antigens include HLA-B27, HLA-A29 (in birdshot chorioretinopathy) and HLA-B51 (in Behçet disease).Radiology X-ray may be used to show coexisting arthritis and chest X-ray may be helpful in sarcoidosis. Classification Uveitis is classified anatomically into anterior, intermediate, posterior, and panuveitic forms—based on the part of the eye primarily affected. Prior to the twentieth century, uveitis was typically referred to in English as "ophthalmia." Anterior uveitis includes iridocyclitis and iritis. Iritis is the inflammation of the anterior chamber and iris. Iridocyclitis is inflammation of the iris and ciliary body with inflammation predominantly confined to ciliary body. Anywhere from two-thirds to 90% of uveitis cases are anterior in location (iritis). This condition can occur as a single episode and subside with proper treatment or may take on a recurrent or chronic nature. Intermediate uveitis, also known as pars planitis, consists of vitritis—which is inflammation of cells in the vitreous cavity, sometimes with snowbanking, or deposition of inflammatory material on the pars plana. There are also "snowballs," which are inflammatory cells in the vitreous. Posterior uveitis or chorioretinitis is the inflammation of the retina and choroid. Pan-uveitis is the inflammation of all layers of the uvea(Iris, ciliary body and choroid). Treatment Uveitis is typically treated with glucocorticoid steroids, either as topical eye drops (prednisolone acetate) or as oral therapy. Prior to the administration of corticosteroids, corneal ulcers must be ruled out. This is typically done using a fluorescence dye test. In addition to corticosteroids, topical cycloplegics, such as atropine or homatropine, may be used. Successful treatment of active uveitis increases T-regulatory cells in the eye, which likely contributes to disease regression. In severe cases an injection of posterior subtenon triamcinolone acetate may also be given to reduce the swelling of the eye. Antimetabolite medications, such as methotrexate are often used for recalcitrant or more aggressive cases of uveitis. Experimental treatments with Infliximab or other anti-TNF infusions may prove helpful. The anti-diabetic drug metformin is reported to inhibit the process that causes the inflammation in uveitis.In the case of herpetic uveitis, anti-viral medications, such as valaciclovir or aciclovir, may be administered to treat the causative viral infection. Prognosis The prognosis is generally good for those who receive prompt diagnosis and treatment, but serious complication including cataracts, uveitic glaucoma, band keratopathy, macular edema and permanent vision loss may result if left untreated. The type of uveitis, as well as its severity, duration, and responsiveness to treatment or any associated illnesses, all factor into the outlook. Epidemiology Uveitis affects approximately 1 in 4500 people and is most common between the ages 20 to 60 with men and women affected equally. In western countries, anterior uveitis accounts for between 50% and 90% of uveitis cases. In Asian countries the proportion is between 28% and 50%. Uveitis is estimated to be responsible for approximately 10%-20% of the blindness in the United States. See also List of systemic diseases with ocular manifestations Intermediate uveitis Uveitis–Glaucoma–Hyphema syndrome References == Bibliography ==

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What does the medical term 'Diabetic cardiomyopathy' encompass?

Diabetic cardiomyopathy is a disorder of the heart muscle in people with diabetes. It can lead to inability of the heart to circulate blood through the body effectively, a state known as heart failure, with accumulation of fluid in the lungs (pulmonary edema) or legs (peripheral edema). Most heart failure in people with diabetes results from coronary artery disease, and diabetic cardiomyopathy is only said to exist if there is no coronary artery disease to explain the heart muscle disorder. Signs and symptoms One particularity of diabetic cardiomyopathy is the long latent phase, during which the disease progresses but is completely asymptomatic. In most cases, diabetic cardiomyopathy is detected with concomitant hypertension or coronary artery disease. One of the earliest signs is mild left ventricular diastolic dysfunction with little effect on ventricular filling. Also, the diabetic patient may show subtle signs of diabetic cardiomyopathy related to decreased left ventricular compliance or left ventricular hypertrophy or a combination of both. A prominent "a" wave can also be noted in the jugular venous pulse, and the cardiac apical impulse may be overactive or sustained throughout systole. After the development of systolic dysfunction, left ventricular dilation and symptomatic heart failure, the jugular venous pressure may become elevated, the apical impulse would be displaced downward and to the left. Systolic mitral murmur is not uncommon in these cases. These changes are accompanied by a variety of electrocardiographic changes that may be associated with diabetic cardiomyopathy in 60% of patients without structural heart disease, although usually not in the early asymptomatic phase. Later in the progression, a prolonged QT interval may be indicative of fibrosis. Given that diabetic cardiomyopathys definition excludes concomitant atherosclerosis or hypertension, there are no changes in perfusion or in atrial natriuretic peptide levels up until the very late stages of the disease, when the hypertrophy and fibrosis become very pronounced. Pathophysiology Defects in cellular processes such as autophagy and mitophagy are thought to contribute to the development of diabetic cardiomyopathy. Diabetic cardiomyopathy is characterized functionally by ventricular dilation, enlargement of heart cells, prominent interstitial fibrosis and decreased or preserved systolic function in the presence of a diastolic dysfunction.While it has been evident for a long time that the complications seen in diabetes are related to the hyperglycemia associated to it, several factors have been implicated in the pathogenesis of the disease. Etiologically, four main causes are responsible for the development of heart failure in diabetic cardiomyopathy: microangiopathy and related endothelial dysfunction, autonomic neuropathy, metabolic alterations that include abnormal glucose use and increased fatty acid oxidation, generation and accumulation of free radicals, and alterations in ion homeostasis, especially calcium transients. Additional effects include inflammation and upregulation of local angiotensin systems. Diabetic cardiomyopathy may be associated with restrictive (HFPEF) and dilated phenotypes (HFREF). HFPEF results predominantly from hyperinsulinemia, hyperglycemia, lipotoxicity, AGEs and microvascular rarefication. HFREF is associated with autoimmunity, hyperglycemia, lipotoxicity, microvascular rarefication and AGE formation. Microangiopathy Microangiopathy can be characterized as subendothelial and endothelial fibrosis in the coronary microvasculature of the heart. This endothelial dysfunction leads to impaired myocardial blood flow reserve as evidence by echocardiography. About 50% of diabetics with diabetic cardiomyopathy show pathologic evidence for microangiopathy such as sub-endothelial and endothelial fibrosis, compared to only 21% of non-diabetic heart failure patients. Over the years, several hypotheses were postulated to explain the endothelial dysfunction observed in diabetes. It was hypothesized that the extracellular hyperglycemia leads to an intracellular hyperglycemia in cells unable to regulate their glucose uptake, most predominantly, endothelial cells. Indeed, while hepatocytes and myocytes have mechanisms allowing them to internalize their glucose transporter, endothelial cells do not possess this ability. The consequences of increased intracellular glucose concentration are fourfold, all resulting from increasing concentration of glycolytic intermediates upstream of the rate-limiting glyceraldehyde-3-phosphate reaction which is inhibited by mechanisms activated by increased free radical formation, common in diabetes. Four pathways, enumerated below all explain part of the diabetic complications. First, it has been widely reported since the 1960s that hyperglycemia causes an increase in the flux through aldose reductase and the polyol pathway. Increased activity of the detoxifying aldose reductase enzyme leads to a depletion of the essential cofactor NADH, thereby disrupting crucial cell processes. Second, increasing fructose 6-phosphate, a glycolysis intermediate, will lead to increased flux through the hexosamine pathway. This produces N-acetyl glucosamine that can add on serine and threonine residues and alter signaling pathways as well as cause pathological induction of certain transcription factors. Third, hyperglycemia causes an increase in diacylglycerol, which is also an activator of the Protein Kinase C (PKC) signaling pathway. Induction of PKC causes multiple deleterious effects, including but not limited to blood flow abnormalities, capillary occlusion and pro-inflammatory gene expression. Finally, glucose, as well as other intermediates such as fructose and glyceraldehyde-3-phosphate, when present in high concentrations, promote the formation of advanced glycation endproducts (AGEs). These, in turn, can irreversibly cross link to proteins and cause intracellular aggregates that cannot be degraded by proteases and thereby, alter intracellular signalling. Also, AGEs can be exported to the intercellular space where they can bind AGE receptors (RAGE). This AGE/RAGE interaction activates inflammatory pathways such as NF-κB, in the host cells in an autocrine fashion, or in macrophages in a paracrine fashion. Neutrophil activation can also lead to NAD(P)H oxidase production of free radicals further damaging the surrounding cells. Finally, exported glycation products bind extracellular proteins and alter the matrix, cell-matrix interactions and promote fibrosis. A major source of increased myocardial stiffness is crosslinking between AGEs and collagen. In fact, a hallmark of uncontrolled diabetes is glycated products in the serum and can be used as a marker for diabetic microangiopathy. Autonomic neuropathy While the heart can function without help from the nervous system, it is highly innervated with autonomic nerves, regulating the heart beat according to demand in a fast manner, prior to hormonal release. The autonomic innervations of the myocardium in diabetic cardiomyopathy are altered and contribute to myocardial dysfunction. Unlike the brain, the peripheral nervous system does not benefit from a barrier protecting it from the circulating levels of glucose. Just like endothelial cells, nerve cells cannot regulate their glucose uptake and suffer the same type of damages listed above. Therefore, the diabetic heart shows clear denervation as the pathology progresses. This denervation correlates with echocardiographic evidence of diastolic dysfunction and results in a decline of survival in patients with diabetes from 85% to 44%. Other causes of denervation are ischemia from microvascular disease and thus appear following the development of microangiopathy. Inflammation Diabetes is associated with increased inflammation, which is mediated by generation of abnormal fatty acids, AGEs and other mechanisms. The resulting cytokine profile promotes hypertrophy and apoptosis of cardiomyocytes, abnormal calcium signaling, impaired myocardial contractility and myocardial fibrosis. Additionally, it may lead to microvascular dysfunction, either directly or via endothelial damage, thereby promoting myocardial ischemia. Diagnosis Diagnostic approaches for diabetic cardiomyopathy include echocardiography, cardiac MRI investigations, Multi‐slice computed tomography (MsCT), and nuclear imaging. Potential risks of the investigation (e.g. exposure to radiation) and diagnostic utility should be weighed for an optimised personalised procedure. Treatment At present, there is no effective specific treatment available for diabetic cardiomyopathy. Treatment centers around intense glycemic control through diet, oral hypoglycemics and frequently insulin and management of heart failure symptoms. There is a clear correlation between increased glycemia and risk of developing diabetic cardiomyopathy, therefore, keeping glucose concentrations as controlled as possible is paramount. Thiazolidinediones are not recommended in patients with NYHA Class III or IV heart failure secondary to fluid retention.As with most other heart diseases, ACE inhibitors can also be administered. An analysis of major clinical trials shows that diabetic patients with heart failure benefit from such a therapy to a similar degree as non-diabetics. Similarly, beta blockers are also common in the treatment of heart failure concurrently with ACE inhibitors. == References ==

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I'm seeking clarification on the medical term 'Avita.' Could you explain it?

Avita may refer to: Australian Green Tree Frog Tretinoin

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Could you offer a clear explanation of the term 'Phlegmasia alba dolens' as used in the medical field?

Phlegmasia alba dolens (also colloquially known as milk leg or white leg; not to be confused with phlegmasia cerulea dolens) is part of a spectrum of diseases related to deep vein thrombosis. Historically, it was commonly seen during pregnancy and in mothers who have just given birth. In cases of pregnancy, it is most often seen during the third trimester, resulting from a compression of the left common iliac vein against the pelvic rim by the enlarged uterus. Today, this disease is most commonly (40% of the time) related to some form of underlying malignancy. Hypercoagulability (a propensity to clot formation) is a well-known state that occurs in many cancer states. The incidence of this disease is not well reported. Cause The disease presumably begins with a deep vein thrombosis that progresses to total occlusion of the deep venous system. It is at this stage that it is called phlegmasia alba dolens. It is a sudden (acute) process. The leg, then, must rely on the superficial venous system for drainage. The superficial system is not adequate to handle the large volume of blood being delivered to the leg via the arterial system. The result is edema, pain and a white appearance (alba) of the leg. The next step in the disease progression is occlusion of the superficial venous system, thereby preventing all venous outflow from the extremity. At this stage it is called phlegmasia cerulea dolens. The leg becomes more swollen and increasingly more painful. Additionally, the edema and loss of venous outflow impedes the arterial inflow. Ischemia with progression to gangrene are potential consequences. Phlegmasia alba dolens is distinguished, clinically, from phlegmasia cerulea dolens in that there is no ischemia and congestion. In severe cases of venous obstruction the arterial pulse may gradually disappear and venous gangrene may ensue. Diagnosis The condition can be identified clinically & as early as possible to prevent further deterioration & complications like embolism, ischaemic necrosis, and gangrene. The diagnosis is confirmed with Doppler ultrasound of the veins of the affected leg, and occasionally other imaging modalities. Treatment The mainstay of the treatment of deep vein thrombosis is with anticoagulation, but in very large DVTs various other modalities may be used to reduce the risk of complications. This may be surgical thrombectomy or catheter-directed thrombolysis. Etymology Phlegmasia alba dolens literally means "painful white edema". It received the name "milk leg" because it was once thought to be caused by the metastasis of milk. References == External links ==

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

What is the significance of the term 'Preauricular sinus and cyst' in the medical field?

Preauricular sinuses and preauricular cysts are two common congenital malformations. Each involves the external ear. The difference between them is that a cyst does not connect with the skin, but a sinus does. Frequency of preauricular sinus differs depending the population: 0.1–0.9% in the US, 0.9% in the UK, and 4–10% in Asia and parts of Africa.Preauricular sinuses are inherited features, and frequently appear next to both ears. Preauricular sinuses can be associated with other defects that are not visible, one example being branchio-oto-renal syndrome. Presentation Complications Occasionally a preauricular sinus or cyst can become infected. Most preauricular sinuses are asymptomatic, and remain untreated unless they become infected too often. Preauricular sinuses can be excised surgically, but often present a high risk of recurrence. Causes Preauricular sinuses and cysts result from developmental defects of the first and second pharyngeal arches. This and other ear malformations are sometimes associated with renal anomalies. In rare circumstances these pits may be seen in genetic conditions such as branchio-oto-renal syndrome; however these conditions are always concurrent with other health concerns. Treatment Courses of treatment typically include the following: Surgical excision is indicated with recurrent fistular infections, preferably after significant healing of the infection. In case of a persistent infection, infection drainage is performed during the excision operation. The operation is generally performed by an appropriately trained specialist surgeon e.g. an otolaryngologist or a pediatric Surgeon. The fistula can be excised as a cosmetic operation even though no infection appeared. The procedure is considered an elective operation in the absence of any associated complications. See also Branchial cleft cyst Thyroglossal cyst Lachiewicz Sibley syndrome List of cutaneous conditions References Bibliography Further reading == External links ==

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Please help me grasp the concept behind the medical term 'Alexis Littré.'

Alexis Littre (17 July 1654 – 3 February 1726) was a French physician and anatomist born in Cordes (currently Cordes-Tolosannes in the department of Tarn-et-Garonne). Biography Littre studied medicine in Montpellier and Paris, receiving his doctorate in 1691. In 1699 he became a member of the Académie des Sciences. In Paris, he taught anatomy and was the author of numerous medical publications. He was the first to give a description of a hernial protrusion of an intestinal diverticulum. This condition is now referred to as "Littres hernia".He also described the mucous urethral glands of the male urethra. These structures were to become known as "Littres glands", and their inflammation is sometimes called "littreitis".In his 1710 treatise Diverses observations anatomiques, Littre was the first to suggest the possibility of performing a lumbar colostomy for an obstruction of the colon.Jean Louis Petit was one of his students. So was Jacques-Bénigne Winslow in 1707. He died in Paris. References Alexis de Littre @ Who Named It Notes External links Online articles by Littré 10 articles (2012-05-15) on the site of the Académie des sciences. Cotlar, Alvin M. (January 2002). "Historical landmarks in operations on the colon—surgeons courageous". Current Surgery. Elsevier. 59 (1): 91–95. doi:10.1016/s0149-7944(01)00606-7. ISSN 0149-7944. PMID 16093113. Bernard Le Bovier de Fontenelle, Éloge de Monsieur Littré, p. 129, at Google Books, 1754, p. 129 (Eulogy)

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I need a basic explanation for the medical term 'Systemic primary carnitine deficiency.'

Systemic primary carnitine deficiency (SPCD) is an inborn error of fatty acid transport caused by a defect in the transporter responsible for moving carnitine across the plasma membrane. Carnitine is an important amino acid for fatty acid metabolism. When carnitine cannot be transported into tissues, fatty acid oxidation is impaired, leading to a variety of symptoms such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The specific transporter involved with SPCD is OCTN2, coded for by the SLC22A5 gene located on chromosome 5. SPCD is inherited in an autosomal recessive manner, with mutated alleles coming from both parents. Acute episodes due to SPCD are often preceded by metabolic stress such as extended fasting, infections or vomiting. Cardiomyopathy can develop in the absence of an acute episode, and can result in death. SPCD leads to increased carnitine excretion in the urine and low levels in plasma. In most locations with expanded newborn screening, SPCD can be identified and treated shortly after birth. Treatment with high doses of carnitine supplementation is effective, but needs to be rigorously maintained for life. Signs and symptoms The presentation of patient with SPCD can be incredibly varied, from asymptomatic to lethal cardiac manifestations. Early cases were reported with liver dysfunction, muscular findings (weakness and underdevelopment), hypoketotic hypoglycemia, cardiomegaly, cardiomyopathy and marked carnitine deficiency in plasma and tissues, combined with increased excretion in urine. Patients who present clinically with SPCD fall into two categories, a metabolic presentation with hypoglycemia and a cardiac presentation characterized by cardiomyopathy. Muscle weakness can be found with either presentation.In countries with expanded newborn screening, SPCD can be identified shortly after birth. Affected infants show low levels of free carnitine and all other acylcarnitine species by tandem mass spectrometry. Not all infants with low free carnitine are affected with SPCD. Some may have carnitine deficiency secondary to another metabolic condition or due to maternal carnitine deficiency. Proper follow-up of newborn screening results for low free carnitine includes studies of the mother to determine whether her carnitine deficiency is due to SPCD or secondary to a metabolic disease or diet. Maternal cases of SPCD have been identified at a higher than expected rate, often in women who are asymptomatic. Some mothers have also been identified through newborn screening with cardiomyopathy that had not been previously diagnosed. The identification and treatment of these asymptomatic individuals is still developing, as it is not clear whether they require the same levels of intervention as patients identified with SPCD early in life based on clinical presentation. Genetics SPCD is an autosomal recessive condition, meaning a mutated allele must be inherited from each parent for an individual to be affected. The gene responsible for the OCTN2 carnitine transporter is SLC22A5, located at 5q31.1-32. SLC22A5 is regulated by peroxisome proliferator-activated receptor alpha. The transporter, OCTN2, is located in the apical membrane of the renal tubular cells, where it plays a role in tubular reabsorption.The defective OCTN2 is unable to recapture carnitine prior to its excretion in urine, leading to the characteristic biochemical findings of massively increased urine carnitine levels and significantly decreased plasma carnitine levels. Decreased levels of plasma carnitine inhibit fatty acid oxidation during times of excessive energy demand. Carnitine is needed to transport long chain fatty acids into the mitochondria, where they can be broken down to produce acetyl-CoA. Individuals with SPCD cannot produce ketone bodies as energy due to the interruption of fatty acid oxidation. Although SPCD is an autosomal recessive condition, heterozygotes have been shown to be at an increased risk for developing benign cardiomyopathy compared to wild type individuals. Diagnosis The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level. When combined with an increased concentration of carnitine in urine, the suspicion of SPCD can often be confirmed by either molecular testing or functional studies assessing the uptake of carnitine in cultured fibroblasts. Treatment Identification of patients presymptomatically via newborn screening has allowed early intervention and treatment. Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life. Individuals who are identified and treated at birth have very good outcomes, including the prevention of cardiomyopathy. Mothers who are identified after a positive newborn screen but are otherwise asymptomatic are typically offered carnitine supplementation as well. The long-term outcomes for asymptomatic adults with SPCD is not known, but the discovery of mothers with undiagnosed cardiomyopathy and SPCD has raised the possibility that identification and treatment may prevent adult-onset manifestations. Incidence Worldwide, SPCD is most common in the Faroe Islands, where at least one out of every 1000 inhabitants of the Faroes have the disorder, according to the Faroese Ministry of Health. Scientists believe that around 10% of the Faroese population are carriers of variants which cause SPCD. These people are not ill, but may have a lower amount of carnitine in their blood than non-carriers. The first Faroese patient was diagnosed with SPCD in 1995, and since then several young people and children in the Faroese Islands have died of cardiac arrest because of SPCD.The addition of SPCD to newborn screening panels has offered insight into the incidence of the disorder around the world. In Taiwan, the incidence of SPCD in newborns was estimated to be approximately 1:67,000, while maternal cases were identified at a higher frequency of approximately 1:33,000. The increased incidence of SPCD in mothers compared to newborns is not completely understood. Estimates of SPCD in Japan have shown a similar incidence of 1:40,000. History Carnitine deficiency has been extensively studied, although most commonly as a secondary finding to other metabolic conditions. The first case of SPCD was reported in the 1980s, in a child with fasting hypoketotic hypoglycemia that resolved after treatment with carnitine supplementation. Later cases were reported with cardiomyopathy and muscle weakness. Newborn screening expanded the potential phenotypes associated with SPCD, to include otherwise asymptomatic adults. References External links GeneReviews/NCBI/NIH/UW entry on Systemic Primary Carnitine Deficiency

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What is the significance of the term 'Psoriasis' in the medical field?

Psoriasis is a long-lasting, noncontagious autoimmune disease characterized by raised areas of abnormal skin. These areas are red, or purple on some people with darker skin, dry, itchy, and scaly. Psoriasis varies in severity from small, localized patches to complete body coverage. Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the Koebner phenomenon.The five main types of psoriasis are plaque, guttate, inverse, pustular, and erythrodermic. Plaque psoriasis, also known as psoriasis vulgaris, makes up about 90% of cases. It typically presents as red patches with white scales on top. Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp. Guttate psoriasis has drop-shaped lesions. Pustular psoriasis presents as small, noninfectious, pus-filled blisters. Inverse psoriasis forms red patches in skin folds. Erythrodermic psoriasis occurs when the rash becomes very widespread, and can develop from any of the other types. Fingernails and toenails are affected in most people with psoriasis at some point in time. This may include pits in the nails or changes in nail color.Psoriasis is generally thought to be a genetic disease that is triggered by environmental factors. If one twin has psoriasis, the other twin is three times more likely to be affected if the twins are identical than if they are nonidentical. This suggests that genetic factors predispose to psoriasis. Symptoms often worsen during winter and with certain medications, such as beta blockers or NSAIDs. Infections and psychological stress can also play a role. The underlying mechanism involves the immune system reacting to skin cells. Diagnosis is typically based on the signs and symptoms.There is no known cure for psoriasis, but various treatments can help control the symptoms. These treatments include steroid creams, vitamin D3 cream, ultraviolet light, and immunosuppressive drugs, such as methotrexate. About 75% of skin involvement improves with creams alone. The disease affects 2–4% of the population. Men and women are affected with equal frequency. The disease may begin at any age, but typically starts in adulthood. Psoriasis is associated with an increased risk of psoriatic arthritis, lymphomas, cardiovascular disease, Crohns disease, and depression. Psoriatic arthritis affects up to 30% of individuals with psoriasis.The word "psoriasis" is from Greek ψωρίασις, meaning "itching condition" or "being itchy" from psora, "itch", and -iasis, "action, condition". Signs and symptoms Plaque psoriasis Psoriasis vulgaris (also known as chronic stationary psoriasis or plaque-like psoriasis) is the most common form and affects 85–90% of people with psoriasis. Plaque psoriasis typically appears as raised areas of inflamed skin covered with silvery-white, scaly skin. These areas are called plaques and are most commonly found on the elbows, knees, scalp, and back. Other forms Additional types of psoriasis comprise about 10% of cases. They include pustular, inverse, napkin, guttate, oral, and seborrheic-like forms. Pustular psoriasis Pustular psoriasis appears as raised bumps filled with noninfectious pus (pustules). The skin under and surrounding the pustules is red and tender. Pustular psoriasis can either be localized or more widespread throughout the body. Two types of localized pustular psoriasis include psoriasis pustulosa palmoplantaris and acrodermatitis continua of Hallopeau; both forms are localized to the hands and feet. Inverse psoriasis Inverse psoriasis (also known as flexural psoriasis) appears as smooth, inflamed patches of skin. The patches frequently affect skin folds, particularly around the genitals (between the thigh and groin), the armpits, in the skin folds of an overweight abdomen (known as panniculus), between the buttocks in the intergluteal cleft, and under the breasts in the inframammary fold. Heat, trauma, and infection are thought to play a role in the development of this atypical form of psoriasis. Napkin psoriasis Napkin psoriasis is a subtype of psoriasis common in infants characterized by red papules with silver scale in the diaper area that may extend to the torso or limbs. Napkin psoriasis is often misdiagnosed as napkin dermatitis (diaper rash). Guttate psoriasis Guttate psoriasis is characterized by numerous small, scaly, red or pink, droplet-like lesions (papules). These numerous spots of psoriasis appear over large areas of the body, primarily the trunk, but also the limbs and scalp. Guttate psoriasis is often triggered by a streptococcal infection, typically streptococcal pharyngitis. Erythrodermic psoriasis Psoriatic erythroderma (erythrodermic psoriasis) involves widespread inflammation and exfoliation of the skin over most of the body surface, often involving greater than 90% of the body surface area. It may be accompanied by severe dryness, itching, swelling, and pain. It can develop from any type of psoriasis. It is often the result of an exacerbation of unstable plaque psoriasis, particularly following the abrupt withdrawal of systemic glucocorticoids. This form of psoriasis can be fatal as the extreme inflammation and exfoliation disrupt the bodys ability to regulate temperature and perform barrier functions. Mouth Psoriasis in the mouth is very rare, in contrast to lichen planus, another common papulosquamous disorder that commonly involves both the skin and mouth. When psoriasis involves the oral mucosa (the lining of the mouth), it may be asymptomatic, but it may appear as white or grey-yellow plaques. Fissured tongue is the most common finding in those with oral psoriasis and has been reported to occur in 6.5–20% of people with psoriasis affecting the skin. The microscopic appearance of oral mucosa affected by geographic tongue (migratory stomatitis) is very similar to the appearance of psoriasis. However, modern studies have failed to demonstrate any link between the two conditions. Seborrheic-like psoriasis Seborrheic-like psoriasis is a common form of psoriasis with clinical aspects of psoriasis and seborrheic dermatitis, and it may be difficult to distinguish from the latter. This form of psoriasis typically manifests as red plaques with greasy scales in areas of higher sebum production such as the scalp, forehead, skin folds next to the nose, the skin surrounding the mouth, skin on the chest above the sternum, and in skin folds. Psoriatic arthritis Psoriatic arthritis is a form of chronic inflammatory arthritis that has a highly variable clinical presentation and frequently occurs in association with skin and nail psoriasis. It typically involves painful inflammation of the joints and surrounding connective tissue, and can occur in any joint, but most commonly affects the joints of the fingers and toes. This can result in a sausage-shaped swelling of the fingers and toes known as dactylitis. Psoriatic arthritis can also affect the hips, knees, spine (spondylitis), and sacroiliac joint (sacroiliitis). About 30% of individuals with psoriasis will develop psoriatic arthritis. Skin manifestations of psoriasis tend to occur before arthritic manifestations in about 75% of cases. Nail changes Psoriasis can affect the nails and produces a variety of changes in the appearance of fingers and toenails. Nail psoriasis occurs in 40–45% of people with psoriasis affecting the skin, and has a lifetime incidence of 80–90% in those with psoriatic arthritis. These changes include pitting of the nails (pinhead-sized depressions in the nail is seen in 70% with nail psoriasis), whitening of the nail, small areas of bleeding from capillaries under the nail, yellow-reddish discoloration of the nails known as the oil drop or salmon spots, dryness, thickening of the skin under the nail (subungual hyperkeratosis), loosening and separation of the nail (onycholysis), and crumbling of the nail. Medical signs In addition to the appearance and distribution of the rash, specific medical signs may be used by medical practitioners to assist with diagnosis. These may include Auspitzs sign (pinpoint bleeding when scale is removed), Koebner phenomenon (psoriatic skin lesions induced by trauma to the skin), and itching and pain localized to papules and plaques. Causes The cause of psoriasis is not fully understood, but many theories exist. Genetics Around one-third of people with psoriasis report a family history of the disease, and researchers have identified genetic loci associated with the condition. Identical twin studies suggest a 70% chance of a twin developing psoriasis if the other twin has the disorder. The risk is around 20% for nonidentical twins. These findings suggest both a genetic susceptibility and an environmental response in developing psoriasis.Psoriasis has a strong hereditary component, and many genes are associated with it, but how those genes work together is unclear. Most of the identified genes relate to the immune system, particularly the major histocompatibility complex (MHC) and T cells. Genetic studies are valuable due to their ability to identify molecular mechanisms and pathways for further study and potential medication targets.Classic genome-wide linkage analysis has identified nine loci on different chromosomes associated with psoriasis. They are called psoriasis susceptibility 1 through 9 (PSORS1 through PSORS9). Within those loci are genes on pathways that lead to inflammation. Certain variations (mutations) of those genes are commonly found in psoriasis. Genome-wide association scans have identified other genes that are altered to characteristic variants in psoriasis. Some of these genes express inflammatory signal proteins, which affect cells in the immune system that are also involved in psoriasis. Some of these genes are also involved in other autoimmune diseases.The major determinant is PSORS1, which probably accounts for 35–50% of psoriasis heritability. It controls genes that affect the immune system or encode skin proteins that are overabundant with psoriasis. PSORS1 is located on chromosome 6 in the MHC, which controls important immune functions. Three genes in the PSORS1 locus have a strong association with psoriasis vulgaris: HLA-C variant HLA-Cw6, which encodes an MHC class I protein; CCHCR1, variant WWC, which encodes a coiled coil protein overexpressed in psoriatic epidermis; and CDSN, variant allele 5, which encodes corneodesmosin, a protein expressed in the granular and cornified layers of the epidermis and upregulated in psoriasis.Two major immune system genes under investigation are interleukin-12 subunit beta (IL12B) on chromosome 5q, which expresses interleukin-12B; and IL23R on chromosome 1p, which expresses the interleukin-23 receptor, and is involved in T cell differentiation. Interleukin-23 receptor and IL12B have both been strongly linked with psoriasis. T cells are involved in the inflammatory process that leads to psoriasis. These genes are on the pathway that upregulate tumor necrosis factor-α and nuclear factor κB, two genes involved in inflammation. The first gene directly linked to psoriasis was identified as the CARD14 gene located in the PSORS2 locus. A rare mutation in the gene encoding for the CARD14-regulated protein plus an environmental trigger was enough to cause plaque psoriasis (the most common form of psoriasis). Lifestyle Conditions reported as worsening the disease include chronic infections, stress, and changes in season and climate. Others factors that might worsen the condition include hot water, scratching psoriasis skin lesions, skin dryness, excessive alcohol consumption, cigarette smoking, and obesity. The effects of stopping cigarette smoking or alcohol misuse have yet to be studied as of 2019. HIV The rate of psoriasis in human immunodeficiency virus-positive (HIV) individuals is comparable to that of HIV-negative individuals, but psoriasis tends to be more severe in people infected with HIV. A much higher rate of psoriatic arthritis occurs in HIV-positive individuals with psoriasis than in those without the infection. The immune response in those infected with HIV is typically characterized by cellular signals from Th2 subset of CD4+ helper T cells, whereas the immune response in psoriasis vulgaris is characterized by a pattern of cellular signals typical of Th1 subset of CD4+ helper T cells and Th17 helper T cells. The diminished CD4+-T cell presence is thought to cause an overactivation of CD8+-T cells, which are responsible for the exacerbation of psoriasis in HIV-positive people. Psoriasis in those with HIV/AIDS is often severe and may be untreatable with conventional therapy. In those with long-term, well-controlled psoriasis, new HIV infection can trigger a severe flare-up of psoriasis and/or psoriatic arthritis. Microbes Psoriasis has been described as occurring after strep throat, and may be worsened by skin or gut colonization with Staphylococcus aureus, Malassezia spp., and Candida albicans. Guttate psoriasis often affects children and adolescents and can be triggered by a recent group A streptococcal infection (tonsillitis or pharyngitis). Medications Drug-induced psoriasis may occur with beta blockers, lithium, antimalarial medications, nonsteroidal anti-inflammatory drugs, terbinafine, calcium channel blockers, captopril, glyburide, granulocyte colony-stimulating factor, interleukins, interferons, lipid-lowering medications,: 197  and paradoxically TNF inhibitors such as infliximab or adalimumab. Withdrawal of corticosteroids (topical steroid cream) can aggravate psoriasis due to the rebound effect. Pathophysiology Psoriasis is characterized by an abnormally excessive and rapid growth of the epidermal layer of the skin. Abnormal production of skin cells (especially during wound repair) and an overabundance of skin cells result from the sequence of pathological events in psoriasis. The sequence of pathological events in psoriasis is thought to start with an initiation phase in which an event (skin trauma, infection, or drugs) leads to activation of the immune system and then the maintenance phase consisting of chronic progression of the disease. Skin cells are replaced every 3–5 days in psoriasis rather than the usual 28–30 days. These changes are believed to stem from the premature maturation of keratinocytes induced by an inflammatory cascade in the dermis involving dendritic cells, macrophages, and T cells (three subtypes of white blood cells). These immune cells move from the dermis to the epidermis and secrete inflammatory chemical signals (cytokines) such as interleukin-36γ, tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-22. These secreted inflammatory signals are believed to stimulate keratinocytes to proliferate. One hypothesis is that psoriasis involves a defect in regulatory T cells, and in the regulatory cytokine interleukin-10. The inflammatory cytokines found in psoriatic nails and joints (in the case of psoriatic arthritis) are similar to those of psoriatic skin lesions, suggesting a common inflammatory mechanism.Gene mutations of proteins involved in the skins ability to function as a barrier have been identified as markers of susceptibility for the development of psoriasis.Deoxyribonucleic acid (DNA) released from dying cells acts as an inflammatory stimulus in psoriasis and stimulates the receptors on certain dendritic cells, which in turn produce the cytokine interferon-α. In response to these chemical messages from dendritic cells and T cells, keratinocytes also secrete cytokines such as interleukin-1, interleukin-6, and tumor necrosis factor-α, which signal downstream inflammatory cells to arrive and stimulate additional inflammation.Dendritic cells bridge the innate immune system and adaptive immune system. They are increased in psoriatic lesions and induce the proliferation of T cells and type 1 helper T cells (Th1). Targeted immunotherapy, as well as psoralen and ultraviolet A (PUVA) therapy, can reduce the number of dendritic cells and favors a Th2 cell cytokine secretion pattern over a Th1/Th17 cell cytokine profile. Psoriatic T cells move from the dermis into the epidermis and secrete interferon-γ and interleukin-17. Interleukin-23 is known to induce the production of interleukin-17 and interleukin-22. Interleukin-22 works in combination with interleukin-17 to induce keratinocytes to secrete neutrophil-attracting cytokines. Diagnosis A diagnosis of psoriasis is usually based on the appearance of the skin. Skin characteristics typical for psoriasis are scaly, erythematous plaques, papules, or patches of skin that may be painful and itch. No special blood tests or diagnostic procedures are usually required to make the diagnosis.The differential diagnosis of psoriasis includes dermatological conditions similar in appearance such as discoid eczema, seborrheic eczema, pityriasis rosea (may be confused with guttate psoriasis), nail fungus (may be confused with nail psoriasis) or cutaneous T cell lymphoma (50% of individuals with this cancer are initially misdiagnosed with psoriasis). Dermatologic manifestations of systemic illnesses such as the rash of secondary syphilis may also be confused with psoriasis.If the clinical diagnosis is uncertain, a skin biopsy or scraping may be performed to rule out other disorders and to confirm the diagnosis. Skin from a biopsy shows clubbed epidermal projections that interdigitate with dermis on microscopy. Epidermal thickening is another characteristic histologic finding of psoriasis lesions. The stratum granulosum layer of the epidermis is often missing or significantly decreased in psoriatic lesions; the skin cells from the most superficial layer of skin are also abnormal as they never fully mature. Unlike their mature counterparts, these superficial cells keep their nuclei. Inflammatory infiltrates can typically be seen on microscopy when examining skin tissue or joint tissue affected by psoriasis. Epidermal skin tissue affected by psoriatic inflammation often has many CD8+ T cells, while a predominance of CD4+ T cells makes up the inflammatory infiltrates of the dermal layer of skin and the joints. Classification Morphological Psoriasis is classified as a papulosquamous disorder and is most commonly subdivided into different categories based on histological characteristics. Variants include plaque, pustular, guttate, and flexural psoriasis. Each form has a dedicated ICD-10 code. Psoriasis can also be classified into nonpustular and pustular types. Pathogenetic Another classification scheme considers genetic and demographic factors. Type 1 has a positive family history, starts before the age of 40, and is associated with the human leukocyte antigen, HLA-Cw6. Conversely, type 2 does not show a family history, presents after age 40, and is not associated with HLA-Cw6. Type 1 accounts for about 75% of persons with psoriasis.The classification of psoriasis as an autoimmune disease has sparked considerable debate. Researchers have proposed differing descriptions of psoriasis and psoriatic arthritis; some authors have classified them as autoimmune diseases while others have classified them as distinct from autoimmune diseases and referred to them as immune-mediated inflammatory diseases. Severity No consensus exists about how to classify the severity of psoriasis. Mild psoriasis has been defined as a percentage of body surface area (BSA)≤10, a Psoriasis Area and Severity Index (PASI) score ≤10, and a Dermatology Life Quality Index (DLQI) score ≤10. Moderate to severe psoriasis was defined by the same group as BSA >10 or PASI score >10 and a DLQI score >10.The DLQI is a 10-question tool used to measure the impact of several dermatologic diseases on daily functioning. The DLQI score ranges from 0 (minimal impairment) to 30 (maximal impairment) and is calculated with each answer being assigned 0–3 points with higher scores indicating greater social or occupational impairment.The PASI is the most widely used measurement tool for psoriasis. It assesses the severity of lesions and the area affected and combines these two factors into a single score from 0 (no disease) to 72 (maximal disease). Nevertheless, the PASI can be too unwieldy to use outside of research settings, which has led to attempts to simplify the index for clinical use. Management While no cure is available for psoriasis, many treatment options exist. Topical agents are typically used for mild disease, phototherapy for moderate disease, and systemic agents for severe disease. There is no evidence to support the effectiveness of conventional topical and systemic drugs, biological therapy, or phototherapy for acute guttate psoriasis or an acute guttate flare of chronic psoriasis. Topical agents Topical corticosteroid preparations are the most effective agents when used continuously for eight weeks; retinoids and coal tar were found to be of limited benefit and may be no better than placebo. Greater benefit has been observed with very potent corticosteroids when compared to potent corticosteroids. Vitamin D analogues such as paricalcitol are superior to placebo. Combination therapy with vitamin D and a corticosteroid are superior to either treatment alone and vitamin D is superior to coal tar for chronic plaque psoriasis.For psoriasis of the scalp, a 2016 review found dual therapy (vitamin D analogues and topical corticosteroids) or corticosteroid monotherapy to be more effective and safer than topical vitamin D analogues alone. Due to their similar safety profiles and minimal benefit of dual therapy over monotherapy, corticosteroid monotherapy appears to be an acceptable treatment for short-term treatment.Moisturizers and emollients such as mineral oil, petroleum jelly, calcipotriol, and decubal (an oil-in-water emollient) were found to increase the clearance of psoriatic plaques. Some emollients have been shown to be even more effective at clearing psoriatic plaques when combined with phototherapy. Certain emollients, though, have no impact on psoriasis plaque clearance or may even decrease the clearance achieved with phototherapy, e.g. the emollient salicylic acid is structurally similar to para-aminobenzoic acid, commonly found in sunscreen, and is known to interfere with phototherapy in psoriasis. Coconut oil, when used as an emollient in psoriasis, has been found to decrease plaque clearance with phototherapy. Medicated creams and ointments applied directly to psoriatic plaques can help reduce inflammation, remove built-up scale, reduce skin turnover, and clear affected skin of plaques. Ointment and creams containing coal tar, dithranol, corticosteroids (i.e. desoximetasone), fluocinonide, vitamin D3 analogues (for example, calcipotriol), and retinoids are routinely used. (The use of the finger tip unit may be helpful in guiding how much topical treatment to use.)Vitamin D analogues may be useful with steroids; steroids alone have a higher rate of side effects. Vitamin D analogues may allow less steroids to be used.Another topical therapy used to treat psoriasis is a form of balneotherapy, which involves daily baths in the Dead Sea. This is usually done for four weeks with the benefit attributed to sun exposure and specifically UVB light. This is cost-effective and it has been propagated as an effective way to treat psoriasis without medication. Decreases of PASI scores greater than 75% and remission for several months have commonly been observed. Side effects may be mild such as itchiness, folliculitis, sunburn, poikiloderma, and a theoretical risk of nonmelanoma cancer or melanoma has been suggested. Some studies indicate no increased risk of melanoma in the long term. Data are inconclusive with respect to nonmelanoma skin cancer risk, but support the idea that the therapy is associated with an increased risk of benign forms of sun-induced skin damage such as, but not limited to, actinic elastosis or liver spots. Dead Sea balneotherapy is also effective for psoriatic arthritis. Tentative evidence indicates that balneophototherapy, a combination of salt bathes and exposure to ultraviolet B-light (UVB), in chronic plaque psoriasis is better than UVB alone. UV phototherapy Phototherapy in the form of sunlight has long been used for psoriasis. UVB wavelengths of 311–313 nanometers are most effective, and special lamps have been developed for this application. The exposure time should be controlled to avoid overexposure and burning of the skin. The UVB lamps should have a timer that turns off the lamp when the time ends. The amount of light used is determined by a persons skin type. Increased rates of cancer from treatment appear to be small. Narrowband UVB therapy has been demonstrated to have similar efficacy to psoralen and ultraviolet A phototherapy (PUVA). A 2013 meta-analysis found no difference in efficacy between NB-UVB and PUVA in the treatment of psoriasis, but NB-UVB is usually more convenient.One of the problems with clinical phototherapy is the difficulty many people have gaining access to a facility. Indoor tanning resources are almost ubiquitous today and could be considered as a means for people to get UV exposure when dermatologist-provided phototherapy is not available. Indoor tanning is already used by many people as a treatment for psoriasis; one indoor facility reported that 50% of its clients were using the center for psoriasis treatment; another reported 36% were doing the same thing. However, a concern with the use of commercial tanning is that tanning beds that primarily emit UVA might not effectively treat psoriasis. One study found that plaque psoriasis is responsive to erythemogenic doses of either UVA or UVB, as exposure to either can cause dissipation of psoriatic plaques. It does require more energy to reach erythemogenic dosing with UVA.UV light therapies all have risks; tanning beds are no exception, being listed by the World Health Organization as carcinogens. Exposure to UV light is known to increase the risks of melanoma and squamous cell and basal cell carcinomas; younger people with psoriasis, particularly those under age 35, are at increased risk from melanoma from UV light treatment. A review of studies recommends that people who are susceptible to skin cancers exercise caution when using UV light therapy as a treatment.A major mechanism of NB-UVB is the induction of DNA damage in the form of pyrimidine dimers. This type of phototherapy is useful in the treatment of psoriasis because the formation of these dimers interferes with the cell cycle and stops it. The interruption of the cell cycle induced by NB-UVB opposes the characteristic rapid division of skin cells seen in psoriasis. The activity of many types of immune cells found in the skin is also effectively suppressed by NB-UVB phototherapy treatments. The most common short-term side effect of this form of phototherapy is redness of the skin; less common side effects of NB-UVB phototherapy are itching and blistering of the treated skin, irritation of the eyes in the form of conjunctival inflammation or inflammation of the cornea, or cold sores due to reactivation of the herpes simplex virus in the skin surrounding the lips. Eye protection is usually given during phototherapy treatments.PUVA combines the oral or topical administration of psoralen with exposure to ultraviolet A (UVA) light. The mechanism of action of PUVA is unknown, but probably involves activation of psoralen by UVA light, which inhibits the abnormally rapid production of the cells in psoriatic skin. There are multiple mechanisms of action associated with PUVA, including effects on the skins immune system. PUVA is associated with nausea, headache, fatigue, burning, and itching. Long-term treatment is associated with squamous cell carcinoma (but not with melanoma). A combination therapy for moderate to severe psoriasis using PUVA plus acitretin resulted in benefit, but acitretin use has been associated with birth defects and liver damage. Systemic agents Psoriasis resistant to topical treatment and phototherapy may be treated with systemic therapies including medications by mouth or injectable treatments. People undergoing systemic treatment must have regular blood and liver function tests to check for medication toxicities. Pregnancy must be avoided for most of these treatments. The majority of people experience a recurrence of psoriasis after systemic treatment is discontinued. Non-biologic systemic treatments frequently used for psoriasis include methotrexate, ciclosporin, hydroxycarbamide, fumarates such as dimethyl fumarate, and retinoids. Methotrexate and ciclosporin are medications that suppress the immune system; retinoids are synthetic forms of vitamin A. These agents are also regarded as first-line treatments for psoriatic erythroderma. Oral corticosteroids should not be used, for they can severely flare psoriasis upon their discontinuation.Biologics are manufactured proteins that interrupt the immune process involved in psoriasis. Unlike generalized immunosuppressive medical therapies such as methotrexate, biologics target specific aspects of the immune system contributing to psoriasis. These medications are generally well-tolerated, and limited long-term outcome data have demonstrated biologics to be safe for long-term use in moderate to severe plaque psoriasis. However, due to their immunosuppressive actions, biologics have been associated with a small increase in the risk for infection.Guidelines regard biologics as third-line treatment for plaque psoriasis following inadequate response to topical treatment, phototherapy, and non-biologic systemic treatments. The safety of biologics during pregnancy has not been assessed. European guidelines recommend avoiding biologics if a pregnancy is planned; anti-TNF therapies such as infliximab are not recommended for use in chronic carriers of the hepatitis B virus or individuals infected with HIV.Several monoclonal antibodies target cytokines, the molecules that cells use to send inflammatory signals to each other. TNF-α is one of the main executor inflammatory cytokines. Four monoclonal antibodies (MAbs) (infliximab, adalimumab, golimumab, and certolizumab pegol) and one recombinant TNF-α decoy receptor, etanercept, have been developed to inhibit TNF-α signaling. Additional monoclonal antibodies, such as ixekizumab, have been developed against pro-inflammatory cytokines and inhibit the inflammatory pathway at a different point than the anti-TNF-α antibodies. IL-12 and IL-23 share a common domain, p40, which is the target of the FDA-approved ustekinumab. In 2017 the US FDA approved guselkumab for plaque psoriasis. There have been few studies of the efficacy of anti-TNF medications for psoriasis in children. One randomized control study suggested that 12 weeks of etanercept treatment reduced the extent of psoriasis in children with no lasting adverse effects.Two medications that target T cells are efalizumab and alefacept. Efalizumab is a monoclonal antibody that specifically targets the CD11a subunit of LFA-1. It also blocks the adhesion molecules on the endothelial cells that line blood vessels, which attract T cells. Efalizumab was voluntarily withdrawn from the European market in February 2009, and from the U.S. market in June 2009, by the manufacturer due to the medications association with cases of progressive multifocal leukoencephalopathy. Alefacept also blocks the molecules that dendritic cells use to communicate with T cells and even causes natural killer cells to kill T cells as a way of controlling inflammation. Apremilast may also be used.Individuals with psoriasis may develop neutralizing antibodies against monoclonal antibodies. Neutralization occurs when an antidrug antibody prevents a monoclonal antibody such as infliximab from binding antigen in a laboratory test. Specifically, neutralization occurs when the anti-drug antibody binds to infliximabs antigen binding site instead of TNF-α. When infliximab no longer binds tumor necrosis factor alpha, it no longer decreases inflammation, and psoriasis may worsen. Neutralizing antibodies have not been reported against etanercept, a biologic medication that is a fusion protein composed of two TNF-α receptors. The lack of neutralizing antibodies against etanercept is probably secondary to the innate presence of the TNF-α receptor, and the development of immune tolerance.A 2021 meta-analysis found that ixekizumab, secukinumab, brodalumab, guselkumab, certolizumab, and ustekinumab were the most effective biologics for treating psoriasis. In general, anti-IL17, anti-IL12/23, anti-IL23, and anti-TNF alpha biologics were found to be more effective than traditional systemic treatments. The immunologic pathways of psoriasis involve Th9, Th17, Th1 lymphocytes, and IL-22. The aforementioned biologic agents hinder different aspects of these pathways.Another treatment for moderate to severe psoriasis is fumaric acid esters (FAE) which may be similar in effectiveness to methotrexate.It has been theorized that antistreptococcal medications may improve guttate and chronic plaque psoriasis; however, the limited studies do not show that antibiotics are effective. Surgery Limited evidence suggests removal of the tonsils may benefit people with chronic plaque psoriasis, guttate psoriasis, and palmoplantar pustulosis. Diet Uncontrolled studies have suggested that individuals with psoriasis or psoriatic arthritis may benefit from a diet supplemented with fish oil rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). A low-calorie diet appears to reduce the severity of psoriasis. Diet recommendations include consumption of cold water fish (preferably wild fish, not farmed) such as salmon, herring, and mackerel; extra virgin olive oil; legumes; vegetables; fruits; and whole grains; and avoid consumption of alcohol, red meat, and dairy products (due to their saturated fat). The effect of consumption of caffeine (including coffee, black tea, mate, and dark chocolate) remains to be determined.Many patients report improvements after consuming less tobacco, caffeine, sugar, nightshades (tomatoes, eggplant, peppers, paprika and white potatoes) and taking probiotics and oral Vitamin D.There is a higher rate of celiac disease among people with psoriasis. When adopting a gluten-free diet, disease severity generally decreases in people with celiac disease and those with anti-gliadin antibodies. Prognosis Most people with psoriasis experience nothing more than mild skin lesions that can be treated effectively with topical therapies.Psoriasis is known to hurt the quality of life of both the affected person and the individuals family members. Depending on the severity and location of outbreaks, individuals may experience significant physical discomfort and some disability. Itching and pain can interfere with basic functions, such as self-care and sleep. Participation in sporting activities, certain occupations, and caring for family members can become difficult activities for those with plaques located on their hands and feet. Plaques on the scalp can be particularly embarrassing, as flaky plaque in the hair can be mistaken for dandruff.Individuals with psoriasis may feel self-conscious about their appearance and have a poor self-image that stems from fear of public rejection and psychosexual concerns. Psoriasis has been associated with low self-esteem and depression is more common among those with the condition. People with psoriasis often feel prejudiced against due to the commonly held incorrect belief that psoriasis is contagious. Psychological distress can lead to significant depression and social isolation; a high rate of thoughts about suicide has been associated with psoriasis. Many tools exist to measure the quality of life of people with psoriasis and other dermatological disorders. Clinical research has indicated individuals often experience a diminished quality of life. Children with psoriasis may encounter bullying.Several conditions are associated with psoriasis. These occur more frequently in older people. Nearly half of individuals with psoriasis over the age of 65 have at least three comorbidities (concurrent conditions), and two-thirds have at least two comorbidities. Cardiovascular disease Psoriasis has been associated with obesity and several other cardiovascular and metabolic disturbances. The number of new cases per year of diabetes is 27% higher in people affected by psoriasis than in those without the condition. Severe psoriasis may be even more strongly associated with the development of diabetes than mild psoriasis. Younger people with psoriasis may also be at increased risk for developing diabetes. Individuals with psoriasis or psoriatic arthritis have a slightly higher risk of heart disease and heart attacks when compared to the general population. Cardiovascular disease risk appeared to be correlated with the severity of psoriasis and its duration. There is no strong evidence to suggest that psoriasis is associated with an increased risk of death from cardiovascular events. Methotrexate may provide a degree of protection for the heart.The odds of having hypertension are 1.58 times ( i.e. 58%) higher in people with psoriasis than those without the condition; these odds are even higher with severe cases of psoriasis. A similar association was noted in people who have psoriatic arthritis—the odds of having hypertension were found to be 2.07 times ( i.e. 107%) greater when compared to odds of the general population. The link between psoriasis and hypertension is not currently understood. Mechanisms hypothesized to be involved in this relationship include the following: dysregulation of the renin–angiotensin system, elevated levels of endothelin 1 in the blood, and increased oxidative stress. The number of new cases of the heart rhythm abnormality atrial fibrillation is 1.31 times ( i.e. 31%) higher in people with mild psoriasis and 1.63 times ( i.e. 63%) higher in people with severe psoriasis. There may be a slightly increased risk of stroke associated with psoriasis, especially in severe cases. Treating high levels of cholesterol with statins has been associated with decreased psoriasis severity, as measured by PASI score, and has also been associated with improvements in other cardiovascular disease risk factors such as markers of inflammation. These cardioprotective effects are attributed to ability of statins to improve blood lipid profile and because of their anti-inflammatory effects. Statin use in those with psoriasis and hyperlipidemia was associated with decreased levels of high-sensitivity C-reactive protein and TNFα as well as decreased activity of the immune protein LFA-1. Compared to individuals without psoriasis, those affected by psoriasis are more likely to satisfy the criteria for metabolic syndrome. Other diseases The rates of Crohn disease and ulcerative colitis are increased when compared with the general population, by a factor of 3.8 and 7.5 respectively. People with psoriasis also have a higher risk of celiac disease. Few studies have evaluated the association of multiple sclerosis with psoriasis, and the relationship has been questioned. Psoriasis has been associated with a 16% increase in overall relative risk for non-skin cancer, thought to be attributed to systemic therapy, particularly methotrexate. People treated with long term systemic therapy for psoriasis have a 52% increased risk cancers of the lung and bronchus, a 205% increase in the risk of developing cancers of the upper gastrointestinal tract, a 31% increase in the risk of developing cancers of the urinary tract, a 90% increase in the risk of developing liver cancer, and a 46% increase in the risk of developing pancreatic cancer. The risk for development of non-melanoma skin cancers is also increased. Psoriasis increases the risk of developing squamous cell carcinoma of the skin by 431% and increases the risk of basal cell carcinoma by 100%. There is no increased risk of melanoma associated with psoriasis. People with psoriasis have a higher risk of developing cancer. Epidemiology Psoriasis is estimated to affect 2–4% of the population of the western world. The rate of psoriasis varies according to age, region and ethnicity; a combination of environmental and genetic factors is thought to be responsible for these differences. It can occur at any age, although it most commonly appears for the first time between the ages of 15 and 25 years. Approximately one third of people with psoriasis report being diagnosed before age 20. Psoriasis affects both sexes equally.Psoriasis affects about 6.7 million Americans and occurs more frequently in adults.Psoriasis is about five times more common in people of European descent than in people of Asian descent.People with inflammatory bowel disease such as Crohn disease or ulcerative colitis are at an increased risk of developing psoriasis. Psoriasis is more common in countries farther from the equator. Persons of white European ancestry are more likely to have psoriasis and the condition is relatively uncommon in African Americans and extremely uncommon in Native Americans. History Scholars believe psoriasis to have been included among the various skin conditions called tzaraath (translated as leprosy) in the Hebrew Bible, a condition imposed as a punishment for slander. The person was deemed "impure" (see tumah and taharah) during their affected phase and is ultimately treated by the kohen. However, it is more likely that this confusion arose from the use of the same Greek term for both conditions. The Greeks used the term lepra (λεπρα) for scaly skin conditions. They used the term psora to describe itchy skin conditions. It became known as Willans lepra in the late 18th century when English dermatologists Robert Willan and Thomas Bateman differentiated it from other skin diseases. Leprosy, they said, is distinguished by the regular, circular form of patches, while psoriasis is always irregular. Willan identified two categories: leprosa graecorum and psora leprosa.Psoriasis is thought to have first been described in Ancient Rome by Cornelius Celsus. The British dermatologist Thomas Bateman described a possible link between psoriasis and arthritic symptoms in 1813.The history of psoriasis is littered with treatments of dubious effectiveness and high toxicity. In the 18th and 19th centuries, Fowlers solution, which contains a poisonous and carcinogenic arsenic compound, was used by dermatologists as a treatment for psoriasis. Mercury was also used for psoriasis treatment during this time period. Sulfur, iodine, and phenol were also commonly used treatments for psoriasis during this era when it was incorrectly believed that psoriasis was an infectious disease. Coal tars were widely used with ultraviolet light irradiation as a topical treatment approach in the early 1900s. During the same time period, psoriatic arthritis cases were treated with intravenously administered gold preparations in the same manner as rheumatoid arthritis. Society and culture The International Federation of Psoriasis Associations (IFPA) is the global umbrella organization for national and regional psoriasis associations and also gathers the leading experts in psoriasis and psoriatic arthritis research for scientific conferences every three years. The Psoriasis International Network, a program of the Fondation René Touraine, gathers dermatologists, rheumatologists and other caregivers involved in the management of psoriasis. Non-profit organizations like the National Psoriasis Foundation in the United States, the Psoriasis Association in the United Kingdom, and Psoriasis Australia offer advocacy and education about psoriasis in their respective countries. Cost The annual cost for treating psoriasis in the United States is estimated as high as $32.5 billion, including $12.2 billion in direct costs. Pharmacy costs are the main source of direct expense, with biologic therapy the most prevalent. These costs increase significantly when co-morbid conditions such as heart disease, hypertension, diabetes, lung disease and psychiatric disorders are factored in. Expenses linked to co-morbidities are estimated at an additional $23,000 per person per year. Research The role of insulin resistance in the pathogenesis of psoriasis is under investigation. Preliminary research has suggested that antioxidants such as polyphenols may have beneficial effects on the inflammation characteristic of psoriasis.Many novel medications being researched during the 2010s target the Th17/IL-23 axis, particularly IL-23p19 inhibitors, as IL-23p19 is present in increased concentrations in psoriasis skin lesions while contributing less to protection against opportunistic infections. Other cytokines such as IL-17 and IL-22 also have been targets for inhibition as they play important roles in the pathogenesis of psoriasis. Another avenue of research has focused on the use of vascular endothelial growth factor inhibitors to treat psoriasis. Oral agents being investigated during the 2010s as alternatives to medications administered by injection include Janus kinase inhibitors, protein kinase C inhibitors, mitogen-activated protein kinase inhibitors, and phosphodiesterase 4 inhibitors, all of which have proven effective in various phase 2 and 3 clinical trials. These agents have potentially severe side-effects due to their immunosuppressive mechanisms. References Further reading External links "Psoriatic arthritis". Genetics Home Reference. "Psoriasis". MedlinePlus. U.S. National Library of Medicine.

You serve as a medical tutor. Your objective is to demystify medical terms, providing thorough explanations that cater to various levels of medical knowledge.

Please help me grasp the concept behind the medical term 'Separation anxiety disorder.'

Separation anxiety disorder (SAD) is an anxiety disorder in which an individual experiences excessive anxiety regarding separation from home and/or from people to whom the individual has a strong emotional attachment (e.g., a parent, caregiver, significant other, or siblings). Separation anxiety is a natural part of the developmental process. It is most common in infants and little children, typically between the ages of six to seven months to three years, although it may pathologically manifest itself in older children, adolescents and adults. Unlike SAD (indicated by excessive anxiety), normal separation anxiety indicates healthy advancements in a childs cognitive maturation and should not be considered a developing behavioral problem.According to the American Psychiatric Association (APA), separation anxiety disorder is an excessive display of fear and distress when faced with situations of separation from the home and/or from a specific attachment figure. The anxiety that is expressed is categorized as being atypical of the expected developmental level and age. The severity of the symptoms ranges from anticipatory uneasiness to full-blown anxiety about separation.SAD may cause significant negative effects within areas of social and emotional functioning, family life, and physical health of the disordered individual. The duration of this problem must persist for at least four weeks and must present itself before a child is eighteen years of age to be diagnosed as SAD in children, but can now be diagnosed in adults with a duration typically lasting six months in adults as specified by the DSM-5. Background The origins of separation anxiety disorder stem from attachment theory which has roots in the attachment theories both of Sigmund Freud and John Bowlby. Freuds attachment theory, which has similarities to learning theory, proposes that infants have instinctual impulses, and when these impulses go unnoticed, it traumatizes the infant. The infant then learns that when their mother is absent, this will be followed by a distressing lack of gratification, thus making the mothers absence a conditioned stimulus that triggers anxiety in the infant who then expects their needs to be ignored. The result of this association is that the child becomes fearful of all situations that include distance from their caregiver. John Bowlbys attachment theory also contributed to the thinking process surrounding separation anxiety disorder. His theory is a framework in which to contextualize the relationships that humans form with one another. Bowlby suggests that infants are instinctively motivated to seek proximity with a familiar caregiver, especially when they are alarmed, and they expect that in these moments they will be met with emotional support and protection. He poses that all infants become attached to their caregivers, however, there are individual differences in the way that these attachments develop. There are 4 main attachment styles according to Bowlby; secure attachment, anxious-avoidant attachment, disorganized attachment, and anxious-ambivalent attachment. Anxious-ambivalent attachment is most relevant here because its description, when an infant feels extreme distress and anxiety when their caregiver is absent and does not feel reassured when they return, is very similar to SAD. Signs and symptoms Academic setting As with other anxiety disorders, children with SAD tend to face more obstacles at school than those without anxiety disorders. Adjustment and relating school functioning have been found to be much more difficult for anxious children. In some severe forms of SAD, children may act disruptively in class or may refuse to attend school altogether. It is estimated that nearly 75% of children with SAD exhibit some form of school refusal behavior.There are several possible manifestations of this disorder when the child is introduced into an academic setting. A child with SAD may protest profusely upon arrival at school. They might have a hard time saying goodbye to their parents and exhibit behaviors like tightly clinging to the parent in a way that makes it nearly impossible for the parent to detach from them. They might scream and cry but in a way that makes it seem as though they were in pain. The child might scream and cry for an extended period of time after his or her parents are gone (for several minutes to upwards of an hour) and refuse to interact with other children or teachers, rejecting their attention. They might feel an overwhelming need to know where their parents are and that they are okay. This is a serious problem because, as children fall further behind in coursework, it becomes increasingly difficult for them to return to school.Short-term problems resulting from academic refusal include poor academic performance or decline in performance, alienation from peers, and conflict within the family.Although school refusal behavior is common among children with SAD, it is important to note that school refusal behavior is sometimes linked to generalized anxiety disorder or possibly a mood disorder. That being said, a majority of children with separation anxiety disorder have school refusal as a symptom. Up to 80% of children who refuse school qualify for a diagnosis of separation anxiety disorder. Home setting Symptoms for SAD might persist even in a familiar and/or comfortable setting for the child, like the home. The child might be afraid to be in a room alone even if they know that their parent is in the next room over. They might fear being alone in the room, or going to sleep in a dark room. Problems might present themselves during bedtime, as the child might refuse to go to sleep unless their parent is near and visible. During the day, the child might "shadow" the parent and cling to their side. Workplace Just how SAD affects a childs attendance and participation in school, their avoidance behaviors stay with them as they grow and enter adulthood. Recently, "the effects of mental illness on workplace productivity have become a prominent concern on both the national and international fronts". In general, mental illness is a common health problem among working adults, 20% to 30% of adults will suffer from at least one psychiatric disorder. Mental illness is linked to decreased productivity, and with individuals diagnosed with SAD their levels at which they function decreases dramatically resulting in partial work-days, increase in number of total absences, and "holding back" when it comes to carrying out and completing tasks. Cause Factors that contribute to the disorder include a combination and interaction of biological, cognitive, environmental, child temperament, and behavioral factors. Children are more likely to develop SAD if one or both of their parents was diagnosed with a psychological disorder. Recent research by Daniel Schechter and colleagues have pointed to difficulties of mothers who have themselves had early adverse experiences such as maltreatment and disturbed attachments with their own caregivers, who then go on to develop responses to their infants and toddlers normative social bids in the service of social referencing, emotion regulation, and joint attention, which responses are linked to these mothers own psychopathology (i.e. maternal post-traumatic stress disorder (PTSD) and depression.) These atypical maternal responses which have been shown to be associated with separation anxiety have been related to disturbances in maternal stress physiologic response to mother-toddler separation as well as lower maternal neural activity in the brain region of the medial prefrontal cortex when mothers with and without PTSD were shown video excerpts of their own and unfamiliar toddlers during mother-child separation versus free-play.Many psychological professionals have suggested that early or traumatic separation from a central caregiver in a childs life can increase the likelihood of them being diagnosed with SAD, school phobia, and depressive-spectrum disorders. Some children can be more vulnerable to SAD due to their temperament, for example, their level of anxiety when placed in new situations. Environmental Most often, the onset of separation anxiety disorder is caused by a stressful life-event, especially a loss of a loved one or pet, but can also include parental divorce, change of school or neighbourhood, natural disasters, or circumstances which forced the individual to be separated from their attachment figure(s). In older individuals, stressful life experiences may include going away to college, moving out for the first time, or becoming a parent. According to the DSM-5 young adults with separation anxiety disorder have different examples of stress, including leaving their parents home, entering a romantic relationship, and becoming a parent. In some cases parental overprotectiveness may be associated with separation anxiety disorder. Genetic and physiological There may be a genetic predisposition in children with separation anxiety disorder. "Separation anxiety disorder in children may be heritable." "Heritability was estimated at 73% in a community sample of 6-year-old twins, with higher rates in girls."A childs temperament can also impact the development of SAD. Timid and shy behaviors may be referred to as "behaviorally inhibited temperaments" in which the child may experience anxiety when they are not familiar with a particular location or person. Mechanism Preliminary evidence shows that heightened activity of the amygdala may be associated with symptoms of separation anxiety disorder. Defects in the ventrolateral and dorsomedial areas of the prefrontal cortex are also correlated to anxiety disorders in children. Diagnosis Separation anxiety occurs in many infants and young children as they are becoming acclimated with their surroundings. This anxiety is viewed as a normal developmental phase between the months of early infancy until age two. Separation anxiety is normal in young children, until they age 3–4 years, when children are left in a daycare or preschool, away from their parent or primary caregiver. Other sources note that a definite diagnosis of SAD should not be presented until after the age of three.Some studies have shown that hormonal influences during pregnancy can result in lower cortisol levels later in life, which can later lead to psychological disorders, such as SAD. It is also important to note significant life changes experienced by the child either previous to or present at the onset of the disorder. For example, children who emigrated from another country at an early age may have a stronger tendency for developing this disorder, as they have already felt displaced from a location they were starting to become accustomed to. It is not uncommon for them to incessantly cling to their caregiver at first upon arrival to the new location, especially if the child is unfamiliar with the language of their new country. These symptoms may diminish or go away as the child becomes more accustomed to the new surroundings. Other sources note that a definite diagnosis of SAD should not be presented until after the age of three. Separation anxiety may be diagnosed as a disorder if the childs anxiety related to separation from the home or attachment figure is deemed excessive; if the level of anxiety surpasses that of the acceptable caliber for the childs developmental level and age; and if the anxiety negatively impacts the childs everyday life.Many psychological disorders begin to emerge during childhood. Nearly two-thirds of adults with psychological disorder show signs of their disorder earlier in life. However, not all psychological disorders are present before adulthood. In many cases, there are no signs during childhood.Behavioral inhibition (BI) plays a large role in many anxiety disorders, SAD included. Compared to children without it, children with BI demonstrate more signs of fear when experiencing a new stimulus, particularly those that are social in nature. Children with BI are at a higher risk for developing a mental disorder, particularly anxiety disorders, than children without BI.Separation anxiety is normal in young children, until they age 3–4 years, when children are left in a daycare or preschool, away from their parent or primary caregiver.To be diagnosed with SAD, one must display at least three of the following criteria: Recurrent excessive distress when anticipating or experiencing separation from home or from major attachment figures Persistent and excessive worry about losing major attachment figures or about possible harm to them, such as illness, injury, disasters, or death Persistent and excessive worry about experiencing an untoward event (e.g., getting lost, being kidnapped, having an accident, becoming ill) that causes separation from a major attachment figure Persistent reluctance or refusal to go out, away from home, to school, to work, or elsewhere because of fear of separation Persistent and excessive fear of or reluctance about being alone or without major attachment figures at home or in other settings Persistent reluctance or refusal to sleep away from home or to go to sleep without being near a major attachment figure Repeated nightmares involving the theme of separation Repeated complaints of physical symptoms (e.g., headaches, stomachaches, nausea, vomiting) when separation from major attachment figures occurs or is anticipated Classification Separation anxiety is common for infants between the ages of eight and fourteen months and occurs as infants begin to understand their own selfhood—or understand that they are separate persons from their primary caregiver. Infants oftentimes look for their caregivers to give them a sense of comfort and familiarity, which causes separation to become challenging. Subsequently, the concept of object permanence emerges—which is when children learn that something still exists when it cannot be seen or heard, thus increasing their awareness of being separated from their caregiver. Consequently, during the developmental period where an infants sense self, incorporating object permanence as well, the child also begins to understand that they can in fact be separated from their primary caregiver. They see this separation as something final though, and dont yet understand that their caregiver will return causing fear and distress for the infant. It is when an individual (infant, child, or otherwise) consistently reacts to separation with excessive anxiety and distress and experiences a great deal of interference from their anxiety that a diagnosis of separation anxiety disorder (SAD) can be warranted.One of the difficulties in the identification of separation anxiety disorder in children is that it is highly comorbid with other behavioral disorders, especially generalized anxiety disorder. Behaviors such as refusal or hesitancy in attending school or homesickness for example, can easily reflect similar symptoms and behavioral patterns that are commonly associated with SAD, but could be an overlap of symptoms. The prevalence of co-occurring disorders in adults with separation anxiety disorder is common and includes a much broader spectrum of diagnostic possibilities. Common co-morbidities can include specific phobias, PTSD, panic disorder, obsessive-compulsive disorder, and personality disorders. It is very common for psychological disorders to overlap and even lead to the manifestation of another, especially when it comes to anxiety disorders. Because of the variation and overlap in symptoms a proper, thorough evaluation of the individual is critical to distinguish the differences and significance. An important signifier to establish a difference between SAD and other anxiety or psychological disorders is to investigate where the individuals fear of separation is stemming from; this can be accomplished by asking "what they fear will occur during a separation from their significant other".What stands out about SAD, as mentioned above, are the avoidance behaviors which present within an individual. Individuals "typically exhibit excessive distress manifested by crying, repeated complaints of physical symptoms (e.g., stomach aches, headaches, etc.), avoidance (e.g., refusing to go to school, to sleep alone, to be left alone in the home, to engage in social events, to go to work, etc.), and engagement in safety behaviors (e.g., frequent calls to or from significant others, or primary caregivers)". Assessment methods Assessment methods include diagnostic interviews, self-report measures from both the parent and child, observation of parent-child interaction, and specialized assessment for preschool-aged children. Various facets of a childs development including social life, feeding and sleep schedules, medical issues, traumatic events experienced, family history of mental or anxiety health issues are explored. The compilation of aspects of a childs life aids in capturing a multi-dimensional view of the childs life.Additionally, while much research has been done in efforts to further understand separation anxiety in regards to the relationship between infants and their caregivers, it was behavioral psychologist, Mary Ainsworth, who devised a behavioral evaluation method, The Strange Situation (1969), which, at the time, was considered to be the most valuable and famous body of research in the study of separation anxiety. The Strange Situation process assisted in evaluating and measuring the individual attachment styles of infants between the ages of 9 and 18 months. In this observational study an environment is created that fluctuates between familiar and unfamiliar situations that would be experienced in everyday life. The variations in stressfulness and the childs responses are observed and, based on the interaction behavior that is directed towards the caregiver, the infant is categorized into one of four different types of attachment styles: 1. Secure, 2. Anxious-avoidant, insecure, 3. Anxious-ambivalent/resistant, insecure and 4. Disorganized/disoriented.Clinicians may utilize interviews as an assessment tool to gauge the symptomatic occurrences to aid in diagnosing SAD. Interviews may be conducted with the child and also with the attachment figure. Interviewing both child and parent separately allows for the clinician to compile different points of view and information.Commonly used interviews include: Anxiety Disorders Interview Schedule for the DSM-IV, Child Parent Versions (ADIS-IV-C/P) Diagnostic Interview Schedule for Children, Version IV (DISC-IV) Schedule for Affective Disorders and Schizophrenia for School-aged Children-Present and lifetime version IV (K-SADS-IV) Self-report measures This form of assessment should not be the sole basis of a SAD diagnosis. It is also important to verify that the child who is reporting on their experiences has the cognitive and communication skills appropriate to accurately comprehend and respond to these measurements. An example of a self-report tool that has been tested is: The Separation Anxiety Assessment Scale for Children (SAAS-C). The scale contains 34 items and is divided into six dimensions. The dimensions in order are: Abandonment, Fear of Being Alone, Fear of Physical Illness, Worry about Calamitous Events, Frequency of Calamitous Events, and Safety Signal Index. The first five dimensions have a total of five items while the last one contains nine items. The scale goes beyond assessing symptoms; it focuses on individual cases and treatment planning. Observation As noted by Altman, McGoey & Sommer, it is important to observe the child, "in multiple contexts, on numerous occasions, and in their everyday environments (home, daycare, preschool)". It is beneficial to view parent and child interactions and behaviors that may contribute to SAD.Dyadic Parent-Child Interaction Coding System and recently the Dyadic Parent-Child Interaction Coding System II (DPICS II) are methods used when observing parents and children interactions.Separation Anxiety Daily Diaries (SADD) have also been used to "assess anxious behaviors along with their antecedents and consequences and may be particularly suited to SAD given its specific focus on parent–child separation" (Silverman & Ollendick, 2005). The diaries are carefully evaluated for validity. Preschool-aged children At the preschool-aged stage, early identification and intervention is crucial. The communication abilities of young children are taken into consideration when creating age-appropriate assessments.A commonly used assessment tool for preschool-aged children (ages 2–5) is the Preschool Age Psychiatric Assessment (PAPA). Additional questionnaires and rating scales that are used to assess the younger population include the Achenbach Scales, the Fear Survey Schedule for Infants and Preschoolers, and The Infant–Preschool Scale for Inhibited Behaviors.Preschool children are also interviewed. Two interviews that are sometimes conducted are Attachment Doll-Play and Emotional Knowledge. In both of the assessments the interviewer depicts a scenario where separation and reunion occur; the child is then told to point at one of the four facial expressions presented. These facial expressions show emotions such as anger or sadness. The results are then analyzed.Behavioral observations are also utilized when assessing the younger population. Observations enable the clinician to view some of the behaviors and emotions in specific contexts. Treatment Non-medication based Non-medication based treatments are the first choice when treating individuals diagnosed with separation anxiety disorder. Counseling tends to be the best replacement for drug treatments. There are two different non-medication approaches to treat separation anxiety. The first is a psychoeducational intervention, often used in conjunction with other therapeutic treatments. This specifically involves educating the individual and their family so that they are knowledgeable about the disorder, as well as parent counseling and guiding teachers on how to help the child. The second is a psychotherapeutic intervention when prior attempts are not effective. Psychotherapeutic interventions are more structured and include behavioral, cognitive-behavioral, contingency, psychodynamic psychotherapy, and family therapy. Exposure and behavioral therapy Behavioral therapies are types of non-medication based treatment which are mainly exposure-based techniques. These include techniques such as systematic desensitization, emotive imagery, participant modelling and contingency management. Behavioral therapies carefully expose individuals by small increments to slowly reduce their anxiety over time and mainly focuses on their behavior. Exposure based therapy works under the principle of habituation that is derived from learning theory. The core concept of exposure therapy is that anxiety about situations, people, and things does not go away when people avoid the things that they fear, but rather, the uncomfortable feelings are simply kept at bay. In order to effectively diminish the negative feelings associated with the situation of fear, one must address them directly. In order to administer this treatment, the therapist and the anxious child might sit together and identify progressively intense situations. As each situation is dealt with masterfully, the child advances to the next phase of intensity. This pattern continues until the child is able to handle being away from their parent in a developmentally typical way that causes them and their caregiver(s) minimal amounts of stress. While there is some controversy about using exposure therapy with children, it is generally agreed upon that exposure therapy in the context of SAD is acceptable as it may be the most effective form of therapy in treating this disorder and there is minimal risk associated with the intervention in this context. Contingency management Contingency management is a form of treatment found to be effective for younger children with SAD. Contingency management revolves around a reward system with verbal or tangible reinforcement requiring parental involvement. A contingency contract is written up between the parent and the child, which entails a written agreement about specific goals that the child will try to achieve and the specific reward the parent will provide once the task is accomplished. When the child undergoing contingency management shows signs of independence or achieves their treatment goals, they are praised or given their reward. This facilitates a new positive experience with what used to be filled with fear and anxiety. Children in preschool who show symptoms of SAD do not have the communicative ability to express their emotions or the self-control ability to cope with their separation anxiety on their own, so parental involvement is crucial in younger cases of SAD. Cognitive behavioral therapy Cognitive behavioral therapy (CBT) focuses on helping children with SAD reduce feelings of anxiety through practices of exposure to anxiety-inducing situations and active metacognition to reduce anxious thoughts.CBT has three phases: education, application and relapse prevention. In the education phase, the individual is informed on the different effects anxiety can have physically and more importantly mentally. By understanding and being able to recognize their reactions, it will help to manage and eventually reduce their overall response.According to Kendall and colleagues, there are four components which must be taught to a child undergoing CBT: Recognizing anxious feelings and behaviors Discussing situations that provoke anxious behaviors Developing a coping plan with appropriate reactions to situations Evaluating effectiveness of the coping planIn the application phase, individuals can take what they know and apply it in real time situations for helpful exposure. The most important aspect of this phase is for the individuals to ultimately manage themselves throughout the process. In the relapse prevention phase, the individual is informed that continued exposure and application of what worked for them is the key to continual progress.A study investigated the content of thoughts in anxious children who suffered from separation anxiety as well as from social phobia or generalized anxiety. The results suggested that cognitive therapy for children suffering from separation anxiety (along with social phobia and generalized anxiety) should be aimed at identifying negative cognition of ones own behavior in the threat of anxiety-evoking situations and to modify these thoughts to promote self-esteem and ability to properly cope with the given situation.Cognitive procedures are a form of treatment found to be ideal for older children with SAD. The theory behind this technique is that the childs dysfunctional thoughts, attitudes, and beliefs are what leads to anxiety and causes anxious behavior. Children who are being treated with cognitive procedures are taught to ask themselves if there is "evidence" to support their anxious thoughts and behaviors. They are taught "coping thoughts" to replace previously distorted thoughts during anxiety-inducing situations such as doing a reality check to assess the realistic danger of a situation and then to praise themselves for handling the situation bravely. Examples of such disordered thoughts include polarized thinking, overgeneralization, filtering (focusing on negative), jumping to conclusions, catastrophizing, emotional reasoning, labeling, "shoulds", and placing blame on self and others. Sometimes therapists will involve parents and teach them behavioral tactics such as contingency management. Medication The use of medication is applied in extreme cases of SAD when other treatment options have been utilized and failed. However, it has been difficult to prove the benefits of drug treatment in patients with SAD because there have been many mixed results. Despite all the studies and testings, there has yet to be a specific medication for SAD. Medication prescribed for adults from the Food and Drug Administration (FDA) are often used and have been reported to show positive results for children and adolescents with SAD.There are mixed results regarding the benefits of using tricyclic antidepressants (TCAs), which includes imipramine and clomipramine. One study suggested that imipramine is helpful for children with "school phobia," who also had an underlying diagnosis of SAD. However, other studies have also shown that imipramine and clomipramine had the same effect of children who were treated with the medication and placebo. The most promising medication is the use of selective serotonin reuptake inhibitors (SSRI) in adults and children. Several studies have shown that patients treated with fluvoxamine were significantly better than those treated with placebo. They showed decreasing anxiety symptoms with short-term and long-term use of the medication. Prognosis Discomfort from separations in children from ages 8 to 14 months is normal. Children oftentimes get nervous or afraid of unfamiliar people and places but if the behavior still occurs after the age of six and if it lasts longer than four weeks, the child might have separation anxiety disorder. About 4% of children have the disorder. Separation anxiety disorder is very treatable especially when caught early on with medication and behavioral therapies. Helping children with separation anxiety to identify the circumstances that elicit their anxiety (upcoming separation events) is important. A childs ability to tolerate separations should gradually increase over time when he or she is gradually exposed to the feared events. Encouraging a child with separation anxiety disorder to feel competent and empowered, as well as to discuss feelings associated with anxiety-provoking events promotes recovery. Children with separation anxiety disorder often respond negatively to perceived anxiety in their caretakers, in that parents and caregivers who also have anxiety disorders may unwittingly confirm a childs unrealistic fears that something terrible may happen if they are separated from each other. Thus, it is critical that parents and caretakers become aware of their own feelings and communicate a sense of safety and confidence about separation. Longitudinal effects Several studies aim to understand the long-term mental health consequences of SAD. SAD contributed to vulnerability and acted as a strong risk factor for developing other mental disorders in people aged 19–30. Specifically disorders including panic disorder and depressive disorders were more likely to occur. Other sources also support the increased likelihood of displaying either of the two psychopathologies with previous history of childhood SAD.Studies show that children who have separation anxiety at younger ages have more complex fear acquisition. This means that there is likely an interplay between associative and non-associative processes concerning fear and anxiety later in life. Epidemiology Anxiety disorders are the most common type of psychopathology to occur in todays youth, affecting from 5–25% of children worldwide. Of these anxiety disorders, SAD accounts for a large proportion of diagnoses. SAD may account for up to 50% of the anxiety disorders as recorded in referrals for mental health treatment. SAD is noted as one of the earliest-occurring of all anxiety disorders. Adult separation anxiety disorder affects roughly 7% of adults. It has also been reported that the clinically anxious pediatric population are considerably larger. For example, according to Hammerness et al. (2008) SAD accounted for 49% of admissions.Research suggests that 4.1% of children will experience a clinical level of separation anxiety. Of that 4.1% it is calculated that nearly a third of all cases will persist into adulthood if left untreated. Research continues to explore the implications that early dispositions of SAD in childhood may serve as risk factors for the development of mental disorders throughout adolescence and adulthood. It is presumed that a much higher percentage of children suffer from a small amount of separation anxiety, and are not actually diagnosed. Multiple studies have found higher rates of SAD in girls than in boys, and that paternal absence may increase the chances of SAD in girls. See also Homesickness Stranger anxiety References External links The Strange Situation: Window on a Childs Past and Future Are you gonna leave me? Separation anxiety is associated with increased amygdala responsiveness and volume

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I'm trying to understand 'Complete androgen insensitivity syndrome' within a medical context. Could you shed some light on it?

Complete androgen insensitivity syndrome (CAIS) is an AIS condition that results in the complete inability of the cell to respond to androgens. As such, the insensitivity to androgens is only clinically significant when it occurs in individuals who are exposed to significant amounts of testosterone at some point in their lives. The unresponsiveness of the cell to the presence of androgenic hormones prevents the masculinization of male genitalia in the developing fetus, as well as the development of male secondary sexual characteristics at puberty, but does allow, without significant impairment, female genital and sexual development in those with the condition. All human fetuses begin fetal development looking similar, with both the Müllerian duct system (female) and the Wolffian duct system (male) developing. It is at the seventh week of gestation that the bodies of unaffected individuals with the XY karyotype begin their masculinization: i.e., the Wolffian duct system is promoted and the Müllerian duct system is suppressed (the reverse happens with typically developing females). This process is triggered by androgens produced by the gonads, which in individuals with the XX karyotype had earlier become ovaries, but in XY individuals typically had become testicles due to the presence of the Y Chromosome. The cells of unaffected XY individuals then masculinize by, among other things, enlarging the genital tubercle into a penis, which in females becomes the clitoris, while what in females becomes the labia fuses to become the scrotum of males (where the testicles will later descend). Individuals affected by CAIS develop a normal external female habitus, despite the presence of a Y chromosome, but internally, they will lack a uterus, and the vaginal cavity will be shallow, while the gonads, having been turned into testicles rather than ovaries in the earlier separate process also triggered by their Y chromosome, will remain undescended in the place where the ovaries would have been. This results not only in infertility in individuals with CAIS, but also presents a risk of gonadal cancer later on in life.CAIS is one of the three categories of androgen insensitivity syndrome (AIS) since AIS is differentiated according to the degree of genital masculinization: complete androgen insensitivity syndrome (CAIS) when the external genitalia is that of a typical female, mild androgen insensitivity syndrome (MAIS) when the external genitalia is that of a typical male, and partial androgen insensitivity syndrome (PAIS) when the external genitalia is partially, but not fully masculinized.Androgen insensitivity syndrome is the largest single entity that leads to 46, XY undermasculinization. Signs and symptoms Physical Individuals with complete androgen insensitivity syndrome (grades 6 and 7 on the Quigley scale) are born phenotypically female, without any signs of genital masculinization, despite having a 46,XY karyotype. Symptoms of CAIS do not appear until puberty, which may be slightly delayed, but is otherwise normal except for absent menses and diminished or absent secondary terminal hair. Axillary hair (i.e. armpit hair) fails to develop in one third of all cases. External genitalia is normal, although the labia and clitoris are sometimes underdeveloped. Vaginal depth varies widely for CAIS women, but is typically shorter than unaffected women; one study of eight women with CAIS measured the average vaginal depth to be 5.9 cm (vs. 11.1 ± 1.0 cm for unaffected women ). In some extreme cases, the vagina has been reported to be aplastic (resembling a "dimple"), though the exact incidence of this is unknown.The gonads in these women are not ovaries, but instead, are testes; during the embryonic stage of development, testes form in an androgen-independent process that occurs due to the influence of the SRY gene on the Y chromosome. They may be located intra-abdominally, at the internal inguinal ring, or may herniate into the labia majora, often leading to the discovery of the condition. Testes in affected women have been found to be atrophic upon gonadectomy.Testosterone produced by the testes cannot be directly used due to the mutant androgen receptor that characterizes CAIS; instead, it is aromatized into estrogen, which effectively feminizes the body and accounts for the normal female phenotype observed in CAIS. However, up to 5% of individuals with CAIS do not have an AR mutation. The receptor in question is encoded by the AR gene located on the X chromosome at Xq11–12. At least 15 different mutations were known in 2003, and they are all recessive, which makes the disease to follow X-linked recessive inheritance.Immature sperm cells in the testes do not mature past an early stage, as sensitivity to androgens is required in order for spermatogenesis to complete. Germ cell malignancy risk, once thought to be relatively high, is now thought to be approximately 2%. Wolffian structures (the epididymides, vasa deferentia, and seminal vesicles) are typically absent, but will develop at least partially in approximately 30% of cases, depending on which mutation is causing the CAIS. The prostate, like the external male genitalia, cannot masculinize in the absence of androgen receptor function, and thus remains in the female form.The Müllerian system (the fallopian tubes, uterus, and upper portion of the vagina) typically regresses due to the presence of anti-Müllerian hormone originating from the Sertoli cells of the testes. These women are thus born without fallopian tubes, a cervix, or a uterus, and the vagina ends "blindly" in a pouch. Müllerian regression does not fully complete in approximately one third of all cases, resulting in Müllerian "remnants". Although rare, a few cases of women with CAIS and fully developed Müllerian structures have been reported. In one exceptional case, a 22-year-old with CAIS was found to have a normal cervix, uterus, and fallopian tubes. In an unrelated case, a fully developed uterus was found in a 22-year-old adult with CAIS.Other subtle differences that have been reported include slightly longer limbs and larger hands and feet due to a proportionally greater stature than unaffected women, larger teeth, minimal or no acne, well developed breasts, and a greater incidence of meibomian gland dysfunction (i.e. dry eye syndromes and light sensitivity). Endocrine Hormone levels have been reported in gonadally intact CAIS women in a number of studies. Hormone levels are similar to those of males, including high testosterone levels and relatively low estradiol levels. However, luteinizing hormone (LH) levels are elevated while sex hormone-binding globulin (SHBG) levels are more consistent with those of females. Women with CAIS have low levels of progesterone similarly to males. The production rates of testosterone, estradiol, and estrone have been reported to be higher in gonadally intact CAIS women than in men. Comorbidity All forms of androgen insensitivity, including CAIS, are associated with infertility, though exceptions have been reported for both the mild and partial forms.CAIS is associated with a decreased bone mineral density. Some have hypothesized that the decreased bone mineral density observed in women with CAIS is related to the timing of gonadectomy and inadequate estrogen supplementation. However, recent studies show that bone mineral density is similar whether gonadectomy occurs before or after puberty, and is decreased despite estrogen supplementation, leading some to hypothesize that the deficiency is directly attributable to the role of androgens in bone mineralization.CAIS is also associated with an increased risk for gonadal tumors (e.g. germ cell malignancy) in adulthood if gonadectomy is not performed. The risk of malignant germ cell tumors in women with CAIS increases with age and has been estimated to be 3.6% at 25 years and 33% at 50 years. The incidence of gonadal tumors in childhood is thought to be relatively low; a recent review of the medical literature found that only three cases of malignant germ cell tumors in prepubescent girls have been reported in association with CAIS in the last 100 years. Some have estimated the incidence of germ cell malignancy to be as low as 0.8% before puberty.Vaginal hypoplasia, a relatively frequent finding in CAIS and some forms of PAIS, is associated with sexual difficulties including vaginal penetration difficulties and dyspareunia.At least one study indicates that individuals with an intersex condition may be more prone to psychological difficulties, due at least in part to parental attitudes and behaviors, and concludes that preventative long-term psychological counseling for parents as well as for affected individuals should be initiated at the time of diagnosis. Lifespan is not thought to be affected by AIS.Despite the well-developed breasts in CAIS women, and for reasons that are not well-understood, breast cancer has never been reported in CAIS women and does not seem to occur or occurs only rarely. Only a case report of juvenile fibroadenoma exists. A few cases of breast cancer have been reported in individuals with partial androgen insensitivity syndrome however. Diagnosis CAIS can only be diagnosed in normal phenotypic females. It is not usually suspected unless the menses fail to develop at puberty, or an inguinal hernia presents during premenarche. As many as 1–2% of prepubertal girls that present with an inguinal hernia will also have CAIS.A diagnosis of CAIS or Swyer syndrome can be made in utero by comparing a karyotype obtained by amniocentesis with the external genitalia of the fetus during a prenatal ultrasound. Many infants with CAIS do not experience the normal, spontaneous neonatal testosterone surge, a fact which can be diagnostically exploited by obtaining baseline luteinizing hormone and testosterone measurements, followed by a human chorionic gonadotropin (hGC) stimulation test.The main differentials for CAIS are complete gonadal dysgenesis (Swyer syndrome) and Müllerian agenesis (Mayer-Rokitansky-Kuster-Hauser syndrome or MRKH). Both CAIS and Swyer syndrome are associated with a 46,XY karyotype, whereas MRKH is not; MRKH can thus be ruled out by checking for the presence of a Y chromosome, which can be done either by fluorescence in situ hybridization (FISH) analysis or on full karyotype. Swyer syndrome is distinguished by the presence of a uterus, poor breast development and shorter stature. The diagnosis of CAIS is confirmed when androgen receptor (AR) gene sequencing reveals a mutation, although up to 5% of individuals with CAIS do not have an AR mutation.Up until the 1990s, a CAIS diagnosis was often hidden from the affected individual, the individuals family, or both. It is current practice to disclose the genotype at the time of diagnosis, particularly when the affected girl is at least of adolescent age. If the affected individual is a child or infant, it is generally up to the parents, often in conjunction with a psychologist, to decide when to disclose the diagnosis. Management Management of AIS is currently limited to symptomatic management; methods to correct a malfunctioning androgen receptor protein that result from an AR gene mutation are not currently available. Areas of management include sex assignment, genitoplasty, gonadectomy in relation to tumor risk, hormone replacement therapy, and genetic and psychological counseling. Non-consensual interventions are still often performed, although general awareness on the resulting psychological traumatization is rising. Sex assignment and sexuality Most individuals with CAIS are raised as females. They are born phenotypically female and are usually heterosexual with a female gender identity; However, at least two case studies have reported male gender identity in individuals with CAIS. Dilation therapy Most cases of vaginal hypoplasia associated with CAIS can be corrected using non-surgical pressure dilation methods. The elastic nature of vaginal tissue, as demonstrated by its ability to accommodate the differences in size between a tampon, a penis, and a babys head, make dilation possible even in cases when the vaginal depth is significantly compromised. Treatment compliance is thought to be critical to achieve satisfactory results. Dilation can also be achieved via the Vecchietti procedure, which stretches vaginal tissues into a functional vagina using a traction device that is anchored to the abdominal wall, subperitoneal sutures, and a mold that is placed against the vaginal dimple. Vaginal stretching occurs by increasing the tension on the sutures, which is performed daily. The non-operative pressure dilation method is currently recommended as the first choice, since it is non-invasive, and highly successful. Vaginal dilation should not be performed before puberty. Gonadectomy While it is often recommended that women with CAIS eventually undergo gonadectomy to mitigate cancer risk, there are differing opinions regarding the necessity and timing of gonadectomy. The risk of malignant germ cell tumors in women with CAIS increases with age and has been estimated to be 3.6% at 25 years and 33% at 50 years. However, only three cases of malignant germ cell tumors in prepubescent girls with CAIS have been reported in the last 100 years. The youngest of these girls was 14 years old. If gonadectomy is performed early, then puberty must be artificially induced using gradually increasing doses of estrogen. If gonadectomy is performed late, then puberty will occur on its own, due to the aromatization of testosterone into estrogen. At least one organization, the Australasian Paediatric Endocrine Group, classifies the cancer risk associated with CAIS as low enough to recommend against gonadectomy, although it warns that the cancer risk is still elevated above the general population, and that ongoing cancer monitoring is essential. Some choose to perform gonadectomy if and when inguinal hernia presents. Estrogen replacement therapy is critical to minimize bone mineral density deficiencies later in life. Hormone replacement therapy Some have hypothesized that supraphysiological levels of estrogen may reduce the diminished bone mineral density associated with CAIS. Data has been published that suggests affected women who were not compliant with estrogen replacement therapy, or who had a lapse in estrogen replacement, experienced a more significant loss of bone mineral density. Progestin replacement therapy is seldom initiated, due to the absence of a uterus. Androgen replacement has been reported to increase a sense of well-being in gonadectomized women with CAIS, although the mechanism by which this benefit is achieved is not well understood. Counseling It is no longer common practice to hide a diagnosis of CAIS from the affected individual or her family. Parents of children with CAIS need considerable support in planning and implementing disclosure for their child once the diagnosis has been established. For parents with young children, information disclosure is an ongoing, collaborative process requiring an individualized approach that evolves in concordance with the childs cognitive and psychological development. In all cases, the assistance of a psychologist experienced in the subject is recommended. Neovaginal construction Many surgical procedures have been developed to create a neovagina, as none of them is ideal. Surgical intervention should only be considered after non-surgical pressure dilation methods have failed to produce a satisfactory result. Neovaginoplasty can be performed using skin grafts, a segment of bowel, ileum, peritoneum, an absorbable adhesion barrier (Interceed, made by Johnson & Johnson), buccal mucosa, amnion, dura mater. or with the support of vaginal stents/expanders. Success of such methods should be determined by sexual function, and not just by vaginal length, as has been done in the past. Ileal or cecal segments may be problematic because of a shorter mesentery, which may produce tension on the neovagina, leading to stenosis. The sigmoid neovagina is thought to be self-lubricating, without the excess mucus production associated with segments of small bowel. Vaginoplasty may create scarring at the introitus (the vaginal opening), which requires additional surgery to correct. Vaginal dilators are required postoperatively to prevent vaginal stenosis from scarring. Inflatable vaginal stents are placed in the vagina deflated and then gently inflated. Other complications include bladder and bowel injuries. Yearly exams are required as neovaginoplasty carries a risk of carcinoma, although carcinoma of the neovagina is uncommon. Neither neovaginoplasty nor vaginal dilation should be performed before puberty. Prognosis Challenges presented to people affected by this condition include: psychologically coming to terms with the condition, difficulties with sexual function, infertility. Long-term studies indicate that with appropriate medical and psychological treatment, women with CAIS can be satisfied with their sexual function and psychosexual development. CAIS women can lead active lives and expect a normal lifespan. Epidemiology It is estimated that CAIS occurs in 1 in 20,400 to 1 in 99,000 individuals with a 46,XY karyotype. Nomenclature Historically, CAIS has been referred to in the literature under a number of other names, including testicular feminization [syndrome] (deprecated) and Morris syndrome. PAIS has also been referred to as Reifenstein syndrome, which should not be confused with CAIS. History The first definitive description of CAIS was reported in 1817. The condition became more widely known after it was reviewed and named testicular feminization by American gynecologist John McLean Morris in 1953. People with CAIS Georgiann Davis Seven Graham Eden Atwood See also Complete estrogen insensitivity syndrome References External links InformationAn Australian parent/patient booklet on CAIS (archived) The Secret of My Sex news article Women With Male DNA All Female news article at ABCnews.com

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I've encountered the term 'Ocular melanosis' while reading about medical topics. What does it refer to exactly?

Ocular melanosis (OM) is a blue-gray and/or brown lesion of the conjunctiva that can be separated into benign conjunctival epithelial melanosis (BCEM) and primary acquired melanosis (PAM), of which the latter is considered a risk factor for uveal melanoma. The disease is caused by an increase of melanocytes in the iris, choroid, and surrounding structures. Overproduction of pigment by these cells can block the trabecular meshwork through which fluid drains from the eye. The increased fluid in the eye leads to increased pressure, which can lead to glaucoma. In humans, this is sometimes known as pigment dispersion syndrome. Benign Conjunctival Epithelial Melanosis BCEM, also referred to as conjunctival hypermelanosis, complexion-associated melanosis, or racial melanosis, is a non-cancerous lesion of the conjunctiva that is more commonly found in dark-skinned individuals (over 90% of lesions are found in black persons and around 5% in white persons). It is due to excess production of melanin in the setting of a normal number of melanocytes in the conjunctiva. It appears very early in life and the pattern does not seem to change upon reaching adulthood. There can be asymmetrical involvement of the eyes, and lesions are usually described as flat, brown, and patchy areas of pigmentation. Primary Acquired Melanosis PAM is a potentially cancerous lesion of the conjunctiva, which has a higher risk of transforming into a malignant melanoma in white persons. Nearly 75% of all melanomas that arise from the conjunctiva have been found to have occurred in the setting of PAM. It is different from BCEM because there is a proliferation, or an increase in the number of melanocytes, which is attributed to greater risk of neoplasia formation. However, PAM may occur without atypia, which has no risk of malignant transformation, or with atypia. It is very important to determine at which age the lesion was first noticed because it is more likely to be a benign nevus, or mole, the earlier it is found. It may appear similar to BCEM since the lesion may also be flat, brown or blue-gray, and diffuse throughout the conjunctiva, but it is almost always only found on one eye. Diagnosis Usually unilateral, flat, patchy, pigmented area that involves the limbus (the border of the cornea and sclera) and interpalpebral (between the eyelids) conjunctiva. Slit-lamp examination. Histopathological examination that shows intraepithelial proliferation of conjunctival epithelial melanocytes. Features that may encourage the ophthalmologist to biopsy the lesion include, but are not limited to:Increasing size or size greater than 5mm Involvement of conjunctiva underneath the eyelids Nodular appearance Appearance of blood vessels surrounding the patch Previous history of melanoma Treatment There are a few management and treatment strategies for PAM. When lesions are small, they can be carefully watched on an annual basis. It is important to compare pictures year to year. However, for medium and large-sized lesions, we can consider surgery (excisional vs incisional biopsy), chemotherapy, or cryotherapy.When a patient has PAM with atypia, an excisional biopsy with cryotherapy is recommended as the treatment. For some patients with diffuse lesions, surgery is not an option. In these cases, the recommendation is cryotherapy in combination with topical mitomycin C, which is a chemotherapeutic agent. == References ==

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Can you break down the meaning of the medical term 'Late onset congenital adrenal hyperplasia' for me?

Late onset congenital adrenal hyperplasia (LOCAH), also known as nonclassic congenital adrenal hyperplasia (NCCAH or NCAH), is a milder form of congenital adrenal hyperplasia (CAH), a group of autosomal recessive disorders characterized by impaired cortisol synthesis that leads to variable degrees of postnatal androgen excess.The causes of LOCAH are the same as of classic CAH, and in the majority of the cases are the mutations in the CYP21A2 gene resulting in corresponding activity changes in the associated P450c21 (21-hydroxylase) enzyme which ultimately leads to excessive androgen production. Other causes, albeit less frequent, are mutations in genes affecting other enzymes involved in steroid metabolism, like 11β-hydroxylase or 3β-hydroxysteroid dehydrogenase. It has a prevalence between 0.1% and 2% depending on population, and is one of the most common autosomal recessive genetic diseases in humans. The pathophysiology is complex and not all individuals are symptomatic. Presentation Patients with LOCAH usually present with signs of hyperandrogenism, rather than of glucocorticoid deficiency, a condition characterized by inadequate cortisol production. Cortisol synthesis impairment is mild but clinically silent. LOCAH patients usually have the same baseline but lower peak cortisol levels comparing to healthy controls. Flatter diurnal cortisol slopes contribute to stress-related dysregulation of central and peripheral circadian mechanisms with negative health outcomes.Due to hyperandrogenism, females may present with symptoms like hirsutism, oligomenorrhea, acne, infertility, and male-pattern baldness.Males are generally asymptomatic, but may present with acne, early balding, chronic prostatitis, chronic pelvic pain syndrome, and very rarely, testicular adrenal rest tumors.While symptoms are usually diagnosed after puberty, children may present with premature adrenarche.The degree of hormonal disorder in patients with LOCAH is relatively mild. However, alterations in the hypothalamic–pituitary–adrenal axis are present even in this mild form of the disease and might contribute to psychiatric vulnerability. Molecular genetics LOCAH is most commonly attributed to mutations in the CYP21A2 gene, which encodes the 21-hydroxylase enzyme. Cases of LOCAH due to deficiencies in other enzymes that are known causes of CAH (3β-hydroxysteroid dehydrogenase, steroid 11β-hydroxylase, etc.) are rare and have no established prevalence estimates.Several severe mutations have been associated with LOCAH: the deletion of the CYP21A2 gene, small gene conversions, the p. I172N (rs6475, c.518T>A, CYP21A2*11) mutation, the c.293-13A/C>G (rs6467, CYP21A2*9) mutation, and the p.Gln318Stop (p.Q318X, rs7755898, c.952C>T, CYP21A2*17) mutation. Besides that, LOCAH due to 21-hydroxylase deficiency can be caused by duplications of CYP21A1P pseudogene and C4B gene. Due to the high degree of homology between the CYP21A2 gene and the CYP21A1P pseudogene, and the complexity of the locus, research on the sequencing level can be difficult. A 2021 study showed that mild genotypes associated with LOCAH have a low concordance rate with those phenotypes, probably due to the complex characteristics of 21-hydroxylase genotyping and the limitation of using massive parallel sequencing alone without combining with other comprehensive methods.The following three mutations to the CYP21A2 gene have been found to result in a moderate reduction in enzyme activity associated with that allele (20–60% residual activity), and are associated with LOCAH: p.V281L (rs6471, c.844G>C, CYP21A2*15); p.P453S (rs6445, c.1360C>T, CYP21A2*19); p.P30L (rs9378251, c.92C>T, CYP21A2*8).A point mutation in exon 7 of CYP21A2, (p.V281L), is commonly found in LOCAH-associated alleles. Carriers for this mutation retain 20%–50% of 21-hydroxylase activity, but are at higher risk of symptoms of androgen excess than carriers of the severe mutations and had higher adrenocorticotropic hormone (ACTH) stimulated 17α-hydroxyprogesterone, suggesting heterozygous mutations on CYP21A2 play an important role in disease.The particularly mild clinical symptoms of LOCAH such as hyperandrogenism, hirsutism and acne or infertility overlap with other diseases such as polycystic ovary syndrome. Biochemical parameters like 17α-hydroxyprogesterone may not be elevated in very mild cases of LOCAH, and may vary between labs that makes interpretation difficult. It may not be possible to perform ACTH stimulation tests in all institutions, depending on the availability of the injectable adrenocorticotropic hormone medication. This is why a comprehensive CYP21A2 genotyping (rather than variant-specific assays alone) is a good way to exclude/confirm 21-hydroxylase deficiency and heterozygosity (carrier) status. Genetic testing can be used to exclude false positive diagnosis based on biochemical parameters alone, even with ACTH stimulation, since elevated 17-OHP levels may be also caused by ovarian or adrenal tumors, rather than by the variants in the CYP21A2 gene. Diagnosis Originally characterized in 1957 by French biochemist Jacques Decourt, LOCAH differs from classic CAH in that it does not cause atypical neonatal genital morphology, is not life-threatening and presents after birth. Unlike classic CAH, LOCAH generally cannot be reliably detected with neonatal screening. Many individuals (both male and female) present no symptoms during childhood and adolescence and only become aware of the possibility of LOCAH due to the diagnosis of another family member. It is thought that 90% of women with LOCAH never receive a diagnosis. In young females, premature pubarche is generally the first symptom to present. The earliest known diagnosis was in a 6 month old female who developed pubic hair. Additional symptoms include acne, menstrual irregularities and hirsutism in females as well as alopecia in males. LOCAH is often misdiagnosed as polycystic ovarian disease (PCOS).LOCAH is often diagnosed in the context of infertility assessment in women. During the follicular phase of the menstrual cycle, progesterone accumulates along with 17α-hydroxyprogesterone which can thin the endometrium and change cervical mucus in a manner similar to the effect of progestogen contraceptives, interferes with the normal menstrual cycle, which can lead to oligomenorrhea or amenorrhea and impairs sperm penetration. Abnormal endometrial development leads to decreased uterine receptivity, which also contributes to infertility. Once attempting to conceive, most women with LOCAH will become pregnant within a year with or without treatment, but women with LOCAH have an increased risk of miscarriage.The diagnostic procedure varies according to the specific enzyme deficiency causing LOCAH and the precise serum androgen levels required for diagnosis are the subject to variance from different measurement methods, refinement in specific cases and are under active research. Some protocols are based on measuring 17α-hydroxyprogesterone levels, with or without ACTH stimulation test. 21-Hydroxylase deficiency Screening The condition of 21-hydroxylase deficiency is screened by measuring serum levels of 17α-hydroxyprogesterone (17-OHP) in the morning and between day 3 and 5 of the menstrual cycle (for females) to reduce the possibility of false positive results. 17-OHP is used as a marker of the 21-hydroxylase enzyme activity since the 1980s. The cutoff basal 17-OHP value is matter of debate. Most commonly, the value of 2.0 ng/mL is used, but a value of 1.7 ng/mL provides better selectivity. Most research on the biochemical diagnosis of LOCAH relied on direct immunoassays, such as radioimmunoassays or time-resolved fluorescence assay to measure 17-OHP, therefore, cross-reactivity and reliability problems of these methods might have caused differences in the 17-OHP cutoff values recommended, so the use of liquid chromatography–mass spectrometry aims to improve the accuracy of 17-OHP measurement and increase diagnostic quality of LOCAH. Randomly timed measurements of 17-OHP have not been shown to be useful for screening since they are often normal and are known to be very high in the luteal phase of the female menstrual cycle. After basal levels have been measured, confirmation is done by administering ACTH, and comparing 17-OHP pre and post test. 17-OHP levels over 10 ng/mL at the 60th minute post stimulation is considered diagnostic for LOCAH. Androgen backdoor pathway In 21-hydroxylase deficiency, especially in mild cases (LOCAH), the androgen "backdoor" pathway may be the reason of androgen excess. This backdoor pathway is not always considered in the clinical evaluation of patients with hyperandrogenism conditions such as LOCAH and may be a source of diagnostic pitfalls and confusion. One case study demonstrated the importance of considering serum 5α-dihydrotestosterone (DHT) levels and the androgen backdoor pathway in a LOCAH diagnosis that would have not been apparent from testosterone levels alone. 11β-Hydroxylase deficiency The activity of 11β-hydroxylase can be determined by observing the basal 11-deoxycortisol level. A level over 10 ng/mL, indicates followup with ACTH stimulation test. The 60th minute post-stimulation 11-deoxycortisol levels higher than 18 ng/mL are diagnostic of LOCAH. 3β-Hydroxysteroid dehydrogenase deficiency The activity of 3β-hydroxysteroid dehydrogenase can be determined by observing the basal 17α-hydroxypregnenolone level. A level above 30 ng/mL and 17α-hydroxypregnenolone/cortisol ratio above 10 SD are diagnostic of LOCAH. Management Management and treatment of LOCAH is case specific and the application of glucocorticoid treatment is not standard as it is in classic CAH. LOCAH is not a life-threatening medical condition and the risks of treatment given prenatally or to asymptomatic children outweigh potential benefits. In appropriate cases, glucocorticoids (usually hydrocortisone in children) are administered to suppress secretion of corticotropin releasing hormone (CRH) produced by hypothalamus and of adrenocorticotropic hormone (ACTH) produced by pituitary gland. This suppression will reduce concentration in blood of sex steroids produced by adrenal glands. Some of the main considerations in treatment include the watchful waiting of symptom severity as well as adverse responses to glucocorticoids administered as drugs, seen in patient bone mineral density, height and weight. For women, an oral contraceptive pill and androgen blockers such as spironolactone or cyproterone acetate are alternatives to glucocorticoids for managing symptoms of androgen excess. Women with LOCAH being treated with hydrocortisone have a lower miscarriage risk. Prevalence According to haplotype association studies, the prevalence of LOCAH in the general white population is estimated to be 1:500 to 1:1000, but in people with a high rate of marriage between relatives, the prevalence rate is as high as 1:50 to 1:100. A 2017 CYP21A2 genotype analysis predicted that the total frequency of LOCAH in the white population of the United States is about 1:200 (95% confidence level, from 1:100 to 1:280).According to a 2017 meta-analysis, the prevalence of LOCAH among women with signs and symptoms of androgen excess is 4.2% globally, and between 1% and 10% depending on the ethnicity of the population being studied.LOCAH-affected individuals account for 88% of Anne Fausto-Sterlings 1.7% prevalence estimate of intersex conditions, which is cited by a number of prominent intersex advocacy organizations. From the clinical perspective, LOCAH is not an intersex condition and including LOCAH in intersex prevalence estimates has been cited as an example of dubious statistical practice. See also Congenital adrenal hyperplasia due to 17α-hydroxylase deficiency Lipoid congenital adrenal hyperplasia References == External links ==

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I'm curious about the meaning of the medical term 'Foot.' Can you give me some insights?

The foot (PL: feet) is an anatomical structure found in many vertebrates. It is the terminal portion of a limb which bears weight and allows locomotion. In many animals with feet, the foot is a separate organ at the terminal part of the leg made up of one or more segments or bones, generally including claws or nails. Etymology The word "foot", in the sense of meaning the "terminal part of the leg of a vertebrate animal" comes from "Old English fot "foot," from Proto-Germanic *fot (source also of Old Frisian fot, Old Saxon fot, Old Norse fotr, Danish fod, Swedish fot, Dutch voet, Old High German fuoz, German Fuß, Gothic fotus "foot"), from PIE root *ped- "foot". The "plural form feet is an instance of i-mutation." Structure The human foot is a strong and complex mechanical structure containing 26 bones, 33 joints (20 of which are actively articulated), and more than a hundred muscles, tendons, and ligaments. The joints of the foot are the ankle and subtalar joint and the interphalangeal joints of the foot. An anthropometric study of 1197 North American adult Caucasian males (mean age 35.5 years) found that a mans foot length was 26.3 cm with a standard deviation of 1.2 cm.The foot can be subdivided into the hindfoot, the midfoot, and the forefoot: The hindfoot is composed of the talus (or ankle bone) and the calcaneus (or heel bone). The two long bones of the lower leg, the tibia and fibula, are connected to the top of the talus to form the ankle. Connected to the talus at the subtalar joint, the calcaneus, the largest bone of the foot, is cushioned underneath by a layer of fat.The five irregular bones of the midfoot, the cuboid, navicular, and three cuneiform bones, form the arches of the foot which serves as a shock absorber. The midfoot is connected to the hind- and fore-foot by muscles and the plantar fascia.The forefoot is composed of five toes and the corresponding five proximal long bones forming the metatarsus. Similar to the fingers of the hand, the bones of the toes are called phalanges and the big toe has two phalanges while the other four toes have three phalanges each. The joints between the phalanges are called interphalangeal and those between the metatarsus and phalanges are called metatarsophalangeal (MTP). Both the midfoot and forefoot constitute the dorsum (the area facing upward while standing) and the planum (the area facing downward while standing). The instep is the arched part of the top of the foot between the toes and the ankle. Bones tibia, fibula tarsus (7): talus, calcaneus, cuneiformes (3), cuboid, and navicular metatarsus (5): first, second, third, fourth, and fifth metatarsal bone phalanges (14)There can be many sesamoid bones near the metatarsophalangeal joints, although they are only regularly present in the distal portion of the first metatarsal bone. Arches The human foot has two longitudinal arches and a transverse arch maintained by the interlocking shapes of the foot bones, strong ligaments, and pulling muscles during activity. The slight mobility of these arches when weight is applied to and removed from the foot makes walking and running more economical in terms of energy. As can be examined in a footprint, the medial longitudinal arch curves above the ground. This arch stretches from the heel bone over the "keystone" ankle bone to the three medial metatarsals. In contrast, the lateral longitudinal arch is very low. With the cuboid serving as its keystone, it redistributes part of the weight to the calcaneus and the distal end of the fifth metatarsal. The two longitudinal arches serve as pillars for the transverse arch which run obliquely across the tarsometatarsal joints. Excessive strain on the tendons and ligaments of the feet can result in fallen arches or flat feet. Muscles The muscles acting on the foot can be classified into extrinsic muscles, those originating on the anterior or posterior aspect of the lower leg, and intrinsic muscles, originating on the dorsal (top) or plantar (base) aspects of the foot. Extrinsic All muscles originating on the lower leg except the popliteus muscle are attached to the bones of the foot. The tibia and fibula and the interosseous membrane separate these muscles into anterior and posterior groups, in their turn subdivided into subgroups and layers. Anterior group Extensor group: the tibialis anterior originates on the proximal half of the tibia and the interosseous membrane and is inserted near the tarsometatarsal joint of the first digit. In the non-weight-bearing leg, the tibialis anterior dorsiflexes the foot and lift its medial edge (supination). In the weight-bearing leg, it brings the leg toward the back of the foot, like in rapid walking. The extensor digitorum longus arises on the lateral tibial condyle and along the fibula, and is inserted on the second to fifth digits and proximally on the fifth metatarsal. The extensor digitorum longus acts similar to the tibialis anterior except that it also dorsiflexes the digits. The extensor hallucis longus originates medially on the fibula and is inserted on the first digit. It dorsiflexes the big toe and also acts on the ankle in the unstressed leg. In the weight-bearing leg, it acts similarly to the tibialis anterior.Peroneal group: the peroneus longus arises on the proximal aspect of the fibula and peroneus brevis below it. Together, their tendons pass behind the lateral malleolus. Distally, the peroneus longus crosses the plantar side of the foot to reach its insertion on the first tarsometatarsal joint, while the peroneus brevis reaches the proximal part of the fifth metatarsal. These two muscles are the strongest pronators and aid in plantar flexion. The peroneus longus also acts like a bowstring that braces the transverse arch of the foot. Posterior group The superficial layer of posterior leg muscles is formed by the triceps surae and the plantaris. The triceps surae consists of the soleus and the two heads of the gastrocnemius. The heads of gastrocnemius arise on the femur, proximal to the condyles, and the soleus arises on the proximal dorsal parts of the tibia and fibula. The tendons of these muscles merge to be inserted onto the calcaneus as the Achilles tendon. The plantaris originates on the femur proximal to the lateral head of the gastrocnemius and its long tendon is embedded medially into the Achilles tendon. The triceps surae is the primary plantar flexor. Its strength becomes most obvious during ballet dancing. It is fully activated only with the knee extended, because the gastrocnemius is shortened during flexion of the knee. During walking it not only lifts the heel, but also flexes the knee, assisted by the plantaris.In the deep layer of posterior muscles, the tibialis posterior arises proximally on the back of the interosseous membrane and adjoining bones, and divides into two parts in the sole of the foot to attach to the tarsus. In the non-weight-bearing leg, it produces plantar flexion and supination, and, in the weight-bearing leg, it proximates the heel to the calf. The flexor hallucis longus arises on the back of the fibula on the lateral side, and its relatively thick muscle belly extends distally down to the flexor retinaculum where it passes over to the medial side to stretch across the sole to the distal phalanx of the first digit. The popliteus is also part of this group, but, with its oblique course across the back of the knee, does not act on the foot. Intrinsic On the top of the foot, the tendons of extensor digitorum brevis and extensor hallucis brevis lie deep in the system of long extrinsic extensor tendons. They both arise on the calcaneus and extend into the dorsal aponeurosis of digits one to four, just beyond the penultimate joints. They act to dorsiflex the digits. Similar to the intrinsic muscles of the hand, there are three groups of muscles in the sole of foot, those of the first and last digits, and a central group: Muscles of the big toe: the abductor hallucis stretches medially along the border of the sole, from the calcaneus to the first digit. Below its tendon, the tendons of the long flexors pass through the tarsal canal. The abductor hallucis is an abductor and a weak flexor, and also helps maintain the arch of the foot. The flexor hallucis brevis arises on the medial cuneiform bone and related ligaments and tendons. An important plantar flexor, it is crucial to ballet dancing. Both these muscles are inserted with two heads proximally and distally to the first metatarsophalangeal joint. The adductor hallucis is part of this group, though it originally formed a separate system (see Contrahens). It has two heads, the oblique head originating obliquely across the central part of the midfoot, and the transverse head originating near the metatarsophalangeal joints of digits five to three. Both heads are inserted into the lateral sesamoid bone of the first digit. The adductor hallucis acts as a tensor of the plantar arches and also adducts the big toe and might plantar flex the proximal phalanx.Muscles of the little toe: Stretching laterally from the calcaneus to the proximal phalanx of the fifth digit, the abductor digiti minimi form the lateral margin of the foot and are the largest of the muscles of the fifth digit. Arising from the base of the fifth metatarsal, the flexor digiti minimi is inserted together with abductor on the first phalanx. Often absent, the opponens digiti minimi originates near the cuboid bone and is inserted on the fifth metatarsal bone. These three muscles act to support the arch of the foot and to plantar flex the fifth digit. Central muscle group: The four lumbricals arise on the medial side of the tendons of flexor digitorum longus and are inserted on the medial margins of the proximal phalanges. The quadratus plantae originates with two slips from the lateral and medial margins of the calcaneus and inserts into the lateral margin of the flexor digitorum tendon. It is also known as the flexor accessorius. The flexor digitorum brevis arises inferiorly on the calcaneus and its three tendons are inserted into the middle phalanges of digits two to four (sometimes also the fifth digit). These tendons divide before their insertions and the tendons of flexor digitorum longus pass through these divisions. Flexor digitorum brevis flexes the middle phalanges. It is occasionally absent. Between the toes, the dorsal and plantar interossei stretch from the metatarsals to the proximal phalanges of digits two to five. The plantar interossei adduct and the dorsal interossei abduct these digits, and are also plantar flexors at the metatarsophalangeal joints. Clinical significance Due to their position and function, feet are exposed to a variety of potential infections and injuries, including athletes foot, bunions, ingrown toenails, Mortons neuroma, plantar fasciitis, plantar warts, and stress fractures. In addition, there are several genetic disorders that can affect the shape and function of the feet, including clubfoot or flat feet. This leaves humans more vulnerable to medical problems that are caused by poor leg and foot alignments. Also, the wearing of shoes, sneakers and boots can impede proper alignment and movement within the ankle and foot. For example, high-heeled shoes are known to throw off the natural weight balance (this can also affect the lower back). For the sake of posture, flat soles with no heels are advised. A doctor who specializes in the treatment of the feet practices podiatry and is called a podiatrist. A pedorthist specializes in the use and modification of footwear to treat problems related to the lower limbs. Fractures of the foot include: Lisfranc fracture – in which one or all of the metatarsals are displaced from the tarsus Jones fracture – a fracture of the fifth metatarsal March fracture – a fracture of the distal third of one of the metatarsals occurring because of recurrent stress Calcaneal fracture Broken toe – a fracture of a phalanx Cuneiform fracture – Due to the ligamentous support of the midfoot, isolated cuneiform fractures are rare. Pronation In anatomy, pronation is a rotational movement of the forearm (at the radioulnar joint) or foot (at the subtalar and talocalcaneonavicular joints). Pronation of the foot refers to how the body distributes weight as it cycles through the gait. During the gait cycle the foot can pronate in many different ways based on rearfoot and forefoot function. Types of pronation include neutral pronation, underpronation (supination), and overpronation. Neutral pronationAn individual who neutrally pronates initially strikes the ground on the lateral side of the heel. As the individual transfers weight from the heel to the metatarsus, the foot will roll in a medial direction, such that the weight is distributed evenly across the metatarsus. In this stage of the gait, the knee will generally, but not always, track directly over the hallux. This rolling inward motion as the foot progresses from heel to toe is the way that the body naturally absorbs shock. Neutral pronation is the most ideal, efficient type of gait when using a heel strike gait; in a forefoot strike, the body absorbs shock instead via flexion of the foot. OverpronationAs with a neutral pronator, an individual who overpronates initially strikes the ground on the lateral side of the heel. As the individual transfers weight from the heel to the metatarsus, however, the foot will roll too far in a medial direction, such that the weight is distributed unevenly across the metatarsus, with excessive weight borne on the hallux. In this stage of the gait, the knee will generally, but not always, track inward. An overpronator does not absorb shock efficiently. Imagine someone jumping onto a diving board, but the board is so flimsy that when it is struck, it bends and allows the person to plunge straight down into the water instead of back into the air. Similarly, an overpronators arches will collapse, or the ankles will roll inward (or a combination of the two) as they cycle through the gait. An individual whose bone structure involves external rotation at the hip, knee, or ankle will be more likely to overpronate than one whose bone structure has internal rotation or central alignment. An individual who overpronates tends to wear down their running shoes on the medial (inside) side of the shoe toward the toe area.When choosing a running or walking shoe, a person with overpronation can choose shoes that have good inside support—usually by strong material at the inside sole and arch of the shoe. It is usually visible. The inside support area is marked by strong greyish material to support the weight when a person lands on the outside foot and then roll onto the inside foot. Underpronation (supination) An individual who underpronates also initially strikes the ground on the lateral side of the heel. As the individual transfers weight from the heel to the metatarsus, the foot will not roll far enough in a medial direction. The weight is distributed unevenly across the metatarsus, with excessive weight borne on the fifth metatarsal, toward the lateral side of the foot. In this stage of the gait, the knee will generally, but not always, track laterally of the hallux. Like an overpronator, an underpronator does not absorb shock efficiently – but for the opposite reason. The underpronated foot is like a diving board that, instead of failing to spring someone in the air because it is too flimsy, fails to do so because it is too rigid. There is virtually no give. An underpronators arches or ankles dont experience much motion as they cycle through the gait. An individual whose bone structure involves internal rotation at the hip, knee, or ankle will be more likely to underpronate than one whose bone structure has external rotation or central alignment. Usually – but not always – those who are bow-legged tend to underpronate. An individual who underpronates tends to wear down their running shoes on the lateral (outside) side of the shoe toward the rear of the shoe in the heel area. Society and culture Humans usually wear shoes or similar footwear for protection from hazards when walking outside. There are a number of contexts where it is considered inappropriate to wear shoes. Some people consider it rude to wear shoes into a house and a Māori Marae should only be entered with bare feet. Foot fetishism is the most common sexual fetish. Other animals A paw is the soft foot of a mammal, generally a quadruped, that has claws or nails (e.g., a cat or dogs paw). A hard foot is called a hoof. Depending on style of locomotion, animals can be classified as plantigrade (sole walking), digitigrade (toe walking), or unguligrade (nail walking). The metatarsals are the bones that make up the main part of the foot in humans, and part of the leg in large animals or paw in smaller animals. The number of metatarsals are directly related to the mode of locomotion with many larger animals having their digits reduced to two (elk, cow, sheep) or one (horse). The metatarsal bones of feet and paws are tightly grouped compared to, most notably, the human hand where the thumb metacarpal diverges from the rest of the metacarpus. Metaphorical and cultural usage The word "foot" is used to refer to a "...linear measure was in Old English (the exact length has varied over time), this being considered the length of a mans foot; a unit of measure used widely and anciently. In this sense the plural is often foot. The current inch and foot are implied from measurements in 12c." The word "foot" also has a musical meaning; a "...metrical foot (late Old English, translating Latin pes, Greek pous in the same sense) is commonly taken to represent one rise and one fall of a foot: keeping time according to some, dancing according to others."The word "foot" was used in Middle English to mean "a person" (c. 1200). The expression "...to put ones best foot foremost first recorded 1849 (Shakespeare has the better foot before, 1596)". The expression to "...put ones foot in (ones) mouth "say something stupid" was first used in 1942. The expression "put (ones) foot in something" meaning to "make a mess of it" was used in 1823.The word "footloose" was first used in the 1690s, meaning "free to move the feet, unshackled"; the more "figurative sense of "free to act as one pleases" was first used in 1873. Like "footloose", "flat-footed" at first had its obvious literal meaning (in 1600, it meant "with flat feet") but by 1912 it meant "unprepared" (U.S. baseball slang). See also References Bibliography France, Diane L. (2008). Human and Nonhuman Bone Identification: A Color Atlas. CRC Press. ISBN 978-1-4200-6286-1. Marieb, Elaine Nicpon; Hoehn, Katja (2007). Human anatomy & physiology. Pearson Education. ISBN 978-0-321-37294-9. Platzer, Werner (2004). Color Atlas of Human Anatomy, Vol. 1: Locomotor System (5th ed.). Thieme. ISBN 3-13-533305-1. "Anatomy of the foot and ankle". Podiatry Channel. Archived from the original on 31 August 2009. Retrieved 21 August 2009. External links Foot at Curlie

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

I've encountered the term 'Mitochondrial encephalomyopathy' while reading about medical topics. What does it refer to exactly?

A mitochondrial encephalomyopathy is a form of encephalomyopathy that is associated with a mitochondrial disease. MELAS syndrome Examples include MELAS syndrome and MERRF syndrome. These conditions can sometimes present together.KSS is sometimes included in this category, but it is not included in this category in MeSH. References == External links ==

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

Could you please explain the term 'Inclusion body myositis' in simple language?

Inclusion body myositis (IBM) () (sometimes called sporadic inclusion body myositis, sIBM) is the most common inflammatory muscle disease in older adults. The disease is characterized by slowly progressive weakness and wasting of both proximal muscles (located on or close to the torso) and distal muscles (close to hands or feet), most apparent in the finger flexors and knee extensors. IBM is often confused with an entirely different class of diseases, called hereditary inclusion body myopathies (hIBM). The "M" in hIBM is an abbreviation for "myopathy" while the "M" in IBM is for "myositis". In IBM, two processes appear to occur in the muscles in parallel, one autoimmune and the other degenerative. Inflammation is evident from the invasion of muscle fibers by immune cells. Degeneration is characterized by the appearance of holes, deposits of abnormal proteins, and filamentous inclusions in the muscle fibers. sIBM is a rare disease, with a prevalence ranging from 1 to 71 individuals per million.Weakness comes on slowly (over months to years) in an asymmetric manner and progresses steadily, leading to severe weakness and wasting of arm and leg muscles. IBM is more common in men than women. Patients may become unable to perform activities of daily living and most require assistive devices within 5 to 10 years of symptom onset. sIBM does not significantly affect life expectancy, although death related to malnutrition and respiratory failure can occur. The risk of serious injury due to falls is increased. There is no effective treatment for the disease as of 2019. Classification and terminology IBM stands for "inclusion body myositis:, not "inclusion body myopathy." The inclusion body refers to a histological finding of rimmed vacules in muscle tissue. However, IBM does not refer to the collection of diseases that feature these inclusion bodies. It refers to a specific disease entity.Multiple genetic diseases that feature inclusion bodies have been grouped into "hereditary inclusion body myopathies (hIBM)." Myopathy is used because inflammation is not a prominent finding. There is inconsistency in what individual disease entities fall under the category of hIBM. The term "sporadic inclusion body myositis" (sIBM) was introduced as a way to refer to IBM to avoid confusion with hIBM. However, one author discourages use of sIBM, as it implies that IBM and hIBM differ only in inheritance; they actually have unrelated mechanisms and manifestations of disease. Signs and symptoms sIBM causes progressive muscle weakness. How sIBM affects individuals is variable, including the age of onset (which generally varies from the forties upwards) and rate of progression. Because of this variability, there is no "textbook case".Common early symptoms include frequent tripping and falling and difficulty going up stairs. Foot drop in one or both feet can occur. Part of the cause for this dysfunction is the early involvement of the quadriceps muscles. Weakness of the tibialis anterior muscle is responsible for foot drop. Another common early symptom is trouble manipulating the fingers, such as difficulty with tasks such as turning doorknobs or gripping keys. Weakness of finger flexion and ankle dorsiflexion occurs early. sIBM also preferentially affects the wrist flexors, biceps, and triceps.During the course of the illness, the patients mobility is progressively restricted as it becomes difficult to bend down, reach for things, and walk quickly. Many patients say they have balance problems and fall easily, as the muscles cannot compensate for an off-balanced posture. Because sIBM makes the leg muscles weak and unstable, patients are very vulnerable to serious injury from tripping or falling down. Although pain has not been traditionally part of the "textbook" description, many patients report severe muscle pain, especially in the thighs. Progressive difficulty swallowing (dysphagia) is present in 40 to 85% of IBM cases and often leads to death from aspiration pneumonia.IBM can also result in diminished capacity for aerobic exercise. This decline is most likely a consequence of the sedentary lifestyle leading to disuse muscle atrophy that is often associated with the symptoms of IBM (i.e. progressive muscle weakness, decreased mobility, and increased level of fatigue). Therefore, one focus of treatment should be the improvement of aerobic capacity.Patients with sIBM usually eventually need to resort to a cane or a walker and in most cases, a wheelchair eventually becomes a necessity. "The progressive course of s-IBM leads slowly to severe disability. Finger functions can become very impaired, such as manipulating pens, keys, buttons, and zippers, pulling handles, and firmly grasping handshakes. Arising from a chair becomes difficult. Walking becomes more precarious. Sudden falls, sometimes resulting in major injury to the skull or other bones, can occur, even from walking on minimally irregular ground or from other minor imbalances outside or in the home, due to weakness of quadriceps and gluteus muscles depriving the patient of automatic posture maintenance. A foot-drop can increase the likelihood of tripping. Dysphagia can occur, usually caused by upper esophageal constriction that often can be symptomatically improved, for several months to years, by bougie dilation per a GI or ENT physician. Respiratory muscle weakness can sometimes eventuate." Causes The cause of IBM is unknown. IBM likely results from the interaction of a number of genetic and environmental factors.There are two major theories about how sIBM is caused. One hypothesis suggests that the inflammation-immune reaction, caused by an unknown trigger – likely an undiscovered virus or an autoimmune disorder – is the primary cause of sIBM and that the degeneration of muscle fibers and protein abnormalities are secondary features. Despite the arguments "in favor of an adaptive immune response in sIBM, a purely autoimmune hypothesis for sIBM is untenable because of the diseases resistance to most immunotherapy."The second school of thought advocates the theory that sIBM is a degenerative disorder related to aging of the muscle fibers and that abnormal, potentially pathogenic protein accumulations in myofibrils play a key causative role in sIBM (apparently before the immune system comes into play). This hypothesis emphasizes the abnormal intracellular accumulation of many proteins, protein aggregation and misfolding, proteosome inhibition, and endoplasmic reticulum (ER) stress.One review discusses the "limitations in the beta-amyloid-mediated theory of IBM myofiber injury."Dalakas (2006) suggested that a chain of events causes IBM – some sort of virus, likely a retrovirus, triggers the cloning of T cells. These T cells appear to be driven by specific antigens to invade muscle fibers. In people with sIBM, the muscle cells display "flags" telling the immune system that they are infected or damaged (the muscles ubiquitously express MHC class I antigens) and this immune process leads to the death of muscle cells. The chronic stimulation of these antigens also causes stress inside the muscle cell in the endoplasmic reticulum (ER) and this ER stress may be enough to cause a self-sustaining T cell response (even after a virus has dissipated). In addition, this ER stress may cause the misfolding of protein. The ER is in charge of processing and folding molecules carrying antigens. In IBM, muscle fibers are overloaded with these major histocompatibility complex (MHC) molecules that carry the antigen protein pieces, leading to more ER stress and more protein misfolding.A self-sustaining T cell response would make sIBM a type of autoimmune disorder. When studied carefully, it has not been possible to detect an ongoing viral infection in the muscles. One theory is that a chronic viral infection might be the initial triggering factor setting IBM in motion. There have been a handful of IBM cases – approximately 15 – that have shown clear evidence of a virus called HTLV-1. The HTLV-1 virus can cause leukemia, but in most cases lies dormant and most people end up being lifelong carriers of the virus. One review says that the best evidence points towards a connection with some type of retrovirus and that a retroviral infection combined with immune recognition of the retrovirus is enough to trigger the inflammation process. amyloid protein The hypothesis that beta amyloid protein is key to IBM has been supported in a mouse model using an Aβ vaccine that was found to be effective against inclusion body myositis in mouse models. Although this vaccine is likely, not safe for human use, it still shows that attacking Aβ has efficacy in mice against IBM. Following up on earlier leads, the Greenberg group report finding that the protein TDP-43 is a very prominent and highly sensitive and specific feature of IBM. This protein is normally found within the nucleus but in IBM is found in the cytoplasm of the cell. This important advance should help develop a new screening technique for IBM and may provide clues in terms of a therapeutic approach Genetics sIBM is not inherited and is not passed on to the children of IBM patients. There are genetic features that do not directly cause IBM but that appear to predispose a person to getting IBM – having this particular combination of genes increases ones susceptibility to getting IBM. Some 67% of IBM patients have a particular combination of human leukocyte antigen genes in a section of the 8.1 ancestral haplotype in the center of the MHC class II region. sIBM is not passed on from generation to generation, although the susceptibility region of genes may be.There are also several rare forms of hereditary inclusion body myopathy that are linked to specific genetic defects and that are passed on from generation to generation. Since these forms do not show features of muscle inflammation, they are classified as myopathies rather than forms of myositis. Because they do not display inflammation as a primary symptom, they may in fact be similar, but different diseases to sporadic inclusion body myositis. There are several different types, each inherited in different ways. See hereditary inclusion body myopathy.A 2007 review concluded there is no indication that the genes responsible for the familial or hereditary conditions are involved in sIBM. Diagnosis Elevated creatine kinase (CK) levels in the blood (at most ~10 times normal) are typical in sIBM but affected individuals can also present with normal CK levels. Electromyography (EMG) studies display variable abnormalities such as increased insertional activity, increased spontaneous activity (fibrillation potentials and sharp waves), and large/broad or short/narrow motor unit potentials. On EMG, recruitment patterns can be reduced or increased. Findings can vary even within the same muscle of an affected individual. Muscle biopsy may display several common findings including; inflammatory cells invading muscle cells, vacuolar degeneration, and inclusion bodies of aggregations of multiple proteins. sIBM is a challenge to the pathologist and even with a biopsy, diagnosis can be ambiguous.A diagnosis of inclusion body myositis was historically dependent on muscle biopsy results. Antibodies to cytoplasmic 5-nucleotidase (cN1A; NT5C1A) have been strongly associated with the condition. However, other inflammatory conditions, such as lupus, can have a positive anti-NT5C1A. As of 2019, it remains to be established whether a positive anti-NT5C1A antibody test can make muscle biopsy unneeded. Muscle imaging can help establish the pattern of muscle involvement and selection of a biopsy site. Differential diagnosis IBM is often initially misdiagnosed as polymyositis. A course of prednisone is typically completed with no improvement and eventually, sIBM is confirmed. sIBM weakness comes on over months or years and progresses steadily, whereas polymyositis has an onset of weeks or months. Muscular dystrophy (e.g. limb girdle muscular dystrophy) must be considered as well. sIBM can be mistaken for physical deconditioning.Hereditary myopathies can mimic sIBM, both in signs and symptoms and in the appearance of muscle biopsies. A small percentage of those initially diagnosed with sIBM are later found to have pathogenic mutations in the genes VCP and SQSTM1, which are known to cause hIBM.IBM has a distinctive pattern of muscle involvement that distinguishes it among inflammatory myopathies. Characteristic of IBM is weakness of finger flexion, knee extension, and ankle dorsiflexion. Other inflammatory myopathies cause a proximal muscle weakness pattern, such as weakness of hip flexion, abduction, and extension, as well as shoulder abduction. IBM and other inflammatory myopathies both cause bicep/tricep weakness. Classification The common type is sIBM; it strikes individuals apparently at random. There is a type that has been observed in multiple siblings in the same generation in several families, termed familial inflammatory sIBM, but it is not passed on from generation to generation. There are also several very rare forms of hereditary inclusion body myopathy (hIBM) that are linked to specific genetic defects and that are passed on from generation to generation, each inherited in different ways. Management There is no standard course of treatment to slow or stop the progression of the disease as of 2019. sIBM patients do not reliably respond to anti-inflammatory, immunosuppressant, or immunomodulatory medications. Most of disease management is supportive care. Prevention of falls is an important consideration. There is no consensus on exercise guidelines; however, physical therapy is recommended to teach the patient a home exercise program, to teach how to compensate during mobility-gait training with an assistive device, transfers and bed mobility. An exercise regimen preferentially minimizes a patients risk of injury and corresponds to the patients goals. Other related disorders When sIBM was originally described, the major feature noted was muscle inflammation. Two other disorders were also known to display muscle inflammation, and sIBM was classified along with them. They are dermatomyositis (DM) and polymyositis (PM) and all three illnesses were called idiopathic (of unknown origin) myositis or inflammatory myopathies.It appears that sIBM and polymyositis share some features, especially the initial sequence of immune system activation, however, polymyositis comes on over weeks or months, does not display the subsequent muscle degeneration and protein abnormalities as seen in IBM, and as well, polymyositis tends to respond well to treatments, IBM does not. IBM is often confused with (misdiagnosed as) polymyositis. Polymyositis that does not respond to treatment is likely IBM.Dermatomyositis shares a number of similar physical symptoms and histopathological traits as polymyositis, but exhibits a skin rash not seen in polymyositis or sIBM. It may have different root causes unrelated to either polymyositis or sIBM.Mutations in valosin-containing protein (VCP) cause multisystem proteinopathy (MSP), which can present (among others) as a rare form of inclusion body myopathy. Epidemiology Prevalence of disease in a rigorous meta-analysis in 2017 was 46 patients per million. The earliest published prevalence was in 2000 and put at 5 per million. A 2017 study in Ireland reported 112 per million. It is not believed that the disease prevalence is increasing with time, but rather diagnostics and reporting are improving.Estimates of the mean age of onset range from 61 to 68 years old. Society and culture In the biographical drama film Father Stu, the protagonist, a boxer-turned-Catholic priest, has sIBM. See also Inflammatory myopathies References External links GeneReview/NIH/UW entry on Inclusion Body Myopathy 2

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I'm encountering the term 'Leukoencephalopathy with vanishing white matter' in medical literature. What's its definition?

Leukoencephalopathy with vanishing white matter (VWM disease) is an autosomal recessive neurological disease. The cause of the disease are mutations in any of the 5 genes encoding subunits of the translation initiation factor eIF2B: EIF2B1, EIF2B2, EIF2B3, EIF2B4, or EIF2B5. The disease belongs to a family of conditions called the Leukodystrophies. Symptoms and signs Onset usually occurs in childhood, however some adult cases have been found. Generally, physicians look for the symptoms in children. Symptoms include cerebellar ataxia, spasticity, optic atrophy, epilepsy, loss of motor functions, irritability, vomiting, coma, and even fever has been tied to VWM. The neurological disorders and symptoms which occur with VWM are not specific to countries; they are the same all over the world. Neurological abnormalities may not always be present in those who experience onset as adults. Symptoms generally appear in young children or infants who were previously developing fairly normally. Causes VWM is a leukodystrophy which has unique biochemical abnormalities. A unique characteristic of VWM is that only oligodendrocytes and astrocytes are negatively affected while other glial cells and neurons seem to be unaffected. This is the central question behind VWM. The real reasons behind this behavior are unknown since the cells are in the brain and have been rarely studied. However, there is a theory which is generally accepted by most experts in the field. The main characteristic of these cells is the fact that they synthesize a lot of proteins. These cells produce a large amount of proteins from a small amount of precursors and so are constantly working and under a reasonable amount of stress. So with a mutation in eIF2B, slight increases in the amount of stress these cells encounter occur, making them more susceptible to failure due to stress. The large amount of oligodendrocytes which display apoptotic characteristics and express apoptotic proteins suggests cell number reduction in the early stages of the disease. Premature ovarian failure has also been associated with diminishing white matter. However through an intensive survey, it was determined that even if an individual has premature ovarian failure, she does not necessarily have VWM. eIF2Bs role eIF2B is the guanine nucleotide-exchange factor for eIF2, and is composed of 5 subunits. The largest subunit, eIF2B5 contains the most mutations for VWM. eIF2B is a complex which is very involved with the regulation of in the translation of mRNA into proteins. eIF2B is essential for the exchange of guanosine diphosphate(GDP) for guanosine-5-triphosphate(GTP) in the initiation of translation via eIF2, because eIF2 is regenerated through this exchange. A decrease in eIF2B activity has been correlated with the onset of VWM. A common factor among VWM patients is mutations in the five subunits of eIF2B (21 discovered thus far), expressed in over 60% of the patients. These mutations lead to the decreased activity of eIF2B. The most common mutation is R113H, which is the mutation of histidine to arginine. The homozygous form of the mutation is the least severe form. This mutation has also been documented in rodents, but they do not acquire VWM, while humans do. Another common mutation is G584A found in the eIF2B5 subunit. A correlation with stress has also been made, as eIF2B plays a central role in stress management – it is essential in down regulation protein synthesis in different stress conditions – and VWM patients are highly sensitive to stress. Protein eIF2B exists in all cells, and if this protein is reduced enough the cell will be negatively affected, and if it is reduced to zero, the cell will die. In affected cells, the protein is reduced to about 50%, which is acceptable for functionality in most cells, but not in glial cells since they synthesize a large amount of proteins constantly and need as many functioning proteins within them as possible. This would lower the baseline of the amount of stress a cell can handle, and thus in a stressed environment, it would have detrimental effects on these cells. Mutations in three of the subunits of eIF2B (2,4,&5) has been seen in both VWM and premature ovarian failure. The North American Cree population has also been found to have a distinctive mutation, R195H, which can lead to VWM. All patients who have been studied only have one mutation present in the gene, causing the eIF2B to still be active, which leads to VWM. If two mutations occurred, then eIF2B activity would be stopped by the body. Neuropathology Upon autopsy, the full effect of VWM has been documented. The gray matter remains normal in all characteristics while the white matter changes texture, becoming soft and gelatinous. Rarefaction of the white matter is seen through light microscopy and the small number of axons and U-fibers that were affected can also be seen. Numerous small cavities in the white matter are also apparent. The key characteristic that sets VWM apart from the other leukodystrophies is the presence of foamy oligodendrocytes. These foamy oligodendrocytes tend to have increased cytoplasmic structures, a greater number of irregular mitochondria and a higher rate of apoptosis. Abnormally shaped astrocytes with fibrile infections are very prevalent throughout the capillaries in the brain. Strangely, astrocytes are affected more than oligodendrocytes; there is even a reduction in the astrocyte progenitors, yet axons remain relatively unharmed. Diagnosis Most diagnosis occurs in the early years of life around 2 to 6 years old. There have been cases in which onset and diagnosis have occurred late into adulthood. Those with onset at this time have different signs, particularly the lack of cognitive deterioration. Overall, detection of adult forms of VWM is difficult as MRI was not a common tool when they were diagnosed. Common signs to look for include chronic progressive neurological deterioration with cerebellar ataxia, spasticity, mental decline, decline of vision, mild epilepsy, hand tremor, the ability to chew and swallow food becomes difficult, rapid deterioration and fibrile infections following head trauma or fright, loss of motor functions, irritability, behavioural changes, vomiting, and even coma. Those who go into coma, if they do come out usually die within a few years. The diagnosis can be difficult if the physician does not take an MRI. Case report on diagnosis of adult-onset VWM The individual was examined at age 32, but he stated that he started noting differences 5 years before. He noticed sexual impotency, social isolation, unexplained aggression and sadness, loss of motivation, inert laughs, auditory hallucinations, thought insertion, delusions, and imperative commenting. He showed very minimal physical impairments, commonly seen in child-onsets. However, his MRI showed characteristic signs of VWM disease. MRI The MRI of patients with VWM shows a well defined leukodystrophy. These MRIs display reversal of signal intensity of the white matter in the brain. Recovery sequences and holes in the white matter are also visible. Over time, the MRI is excellent at showing rarefaction and cystic degeneration of the white matter as it is replaced by fluid. To show this change, displaying white matter as a high signal (T2-weighted), proton density, and Fluid attenuated inversion recovery (FLAIR) images are the best approach. T2-weighted images also displaying cerebrospinal fluid and rarefied/cystic white matter. To view the remaining tissue, and get perspective on the damage done (also helpful in determining the rate of deterioration) (T1-weighted), proton density, and FLAIR images are ideal as they show radiating stripe patterns in the degenerating white matter. A failure of MRI images is their ineffectiveness and difficulty in interpretation in infants since the brain has not fully developed yet. Though some patterns and signs may be visible, it is still difficult to conclusively diagnose. This often leads to misdiagnosis in infants particularly if the MRI results in equivocal patterns or because of the high water content in infants brains. The easiest way to fix this problem is a follow-up MRI in the following weeks. A potentially similar appearance of MRI with white matter abnormalities and cystic changes may be seen in some patients with hypomelanosis of Ito, some forms of Lowes (oculocerebrorenal) disease, or some of the mucopolysaccharidoses. Common misdiagnosis Often with VWM, the lack of knowledge of the disease causes a misdiagnosis among physicians. As VWM is a member of the large group of leukodystrophy syndromes, it is often misdiagnosed as another type such as metachromatic leukodystrophy. More often than not, it is simply classified as a non-specific leukodystrophy. The characteristics of the brain upon autopsy are often very similar to atypical diffuse sclerosis, such as the presence of fibrillary astrocytes and scant sudanophilic lipids. Adult-onset VWM disease can present with psychosis and may be hard to differentiate from schizophrenia. Common misdiagnosis from misinterpreting the MRI include asphyxia, congenital infections, metabolic diseases.Multiple sclerosis is often a misdiagnosis, but only in children due to its neurological characteristics, onset in early years, and MRI abnormalities. However, there are many differences between the two diseases. The glial cells express a loss of myelin. This loss of myelin is different from that seen in other diseases where hypomyelination occurs. In VWM, the cells never produce the normal amounts, whereas with diseases like MS, the cells normal amounts are deteriorated. Also, with MS, the demyelination occurs due to inflammation, which is not the case in VWM. Cell differences include a lower penetration of the macrophages and microglia, as well as the lack of T cells and B cells in VWM. Finally, patients with MS have widespread demyelination, but those with VWM only express demyelination in a localized area.Some atypical forms of multiple sclerosis (multiple sclerosis with cavitary lesions) can be specially difficult to differentiate but there are some clues in MRI imaging that can help. Treatment There are no treatments, only precautions which can be taken, mainly to reduce trauma to the head and avoiding physiological stress. Melatonin has been shown to provide cytoprotective traits to glial cells exposed to stressors such as excitotoxicity and oxidative stress. These stressors would be detrimental to cells with a genetically reduced activity of protein eIF2B. However, research connecting these ideas have not been conducted yet. Epidemiology Extensive pathological and biochemical tests were performed, however the cause was found by studying a small population in which mutations in the eIF2B gene were found. No effective systemic studies have been conducted to determine the incidence around the world, but through the studies conducted thus far, it appears to be more prevalent in the white populations. VWM appears to have a lower number of cases in the Middle East, and Turkey has not yet had a reported case. Its prevalence is limited by the physicians ability to identify the disease. As of 2006, more than 200 people have been identified with VWM, many of whom were originally diagnosed with an unclassified leukodystrophy. History The first time this disease was documented was in 1962 when Eickle studied a 36-year-old woman. Her first symptoms, gait difficulties and secondary amenorrhoea, occurred when she was 31 years old. Throughout the duration of her life, she experienced chronic episodes with extensive deterioration of her brain following minor physical trauma. Upon death, autopsy was performed in which the cerebral white matter displayed dispersed cystic areas. These areas were surrounded by a dense net of oligodendrocytes in which only mild fibrillary astrocytes and scant sudanophilic lipids were found.As the years progressed, more accounts of similar patients with similar symptoms were documented; however no one classified all the accounts as the same disease. It was not until 1993-94 when Dr. Hanefeld and Dr. Schiffmann and their colleagues identified the disease as childhood-onset progressive leukoencephalopathy. They determined it was autosomal recessive. They too saw that head trauma was a trigger for the onset of VWM. The key factor which allowed them to connect these patients together was the results of the magnetic-resonance spectroscopy in which the normal white matter signals were gone and often replaced with resonances indicative of lactate and glucose. They determined the cause was hypomyelination. in 1997–98, Dr. Marjo S. van der Knaap and colleagues saw the same characteristics in another set of patients, but these patients also expressed febrile infections. Dr. van der Knaap used MRI as well as magnetic-resonance spectroscopy and determined that ongoing cystic degeneration of the cerebral white matter and matter rarefaction was more descriptive of the disease rather than hypomyelination and proposed the name vanishing white matter. The name proposed by Dr. Schiffmann in 1994, childhood ataxia with central hypomyelination (CACH) is another commonly accepted name. See also The Stennis Foundation CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) Progressive multifocal leukoencephalopathy Metachromatic leukodystrophy General leukoencephalopathies References External links "Leukoencephalopathy with vanishing white matter". Neurographics. 2 (1). March 2012.

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I'm trying to understand 'Bipolar II disorder' within a medical context. Could you shed some light on it?

Bipolar II disorder (BP-II) is a mood disorder on the bipolar spectrum, characterized by at least one episode of hypomania and at least one episode of major depression. Diagnosis for BP-II requires that the individual must never have experienced a full manic episode. Otherwise, one manic episode meets the criteria for bipolar I disorder (BP-I).Hypomania is a sustained state of elevated or irritable mood that is less severe than mania yet may still significantly affect the quality of life and result in permanent consequences including reckless spending, damaged relationships and poor judgment.: 1651  Unlike mania, hypomania is not associated with psychosis. The hypomanic episodes associated with BP-II must last for at least four days.Commonly, depressive episodes are more frequent and more intense than hypomanic episodes. Additionally, when compared to BP-I, type II presents more frequent depressive episodes and shorter intervals of well-being. The course of BP-II is more chronic and consists of more frequent cycling than the course of BP-I. Finally, BP-II is associated with a greater risk of suicidal thoughts and behaviors than BP-I or unipolar depression. Although BP-II is commonly perceived to be a milder form of type I, this is not the case. Types I and II present equally severe burdens.BP-II is notoriously difficult to diagnose. Patients usually seek help when they are in a depressed state, or when their hypomanic symptoms manifest themselves in unwanted effects, such as high levels of anxiety, or the seeming inability to focus on tasks. Because many of the symptoms of hypomania are often mistaken for high-functioning behavior or simply attributed to personality, patients are typically not aware of their hypomanic symptoms. In addition, many people with BP-II have periods of normal affect. As a result, when patients seek help, they are very often unable to provide their doctor with all the information needed for an accurate assessment; these individuals are often misdiagnosed with unipolar depression. BP-II is more common than BP-I, while BP-II and major depressive disorder have about the same rate of diagnosis. Of all individuals initially diagnosed with major depressive disorder, between 40% and 50% will later be diagnosed with either BP-I or BP-II. Substance use disorders (which have high co-morbidity with BP-II) and periods of mixed depression may also make it more difficult to accurately identify BP-II. Despite the difficulties, it is important that BP-II individuals be correctly assessed so that they can receive the proper treatment. Antidepressant use, in the absence of mood stabilizers, is correlated with worsening BP-II symptoms. Causes Multiple factors contribute to the development of bipolar spectrum disorders, although there have been very few studies conducted to examine the possible causes of BP-II specifically. While no identifiable single dysfunctions in specific neurotransmitters have been found, preliminary data has shown that calcium signal transmission, the glutamatergic system, and hormonal regulation play a role in the pathophysiology of the disease. The cause of Bipolar disorder can be attributed to misfiring neurotransmitters that overstimulate the amygdala, which in turn causes the prefrontal cortex to stop working properly. The bipolar patient becomes overwhelmed with emotional stimulation with no way of understanding it, which can trigger mania and exacerbate the effects of depression. Signs and symptoms Bipolar disorder is characterized by marked swings in mood, activity, and behavior. BP-II is characterized by periods of hypomania, which may occur before, after, or independently of a depressive episode. Hypomania Hypomania is the signature characteristic of BP-II, defined by an experience of elevated mood. A patients mood is typically cheerful, enthusiastic, euphoric, or irritable. In addition, they can present with symptoms of inflated self-esteem or grandiosity, decreased need for sleep, talkativeness or pressured speech, flight of ideas or rapid cycling of thoughts, distractibility, increased goal-directed activity, psychomotor agitation, and/or excessive involvement in activities that have a high potential for painful consequences (engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments.)Hypomania is distinct from mania. During a typical hypomanic episode, patients may present as upbeat, may show signs of poor judgment or display signs of increased energy despite lack of sleep, but do not meet the full criteria for an acute manic episode. Patients may display elevated confidence, but do not express delusional thoughts as in mania. They can experience increase in goal-directed activity and creativity, but do not reach the severity of aimlessness and disorganization. Speech may be rapid, but interruptible. Patients with hypomania never present with psychotic symptoms and do not reach the severity to require psychiatric hospitalization.For these reasons, hypomania commonly goes unnoticed. Individuals often will only seek treatment during a depressive episode, and their history of hypomania may go undiagnosed. Although hypomania may increase functioning, episodes require treatment as they may indicate increasing instability and can precipitate a depressive episode. Depressive episodes It is during depressive episodes that BP-II patients often seek help. Symptoms may be syndromal or subsyndromal.Depressive episodes in BP-II can present similarly to those experienced in unipolar depressive disorders. Patients characteristically experience a depressed mood and may describe themselves as feeling sad, gloomy, down in the dumps, hopeless, or for most of the day, nearly every day. In children, this can present with an irritable mood. Most patients report significant fatigue, loss of energy, or tiredness. Patients or their family members may note diminished interest in usual activities such as sex, hobbies, or daily routines. Many patients report a change in appetite along with associated weight change. Sleep disturbances may be present, and can manifest as problems falling or staying asleep, frequent awakenings, excessive sleep, or difficulties getting up in the morning. Around half of depressed patients develop changes in psychomotor activity, described as slowness in thinking, speaking, or movement. Conversely, they may also present with agitation, with inability to sit still or wringing their hands. Changes in posture, speech, facial expression, and grooming can be observed. Other signs and symptoms include changes in posture and facial expression, slowed speech, poor hygiene, unkempt appearance, feelings of guilt, shame, or helplessness, diminished ability to concentrate, nihilistic thoughts, and suicidal ideation.Many experts in the field have attempted to find reliable differences between BP-I depressive episodes and episodes of major depressive disorder, but the data is inconsistent. However, some clinicians report that patients who came in with a depressive episode, but were later diagnosed as having bipolar disorder often presented with hypersomnia, increased appetite, psychomotor retardation, and a history of antidepressant-induced hypomania. Evidence also suggests that BP-II is strongly associated with atypical depression. Mood episodes with mixed features A mixed episode is defined by the presence of a hypomanic or depressive episode that is accompanied by symptoms of the opposite polarity. This is commonly referred to as a mood episode with mixed features (e.g. depression with mixed features or hypomania with mixed features), but can also be referred to as mixed episodes or mixed states. For example, a patient with depression with mixed features may have a depressed mood, but has simultaneous symptoms of rapid speech, increased energy, and flight of ideas. Conversely, a patient with hypomania with mixed features will present with the full criteria for a hypomanic episode, but with concurrent symptoms of decreased appetite, loss of interest, and low energy.Episodes with mixed features can last up to several months. They occur more frequently in patients with an earlier onset of bipolar disorder, are associated with higher frequency of episodes, and are associated with a greater risk of substance use, anxiety disorders, and suicidality. In addition, they are associated with increased treatment resistance compared to non-mixed episodes. Relapse Bipolar disorder is often a lifelong condition, and patients should be followed up regularly for relapse prevention. Although BP-II is thought to be less severe than BP-I in regard to symptom intensity, BP-II is associated with higher frequencies of rapid cycling and depressive episodes. In the case of a relapse, patients may experience new onset sleep disturbance, racing thoughts and/or speech, anxiety, irritability, and increase in emotional intensity. Family and/or friends may notice that patients are arguing more frequently with them, spending more money than usual, are increasing their binging on food, drugs, or alcohol, and may suddenly start taking on many projects at once. These symptoms often occur and are considered early warning signs.Psychosocial factors in a persons life can trigger a relapse in patients with BP-II. These include stressful life events, criticism from peers or relatives, and a disrupted circadian rhythm. In addition, the addition of antidepressant medications can trigger a hypomanic episode. Comorbid conditions Comorbid conditions are extremely common in individuals with BP-II. In fact, individuals are twice as likely to present a comorbid disorder than not. These include anxiety, eating, personality (cluster B), and substance use disorders. For BP-II, the most conservative estimate of lifetime prevalence of alcohol or other substance use disorders is 20%. In patients with comorbid substance use disorder and BP-II, episodes have a longer duration and treatment compliance decreases. Preliminary studies suggest that comorbid substance use is also linked to increased risk of suicidality. Diagnosis BP-II is diagnosed according to the criteria established in the American Psychiatric Associations Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). In addition, alternative diagnostic criteria is established in the World Health Organizations International Classification of Diseases-10th Revision (ICD-10). The diagnostic criteria are established from self-reported experiences from patients or their family members, the psychiatric assessment, and the mental status examination. In addition, Screening instruments like the Mood Disorders Questionnaire are helpful tools in determining a patients status on the bipolar spectrum. In addition, certain features have been shown to increase the chances that depressed patients have a bipolar disorder, including atypical symptoms of depression like hypersomnia and hyperphagia, a family history of bipolar disorder, medication-induced hypomania, recurrent or psychotic depression, antidepressant refractory depression, and early or postpartum depression. DSM-5 criteria According to the DSM-5, a patient diagnosed with BP-II will have experienced at least one hypomanic episode, at least one major depressive episodes, and no manic episode. Furthermore, the occurrence of the mood episodes are not better explained by schizoaffective disorder, schizophrenia, delusional disorder, or other specified or unspecified schizophrenia spectrum and other psychotic disorder. The final criteria that must be met is that the mood episodes cause clinically significant distress or impairment in social, occupational, or other important areas of functioning (from the depressive symptoms or the unpredictability of cycling between periods of depression and hypomania).A hypomanic episode is established if a patients symptoms last for most of the day each day for at least four days. Furthermore, three or more of the following symptoms must be present: Inflated sense of self-esteem or grandiose thoughts, feeling well rested despite getting low amounts of sleep (3 hours), talkativeness, racing thoughts, distractibility, and increase in goal-directed activity or psychomotor agitation, or excessive involvement in activities with high risk of painful consequences. Per DSM-5 criteria, a major depressive episode consists of the presence of a depressed mood or loss of interest/pleasure in activities (anhedonia). In addition to the former symptoms, five out of the nine following symptoms must occur for more than two weeks (to the extent in which it impairs functioning): weight loss/gain, insomnia or hypersomnia, psychomotor agitation or retardation, fatigue, feelings of worthlessness/inappropriate guilt, decreased concentration, or thoughts of death/suicide.Specifiers: With current or most recent episode hypomanic or depressed With partial remission or full remission With mild, moderate, or severe severity With anxious distress With catatonic features With mood congruent psychotic features With peripartum onset With seasonal pattern (applies only to the pattern of major depressive episodes) With rapid cycling. ICD-11 According to the ICD-11, a BP-II patient will have experienced episodic experiences of one or more hypomaniac episodes and one or more major depressive episodes, and no history of a manic episode or mixed episode. These symptoms cannot be explained by other diagnoses such as Cyclothymia ADHD Oppositional Defiant Disorder Schizophrenia and other primary psychotic disorders Substance-Use Disorder Personality Disorders Other Mental illness Physical issues such as a brain tumorThe specifiers are the same as the DSM-5 with the exception of catatonic features and if symptoms have occurred with or without psychosis about 6 weeks after childbirth Differential diagnoses The signs and symptoms of BP-II may overlap significantly with those of other conditions. Thus, a comprehensive history, medication review, and laboratory work are key to diagnosing BP-II and differentiating it from other conditions. The differential diagnosis of BP-II is as follows: unipolar major depression, borderline personality disorder, posttraumatic stress disorder, substance use disorders, and attention deficit hyperactivity disorder.: 1653–7  In clinical practice, the difficulty of diagnosing BP-II depends on the accurate detection of hypomania, which is frequently dismissed by patients. Patients can present with increased productivity and energy with the absence of signs of instability or disturbance. As such, there is a risk that BP-II is misdiagnosed as generalized anxiety disorder or unipolar major depression. An accurate evaluation of differential diagnoses are crucial, as they guide treatment and prognostic implications.Major differences between BP-I and BP-II have been identified in their clinical features, comorbidity rates and family histories. During depressive episodes, BP-II patients tend to show higher rates of psychomotor agitation, guilt, shame, suicidal ideation, and suicide attempts. BP-II patients have shown higher lifetime comorbidity rates of phobias, anxiety disorders, substance use, and eating disorders. In addition, there is a higher correlation between BP-II patients and family history of psychiatric illness, including major depression and substance-related disorders compared to BP-I. The occurrence rate of psychiatric illness in first degree relatives of BP-II patients was 26.5%, versus 15.4% in BP-I patients. Management Although BP-II is a prevalent condition associated with morbidity and mortality, there has been an absence of robust clinical trials and systematic reviews that investigate the efficacy of pharmacologic treatments for the hypomanic and depressive phases of BP-II. Thus, the current treatment guidelines for the symptoms of BP-II are derived and extrapolated from the treatment guidelines in BP-I, along with limited randomized controlled trials published in the literature.: 1697 The treatment of BP-II consists of the following: treatment of hypomania, treatment of major depression, and maintenance therapy for the prevention of relapse of hypomania or depression. As BP-II is a chronic condition, the goal of treatment is to achieve remission of symptoms and prevention of self-harm in patients. Treatment modalities of BP-II include medication-based pharmacotherapy, along with various forms of psychotherapy. Medications The most common pharmacologic agents utilized in the treatment of BP-II includes mood stabilizers, antipsychotics, and antidepressants. Mood stabilizers Mood stabilizers used in the treatment of hypomanic and depressive episodes of BP-II include lithium, and the anticonvulsant medications valproate, carbamazepine, lamotrigine, and topiramate.There is strong evidence that lithium is effective in treating both the depressive and hypomanic symptoms in BP-II, along with the reduction of hypomanic switch in patients treated with antidepressants. Furthermore, lithium is the only mood stabilizer to demonstrate a decrease in suicide and self-harm in patients with mood disorders. Due to lithiums narrow therapeutic index, lithium levels must be monitored regularly for prevention of lithium toxicity. There is also evidence that the anticonvulsants valproate, lamotrigine, carbamazepine, and topiramate are effective in the reduction of symptoms of hypomanic and depressive episodes of bipolar disorder. Potential mechanisms contributing to these effects include a decrease in brain excitation due to blockage of low-voltage sodium-gated channels, decrease in glutamate and excitatory amino acids, and potentiation of levels of GABA. There is evidence that lamotrigine decreases the risk of relapse in rapid-cycling BP-II. It is more effective in BP-II than BP-I, suggesting that lamotrigine is more effective for the treatment of depressive rather than manic episodes. Doses ranging from 100 to 200 mg have been reported to have the most efficacy, while experimental doses of 400 mg have rendered little response. A large, multicenter trial comparing carbamazepine and lithium over two and a half years found that carbamazepine was superior in terms of preventing future episodes of BP-II, although lithium was superior in individuals with BP-I. There is also some evidence for the use of valproate and topiramate, although the results for the use of gabapentin have been disappointing. Antipsychotics Antipsychotics are utilized as a second line option for hypomanic episodes, typically indicated patients who do not respond to mood stabilizers. However, quetiapine is the only antipsychotic that has demonstrated efficacy in multiple meta-analyses of Randomized controlled trials for treating acute BP-II depression, and is a first-line option for patients with BP-II depression.: 1697  Other antipsychotics that are used to treat BP-II include lurasidone, olanzapine, cariprazine, aripiprazole, asenapine, paliperidone, risperidone, ziprasidone, haloperidol, and chlorpromazine. As a class, the first generation antipsychotics are associated with movement disorders, along with anticholinergic side effects compared with second generation antipsychotics. Antidepressants There is evidence to support the use of SSRI and SNRI antidepressants in BP-II, but the use of these treatments are controversial. Potential risks of antidepressant pharmacotherapy in patients with bipolar disorder include increased mood cycling, development of rapid cycling, dysphoria, and switch to hypomania. In addition, the evidence for their efficacy in bipolar depression is mixed. Thus, in most cases, antidepressant monotherapy in patients with BP-II is not recommended. However, antidepressants may provide benefit some patients when used in addition to mood stabilizers and antipsychotics, as these drugs reduce the risk of manic/hypomanic switching. However, the risk still exists, and should be used with caution. Non-pharmaceutical therapies Although medication therapy is the standard of care for treatment of both BP-I and BP-II, additional non-pharmaceutical therapies can also help those with the illness. Benefits include prevention of relapse and improved maintenance medication adherence. These include psychotherapy (e.g. cognitive behavioral therapy, psychodynamic therapy, psychoanalysis, interpersonal therapy, behavioral therapy, cognitive therapy, and family-focused therapy), social rhythm therapy, art therapy, music therapy, psychoeducation, mindfulness, and light therapy. Meta-analyses in the literature has shown that psychotherapy plus pharmacotherapy was associated with a lower relapse rate compared with patients treated with pharmacotherapy alone. However, relapse can still occur, despite continued medication and therapy. People with bipolar disorder may develop dissociation to match each mood they experience. For some, this is done intentionally, as a means by which to escape trauma or pain from a depressive period, or simply to better organize ones life by setting boundaries for ones perceptions and behaviors. Prognosis There is evidence to suggest that BP-II has a more chronic course of illness than BP-I. This constant and pervasive course of the illness leads to an increased risk in suicide and more hypomanic and major depressive episodes with shorter periods between episodes than BP-I patients experience. The natural course of BP-II, when left untreated, leads to patients spending the majority of their lives with some symptoms, primarily stemming from depression. Their recurrent depression results in personal distress and disability.This disability can present itself in the form of psychosocial impairment, which has been suggested to be worse in BP-II patients than in BP-I patients. Another facet of this illness that is associated with a poorer prognosis is rapid cycling, which denotes the occurrence of four or more major Depressive, Hypomanic, and/or mixed episodes in a 12-month period. Rapid cycling is quite common in those with BP-II, much more so in women than in men (70% vs. 40%), and without treatment leads to added sources of disability and an increased risk of suicide. Women are more prone to rapid cycling between hypomanic episodes and depressive episodes. To improve a patients prognosis, long-term therapy is most favorably recommended for controlling symptoms, maintaining remission and preventing relapses. With treatment, patients have been shown to present a decreased risk of suicide (especially when treated with lithium) and a reduction of frequency and severity of their episodes, which in turn moves them toward a stable life and reduces the time they spend ill. To maintain their state of balance, therapy is often continued indefinitely, as around 50% of the patients who discontinue it relapse quickly and experience either full-blown episodes or sub-syndromal symptoms that bring significant functional impairments. Functioning The deficits in functioning associated with BP-II stem mostly from the recurrent depression that BP-II patients experience. Depressive symptoms are much more disabling than hypomanic symptoms and are potentially as, or more disabling than mania symptoms. Functional impairment has been shown to be directly linked with increasing percentages of depressive symptoms, and because sub-syndromal symptoms are more common—and frequent—in BP-II, they have been implicated heavily as a major cause of psychosocial disability. There is evidence that shows the mild depressive symptoms, or even sub-syndromal symptoms, are responsible for the non-recovery of social functioning, which furthers the idea that residual depressive symptoms are detrimental for functional recovery in patients being treated for BP-II. It has been suggested that symptom interference in relation to social and interpersonal relationships in BP-II is worse than symptom interference in other chronic medical illnesses such as cancer. This social impairment can last for years, even after treatment that has resulted in a resolution of mood symptoms.The factors related to this persistent social impairment are residual depressive symptoms, limited illness insight (a very common occurrence in patients with BP-II), and impaired executive functioning. Impaired ability in executive functions is directly tied to poor psychosocial functioning, a common side-effect in patients with BP-II.The impact on a patients psychosocial functioning stems from the depressive symptoms (more common in BP-II than BP-I). An increase in these symptoms severity seems to correlate with a significant increase in psychosocial disability. Psychosocial disability can present itself in poor semantic memory, which in turn affects other cognitive domains like verbal memory and (as mentioned earlier) executive functioning leading to a direct and persisting impact on psychosocial functioning.An abnormal semantic memory organization can manipulate thoughts and lead to the formation of delusions and possibly affect speech and communication problems, which can lead to interpersonal issues. BP-II patients have also been shown to present worse cognitive functioning than those patients with BP-I, though they demonstrate about the same disability when it comes to occupational functioning, interpersonal relationships, and autonomy. This disruption in cognitive functioning takes a toll on their ability to function in the workplace, which leads to high rates of work loss in BP-II patient populations. After treatment and while in remission, BP-II patients tend to report a good psychosocial functioning but they still score less than patients without the disorder. These lasting impacts further suggest that a prolonged period of untreated BP-II can lead to permanent adverse effects on functioning. Recovery and recurrence BP-II has a chronic relapsing nature. It has been suggested that BP-II patients have a higher degree of relapse than BP-I patients. Generally, within four years of an episode, around 60% of patients will relapse into another episode. Some patients are symptomatic half the time, either with full on episodes or symptoms that fall just below the threshold of an episode.Because of the nature of the illness, long-term therapy is the best option and aims to not only control the symptoms but to maintain sustained remission and prevent relapses from occurring. Even with treatment, patients do not always regain full functioning, especially in the social realm. There is a very clear gap between symptomatic recovery and full functional recovery for both BP-I and BP-II patients. As such, and because those with BP-II spend more time with depressive symptoms that do not quite qualify as a major depressive episode, the best chance for recovery is to have therapeutic interventions that focus on the residual depressive symptoms and to aim for improvement in psychosocial and cognitive functioning. Even with treatment, a certain amount of responsibility is placed in the patients hands; they have to be able to assume responsibility for their illness by accepting their diagnosis, taking the required medication, and seeking help when needed to do well in the future.Treatment often lasts after remission is achieved, and the treatment that worked is continued during the continuation phase (lasting anywhere from 6–12 months) and maintenance can last 1–2 years or, in some cases, indefinitely. One of the treatments of choice is Lithium, which has been shown to be very beneficial in reducing the frequency and severity of depressive episodes. Lithium prevents mood relapse and works especially well in BP-II patients who experience rapid-cycling. Almost all BP-II patients who take lithium have a decrease in the amount of time they spend ill and a decrease in mood episodes.Along with medication, other forms of therapy have been shown to be beneficial for BP-II patients. A treatment called a "well-being plan" serves several purposes: it informs the patients, protects them from future episodes, teaches them to add value to their life, and works toward building a strong sense of self to fend off depression and reduce the desire to succumb to the seductive hypomanic highs. The plan has to aim high. Otherwise, patients will relapse into depression. A large part of this plan involves the patient being very aware of warning signs and stress triggers so that they take an active role in their recovery and prevention of relapse. Mortality Several studies have shown that the risk of suicide is higher in patients who have BP-II than those with BP-I, and especially higher than patients with major depressive disorder.In results of a summary of several lifetime study experiments, it was found that 24% of BP-II patients experienced suicidal ideation or suicide attempts compared to 17% in BP-I patients and 12% in major depressive patients. Bipolar disorders, in general, are the third leading cause of death in 15- to 24-year-olds. BP-II patients were also found to employ more lethal means and have more complete suicides overall.BP-II patients have several risk factors that increase their risk of suicide. The illness is very recurrent and results in severe disabilities, interpersonal relationship problems, barriers to academic, financial, and vocational goals, and a loss of social standing in their community, all of which increase the likelihood of suicide. Mixed symptoms and rapid-cycling, both very common in BP-II, are also associated with an increased risk of suicide. The tendency for BP-II to be misdiagnosed and treated ineffectively, or not at all in some cases, leads to an increased risk.As a result of the high suicide risk for this group, reducing the risk and preventing attempts remains a main part of the treatment; a combination of self-monitoring, close supervision by a therapist, and faithful adherence to their medication regimen will help to reduce the risk and prevent the likelihood of suicide.Suicide is a common endpoint for many patients with severe psychiatric illness. The mood disorders (depression and bipolar) are by far the most common psychiatric conditions associated with suicide. At least 25% to 50% of patients with bipolar disorder also attempt suicide at least once. Aside from lithium—which is the most demonstrably effective treatment against suicide—little is known about contributions of specific mood-altering treatments to minimizing mortality rates in persons with either major mood disorders or bipolar depression specifically. Suicide is usually a manifestation of severe psychiatric distress that is often associated with a diagnosable and treatable form of depression or other mental illness. In a clinical setting, an assessment of suicidal risk must precede any attempt to treat psychiatric illness. Epidemiology The global estimated lifetime prevalence of bipolar disorder among adults range from 1 to 3 percent. The annual incidence is estimated to vary from 0.3 to 1.2 percent worldwide. According to the World Mental Health Survey Initiative, the lifetime prevalence of BP-II was found to be 0.4%, with a 12-month prevalence of 0.3%. Other meta-analyses have found lifetime prevalence of BP-II up to 1.57%. In the United States, the estimated lifetime prevalence of BP-II was found to be 1.1%, with a 12-month prevalence of 0.8%. The mean age of onset for BP-II was 20 years. Thus far, there have been no studies that have conclusively demonstrated that an unequal distribution of bipolar disorders across sex and ethnicity exists.It must be noted that a vast majority of studies and meta-analysis do not differentiate between BP-I and BP-II, and current epidemiology data may not accurately describe true prevalence and incidence. In addition, BP-II is underdiagnosed in practice, and it is easy to miss milder forms of the condition. History In 19th century psychiatry, mania covered a broad range of intensity, and hypomania was equated by some to concepts of partial insanity or monomania. A more specific usage was advanced by the German neuro-psychiatrist Emanuel Ernst Mendel in 1881, who wrote "I recommend (taking under consideration the word used by Hippocrates) to name those types of mania that show a less severe phenomenological picture, hypomania". Narrower operational definitions of hypomania were developed from the 1960s/1970s. The first diagnostic distinction to be made between manic-depression involving mania and involving hypomania came from Carl Gustav Jung in 1903. In his paper, Jung introduced the non-psychotic version of the illness with the statement, "I would like to publish a number of cases whose peculiarity consists in chronic hypomanic behavior" where "it is not a question of real mania at all but of a hypomanic state which cannot be regarded as psychotic." Jung illustrated the hypomanic variation with five case histories, each involving hypomanic behavior, occasional bouts of depression, and mixed mood states, which involved personal and interpersonal upheaval for each patient.In 1975, Jungs original distinction between mania and hypomania gained support. Fieve and Dunner published an article recognizing that only individuals in a manic state require hospitalization. It was proposed that the presentation of either the one state or the other differentiates two distinct diseases; the proposition was initially met with skepticism. However, studies since confirm that BP-II is a phenomenologically distinct disorder.Empirical evidence, combined with treatment considerations, led the DSM-IV Mood Disorders Work Group to add BP-II as its own entity in the 1994 publication. Only one other mood disorder was added to this edition, indicating the conservative nature of the DSM-IV work group. In May 2013, the DSM-5 was released. Two revisions to the existing BP-II criteria are anticipated. The first expected change will reduce the required duration of a hypomanic state from four to two days. The second change will allow hypomania to be diagnosed without the manifestation of elevated mood; that is, increased energy/activity will be sufficient. The rationale behind the latter revision is that some individuals with BP-II manifest only visible changes in energy. Without presenting elevated mood, these individuals are commonly misdiagnosed with major depressive disorder. Consequently, they receive prescriptions for antidepressants, which unaccompanied by mood stabilizers, may induce rapid cycling or mixed states. Society and culture Heath Black revealed in his autobiography, Black, that he has been diagnosed with BP-II. Maria Bamford has been diagnosed with BP-II. Geoff Bullock, singer-songwriter, was diagnosed with BP-II. Mariah Carey was diagnosed with BP-II in 2001. In 2018, publicly revealed and actively seeking treatment in the form of therapy and medication. Charmaine Dragun, former Australian journalist/newsreader. Inquest concluded she had BP-II. Joe Gilgun has been diagnosed with BP-II. Shane Hmiel has been diagnosed with BP-II. Jesse Jackson Jr. has been diagnosed with BP-II. Thomas Eagleton received a diagnosis of BP-II from Dr. Frederick K. Goodwin. Carrie Fisher had been diagnosed with BP-II. Demi Lovato has been diagnosed with BP-II. Evan Perry, subject of the documentary Boy Interrupted, was diagnosed with BP-II. Richard Rossi, filmmaker, musician, and maverick minister was diagnosed with BP-II. Rumer has been diagnosed with BP-II. Catherine Zeta-Jones received treatment for BP-II after dealing with the stress of her husbands throat cancer. According to her publicist, Zeta-Jones made a decision to check into a mental health facility for a brief stay. See also == References ==

You act as a medical communicator. Your goal is to translate medical terms into comprehensive, yet straightforward language for all readers.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Hydroxypropyl cellulose'?

Hydroxypropyl cellulose (HPC) is a derivative of cellulose with both water solubility and organic solubility. It is used as an excipient, and topical ophthalmic protectant and lubricant. Chemistry HPC is an ether of cellulose in which some of the hydroxyl groups in the repeating glucose units have been hydroxypropylated forming -OCH2CH(OH)CH3 groups using propylene oxide. The average number of substituted hydroxyl groups per glucose unit is referred to as the degree of substitution (DS). Complete substitution would provide a DS of 3. Because the hydroxypropyl group added contains a hydroxyl group, this can also be etherified during preparation of HPC. When this occurs, the number of moles of hydroxypropyl groups per glucose ring, moles of substitution (MS), can be higher than 3. Because cellulose is very crystalline, HPC must have an MS about 4 in order to reach a good solubility in water. HPC has a combination of hydrophobic and hydrophilic groups, so it has a lower critical solution temperature (LCST) at 45 °C. At temperatures below the LCST, HPC is readily soluble in water; above the LCST, HPC is not soluble. HPC forms liquid crystals and many mesophases according to its concentration in water. Such mesophases include isotropic, anisotropic, nematic and cholesteric. The last one gives many colors such as violet, green and red. Uses Lacrisert, manufactured by Aton Pharma, is a formulation of HPC used for artificial tears. It is used to treat medical conditions characterized by insufficient tear production such as keratoconjunctivitis sicca), recurrent corneal erosions, decreased corneal sensitivity, exposure and neuroparalytic keratitis. HPC is also used as a lubricant for artificial eyes. HPC is used as a thickener, a low level binder and as an emulsion stabiliser with E number E463. In pharmaceuticals it is used as a binder in tablets. HPC is used as a sieving matrix for DNA separations by capillary and microchip electrophoresis.HPC is the main ingredient in Cellugel, which is used in book conservation. Cellugel is described as "A safe, penetrating consolidant for leather book covers affected by red rot" and is produced by Preservation Solutions. See also Carboxymethyl cellulose Methyl cellulose Hypromellose == Notes and references ==

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I'm curious about the meaning of the medical term 'Gatifloxacin.' Can you give me some insights?

Gatifloxacin (brand names Gatiflo, Tequin, and Zymar) is an antibiotic of the fourth-generation fluoroquinolone family, that like other members of that family, inhibits the bacterial enzymes DNA gyrase and topoisomerase IV. It was patented in 1986 and approved for medical use in 1999. Side effects A Canadian study published in the New England Journal of Medicine in March 2006, claimed that Tequin can have significant side effects including dysglycemia. An editorial by Jerry Gurwitz in the same issue called for the Food and Drug Administration (FDA) to consider giving Tequin a black box warning. This editorial followed distribution of a letter dated February 15 by Bristol-Myers Squibb to health care providers indicating action taken with the FDA to strengthen warnings for the medication. Subsequently, Bristol-Myers Squibb reported it would stop manufacture of Tequin, end sales of the drug after existing stockpiles were exhausted, and return all rights to Kyorin.By contrast, ophthalmic gatifloxacin is generally well tolerated. The observed systemic concentration of the drug following oral administration of 400 mg (0.01 ounces) gatifloxacin is approximately 800 times higher than that of the 0.5% gatifloxacin eye drop. Given as an eye drop, gatifloxacin has very low systemic exposure. Therefore, the systemic exposures resulting from the gatifloxacin ophthalmic solution are not likely to pose any risk for systemic toxicities. Contraindications Hypersensitivity Society and culture Availability Gatifloxacin is currently available in the US and Canada only as an ophthalmic solution.In 2011, the Union Health and Family Welfare Ministry of India banned the manufacture, sale, and distribution of gatifloxacin because of its adverse side effects.In China, gatifloxacin is sold in tablet as well as in eye drop formulations. Brand names Bristol-Myers Squibb introduced gatifloxacin in 1999 under the proprietary name Tequin for the treatment of respiratory tract infections, having licensed the medication from Kyorin Pharmaceutical Company of Japan. Allergan produces it in eye-drop formulation under the names Zymar, Zymaxid and Zylopred. In many countries, gatifloxacin is also available as tablets and in various aqueous solutions for intravenous therapy. == References ==

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I'd like to learn more about the medical term 'Gastroptosis.' Can you provide some details?

Gastroptosis is the abnormal downward displacement of the stomach. It is not a life-threatening condition. The condition frequently causes digestive symptoms and constipation. It is much more prominent in women than men. Gastroptosis is diagnosed with x-ray using barium contrast. See also Visceroptosis References == External links ==

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'm seeking clarification on the medical term 'Floxuridine.' Could you explain it?

Floxuridine (also 5-fluorodeoxyuridine) is an oncology drug that belongs to the class known as antimetabolites. Specifically, floxuridine is a pyrimidine analog, classified as a deoxyuridine. The drug is usually administered via an artery, and most often used in the treatment of colorectal cancer. The quality of life and survival rates of individuals that receive continuous hepatic artery infusion of floxuridine for colorectal cancer metastases is significantly higher than control groups. Floxuridine can also be prescribed for the treatment of kidney and stomach cancers. In vitro uses of floxuridine include 5-minute treatments of fluorouracil, floxuridine, and mitomycin to increase cell proliferation in Tenons capsule fibroblasts. Biosynthesis Immobilized Aeromonas salmonicida ATCC 27013, when exposed to thymidine and 5-fluorouracil in phosphate buffer at room temperature for one hour, can synthesize floxuridine and thymine. Pharmacology Floxuridine primarily works by stopping the growth of newly born cells. The drug essentially stops DNA from forming in new and rapidly developing cells, which is a sign of a cancerous cell. Therefore, the floxuridine kills the cancerous cells. For colorectal cancer and hepatic metastases, an average adult should be given an intra-arterial dosage of 0.1–0.6 mg/kg/day as a continuous infusion, continued until intolerable toxicity is reached (white blood cell count < 3,500/mm3 or platelet count < 100,000/mm3). Lethal dosages for other species are below. LD50 is the lethal dose at which half of organisms exposed to the drug die. Pharmacodynamics Floxuridine is a pyrimidine analog that acts as an inhibitor of the S-phase of cell division. This selectively kills rapidly dividing cells. Antimetabolites masquerade as pyrimidine-like molecules which prevents normal pyrimidines from being incorporated into DNA during the S phase of the cell cycle. Fluorouracil (the end-product of catabolism of floxuridine) blocks an enzyme which converts cytosine nucleosides into the deoxy derivative. In addition, DNA synthesis is further inhibited because fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand. Mechanism of action Floxuridine is rapidly catabolized to 5-fluorouracil, which is the active form of the drug. The primary effect is interference with DNA synthesis and to a lesser extent, inhibition of RNA formation through the drugs incorporation into RNA, thus leading to the production of fraudulent RNA. Fluorouracil also inhibits uracil riboside phosphorylase, which prevents the utilization of preformed uracil in RNA synthesis. As well, the monophosphate of floxuridine, 5-fluoro-2-deoxyuridine-5-phosphate (FUDR-MP) inhibits the enzyme thymidylate synthetase. This leads to the inhibition of methylation of deoxyuridylic acid to thymidylic acid, thus interfering with DNA synthesis. Route of elimination The drug is excreted intact and as urea, fluorouracil, α-fluoro-β-ureidopropionic acid, dihydrofluorouracil, α-fluoro-β-guanidopropionic acid, and α-fluoro-β-alanine in the urine; it is also expired as respiratory carbon dioxide. Side effects Side effects include: Common (30% of patients) Low blood counts. Your white and red blood cells and platelets may temporarily decrease. This can put you at increased risk for infection, anemia and/or bleeding. Mouth sores Diarrhea (may be severe) Less common (10–29% of patients) Poor appetite Nausea and vomiting Hair loss Elevated liver enzymes (temporary increase in alkaline phosphatase, lactate dehydrogenase, transaminase, and bilirubin). This is seen more with the intra-arterial infusion directly into the liver. Hand-foot syndrome (Palmar-plantar erythrodysesthesia or PPE) -skin rash, swelling, redness, pain and/or peeling of the skin on the palms of hands and soles of feet Stomach ulcers (This is seen more with the intra-arterial infusion). Contact your health provider immediately Fever of 100.4 °F (38 °C) or higher, chills (possible signs of infection). Contact your health provider Diarrhea (2 episodes in a 24-hour period) Nausea (interferes with ability to eat and unrelieved with prescribed medication) Vomiting (vomiting more than 4–5 times in a 24-hour period) Mouth sores (painful redness, swelling or ulcers) Unusual bleeding or bruising Black or tarry stools, or blood in your stools Blood in the urine Yellowing of the skin or eyes Tingling or burning, redness, swelling of the palms of the hands or soles of feet Other Fertility for both men and women may be affected by floxuridine. Use in research Apart from its use in chemotherapy, floxuridine is also used in aging research employing a C. elegans model, namely to stop growth and to prevent reproduction. The latter is brought about by treatment of larvae close to maturity with low doses of floxuridine that, even though allowing normal maturation, causes reproducing individuals to lay eggs that are unable to hatch. This limits the population to a single generation allowing quantification of aging processes and measurement of longevity. It has, however, been indicated that floxuridin exposure by itself increases life expectancy potentially leading to flawed data in respective studies. History Floxuridine first gained FDA approval in December 1970 under the brand name FUDR. The drug was initially marketed by Roche, which also did a lot of the initial work on 5-fluorouracil. The National Cancer Institute was an early developer of the drug. Roche sold its FUDR product line in 2001 to F H Faulding, which became Mayne Pharma. Alternative names Synonyms for floxuridine include: == References ==

You are a medical knowledge base. Your task is to elucidate medical terminology, offering insights into their meanings, origins, and applications.

Could you please explain the term 'Amifampridine' in simple language?

Amifampridine is used as a drug, predominantly in the treatment of a number of rare muscle diseases. The free base form of the drug has been used to treat congenital myasthenic syndromes and Lambert–Eaton myasthenic syndrome (LEMS) through compassionate use programs since the 1990s and was recommended as a first line treatment for LEMS in 2006, using ad hoc forms of the drug, since there was no marketed form. Around 2000 doctors at Assistance Publique – Hôpitaux de Paris created a phosphate salt form, which was developed through a series of companies ending with BioMarin Pharmaceutical which obtained European approval in 2009 under the trade name Firdapse, and which licensed the US rights to Catalyst Pharmaceuticals in 2012. As of January 2017, Catalyst and another US company, Jacobus Pharmaceutical, which had been manufacturing and giving it away for free since the 1990s, were both seeking FDA approval for their iterations and marketing rights. Amifampridine phosphate has orphan drug status in the EU for Lambert–Eaton myasthenic syndrome and Catalyst holds both an orphan designation and a breakthrough therapy designation in the US. In May 2019 the U.S. Food and Drug Administration (FDA) approved amifampridine tablets under the trade name Ruzurgi for the treatment of Lambert-Eaton myasthenic syndrome (LEMS) in patients 6 to less than 17 years of age. This is the first FDA approval of a treatment specifically for pediatric patients with LEMS. The FDA granted the approval of Ruzurgi to Jacobus Pharmaceutical. The only other treatment approved for LEMS (Firdapse) is only approved for use in adults. Medical uses Amifampridine is used to treat many of the congenital myasthenic syndromes, particularly those with defects in choline acetyltransferase, downstream kinase 7, and those where any kind of defect causes "fast channel" behaviour of the acetylcholine receptor. It is also used to treat symptoms of Lambert–Eaton myasthenic syndrome. Contraindications Because it affects voltage-gated ion channels in the heart, it is contraindicated in people with long QT syndrome and in people taking a drug that might prolong QT time like sultopride, disopyramide, cisapride, domperidone, rifampicin or ketoconazol. It is also contraindicated in people with epilepsy or badly controlled asthma. Adverse effects The dose-limiting side effects include tingling or numbness, difficulty sleeping, fatigue, and loss of muscle strength.Amifampridine can cause seizures, especially but not exclusively when given at high doses and/or in particularly vulnerable individuals who have a history of seizures. Interactions The combination of amifampridine with pharmaceuticals that prolong QT time increases the risk of ventricular tachycardia, especially torsade de pointes; and combination with drugs that lower the seizure threshold increases the risk of seizures. Interactions via the livers cytochrome P450 enzyme system are considered unlikely. Pharmacology Mechanism of action In Lambert–Eaton myasthenic syndrome, acetylcholine release is inhibited as antibodies involved in the host response against certain cancers cross-react with Ca2+ channels on the prejunctional membrane. Amifampridine works by blocking potassium channel efflux in nerve terminals so that action potential duration is increased. Ca2+ channels can then be open for a longer time and allow greater acetylcholine release to stimulate muscle at the end plate. Pharmacokinetics Amifampridine is quickly and almost completely (93–100%) absorbed from the gut. In a study with 91 healthy subjects, maximum amifampridine concentrations in blood plasma were reached after 0.6 (±0.25) hours when taken without food, or after 1.3 (±0.9) hours after a fatty meal, meaning that the speed of absorption varies widely. Biological half-life (2.5±0.7 hrs) and the area under the curve (AUC = 117±77 ng∙h/ml) also vary widely between subjects, but are nearly independent of food intake.The substance is deactivated by acetylation via N-acetyltransferases to the single metabolite 3-N-acetylamifampridine. Activity of these enzymes (primarily N-acetyltransferase 2) in different individuals seems to be primarily responsible for the mentioned differences in half-life and AUC: the latter is increased up to 9-fold in slow metabolizers as compared to fast metabolizers.Amifampridine is eliminated via the kidneys and urine to 74–81% as N-acetylamifampridine and to 19% in unchanged form. Chemistry 3,4-Diaminopyridine is a pale yellow to pale brown crystalline powder that melts at about 218–220 °C (424–428 °F) under decomposition. It is readily soluble in methanol, ethanol and hot water, but only slightly in diethyl ether. Solubility in water at 20 °C (68 °F) is 25 g/L. The drug formulation amifampridine phosphate contains the phosphate salt, more specifically 4-aminopyridine-3-ylammonium dihydrogen phosphate. This salt forms prismatic, monoclinic crystals (space group C2/c) and is readily soluble in water. The phosphate salt is stable, and does not require refrigeration. History The development of amifampridine and its phosphate has brought attention to orphan drug policies that grant market exclusivity as an incentive for companies to develop therapies for conditions that affect small numbers of people.Amifampridine, also called 3,4-DAP, was discovered in Scotland in the 1970s, and doctors in Sweden first showed its use in LEMS in the 1980s.In the 1990s, doctors in the US, on behalf of Muscular Dystrophy Association, approached a small family-owned manufacturer of active pharmaceutical ingredients in New Jersey, Jacobus Pharmaceuticals, about manufacturing amifampridine so they could test it in clinical trials. Jacobus did so, and when the treatment turned out to be effective, Jacobus and the doctors were faced with a choice — invest in clinical trials to get FDA approval or give the drug away for free under a compassionate use program to about 200 patients out of the estimated 1500-3000 LEMS patients in the U.S.. Jacobus elected to give the drug away to this subset of LEMS patients, and did so for about twenty years.Doctors at the Assistance Publique – Hôpitaux de Paris had created a phosphate salt of 3,4-DAP (3,4-DAPP), and obtained an orphan designation for it in Europe in 2002. The hospital licensed the intellectual property on the phosphate form to the French biopharma company OPI, which was acquired by EUSA Pharma in 2007, and the orphan application was transferred to EUSA in 2008. In 2008 EUSA submitted an application for approval to market the phosphate form to the European Medicines Agency under the brand name Zenas. EUSA, through a vehicle called Huxley Pharmaceuticals, sold the rights to 3,4-DAPP to BioMarin in 2009, the same year that 3,4-DAPP was approved in Europe under the new name Firdapse.The licensing of Firdapse in 2010 in Europe led to a sharp increase in price for the drug. In some cases, this has led to hospitals using an unlicensed form rather than the licensed agent, as the price difference proved prohibitive. BioMarin has been criticized for licensing the drug on the basis of previously conducted research, and yet charging exorbitantly for it. A group of UK neurologists and pediatricians petitioned to prime minister David Cameron in an open letter to review the situation. The company responded that it submitted the licensing request at the suggestion of the French government, and points out that the increased cost of a licensed drug also means that it is monitored by regulatory authorities (e.g. for uncommon side effects), a process that was previously not present in Europe. A 2011 Cochrane review compared the cost of the 3,4-DAP and 3,4-DAPP in the UK and found an average price for 3,4-DAP base of £1/tablet and an average price for 3,4-DAP phosphate of £20/tablet; and the authors estimated a yearly cost per person of £730 for the base versus £29,448 for the phosphate formulation.Meanwhile, in Europe, a task force of neurologists had recommended 3,4-DAP as the firstline treatment for LEMS symptoms in 2006, even though there was no approved form for marketing; it was being supplied ad hoc.: 5  In 2007 the drugs international nonproprietary name was published by the WHO.In the face of the seven-year exclusivity that an orphan approval would give to Biomarin, and of the increase in price that would accompany it, Jacobus began racing to conduct formal clinical trials in order to get approval for the free base form before BioMarin; its first Phase II trial was opened in January 2012.In October 2012, while BioMarin had a Phase III trial ongoing in the US, it licensed the US rights to 3,4-DAPP, including the orphan designation and the ongoing trial, to Catalyst Pharmaceuticals. Catalyst anticipated that it could earn $300 to $900 million per year in sales at peak sales for treatment of people with LEMS and other indications, and analysts anticipated the drug would be priced at around. $100,000 in the US. Catalyst went on to obtain a breakthrough therapy designation for 3,4-DAPP in LEMS in 2013, an orphan designation for congenital myasthenic syndromes in 2015 and an orphan designation for myasthenia gravis in 2016.In August 2013, analysts anticipated that FDA approval would be granted to Catalyst in LEMS by 2015.In October 2014, Catalyst began making available under an expanded access program.In March 2015, Catalyst obtained an orphan designation for the use of 3,4-DAPP to treat of congenital myasthenic syndrome. In April 2015, Jacobus presented clinical trial results with 3,4-DAP at a scientific meeting.In December 2015 a group of 106 neuromuscular doctors who had worked with both Jacobus and BioMarin/Catalyst published an editorial in the journal, Muscle & Nerve, expressing concern about the potential for the price of the drug to be dramatically increased should Catalyst obtain FDA approval, and stating that 3,4-DAPP represented no real innovation and didnt deserve exclusivity under the Orphan Drug Act, which was meant to spur innovation to meet unmet needs. Catalyst responded to this editorial with a response in 2016 that explained that Catalyst was conducting a full range of clinical and non-clinical studies necessary to obtain approval in order to specifically address the unmet need among the estimated 1500-3000 LEMs patients since about 200 were receiving the product through compassionate use – and that this is exactly what the Orphan Drug Act was intended to do: deliver approved products to orphan drug populations so that all patients have full access.In December 2015, Catalyst submitted its new drug application to the FDA, and in February 2016 the FDA refused to accept it, on the basis that it wasnt complete. In April 2016 the FDA told Catalyst it would have to gather further data. Catalyst cut 30% of its workforce, mainly from the commercial team it was building to support an approved product, to save money to conduct the trials. In March 2018 the company re-submitted its NDA. The FDA approved amifampridine for the treatment of adults with Lambert-Eaton myasthenic syndrome on November 29, 2018.In February 2019, U.S. Senator Bernie Sanders questioned the high price ($375,000) charged by Catalyst Pharmaceuticals for Firdapse.In May 2019, the privately held US company Jacobus Pharmaceutical, Princeton, New Jersey gained approval by the FDA for amifampridine tablets (Ruzurgi) for the treatment of LEMS in patients 6 to less than 17 years of age. This is the first FDA approval of a treatment specifically for pediatric patients with LEMS. Firdapse is only approved for use in adults. Although Ruzurgi has been approved for pediatric patients, this approval makes it possible for adults with LEMS to get the drug off-label. Jacobus Pharmaceutical had been manufacturing and giving it away for free since the 1990s. The FDA decision dropped the stock of Catalyst Pharmaceuticals. The companys stock price has dropped about 50%. Research Amifampridine has also been proposed for the treatment of multiple sclerosis (MS). A 2002 Cochrane systematic review found that there was no unbiased data to support its use for treating MS. There was no change as of 2012. References External links "Amifampridine". Drug Information Portal. U.S. National Library of Medicine. "Amifampridine phosphate". Drug Information Portal. U.S. National Library of Medicine.

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I'd like to learn more about the medical term 'Atoltivimab/maftivimab/odesivimab.' Can you provide some details?

Atoltivimab/maftivimab/odesivimab, sold under the brand name Inmazeb, is a fixed-dose combination of three monoclonal antibodies for the treatment of Zaire ebolavirus (Ebola virus). It contains atoltivimab, maftivimab, and odesivimab-ebgn and was developed by Regeneron Pharmaceuticals.The most common side effects include fever, chills, tachycardia (fast heart rate), tachypnea (fast breathing), and vomiting; however, these are also common symptoms of Ebola virus infection.Atoltivimab/maftivimab/odesivimab is the first FDA-approved treatment for Zaire ebolavirus. Atoltivimab/maftivimab/odesivimab was approved for medical use in the United States in October 2020. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Atoltivimab/maftivimab/odesivimab is indicated for the treatment of infection caused by Zaire ebolavirus. Contraindications People who receive atoltivimab/maftivimab/odesivimab should avoid the concurrent administration of a live vaccine due to the treatments potential to inhibit replication of a live vaccine virus indicated for prevention of Ebola virus infection and possibly reduce the vaccines efficacy. Pharmacology Mechanism of action Atoltivimab/maftivimab/odesivimab is a combination of Zaire ebolavirus glycoprotein-directed human monoclonal antibodies. The three antibodies target the glycoprotein that is on the surface of the Ebola virus. This glycoprotein normally attaches to the cell via a receptor and fuses the viral and host cell membranes allowing the virus to enter the cell. The antibodies can bind to it simultaneously at three different locations and block attachment and entry of the virus.This combination drug targets the Zaire species of Ebola virus. The Sudan and Bundibugyo strains have also caused outbreaks, and it is unlikely that it would be effective against these strains. History Early development The 2014 Ebola outbreak killed more than 11,300 people. Regeneron used its VelociGene, VelocImmune and VelociMab antibody discovery and production technologies and coordinated with the U.S. governments Biomedical Advanced Research and Development Authority (BARDA). The therapy was developed in six months and a Phase 1 trial in healthy humans was completed in 2015. PALM trial During the 2018 Équateur province Ebola outbreak, a similar monoclonal antibody treatment, mAb114, was requested by the Democratic Republic of Congo (DRC) Ministry of Public Health. mAb114 was approved for compassionate use by the World Health Organization MEURI ethical protocol and at DRC ethics board. mAb114 was sent along with other therapeutic agents to the outbreak sites. However, the outbreak came to a conclusion before any therapeutic agents were given to patients.Approximately one month following the conclusion of the Équateur province outbreak, a distinct outbreak was noted in Kivu in the DRC (2018–20 Kivu Ebola outbreak). Once again, mAb114 received approval for compassionate use by WHO MEURI and DRC ethic boards and has been given to many patients under these protocols. In November 2018, the Pamoja Tulinde Maisha (PALM [together save lives]) open-label randomized clinical control trial was begun at multiple treatment units testing mAb114, REGN-EB3 and remdesivir to ZMapp. Despite the difficulty of running a clinical trial in a conflict zone, investigators have enrolled 681 patients towards their goal of 725. This is the second largest outbreak with (as of January 2020) over 3,400 confirmed or probable cases, including more than 2,200 who have died.An interim analysis by the Data Safety and Monitoring Board (DSMB) of the first 499 patient found that mAb114 and REGN-EB3 were superior to the comparator ZMapp. Overall mortality of patients in the ZMapp and Remdesivir groups were 49% and 53% compared to 34% and 29% for mAb114 and REGN-EB3. When looking at patients who arrived early after disease symptoms appeared, survival was 89% for mAB114 and 94% for REGN-EB3. While the study was not powered to determine whether there is any difference between REGN-EB3 and mAb114, the survival difference between those two therapies and ZMapp was significant. This led to the DSMB halting the study and PALM investigators dropping the remdesivir and ZMapp arms from the clinical trial. All patients in the outbreak who elect to participate in the trial will now be given either mAb114 or REGN-EB3.In August 2019, Congolese health officials announced it was more effective compared to two other treatments being used at the time.Among patients treated with it, 34% died; the mortality rate improved if the drug was administered soon after infection, in a timely diagnosis – critical for those infected with diseases like Ebola that can cause sepsis and, eventually, multiple organ dysfunction syndrome, more quickly than other diseases. The survival rate if the drug was administered shortly after the infection was 89%. Atoltivimab/maftivimab/odesivimab was evaluated in 382 adult and pediatric participants with confirmed Zaire ebolavirus infection in one clinical trial (the PALM trial) and as part of an expanded access program conducted in the Democratic Republic of the Congo (DRC) during an Ebola virus outbreak in 2018/2019. In the PALM trial, the safety and efficacy of atoltivimab/maftivimab/odesivimab was evaluated in a multi-center, open-label, randomized controlled trial, in which 154 participants received atoltivimab/maftivimab/odesivimab (50 mg of each monoclonal antibody) intravenously as a single infusion, and 168 participants received an investigational control. The trial enrolled pediatric and adult participants (including pregnant women) with Zaire ebolavirus infection. All participants received standard, supportive care for the disease. The participants and the health care providers knew which treatment was being given. The primary efficacy endpoint was 28-day mortality. The primary analysis population was all participants who were randomized and concurrently eligible to receive either atoltivimab/maftivimab/odesivimab or the investigational control during the same time period of the trial. Of the 154 participants who received atoltivimab/maftivimab/odesivimab, 33.8% died after 28 days, compared to 51% of the 153 participants who received a control. In the expanded access program, an additional 228 participants received atoltivimab/maftivimab/odesivimab. Regulatory status The FDA granted the application of atoltivimab/maftivimab/odesivimab-ebgn orphan drug and breakthrough therapy designations. The FDA granted the approval of Inmazeb to Regeneron Pharmaceuticals with an indication for the treatment of infection caused by Zaire ebolavirus in October 2020.The drug has also received orphan drug designation from the European Medicines Agency. References Further reading External links "Atoltivimab". Drug Information Portal. U.S. National Library of Medicine. "Maftivimab". Drug Information Portal. U.S. National Library of Medicine. "Odesivimab". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT03719586 for "Investigational Therapeutics for the Treatment of People With Ebola Virus Disease" at ClinicalTrials.gov "Making a Drug You Hope No One Will Ever Need". Regeneron Pharmaceuticals.

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I'm encountering the term 'Relative afferent pupillary defect' in medical literature. What's its definition?

A relative afferent pupillary defect (RAPD), also known as a Marcus Gunn pupil, is a medical sign observed during the swinging-flashlight test whereupon the patients pupils dilate when a bright light is swung from the unaffected eye to the affected eye. The affected eye still senses the light and produces pupillary sphincter constriction to some degree, albeit reduced. Depending on severity, different symptoms may appear during the swinging flash light test: Mild RAPD will presents as a weak pupil constriction initially, after which dilation continues to happen. When RAPD is moderate, pupil size will remain, after which it dilates When RAPD is severe, the pupil will dilate quickly Cause The most common cause of Marcus Gunn pupil is a lesion of the optic nerve (between the retina and the optic chiasm) due to glaucoma, or severe retinal disease, or due to multiple sclerosis. It is named after Scottish ophthalmologist Robert Marcus Gunn. A second common cause of Marcus Gunn pupil is a contralateral optic tract lesion, due to the different contributions of the intact nasal and temporal hemifields. Diagnosis The Marcus Gunn pupil is a relative afferent pupillary defect indicating a decreased pupillary response to light in the affected eye.In the swinging flashlight test, a light is alternately shone into the left and right eyes. A normal response would be equal constriction of both pupils, regardless of which eye the light is directed at. This indicates an intact direct and consensual pupillary light reflex. When the test is performed in an eye with an afferent pupillary defect, light directed in the affected eye will cause only mild constriction of both pupils (due to decreased response to light from the afferent defect), while light in the unaffected eye will cause a normal constriction of both pupils (due to an intact efferent path, and an intact consensual pupillary reflex). Thus, light shone in the affected eye will produce less pupillary constriction than light shone in the unaffected eye.Anisocoria is absent. A Marcus Gunn pupil is seen, among other conditions, in optic neuritis. It is also common in retrobulbar optic neuritis due to multiple sclerosis but only for 3–4 weeks, until the visual acuity begins to improve in 1–2 weeks and may return to normal.A total CN II lesion, in which the affected eye perceives no light, is very similar to a Marcus Gunn pupil; to distinguish them, in a CNII total lesion shining the light in the affected eye produces zero dilation nor constriction. See also References == External links ==

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I'm seeking clarification on the medical term 'Sitagliptin/simvastatin.' Could you explain it?

Sitagliptin/simvastatin, sold under the brand name Juvisync, is a fixed-dose combination anti-diabetic medication used to treat type 2 diabetes and hypercholesterolemia. It contains sitagliptin and simvastatin. Sitagliptin is a dipeptidyl peptidase-4 inhibitor and simvastatin is an HMG-CoA reductase inhibitor. These two disorders commonly occur in people at the same time, and have been typically treated with administration of these medications separately. The combination was approved in 2011, and sold under the brand name Juvisync by Merck. Juvisync was later removed from the market in 2013, due to business reasons. History In 1991, Merck & Cos simvastatin was approved as an HMG-COA inhibitor to lower the levels of LDL cholesterol. In 2006, Merck & Cos sitagliptin was approved by the FDA for treatment of diabetes mellitus type 2. Regulation Juvisync was the first product to combine a cholesterol lowering drug with a type 2 diabetes drug in the same tablet. Nonclinical toxicology Sitagliptin: Using male and female rats, a two-year carcinogenicity study was carried out with doses of 50, 150, and 500 mg/kg/day. The 500 mg/kg dose has exposure limits of 60 times what would be seen in the highest dose in humans. At this dose, liver adenoma/carcinoma was seen. Tumors were not seen from the smaller doses. Nomutagenic or clastogenic effects were seen from tests using several assays (CHO, rat, etc.). Fertility studies in rats showed no teratogenic effects.Simvastatin: No tumorigenic effect was seen in a 72-week carcinogenicity study using mice at the low dose levels. However, at the higher dose levels (eight and 16 times the human dose equivalent), liver carcinomas and adenomas, lung adenomas, and adenomas of the Harderian gland occurred. No mutagenic effects were seen in assays. Testicular atrophy was noted in dogs and rats at four and eight times the human exposure, respectively. Limitations of use It should not be used in patients with type 1 diabetes, diabetic ketoacidosis, pancreatitis, Fredrickson types I and V dyslipidemias, and severe renal impairment. Drug interactions Juvisync should not be used with: strong CYP3A4 inhibitors, cyclosporine, danazol, gemfibrozil, and other fibrates. Caution should be used and the patient should be monitored if they are taking the following: amiodarone, dronedarone, ranolazine, calcium channel blockers, niacin, digoxin, coumarin anticoagulants, and colchicine. References External links "Juvisync". Drug Information Portal. U.S. National Library of Medicine.

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I'd like to learn more about the medical term 'Solitary cutaneous leiomyoma.' Can you provide some details?

Solitary cutaneous leiomyoma typically presents as a deeply circumscribed, freely movable, rounded nodule ranging from 2 to 15 mm in diameter, with overlying skin that may have a reddish or violaceous tint.: 627 See also Multiple cutaneous leiomyoma Leiomyoma Skin lesion == References ==

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The term 'Narcolepsy' keeps coming up in medical discussions. What does it stand for?

Narcolepsy is a long-term neurological disorder that involves a decreased ability to regulate sleep–wake cycles. Symptoms often include periods of excessive daytime sleepiness and brief involuntary sleep episodes. About 70% of those affected also experience episodes of sudden loss of muscle strength, known as cataplexy. Narcolepsy paired with cataplexy is evidenced to be an autoimmune disorder. These experiences of cataplexy can be brought on by strong emotions. Less commonly, there may be vivid hallucinations or an inability to move (sleep paralysis) while falling asleep or waking up. People with narcolepsy tend to sleep about the same number of hours per day as people without, but the quality of sleep tends to be lessened.Narcolepsy is a clinical syndrome of hypothalamic disorder, however, the exact cause of narcolepsy is unknown, with potentially several causes. In up to 10% of cases, there is a family history of the disorder. Often, those affected have low levels of the neuropeptide orexin, which may be due to an autoimmune disorder triggered in genetically susceptible individuals by infection with H1N1 influenza. In rare cases, narcolepsy can be caused by traumatic brain injury, tumors, or other diseases affecting the parts of the brain that regulate wakefulness or REM sleep. Diagnosis is typically based on the symptoms and sleep studies, after ruling out other potential causes. Excessive daytime sleepiness can also be caused by other sleep disorders such as sleep apnea, major depressive disorder, anemia, heart failure, drinking alcohol and not getting enough sleep. Cataplexy may be mistaken for seizures.While there is no cure, a number of lifestyle changes and medications may help. Lifestyle changes include taking regular short naps and sleep hygiene. Medications used include modafinil, sodium oxybate and methylphenidate. While initially effective, tolerance to the benefits may develop over time. Tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs) may improve cataplexy.Estimates of frequency range from 0.2 to 600 per 100,000 people in various countries. The condition often begins in childhood, with males and females being affected equally. Untreated narcolepsy increases the risk of motor vehicle collisions and falls.Narcolepsy can occur anytime between early childhood and 50 years typically, however, there is no upper age limit to getting it, 15 and 36 years of age being the peak time periods of when it occurs. Signs and symptoms There are two main characteristics of narcolepsy: excessive daytime sleepiness and abnormal REM sleep. Excessive daytime sleepiness occurs even after adequate night time sleep. A person with narcolepsy is likely to become drowsy or fall asleep, often at inappropriate or undesired times and places, or just be very tired throughout the day. Narcoleptics may not be able to experience the amount of restorative deep sleep that healthy people experience due to abnormal REM regulation – they are not "over-sleeping". Narcoleptics typically have higher REM sleep density than non-narcoleptics, but also experience more REM sleep without atonia. Many narcoleptics have sufficient REM sleep, but do not feel refreshed or alert throughout the day. This can feel like living their entire lives in a constant state of sleep deprivation.Excessive sleepiness can vary in severity, and it appears most commonly during monotonous situations that dont require much interaction. Daytime naps may occur with little warning and may be physically irresistible. These naps can occur several times a day. They are typically refreshing, but only for a few hours or less. Vivid dreams may be experienced on a regular basis, even during very brief naps. Drowsiness may persist for prolonged periods or remain constant. In addition, night-time sleep may be fragmented, with frequent awakenings. A second prominent symptom of narcolepsy is abnormal REM sleep. Narcoleptics are unique in that they enter into the REM phase of sleep in the beginnings of sleep, even when sleeping during the day.The classic symptoms of the disorder, often referred to as the "tetrad of narcolepsy," are cataplexy, sleep paralysis, hypnagogic hallucinations, and excessive daytime sleepiness. Other symptoms may include automatic behaviors and night-time wakefulness. These symptoms may not occur in all people with narcolepsy. Cataplexy is an episodic loss of muscle function, ranging from slight weakness such as limpness at the neck or knees, sagging facial muscles, weakness at the knees often referred to as "knee buckling", or inability to speak clearly, to a complete body collapse. Episodes may be triggered by sudden emotional reactions such as laughter, anger, surprise, or fear. The person remains conscious throughout the episode. In some cases, cataplexy may resemble epileptic seizures. Usually speech is slurred and vision is impaired (double vision, inability to focus), but hearing and awareness remain normal. Cataplexy also has a severe emotional impact on narcoleptics, as it can cause extreme anxiety, fear, and avoidance of people or situations that might elicit an attack. Cataplexy is generally considered to be unique to narcolepsy and is analogous to sleep paralysis in that the usually protective paralysis mechanism occurring during sleep is inappropriately activated. The opposite of this situation (failure to activate this protective paralysis) occurs in rapid eye movement behavior disorder. Periods of wakefulness at night Sleep paralysis is the temporary inability to talk or move when waking (or less often, when falling asleep). It may last a few seconds to minutes. This is often frightening but is not dangerous. Hypnagogic hallucinations are vivid, often frightening, dreamlike experiences that occur while dozing or falling asleep. Hypnopompic hallucinations refer to the same sensations while awakening from sleep. These hallucinations may manifest in the form of visual or auditory sensations.In most cases, the first symptom of narcolepsy to appear is excessive and overwhelming daytime sleepiness. The other symptoms may begin alone or in combination months or years after the onset of the daytime naps. There are wide variations in the development, severity, and order of appearance of cataplexy, sleep paralysis, and hypnagogic hallucinations in individuals. Only about 20 to 25 percent of people with narcolepsy experience all four symptoms. The excessive daytime sleepiness generally persists throughout life, but sleep paralysis and hypnagogic hallucinations may not. Many people with narcolepsy also have insomnia for extended periods of time. The excessive daytime sleepiness and cataplexy often become severe enough to cause serious problems in a persons social, personal, and professional life. Normally, when an individual is awake, brain waves show a regular rhythm. When a person first falls asleep, the brain waves become slower and less regular, which is called non-rapid eye movement (NREM) sleep. After about an hour and a half of NREM sleep, the brain waves begin to show a more active pattern again, called REM sleep (rapid eye movement sleep), when most remembered dreaming occurs. Associated with the EEG-observed waves during REM sleep, muscle atonia is present called REM atonia.In narcolepsy, the order and length of NREM and REM sleep periods are disturbed, with REM sleep occurring at sleep onset instead of after a period of NREM sleep. Also, some aspects of REM sleep that normally occur only during sleep, like lack of muscular control, sleep paralysis, and vivid dreams, occur at other times in people with narcolepsy. For example, the lack of muscular control can occur during wakefulness in a cataplexy episode; it is said that there is an intrusion of REM atonia during wakefulness. Sleep paralysis and vivid dreams can occur while falling asleep or waking up. Simply put, the brain does not pass through the normal stages of dozing and deep sleep but goes directly into (and out of) rapid eye movement (REM) sleep.As a consequence night time sleep does not include as much deep sleep, so the brain tries to "catch up" during the day, hence excessive daytime sleepiness. People with narcolepsy may visibly fall asleep at unpredicted moments (such motions as head bobbing are common). People with narcolepsy fall quickly into what appears to be very deep sleep, and they wake up suddenly and can be disoriented when they do (dizziness is a common occurrence). They have very vivid dreams, which they often remember in great detail. People with narcolepsy may dream even when they only fall asleep for a few seconds. Along with vivid dreaming, people with narcolepsy are known to have audio or visual hallucinations prior to falling asleep.Narcoleptics can gain excess weight; children can gain 20 to 40 lb (9 to 18 kg) when they first develop narcolepsy; in adults the body-mass index is about 15% above average. Causes The exact cause of narcolepsy is unknown, and it may be caused by several distinct factors. The mechanism involves the loss of orexin-releasing neurons within the lateral hypothalamus (about 70,000 neurons).Some researches indicated that people with type 1 narcolepsy (narcolepsy with cataplexy) have a lower level of orexin (hypocretin), which is a chemical contributing to the regulation of wakefulness and REM Sleep. It also acts as a neurotransmitter to enable nerve cells to communicate.In up to 10% of cases there is a family history of the disorder. Family history is more common in narcolepsy with cataplexy. There is a strong link with certain genetic variants, which may make T-cells susceptible to react to the orexin-releasing neurons (autoimmunity) after being stimulated by infection with H1N1 influenza. In addition to genetic factors, low levels of orexin peptides have been correlated with a history of infection, diet, contact with toxins such as pesticides, and brain injuries due to head trauma, brain tumors or strokes. Genetics The primary genetic factor that has been strongly implicated in the development of narcolepsy involves an area of chromosome 6 known as the human leukocyte antigen (HLA) complex. Specific variations in HLA genes are strongly correlated with the presence of narcolepsy (HLA DQB1*06:02, frequently in combination with HLA DRB1*15:01); however, these variations are not required for the condition to occur and sometimes occur in individuals without narcolepsy. These genetic variations in the HLA complex are thought to increase the risk of an auto-immune response to orexin-releasing neurons in the lateral hypothalamus.The allele HLA-DQB1*06:02 of the human gene HLA-DQB1 was reported in more than 90% of people with narcolepsy, and alleles of other HLA genes such as HLA-DQA1*01:02 have been linked. A 2009 study found a strong association with polymorphisms in the TRAC gene locus (dbSNP IDs rs1154155, rs12587781, and rs1263646). A 2013 review article reported additional but weaker links to the loci of the genes TNFSF4 (rs7553711), Cathepsin H (rs34593439), and P2RY11-DNMT1 (rs2305795). Another gene locus that has been associated with narcolepsy is EIF3G (rs3826784). H1N1 Influenza Type 1 narcolepsy is caused by hypocretin/orexin neuronal loss. T-cells have been demonstrated to be cross-reactive to both a particular piece of the hemagglutinin flu protein of the pandemic 2009 H1N1 and the amidated terminal ends of the secreted hypocretin peptides.Genes associated with narcolepsy mark the particular HLA heterodimer (DQ0602) involved in presentation of these antigens and modulate expression of the specific T cell receptor segments (TRAJ24 and TRBV4-2) involved in T cell receptor recognition of these antigens, suggesting causality.A link between GlaxoSmithKlines H1N1 flu vaccine Pandemrix and narcolepsy has been found in both children and adults. In 2010, Finlands National Institute of Health and Welfare recommended that Pandemrix vaccinations be suspended pending further investigation into narcolepsy. In 2018, it was demonstrated that T-cells stimulated by Pandemrix were cross-reactive by molecular mimicry with part of the hypocretin peptide, the loss of which is associated with type I narcolepsy. Pathophysiology Loss of neurons Orexin, otherwise known as hypocretin, is a neuropeptide that acts within the brain to regulate appetite and wakefulness as well as a number of other cognitive and physiological processes. Loss of these orexin-producing neurons causes narcolepsy and most individuals with narcolepsy have a reduced number of these neurons in their brains. Selective destruction of the HCRT/OX neurons with preservation of proximate structures suggests a highly specific autoimmune pathophysiology. Cerebrospinal fluid HCRT-1/OX-A is undetectable in up to 95% of patients with type 1 narcolepsy.The system which regulates sleep, arousal, and transitions between these states in humans is composed of three interconnected subsystems: the orexin projections from the lateral hypothalamus, the reticular activating system, and the ventrolateral preoptic nucleus. In narcoleptic individuals, these systems are all associated with impairments due to a greatly reduced number of hypothalamic orexin projection neurons and significantly fewer orexin neuropeptides in cerebrospinal fluid and neural tissue, compared to non-narcoleptic individuals. Those with narcolepsy generally experience the REM stage of sleep within five minutes of falling asleep, while people who do not have narcolepsy (unless they are significantly sleep deprived) do not experience REM until after a period of slow-wave sleep, which lasts for about the first hour or so of a sleep cycle. Disturbed sleep states The neural control of normal sleep states and the relationship to narcolepsy are only partially understood. In humans, narcoleptic sleep is characterized by a tendency to go abruptly from a waking state to REM sleep with little or no intervening non-REM sleep. The changes in the motor and proprioceptive systems during REM sleep have been studied in both human and animal models. During normal REM sleep, spinal and brainstem alpha motor neuron hyperpolarization produces almost complete atonia of skeletal muscles via an inhibitory descending reticulospinal pathway. Acetylcholine may be one of the neurotransmitters involved in this pathway. In narcolepsy, the reflex inhibition of the motor system seen in cataplexy has features normally seen only in normal REM sleep. Diagnosis The third edition of the International Classification of Sleep Disorders (ICSD-3) differentiates between narcolepsy with cataplexy (type 1) and narcolepsy without cataplexy (type 2), while the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) uses the diagnosis of narcolepsy to refer to type 1 narcolepsy only. The DSM-5 refers to narcolepsy without cataplexy as hypersomnolence disorder. The most recent edition of the International Classification of Diseases, ICD-11, currently identifies three types of narcolepsy: type 1 narcolepsy, type 2 narcolepsy, and unspecified narcolepsy.ICSD-3 diagnostic criteria posits that the individual must experience "daily periods of irrepressible need to sleep or daytime lapses into sleep" for both subtypes of narcolepsy. This symptom must last for at least three months. For a diagnosis of type 1 narcolepsy, the person must present with either cataplexy, a mean sleep latency of less than 8 minutes, and two or more sleep-onset REM periods (SOREMPs), or they must present with a hypocretin-1 concentration of less than 110 pg/mL. A diagnosis of type 2 narcolepsy requires a mean sleep latency of less than 8 minutes, two or more SOREMPs, and a hypocretin-1 concentration of more than 110 pg/mL. In addition, the hypersomnolence and sleep latency findings cannot be better explained by other causes.DSM-5 narcolepsy criteria requires that the person to display recurrent periods of "an irrepressible need to sleep, lapsing into sleep, or napping" for at least three times a week over a period of three months. The individual must also display one of the following: cataplexy, hypocretin-1 concentration of less than 110 pg/mL, REM sleep latency of less than 15 minutes, or a multiple sleep latency test (MSLT) showing sleep latency of less than 8 minutes and two or more SOREMPs. For a diagnosis of hypersomnolence disorder, the individual must present with excessive sleepiness despite at least 7 hours of sleep as well as either recurrent lapses into daytime sleep, nonrestorative sleep episodes of 9 or more hours, or difficulty staying awake after awakening. In addition, the hypersomnolence must occur at least three times a week for a period of three months, and must be accompanied by significant distress or impairment. It also cannot be explained by another sleep disorder, coexisting mental or medical disorders, or medication. Tests Diagnosis is relatively easy when all the symptoms of narcolepsy are present, but if the sleep attacks are isolated and cataplexy is mild or absent, diagnosis is more difficult. Three tests that are commonly used in diagnosing narcolepsy are polysomnography (PSG), the multiple sleep latency test (MSLT), and the Epworth Sleepiness Scale (ESS). These tests are usually performed by a sleep specialist.Polysomnography involves the continuous recording of sleep brain waves and a number of nerve and muscle functions during night time sleep. When tested, people with narcolepsy fall asleep rapidly, enter REM sleep early, and may often awaken during the night. The polysomnogram also helps to detect other possible sleep disorders that could cause daytime sleepiness.The Epworth Sleepiness Scale is a brief questionnaire that is administered to determine the likelihood of the presence of a sleep disorder, including narcolepsy.The multiple sleep latency test is performed after the person undergoes an overnight sleep study. The person will be asked to sleep once every 2 hours, and the time it takes for them to do so is recorded. Most individuals will fall asleep within 5 to 8 minutes, as well as display REM sleep faster than non-narcoleptic people.Measuring orexin levels in a persons cerebrospinal fluid sampled in a spinal tap may help in diagnosing narcolepsy, with abnormally low levels serving as an indicator of the disorder. This test can be useful when MSLT results are inconclusive or difficult to interpret. Treatment Orexin replacement People with narcolepsy can be substantially helped, but not cured. However, the technology exists in early form such as experiments in using the prepro-orexin transgene via gene editing restored normal function in mice models by making other neurons produce orexin after the original set have been destroyed, or replacing the missing orexinergic neurons with hypocretin stem cell transplantation, are both steps in that direction for fixing the biology effectively permanently once applied in humans. Additionally effective ideal non-gene editing and chemical-drug methods involve hypocretin treatments methods such as future drugs like hypocretin agonists (such as danavorexton) or hypocretin replacement, in the form of hypocretin 1 given intravenous (injected into the veins), intracisternal (direct injection into the brain), and intranasal (sprayed through the nose), the latter being low in efficacy, at the low amount used in current experiments but may be effective at very high doses in the future. Behavioral General strategies like people and family education, sleep hygiene and medication compliance, and discussion of safety issues for example driving license can be useful. Potential side effects of medication can also be addressed. Regular follow-up is useful to be able to monitor the response to treatment, to assess the presence of other sleep disorders like obstructive sleep apnea, and to discuss psychosocial issues.In many cases, planned regular short naps can reduce the need for pharmacological treatment of the EDS, but only improve symptoms for a short duration. A 120-minute nap provided benefit for 3 hours in the persons alertness whereas a 15-minute nap provided no benefit. Daytime naps are not a replacement for night time sleep. Ongoing communication between the health care provider, person, and their family members is important for optimal management of narcolepsy. Medications The main treatment of excessive daytime sleepiness in narcolepsy is central nervous system stimulants such as methylphenidate, amphetamine, dextroamphetamine, modafinil, and armodafinil. In late 2007 an alert for severe adverse skin reactions to modafinil was issued by the FDA. Pemoline was previously used but was withdrawn due to toxicity.Another drug that is used is atomoxetine, a non-stimulant and a norepinephrine reuptake inhibitor (NRI), which has no addiction liability or recreational effects. Other NRIs like viloxazine and reboxetine have also been used in the treatment of narcolepsy. Additional related medications include mazindol and selegiline.Another FDA-approved treatment option for narcolepsy is sodium oxybate, also known as sodium gamma-hydroxybutyrate (GHB). It can be used for cataplexy associated with narcolepsy and excessive daytime sleepiness associated with narcolepsy. Several studies also showed that sodium oxybate is effective to treat cataplexy.Solriamfetol is a new molecule indicated for narcolepsy of type 1 and 2. Solriamfetol works by inhibiting the reuptake of the monoamines via the interaction with both the dopamine transporter and the norepinephrine transporter. This mechanism differs from that of the wake-promoting agents modafinil and armodafinil. These are thought to bind primarily at the dopamine transporter to inhibit the reuptake of dopamine. Solriamfetol also differs from amphetamines as it does not promote the release of norepinephrine in the brain.Narcolepsy has sometimes been treated with selective serotonin reuptake inhibitors and tricyclic antidepressants, such as clomipramine, imipramine, or protriptyline, as well as other drugs that suppress REM sleep. Venlafaxine, an antidepressant which blocks the reuptake of serotonin and norepinephrine, has shown usefulness in managing symptoms of cataplexy, however, it has notable side-effects including sleep disruption. The antidepressant class is used mainly for the treatment of cataplexy, for people with narcolepsy without cataplexy these are usually not used. Children Common behavioral treatments for childhood narcolepsy include improved sleep hygiene, scheduled naps, and physical exercise.Many medications are used in treating adults and may be used to treat children. These medications include central nervous system stimulants such as methylphenidate, modafinil, amphetamine, and dextroamphetamine. Other medications, such as sodium oxybate or atomoxetine may also be used to counteract sleepiness. Medications such as sodium oxybate, venlafaxine, fluoxetine, and clomipramine may be prescribed if the child presents with cataplexy. Epidemiology Estimates of frequency range from 0.2 per 100,000 in Israel to 600 per 100,000 in Japan. These differences may be due to how the studies were conducted or the populations themselves.In the United States, narcolepsy is estimated to affect as many as 200,000 Americans, but fewer than 50,000 are diagnosed. The prevalence of narcolepsy is about 1 per 2,000 persons. Narcolepsy is often mistaken for depression, epilepsy, the side effects of medications, poor sleeping habits or recreational drug use, making misdiagnosis likely. While narcolepsy symptoms are often confused with depression, there is a link between the two disorders. Research studies have mixed results on co-occurrence of depression in people with narcolepsy, as the numbers quoted by different studies are anywhere between 6% and 50%.Narcolepsy can occur in both men and women at any age, although typical symptom onset occurs in adolescence and young adulthood. There is about a ten-year delay in diagnosing narcolepsy in adults. Cognitive, educational, occupational, and psychosocial problems associated with the excessive daytime sleepiness of narcolepsy have been documented. For these to occur in the crucial teen years when education, development of self-image, and development of occupational choice are taking place is especially devastating. While cognitive impairment does occur, it may only be a reflection of the excessive daytime somnolence. Society and culture In 2015, it was reported that the British Department of Health was paying for sodium oxybate medication at a cost of £12,000 a year for 80 people who are taking legal action over problems linked to the use of the Pandemrix swine flu vaccine. Sodium oxybate is not available to people with narcolepsy through the National Health Service. Name The term "narcolepsy" is from the French narcolepsie. The French term was first used in 1880 by Jean-Baptiste-Édouard Gélineau, who used the Greek νάρκη (narkē), meaning "numbness", and λῆψις (lepsis) meaning "attack". Research Histamine-directed medications It remains to be seen whether H3 antagonists (i.e., compounds such as pitolisant that promote the release of the wakefulness-promoting molecule amine histamine) will be particularly useful as wake-promoting agents. However, usage now does exist in various nations such as in France, United Kingdoms (NHS as of September 2016) after being given marketing authorisation by European Commission on the advice of the European Medicines Agency and in the United States by the approval of the Food and Drug Administration (FDA) as of August 2019. GABA-directed medications Given the possible role of hyper-active GABAA receptors in the primary hypersomnias (narcolepsy and idiopathic hypersomnia), medications that could counteract this activity are being studied to test their potential to improve sleepiness. These currently include clarithromycin and flumazenil. Flumazenil Flumazenil is the only GABAA receptor antagonist on the market as of Jan 2013, and it is currently manufactured only as an intravenous formulation. Given its pharmacology, researchers consider it to be a promising medication in the treatment of primary hypersomnias. Results of a small, double-blind, randomized, controlled clinical trial were published in November 2012. This research showed that flumazenil provides relief for most people whose CSF contains the unknown "somnogen" that enhances the function of GABAA receptors, making them more susceptible to the sleep-inducing effect of GABA. For one person, daily administration of flumazenil by sublingual lozenge and topical cream has proven effective for several years. A 2014 case report also showed improvement in primary hypersomnia symptoms after treatment with a continuous subcutaneous flumazenil infusion. The supply of generic flumazenil was initially thought to be too low to meet the potential demand for treatment of primary hypersomnias. However, this scarcity has eased, and dozens of people are now being treated with flumazenil off-label. Clarithromycin In a test tube model, clarithromycin (an antibiotic approved by the FDA for the treatment of infections) was found to return the function of the GABA system to normal in people with primary hypersomnias. Investigators therefore treated a few people with narcolepsy with off-label clarithromycin, and most felt their symptoms improved with this treatment. In order to help further determine whether clarithromycin is truly beneficial for the treatment of narcolepsy and idiopathic hypersomnia, a small, double-blind, randomized, controlled clinical trial was completed in 2012. "In this pilot study, clarithromycin improved subjective sleepiness in GABA-related hypersomnia. Larger trials of longer duration are warranted." In 2013, a retrospective review evaluating longer-term clarithromycin use showed efficacy in a large percentage of people with GABA-related hypersomnia. "It is important to note that the positive effect of clarithromycin is secondary to a benzodiazepine antagonist-like effect, not its antibiotic effects, and treatment must be maintained." Orexin receptor agonists Orexin-A (a.k.a. hypocretin-1) has been shown to be strongly wake-promoting in animal models, but it does not cross the blood–brain barrier. The first line treatment for narcolepsy, modafinil, has been found to interact indirectly with the orexin system. It is also likely that an orexin receptor agonist will be found and developed for the treatment of hypersomnia. One such agent which is currently in clinical trials is danavorexton. L-carnitine Abnormally low levels of acylcarnitine have been observed in people with narcolepsy. These same low levels have been associated with primary hypersomnia in general in mouse studies. “Mice with systemic carnitine deficiency exhibit a higher frequency of fragmented wakefulness and rapid eye movement (REM) sleep, and reduced locomotor activity.” Administration of acetyl-L-carnitine was shown to improve these symptoms in mice. A subsequent human trial found that people with narcolepsy given L-carnitine spent less total time in daytime sleep than people who were given a placebo. Animal models Animal studies try to mimic the disorder in humans by either modifying the Hypocretin/Orexin receptors or by eliminating this peptide. An orexin deficit caused by the degeneration of hypothalamic neurons is suggested to be one of the causes of narcolepsy. More recent clinical studies on both animals and humans have also revealed that hypocretin is involved in other functions beside regulation of wakefulness and sleep. These functions include autonomic regulation, emotional processing, reward learning behaviour or energy homeostasis. In studies where the concentration of the hypocretin was measured under different circumstances, it was observed that the hypocretin levels increased with the positive emotion, anger or social interaction but stayed low during sleep or during pain experience.The most reliable and valid animal models developed are the canine (narcoleptic dogs) and the rodent (orexin-deficient mice) ones which helped investigating the narcolepsy and set the focus on the role of orexin in this disorder. Dog models Dogs, as well as other species like cats or horses, can also exhibit spontaneous narcolepsy with similar symptoms as the ones reported in humans. The attacks of cataplexy in dogs can involve partial or full collapse. Narcolepsy with cataplexy was identified in a few breeds like Labrador retrievers or Doberman pinschers where it was investigated the possibility to inherit this disorder in the autosomal recessive mode. According to a reliable canine model for narcolepsy would be the one in which the narcoleptic symptoms are the result of a mutation in the gene HCRT 2. The animals affected exhibited excessive daytime sleepiness with a reduced state of vigilance and severe cataplexy resulted after palatable food and interactions with the owners or with other animals. Rodent models Mice that are genetically engineered to lack orexin genes demonstrate many similarities to human narcolepsy. During nocturnal hours, when mice are normally present, those lacking orexin demonstrated murine cataplexy and displayed brain and muscle electrical activity similar to the activity present during REM and NREM sleep. This cataplexy is able to be triggered through social interaction, wheel running, and ultrasonic vocalizations. Upon awakening, the mice also display behavior consistent with excessive daytime sleepiness.Mice models have also been used to test whether the lack of orexin neurons is correlated with narcolepsy. Mice whose orexin neurons have been ablated have shown sleep fragmentation, SOREMPs, and obesity.Rat models have been used to demonstrate the association between orexin deficiency and narcoleptic symptoms. Rats who lost the majority of their orexinergic neurons exhibited multiple SOREMPs as well as less wakefulness during nocturnal hours, shortened REM latency, and brief periods of cataplexy. References External links "Narcolepsy Information Page". National Institute of Neurological Disorders and Stroke.

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

Can you demystify the medical term 'Sequela' for me?

A sequela (UK: , US: ; usually used in the plural, sequelae ) is a pathological condition resulting from a disease, injury, therapy, or other trauma. Derived from the Latin word, meaning “sequel”, it is used in the medical field to mean a complication or condition following a prior illness or disease.A typical sequela is a chronic complication of an acute condition—in other words, a long-term effect of a temporary disease or injury—which follows immediately from the condition. Sequelae differ from late effects, which can appear long after—even several decades after—the original condition has resolved. In general, non-medical usage, the terms sequela and sequelae mean consequence and consequences. Examples and uses Chronic kidney disease, for example, is sometimes a sequela of diabetes; "chronic constipation" or more accurately "obstipation" (that is, inability to pass stool or gas) is a sequela to an intestinal obstruction; and neck pain is a common sequela of whiplash or other trauma to the cervical vertebrae. Post-traumatic stress disorder may be a psychological sequela of rape. Sequelae of traumatic brain injury include headache, dizziness, anxiety, apathy, depression, aggression, cognitive impairments, personality changes, mania, and psychosis. COVID-19 is also known to cause post-acute sequelae, known as long COVID, post-COVID syndrome, or post-acute sequelae of COVID-19 (PASC). This refers to the continuation of COVID-19 symptoms or the development of new ones, four or more weeks after the initial infection; these symptoms may persist for weeks and months. Post-COVID syndrome can occur in individuals who were asymptomatic for COVID, as well as those ranging from mild illness to severe hospitalization. These most commonly reported sequelae include fatigue, shortness of breath, chest pain, loss of smell, and brain fog; symptoms drastically range, from mild illness to severe impairment.Some conditions may be diagnosed retrospectively from their sequelae. An example is pleurisy. Other examples of sequelae include those following neurological injury; including aphasia, ataxia, hemi- and quadriplegia, and any number of other changes that may be caused by neurological trauma. Note that these pathologies can be related to both physical and chemical traumas, as both can cause lingering neuronal damage. The phrase status post, abbreviated in writing as s/p, is used to discuss sequelae with reference to their cause. Clinicians typically use the phrase to refer to acute traumatic conditions. For example: "the patient had neck pain status post a motor vehicle accident". Rheumatic fever is a non-suppurative sequela of a primary infection of group A Streptococcus bacteria. Glomerulonephritis can also be a non-suppurative sequela of Streptococcus pyogenes. References Further reading Lindsay, James (1997). "Chronic Sequelae of Foodborne Disease". Emerging Infectious Diseases. 3 (4): 443–452. doi:10.3201/eid0304.970405. PMC 2640087. PMID 9366595. External links Traumatic causes of Tempormandibular Joints Disorder (dysfunction)

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

I need a basic explanation for the medical term 'Achondrogenesis.'

Achondrogenesis is a number of disorders that are the most severe form of congenital chondrodysplasia (malformation of bones and cartilage). These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result of their serious health problems, infants with achondrogenesis are usually born prematurely, are stillborn, or die shortly after birth from respiratory failure. Some infants, however, have lived for a while with intensive medical support. Researchers have described at least three forms of achondrogenesis, designated as Achondrogenesis type 1A, achondrogenesis type 1B and achondrogenesis type 2. These types are distinguished by their signs and symptoms, inheritance pattern, and genetic cause. Other types of achondrogenesis may exist, but they have not been characterized or their cause is unknown. Achondrogenesis type 1A is caused by a defect in the microtubules of the Golgi apparatus. In mice, a nonsense mutation in the thyroid hormone receptor interactor 11 gene (Trip11), which encodes the Golgi microtubule-associated protein 210 (GMAP-210), resulted in defects similar to the human disease. When their DNA was sequenced, human patients with achondrogenesis type 1A also had loss-of-function mutations in GMAP-210. GMAP-210 moves proteins from the endoplasmic reticulum to the Golgi apparatus. Because of the defect, GMAP-210 is not able to move the proteins, and they remain in the endoplasmic reticulum, which swells up. The loss of Golgi apparatus function affects some cells, such as those responsible for forming bone and cartilage, more than others.Achondrogenesis type 1B is caused by a similar mutation in SLC26A2, which encodes a sulfate transporter. Achondrogenesis, type 2 is one of several skeletal disorders caused by mutations in the COL2A1 gene. Achondrogenesis, type 2 and hypochondrogenesis (a similar skeletal disorder) together affect 1 in 40,000 to 60,000 births. References This article incorporates public domain text from The U.S. National Library of Medicine == External links ==

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

I'd like to learn more about the medical term 'Macrocytosis.' Can you provide some details?

Macrocytosis is the enlargement of red blood cells with near-constant hemoglobin concentration, and is defined by a mean corpuscular volume (MCV) of greater than 100 femtolitres (the precise criterion varies between laboratories). The enlarged erythrocytes are called macrocytes or megalocytes (both words have roots meaning "big cell"). As a symptom its cause may be relatively benign and need no treatment or it may indicate a serious underlying illness. Causes In humans, most commonly (especially when the increase in size is mild, and just above normal range) the cause is bone marrow dysplasia secondary to alcohol use disorder. Poor absorption of vitamin B12 in the digestive tract can also cause macrocytosis. Gastrointestinal diseases that may cause macrocytosis include celiac disease (severe sensitivity to gluten from wheat and other grains that causes intestinal damage) and Crohns disease (inflammatory bowel disease that can affect any part of the gastrointestinal tract). Other causes may include: megaloblastosis (vitamin B12 or folate deficiency) because slowly dividing erythrocytes accumulate cytoplasmic components, resulting in larger-than-normal cells. hypothyroidism chronic obstructive pulmonary disease (COPD) aplastic anemia reticulocytosis (commonly from hemolysis or a recent history of blood loss). liver disease because of an increase in circulating phospholipids and cholesterol, which bind on erythrocytes and induce membrane expansion myeloproliferative disease myelodysplastic syndrome which most commonly presents with macrocytic anemia chronic exposure to benzene pregnancy (most common, and requires no treatment as the person affected will return to normal post-partum) Certain anti-inflammatory drugs, e.g. salazopyrin, azathioprine. Complications No complications arise from macrocytosis itself and a prognosis will be determined from its cause. See also Macrocytic anemia References == External links ==

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

I'm trying to understand 'Oral and maxillofacial pathology' within a medical context. Could you shed some light on it?

Oral and maxillofacial pathology refers to the diseases of the mouth ("oral cavity" or "stoma"), jaws ("maxillae" or "gnath") and related structures such as salivary glands, temporomandibular joints, facial muscles and perioral skin (the skin around the mouth). The mouth is an important organ with many different functions. It is also prone to a variety of medical and dental disorders.The specialty oral and maxillofacial pathology is concerned with diagnosis and study of the causes and effects of diseases affecting the oral and maxillofacial region. It is sometimes considered to be a specialty of dentistry and pathology. Sometimes the term head and neck pathology is used instead, which may indicate that the pathologist deals with otorhinolaryngologic disorders (i.e. ear, nose and throat) in addition to maxillofacial disorders. In this role there is some overlap between the expertise of head and neck pathologists and that of endocrine pathologists. Diagnosis The key to any diagnosis is thorough medical, dental, social and psychological history as well as assessing certain lifestyle risk factors that may be involved in disease processes. This is followed by a thorough clinical investigation including extra-oral and intra-oral hard and soft tissues.It is sometimes the case that a diagnosis and treatment regime are possible to determine from history and examination, however it is good practice to compile a list of differential diagnoses. Differential diagnosis allows for decisions on what further investigations are needed in each case.There are many types of investigations in diagnosis of oral and maxillofacial diseases, including screening tests, imaging (radiographs, CBCT, CT, MRI, ultrasound) and histopathology (biopsy). Biopsy A biopsy is indicated when the patients clinical presentation, past history or imaging studies do not allow a definitive diagnosis. A biopsy is a surgical procedure that involves the removal of a piece of tissue sample from the living organism for the purpose of microscopic examination. In most cases, biopsies are carried out under local anaesthesia. Some biopsies are carried out endoscopically, others under image guidance, for instance ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) in the radiology suite. Examples of the most common tissues examined by means of a biopsy include oral and sinus mucosa, bone, soft tissue, skin and lymph nodes.Types of biopsies typically used for diagnosing oral and maxillofacial pathology are: Excisional biopsy: A small lesion is totally excised. This method is preferred, if the lesions are approximately 1 cm or less in diameter, clinically and seemingly benign and surgically accessible. Large lesions which are more diffused and dispersed in nature or those which are seemed to be more clinically malignant are not conducive to total removal.Incisional biopsy: A small portion of the tissue is removed from an abnormal-looking area for examination. This method is useful in dealing with large lesions. If the abnormal region is easily accessed, the sample may be taken at your doctors office. If the tumour is deeper inside the mouth or throat, the biopsy may need to be performed in an operating room. General anaesthesia is administered to eliminate any pain.Exfoliative cytology: A suspected area is gently scraped to collect a sample of cells for examination. These cells are placed on a glass slide and stained with dye, so that they can be viewed under a microscope. If any cells appear abnormal, a deeper biopsy will be performed. Diseases Oral and maxillofacial pathology can involve many different types of tissues of the head. Different disease processes affect different tissues within this region with various outcomes. A great many diseases involve the mouth, jaws and orofacial skin. The following list is a general outline of pathologies that can affect oral and maxillofacial region; some are more common than others. This list is by no means exhaustive. Congenital Malocclusion Cleft lip and palate Cleft lip and palate is one of the most common occurring multi-factorial congenital disorder occurring in 1 in 500-1000 live births in several forms. The most common form is combined cleft lip and palate and it accounts for approximately 50% of the cases whereas isolated cleft lip concerns 20% of the patients.People with cleft, lip and palate malformation tend to be less social and report lower self-esteem, anxiety and depression related to their facial malformation. One of the major goals in the treatment of patients with cleft is to enhance social acceptance by surgical reconstruction. A cleft lip is an opening of the upper lip mainly due to the failure of fusion of the medial nasal processes with the palatal processes, a cleft palate is the opening of the soft and hard palate in the mouth which is due to the failure of the palatal shelves to fuse together.The palates main function is to demarcate the nasal and oral cavity, without which the patient will have problems with swallowing, eating and speech. Thus affecting the quality of life and in some cases certain functions.Some examples include food going up into the nasal cavity during swallowing as the soft palate is not present to close the cavity during the process. Speech is also affected as the nasal cavity is a source of resonance during speech and failure to manipulate spaces in the cavities will result in the lack of ability to produce certain consonants in audible language. Macroglossia Is a rare condition, categorised by tongue enlargement which will eventually create a crenated border in relation to the embrasures between the teeth. Hereditary Cause Vascular malformations Down syndrome Beckwith-Wiedemann syndrome Duchenne muscular dystrophy Neurofibromatosis type Is Acquired Causes Carcinoma Lingual Thyroid Myxedema Amyloidosis Consequences Noisy breaths, obstructs airway if severe Drooling Difficult in eating Lisping speech Open-bite Protruding tongue, may ulcerate and undergo necrosis Treatments For mild cases, surgical treatment is not mandatory but if speech is affected, speech therapy may be useful. Reduction glossectomy may be required for severe cases. Ankyloglossia Stafne defect Torus palatinus Torus mandibularis Eagle syndrome, Is a condition where there is an abnormal ossification of the stylohyoid ligament. This leads to an increase in the thickness and the length of the stylohyoid process and the ligament. Pain is felt due to the pressure applied to the internal jugular vein. Eagle syndrome occurs due to elongation of the styloid process or calcification of the stylohyoid ligament. However, the cause of the elongation has not been known clearly. It could occur spontaneously or could arise since birth. Usually normal stylohyoid process is 2.5–3 cm in length, if the length is longer than 3 cm, it is classified as an elongated stylohyoid process. Acquired Vascular Infective Bacterial (Plaque-induced) gingivitis—A common periodontal (gum) disease is Gingivitis. Periodontal refers to the area the infection affects, which include the teeth, gums, and tissues surrounding the teeth. Bacteria cause inflammation of the gums which become red, swollen and can bleed easily. The bacteria along with mucus form a sticky colorless substance called plaque which harbours the bacteria. Plaque that is not removed by brushing and flossing hardens to form tartar that brushing doesnt clean. Smoking is a major risk factor. Treatment of gingivitis is dependent on how severe and how far the disease has progressed. If the disease is not too severe it is possible to treat it with chlorhexidine rinse and brushing with fluoride toothpaste to kill the bacteria and remove the plaque, but once the infection has progressed antibiotics may be needed to kill the bacteria. Periodontitis—When gingivitis is not treated it can advance to periodontitis, when the gums pull away from the teeth and form pockets that harbor the bacteria. Bacterial toxins and the bodys natural defenses start to break down the bone and connective tissues. The tooth may eventually become loose and have to be removed. Scarlet fever is caused by a particular streptococci species, Streptococci Pyogenes, and is classified be a severe form of bacterial sore throat. The condition involves the release of pyrogenic and erythrogenic endotoxins from the immune system. It starts as tonsilitis and pharyngitis before involving the soft palate and the tongue. It usually occurs in children where a fever occurs and an erythematous rash develops on the face and spreads to most part of the body. If not treated, late stages of this condition may include a furred, raw, red tongue. Treatment options include penicillin and the prognosis is generally excellent.Viral Herpes simplex (infection with herpes simplex virus, or HSV) is very common in the mouth and lips. This virus can cause blisters and sores around the mouth (herpetic gingivostomatitis) and lips (herpes labialis). HSV infections tend to recur periodically. Although many people get infected with the virus, only 10% actually develop the sores. The sores may last anywhere from 3–10 days and are very infectious. Some people have recurrences either in the same location or at a nearby site. Unless the individual has an impaired immune system, e.g., owing to HIV or cancer-related immune suppression, recurrent infections tend to be mild in nature and may be brought on by stress, sun, menstrual periods, trauma or physical stress. Mumps of the salivary glands is a viral infection of the parotid glands. This results in painful swelling at the sides of the mouth in both adults and children, which leads to a sore throat, and occasionally pain in chewing. The infection is quite contagious. Today mumps is prevented by getting vaccinated in infancy, by a "Measles, Mumps, Rubella" (MMR) vaccination and subsequent boosters. There is no specific treatment for mumps except for hydration and painkillers with complete recovery ranging from 5–10 days. Sometimes mumps can cause inflammation of the brain, pancreatitis, testicular swelling or hearing loss.Fungal Oral candidiasis is by far the most common fungal infection that occurs in the mouth. It usually occurs in immunocompromised individuals. Individuals who have undergone a transplant, HIV, cancer or use corticosteroids commonly develop candida of the mouth and oral cavity. Other risk factors are dentures and tongue piercing. The typical signs are a white patch that may be associated with burning, soreness, irritation or a white cheesy like appearance. Once the diagnosis is made, candida can be treated with a variety of anti fungal drugs. Traumatic Chemical, thermal, mechanical or electrical trauma to the oral soft tissues can cause traumatic oral ulceration. Autoimmune Sjögren syndrome is an autoimmune chronic inflammatory disorder characterised by some of the bodys own immune cells infiltrating and destroying lacrimal and salivary glands (and other exocrine glands). There are two types of Sjögrens syndrome: primary and secondary. In primary Sjögrens syndrome (pSS) individuals have dry eyes (keratoconjunctivitis sicca) and a dry mouth (xerostomia). Based on a meta-analysis, the prevalence of pSS worldwide is estimated to 0.06%, with 90% of the patients being female. In secondary Sjögrens syndrome (sSS), individuals have a dry mouth, dry eyes and a connective tissue disorder such as rheumatoid arthritis (prevalence 7% in the UK), systemic lupus erythematosus (prevalence 6.5%–19%) and systemic sclerosis (prevalence 14%–20.5%). Additional features and symptoms include: Erythema and lobulation of the tongue Oral discomfort Difficulty in swallowing and talking Altered taste Poor retention of dentures (if worn) Oral fungal and bacterial infections Salivary glands swelling Dryness of skin; nose; throat; vagina Peripheral neuropathies Pulmonary; thyroid; and renal disorders; Arthralgias and myalgias;Tests used to diagnose Sjögrens syndrome include: tear break-up time and Schirmer tests a minor salivary gland biopsy taken from the lip blood tests salivary flow rateThere is no cure for Sjogrens syndromeis disease however there are treatments used to help with the associated symptoms. Eye care: artificial tears, moisture chamber spectacles, punctal plugs, pilocarpine medication Mouth care: increase oral intake, practice good oral hygiene, use sugar free gum (to increase saliva flow), regular use of mouth rinses, pilocarpine medication, reduce alcohol intake and smoking cessation. Saliva substitutes are also available as a spray, gel, gum or in the form of a medicated sweet Dry skin: creams, moisturising soaps Vaginal dryness: lubricant, oestrogen creams, hormonal replacement therapy Muscle and joint pains: Non-steroidal anti-inflammatory drugsComplications of Sjogrens syndrome include ulcers that can develop on the surface of the eyes if the dryness is not treated. These ulcers can then cause more worrying issues such as loss of eye sight and life long damage. Individuals with Sjögrens syndrome have a slightly increased risk of developing non-Hodgkin Lymphoma, a type of cancer. Other conditions such as peripheral neuropathy, Raynauds phenomenon, kidney problems, underactive thyroid gland and irritable bowel syndrome have been linked to Sjogrens syndrome Metabolic Inflammatory Angioedema Neurological Neoplastic Oral cancer may occur on the lips, tongue, gums, floor of the mouth or inside the cheeks. The majority of cancers of the mouth are squamous cell carcinoma. Oral cancers are usually painless in the initial stages or may appear like an ulcer. Causes of oral cancer include smoking, excessive alcohol consumption, exposure to sunlight (lip cancer), chewing tobacco, infection with human papillomavirus, and hematopoietic stem cell transplantation. The earlier the oral cancer is diagnosed, the better the chances for full recovery. If you have a suspicious mass or ulcer on the mouth which has been persistent, then you should always get a dentist to look at it. Diagnosis is usually made with a biopsy and the treatment depends on the exact type of cancer, where it is situated, and extent of spreading. Degenerative Environmental Unknown There are many oral and maxillofacial pathologies which are not fully understood. Burning mouth syndrome (BMS) is a disorder where there is a burning sensation in the mouth that has no identifiable medical or dental cause. The disorder can affect anyone but tends to occur most often in middle aged women. BMS has been hypothesized to be linked to a variety of factors such as the menopause, dry mouth (xerostomia) and allergies. BMS usually lasts for several years before disappearing for unknown reasons. Other features of this disorder include anxiety, depression and social isolation. There is no cure for this disorder and treatment includes use of hydrating agents, pain medications, vitamin supplements or the usage of antidepressants. Aphthous stomatitis is a condition where ulcers (canker sores) appear on the inside of the mouth, lips and on tongue. Most small canker sores disappear within 10–14 days. Canker sores are most common in young and middle aged individuals. Sometimes individuals with allergies are more prone to these sores. Besides an awkward sensation, these sores can also cause pain or tingling or a burning sensation. Unlike herpes sores, canker sores are always found inside the mouth and are usually less painful. Good oral hygiene does help but sometime one may have to use a topical corticosteroid. Migratory stomatitis is a condition that involves the tongue and other oral mucosa. The common migratory glossitis (geographic tongue) affects the anterior two thirds of the dorsal and lateral tongue mucosa of 1% to 2.5% of the population, with one report of up to 12.7% of the population. The tongue is often fissured, especially. in elderly individuals. In the American population, a lower prevalence was reported among Mexican Americans (compared with Caucasians and African Americans) and cigarette smokers. When other oral mucosa, beside the dorsal and lateral tongue, are involved, the term migratory stomatitis (or ectopic geographic tongue) is preferred. In this condition, lesions infrequently involve also the ventral tongue and buccal or labial mucosa. They are rarely reported on the soft palate and floor of the mouth. Specialty Oral and maxillofacial pathology, previously termed oral pathology, is a speciality involved with the diagnosis and study of the causes and effects of diseases affecting the oral and maxillofacial regions (i.e. the mouth, the jaws and the face). It can be considered a speciality of dentistry and pathology. Oral pathology is a closely allied speciality with oral and maxillofacial surgery and oral medicine. The clinical evaluation and diagnosis of oral mucosal diseases are in the scope of oral & maxillofacial pathology specialists and oral medicine practitioners, both disciplines of dentistry. When a microscopic evaluation is needed, a biopsy is taken, and microscopically observed by a pathologist. The American Dental Association uses the term oral and maxillofacial pathology, and describes it as "the specialty of dentistry and pathology which deals with the nature, identification, and management of diseases affecting the oral and maxillofacial regions. It is a science that investigates the causes, processes and effects of these diseases."In some parts of the world, oral and maxillofacial pathologists take on responsibilities in forensic odontology. Geographic variation United Kingdom There are approximately 30 consultant oral and maxillofacial pathologists in the UK. A dental degree is mandatory, but a medical degree is not. The shortest pathway to becoming an oral pathologist in the UK is completion of 2 years general professional training and then 5 years in a diagnostic histopathology training course. After passing the required Royal College of Pathologists exams and gaining a Certificate of Completion of Specialist Training, the trainee is entitled to apply for registration as a specialist. Many oral and maxillofacial pathologists in the UK are clinical academics, having undertaken a PhD either prior to or during training. Generally, oral and maxillofacial pathologists in the UK are employed by dental or medical schools and undertake their clinical work at university hospital departments. New Zealand There are 5 practising Oral Pathologists in New Zealand (as of May 2013). Oral pathologists in New Zealand also take part in forensic evaluations. See also Tongue disease Salivary gland disease Head and neck cancer Oral surgery Tooth pathology References Further reading Fechner RE (2002). "A Brief History of Head and Neck Pathology". Modern Pathology. 15 (3): 221–228. doi:10.1038/modpathol.3880519. PMID 11904339. External links Media related to Diseases and disorders of oral cavity, salivary glands and jaws at Wikimedia Commons British Society of Oral & Maxillo-facial Pathologists Website Academy of Oral and Maxillofacial Pathology Website

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Can you break down the meaning of the medical term '8p23.1 duplication syndrome' for me?

8p23.1 duplication syndrome is a rare genetic disorder caused by a duplication of a region from human chromosome 8. This duplication syndrome has an estimated prevalence of 1 in 64,000 births and is the reciprocal of the 8p23.1 deletion syndrome. The 8p23.1 duplication is associated with a variable phenotype including one or more of speech delay, developmental delay, mild dysmorphism, with prominent forehead and arched eyebrows, and congenital heart disease (CHD). Presentation The phenotypic data on 11 patients indicated that cases are not always ascertained for CHD but that CHD was the most common single feature found in 6 out of 11 individuals. Developmental delay and/or learning difficulties were found in 5 out of 11 cases, but one prenatal case was developing normally at 15 months of age (Case 1,). Three other prenatal cases could not yet be reliably assessed. A variable degree of facial dysmorphism was present in 5 out of 11 individuals. Partial toe syndactyly has been found in one mother and son diad and adrenal anomalies in two probands but not in the duplicated mother of one of them. The phenotype is compatible with independent adult life with varying degrees of support. Duplication of the GATA4 transcription factor (OMIM: 600576) is believed to underlie the congenital heart disease and other genes, common to the duplication and deletion syndromes, can be regarded as candidates for the 8p23.1 duplication syndrome. These include the SOX7 transcription factor (OMIM: 612202) for both CHD and developmental delay and the TNKS gene (OMIM: 603303) for behavioural difficulties. The diaphragmatic hernia found in the 8p23.1 deletion syndrome has not been found in the 8p23.1 duplication syndrome to date. The duplication may be associated with copy number changes of the adjacent olfactory receptor/defensin repeats (ORDRs) that predispose to the 8p23.1 deletion and duplication syndromes. High total copy numbers of these repeats have been associated with predisposition to psoriasis and low copy number with predisposition to Crohns disease. Genetics The duplication includes ~3.75 Mb between the distal and proximal ORDRs at either end of band 8p23.1. The copy number of the adjacent repeats may also be altered. The 8p23.1 duplication syndrome cannot be distinguished using conventional cytogenetics from high level copy number variation of the repeats themselves.Both de novo cases and families with transmitted duplications from parents of both sex are known. The duplication is believed to arise de novo as a result of non-allelic homologous recombination (NAHR) between the proximal and distal ORDRs. NAHR is also thought to give rise to the reciprocal microdeletion syndrome, the polymorphic inversion between the ORDRs and a variety of other large scale abnormalities involving the short arm of chromosome 8. Diagnosis Phenotypes See also Chromosome 8 (human) References External links DECIPHER database description

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I've encountered the term 'Carotid artery dissection' while reading about medical topics. What does it refer to exactly?

Carotid artery dissection is a separation of the layers of the artery wall supplying oxygen-bearing blood to the head and brain and is the most common cause of stroke in young adults. (Dissection is a blister-like de-lamination between the outer and inner walls of a blood vessel, generally originating with a partial leak in the inner lining.)Dissection may occur after physical trauma to the neck, such as a blunt injury (e.g. traffic collision), strangulation, but may also happen spontaneously. Signs and symptoms The signs and symptoms of carotid artery dissection may be divided into ischemic and non-ischemic categories:Non-ischemic signs and symptoms: Localised headache, particularly around one of the eyes Neck pain Swollen tongue Decreased pupil size with drooping of the upper eyelid (Horner syndrome) Pulsatile tinnitusIschemic signs and symptoms: Temporary vision loss Ischemic stroke Causes The causes of internal carotid artery dissection can be broadly categorized into two classes: spontaneous or traumatic. Spontaneous Once considered uncommon, spontaneous carotid artery dissection is an increasingly recognized cause of stroke that preferentially affects the middle-aged.The incidence of spontaneous carotid artery dissection is low, and incidence rates for internal carotid artery dissection have been reported to be 2.6 to 2.9 per 100,000.Observational studies and case reports published since the early 1980s show that patients with spontaneous internal carotid artery dissection may also have a history of stroke in their family and/or hereditary connective tissue disorders, such as Marfan syndrome, Ehlers-Danlos syndrome, autosomal dominant polycystic kidney disease, pseudoxanthoma elasticum, fibromuscular dysplasia, and osteogenesis imperfecta type I. IgG4-related disease involving the carotid artery has also been observed as a cause.However, although an association with connective tissue disorders does exist, most people with spontaneous arterial dissections do not have associated connective tissue disorders. Also, the reports on the prevalence of hereditary connective tissue diseases in people with spontaneous dissections are highly variable, ranging from 0% to 0.6% in one study to 5% to 18% in another study.Internal carotid artery dissection can also be associated with an elongated styloid process (known as Eagle syndrome when the elongated styloid process causes symptoms). Traumatic Carotid artery dissection is thought to be more commonly caused by severe violent trauma to the head and/or neck. An estimated 0.67% of patients admitted to the hospital after major motor vehicle accidents were found to have blunt carotid injury, including intimal dissections, pseudoaneurysms, thromboses, or fistulas. Of these, 76% had intimal dissections, pseudoaneurysms, or a combination of the two. Sports-related activities such as surfing and Jiu-Jitsu have been reported as causes of carotid artery dissection. The probable mechanism of injury for most internal carotid injuries is rapid deceleration, with resultant hyperextension and rotation of the neck, which stretches the internal carotid artery over the upper cervical vertebrae, producing an intimal tear. After such an injury, the patient may remain asymptomatic, have a hemispheric transient ischemic event, or have a stroke.Artery dissection has also been reported in association with some forms of neck manipulation. There is significant controversy about the level of risk of stroke from neck manipulation. It may be that manipulation can cause dissection, or it may be that the dissection is already present in some people who seek manipulative treatment. At this time, conclusive evidence does not exist to support either a strong association between neck manipulation and stroke, or no association. Pathophysiology Arterial dissection of the carotid arteries occurs when a small tear forms in the innermost lining of the arterial wall (known as the tunica intima). Blood is then able to enter the space between the inner and outer layers of the vessel, causing narrowing (stenosis) or complete occlusion. The stenosis that occurs in the early stages of arterial dissection is a dynamic process and some occlusions can return to stenosis very quickly. When complete occlusion occurs, it may lead to ischaemia. Often, even a complete occlusion is totally asymptomatic because bilateral circulation keeps the brain well perfused. However, when blood clots form and break off from the site of the tear, they form emboli, which can travel through the arteries to the brain and block the blood supply to the brain, resulting in an ischaemic stroke, otherwise known as a cerebral infarction. Blood clots, or emboli, originating from the dissection are thought to be the cause of infarction in the majority of cases of stroke in the presence of carotid artery dissection. Cerebral infarction causes irreversible damage to the brain. In one study of patients with carotid artery dissection, 60% had infarcts documented on neuroimaging. Treatment The goal of treatment is to prevent the development or continuation of neurologic deficits. Treatments include observation, anti-platelet agents, anticoagulation, stent implantation, carotid endarterectomy, and carotid artery ligation. Epidemiology 70% of patients with carotid arterial dissection are between the ages of 35 and 50, with a mean age of 47 years. See also Aortic dissection Vertebral artery dissection References == External links ==

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I'm trying to understand 'Osteochondritis dissecans' within a medical context. Could you shed some light on it?

Osteochondritis dissecans (OCD or OD) is a joint disorder primarily of the subchondral bone in which cracks form in the articular cartilage and the underlying subchondral bone. OCD usually causes pain during and after sports. In later stages of the disorder there will be swelling of the affected joint which catches and locks during movement. Physical examination in the early stages does only show pain as symptom, in later stages there could be an effusion, tenderness, and a crackling sound with joint movement. OCD is caused by blood deprivation of the secondary physes around the bone core of the femoral condyle. This happens to the epiphyseal vessels under the influence of repetitive overloading of the joint during running and jumping sports. During growth such chondronecrotic areas grow into the subchondral bone. There it will show as bone defect area under articular cartilage. The bone will then possibly heal to the surrounding condylar bone in 50% of the cases. Or it will develop into a pseudarthrosis between condylar bone core and osteochondritis flake leaving the articular cartilage it supports prone to damage. The damage is executed by ongoing sport overload. The result is fragmentation (dissection) of both cartilage and bone, and the free movement of these bone and cartilage fragments within the joint space, causing pain, blockage and further damage. OCD has a typical anamnesis with pain during and after sports without any history of trauma. Some symptoms of late stages of osteochondritis dissecans are found with other diseases like rheumatoid disease of children and meniscal ruptures. However, the disease can be confirmed by X-rays, computed tomography (CT) or magnetic resonance imaging (MRI) scans. Non-surgical treatment is successful in 50% of the cases. If in late stages the lesion is unstable and the cartilage is damaged, surgical intervention is an option as the ability for articular cartilage to heal is limited. When possible, non-operative forms of management such as protected reduced or non-weight bearing and immobilization are used. Surgical treatment includes arthroscopic drilling of intact lesions, securing of cartilage flap lesions with pins or screws, drilling and replacement of cartilage plugs, stem cell transplantation, and in very difficult situation in adults joint replacement. After surgery rehabilitation is usually a two-stage process of unloading and physical therapy. Most rehabilitation programs combine efforts to protect the joint with muscle strengthening and range of motion. During an immobilization period, isometric exercises, such as straight leg raises, are commonly used to restore muscle loss without disturbing the cartilage of the affected joint. Once the immobilization period has ended, physical therapy involves continuous passive motion (CPM) and/or low impact activities, such as walking or swimming. OCD occurs in 15 to 30 people per 100,000 in the general population each year. Although rare, it is an important cause of joint pain in physically active children and adolescents. Because their bones are still growing, adolescents are more likely than adults to recover from OCD; recovery in adolescents can be attributed to the bones ability to repair damaged or dead bone tissue and cartilage in a process called bone remodeling. While OCD may affect any joint, the knee tends to be the most commonly affected, and constitutes 75% of all cases. Franz König coined the term osteochondritis dissecans in 1887, describing it as an inflammation of the bone–cartilage interface. Many other conditions were once confused with OCD when attempting to describe how the disease affected the joint, including osteochondral fracture, osteonecrosis, accessory ossification center, osteochondrosis, and hereditary epiphyseal dysplasia. Some authors have used the terms osteochondrosis dissecans and osteochondral fragments as synonyms for OCD. Signs and symptoms In osteochondritis dissecans, fragments of cartilage or bone become loose within a joint, leading to pain and inflammation. These fragments are sometimes referred to as joint mice. OCD is a type of osteochondrosis in which a lesion has formed within the cartilage layer itself, giving rise to secondary inflammation. OCD most commonly affects the knee, although it can affect other joints such as the ankle or the elbow.People with OCD report activity-related pain that develops gradually. Individual complaints usually consist of mechanical symptoms including pain, swelling, catching, locking, popping noises, and buckling / giving way; the primary presenting symptom may be a restriction in the range of movement. Symptoms typically present within the initial weeks of stage I; however, the onset of stage II occurs within months and offers little time for diagnosis. The disease progresses rapidly beyond stage II, as OCD lesions quickly move from stable cysts or fissures to unstable fragments. Non-specific symptoms, caused by similar injuries such as sprains and strains, can delay a definitive diagnosis.Physical examination typically reveals fluid in the joint, tenderness, and crepitus. The tenderness may initially spread, but often reverts to a well-defined focal point as the lesion progresses. Just as OCD shares symptoms with common maladies, acute osteochondral fracture has a similar presentation with tenderness in the affected joint, but is usually associated with a fatty hemarthrosis. Although there is no significant pathologic gait or characteristic alignment abnormality associated with OCD, the patient may walk with the involved leg externally rotated in an attempt to avoid tibial spine impingement on the lateral aspect of the medial condyle of the femur. Causes Despite much research, the causes remain unclear but include repetitive physical trauma, ischemia (restriction of blood flow), hereditary and endocrine factors, avascular necrosis (loss of blood flow), rapid growth, deficiencies and imbalances in the ratio of calcium to phosphorus, and problems of bone formation. Although the name "osteochondritis" implies inflammation, the lack of inflammatory cells in histological examination suggests a non-inflammatory cause. It is thought that repetitive microtrauma, which leads to microfractures and sometimes an interruption of blood supply to the subchondral bone, may cause subsequent localized loss of blood supply or alteration of growth.Trauma, rather than avascular necrosis, is thought to cause osteochondritis dissecans in juveniles. In adults, trauma is thought to be the main or perhaps the sole cause, and may be endogenous, exogenous or both. The incidence of repetitive strain injury in young athletes is on the rise and accounts for a significant number of visits to primary care; this reinforces the theory that OCD may be associated with increased participation in sports and subsequent trauma. High-impact sports such as gymnastics, soccer, basketball, lacrosse, football, tennis, squash, baseball and weight lifting may put participants at a higher risk of OCD in stressed joints (knees, ankles and elbows).Recent case reports suggest that some people may be genetically predisposed to OCD. Families with OCD may have mutations in the aggrecan gene. Studies in horses have implicated specific genetic defects. Pathophysiology Osteochondritis dissecans differs from "wear and tear" degenerative arthritis, which is primarily an articular surface problem. Instead, OCD is a problem of the bone underlying the cartilage, which may secondarily affect the articular cartilage. Left untreated, OCD can lead to the development of degenerative arthritis secondary to joint incongruity and abnormal wear patterns.OCD occurs when a loose piece of bone or cartilage partially (or fully) separates from the end of the bone, often because of a loss of blood supply (osteonecrosis) and decalcification of the trabecular bone matrix. The loose piece may stay in place or slide around, making the joint stiff and unstable. OCD in humans most commonly affects the knees, ankles, and elbow but can affect any joint.In skeletally immature individuals, the blood supply to the epiphyseal bone is good, supporting both osteogenesis and chondrogenesis. With disruption of the epiphyseal plate vessels, varying degrees and depth of necrosis occur, resulting in a cessation of growth to both osteocytes and chondrocytes. In turn, this pattern leads to disordered ossification of cartilage, resulting in subchondral avascular necrosis and consequently OCD.Four minor stages of OCD have been identified after trauma. These include revascularization and formation of granulation (scar) tissue, absorption of necrotic fragments, intertrabecular osteoid deposition, and remodeling of new bone. With delay in the revascularization stage, an OCD lesion develops. A lesion can lead to articular-surface irregularities, which in turn may cause progressive arthritic deterioration. Diagnosis To diagnose osteochondritis dissecans, an X-ray, CT scan or MRI scan can be performed to show necrosis of subchondral bone, formation of loose fragments, or both. Occasionally a nuclear medicine bone scan is used to assess the degree of loosening within the joint. Physical examination Physical examination often begins with examination of the patients gait. In OCD of the knee, people may walk with the involved leg externally rotated in an attempt to avoid tibial spine impingement on the lateral aspect of the medial condyle of the femur.Next, the examining physician may check for weakness of the quadriceps. This examination may reveal fluid in the joint, tenderness, and crepitus. The Wilson test is also useful in locating OCD lesions of the femoral condyle. The test is performed by slowly extending the knee from 90 degrees, maintaining internal rotation. Pain at 30 degrees of flexion and relief with tibial external rotation is indicative of OCD.Physical examination of a patient with ankle OCD often returns symptoms of joint effusion, crepitus, and diffuse or localized tenderness. Examination often reveals symptoms of generalized joint pain, swelling, and times with limited range of motion. Some with loose body lesions may report catching, locking, or both. The possibility of microtrauma emphasizes a need for evaluation of biomechanical forces at the knee in a physical examination. As a result, the alignment and rotation of all major joints in the affected extremity is common, as are extrinsic and intrinsic abnormalities concerning the affected joint, including laxity. Diagnostic imaging X-rays show lucency of the ossification on the anterior aspect of the knee in juvenile patients. In older people, the lesion typically appears as an area of osteosclerotic bone with a radiolucent line between the osteochondral defect and the epiphysis. The visibility of the lesion depends on its location and on the amount of knee flexion used. Harding described the lateral X-ray as a method to identify the site of an OCD lesion.Magnetic resonance imaging (MRI) is useful for staging OCD lesions, evaluating the integrity of the joint surface, and distinguishing normal variants of bone formation from OCD by showing bone and cartilage edema in the area of the irregularity. MRI provides information regarding features of the articular cartilage and bone under the cartilage, including edema, fractures, fluid interfaces, articular surface integrity, and fragment displacement. A low T1 and high T2 signal at the fragment interface is seen in active lesions. This indicates an unstable lesion or recent microfractures. While MRI and arthroscopy have a close correlation, X-ray films tend to be less inductive of similar MRI results.Computed tomography (CT) scans and Technetium-99m bone scans are also sometimes used to monitor the progress of treatment. Unlike plain radiographs (X-rays), CT scans and MRI scans can show the exact location and extent of the lesion. Technetium bone scans can detect regional blood flow and the amount of osseous uptake. Both of these seem to be closely correlated to the potential for healing in the fragment. Classification OCD is classified by the progression of the disease in stages. There are two main staging classifications used; one is determined by MRI diagnostic imaging while the other is determined arthroscopically. However, both stagings represent the pathological conditions associated with OCDs natural progression.While the arthroscopic classification of bone and cartilage lesions is considered standard, the Anderson MRI staging is the main form of staging used in this article. Stages I and II are stable lesions. Stages III and IV describe unstable lesions in which a lesion of the cartilage has allowed synovial fluid between the fragment and bone. Treatment Treatment options include modified activity with or without weight bearing; immobilization; cryotherapy; anti-inflammatory medication; drilling of subchondral bone; microfracture; removal or reattachment of loose bodies; mosaicplasty and osteoarticular transfer system (OATS) procedures. The primary goals of treatment are: Enhance the healing potential of subchondral bone; Fix unstable fragments while maintaining joint congruity; and Replace damaged bone and cartilage with implanted tissues or cells that can grow cartilage.The articular cartilages capacity for repair is limited: partial-thickness defects in the articular cartilage do not heal spontaneously, and injuries of the articular cartilage which fail to penetrate subchondral bone tend to lead to deterioration of the articular surface. As a result, surgery is often required in even moderate cases where the osteochondral fragment has not detached from the bone (Anderson Stage II, III). Non-surgical Candidates for non-operative treatment are limited to skeletally immature teenagers with a relatively small, intact lesion and the absence of loose bodies. Non-operative management may include activity modification, protected weight bearing (partial or non-weight bearing), and immobilization. The goal of non-operative intervention is to promote healing in the subchondral bone and prevent potential chondral collapse, subsequent fracture, and crater formation.Once candidates for treatment have been screened, treatment proceeds according to the lesions location. For example, those with OCD of the knee are immobilized for four to six weeks or even up to six months in extension to remove shear stress from the involved area; however, they are permitted to walk with weight bearing as tolerated. X-rays are usually taken three months after the start of non-operative therapy; if they reveal that the lesion has healed, a gradual return to activities is instituted. Those demonstrating healing by increased radiodensity in the subchondral region, or those whose lesions are unchanged, are candidates to repeat the above described three-month protocol until healing is noted. Surgery The choice of surgical versus non-surgical treatments for osteochondritis dissecans is controversial. Consequently, the type and extent of surgery necessary varies based on patient age, severity of the lesion, and personal bias of the treating surgeon—entailing an exhaustive list of suggested treatments. A variety of surgical options exist for the treatment of persistently symptomatic, intact, partially detached, and completely detached OCD lesions. Post-surgery reparative cartilage is inferior to healthy hyaline cartilage in glycosaminoglycan concentration, histological, and immunohistochemical appearance. As a result, surgery is often avoided if non-operative treatment is viable. Intact lesions If non-surgical measures are unsuccessful, drilling may be considered to stimulate healing of the subchondral bone. Arthroscopic drilling may be performed by using an antegrade (from the front) approach from the joint space through the articular cartilage, or by using a retrograde (from behind) approach through the bone outside of the joint to avoid penetration of the articular cartilage. This has proven successful with positive results at one-year follow-up with antegrade drilling in nine out of eleven teenagers with the juvenile form of OCD, and in 18 of 20 skeletally immature people (follow-up of five years) who had failed prior conservative programs. Hinged lesions Pins and screws can be used to secure flap (sometimes referred to as hinged) lesions. Bone pegs, metallic pins and screws, and other bioresorbable screws may be used to secure these types of lesions. Full thickness lesions The three methods most commonly used in treating full thickness lesions are arthroscopic drilling, abrasion, and microfracturing. In 1946, Magnusson established the use of stem cells from bone marrow with the first surgical debridement of an OCD lesion. These cells typically differentiate into fibrocartilage and rarely form hyaline cartilage. While small lesions can be resurfaced using this form of surgery, the repair tissue tends to have less strength than normal hyaline cartilage and must be protected for 6 to 12 months. Results for large lesions tend to diminish over time; this can be attributed to the decreased resilience and poor wear characteristics of the fibrocartilage.In attempts to address the weaker structure of the reparative fibrocartilage, new techniques have been designed to fill the defect with tissue that more closely simulates normal hyaline articular cartilage. One such technique is autologous chondrocyte implantation (ACI), which is useful for large, isolated femoral defects in younger people. In this surgery, chondrocytes are arthroscopically extracted from the intercondylar notch of the articular surface. The chondrocytes are grown and injected into the defect under a periosteal patch. ACI surgery has reported good to excellent results for reduced swelling, pain and locking in clinical follow-up examinations. However, some physicians have preferred to use undifferentiated pluripotential cells, such as periosteal cells and bone marrow stem cells, as opposed to chondrocytes. These too have demonstrated the ability to regenerate both the cartilage and the underlying subchondral bone.Similar to OATS, arthroscopic articular cartilage paste grafting is a surgical procedure offering cost-effective, long-lasting results for stage IV lesions. A bone and cartilage paste derived from crushed plugs of the non-weight-bearing intercondylar notch can achieve pain relief, repair damaged tissue, and restore function. Unstable lesions Some methods of fixation for unstable lesions include countersunk compression screws and Herbert screws or pins made of stainless steel or materials that can be absorbed by the body. If loose bodies are found, they are removed. Although each case is unique and treatment is chosen on an individual basis, ACI is generally performed on large defects in skeletally mature people. Rehabilitation Continuous passive motion (CPM) has been used to improve healing of the articular surface during the postoperative period for people with full-thickness lesions. It has been shown to promote articular cartilage healing for small (< 3 mm in diameter) lesions in rabbits. Similarly, Rodrigo and Steadman reported that CPM for six hours per day for eight weeks produced an improved clinical outcome in humans.A rehabilitation program often involves protection of the compromised articular surface and underlying subchondral bone combined with maintenance of strength and range of motion. Post-operative analgesics, namely a mix of opioids and NSAIDs, are usually required to control pain, inflammation and swelling. Straight leg raising and other isometric exercises are encouraged during the post-operative or immobilization period. A six to eight-week home or formal physical therapy program is usually instituted once the immobilization period has ended, incorporating range of motion, stretching, progressive strengthening, and functional or sport-specific training. During this time, patients are advised to avoid running and jumping, but are permitted to perform low impact activities, such as walking or swimming. If patients return to activity before the cartilage has become firm, they will typically complain of pain during maneuvers such as squatting or jumping. Prognosis The prognosis after different treatments varies and is based on several factors which include the age of the patient, the affected joint, the stage of the lesion and, most importantly, the state of the growth plate. It follows that the two main forms of osteochondritis dissecans are defined by skeletal maturity. The juvenile form of the disease occurs in open growth plates, usually affecting children between the ages of 5 and 15 years. The adult form commonly occurs between ages 16 to 50, although it is unclear whether these adults developed the disease after skeletal maturity or were undiagnosed as children.The prognosis is good for stable lesions (stage I and II) in juveniles with open growth plates; treated conservatively—typically without surgery—50% of cases will heal. Recovery in juveniles can be attributed to the bones ability to repair damaged or dead bone tissue and cartilage in a process called bone remodeling. Open growth plates are characterized by increased numbers of undifferentiated chondrocytes (stem cells) which are precursors to both bone and cartilaginous tissue. As a result, open growth plates allow for more of the stem cells necessary for repair in the affected joint. Unstable, large, full-thickness lesions (stage III and IV) or lesions of any stage found in the skeletally mature are more likely to fail non-operative treatment. These lesions offer a worse prognosis and surgery is required in most cases. Epidemiology OCD is a relatively rare disorder, with an estimated incidence of 15 to 30 cases per 100,000 persons per year. Widuchowski W et al. found OCD to be the cause of articular cartilage defects in 2% of cases in a study of 25,124 knee arthroscopies. Although rare, OCD is noted as an important cause of joint pain in active adolescents. The juvenile form of the disease occurs in children with open growth plates, usually between the ages 5 and 15 years and occurs more commonly in males than females, with a ratio between 2:1 and 3:1. However, OCD has become more common among adolescent females as they become more active in sports. The adult form, which occurs in those who have reached skeletal maturity, is most commonly found in people 16 to 50 years old.While OCD may affect any joint, the knee—specifically the medial femoral condyle in 75–85% of knee cases—tends to be the most commonly affected, and constitutes 75% of all cases. The elbow (specifically the capitulum of the humerus) is the second most affected joint with 6% of cases; the talar dome of the ankle represents 4% of cases. Less frequent locations include the patella, vertebrae, the femoral head, and the glenoid of the scapula.The oldest case of OCD was identified on the temporo-mandibular joint of the Qafzeh 9 fossil. History The condition was initially described by Alexander Monro (primus) in 1738. In 1870, James Paget described the disease process for the first time, but it was not until 1887 that Franz König published a paper on the cause of loose bodies in the joint. In his paper, König concluded that: Trauma had to be very severe to break off parts of the joint surface. Less severe trauma might contuse the bone to cause an area of necrosis which might then separate. In some cases, the absence of notable trauma made it likely that there existed some spontaneous cause of separation.König named the disease "osteochondritis dissecans", describing it as a subchondral inflammatory process of the knee, resulting in a loose fragment of cartilage from the femoral condyle. In 1922, Kappis described this process in the ankle joint. On review of all literature describing transchondral fractures of the talus, Berndt and Harty developed a classification system for staging of osteochondral lesions of the talus (OLTs). The term osteochondritis dissecans has persisted, and has since been broadened to describe a similar process occurring in many other joints, including the knee, hip, elbow, and metatarsophalangeal joints. Notable cases Michael Russell, American tennis player Kristina Vaculik, Canadian artistic gymnast Jonathan Vilma, American football linebacker Seo In-guk, Korean actor Veterinary aspects OCD also is found in animals, and is of particular concern in horses, as there may be a hereditary component in some horse breeds. Feeding for forced growth and selective breeding for increased size are also factors. OCD has also been studied in other animals—mainly dogs, especially the German Shepherd—where it is a common primary cause of elbow dysplasia in medium-large breeds.In animals, OCD is considered a developmental and metabolic disorder related to cartilage growth and endochondral ossification. Osteochondritis itself signifies the disturbance of the usual growth process of cartilage, and OCD is the term used when this affects joint cartilage causing a fragment to become loose.According to the Columbia Animal Hospital the frequency of affected animals is dogs, humans, pigs, horses, cattle, chickens, and turkeys, and in dogs the most commonly affected breeds include the German Shepherd, Golden and Labrador Retriever, Rottweiler, Great Dane, Bernese Mountain Dog, and Saint Bernard. Although any joint may be affected, those commonly affected by OCD in the dog are: shoulder (often bilaterally), elbow, knee and tarsus.The problem develops in puppyhood although often subclinically, and there may be pain or stiffness, discomfort on extension, or other compensating characteristics. Diagnosis generally depends on X-rays, arthroscopy, or MRI scans. While cases of OCD of the stifle go undetected and heal spontaneously, others are exhibited in acute lameness. Surgery is recommended once the animal has been deemed lame.Osteochondritis dissecans is difficult to diagnose clinically as the animal may only exhibit an unusual gait. Consequently, OCD may be masked by, or misdiagnosed as, other skeletal and joint conditions such as hip dysplasia. References External links Radiology MR and CT of OCD

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

I've encountered the term 'Hutchinsons triad' while reading about medical topics. What does it refer to exactly?

Hutchinsons triad is named after Sir Jonathan Hutchinson (1828–1913). It is a common pattern of presentation for congenital syphilis, and consists of three phenomena: interstitial keratitis, malformed teeth (Hutchinson incisors and mulberry molars), and eighth nerve deafness. There may also be a deformity on the nose known as saddle nose deformity. == References ==

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I'm not familiar with the medical term 'Edaravone.' Could you provide some insights?

Edaravone, sold under the brand name Radicava among others, is a medication used to treat stroke and amyotrophic lateral sclerosis (ALS). It is given by intravenous infusion and by mouth.The most common side effects include bruising (contusions), problems walking (gait disturbances), and headaches.The mechanism by which edaravone might be effective is unknown. The medication is known to be an antioxidant, and oxidative stress has been hypothesized to be part of the process that kills neurons in people with ALS.The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses Edaravone is used to help people recover from stroke in Japan, and is used to treat ALS in the US and Japan. Adverse effects The label carries a warning about the potential for hypersensitivity reactions to edaravone, and adverse effects include bruising, gait disturbances, headache, skin inflammation, eczema, problems breathing, excess sugar in urine, and fungal skin infections.The following adverse effects in at least 2% more people given the medication than were given placebo: bruising, gait disturbances, headache, skin inflammation, eczema, problems breathing, excess sugar in urine, and fungal skin infections.There is no data on whether it is safe for pregnant women to take, and it is unknown if edaravone is secreted in breast milk. Pharmacology The mechanism by which edaravone might be effective in ALS is unknown. The medication is known to be an antioxidant, and oxidative stress has been hypothesized to be part of the process that kills neurons in people with ALS.The half-life of edaravone is 4.5 to 6 hours and the half-lives of its metabolites are 2 to 3 hours. It is metabolized to a sulfate conjugate and a glucuronide conjugate, neither of which are active. It is primarily excreted in urine as the glucuronide conjugate form. History Researchers first developed the free radical scavenger edaravone in late 1980s as a treatment for stroke. The approach, introduced by Koji Abe, now at Okayama University Hospital in Japan, aimed to prevent the swelling of the brain which may occur after a stroke.It has been marketed in Japan by Mitsubishi Pharma for stroke since 2001 and is now generic.Mitsubishi Tanabe started a phase III clinical trial in ALS in 2011, in Japan, and by June 2015, it had been approved for that use in Japan. The company had received Orphan Drug Designation for edaravone from the FDA and EU by 2016.It was approved for ALS in the US in 2017, based on a small randomized controlled clinical trial with people who had early-stage ALS in Japan, who were administered the medication for 6 months; it had failed two earlier trials in people with all stages of ALS.In May 2017, I.V. edaravone was approved by the FDA to treat people with amyotrophic lateral sclerosis (ALS) in the United States. The FDA approval was conditioned on Mitsubishi Tanabe completing several additional studies to clarify the risks of cancer and liver disease, among other effects of the medication.Formulation of edaravone by mouth called TW001 (mixture of the edaravone and SBE-HP-βCD ) has been under development by Treeway for ALS; as of 2015, it had successfully completed Phase I trial and had received orphan status in the US and in the European Union.An oral formulation of edaravone was approved for medical use in the United States in May 2022. The effectiveness of oral edaravone is based on a study that showed comparable levels of oral edaravone in the bloodstream to the levels from the IV formulation of edaravone. The efficacy of edaravone for the treatment of ALS was previously demonstrated in a six-month clinical trial that served as the basis for approval in 2017. In that trial, 137 participants were randomized to receive edaravone or placebo. At week 24, individuals receiving edaravone declined less on a clinical assessment of daily functioning compared to those receiving placebo. Society and culture Economics The price for the medication when it launched in Japan for stroke in 2001, was set by the Japanese government at 9,931 yen/ampule.When the medication launched in Japan for ALS in 2001, the price was $35,000; the price in Japan in 2017 was $5,000, the US price at launch was around $145,000. In the US the medication was approved for all people with ALS but it was unclear at approval whether insurers would agree to pay for the medication for all people with ALS, or only people in the early stages of the disease. There are three filed trials for edaravone, demonstrating it may work in less than 5% of all ALS population. Brand names Brand names include Radicut, ラジカット, Radicava, Xavron. References Further reading Yoshino H (March 2019). "Edaravone for the treatment of amyotrophic lateral sclerosis". Expert Rev Neurother. 19 (3): 185–193. doi:10.1080/14737175.2019.1581610. PMID 30810406. S2CID 73490631. Canadian Agency for Drugs and Technologies in Health (April 2019). Pharmacoeconomic Review Report: Edaravone (Radicava): (Mitsubishi Tanabe Pharma Corporation). CADTH Common Drug Reviews. PMID 31211530. NBK542526. External links "Edaravone". Drug Information Portal. U.S. National Library of Medicine.

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What does the medical term 'Ecallantide' encompass?

Ecallantide (trade name Kalbitor) is a drug used for the treatment of hereditary angioedema (HAE) and in the prevention of blood loss in cardiothoracic surgery. It is an inhibitor of the protein kallikrein and a 60-amino acid polypeptide which was developed from a Kunitz domain through phage display to mimic antibodies inhibiting kallikrein. Medical uses Angioedema On November 27, 2009, ecallantide was approved by the FDA for the treatment of acute attacks of hereditary angioedema for persons over 16 years of age. A single dose requires three separate injections, which are given under the skin.Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors. Adverse effects The most common adverse effects are headache, nausea, fatigue and diarrhea. Less common, but observed in more than 5% of patients in clinical trials, are respiratory tract infections, fever, vomiting, itching and upper abdominal pain. Up to 4% of patients showed anaphylaxis, which led to a black box warning in the US. Interactions As of 2011, no interaction studies have been conducted. Mechanism of action HAE is caused by a mutation of the C1-inhibitor gene. Defective or missing C1-inhibitor permits activation of kallikrein, a protease that is responsible for liberating bradykinin from its precursor kininogen. An excess of bradykinin leads to fluid leakage from blood vessels, causing swelling of tissues typical of HAE. Ecallantide suppresses this pathogenetic mechanism by selectively and reversibly inhibiting the activity of plasma kallikrein. Ecallantides inhibitory constant (Ki) for kallikrein is 25 picoMolar, indicating high affinity. See also Icatibant, another drug for the treatment of HAE == References ==

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I'm encountering the term 'Secondary glaucoma' in medical literature. What's its definition?

Secondary glaucoma is a collection of progressive optic nerve disorders associated with a rise in intraocular pressure (IOP) which results in the loss of vision. In clinical settings, it is defined as the occurrence of IOP above 21 mmHg requiring the prescription of IOP-managing drugs. It can be broadly divided into two subtypes: secondary open-angle glaucoma and secondary angle-closure glaucoma, depending on the closure of the angle between the cornea and the iris. Principal causes of secondary glaucoma include optic nerve trauma or damage, eye disease, surgery, neovascularization, tumours and use of steroid and sulfa drugs. Risk factors for secondary glaucoma include uveitis, cataract surgery and also intraocular tumours. Common treatments are designed according to the type (open-angle or angle-closure) and the underlying causative condition, in addition to the consequent rise in IOP. These include drug therapy, the use of miotics, surgery or laser therapy. Pathophysiology Secondary glaucoma has different forms based on the varying underlying ocular conditions. These conditions result in an increase in IOP that manifests as secondary glaucoma. Paediatric congenital cataract associated glaucoma Based on the onset of secondary glaucoma in paediatric patients, it can be classified into early-stage and late-stage glaucoma cases. Early-stage secondary glaucoma, observed as angle-closure glaucoma, results from the blockage and inflammation of the peripheral anterior synechiae structure. However, early-stage secondary glaucoma rarely occurs with the readily available prescription of anti-inflammatory medications. On the other hand, late-stage glaucoma is commonly associated with open-angle glaucoma but the mechanisms are currently unconfirmed. Yet, it is believed to be closely related to the onset of trabeculitis or vitreous toxicity.In paediatric congenital cataract patients under the age of two, cataract surgery is considered and frequently employed as the primary treatment. There are two types of therapeutic combination, primary and secondary lens implantation (IOL). In primary IOL, cataract surgery is performed alongside immediate implantation of IOL. However, in secondary IOL implantation, the patient is prescribed aphakic glasses or contact lenses till the implantation of IOL after a varied period of time between a few months or years. Primary IOL implantation is observed to significantly reduce and avoid the occurrence of secondary glaucoma in paediatric patients under the age of two. Herpetic anterior uveitis associated glaucoma In patients diagnosed with herpetic anterior uveitis, elevated IOP and secondary glaucoma are often detected. This is due to two main reasons, the blockage of vitreous flow resulting from inflammation in the structures of the trabecular meshwork, and the sedimentation of inflamed cells. Specifically for viral anterior uveitis, patients with IOP levels above 30 mmHg are often suffer from secondary glaucoma caused by cytomegalovirus. Other forms of secondary glaucoma Pigmentary glaucoma: In pigmentary glaucoma, the obstruction of the trabecular meshwork caused by iris pigment release results in increased IOP. This release in iris pigment occurs as a result of the interaction of a flaccid iris with the zonular fibres.Exfoliation syndrome: Exfoliation syndrome is a classic cause of secondary open-angle glaucoma, a common symptom of exfoliation syndrome is a cloudy layer on the anterior lens capsule.Aphakic and pseudophakic glaucoma: Aphakic glaucoma is a common side-effect of cataract surgery which causes an increase in IOP.Corticosteroid-induced glaucoma: Corticosteroids is a risk factor for the development of secondary glaucoma, as there had been increased IOP observed as a drug side-effect.Post-traumatic glaucoma: Trauma to the eye is often observed to cause secondary glaucoma. The incidence is notably higher in populations with increased levels of physical activity.Ghost-cell glaucoma: Ruptured red blood cells will release haemoglobin in the form of Heinz bodies, which are potent in increasing the IOP level.Inflammatory glaucoma: The inflammatory reaction will affect the drainage of aqueous humour in the eye, causing an increase in IOP.Glaucoma associated with ocular tumours: Although each tumour subtype has its own mechanism in causing secondary glaucoma, the general cause is the restriction of the meshwork resulting in the obstruction of aqueous humour flow.Increased episcleral venous pressure: According to the Goldmann equation, the relationship between episcleral venous pressure (EVP) is directly proportional to the IOP. Therefore, an increase in the EVP will result in an increase in IOP. Neovascular glaucoma: As a consequence of neovascularisation, or the formation of new blood vessels and supporting connective structures, there is blockage of the anterior chamber angle. This leads to elevation of IOP causing neovascular glaucoma. Epidemiology The overall prevalence of secondary glaucoma across China between 1990 and 2015 was reported to be 0.15%, lower than the overall estimates for East Asia (0.39%). Varying forms of secondary glaucoma Pigmentary glaucoma has lower incidence in Black and Asian populations, due to their characteristically thicker irises that result in a lower likelihood of pigment release, as compared to the White populations. Incidence of exfoliation syndrome-caused secondary glaucoma is estimated to be approximately 10% of the glaucoma patient population in the United States and over 20% of the patient population in Iceland and Finland.In populations above the age of 40, neovascular glaucoma has a prevalence of 0.4% worldwide. The incidence of pigmentary glaucoma decreases with age while in exfoliation syndrome the incidence increases with age. However, given the derived nature of secondary glaucoma, there may be no significant association between age, ethnicity or gender and the prevalence of the condition.Secondary glaucoma indicated after congenital cataract surgery is found between 6 and 24% of the cases noted, whereas, secondary glaucoma caused by primary IOL implantation was observed as 9.5%. Additionally, for patients with aphakia and secondary IOL implantation, 15.1% of the cases were determined. The incidence risk in primary IOL implantation in children with cataract in both eyes is lower than secondary IOL implantation and aphakic condition. However, this difference is not observed in the general population and populations with cataract in one eye.Due to lack of concrete and specific epidemiological evidence, further research is required to accurately estimate the prevalence of secondary glaucoma and its subtypes. Risk factors In general, elevated IOP is a major risk factor in the development of secondary glaucoma. However, there are several risk factors contributing to the fluctuation in IOP levels. Uveitis Secondary glaucoma is commonly associated with uveitis. Uveitis is the inflammation of the uvea, a middle layer tissue of the eye consisting of the ciliary body, choroid and iris. Various causes have been identified as potential risk factors contributing to the occurrence of secondary glaucoma. These include viral anterior uveitis due to cytomegalovirus infection, and herpetic anterior uveitis caused by herpes simplex virus. The observed pathophysiology of secondary glaucoma in uveitis is found to be linked to the increase and fluctuation of IOP. Inflammation of eye tissues contributes to the blockage of IOP produced in the ciliary body. This results in the accumulation of aqueous and thus elevated IOP, which is a common risk factor for the progression of secondary glaucoma. Paediatric congenital cataract surgery Paediatric congenital cataract surgery is also identified as a risk factor for the progression of secondary glaucoma. Cataract is an ocular disease, identified by the progressive clouding of the lens. Surgical procedures are often employed to replace the lens and allow for clear vision. However, there is an increased risk of secondary glaucoma development in children due to the secondary IOL implantation procedure. The increased inflammatory sensitivity in the anterior chamber angle may contribute to the risks of secondary glaucoma. Intraocular tumour Intraocular tumours (uveal and retinal tumours) are also found to be closely associated with the development of secondary glaucoma. The pathophysiology of secondary glaucoma in these cases is affected by the type of tumour, location and other tumour-associated factors. Among the many subtypes of uveal tumours, secondary glaucoma is the most prominent among patients with trabecular meshwork iris melanoma. The blockage of vitreous flow due to inflammation in the structures of the trabecular meshwork is also observed in herpetic anterior uveitis patients. In addition to this, angle invasion is a mechanism that is observed to contribute greatly to the development of secondary glaucoma in patients with iris tapioca melanoma, iris lymphoma, choroidal melanoma, and medulloepithelioma. Treatment and management Pharmacological interventions Miotic drugs are a class of cholinergic drugs that are frequently employed in the treatment and management of all types of glaucoma. These drugs stimulate the contraction of the pupil causing the iris to pull away from the trabecular meshwork. Consequently, the normal drainage of the aqueous humour is restored, relieving IOP. In addition to causing a direct effect on IOP, these drugs are applied to reduce pigment release (from the iris pigment epithelium) in the treatment of pigmentary glaucoma. Despite the advantages, the widespread use of miotic drugs is limited by its associated side effects. There is an increased risk of development of posterior synechiae in glaucoma secondary to exfoliation syndrome and ocular trauma. Other side effects include increased risk of miosis-induced headaches, blurred vision, retinal detachment and damage to the blood-aqueous barrier.Alternative drugs which can reduce the synthesis of aqueous humour, called aqueous suppressants, or increase the drainage of aqueous humour emerged as effective first-line treatments. Aqueous suppressants include beta-blockers, alpha-agonists and carbonic anhydrase inhibitors. They are particularly effective in treating corticosteroid, uveitic, aphakic, pseudophakic, ghost-cell and post-traumatic glaucoma. Prostaglandin analogues increase aqueous drainage and are thus used in the reduction of IOP. There are contradictory findings regarding the occurrence of prostaglandin analogue mediated side effects in the treatment of uveitic glaucoma. It was previously identified that the side effects comprise damage to the blood-aqueous barrier, cystoid macular oedema, risk of developing anterior uveitis and recurrence of keratitis caused by herpes simplex virus. However, current scientific evidence only supports the reactivation of herpes simplex keratitis among the other side effects.In uveitic and inflammatory glaucoma, reduction in inflammation is a critical step during the treatment and management process. This is commonly done using corticosteroids coupled with immunosuppressants. Steroidal treatment is also used in management of aphakic, pseudophakic, and post-traumatic glaucoma. Inflammatory glaucoma may further be treated using cycloplegics, a class of drugs that treats pain, ciliary spasm, uveoscleral tract blockage and disrupted blood-aqueous barrier linked with this form of glaucoma. While some studies recommend the use of anti-vascular endothelial growth factor drugs for inhibition of neovascularization in neovascular glaucoma, there is a lack of substantial evidence for the effectiveness of this treatment method. Laser therapy Among different laser therapies, laser peripheral iridotomy and laser trabeculoplasty are the most common procedures for secondary glaucoma. Both methods involve creating new outlets for the aqueous humour to flow out of, effectively reducing the IOP. In peripheral laser iridotomy, the opening is created in the iris tissue while in trabeculoplasty, this opening is made in the trabecular meshwork. Further, there are two types of laser trabeculoplasty: argon laser trabeculoplasty and selective laser trabeculoplasty.Laser peripheral iridotomy has high efficacy in the treatment of pigmentary glaucoma. Argon laser trabeculoplasty is effective in the management of corticosteroid and pigmentary glaucoma. However, this is often contraindicated due to high rates of failure in patients with uveitic glaucoma. For uveitic glaucoma, treatment with selective laser trabeculoplasty is associated with fewer adverse effects and risks of failure. Surgical treatment Surgical procedures are effective in cases where pharmacological management is not successful or suitable. Such methods work by facilitating aqueous outflow through the modification of the obstructing trabecular meshwork using trabeculectomy, goniotomy, non-penetrating deep sclerectomy or canaloplasty. Alternatively, introduction of new drainage pathways may also be achieved by the implantation of glaucoma shunts or glaucoma drainage devices.Trabeculectomy is held as the gold standard for surgical management of glaucoma. Studies indicate that treatment of uveitic glaucoma using trabeculectomy with antimetabolites administration has a high success rate of 62%-81%. Thus, it is also commonly used in the treatment of pigmentary glaucoma. Drainage tube implants are also implicated in treatment of uveitic and inflammatory glaucoma.Minimally invasive glaucoma surgery is performed in order to overcome the risks and adverse effects associated with conventional surgical procedures. However, there are limited studies testing the efficacy of utilising this type of surgery for the treatment of uveitic glaucoma.In addition to the direct reduction of IOP, surgical procedures are used to remove blood, viscoelastic fluid and debris in glaucoma caused by cataract extraction and ocular trauma. They may also be utilized to remove depot steroids in corticosteroid glaucoma and ghost cells from the vitreous humour in ghost-cell glaucoma through a procedure known as vitrectomy. == References ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Butenafine'?

Butenafine, sold under the brand names Lotrimin Ultra, Mentax, and Butop (India), is a synthetic benzylamine antifungal. It is structurally related to synthetic allylamine antifungals such as terbinafine. Medical uses Butenafine is indicated for the topical treatment of tinea (pityriasis) versicolor due to Malassezia furfur, as well as athletes foot (Tinea pedis), ringworm (Tinea corporis) and jock itch (Tinea cruris) due to Epidermophyton floccosum, Trichophyton mentagrophytes, Trichophyton rubrum, and Trichophyton tonsurans. It also displays superior activity against Candida albicans than terbinafine and naftifine. Butenafine demonstrates low minimum inhibitory concentrations against Cryptococcus and Aspergillus. There is some evidence that it is effective against dermatophyte infections of the toenails, but needs to be applied daily for prolonged periods (at least one year). Typical usage For 1% cream: for adults and children 12 years and older: wash the affected skin with soap and water and dry completely before applying apply once a day to affected skin for 2 weeks or as directed by a doctor wash hands after each use children under 12 years: ask a doctor Available forms Butenafine is typically available as a 1% topical cream. Pharmacology Like the allylamine antifungals, butenafine works by inhibiting the synthesis of ergosterol by inhibiting squalene epoxidase, an enzyme responsible for the creation of sterols needed in fungal cell membranes. Lacking ergosterol, the cell membranes increase in permeability, allowing their contents to leak out. Furthermore, inhibition of squalene epoxidase leads to a toxic buildup of squalene. This double action of butenafine (increased membrane permeability and toxic buildup of squalene) makes butenafine fungicidal rather than merely fungistatic. In addition to being an antifungal, butenafine is an anti inflammatory. Because fungal skin infections are often accompanied by significant inflammation, this is a desirable property. The fact that butenafine has intrinsic anti inflammatory properties is also desirable since it is not necessary to add cortical steroids (which decrease the ability to fight infection) to reduce inflammation. Chemistry Butenafine hydrochloride is an odorless white crystalline powder that is freely soluble in methanol, ethanol, and chloroform, and slightly soluble in water. == References ==

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I'm looking for a concise explanation of the medical term 'Lindane.'

Lindane, also known as gamma-hexachlorocyclohexane (γ-HCH), gammaxene, Gammallin and benzene hexachloride (BHC), is an organochlorine chemical and an isomer of hexachlorocyclohexane that has been used both as an agricultural insecticide and as a pharmaceutical treatment for lice and scabies.Lindane is a neurotoxin that interferes with GABA neurotransmitter function by interacting with the GABAA receptor-chloride channel complex at the picrotoxin binding site. In humans, lindane affects the nervous system, liver, and kidneys, and may well be a carcinogen. Whether lindane is an endocrine disruptor is unclear.The World Health Organization classifies lindane as "moderately hazardous", and its international trade is restricted and regulated under the Rotterdam Convention on Prior Informed Consent. In 2009, the production and agricultural use of lindane was banned under the Stockholm Convention on persistent organic pollutants. A specific exemption to that ban allows it to continue to be used as a second-line pharmaceutical treatment for lice and scabies. History and use The chemical was originally synthesized in 1825 by Faraday. It is named after the Dutch chemist Teunis van der Linden (1884–1965), the first to isolate and describe γ-hexachlorcyclohexane in 1912. The fact that mixtures of isomers of hexachlorocyclohexane have insecticidal activity is a case of multiple discovery. Work in the 1930s at the Jealotts Hill laboratories of Imperial Chemical Industries Ltd (ICI) led in 1942 to the realization that the γ isomer was the key active component in the mixture which had hitherto been tested. Development work in the UK was accelerated because at that time in World War II imports of derris containing the insecticide rotenone were restricted owing to the Japanese occupation of Malaya and alternatives were urgently needed. In trials in 1943 it was found that a five-fold increase in the yield of oats and wheat was achieved using a dust formulation of the available material, owing to its efficacy against wireworm pests. By the end of 1945, γ-hexachlorcyclohexane of 98% purity became available and ICI commercialised a seed treatment launched in 1949 as Mergamma A, containing 1% mercury and 20% lindane. Subsequently, lindane has been used to treat food crops and forestry products, as a seed or soil treatment, and to treat livestock and pets. It was used as a household pesticide as the active pesticide ingredient of an insecticidal floor wax product called "Freewax". It has also been used as pharmaceutical treatment for lice and scabies, formulated as a shampoo or lotion. Between 1950 and 2000, an estimated 600,000 tonnes of lindane were produced globally, and the vast majority of which was used in agriculture. It has been manufactured by several countries, including the United States, China, Brazil, and several European countries, but as of 2007, only India and possibly Russia are still producing it. By November 2006, the use of lindane had been banned in 52 countries and restricted in 33 others. Seventeen countries, including the US and Canada, allowed either limited agricultural or pharmaceutical use. In 2009, an international ban on the use of lindane in agriculture was implemented under the Stockholm Convention on Persistent Organic Pollutants. A specific exemption allows for it to continue to be used in second-line treatments for the head lice and scabies for five more years. The production of the lindane isomers α- and β-hexachlorocyclohexane was also banned. Although the US has not ratified the Convention, it has similarly banned agricultural uses while still allowing its use as a second-line lice and scabies treatment. United States In the US, lindane pesticide products were regulated by the U.S. Environmental Protection Agency (EPA), while lindane medications are regulated by the Food and Drug Administration (FDA). It was registered as an agricultural insecticide in the 1940s, and as pharmaceutical in 1951. The EPA gradually began restricting its agricultural use in the 1970s due to concerns over its effects on human health and the environment. By 2002, its use was limited to seed treatments for just six crops, and in 2007, these last uses were cancelled. Pharmaceutical uses Lindane medications continue to be available in the US, though since 1995, they have been designated "second-line" treatments, meaning they should be prescribed when other "first-line" treatments have failed or cannot be used. In December 2007, the FDA sent a Warning Letter to Morton Grove Pharmaceuticals, the sole U.S. manufacturer of lindane products, requesting that the company correct misleading information on two of its lindane websites. The letter said, in part, that the materials "are misleading in that they omit and/or minimize the most serious and important risk information associated with the use of Lindane Shampoo, particularly in pediatric patients; include a misleading dosing claim; and overstate the efficacy of Lindane Shampoo."California banned the pharmaceutical lindane, effective 2002, and the Michigan House of Representatives passed a bill in 2009 to restrict its use to doctors offices. A recent analysis of the California ban concluded that a majority of pediatricians had not experienced problems treating lice or scabies since that ban took effect. The study also documented a marked decrease in lindane wastewater contamination and a dramatic decline in lindane poisoning incidents reported to poison control centers. The authors concluded, "The California experience suggests elimination of pharmaceutical lindane produced environmental benefits, was associated with a reduction in reported unintentional exposures and did not adversely affect head lice and scabies treatment."The Persistent Organic Pollutants Review Committee of the Stockholm Convention on Persistent Organic Pollutants considers the use of lindane in agriculture as largely redundant, with other, less toxic and less persistent pesticides. In the case of pharmaceutical use, the committee noted, "alternatives for pharmaceutical uses have often failed for scabies and lice treatment and the number of available alternative products for this use is scarce. For this particular case, a reasonable alternative would be to use lindane as a second-line treatment when other treatments fail, while potential new treatments are assessed." Other uses Pest repellent Lindane is a bird repellent. Rudd & Genelly 1954 noticed that bird pests seemed uninterested in treated seeds, specifically pheasants and blackbirds around Davis, CA, US. They tested its repellent effect on pheasants and found it effective, speculating that it may be usable as a general bird repellent. Preparation Lindane is prepared by treating chlorine with benzene in the presence of sunlight and in the absence of oxygen as well as substitution catalysts. Human health effects The EPA and WHO both classify lindane as "moderately" acutely toxic. It has an oral LD50 of 88 mg/kg in rats and a dermal LD50 of 1000 mg/kg. Most of the adverse human health effects reported for lindane have been related to agricultural uses and chronic, occupational exposure of seed-treatment workers.Exposure to large amounts of lindane can harm the nervous system, producing a range of symptoms from headache and dizziness to seizures, convulsions, and more rarely, death. Lindane has not been shown to affect the immune system in humans, and it is not considered to be genotoxic. Prenatal exposure to β-HCH, an isomer of lindane and production byproduct, has been associated with altered thyroid hormone levels and could affect brain development.The Occupational Safety and Health Administration and National Institute for Occupational Safety and Health have set occupational exposure limits (permissible exposure and recommended exposure, respectively) for lindane at 0.5 mg/m3 at a time-weighted average of eight hours for skin exposure. People can be exposed to lindane in the workplace by inhaling it, absorbing it through their skin, swallowing it, and eye contact. At levels of 50 mg/m3, lindane is immediately dangerous to life and health.It is classified as an extremely hazardous substance in the United States as defined in section 302 of the U.S. Emergency Planning and Community Right-to-Know Act (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities. Cancer risk Based primarily on evidence from animal studies, most evaluations of lindane have concluded that it may possibly cause cancer. In 2015, the International Agency for Research on Cancer classified lindane as a known human carcinogen, and in 2001 the EPA concluded there was "suggestive evidence of carcinogenicity, but not sufficient to assess human carcinogenic potential." The U.S. Department of Health and Human Services determined that all isomers of hexachlorocyclohexane, including lindane, "may reasonably be anticipated to cause cancer in humans," and in 1999, the EPA characterized the evidence carcinogenicity for lindane as "suggestive ... of carcinogenicity, but not sufficient to assess human carcinogenic potential." Lindane and its isomers have also been on Californias Proposition 65 list of known carcinogens since 1989. In contrast, the World Health Organization concluded in 2004 that "lindane is not likely to pose a carcinogenic risk to humans." Indias BIS considers Lindane a "confirmed carcinogen". Adverse reactions A variety of adverse reactions to lindane pharmaceuticals have been reported, ranging from skin irritation to seizures, and, in rare instances, death. The most common side effects are burning sensations, itching, dryness, and rash. While serious effects are rare and have most often resulted from misuse, adverse reactions have occurred when used properly. The FDA, therefore, requires a so-called black box warning on lindane products, which explains the risks of lindane products and their proper use.The black box warning emphasizes that lindane should not be used on premature infants and individuals with known uncontrolled seizure disorders, and should be used with caution in infants, children, the elderly, and individuals with other skin conditions (e.g., dermatitis, psoriasis) and people who weigh less than 110 lb (50 kg), as they may be at risk of serious neurotoxicity. Environmental contamination Lindane is a persistent organic pollutant: it is relatively long-lived in the environment, it is transported long distances by natural processes like global distillation, and it can bioaccumulate in food chains, though it is rapidly eliminated when exposure is discontinued.The production and agricultural use of lindane are the primary causes of environmental contamination, and levels of lindane in the environment have been decreasing in the U.S., consistent with decreasing agricultural usage patterns. The production of lindane generates large amounts of waste hexachlorocyclohexane isomers, and "every ton of lindane manufactured produces about nine tons of toxic waste." Modern manufacturing standards for lindane involve the treatment and conversion of waste isomers to less toxic molecules, a process known as "cracking".When lindane is used in agriculture, an estimated 12–30% of it volatilizes into the atmosphere, where it is subject to long-range transport and can be deposited by rainfall. Lindane in soil can leach to surface and even ground water, and can bioaccumulate in the food chain. However, biotransformation and elimination are relatively rapid when exposure is discontinued. Most exposure of the general population to lindane has resulted from agricultural uses and the intake of foods, such as produce, meats, and milk, produced from treated agricultural commodities. Human exposure has decreased significantly since the cancellation of agricultural uses in 2006. Even so, the CDC published in 2005 its Third National Report on Human Exposures to Environmental Chemicals, which found no detectable amounts of lindane in human blood taken from a random sampling of about 5,000 people in the US as part of the NHANES study (National Health and Nutrition Examination Survey at: https://www.cdc.gov/nchs/nhanes/about_nhanes.htm). The lack of detection of lindane in this large human "biomonitoring" study likely reflects the increasingly limited agricultural uses of lindane over the last two decades. The cancellation of agricultural uses in the United States will further reduce the amount of lindane introduced into the environment by more than 99%.Over time, lindane is broken down in soil, sediment, and water into less harmful substances by algae, fungi, and bacteria; however, the process is relatively slow and dependent on ambient environmental conditions. Lindane residues in honey and beeswax are reported to be the highest of any historical or current pesticide and to continue to pose a threat to honeybee health. The ecological impact of lindanes environmental persistence continues to be debated. The US EPA determined in 2002 that the agency does not believe that lindane contaminates drinking water in excess of levels considered safe. U.S. Geological Survey teams concluded the same in 1999 and 2000. With regard to lindane medications, the EPA conducted "down-the-drain" estimates of the amount of lindane reaching public water supplies and concluded that lindane levels from pharmaceutical sources were "extremely low" and not of concern.Note that the EPA has set the maximum contaminant level or "MCL" for lindane allowed in public water supplies and considered safe for drinking at 200 parts per trillion (ppt). By comparison, the state of California imposes a lower MCL for lindane of 19 ppt. However, the California standard is based on a dated 1988 national water criterion that was subsequently revised by the EPA in 2003 to 980 ppt. The EPA stated that the change resulted from "significant scientific advances made in the last two decades particularly in the areas of cancer and noncancer risk assessments." While the EPA considered raising the MCL standard for lindane to 980 ppt at that time, the change was never implemented because states had little difficulty in maintaining lindane levels below the 200 ppt MCL limit already in place. Today, the legally enforceable MCL standard for lindane is 200 ppt, while the national water criterion for lindane is 980 ppt. Isomers Lindane is the gamma isomer of hexachlorocyclohexane ("γ-HCH"). In addition to the issue of lindane pollution, some concerns are related to the other isomers of HCH, namely alpha-HCH and beta-HCH, which are notably more toxic than lindane, lack its insecticidal properties, and are byproducts of lindane production. In the 1940s and 1950s, lindane producers stockpiled these isomers in open heaps, which led to ground and water contamination. The International HCH and Pesticide Forum has since been established to bring together experts to address the clean-up and containment of these sites. Modern manufacturing standards for lindane involve the treatment and conversion of waste isomers to less toxic industrial chemicals, a process known as "cracking". Today, only a few production plants remain active worldwide to accommodate public-health uses of lindane and declining agricultural needs. Lindane has not been manufactured in the U.S. since the mid-1970s, but continues to be imported. See also Benzene hexachloride (disambiguation) References External links Government and organizations FDA Information on Lindane EPA Information on Lindane Gamma Hexachlorocyclohexane Fact Sheet Agency for Toxics and Disease Registry: Toxicological Profile for Hexachlorocyclohexane Lindane in the Pesticide Properties DataBase (PPDB) World Health Organization Background Document on Lindane for Drinking-Water Quality Guidelines Lindane Chemistry and Uses World Health Organization: Lindane (EHC 124) "Lindane Facts" - Website run by Morton Grove Pharmaceuticals U.S. National Library of Medicine: Hazardous Substances Databank – Lindane News stories and opinion articles "Mom and Pros Tackle Lice" - NPR story from 2006 Pepsi and Coca-Cola - Lindane in drinks in India - news story from 2006 India - Pesticides in Coke & Pepsi drinks - news story from 2003

You are a resource for medical understanding. Offer detailed explanations of medical terms, making complex concepts clear and comprehensible.

Can you demystify the medical term 'Mifepristone' for me?

Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of pregnancy. It is also effective in the second trimester of pregnancy. Effectiveness should be verified two weeks after use. It is taken by mouth.Common side effects include abdominal pain, feeling tired, and vaginal bleeding. Serious side effects may include heavy vaginal bleeding, bacterial infection, and birth defects if the pregnancy does not end. If used, appropriate follow up care needs to be available. Mifepristone is an antiprogestogen. It works by blocking the effects of progesterone, making both the cervix and uterine vessels dilate and causing uterine contraction.Mifepristone was developed in 1980 and came into use in France in 1987. It became available in the United States in 2000. It is on the World Health Organizations List of Essential Medicines. Mifepristone was approved by Health Canada in 2015 and became available in Canada in January 2017. Cost and availability limits access in many parts of the developing world. Medical uses Abortion Mifepristone followed by a prostaglandin analog (misoprostol or gemeprost) is used for medical abortion. Medical organizations have found this combination to be safe and effective. Guidelines from the Royal College of Obstetricians and Gynaecologists describe medication abortion using mifepristone and misoprostol as effective and appropriate at any gestational age. The World Health Organization and the American Congress of Obstetricians and Gynecologists recommend mifepristone followed by misoprostol for first- and second-trimester medical abortion. Mifepristone alone is less effective, resulting in abortion within 1–2 weeks in anywhere from 54% to 92% of pregnancies, according to review of 13 studies. Cushings syndrome Mifepristone is used for the medical treatment of high blood sugar caused by high cortisol levels in the blood (hypercortisolism) in adults with endogenous Cushings syndrome who also have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery. Other Mifepristone at low doses has been used for emergency contraception. It may also be used together with misoprostol for early pregnancy loss. Mifepristone has also been used to treat symptomatic leiomyoma (uterine fibroids) and endometriosis. Side effects Serious complications with mifepristone are rare with about 0.04%–0.9% requiring hospitalization and 0.05% requiring blood transfusion.Nearly all women using the mifepristone/misoprostol regimen experienced abdominal pain, uterine cramping, and vaginal bleeding or spotting for an average of 9–16 days. For most women, the most severe cramps after use of misoprostol last for less than 6 hours and can generally be managed with ibuprofen. Up to 8% of women experienced some type of bleeding for 30 days or more. Other less common side effects included nausea, vomiting, diarrhea, dizziness, fatigue, and fever. Pelvic inflammatory disease is a very rare but serious complication. Excessive bleeding and incomplete termination of a pregnancy require further intervention by a doctor (such as a repeat dose of misoprostol or a vacuum aspiration). Mifepristone is contraindicated in the presence of adrenal failure, long-term oral corticosteroid therapy (although inhaled and topical steroids are fine), hemorrhagic disorders, inherited porphyria, and hemophilia or anticoagulant use. Women with an intrauterine device in their uterus should remove the IUD prior to medication abortion to avoid unnecessary cramping. Mifepristone is not effective in treating ectopic pregnancy. A postmarketing summary found, of about 1.52 million women who had received mifepristone until April 2011 in the United States, 14 were reported to have died after application. Eight of these cases were associated with sepsis; the other six had various causes such as drug abuse and suspected murder. Other incidents reported to the FDA included 612 nonlethal hospitalizations, 339 blood transfusions, 48 severe infections, and 2,207 (0.15%) adverse events altogether. Cancer No long-term studies to evaluate the carcinogenic potential of mifepristone have been performed. This is in accord with ICH guidelines, which do not require carcinogenicity testing in nongenotoxic drugs intended for administration for less than six months. Pregnancy Mifepristone alone results in abortion within 1–2 weeks in 54% to 92% of pregnancies. The effectiveness increases to greater than 90% if misoprostol is given after the mifepristone. There is no evidence that the effects of mifepristone can be reversed, although some anti-abortion groups claim that it can be reversed by giving progesterone. Researchers in the United States initiated a trial of the so-called "reversal" regimen in 2019, but stopped prematurely due to serious safety concerns about using mifepristone without follow-up misoprostol. Giving progesterone has not been shown to halt medication abortion, and not completing the combination regimen of mifepristone and misoprostol may cause serious bleeding.In those who continue pregnancy after use of mifepristone together with misoprostol for termination, birth defects may occur. Exposure to a single large dose of mifepristone in newborn rats was not associated with any reproductive problems, although chronic low-dose exposure of newborn rats to mifepristone was associated with structural and functional reproductive abnormalities. Studies in mice, rats, and rabbits revealed developmental abnormalities for rabbits, but not rats or mice. Pharmacology Pharmacodynamics Mifepristone is a steroidal antiprogestogen (IC50 = 0.025 nM for the PR), as well as an antiglucocorticoid (IC50 = 2.2 nM for the GR) and antiandrogen (IC50 = 10 nM for the AR) to a much lesser extent. It antagonizes cortisol action competitively at the receptor level.In the presence of progesterone, mifepristone acts as a competitive progesterone receptor antagonist (in the absence of progesterone, mifepristone acts as a partial agonist). Mifepristone is a 19-nor steroid with a bulky p-(dimethylamino) phenyl substituent above the plane of the molecule at the 11β-position responsible for inducing or stabilizing an inactive receptor conformation and a hydrophobic 1-propynyl substituent below the plane of the molecule at the 17α-position that increases its progesterone receptor binding affinity.In addition to being an antiprogestogen, mifepristone is also an antiglucocorticoid and a weak antiandrogen. Mifepristones relative binding affinity at the progesterone receptor is more than twice that of progesterone, its relative binding affinity at the glucocorticoid receptor is more than three times that of dexamethasone and more than ten times that of cortisol. Its relative binding affinity at the androgen receptor is less than one-third that of testosterone, and it does not bind to the estrogen receptor or the mineralocorticoid receptor.Mifepristone as a regular contraceptive at 2 mg daily prevents ovulation (1 mg daily does not). A single preovulatory 10-mg dose of mifepristone delays ovulation by three to four days and is as effective an emergency contraceptive as a single 1.5-mg dose of the progestin levonorgestrel.In women, mifepristone at doses greater or equal to 1 mg/kg antagonizes the endometrial and myometrial effects of progesterone. In humans, an antiglucocorticoid effect of mifepristone is manifested at doses greater or equal to 4.5 mg/kg by a compensatory increase in ACTH and cortisol. In animals, a weak antiandrogenic effect is seen with prolonged administration of very high doses of 10 to 100 mg/kg.In medication abortion regimens, mifepristone blockade of progesterone receptors directly causes endometrial decidual degeneration, cervical softening and dilatation, release of endogenous prostaglandins, and an increase in the sensitivity of the myometrium to the contractile effects of prostaglandins. Mifepristone-induced decidual breakdown indirectly leads to trophoblast detachment, resulting in decreased syncytiotrophoblast production of hCG, which in turn causes decreased production of progesterone by the corpus luteum (pregnancy is dependent on progesterone production by the corpus luteum through the first nine weeks of gestation—until placental progesterone production has increased enough to take the place of corpus luteum progesterone production). When followed sequentially by a prostaglandin, mifepristone 200 mg is (100 mg may be, but 50 mg is not) as effective as 600 mg in producing a medical abortion.Contragestion is a term promoted by Étienne-Émile Baulieu in the context of his advocacy of mifepristone, defining it as inclusive of some hypothesized mechanisms of action of some contraceptives and those of mifepristone to induce abortion. Baulieus definition of a contragestive included any birth control method that could possibly act after fertilization and before nine-weeks gestational age. Pharmacokinetics The elimination half-life is complex; according to the label: "After a distribution phase, elimination is at first slow, the concentration decreasing by a half between about 12 and 72 hours, and then more rapid, giving an elimination half-life of 18 hours. With radio receptor assay techniques, the terminal half-life is of up to 90 hours, including all metabolites of mifepristone able to bind to progesterone receptors." Metapristone is the major metabolite of mifepristone. Chemistry Mifepristone, also known as 11β-(4-(dimethylamino)phenyl)-17α-(1-propynyl)estra-4,9-dien-17β-ol-3-one, is a synthetic estrane steroid and a derivative of steroid hormones like progesterone, cortisol, and testosterone. It has substitutions at the C11β and C17α positions and double bonds at the C4(5) and C9(10) positions. History 1980–1987 In April 1980, as part of a formal research project at the French pharmaceutical company Roussel-Uclaf for the development of glucocorticoid receptor antagonists, endocrinologist Étienne-Émile Baulieu and chemist Georges Teutsch synthesized mifepristone (RU-38486, the 38,486th compound synthesized by Roussel-Uclaf from 1949 to 1980; shortened to RU-486), which was discovered to also be a progesterone receptor antagonist. In October 1981, Étienne-Émile Baulieu, a consultant to Roussel-Uclaf, arranged tests of its use for medical abortion in 11 women in Switzerland by gynecologist Walter Herrmann at the University of Genevas Cantonal Hospital, with successful results announced on 19 April 1982. On 9 October 1987, following worldwide clinical trials in 20,000 women of mifepristone with a prostaglandin analogue (initially sulprostone or gemeprost, later misoprostol) for medical abortion, Roussel-Uclaf sought approval in France for their use for medical abortion, with approval announced on 23 September 1988. 1988–1990 On 21 October 1988, in response to antiabortion protests and concerns of majority (54.5%) owner Hoechst AG of Germany, Roussel-Uclafs executives and board of directors voted 16 to 4 to stop distribution of mifepristone, which they announced on 26 October 1988. Two days later, the French government ordered Roussel-Uclaf to distribute mifepristone in the interests of public health. French Health Minister Claude Évin explained: "I could not permit the abortion debate to deprive women of a product that represents medical progress. From the moment Government approval for the drug was granted, RU-486 became the moral property of women, not just the property of a drug company." Following use by 34,000 women in France from April 1988 to February 1990 of mifepristone distributed free of charge, Roussel-Uclaf began selling Mifegyne (mifepristone) to hospitals in France in February 1990 at a price (negotiated with the French government) of US$48 (equivalent to $99.56 in 2021) per 600-mg dose.Aside from "did not want to get in the middle of the national battle over abortion" in the United States, Hoechst had another reason cited by The New York Post: "During World War II, Hoechst was called I.G. Farben, the firm that manufactured" the poison gas that killed so many in the concentration camps. 1991–1996 Mifegyne was subsequently approved in Great Britain on 1 July 1991, and in Sweden in September 1992, but until his retirement in late April 1994, Hoechst AG chairman Wolfgang Hilger, a devout Roman Catholic, blocked any further expansion in availability. On 16 May 1994, Roussel-Uclaf announced it was donating without remuneration all rights for medical uses of mifepristone in the United States to the Population Council, which subsequently licensed mifepristone to Danco Laboratories, a new single-product company immune to antiabortion boycotts, which won FDA approval as Mifeprex on 28 September 2000. 1997–1999 On 8 April 1997, after buying the remaining 43.5% of Roussel-Uclaf stock in early 1997, Hoechst AG (US$30 (equivalent to $51.83 in 2021) billion annual revenue) announced the end of its manufacture and sale of Mifegyne (US$3.44 (equivalent to $5.94 in 2021) million annual revenue) and the transfer of all rights for medical uses of mifepristone outside of the United States to Exelgyn S.A., a new single-product company immune to antiabortion boycotts, whose CEO was former Roussel-Uclaf CEO Édouard Sakiz. In 1999, Exelgyn won approval of Mifegyne in 11 additional countries, and in 28 more countries over the following decade. Society and culture Mifepristone is on the World Health Organizations List of Essential Medicines. Since 2019 it has been included on the core list, with misoprostol, with a special note "where permitted under national law and where culturally acceptable". Frequency of use United States Medication abortions voluntarily reported by 33 U.S. states to the Centers for Disease Control and Prevention (CDC) have increased as a percentage of total abortions every year since the approval of mifepristone: 1.0% in 2000, 2.9% in 2001, 5.2% in 2002, 7.9% in 2003, 9.3% in 2004, 9.9% in 2005, 10.6% in 2006, and 13.1% in 2007 (20.3% of those at less than 9 weeks gestation).A Guttmacher Institute survey of abortion providers estimated that medication abortions accounted for 17% of all abortions and slightly over 25% of abortions before 9 weeks gestation in the United States in 2008 (94% of nonhospital medication abortions used mifepristone and misoprostol, 6% used methotrexate and misoprostol). Medication abortions accounted for 32% of first trimester abortions at Planned Parenthood clinics in the United States in 2008. Considering abortions performed in non-hospital facilities, medication abortions accounted for 24% in 2011 and 31% in 2014. In 2014, facilities that provided a relatively small number of abortions (fewer than 400 procedures per year) were more likely to perform them with medication. Medication abortions accounted for 39% of all U.S. abortions in 2017, and 54% in 2020. Europe In France, the percentage of medication abortions of all abortions continues to increase: 38% in 2003, 42% in 2004, 44% in 2005, 46% in 2006, 49% in 2007 (vs. 18% in 1996). In England and Wales, 52% of early abortions (less than 9 weeks gestation) in 2009 were medication-based; the percentage of all abortions that are medication-based has increased every year for the past 14 years (from 5% in 1995 to 40% in 2009) and has more than doubled in the last five years. In Scotland, 81.2% of early abortions in 2009 were medication-based (up from 55.8% in 1992 when medication abortion was introduced); the percentage of all abortions that are medication-based has increased every year for the past 17 years (from 16.4% in 1992 to 69.9% in 2009). In Sweden, 85.6% of early abortions and 73.2% of abortions before the end of the 12th week of gestation in 2009 were medication-based; 68.2% of all abortions in 2009 were medication-based. In Great Britain and Sweden, mifepristone is licensed for use with vaginal gemeprost or oral misoprostol. As of 2000, more than 620,000 women in Europe had had medication abortions using a mifepristone regimen. In Denmark, mifepristone was used in between 3,000 and 4,000 of just over 15,000 abortions in 2005. Legal status United States Mifepristone was approved for abortion in the United States by the FDA in September 2000. It is legal and available in all 50 states, Washington, D.C., Guam, and Puerto Rico. It is a prescription drug, but was not initially available to the public through pharmacies; its distribution is primarily restricted to specially qualified licensed physicians, sold by Danco Laboratories under the trade name Mifeprex. As of September 2021, in 32 states, the drug could only be provided by a licensed physician, and in 19 states, the prescribing clinician was required to be physically in the room with the patient while they are taking the drug.Roussel Uclaf did not seek U.S. approval, so in the United States legal availability was not initially possible. The United States banned importation of mifepristone for personal use in 1989, a decision supported by Roussel Uclaf. In 1994, Roussel Uclaf gave the U.S. drug rights to the Population Council in exchange for immunity from any product liability claims. The Population Council sponsored clinical trials in the United States. The drug went on approvable status from 1996. Production was intended to begin through the Danco Group in 1996, but they withdrew briefly in 1997 due to a corrupt business partner, delaying availability again.In 2016, the US Food and Drug Administration approved mifepristone, to end a pregnancy through 70 days gestation (70 days or less since the first day of a womans last menstrual period). The approved dosing regimen is 200 mg of mifepristone taken by mouth (swallowed). 24 to 48 hours after taking mifepristone, 800 mcg (micrograms) of misoprostol is taken buccally (in the cheek pouch), at a location appropriate for the patient.Mifepristone tablets have a marketing authorization in the United States for the treatment of high blood sugar caused by high cortisol levels in the blood (hypercortisolism) in adults with endogenous Cushings syndrome who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or cannot have surgery.In 2019, the first generic form of mifepristone in the United States became available, manufactured by GenBioPro.Due to the COVID-19 pandemic, safe access to mifepristone was a concern, and the American College of Obstetricians and Gynecologists among other groups filed a lawsuit to relax the FDAs rule as to allow mifepristone to be acquired from mail-order and retail pharmacies. While the Fourth Circuit had granted a preliminary injunction to allow this distribution, the Supreme Court of the United States issued a stay order in January 2021 to retain the FDAs rule pending the results of the ongoing litigation.On 16 December 2021, the FDA voluntarily adopted a new rule permanently relaxing the requirement that the pill be obtained in person, allowing it to be sent through the mail. A prescription is still required, so that a doctor can screen for risk factors that would make taking the pill unsafe for the mother. Subsection H Some drugs are approved by the FDA under subsection H, which has two subparts. The first sets forth ways to rush experimental drugs, such as aggressive HIV and cancer treatments, to market when speedy approval is deemed vital to the health of potential patients. The second part of subsection H applies to drugs that not only must meet restrictions for use due to safety requirements, but also are required to meet postmarketing surveillance to establish that the safety results shown in clinical trials are seconded by use in a much wider population. Until December 2021, Mifepristone was approved under the second part of subsection H. The result is that women could not pick the drug up at a pharmacy, but were required to receive it directly from a doctor. Due to the possibility of adverse reactions such as excessive bleeding, which may require a blood transfusion, and incomplete abortion, which may require surgical intervention, the drug was only considered safe if a physician who is capable of administering a blood transfusion or a surgical abortion is available to the patient in the event of such emergencies. The approval of mifepristone under subsection H included a black box warning. Europe Outside the United States, mifepristone is marketed and distributed by Exelgyn Laboratories under the tradename Mifegyne. It was approved for use in France in 1988 (initial marketing in 1989), the United Kingdom in 1991, Sweden in 1992, then Austria, Belgium, Denmark, Finland, Germany, Greece, Luxembourg, the Netherlands, Spain, and Switzerland in 1999. In 2000, it was approved in Norway, Russia and Ukraine. Serbia and Montenegro approved it in 2001, Belarus and Latvia in 2002, Estonia in 2003, Moldova in 2004, Albania and Hungary in 2005, Portugal in 2007, Romania in 2008, Bulgaria, Czech Republic and Slovenia in 2013. In Italy, clinical trials have been constrained by protocols requiring women be hospitalized for three days, but the drug was finally approved on 30 July 2009 (officialized later in the year), despite strong opposition from the Vatican. In Italy, the pill must be prescribed and used in a clinical structure and is not sold at chemists. It was approved in Hungary in 2005, but as of 2005 had not been released on the market yet, and was the target of protests. Mifepristone is currently licensed in Ireland for use of abortions up to 12 weeks since it was legalised in 2018. Mifepristone is not available in Poland, where abortion is highly restricted.Mifepristone 200 mg tablets (Mifegyne, Mifepristone Linepharma, Medabon) have marketing authorizations in the European Economic Area from the European Medicines Agency (EMA) for: Early first trimester medication abortion when followed by a prostaglandin analog (misoprostol or gemeprost) through 63 days gestational age Second trimester medication abortion when followed by a prostaglandin analog Cervical softening and dilation prior to first trimester surgical abortion Induction of labor after fetal death in utero when prostaglandin analogs and oxytocin are contraindicated Other countries Mifepristone was banned in Australia in 1996. In late 2005, a private members bill was introduced to the Australian Senate to lift the ban and transfer the power of approval to the Therapeutic Goods Administration (TGA). The move caused much debate in the Australian media and among politicians. The bill passed the Senate on 10 February 2006, and mifepristone is now legal in Australia. It is provided regularly at several specialized abortion clinics per state. Mifepristone 200 mg tablets have marketing authorizations in Australia from the TGA for early first trimester medication abortion when followed by the prostaglandin analog misoprostol through 63 days gestational age and second trimester medication abortion when followed by a prostaglandin analog.In New Zealand, pro-abortion rights doctors established an import company, Istar, and submitted a request for approval to Medsafe, the New Zealand pharmaceutical regulatory agency. After a court case brought by Right to Life New Zealand failed, use of mifepristone was permitted.Mifepristone was approved in Israel in 1999.Clinical trials of mifepristone in China began in 1985. In October 1988, China became the first country in the world to approve mifepristone. Chinese organizations tried to purchase mifepristone from Roussel Uclaf, which refused to sell it to them, so in 1992 China began its own domestic production of mifepristone. In 2000, the cost of medication abortion with mifepristone was higher than surgical abortion and the percentage of medication abortions varied greatly, ranging from 30% to 70% in cities to being almost nonexistent in rural areas. A report from the United States Embassy in Beijing in 2000 said mifepristone had been widely used in Chinese cities for about two years, and that according to press reports, a black market had developed with many women starting to buy it illegally (without a prescription) from private clinics and drugstores for about US$15 (equivalent to $23.6 in 2021), causing Chinese authorities to worry about medical complications from use without physician supervision.In 2001, mifepristone was approved in Taiwan. Vietnam included mifepristone in the National Reproductive Health program in 2002.Mifepristone is approved in only one sub-Saharan African country—South Africa, where it was approved in 2001. It is also approved in one north African country—Tunisia, also in 2001.Mifepristone was approved for use in India in 2002, where medication abortion is referred to as "medical termination of pregnancy". It is only available under medical supervision, not by prescription, due to adverse reactions such as excessive bleeding, and criminal penalties are given for buying or selling it on the black market or over-the-counter at pharmacies.medication abortion used to be available in Canada but on a limited basis using methotrexate and misoprostol. Clinical trials were done in 2000 in various Canadian cities comparing methotrexate to mifepristone, after approbation by the federal government. While both drugs had overall similar results, mifepristone was found to act faster. Health Canada gave approval to mifepristone in July 2015. Initially, its use was limited to seven weeks into a pregnancy, but this was changed to nine weeks in 2017. The previous requirement of written consent from the woman was also ended at the same time. It can be dispensed directly to a patient by a pharmacist or a prescribing health professional. Women are required to have an ultrasound to ensure the pregnancy is not ectopic.Mifepristone was registered for use in Azerbaijan, Georgia, and Uzbekistan in 2002, in Guyana and Moldova in 2004, in Mongolia in 2005, and in Armenia in 2007.Low dose mifepristone tablets (Bi Yun, Fu Nai Er, Hou Ding Nuo, Hua Dian, Si Mi An) for emergency contraception are available directly from a pharmacist without a prescription and with a prescription in China.Low dose mifepristone tablets for emergency contraception are available by prescription in Armenia (Gynepriston), Russia (Agesta, Gynepriston, Mifepristone 72, Negele), Ukraine (Gynepriston), and Vietnam (Mifestad 10, Ciel EC). Controversy Many anti-abortion groups in the United States actively campaigned against the approval of mifepristone and continue to actively campaign for its withdrawal. They cite either ethical issues with abortion or safety concerns regarding the drug and the adverse reactions associated with it. In March 2022, during a debate in the Kentucky House of Representatives about anti-abortion legislation, Republican representative Danny Bentley made several false claims, including the assertion that mifepristone had originally been called Zyklon B and had been developed by the Nazis during World War Two. After several Jewish advocacy groups including the American Jewish Committee complained about Bentleys comments, he later apologized for any harm he had caused, stating that he "clearly should have been more sensitive with (his) comments", but failed to correct the false statement regarding the development of the drug.Religious and anti-abortion groups outside the United States have also protested mifepristone, especially in Germany and Australia. Research The original target for the research group was the discovery and development of compounds with antiglucocorticoid properties. These antiglucocorticoid properties are of great interest in the treatment of severe mood disorders and psychosis, although a review of published articles was inconclusive on their efficacy, and considered the use of these drugs in mood disorders at proof of concept stage.Use of mifepristone as a cervical ripening agent has been described. The medication has been studied as an antiandrogen in the treatment of prostate cancer. Mifepristone showed no detectable anti-HIV activity in clinical trials.Mifepristone showed initial promise in psychotic major depression, a difficult-to-treat form of depression, but a phase-III clinical trial was terminated early due to lack of efficacy. It has been studied in bipolar disorder, post traumatic stress disorder, and anorexia nervosa. References External links "Mifepristone". Drug Information Portal. U.S. National Library of Medicine.

You serve as a medical tutor. Your objective is to demystify medical terms, providing thorough explanations that cater to various levels of medical knowledge.

I'm not familiar with the medical term 'Snatiation.' Could you provide some insights?

Snatiation is a term coined to refer to the a medical condition originally termed "stomach sneeze reflex", which is characterized by uncontrollable bursts of sneezing brought on by fullness of the stomach, typically immediately after a large meal. The type of food consumed does not appear to affect its occurrence. It is reported, based on a preliminary study, to be passed along genetically as an autosomal dominant trait, as first described by Ahmad Teebi and Qasem Al-Saleh in 1989. The term "snatiation", coined shortly thereafter in a humorous letter to the Journal of Medical Genetics by Judith G. Hall, is a portmanteau of the words sneeze and satiation. Similar in nature to this condition is gustatory rhinitis, which involves rhinorrhea induced by certain foods, such as spicy foods. See also Photic sneeze reflex References External links Online Mendelian Inheritance in Man (OMIM): Gastric Sneezing - 137130

You are a conduit for medical education. Your task is to offer detailed explanations of medical terms, ensuring they are understandable and precise.

I've encountered the term 'Sporotrichosis' while reading about medical topics. What does it refer to exactly?

Sporotrichosis, also known as rose handlers disease, is a fungal infection that affects skin, lungs, bone and joint, and can be widespread. It presents with firm painless nodules that later ulcerate. It can be localized or widespread. The disease progresses over a week to several months after the initial exposure to the fungus. Serious complications can also develop in people who have a weakened immune system.Sporotrichosis is caused by fungi of the Sporothrix schenckii species complex. Because S. schenckii is naturally found in soil, hay, sphagnum moss, and plants, it usually affects farmers, gardeners, and agricultural workers. It enters through small cuts in the skin to cause the infection. In case of sporotrichosis affecting the lungs, the fungal spores enter by breathing in. Sporotrichosis can also be acquired from handling cats with the disease; it is an occupational hazard for veterinarians.Treatment depends on the site and extent of infection. Topical antifungals can be applied to skin lesions. Deep infection in lungs may require surgery. Medications used include Itraconazole, posaconazole and amphotericin B. With treatment most people recover. The outcome may not be so good if there is a weak immune system or widespread disease.The causal fungus is found worldwide. The species was named for Benjamin Schenck, a medical student who in 1896 was the first to isolate it from a human specimen.It has been reported in cats, mules, dogs, mice and rats. Signs and symptoms Cutaneous or skin sporotrichosisThis is the most common form of this disease. Symptoms of this form include nodular lesions or bumps in the skin, at the point of entry and also along lymph nodes and vessels. The lesion starts off small and painless, and ranges in color from pink to purple. Left untreated, the lesion becomes larger and look similar to a boil and more lesions will appear, until a chronic ulcer develops.Usually, cutaneous sporotrichosis lesions occur in the finger, hand, and arm.Pulmonary sporotrichosisThis rare form of the disease occur when S. schenckii spores are inhaled. Symptoms of pulmonary sporotrichosis include productive coughing, nodules and cavitations of the lungs, fibrosis, and swollen hilar lymph nodes. Patients with this form of sporotrichosis are susceptible to developing tuberculosis and pneumoniaDisseminated sporotrichosisWhen the infection spreads from the primary site to secondary sites in the body, the disease develops into a rare and critical form called disseminated sporotrichosis. The infection can spread to joints and bones (called osteoarticular sporotrichosis) as well as the central nervous system and the brain (called sporotrichosis meningitis).The symptoms of disseminated sporotrichosis include weight loss, anorexia, and appearance of bony lesions. Complications Sporotrichosis lesions on the skin can become infected with bacteria. Cellulitis may also occur. Diagnosis Sporotrichosis is a chronic disease with slow progression and often subtle symptoms. It is difficult to diagnose, as many other diseases share similar symptoms and therefore must be ruled out. Patients with sporotrichosis will have antibody against the fungus S. schenckii, however, due to variability in sensitivity and specificity, it may not be a reliable diagnosis for this disease. The confirming diagnosis remains culturing the fungus from the skin, sputum, synovial fluid, and cerebrospinal fluid. Smears should be taken from the draining tracts and ulcers. Cats with sporotrichosis are unique in that the exudate from their lesions may contain numerous organisms. This makes cytological evaluation of exudate a valuable diagnostic tool in this species. Exudate is pyogranulomatous and phagocytic cells may be packed with yeast forms. These are variable in size, but many are cigar-shaped. Differential diagnosis Differential diagnosis includes: leishmaniasis, nocardiosis, mycobacterium marinum, cat-scratch disease, leprosy, syphilis, sarcoidosis and tuberculosis. Prevention The majority of sporotrichosis cases occur when the fungus is introduced through a cut or puncture in the skin while handling vegetation containing the fungal spores. Prevention of this disease includes wearing long sleeves and gloves while working with soil, hay bales, rose bushes, pine seedlings, and sphagnum moss. The risk of sporotrichosis in cats is increased in male cats that roam outdoors. Accordingly, the risk may be reduced by keeping cats indoors or neutering them. Isolating infected animals can also be a preventive measure. The risk of spread from infected cats to humans can be reduced by appropriate biosafety measures, including wearing protective equipment when handling a cat with suspected sporotrichosis and by washing hands, arms and clothing after handling the cat. Treatment Treatment of sporotrichosis depends on the severity and location of the disease. The following are treatment options for this condition: Oral potassium iodidePotassium iodide is an anti-fungal drug that is widely used as a treatment for cutaneous sporotrichosis. Despite its wide use, there is no high-quality evidence for or against this practice. Further studies are needed to assess the efficacy and safety of oral potassium iodide in the treatment of sporotrichosis.Itraconazole (Sporanox) and fluconazoleThese are antifungal drugs. Itraconazole is currently the drug of choice and is significantly more effective than fluconazole. Fluconazole should be reserved for patients who cannot tolerate itraconazole.Amphotericin BThis antifungal medication is delivered intravenously. Many patients, however, cannot tolerate Amphotericin B due to its potential side effects of fever, nausea, and vomiting. Lipid formulations of amphotericin B are usually recommended instead of amphotericin B deoxycholate because of a better adverse-effect profile. Amphotericin B can be used for severe infection during pregnancy. For children with disseminated or severe disease, amphotericin B deoxycholate can be used initially, followed by itraconazole.In case of sporotrichosis meningitis, the patient may be given a combination of Amphotericin B and 5-fluorocytosine/Flucytosine.Terbinafine500mg and 1000mg daily dosages of terbinafine for twelve to 24 weeks has been used to treat cutaneous sporotrichosis.Newer triazolesSeveral studies have shown that posaconazole has in vitro activity similar to that of amphotericin B and itraconazole; therefore, it shows promise as an alternative therapy. However, voriconazole susceptibility varies. Because the correlation between in vitro data and clinical response has not been demonstrated, there is insufficient evidence to recommend either posaconazole or voriconazole for treatment of sporotrichosis at this time.SurgeryIn cases of bone infection and cavitary nodules in the lungs, surgery may be necessary.Heat therapyHeat creates higher tissue temperatures, which may inhibit fungus growth while the immune system counteracts the infection. The "pocket warmer" used for this purpose has the advantage of being able to maintain a constant temperature of 44 degrees-45 degrees C on the skin surface for several hours, while permitting unrestricted freedom of movement. The duration of treatment depends on the type of lesion, location, depth, and size. Generally, local application for 1-2 h per day, or in sleep time, for 5-6 weeks seems to be sufficient. Other animals Sporotrichosis can be diagnosed in domestic and wild mammals. In veterinary medicine it is most frequently seen in cats and horses. Cats have a particularly severe form of cutaneous sporotrichosis. Infected cats may exhibit abscesses, cellulitis, or draining wounds that fail to respond to antibiotic treatment.Sporotrichosis can spread from nonhuman animals to humans (zoonosis). Infected cats in particular exude large quantities of Sporothrix organisms from their skin leasions and can spread the infection to people who handle them. Although cats are the most common animal source, the infection has also been known to spread to humans from dogs, rats, squirrels, and armadillos. See also Mucormycosis List of cutaneous conditions References External links Sporotrichosis by Health in Plain English (with pictures) Sporotrichosis by Centers for Disease Control and Prevention (CDC)

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

I'm seeking clarification on the medical term 'Papulosquamous disorder.' Could you explain it?

A papulosquamous disorder is a condition which presents with both papules and scales, or both scaly papules and plaques.Examples include psoriasis, lichen planus, and pityriasis rosea. See also List of cutaneous conditions References Further reading Norman RA, Blanco PM (2003). "Papulosquamous diseases in the elderly". Dermatologic Therapy. 16 (3): 231–42. doi:10.1046/j.1529-8019.2003.01633.x. PMID 14510880. http://www.emedicine.com/derm/index.shtml#papulosquamous == External links ==

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

I'm not familiar with the medical term 'Precocious puberty.' Could you provide some insights?

In medicine, precocious puberty is puberty occurring at an unusually early age. In most cases, the process is normal in every aspect except the unusually early age and simply represents a variation of normal development. In a minority of children with precocious puberty, the early development is triggered by a disease such as a tumor or injury of the brain. Even when there is no disease, unusually early puberty can have adverse effects on social behavior and psychological development, can reduce adult height potential, and may shift some lifelong health risks. Central precocious puberty can be treated by suppressing the pituitary hormones that induce sex steroid production. The opposite condition is delayed puberty.The term is used with several slightly different meanings that are usually apparent from the context. In its broadest sense, and often simplified as early puberty, "precocious puberty" sometimes refers to any physical sex hormone effect, due to any cause, occurring earlier than the usual age, especially when it is being considered as a medical problem. Stricter definitions of "precocity" may refer only to central puberty starting before a statistically specified age based on percentile in the population (e.g., 2.5 standard deviations below the population mean), on expert recommendations of ages at which there is more than a negligible chance of discovering an abnormal cause, or based on opinion as to the age at which early puberty may have adverse effects. A common definition for medical purposes is onset before 8 years in girls or 9 years in boys. Causes Early pubic hair, breast, or genital development may result from natural early maturation or from several other conditions. Central If the cause can be traced to the hypothalamus or pituitary, the cause is considered central. Other names for this type are complete or true precocious puberty.Causes of central precocious puberty can include: hypothalamic hamartoma produces pulsatile gonadotropin-releasing hormone (GnRH) Langerhans cell histiocytosis McCune–Albright syndromeCentral precocious puberty can also be caused by brain tumors, infection (most commonly tuberculous meningitis, especially in developing countries), trauma, hydrocephalus, and Angelman syndrome. Precocious puberty is associated with advancement in bone age, which leads to early fusion of epiphyses, thus resulting in reduced final height and short stature.Adrenocortical oncocytomas are rare with mostly benign and nonfunctioning tumors. There have been only three cases of functioning adrenocortical oncocytoma that have been reported up until 2013. Children with adrenocortical oncocytomas will present with "premature pubarche, clitoromegaly, and increased serum dehydroepiandrosterone sulfate and testosterone" which are some of the presentations associated with precocious puberty.Precocious puberty in girls begins before the age of 8. The youngest mother on record is Lina Medina, who gave birth at the age of either 5 years, 7 months and 17 days or 6 years 5 months as mentioned in another report."Central precocious puberty (CPP) was reported in some patients with suprasellar arachnoid cysts (SAC), and SCFE (slipped capital femoral epiphysis) occurs in patients with CPP because of rapid growth and changes of growth hormone secretion."If no cause can be identified, it is considered idiopathic or constitutional. Peripheral Secondary sexual development induced by sex steroids from other abnormal sources is referred to as peripheral precocious puberty or precocious pseudopuberty. It typically presents as a severe form of disease with children. Symptoms are usually as a sequelae from adrenal hyperplasia (because of 21-hydroxylase deficiency or 11-beta hydroxylase deficiency, the former being more common), which includes but is not limited to hypertension, hypotension, electrolyte abnormalities, ambiguous genitalia in females, signs of virilization in females. Blood tests will typically reveal high level of androgens with low levels of cortisol. Causes can include: Endogenous sources Gonadal tumors (such as arrhenoblastoma) Adrenal tumors Germ cell tumor Congenital adrenal hyperplasia McCune–Albright syndrome Silver–Russell syndrome Familial male-limited precocious puberty (testotoxicosis) Exogenous hormones Environmental exogenous hormones As treatment for another condition Isosexual and heterosexual Generally, patients with precocious puberty develop phenotypically appropriate secondary sexual characteristics. This is called isosexual precocity.In some cases, a patient may develop characteristics of the opposite sex. For example, a male may develop breasts and other feminine characteristics, while a female may develop a deepened voice and facial hair. This is called heterosexual or contrasexual precocity. It is very rare in comparison to isosexual precocity and is usually the result of unusual circumstances. As an example, children with a very rare genetic condition called aromatase excess syndrome – in which exceptionally high circulating levels of estrogen are present – usually develop precocious puberty. Males and females are hyper-feminized by the syndrome. The "opposite" case would be the hyper-masculinisation of both male and female patients with congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency, in which there is an excess of androgens. Thus, in the aromatase excess syndrome the precocious puberty is isosexual in females and heterosexual in males, whilst in the CAH its isosexual in males and heterosexual in females. Research Although the causes of early puberty are still somewhat unclear, girls who have a high-fat diet and are not physically active or are obese are more likely to physically mature earlier. "Obese girls, defined as at least 10 kilograms (22 pounds) overweight, had an 80 percent chance of developing breasts before their ninth birthday and starting menstruation before age 12 – the western average for menstruation is about 12.7 years." In addition to diet and exercise habits, exposure to chemicals that mimic estrogen (known as xenoestrogens) is another possible cause of early puberty in girls. Bisphenol A, a xenoestrogen found in hard plastics, has been shown to affect sexual development. "Factors other than obesity, however, perhaps genetic and/or environmental ones, are needed to explain the higher prevalence of early puberty in black versus white girls." While more girls are increasingly entering puberty at younger ages, new research indicates that some boys are actually starting later (delayed puberty). "Increasing rates of obese and overweight children in the United States may be contributing to a later onset of puberty in boys, say researchers at the University of Michigan Health System."High levels of beta-hCG in serum and cerebrospinal fluid observed in a 9-year-old boy suggest a pineal gland tumor. The tumor is called a chorionic gonadotropin secreting pineal tumor. Radiotherapy and chemotherapy reduced tumor and beta-hCG levels normalized.In a study using neonatal melatonin on rats, results suggest that elevated melatonin could be responsible for some cases of early puberty.Familial cases of idiopathic central precocious puberty (ICPP) have been reported, leading researchers to believe there are specific genetic modulators of ICPP. Mutations in genes such as LIN28, and LEP and LEPR, which encode leptin and the leptin receptor, have been associated with precocious puberty. The association between LIN28 and puberty timing was validated experimentally in vivo, when it was found that mice with ectopic over-expression of LIN28 show an extended period of pre-pubertal growth and a significant delay in puberty onset.Mutations in the kisspeptin (KISS1) and its receptor, KISS1R (also known as GPR54), involved in GnRH secretion and puberty onset, are also thought to be the cause for ICPP However, this is still a controversial area of research, and some investigators found no association of mutations in the LIN28 and KISS1/KISS1R genes to be the common cause underlying ICPP.The gene MKRN3, which is a maternally imprinted gene, was first cloned by Jong et al. in 1999. MKRN3 was originally named Zinc finger protein 127. It is located on human chromosome 15 on the long arm in the Prader-Willi syndrome critical region2, and has since been identified as a cause of premature sexual development or CPP. The identification of mutations in MKRN3 leading to sporadic cases of CPP has been a significant contribution to better understanding the mechanism of puberty. MKRN3 appears to act as a "brake" on the central hypothalamic-pituitary access. Thus, loss of function mutations of the protein allow early activation of the GnRH pathway and cause phenotypic CPP. Patients with a MKRN3 mutation all display the classic signs of CCP including early breast and testes development, increased bone aging and elevated hormone levels of GnRH and LH. Diagnosis Studies indicate that breast development in girls and the appearance of pubic hair in both girls and boys are starting earlier than in previous generations. As a result, "early puberty" in children as young as 9 and 10 is no longer considered abnormal, particularly with girls. Although it is not considered as abnormal, it may be upsetting to parents and can be harmful to children who mature physically at a time when they are immature mentally.No age reliably separates normal from abnormal processes in children, but the following age thresholds for evaluation are thought to minimize the risk of missing a significant medical problem: Breast development in boys before appearance of pubic hair or testicular enlargement Pubic hair or genital enlargement (gonadarche) in boys with onset before 9 years Pubic hair (pubarche) before 8 or breast development (thelarche) in girls with onset before 7 years Menstruation (menarche) in girls before 10 yearsMedical evaluation is sometimes necessary to recognize the few children with serious conditions from the majority who have entered puberty early but are still medically normal. Early sexual development warrants evaluation because it may: induce early bone maturation and reduce eventual adult height indicate the presence of a tumour or other serious problem cause the child, particularly a girl, to become an object of adult sexual interest. Treatment One possible treatment is with anastrozole. GnRH agonists, including histrelin, triptorelin, or leuprorelin, are other possible treatments. Non-continuous use of GnRH agonists stimulates the pituitary gland to release follicle stimulating hormone (FSH) and luteinizing hormone (LH). Prognosis Early puberty is posited to put girls at higher risk of sexual abuse; however, a causal relationship is, as yet, inconclusive. Early puberty also puts girls at a higher risk for teasing or bullying, mental health disorders and short stature as adults. Girls as young as 8 are increasingly starting to menstruate, develop breasts and grow pubic and underarm hair; these "biological milestones" typically occurred only at 13 or older in the past. African-American girls are especially prone to early puberty.Though boys face fewer problems from early puberty than girls do, early puberty is not always positive for boys. Early sexual maturation in boys can be accompanied by increased aggressiveness due to the surge of pubertal hormones. Because they appear older than their peers, pubescent boys may face increased social pressure to conform to adult norms; society may view them as more emotionally advanced, although their cognitive and social development may lag behind their physical development. Studies have shown that early-maturing boys are more likely to be sexually active and are more likely to participate in risky behaviors. History Pubertas praecox is the Latin term used by physicians from the 1790s onward. Various hypotheses and inferences on pubertal (menstrual, procreative) timing are attested since ancient times, which, well into early modernity were explained on the basis of temperamental, humoral and Jungian "complexional" causes, or general or local "plethora" (blood excess). Endocrinological (hormonal) theories and discoveries are a twentieth-century development. See also List of youngest birth mothers List of youngest birth fathers Premature menopause Premature ovarian failure References == External links ==

You are a facilitator of medical knowledge. Provide thorough and accessible explanations of medical terms, catering to both specialists and non-specialists.

Could you offer a clear explanation of the term 'Toxic oil syndrome' as used in the medical field?

Toxic oil syndrome (TOS) or simply toxic syndrome (Spanish: síndrome del aceite tóxico or síndrome tóxico) is a musculoskeletal disease. A 1981 outbreak in Spain which affected about 20,000 people, with over 300 dying within a few months and a few thousand remaining disabled, is thought to have been caused by contaminated colza (rapeseed) oil. It was unique because of its size, the novelty of the clinical condition, and the complexity of its aetiology. Its first appearance was as a lung disease, with unusual features, though the symptoms initially resembled a lung infection. The disease appeared to be restricted to certain geographical localities, and several members of a family could be affected, even while their neighbours had no symptoms. Following the acute phase, a range of other chronic symptoms was apparent. Alternative mechanisms The conclusion of the Joint WHO/CISAT Scientific Committee for the Toxic Oil Syndrome from 2002, that oil was the cause for TOS, is based only on epidemiological evidence, since up to now, experimental studies performed in a variety of laboratory animals have failed to reproduce the symptoms of human TOS. None of the in vivo or in vitro studies performed with toxic-oil-specific components, such as fatty acid anilides, and esters of 3-(N-phenylamino)-1,2-propanediol (abbreviated as PAP), have provided evidence that these markers are causally involved in the pathogenesis of TOS.Specifically, three possible causative agents of TOS are PAP (3-(N-phenylamino)-1,2-propanediol), the 1,2-dioleoyl ester of PAP (abbreviated OOPAP), and the 3-oleoyl ester of PAP (abbreviated OPAP). These three compounds are formed by means of similar chemical processes, and oil that contains one of the three substances is likely to contain the other two. Oil samples that are suspected to have been ingested by people who later developed TOS often contain all three of these contaminants (among other substances), but are most likely to contain OOPAP. However, when these three substances were given to laboratory animals, OOPAP was not acutely toxic, PAP was toxic only after injection, but not after oral administration, and OPAP was toxic only after injection of high doses. Therefore, none of these three substances is thought to cause TOS. Similar results were obtained after administration of fatty acid anilides.Data discrepancies combined with both a high level of secrecy surrounding the huge investigation and the fact that the first cases of the syndrome were located in Madrid (near the U.S. military base in Torrejón de Ardoz) spread the idea of a conspiracy. Several of those affected by TOS claim they never consumed any of the tainted oil products. Furthermore, the tainted oil was primarily sold in low-cost street markets; yet, a considerable percentage of the patients were wealthy. Another theory suggests the toxic reaction was triggered by organophosphate poisoning (e. g., from pesticide residues in tomatoes) and covered up by the Spanish government and the WHO. See also Eosinophilia-myalgia syndrome Ginger Jake Health crisis The Jungle List of food contamination incidents References External links WHO Report: Toxic Oil Syndrome - Ten years of progress

You are a medical advisor. Your role is to break down medical terminology into clear, detailed explanations for a general audience.

Could you provide a brief overview of 'Erectile dysfunction' in a medical context?

Erectile dysfunction (ED), also called impotence, is the type of sexual dysfunction in which the penis fails to become or stay erect during sexual activity. It is the most common sexual problem in men. Through its connection to self-image and to problems in sexual relationships, erectile dysfunction can cause psychological harm. In about 80% of cases, physical causes can be identified. These include cardiovascular disease; diabetes mellitus; neurological problems, such as those following prostatectomy; hypogonadism; and drug side effects. About 10% of cases are psychological impotence, caused by thoughts or feelings; here, there is a strong response to placebo treatment. The term erectile dysfunction is not used for other disorders of erection, such as priapism. Treatment involves addressing the underlying causes, lifestyle modifications, and addressing psychosocial problems. In many cases, treatment is attempted by drugs, specifically PDE5 inhibitors (such as sildenafil), which dilate blood vessels, allowing more blood to flow through the spongy tissue of the penis (akin to opening a valve further in order to allow more water to enter a fire hose). Other treatments, less commonly used, include prostaglandin pellets, inserted in the urethra; smooth-muscle relaxants and vasodilators, injected into the penis; penile implants; penis pumps; and vascular reconstructive surgery. Signs and symptoms ED is characterized by the regular or repeated inability to achieve or maintain an erection of sufficient rigidity to accomplish sexual activity. It is defined as the "persistent or recurrent inability to achieve and maintain a penile erection of sufficient rigidity to permit satisfactory sexual activity for at least 3 months." Psychological impact ED often has an impact on the emotional well-being of both men and their partners. Many men do not seek treatment due to feelings of embarrassment. About 75% of diagnosed cases of ED go untreated. Causes Causes of or contributors to ED include the following: Diets high in saturated fat are linked to heart diseases, and men with heart diseases are more likely to experience ED. By contrast, plant-based diets show a lower risk for ED. Prescription drugs (e.g., SSRIs, beta blockers, antihistamines, alpha-2 adrenergic receptor agonists, thiazides, hormone modulators, and 5α-reductase inhibitors) Neurogenic disorders (e.g., diabetic neuropathy, temporal lobe epilepsy, multiple sclerosis, Parkinsons disease, multiple system atrophy) Cavernosal disorders (e.g., Peyronies disease) Hyperprolactinemia (e.g., due to a prolactinoma) Psychological causes: performance anxiety, stress, and mental disorders Surgery (e.g., radical prostatectomy) Ageing: after age 40 years, ageing itself is a risk factor for ED, although numerous other pathologies that may occur with ageing, such as testosterone deficiency, cardiovascular diseases, or diabetes, among others, appear to have interacting effects Kidney disease: ED and chronic kidney disease have pathological mechanisms in common, including vascular and hormonal dysfunction, and may share other comorbidities, such as hypertension and diabetes mellitus that can contribute to ED Lifestyle habits, particularly smoking, which is a key risk factor for ED as it promotes arterial narrowing. Due to its propensity for causing detumescence and erectile dysfunction, some studies have described tobacco as an anaphrodisiacal substance. COVID-19: preliminary research indicates that COVID-19 viral infection may affect sexual and reproductive healthSurgical intervention for a number of conditions may remove anatomical structures necessary to erection, damage nerves, or impair blood supply. ED is a common complication of treatments for prostate cancer, including prostatectomy and destruction of the prostate by external beam radiation, although the prostate gland itself is not necessary to achieve an erection. As far as inguinal hernia surgery is concerned, in most cases, and in the absence of postoperative complications, the operative repair can lead to a recovery of the sexual life of people with preoperative sexual dysfunction, while, in most cases, it does not affect people with a preoperative normal sexual life.ED can also be associated with bicycling due to both neurological and vascular problems due to compression. The increased risk appears to be about 1.7-fold.Concerns that use of pornography can cause ED have little support in epidemiological studies, according to a 2015 literature review. According to Gunter de Win, a Belgian professor and sex researcher, "Put simply, respondents who watch 60 minutes a week and think theyre addicted were more likely to report sexual dysfunction than those who watch a care-free 160 minutes weekly." Pathophysiology Penile erection is managed by two mechanisms: the reflex erection, which is achieved by directly touching the penile shaft, and the psychogenic erection, which is achieved by erotic or emotional stimuli. The former involves the peripheral nerves and the lower parts of the spinal cord, whereas the latter involves the limbic system of the brain. In both cases, an intact neural system is required for a successful and complete erection. Stimulation of the penile shaft by the nervous system leads to the secretion of nitric oxide (NO), which causes the relaxation of the smooth muscles of the corpora cavernosa (the main erectile tissue of the penis), and subsequently penile erection. Additionally, adequate levels of testosterone (produced by the testes) and an intact pituitary gland are required for the development of a healthy erectile system. As can be understood from the mechanisms of a normal erection, impotence may develop due to hormonal deficiency, disorders of the neural system, lack of adequate penile blood supply or psychological problems. Spinal cord injury causes sexual dysfunction, including ED. Restriction of blood flow can arise from impaired endothelial function due to the usual causes associated with coronary artery disease, but can also be caused by prolonged exposure to bright light. Diagnosis In many cases, the diagnosis can be made based on the persons history of symptoms. In other cases, a physical examination and laboratory investigations are done to rule out more serious causes such as hypogonadism or prolactinoma.One of the first steps is to distinguish between physiological and psychological ED. Determining whether involuntary erections are present is important in eliminating the possibility of psychogenic causes for ED. Obtaining full erections occasionally, such as nocturnal penile tumescence when asleep (that is, when the mind and psychological issues, if any, are less present), tends to suggest that the physical structures are functionally working. Similarly, performance with manual stimulation, as well as any performance anxiety or acute situational ED, may indicate a psychogenic component to ED.Another factor leading to ED is diabetes mellitus, a well known cause of neuropathy). ED is also related to generally poor physical health, poor dietary habits, obesity, and most specifically cardiovascular disease, such as coronary artery disease and peripheral vascular disease. Screening for cardiovascular risk factors, such as smoking, dyslipidemia, hypertension, and alcoholism, is helpful.In some cases, the simple search for a previously undetected groin hernia can prove useful since it can affect sexual functions in men and is relatively easily curable.The current diagnostic and statistical manual of mental diseases (DSM-IV) lists ED. Ultrasonography Penile ultrasonography with doppler can be used to examine the erect penis. Most cases of ED of organic causes are related to changes in blood flow in the corpora cavernosa, represented by occlusive artery disease (in which less blood is allowed to enter the penis), most often of atherosclerotic origin, or due to failure of the veno-occlusive mechanism (in which too much blood circulates back out of the penis). Before the Doppler sonogram, the penis should be examined in B mode, in order to identify possible tumors, fibrotic plaques, calcifications, or hematomas, and to evaluate the appearance of the cavernous arteries, which can be tortuous or atheromatous.Erection can be induced by injecting 10–20 µg of prostaglandin E1, with evaluations of the arterial flow every five minutes for 25–30 min (see image). The use of prostaglandin E1 is contraindicated in patients with predisposition to priapism (e.g., those with sickle cell anemia), anatomical deformity of the penis, or penile implants. Phentolamine (2 mg) is often added. Visual and tactile stimulation produces better results. Some authors recommend the use of sildenafil by mouth to replace the injectable drugs in cases of contraindications, although the efficacy of such medication is controversial.Before the injection of the chosen drug, the flow pattern is monophasic, with low systolic velocities and an absence of diastolic flow. After injection, systolic and diastolic peak velocities should increase, decreasing progressively with vein occlusion and becoming negative when the penis becomes rigid (see image below). The reference values vary across studies, ranging from > 25 cm/s to > 35 cm/s. Values above 35 cm/s indicate the absence of arterial disease, values below 25 cm/s indicate arterial insufficiency, and values of 25–35 cm/s are indeterminate because they are less specific (see image below). The data obtained should be correlated with the degree of erection observed. If the peak systolic velocities are normal, the final diastolic velocities should be evaluated, those above 5 cm/s being associated with venogenic ED. Other workup methods Penile nerves function Tests such as the bulbocavernosus reflex test are used to ascertain whether there is enough nerve sensation in the penis. The physician squeezes the glans (head) of the penis, which immediately causes the anus to contract if nerve function is normal. A physician measures the latency between squeeze and contraction by observing the anal sphincter or by feeling it with a gloved finger in the anus.Nocturnal penile tumescence (NPT) It is normal for a man to have five to six erections during sleep, especially during rapid eye movement (REM). Their absence may indicate a problem with nerve function or blood supply in the penis. There are two methods for measuring changes in penile rigidity and circumference during nocturnal erection: snap gauge and strain gauge. A significant proportion [give us the percentage] of men who have no sexual dysfunction nonetheless do not have regular nocturnal erections.Penile biothesiometry This test uses electromagnetic vibration to evaluate sensitivity and nerve function in the glans and shaft of the penis.Dynamic infusion cavernosometry (DICC) Technique in which fluid is pumped into the penis at a known rate and pressure. It gives a measurement of the vascular pressure in the corpus cavernosum during an erection.Corpus cavernosometry Cavernosography measurement of the vascular pressure in the corpus cavernosum. Saline is infused under pressure into the corpus cavernosum with a butterfly needle, and the flow rate needed to maintain an erection indicates the degree of venous leakage. The leaking veins responsible may be visualized by infusing a mixture of saline and x-ray contrast medium and performing a cavernosogram. In Digital Subtraction Angiography (DSA), the images are acquired digitally.Magnetic resonance angiography (MRA) This is similar to magnetic resonance imaging. Magnetic resonance angiography uses magnetic fields and radio waves to provide detailed images of the blood vessels. The doctor may inject into the patients bloodstream a contrast agent, which causes vascular tissues to stand out against other tissues, so that information about blood supply and vascular anomalies is easier to gather. Treatment Treatment depends on the underlying cause. In general, exercise, particularly of the aerobic type, is effective for preventing ED during midlife. Counseling can be used if the underlying cause is psychological, including how to lower stress or anxiety related to sex. Medications by mouth and vacuum erection devices are first-line treatments,: 20, 24  followed by injections of drugs into the penis, as well as penile implants.: 25–26  Vascular reconstructive surgeries are beneficial in certain groups. Treatments, other than surgery, do not fix the underlying physiological problem, but are used as needed before sex. Medications The PDE5 inhibitors sildenafil (Viagra), vardenafil (Levitra) and tadalafil (Cialis) are prescription drugs which are taken by mouth.: 20–21  As of 2018, sildenafil is available in the UK without a prescription. Additionally, a cream combining alprostadil with the permeation enhancer DDAIP has been approved in Canada as a first line treatment for ED. Penile injections, on the other hand, can involve one of the following medications: papaverine, phentolamine, and prostaglandin E1, also known as alprostadil. In addition to injections, there is an alprostadil suppository that can be inserted into the urethra. Once inserted, an erection can begin within 10 minutes and last up to an hour. Medications to treat ED may cause a side effect called priapism. Prevalence of medical diagnosis In a study published in 2016, based on US health insurance claims data, out of 19,833,939 US males aged ≥18 years, only 1,108,842 (5.6%), were medically diagnosed with erectile dysfunction or on a PDE5I prescription (μ age 55.2 years, σ 11.2 years). Prevalence of diagnosis or prescription was the highest for age group 60–69 at 11.5%, lowest for age group 18–29 at 0.4%, and 2.1% for 30–39, 5.7% for 40–49, 10% for 50–59, 11% for 70–79, 4.6% for 80–89, 0.9% for ≥90, respectively. Focused shockwave therapy Focused shockwave therapy involves passing short, high frequency acoustic pulses through the skin and into the penis. These waves break down any plaques within the blood vessels, encourage the formation of new vessels, and stimulate repair and tissue regeneration.Focused shockwave therapy appears to work best for men with vasculogenic ED, which is a blood vessel disorder that affects blood flow to tissue in the penis. The treatment is painless and has no known side effects. Treatment with shockwave therapy can lead to a significant improvement of the IIEF (International Index of Erectile Function). Testosterone Men with low levels of testosterone can experience ED. Taking testosterone may help maintain an erection. Men with type 2 diabetes are twice as likely to have lower levels of testosterone, and are three times more likely to experience ED than non-diabetic men. Pumps A vacuum erection device helps draw blood into the penis by applying negative pressure. This type of device is sometimes referred to as penis pump and may be used just prior to sexual intercourse. Several types of FDA approved vacuum therapy devices are available under prescription. When pharmacological methods fail, a purpose-designed external vacuum pump can be used to attain erection, with a separate compression ring fitted to the base of the penis to maintain it. These pumps should be distinguished from other penis pumps (supplied without compression rings) which, rather than being used for temporary treatment of impotence, are claimed to increase penis length if used frequently, or vibrate as an aid to masturbation. More drastically, inflatable or rigid penile implants may be fitted surgically. Surgery Often, as a last resort, if other treatments have failed, the most common procedure is prosthetic implants which involves the insertion of artificial rods into the penis.: 26  Some sources show that vascular reconstructive surgeries are viable options for some people. Alternative medicine The Food and Drug Administration (FDA) does not recommend alternative therapies to treat sexual dysfunction. Many products are advertised as "herbal viagra" or "natural" sexual enhancement products, but no clinical trials or scientific studies support the effectiveness of these products for the treatment of ED, and synthetic chemical compounds similar to sildenafil have been found as adulterants in many of these products. The FDA has warned consumers that any sexual enhancement product that claims to work as well as prescription products is likely to contain such a contaminant. A 2021 review indicated that ginseng had "only trivial effects on erectile function or satisfaction with intercourse compared to placebo". History Attempts to treat ED date back well over 1,000 years. In the 8th century, men of Ancient Rome and Greece wore talismans of rooster and goat genitalia, believing these talismans would serve as an aphrodisiac and promote sexual function. In the 13th century Albertus Magnus recommended ingesting roasted wolf penis as a remedy for impotence.During the late 16th and 17th centuries in France, male impotence was considered a crime, as well as legal grounds for a divorce. The practice, which involved inspection of the complainants by court experts, was declared obscene in 1677.The first successful vacuum erection device, or penis pump, was developed by Vincent Marie Mondat in the early 1800s. A more advanced device, based on a bicycle pump, was developed by Geddings Osbon, a Pentecostal preacher, in the 1970s. In 1982, he received FDA approval to market the product as the ErecAid®.John R. Brinkley initiated a boom in male impotence cures in the U.S. in the 1920s and 1930s. His radio programs recommended expensive goat gland implants and "mercurochrome" injections as the path to restored male virility, including operations by surgeon Serge Voronoff. Modern drug therapy for ED made a significant advance in 1983, when British physiologist Giles Brindley dropped his trousers and demonstrated to a shocked Urodynamics Society audience his papaverine-induced erection. The drug Brindley injected into his penis was a non-specific vasodilator, an alpha-blocking agent, and the mechanism of action was clearly corporal smooth muscle relaxation. The effect that Brindley discovered established the fundamentals for the later development of specific, safe, and orally effective drug therapies.The current first-line treatment for ED, the oral PDE5 inhibitor, was introduced by Pfizer in 1999. Anthropology Anthropological research presents ED not as a disorder but, as a normal, and sometimes even welcome sign of healthy aging. Wentzells study of 250 Mexican men in their 50s and 60s found that “most simply did not see decreasing erectile function as a biological pathology”. The men interviewed described the decrease in erectile function “as an aid for aging in socially appropriate ways”. A common theme amongst the interviewees showed that respectable older men shifted their focus toward the domestic sphere into a “second stage of life”. The Mexican men of this generation often pursued sex outside of marriage; decreasing erectile function acted as an aid to overcoming infidelity thus helping to attain the ideal “second stage” of life. A 56-year-old about to retire from the public health service said he would now "dedicate myself to my wife, the house, gardening, caring for the grandchildren—the Mexican classic". Wentzell found that treating ED as a pathology was antithetical to the social view these men held of themselves, and their purpose at this stage of their lives. In the 20th and 21st centuries, anthropologists investigated how common treatments for ED are built upon assumptions of institutionalized social norms. In offering a range of clinical treatments to ‘correct’ a persons ability to produce an erection, biomedical institutions encourage the public to strive for prolonged sexual function. Anthropologists argue that a biomedical focus places emphasis on the biological processes of fixing the body thereby disregarding holistic ideals of health and aging. By relying on a wholly medical approach, Western biomedicine can become blindsided by bodily dysfunctions which can be understood as appropriate functions of age, and not as a medical problem. Anthropologists understand that a biosocial approach to ED considers a persons decision to undergo clinical treatment more likely a result of "society, political economy, history, and culture" than a matter of personal choice. In rejecting biomedical treatment for ED, men can challenge common forms of medicalized social control by deviating from what is considered the normal approach to dysfunction. Lexicology The Latin term impotentia coeundi describes simple inability to insert the penis into the vagina; it is now mostly replaced by more precise terms, such as erectile dysfunction (ED). The study of ED within medicine is covered by andrology, a sub-field within urology. Research indicates that ED is common, and it is suggested that approximately 40% of males experience symptoms compatible with ED, at least occasionally. The condition is also on occasion called phallic impotence. Its antonym, or opposite condition, is priapism. References Further reading Carson, Culley; Faria, Geraldo; Hellstrom, Wayne J. G.; Krishnamurti, Sudhakar; Minhas, Suks; Moncada, Ignacio; Montague, Drogo K. (1 January 2010). "Implants, Mechanical Devices, and Vascular Surgery for Erectile Dysfunction". Journal of Sexual Medicine. Wiley. 7 (1): 501–523. doi:10.1111/j.1743-6109.2009.01626.x. PMID 20092450. External links Erectile dysfunction at Curlie

You serve as a guide in the medical field. Explain medical terms thoroughly, ensuring the information is both insightful and comprehensible.

What does the medical term 'Choanal atresia' encompass?

Choanal atresia is a congenital disorder where the back of the nasal passage (choana) is blocked, usually by abnormal bony or soft tissue (membranous) due to failed hole development of the nasal fossae during prenatal development. It causes persistent rhinorrhea, and with bilateral choanal atresia and obstructed airway that can cause cyanosis and hypoxia. Choanal atresia is diagnosed based on the inability to place a nasal catheter, and radiology results (particularly CT scans). Treatment involves maintaining an open airway, and may involve surgery to reopen the airway, potentially with a stent. Choanal atresia is a fairly rare condition, affecting between 1 in 7,000 to 1 in 5,000 live births. Presentation Choanal atresia can be unilateral or bilateral. A unilateral choanal atresia may not be detected until much later in life because the baby manages to get along with only one nostril available for breathing. Symptoms are minor, including persistent rhinorrhea (mainly normal mucus) and chronic sinusitis. Bilateral choanal atresia is a life-threatening condition because the baby will be unable to breathe directly after birth as babies are obligate nasal breathers (they mainly use their noses to breathe). In some cases, this may present as cyanosis while the baby is feeding, because the oral air passages are blocked by the tongue, further restricting the airway. Cyanosis may improve when the baby cries, as the oral airway is used. These babies may require airway resuscitation soon after birth. Associated conditions Choanal atresia is associated with a higher risk of other airway problems, including: tracheomalacia. laryngomalacia. subglottic stenosis.Sometimes, babies born with choanal atresia also have other abnormalities: coloboma. heart defects and cardiovascular disease. intellectual disability. growth impairment. genital hypoplasia. CHARGE syndrome. others.Also any condition that causes significant depression of the nasal bridge or midface retraction can be associated with choanal atresia. Examples include the craniosynostosis syndromes such as Crouzon syndrome, Pfeiffer syndrome, Treacher Collins syndrome, Apert syndrome, and Antley-Bixler syndrome. Cause Choanal atresia is caused by problems with the development of the nasal cavity and the palate. Development begins with neural crest cells. Frontonasal processes fold, forming nasal placodes (nasal pits). The nasobuccal membrane must rupture in places to form the choanae. A number of theories exist as to how this developmental process causes choanal atresia. Risk factors Very few risk factors for choanal atresia have been identified. In general, choanal atresia is associated with a higher risk of other birth defects. Bilateral choanal atresia is more associated than unilateral choanal atresia.While causes are unknown, both genetic and environmental triggers are suspected. One study suggests that chemicals that act as endocrine disrupters may put an unborn infant at risk. A 2012 epidemiological study looked at atrazine, a commonly used herbicide in the U.S., and found that women who lived in counties in Texas with the highest levels of this chemical being used to treat agricultural crops were 80 times more likely to give birth to infants with choanal atresia or stenosis compared to women who lived in the counties with the lowest levels. Another epidemiological report in 2010 found even higher associations between increased incidents of choanal atresia and exposure to second-hand-smoke, coffee consumption, high maternal zinc and B-12 intake and exposure to anti-infective urinary tract medications. The anti-thyroid medication methimazole has been associated with the development of choanal atresia in rare cases if given during the first trimester of pregnancy. Mechanism Choanal atresia causes closure of the posterior choanae in the nasal cavity. Around 30% of these affect just the bone, while around 70% affect both bone and membranes. Bones affected can include the body of the sphenoid bone, the vomer, the medial pterygoid process of the sphenoid bone, and the horizontal plate of the palatine bone. Diagnosis Nasal catheter Choanal atresia can be suspected if it is impossible to insert a nasal catheter. The length of catheter that can be inserted indicates where choanal atresia has occurred: shorter distances indicate a problem with the vomer, while longer distances indicate a problem with the posterior choanae. Mucus can be cleared (using suction) to visualise the abnormality. Radiology Diagnosis is confirmed using CT scan. This is also useful for differential diagnosis. Treatment Airway management As bilateral choanal atresia is an emergency, the airway is secured. A small tube may be placed to the laryngopharynx. Tracheal intubation can also be used. If surgery cannot be performed soon after birth, tracheostomy may have better outcomes. Surgery Surgery may be used to reopen the airway, particularly with bilateral choanal atresia. This may be approaches through the nasal cavity or through the palate (accessed through the mouth). A stent may be inserted to keep the newly formed airway patent. Repeated dilatation may be performed. CT guidance may be used. Epidemiology Choanal atresia is fairly rare. It may have a frequency between 1 in 7,000 births and 1 in 5,000 births. History Choanal atresia was first described by Roederer in 1755. Society and culture In the movie City of Angels, Dr. Maggie Rice (played by Meg Ryan) correctly diagnoses the cause of a newborn babys failure to thrive as due to choanal atresia. References == External links ==

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Could you please explain the term 'Myhre syndrome' in simple language?

Myhre syndrome is a rare genetic disorder inherited in an autosomal dominant fashion. It is caused by mutation in SMAD4 gene. Signs and symptoms The clinical presentation is variable but includes developmental and growth delay athletic muscular built skeletal anomalies joint stiffness characteristic facial appearance deafness variable cognitive deficits tracheal stenosis aortic stenosis pyloric stenosisThe facial abnormalities include: blepharophimosis (an abnormally narrow gap between the upper and lower eyelids) maxillary hypoplasia (underdevelopment of the upper jaw) prognathism (prominent lower jaw)The skeletal abnormalities include: short stature square body shape broad ribs iliac hypoplasia brachydactyly flattened vertebrae thickened calvariaCongenital heart disease and undescended testes have also been reported in association with this syndrome. Genetics Myhre syndrome is due to mutations in the SMAD4 gene. This gene encodes a protein - transducer mediating transforming growth factor beta. Some researchers believe that the SMAD4 gene mutations that cause Myhre syndrome impair the ability of the SMAD4 protein to attach (bind) properly with the other proteins involved in the signaling pathway. Other studies have suggested that these mutations result in an abnormally stable SMAD4 protein that remains active in the cell longer. Changes in SMAD4 binding or availability may result in abnormal signaling in many cell types, which affects development of several body systems and leads to the signs and symptoms of Myhre syndrome.The patients of this disease exhibit hypertrophic phenotype in their muscle tissues. Myostatin target genes are found to be downregulated while bone morphogenetic protein (BMP) target genes display both upregulated and downregulated genotypes. Diagnosis Treatment History This disorder was first reported in 1981. It has many similarities to LAPS Syndrome and they both arise from the same mutations in the SMAD4 gene. It is believed that they are the same syndrome. References This article incorporates text from the United States National Library of Medicine ([1]), which is in the public domain. == External links ==

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I'm not familiar with the medical term 'Mitochondrial DNA depletion syndrome.' Could you provide some insights?

Mitochondrial DNA depletion syndrome (MDS or MDDS), or Alpers disease, is any of a group of autosomal recessive disorders that cause a significant drop in mitochondrial DNA in affected tissues. Symptoms can be any combination of myopathic, hepatopathic, or encephalomyopathic. These syndromes affect tissue in the muscle, liver, or both the muscle and brain, respectively. The condition is typically fatal in infancy and early childhood, though some have survived to their teenage years with the myopathic variant and some have survived into adulthood with the SUCLA2 encephalomyopathic variant. There is currently no curative treatment for any form of MDDS, though some preliminary treatments have shown a reduction in symptoms. Signs and symptoms All forms of MDDS are very rare. MDDS causes a wide range of symptoms, which can appear in newborns, infants, children, or adults, depending on the class of MDDS; within each class symptoms are also diverse.In MDDS associated with mutations in TK2, infants generally develop normally, but by around two years of age, symptoms of general muscle weakness (called "hypotonia"), tiredness, lack of stamina, and difficulty feeding begin to appear. Some toddlers start to lose control of the muscles in their face, mouth, and throat, and may have difficulty swallowing. Motor skills that had been learned may be lost, but generally the functioning of the brain and ability to think are not affected.In MDDS associated with mutations in SUCLA2 or SUCLG1 that primarily affect the brain and muscle, hypotonia generally arises in infants before they are 6 months old, their muscles begin wasting away, and there is delay in psychomotor learning (learning basic skills like walking, talking, and intentional, coordinated movement). The spine often begins to curve (scoliosis or kyphosis), and the child often has abnormal movements (dystonia, athetosis or chorea), difficulty feeding, acid reflux, hearing loss, stunted growth, and difficulty breathing that can lead to frequent lung infections. Sometime epilepsy develops.In MDDS associated with mutations in RRM2B that primarily affect the brain and muscle, there is again hypotonia in the first months, symptoms of lactic acidosis like nausea, vomiting, and rapid deep breathing, failure to thrive including the head remaining small, delay or regression in moving, and hearing loss. Many body systems are affected. The Charlie Gard case was associated with this sub form of the disease.In MDDS associated with mutations in DGUOK that primarily affect the brain and the liver, there are two forms. There is an early-onset form in which symptoms arise from problems in many organs in the first week of life, especially symptoms of lactic acidosis as well as low blood sugar. Within weeks of birth they can develop liver failure and the associated jaundice and abdominal swelling, and many neurological problems including developmental delays and regression, and uncontrolled eye movement. Rarely within this class of already rare diseases, symptoms only relating to liver disease emerge later in infancy or in childhood.In MDDS associated with mutations in MPV17 that primarily affect the brain and the liver, the symptoms are similar to those caused by DGUOK and also emerge shortly after birth, generally with fewer and less severe neurological problems. There is a subset of people of Navajo descent who develop Navajo neurohepatopathy, who in addition to these symptoms also have easily broken bones that do not cause pain, deformed hands or feet, and problems with their corneas.In MDDS associated with mutations in POLG that primarily affect the brain and the liver, the symptoms are very diverse and can emerge anytime from shortly after birth to old age. The first signs of the disease, which include intractable seizures and failure to meet meaningful developmental milestones, usually occur in infancy, after the first year of life, but sometimes as late as the fifth year. Primary symptoms of the disease are developmental delay, progressive intellectual disability, hypotonia (low muscle tone), spasticity (stiffness of the limbs) possibly leading to quadriplegia, and progressive dementia. Seizures may include epilepsia partialis continua, a type of seizure that consists of repeated myoclonic (muscle) jerks. Optic atrophy may also occur, often leading to blindness. Hearing loss may also occur. Additionally, although physical signs of chronic liver dysfunction may not be present, many people experience liver impairment leading to liver failure.In MDDS associated with mutations in PEO1/C10orf2 that primarily affect the brain and the liver, symptoms emerge shortly after birth or in early infancy, with hypotonia, symptoms of lactic acidosis, enlarged liver, feeding problems, lack of growth, and delay of psychomotor skills. Neurologically, development is slowed or stopped, and epilepsy emerges, as do sensory problems like loss of eye control and deafness, and neuromuscular problems like a lack of reflexes, muscular atrophy, and twitching, and epilepsy.In MDDS associated with mutations in the genes associated with mutations in ECGF1/TYMP that primarily affects the brain and the gastrointestinal tract, symptoms can emerge any time in the first fifty years of life; most often they emerge before the person turns 20. Weight loss is common as is a lack of the ability of the stomach and intestines to automatically expand and contract and thus move through it (called gastrointestinal motility) – this leads to feeling full after eating only small amounts of food, nausea, acid reflux, All affected individuals develop weight loss and progressive gastrointestinal dysmotility manifesting as early satiety, nausea, diarrhea, vomiting, and stomach pain and swelling. People also develop neuropathy, with weakness and tingling. There are often eye problems, and intellectual disability. Causes MDDS is caused by mutations that may be inherited from the parents or may form spontaneously during development of the fetus. MDDS is associated with mutations in the genes TK2, SUCLA2, RRM2B, DGUOK, POLG, TYMP, SUCLG1, and TWNK.Myopathic MDS is strongly correlated to a variety of mutations in the gene TK2, seeing a reduction of TK2 activity to less than 32% in people with MDS found with the mutation. Because TK2 plays a key role in the mitochondrial salvage pathways of several deoxyribonucleoside triphosphates (dNTPs), a lowered activity would lead to less cycling of nucleotides. This lack of nucleotide recycling is detrimental since the mitochondria cannot synthesize entirely new deoxynucleotides, and the inner membrane of the mitochondria prevents the negatively charged nucleotides of the cytosol from entering.The SUCLA2 gene codes for the beta-subunit of SCS-A. This enzyme catalyzes the synthesis of succinate and coenzyme A into succinyl-CoA, but is also associated with the complex formed by nucleoside diphosphate kinase (NDPK) in the last step of the dNTP salvage pathway.The RRM2B gene, which is expressed in the cell nucleus, codes for one of two versions of the R2 subunit of ribonucleotide reductase, which generates nucleotide precursors required for DNA replication by reducing ribonucleoside diphosphates to deoxyribonucleoside diphosphates. The version of R2 encoded by RRM2B is induced by TP53, and is required for normal DNA repair and mtDNA synthesis in non-proliferating cells. The other form of R2 is expressed only in dividing cells.The DGUOK gene encodes for mitochondrial deoxyguanosine kinase (dGK), which catalyzes the phosphorylation of deoxyribonucleosides into nucleotides. POLG encodes for the catalytic subunit pol γA, which is part of mitochondrial DNA polymerase.Other causes are mutations of thymidine phosphorylase (TyMP), succinate-CoA ligase, alpha sub unit (SUCLG1) and TWNK (also known as PEO1 and C10orf2). Diagnosis MDDS is diagnosed based on systemic symptoms presenting in infants, followed by a clinical examination and laboratory tests (for example, high lactate levels are common) medical imaging, and usually is finally confirmed and formally identified by genetic testing. Classification MDDS are a group of genetic disorders that share a common pathology — a lack of functioning DNA in mitochondria. There are generally four classes of MDDS: a form that primarily affects muscle associated with mutations in the TK2 gene; a form that primarily affects the brain and muscle associated with mutations in the genes SUCLA2, SUCLG1, or RRM2B; a form that primarily affects the brain and the liver associated with mutations in DGUOK, MPV17, POLG, or TWNK (also called PEO1); and a form that primarily affects the brain and the gastrointestinal tract associated with mutations in ECGF1 (also called TYMP). Treatment There are no treatments for MDDS, but some of the symptoms can be managed. For survivors living with MDDS, there are drugs to control epilepsy, and physical therapy can help with muscle control. Liver transplants may benefit people with liver involvement. Prognosis Myopathic form The TK2 related myopathic form results in muscle weakness, rapidly progresses, leading to respiratory failure and death within a few years of onset. The most common cause of death is pulmonary infection. Only a few people have survived to late childhood and adolescence. Encephalomyopathic form SUCLA2 and RRM2B related forms result in deformities to the brain. A 2007 study based on 12 cases from the Faroe Islands (where there is a relatively high incidence due to a founder effect) suggested that the outcome is often poor with early lethality. More recent studies (2015) with 50 people with SUCLA2 mutations, with range of 16 different mutations, show a high variability in outcomes with a number of people surviving into adulthood (median survival was 20 years). There is significant evidence (p = 0.020) that people with missense mutations have longer survival rates, which might mean that some of the resulting protein has some residual enzyme activity.RRM2B mutations have been reported in 16 infants with severe encephalomyopathic MDS that is associated with early-onset (neonatal or infantile), multi-organ presentation, and mortality during infancy. Hepatopathic form DGUOK, POLG, and MPV17 related forms result in defects to the liver. Liver dysfunction is progressive in the majority of individuals with both forms of DGUOK-related MDS and is the most common cause of death. For children with the multi-organ form, liver transplantation provides no survival benefit.Liver disease typically progresses to liver failure in affected children with MPV17-related MDS and liver transplantation remains the only treatment option for liver failure. Approximately half of affected children reported did not undergo liver transplantation and died because of progressive liver failure – the majority during infancy or early childhood. A few children were reported to survive without liver transplantation. Research Nucleoside bypass therapy is an experimental treatment aimed to restore the normal levels of deoxyribonucleotides (dNTPs) in mitochondria. See also Charlie Gard case References == External links ==

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

Please help me grasp the concept behind the medical term '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

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I'm encountering the term 'Carnivore protoparvovirus 1' in medical literature. What's its definition?

Carnivore protoparvovirus 1 (CPPV 1) is a species of parvovirus that infects carnivorans. It causes a highly contagious disease in both dogs and cats. The disease is generally divided into two major genogroups: CPV-1 containing the classical feline panleukopenia virus (FPLV), and CPV-2 containing the canine parvovirus (CPV) which appeared in the 1970s.FPLV is known to infect all wild and domestic members of the felid (cat) family worldwide. It is a highly contagious, severe infection that causes gastrointestinal, immune system, and nervous system disease. Its primary effect is to decrease the number of white blood cells, causing the disease known as feline panleukopenia. It was once thought that only CPV-1 or FPLV infects cats. However, it has been confirmed that a feline panleukopenia illness can be caused by CPV 2a, 2b, and 2c.FPLV is commonly referred to as: feline infectious enteritis virus (FIE) feline parvovirus (FPV or FP or "feline parvo") feline parvoviral enteritisIt is sometimes confusingly referred to as "cat plague" and "feline distemper".In addition to members of the felid family, it can also affect other carnivorans (e.g. raccoon, mink). Etymology Formed within English using elements derived from Greek: pan- a combining form meaning "universal" or "worldwide", -leuco- a combining form meaning (in biologic sciences) "white blood cell", and -penia a combining form meaning "loss of" or "decrease of". Thus the word means universal loss of white blood cells. The universal part refers to both its worldwide distribution and to the fact that all species of cats are infected. Transmission The feline panleukopenia virus is considered ubiquitous, meaning it is in virtually every place that is not regularly disinfected. The infection is highly contagious among unvaccinated cats.Antibodies against FPLV, produced by the adaptive immune system, play an important role in the feline response to the virus. Maternally-derived antibodies (MDA) efficiently protect kittens from fatal infection. This passively acquired immunity is later replaced by an active immune response obtained by vaccination or as a consequence of a natural infection. In kittens, the period of greatest susceptibility to infection is when maternal antibodies are absent, or waning, and vaccine-induced immunity has not yet fully developed.Free-roaming cats are thought to be exposed to the virus during their first year of life. Those that develop a subclinical infection or survive acute illness mount a robust, long-lasting, protective immune response.An infected cat sheds large amounts of virus in all body secretions including feces, vomit, urine, saliva, and mucus during the acute phase of illness. It can continue to shed the virus for as long as 6 weeks after recovery. Subclinically ill cats can also shed the virus in body secretions. The virus can be carried or transferred on an infected object (such as bedding, food dishes, fur) or by other animals, fleas, and humans (see: fomites). It persists long after evidence of the original body secretion has faded away, and can be transported long distances. Like all parvoviruses, FPLV is extremely resistant to inactivation and can survive for longer than one year in a suitable environment. Kitten deaths have been reported in households of fully vaccinated cats, possibly because of exposure to large amounts of virus in the environment.Infection occurs when the virus enters the body through the mouth or nose. Whether illness results or not depends on the immunity in the victim vs. the number of individual virus particles (i.e. the amount of virus) entering the body. Clinical signs The clinical manifestations of FPLV are variable based on the dose of the virus, the age of the cat, potential breed predispositions, and prior immunity from maternal antibodies, previous exposure, or vaccination. Most infections are subclinical, as evidenced by the high seroprevalence of anti-FPV antibodies among some populations of unvaccinated, healthy cats. The cats that become clinically ill are usually less than one year old, but older cats are also at risk. There is high mortality in clinically affected kittens and sudden death can occur.Clinical signs usually develop in 4–6 days after exposure, but can show in 2–14 days. The virus infects and destroys actively dividing cells in bone marrow, lymphoid tissues, intestinal epithelium, and—in very young animals—in the cerebellum and retina. The virus primarily attacks the lining of the gastrointestinal tract, causing internal ulceration and, ultimately, total sloughing of the intestinal epithelium. Primary signs include: anorexia lethargy profuse watery to bloody diarrhea (bloody diarrhea is more common in dogs with parvovirus than cats) vomiting (most common in cats)Clinical laboratory findings include (but are not limited to): electrolyte and total protein concentrations that reflect dehydration, vomiting, and diarrhea. leukopenia lymphopenia neutropenia thrombocytopeniaOther signs include: fever, loss of skin elasticity due to dehydration, abdominal pain, sternal recumbency with splayed legs and head droop, nasal discharge and conjunctivitis. Cats may sit at a water bowl, but not drink. Terminal cases are hypothermic and may develop septic shock and disseminated intravascular coagulation.Infection in pregnant cats can result in fetal resorption, mummification, abortion, or stillbirth of neonates. Fetuses infected in utero that survive and kittens less than a few weeks of age that become infected can have cerebellar hypoplasia, retinal dysplasia, and optic neuropathy. Diagnosis A presumptive clinical diagnosis of FPLV can be made for kittens with appropriate signalment, history, clinical findings and the history of no prior vaccination.The clinical diagnosis is usually supported by documenting parvovirus antigen in feces by ELISA (enzyme-linked immunosorbent assay) and PCR (polymerase chain reaction) assays. The availability of validated assays varies by country but is becoming more common. PCR assays are so sensitive that FPV DNA can be amplified from feces of cats vaccinated with modified live strains of the virus. At least one of the ELISA antigen tests for dogs (SNAP®Parvo; IDEXX Laboratories) detects FPV in feline feces and has a cut point for a positive test result that excludes most vaccinated cats. Thus, this ELISA is superior to PCR for screening cats for FPV infection and can also be performed in the veterinary clinic. (These are only approved and licensed for detecting canine parvovirus, but it is generally known that they also detect FPL viral antigen in feline feces. These tests are used extra-label because they allow rapid, inexpensive, in-house detection of the virus.) Some cats will have completed the shedding period by the time the test is run, leading to false-negative results. Electron microscopy, virus isolation and seroconversion can also be used to document active or recent infection. Leukopenia on a complete blood count (nadir 50–3,000 WBC/μL) supports a diagnosis of FPLV. In an unvaccinated cat, the presence of antibodies against FPV indicates that the cat either has the disease or has had the disease in the past. Elevated IgM titers (1:10 or greater) indicate active infection and if clinical signs are obvious (diarrhea, panleukopenia) the prognosis is poor. Elevated IgG titers (1:100 or greater) in a cat with clinical signs indicates a better prognosis.Differential diagnoses include salmonellosis, enteric toxins, feline immunodeficiency virus (FIV), feline leukemia virus (FeLV), cryptosporidiosis, pancreatitis, septicaemia with acute endotoxemia, toxoplasmosis, peritonitis, and lymphoma. Treatment To contain the virus, cats with suspected or diagnosed FPLV should be kept in isolation.It requires immediate, aggressive treatment if the cat is to survive, as it can be fatal in less than 24 hours. Several articles and publications provide guidance for rescuers and veterinarians for optimizing outcomes.Treatment involves: anti-emetics IV antibiotics intravenous fluids with electrolytes injections of vitamin B plasma or whole blood transfusionFeeding should be continued as long as possible. A highly digestible diet is preferred, but the individual animals preferences may dictate giving whatever it will eat. In anorexic, hypoproteinemic, vomiting and diarrheic cats parenteral nutrition is required.In a disease outbreak, unvaccinated kittens or adults can be given anti-FPV serum containing FPV antibodies injected subcutaneously or intraperitoneal. This may provide protection for 2–4 weeks. Therapeutic efficacy of anti-FPV serum has been demonstrated in dogs, and similar beneficial effects may be expected in cats.Several studies have shown recombinant feline interferon omega is effective in the treatment of parvoviral enteritis in dogs and also inhibits replication of FPV in cell culture. So far no data are available on its efficacy in FPV-infected cats. Complications Cats typically die due to complications associated with sepsis, dehydration, and disseminated intravascular coagulopathy (DIC). Leukocytopenia predisposes patients to secondary infections, especially bacterial and fungal, though secondary viral infections also occur. It has been stated that cats with FPLV may be at risk for endocarditis or cardiomyopathy (since CPV-2 is a well-known cause of viral myocarditis in young puppies), but a 2017 retrospective study concluded that "Feline Panleukopenia Virus Is Not Associated With Myocarditis or Endomyocardial Restrictive Cardiomyopathy in Cats". Prognosis Mortality in affected felid litters varies between 20 and 100%. Mortality of FPLV is 25–90% in domestic cats with the acute form of the disease and up to 100% in cats with peracute disease.In 2010, a retrospective study of 244 infected cats showed that "leukocyte and thrombocyte counts as well as serum albumin and potassium concentrations at presentation are prognostic indicators in cats with panleukopenia, whereas vaccination status, age, clinical signs, and housing conditions are not."A survival rate of about 50% has been reported with supportive therapies. Cats with FPLV that survive the first 5 days of treatment usually recover, however the decrease in the cats white blood cells compromises its immune system, leaving it vulnerable to secondary infection.Lifelong immunity is thought to follow recovery from disease, and a carrier state of the disease has never been identified. Preventing transmission from infected cats Quarantine/isolation Cats with suspected or diagnosed FPLV should be kept in isolation. This non-enveloped virus is very resistant to environmental conditions and many disinfectants, is highly contagious, and rapidly accumulates in the environment due to high shedding of virus from affected animals. Strict protocols for containment – with isolation, minimal handling, and disinfection of all potential sources of fomites – is warranted. Recovered cats can still shed the virus for up to 6 weeks and can carry it on their body for prolonged periods. Vaccination The practice of recommending and giving vaccines on a fixed schedule with annual boosters has been widely discarded. Current recommendations are based on the philosophy of vaccinating each cat no more frequently than necessary. These recommendations take into account considerations for the efficacy and longevity of each specific vaccine; the exposure, risk, and need of different cat populations; and socioeconomic limitations.Recommendations vary for: animal shelters boarding facilities (or animals going into them) breeders community cats (free-roaming and/or feral) or TNR (Trap Neuter Return) programs owned pets (and based on "inside only" or "in and out")The FPLV vaccination is considered a "core" (essential for health) vaccine and is recommended for all domestic cats. Even cats kept indoors can be infected from fomite transmission.Several types and brands of commercial FPLV vaccines are available to induce acquired immunity. These include: killed virus ("non-infectious") adjuvanted killed virus non adjuvanted modified-live virus (MLV or "infectious") adjuvanted modified-live virus non adjuvantedCombination vaccines that protect against several common viruses, including FPLV, are also available. Selection or use of a specific type/brand of a vaccine may vary depending on the overall risk of viral infection to the specific animal in its environment, along with considerations for the time it takes to confer protection, its overall efficacy, the animals health, and the potential risks associated with MLV vs killed, adjuvanted vs nonadjuvanted, intranasal/ocular vs injection. Modified-live FPLV vaccines are not recommended in pregnant queens, very young kittens, or cats with FIV or FeLV.Kittens without maternally derived antibodies are especially vulnerable. FPLV vaccination can start as early as 4 weeks of age for kittens at high risk but are usually started at 6 weeks, then given every 3 – 4 weeks until 16 weeks of age. For cats older than 16 weeks, 2 doses, 3 to 4 weeks apart is generally recommended, followed by a 6-month to 1-year booster. Thereafter, a booster vaccination every 3 years is usually recommended; a blood titer test can be done to determine individual antibody levels for catering the timing of boosters. References External links Feline Distemper (Panleukopenia) from The Pet Health Library How to Limit Parvo in Shelters, Rescues and Transfer Animals

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I'm not familiar with the medical term 'Hereditary fructose intolerance.' Could you provide some insights?

Hereditary fructose intolerance (HFI) is an inborn error of fructose metabolism caused by a deficiency of the enzyme aldolase B. Individuals affected with HFI are asymptomatic until they ingest fructose, sucrose, or sorbitol. If fructose is ingested, the enzymatic block at aldolase B causes an accumulation of fructose-1-phosphate which, over time, results in the death of liver cells. This accumulation has downstream effects on gluconeogenesis and regeneration of adenosine triphosphate (ATP). Symptoms of HFI include vomiting, convulsions, irritability, poor feeding as a baby, hypoglycemia, jaundice, hemorrhage, hepatomegaly, hyperuricemia and potentially kidney failure. While HFI is not clinically a devastating condition, there are reported deaths in infants and children as a result of the metabolic consequences of HFI. Death in HFI is always associated with problems in diagnosis.HFI is an autosomal recessive condition caused by mutations in the ALDOB gene, located at 9q31.1. HFI is typically suspected based on dietary history, especially in infants who become symptomatic after breast feeding. This suspicion is typically confirmed by molecular analysis Treatment of HFI involves strict avoidance of fructose in the diet. Older patients with HFI typically self-select a diet low in fructose, even before being diagnosed. Presentation The key identifying feature of HFI is the appearance of symptoms with the introduction of fructose to the diet. Affected individuals are asymptomatic and healthy, provided they do not ingest foods containing fructose or any of its common precursors, sucrose and sorbitol. In the past, infants often became symptomatic when they were introduced to formulas that were sweetened with fructose or sucrose. These sweeteners are not common in formulas used today. Symptoms such as vomiting, nausea, restlessness, pallor, sweating, trembling and lethargy can also first present in infants when they are introduced to fruits and vegetables. These can progress to apathy, coma and convulsions if the source is not recognized early.When patients are diagnosed with HFI, a dietary history will often reveal an aversion to fruit and other foods that contain large amounts of fructose. Most adult patients do not have any dental caries. Fructose metabolism After ingestion, fructose is converted to fructose-1-phosphate in the liver by fructokinase. Deficiencies of fructokinase cause essential fructosuria, a clinically benign condition characterized by the excretion of unmetabolized fructose in the urine. Fructose-1-phosphate is metabolized by aldolase B into dihydroxyacetone phosphate and glyceraldehyde. HFI is caused by a deficiency of aldolase B.A deficiency of aldolase B results in an accumulation of fructose-1-phosphate, and trapping of phosphate (fructokinase requires adenosine triphosphate (ATP)). The downstream effects of this enzyme block are the inhibition of glucose production and reduced regeneration of ATP. Diagnosis Because of the ease of therapy (dietary exclusion of fructose), HFI can be effectively managed if properly diagnosed. In HFI, the diagnosis of homozygotes is difficult, requiring a genomic DNA screening with allele-specific probes or an enzyme assay from a liver biopsy. Once identified, parents of infants who carry mutant aldolase B alleles leading to HFI, or older individuals who have clinical histories compatible with HFI can be identified and counselled with regard to preventive therapy: dietary exclusion of foods containing fructose, sucrose, or sorbitol. If possible, individuals who suspect they might have HFI should avoid testing via fructose challenge as the results are non-conclusive for individuals with HFI, and even if the diagnostic administration of fructose is properly controlled, profound hypoglycemia and its sequelae can threaten the patients well-being. Treatment Treatment of HFI depends on the stage of the disease, and the severity of the symptoms. Stable patients without acute intoxication events are treated by careful dietary planning that avoids fructose and its metabolic precursors. Fructose is replaced in the diet by glucose, maltose or other sugars. Management of patients with HFI often involves dietitians who have a thorough knowledge of what foods are acceptable. See also Fructose malabsorption References == External links ==

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I'm seeking clarification on the medical term 'Urethral hypermobility.' Could you explain it?

Urethral hypermobility is a condition of excessive movement of the female urethra due to a weakened urogenital diaphragm. It describes the instability of the urethra in relation to the pelvic floor muscles. A weakened pelvic floor muscle fails to adequately close the urethra and hence can cause stress urinary incontinence. This condition can be measured with anterior compartment descent. It is sometimes treated with urethral bulking injections. == References ==

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

What is the significance of the term 'Depression in childhood and adolescence' in the medical field?

Depression is a mental disorder characterized by prolonged unhappiness or irritability, accompanied by a constellation of somatic and cognitive signs and symptoms such as fatigue, apathy, sleep problems, loss of appetite, loss of engagement; low self-regard or worthlessness; difficulty concentrating or indecisiveness; or recurrent thoughts of death or suicide. Depression in childhood and adolescence is similar to adult major depressive disorder, although young sufferers may exhibit increased irritability or behavioral dyscontrol instead of the more common sad, empty, or hopeless feelings seen with adults. Children who are under stress, experiencing loss, or have other underlying disorders are at a higher risk for depression. Childhood depression is often comorbid with mental disorders outside of other mood disorders; most commonly anxiety disorder and conduct disorder. Depression also tends to run in families. In a 2016 Cochrane review cognitive behavior therapy (CBT), third wave CBT and interpersonal therapy demonstrated small positive benefits in the prevention of depression. Psychologists have developed different treatments to assist children and adolescents suffering from depression, though the legitimacy of the diagnosis of childhood depression as a psychiatric disorder, as well as the efficacy of various methods of assessment and treatment, remains controversial. Base rates and prevalence About 8% of children and adolescents suffer from depression. In 2016, 51 percent of students (teens) who visited a counseling center reported having anxiety, followed by depression (41 percent), relationship concerns (34 percent) and suicidal ideation (20.5 percent). Many students reported experiencing multiple conditions at once. Research suggests that the prevalence of children with Major Depressive Disorder in Western cultures ranges from 1.9% to 3.4% among primary school children. Amongst teenagers, up to 9% meet criteria for depression in a given moment and approximately 20% experience depression sometime during adolescence. Studies have also found that among children diagnosed with a depressive episode, there is a 70% rate of recurrence within five years. Furthermore, 50% of children with depression will have a recurrence at least once during their adulthood. While there is no gender difference in depression rates up until age 15, after that age the rate among women doubles compared to men. However, in terms of recurrence rates and symptom severity there is no gender difference. In an attempt to explain these findings, one theory asserts that preadolescent women on average have more risk factors for depression when compared to men. These risk factors then combine with the typical stresses and challenges of adolescent development to trigger the onset of depression. Depression in youth and adolescence is associated with a wide array of outcomes that can come later in life for the affected individual. Some of these outcomes include poor physical and mental health, trouble functioning socially, and suicide. Suicidal intent Like their adult counterparts, children and adolescent depression sufferers are at an increased risk of attempting or committing suicide. Suicide is the third leading cause of death among 15-to-19-year-olds. Adolescent males may be at an even higher risk of suicidal behavior when also presenting with a conduct disorder. In the 1990s, the National Institute of Mental Health (NIMH) found that up to 7% of adolescents who develop major depressive disorder may commit suicide as young adults. Such statistics demonstrate the importance of interventions by family and friends, the importance of early diagnosis, and treatment by medical staff, in order to prevent suicide amongst at-risk youth. However, some data showed an opposite conclusion. Most depression symptoms are reported more frequently by females; such as sadness (reported by 85.1% of women and 54.3% of men) and crying (approximately 63.4% of women and 42.9% of men). Women have a higher probability to experience depression than men with the prevalences of 19.2% and 13.5% respectively. Risk factor Risk factors for adolescent depression include female sex, a family history of depression, a personal history of trauma, family conflict, minority sexual orientation, or having a chronic medical illness. There tends to be higher prevalence rates and more severe symptoms in adolescent girls when compared to adolescent boys. These higher rates are also applicable in older adolescents when compared to younger adolescents. This may be due to hormonal fluctuations may that make adolescent women to be more vulnerable to depression. The fact that increased prevalence of depression correlates with hormonal changes in women, particularly during puberty, suggests that female hormones may be a trigger for depression. The gender gap in depression between adolescent men and women is mostly due to young womens lower levels of positive thinking, need for approval, and self-focusing negative conditions. Frequent exposure to victimization or bullying was related to high risks of depression, ideation and suicide attempts compared to those not involved in bullying. Nicotine dependence is also associated with depression, anxiety, and poor dieting, mostly in young men. Although causal direction has not been established, involvement in any sex or drug use is cause for concern. Children who develop major depression are more likely to have a family history of the disorder (often a parent who experienced depression at an early age) than patients with adolescent- or adult-onset depression. Adolescents with depression are also likely to have a family history of depression, though the correlation is not as high as it is for children. Comorbidity There is also a substantial comorbidity rate with depression in children with anxiety disorder, conduct disorder, and impaired social functioning. Particularly, there is a high comorbidity rate with anxiety, ranging from 15.9% to 75%. Conduct disorders also have a significant comorbidity with depression in children and adolescents with a rate of 23% in one longitudinal study. Beyond other clinical disorders, there is also an association between depression in childhood, poor psychosocial and academic outcomes, as well as a higher risk for substance abuse and suicide.The prevalence of psychiatric comorbidities during adolescence may vary by race and ethnicity. Social causes Adolescents are engaged in a search for identity and meaning in their lives. They have also been regarded as a unique group with a wide range of difficulties and problems in their transition to adulthood. Academic pressure, intrapersonal and interpersonal difficulties, death of loved ones, illnesses, and loss of relationships, have shown to be significant stressors in young people. While it is a normal part of development in adolescence to experience distressing and disabling emotions, there is an increasing incidence of mental illness globally. This is due mainly because of the breakdown in traditional social and family structures. Depression is usually a response to life events such as relationship issues, financial problems, physical illness, bereavement, etc. Some people can become depressed for no obvious reason and their suffering is just as real as those reacting from life events. Psychological makeup can also play a role in vulnerability to depression. People who have low self-esteem, constantly view themselves and the world with pessimism, or are readily overwhelmed by stress, may be especially prone to depression. Community surveys find that women are more likely than men to say they are under stress. Other studies suggest that women are more likely than men to become depressed in response to a stressful event. Women are also more likely to experience certain kinds of severe stress such as child sexual abuse, adult sexual assaults, and domestic violence. Diagnosis According to the DSM-IV, children must exhibit either a depressed mood or a loss of interest/pleasure in normal activities. These activities may include school, extracurricular activities, or peer interactions. Depressive moods in children can be expressed as being unusually irritable. These expressions may be displayed by "acting out," behaving recklessly, or reacting with anger/hostility. Children who do not have the cognitive or language development to properly express mood states can also exhibit their mood through physical complaints such as showing sad facial expressions (frowning) and poor eye contact. A child must also exhibit four other symptoms in order to be clinically diagnosed. However, according to the Omnigraphics Health References Series: Depression Sourcebook, Third Edition, a more calculated evaluation must be given by a medical or mental health professional such as a physiologist or psychiatrist. Following the bases of symptoms, signs include but are not limited to, an unusual change in sleep habits (for example, trouble sleeping or overly indulged sleeping hours); a significant amount of weight gain/loss by the lack or excessive eating; experiencing aches/pains for no apparent reason that can found; and an inability to concentrate on tasks or activities. If these symptoms are present for a period of two weeks or longer, it is safe to make the assumption that the child, or anybody else for that matter, is falling into major depression. Assessment It is recommended by the American Academy of Pediatrics that primary care providers screen children and adolescents for depression with validated screening tools, self-rated, or clinician-administered ones, once per year. However, there is no universally recommended screening tool and the clinician is free to choose from various validated ones based on personal preference. Once the screening tool indicates the potential presence of a depression, a thorough diagnostic assessment is recommended. In early 2016, the USPSTF released an updated recommendation for the screening of adolescents ages 12 to 18 years for major depressive disorder (MDD). Appropriate treatment and follow-up should be provided for adolescents who screen positive. Correlation between adolescent depression and adulthood obesity According to research conducted by Laura P. Richardson et al., major depression occurred in 7% of the cohort during early adolescence (11, 13, and 15 years of age) and 27% during late adolescence (18 and 21 years of age). At 26 years of age, 12% of study members were obese. After adjusting for each individuals baseline body mass index (calculated as the weight in kilograms divided by the square of height in meters), depressed late-adolescent girls were at a greater than 2-fold increased risk for obesity in adulthood compared with their non-depressed female peers (relative risk, 2.32; 95% confidence interval, 1.29-3.83). A dose-response relationship between the number of episodes of depression during adolescence and the risk for adult obesity was also observed in female subjects. The association was not observed for late adolescent boys or for early adolescent boys or girls. Correlation between child depression and adolescent cardiac risks According to research by RM Carney et al., any history of child depression influences the occurrence of adolescent cardiac risk factors, even if individuals no longer suffer from depression. They are much more likely to develop heart disease as adults. Distinction from major depressive disorder in adults While there are many similarities to adult depression, especially in expression of symptoms, there are many differences that create a distinction between the two diagnoses. Research has shown that when a childs age is younger at diagnosis, typically there will be a more noticeable difference in the expression of symptoms from the classic signs in adult depression. One major difference between the symptoms exhibited in adults and in children is that children have higher rates of internalization; therefore, symptoms of child depression are more difficult to recognize. One major cause of this difference is that many of the neurobiological effects in the brain of adults with depression are not fully developed until adulthood. Therefore, in a neurological sense children and adolescents express depression differently. Treatment Clinicians often divide treatment into three phases: In the acute phase, which usually lasts six to 12 weeks, the goal is to relieve symptoms. In the continuation phase, which can last for several more months, the goal is to maximize improvements. At this stage, clinicians may make adjustments to the dose of a medication. In the maintenance phase, the aim is to prevent relapse. Sometimes the dose of a drug is lowered at this stage, or psychotherapy carries more of the weight. Unique differences in life experience, temperament, and biology make treatment a complex matter; no single treatment is right for everyone. Psychotherapy and medications are commonly used treatment options. In some research, adolescents showed a preference for psychotherapy rather than antidepressant medication for treatment. For adolescents, cognitive behavioral therapy and interpersonal therapy have been empirically supported as effective treatment options. Studies have shown that a combination of psychotherapy and medication is the most effective treatment. Pediatric massage therapy may have an immediate effect on a childs emotional state at the time of the massage, but sustained effects on depression have not been identified.Treatment programs have been developed that help reduce the symptoms of depression. These treatments focus on immediate symptom reduction by concentrating on teaching children skills pertaining to primary and secondary control. While much research is still needed to confirm this treatment programs efficacy, one study showed it to be effective in children with mild or moderate depressive symptoms.Identification and treatment of concomitant parental depression is associated with improved responses to treatment in adolescents with depression as having a parent with depression may negatively affect a young persons response to therapy as well as their outlook on depression. Talk therapy There are a variety of common types of talk therapy. These can assist people to live more fully, help improve good feelings, and have a better life. Effective psychotherapy for children always includes parent involvement, teaching skills that are practiced at home or at school, and measures of progress that are tracked over time. In many types, men are encouraged to open up more emotionally and communicate their personal distress, while women are encouraged to be assertive of their own strengths. Often psychotherapy teaches coping skills while allowing the teens or children to explore feelings and events in a safe environment.Severe depression, low global functioning, higher scores on suicidality scales, co-existing anxiety, distorted thought processes and feelings of hopelessness are characteristics of adolescent depression that are associated with a poor response to psychotherapy. If there is concomitant family conflict then interpersonal therapy is more effective than cognitive therapy. Talk therapy is one of the best forms of therapy, as the depressed person finds a solace in the one whom he/she is talking to. Through this means, the counselor is able to know and understood fully the mind of the depressed individual. Many people are depressed and simply needs the right person to talk to. This is where the talk therapy comes in as a very helpful solution to those who are in need of it. Cognitive therapy Cognitive therapy aims to change harmful ways of thinking and reframe negative thoughts in a more positive way. Aims of cognitive therapy include various steps of patient learning. During cognitive behavioral therapy, children and adolescents with depression work with therapists to learn about their diagnosis, how to identify and reshape negative thought patterns, and how to increase engagement in enjoyable activities. CBT-trained therapists work with individuals, families, and groups. The approach can be used to help anyone irrespective of ability, culture, race, gender, or sexual preference. It can be applied with or without concurrent psychopharmacological medication, depending on the severity or nature of each patients problem. The duration of cognitive-behavioral therapy varies, although it typically is thought of as one of the briefer psychotherapeutic treatments. Especially in research settings, duration of CBT is usually short, between 10 and 20 sessions. In routine clinical practice, duration varies depending on patient comorbidity, defined treatment goals, and the specific conditions of the health care system. Behavioral therapy Behavioral therapy helps change harmful ways of acting and gain control over behavior which is causing problems. Interpersonal therapy Interpersonal therapy helps one learn to relate better with others, express feelings, and develop better social skills. Interpersonal therapy helps the patient identify and cope through reoccurring conflicts within their relationships. Typically, the therapy will focus on one of the four specific problems, grief, social isolation, conflicts about roles and social expectations, or the effect of a major life change. Family therapy The principles of group dynamics are relevant to family therapists who must not only work with individuals, but with entire family systems. Family counseling can help families understand how a childs individual challenges may affect relations with parents and siblings and vice versa.Therapists strive to understand not just what the group members say, but how these ideas are communicated (process). Therapists can help families improve the way they relate and thus enhance their own capacity to deal with the content of their problems by focusing on the process of their discussions. Virginia Satir expanded on the concept of how individuals behave and communicate in groups by describing several family roles that can serve to stabilize expected characteristic behavior patterns in a family. For instance, if one child is considered to be a "rebel child", a sibling may take on the role of the "good child" to alleviate some of the stress in the family. This concept of role reciprocity is helpful in understanding family dynamics because the complementary nature of roles makes behaviors more resistant to change. It is good to understand that most depression in children and adolescents begin right in the home. Parents are advised to treat their children properly and learn to fully understand their child/children, and also give them adequate attention, love, care and quick response to their useful needs. Parents and Guardians should detest ignoring their children or wards and give them attention because neglect can lead to shame, loss of self-confidence, frustration and finally depression. Antidepressants As of 2021, the FDA has approved the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and escitalopram for the treatment of depression in adolescents but other SSRIS or serotonin norepinephrine reuptake inhibitors (SNRIs) are often used off label for treatment. Clinicians usually recommend one of these SSRIs as a first line treatment for depression in adolescence. These drugs act on the serotonin system that affects mood, arousal, anxiety, impulses, and aggression. SSRIs also appear to indirectly influence other neurotransmitter systems, including those involving norepinephrine and dopamine. Some possible adverse reactions of SSRIs include headache, gastrointestinal side effects, dry mouth, sedation or insomnia and activation. Activation refers to a state of psychomotor agitation that includes symptoms of insomnia, disinhibition and restlessness that may result in discontinuation of a medication. There is a rare risk of suicidal thoughts or behaviors with SSRIs especially when treatment is started or the dose is increased, with the rate being up to 0.7% as compared to placebo in early meta analyses of SSRIs in the treatment of adolescent depression. This led the FDA to issue a black box warning regarding this risk. Once remission is achieved, the medications are continued for at least 6 to 12 months and then there is consideration of discontinuing them. Early or premature discontinuation of medications, prior to 6 to 12 months of having achieved remission, is associated with an increased risk of relapse of the depression.The combination of psychotherapy with medications has been shown to be more effective for the treatment of depression in adolescence than medications alone.Other medications can be added to SSRIs if a partial response is achieved and further improvement is needed; these agents include lithium, bupropion and atypical antipsychotics. These options are medications that work in different ways. Bupropion (Wellbutrin) works through the neurotransmitters norepinephrine and dopamine, while mirtazapine (Remeron) affects transmission of norepinephrine and serotonin. The drugs venlafaxine (Effexor) and duloxetine (Cymbalta) work in part by simultaneously inhibiting the reuptake of serotonin and norepinephrine. The oldest drugs on the market are not prescribed often, but may be a good option for some women. These include tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs). TCAs may cause side effects like dry mouth, constipation, or dizziness. MAOIs can cause sedation, insomnia, dizziness, and weight gain. To avoid the risk of a rapid rise in blood pressure, people taking MAOIs must also avoid eating a substance called tyramine, found in yogurt, aged cheese, pickles, beer, and red wine. Some drug side effects subside with time, while others may lessen when a drug dose is lowered. Research Differences in the brains structure and function appear to be present in adolescents with depression though this may depend on age. Younger adolescents, mostly under the age of 18, with depression have shown greater white matter volume within frontal regions of the brain, greater cortical thickness in the anterior cingulate cortex and medial orbitofrontal cortex, as well as greater functional connectivity between cortico-limbic brain regions. Whereas older adolescents, mostly above the age of 18, appear to show lower cortical surface area in regions including the lingual, occipital gyri, as well as medial orbitofrontal and motor cortices. Results such as these have led to the hypothesis that the biological causes of depression may in part be neurodevelopmental, with its biological underpinnings forming early on in brain development. History Although antidepressants were used by child and adolescent psychiatrists to treat major depressive disorder, they were not always used in young people with a comorbid conduct disorder because of the risks of overdose in such a population. Tricyclic antidepressant were the predominant antidepressants used at that time in this population. With the advent of selective serotonin re-uptake inhibitors (SSRIs), child and adolescent psychiatrists probably began prescribing more anti-depressants in the comorbid conduct disorder/major depressive group because of the lower risk of serious harm in overdose. This raises the possibility that more effective treatment of these young people might also improve their outcomes in adult life. Although treatment rates are becoming more stable, there is a trend that suggests that little progress has been made in narrowing the mental health treatment gap for adolescent depression. The FDA has also placed a black box warning on using antidepressants, leading doctors to be hesitant on prescribing them to adolescents. Controversies Throughout the development and research of this disorder, controversies have emerged over the legitimacy of depression in childhood and adolescence as a diagnosis, the proper measurement and validity of scales to diagnose, and the safety of particular treatments. Legitimacy as a diagnosis In early research of depression in children, there was debate as to whether or not children could clinically fit the criteria for major depressive disorder. However, since the 1970s, it has been accepted among the psychological community that depression in children can be clinically significant. The more pertinent controversy in psychology today centers around the clinical significance of sub-threshold mood disorders. This controversy stems from the debate regarding the definition of the specific criteria for a clinically significant depressed mood in relation to the cognitive and behavioral symptoms. Some psychologists argue that the effects of mood disorders in children and adolescents that exist (but do not fully meet the criteria for depression) do not have severe enough risks. Children in this area of severity, they argue, should receive some sort of treatment since the effects could still be severe. However, since there has yet to be enough research or scientific evidence to support that children that fall within the area just shy of a clinical diagnosis require treatment, other psychologists are hesitant to support the dispensation of treatment. Diagnosis controversy In order to diagnose a child with depression, different screening measures and reports have been developed to help clinicians make a proper decision. However, the accuracy and effectiveness of certain measures that help psychologists diagnose children have come into question. Due to absence of strong evidence that screening children and adolescents for depression leads to improved mental health outcomes, it has been questioned whether it causes more harm than benefit. Questions have also surfaced about the safety and effectiveness of antidepressant medications. Measurement reliability The effectiveness of dimensional child self-report checklists has been criticized. Although literature has documented strong psychometric properties, other studies have shown a poor specificity at the top end of scales, resulting in most children with high scores not meeting the diagnostic criteria for depression. Another issue with reliability of measurement for diagnosis occurs in parent, teacher, and child reports. One study, which observed the similarities between child self-report and parent reports on the childs symptoms of depression, acknowledged that on more subjective symptom reports measures, the agreement was not significant enough to be considered reliable. Two self-report scales demonstrated an erroneous classification of 25% of children in both the depressed and controlled samples. A large concern in the use of self-report scales is the accuracy of the information collected. The main controversy is caused by uncertainty about how the data from these multiple informants can or should be combined to determine whether a child can be diagnosed with depression. Treatment issues The controversy over the use of antidepressants began in 2003 when Great Britains Department of Health stated that, based on data collected by the Medicines and Healthcare products Regulatory Agency, paroxetine (an antidepressant) should not be used on patients under the age of 18. Since then, the United States Food and Drug Administration (FDA) has issued a warning describing the increased risk of adverse effects of antidepressants used as treatment in those under the age of 18. The main concern is whether the risks outweigh the benefits of the treatment. In order to decide this, studies often look at the adverse effects caused by the medication in comparison to the overall symptom improvement. While multiple studies have shown an improvement or efficacy rate of over 50%, the concern of severe side effects – such as suicidal ideation or suicidal attempts, worsening of symptoms, or increase in hostility – are still concerns when using antidepressants. However, an analysis of multiple studies argues that while the risk of suicidal ideation or attempt is present, the benefits significantly outweigh the risks. Due to the variability of these studies, it is currently recommended that if antidepressants are chosen as a method of treatment for children or adolescents, the clinician monitor closely for adverse symptoms, since there is still no definitive answer on why they are depressed. == References ==

You serve as an encyclopedia of medical terms. Deliver clear, detailed explanations, making medical language understandable to a diverse audience.

I'm curious about the meaning of the medical term 'Transient ischemic attack.' Can you give me some insights?

A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same symptoms associated with strokes, such as weakness or numbness on one side of the body, sudden dimming or loss of vision, difficulty speaking or understanding language, slurred speech, or confusion. All forms of stroke, including TIA, result from a disruption in blood flow to the central nervous system. A TIA is caused by a temporary disruption in blood flow to the brain, or cerebral blood flow (CBF). The primary difference between a major stroke and the TIAs minor stroke is how much tissue death (infarction) can be detected afterwards through medical imaging. While a TIA must by definition be associated with symptoms, strokes can also be symptomatic or silent. In silent stroke, also known as silent cerebral infarct (SCI), there is permanent infarction detectable on imaging, but there are no immediately observable symptoms. The same person can have major strokes, minor strokes, and silent strokes, in any order.The occurrence of a TIA is a risk factor for having a major stroke, and many people with TIA have a major stroke within 48 hours of the TIA. All forms of stroke are associated with increased risk of death or disability. Recognition that a TIA has occurred is an opportunity to start treatment, including medications and lifestyle changes, to prevent future strokes. Signs and symptoms Signs and symptoms of TIA are widely variable and can mimic other neurologic conditions, making the clinical context and physical exam crucial in ruling in or out the diagnosis. The most common presenting symptoms of TIA are focal neurologic deficits, which can include, but are not limited to: Amaurosis fugax (painless, temporary loss of vision) One-sided facial droop One-sided motor weakness Diplopia (double vision) Problems with balance and spatial orientation or dizziness Visual field deficits, such as homonymous hemianopsia or monocular blindness Sensory deficits in one or more limbs and of the face Loss of ability to understand or express speech (aphasia) Difficulty with articulation of speech (dysarthria) Unsteady gait Difficulties with swallowing (dysphagia)Numbness or weakness generally occur on the opposite side of the body from the affected hemisphere of the brain. A detailed neurologic exam, including a thorough cranial nerve exam, is important to identify these findings and to differentiate them from mimickers of TIA. Symptoms such as unilateral weakness, amaurosis fugax, and double vision have higher odds of representing TIA compared to memory loss, headache, and blurred vision. Below is a table of symptoms at presentation, and what percentage of the time they are seen in TIAs versus conditions that mimic TIA. In general, focal deficits make TIA more likely, but the absence of focal findings do not exclude the diagnosis and further evaluation may be warranted if clinical suspicion for TIA is high (see "Diagnosis" section below). TIA versus mimics Non-focal symptoms such as amnesia, confusion, incoordination of limbs, unusual cortical visual symptoms (such as isolated bilateral blindness or bilateral positive visual phenomena), headaches and transient loss of consciousness are usually not associated with TIA, however patient assessment is still needed. Public awareness on the need to seek a medical assessment for these non-focal symptoms is also low, and can result in a delay by patients to seek treatmentSymptoms of TIAs can last on the order of minutes to one–two hours, but occasionally may last for a longer period of time. TIAs used to be defined as ischemic events in the brain that last less than 24 hours, but given the variation in duration of symptoms, this definition holds less significance. A pooled study of 808 patients with TIAs from 10 hospitals showed that 60% lasted less than one hour, 71% lasted less than two hours, and 14% lasted greater than six hours. Importantly, patients with symptoms that last more than one hour are more likely to have permanent neurologic damage, making prompt diagnosis and treatment important to maximize recovery. Cause The most common underlying pathology leading to TIA and stroke is a cardiac condition called atrial fibrillation, where poor coordination of contraction leads to a formation of a clot in the atrial chamber that can become dislodged and travel to a cerebral artery. Unlike in stroke, the blood flow can become restored prior to infarction which leads to the resolution of neurologic symptoms. Another common culprit of TIA is an atherosclerotic plaque located in the common carotid artery, typically by the bifurcation between the internal and external carotids, that becomes an embolism to the brain vasculature similar to the clot in the prior example. A portion of the plaque can become dislodged and lead to embolic pathology in the cerebral vessels.In-situ thrombosis, an obstruction that forms directly in the cerebral vasculature unlike the remote embolism previously mentioned, is another vascular occurrence with possible presentation as TIA. Also, carotid stenosis secondary to atherosclerosis narrowing the diameter of the lumen and thus limiting blood flow is another common cause of TIA. Individuals with carotid stenosis may present with TIA symptoms, thus labeled symptomatic, while others may not experience symptoms and be asymptomatic. Risk factors Risk factors associated with TIA are categorized as modifiable or non-modifiable. Non-modifiable risk factors include age greater than 55, sex, family history, genetics, and race/ethnicity. Modifiable risk factors include cigarette smoking, hypertension (elevated blood pressure), diabetes, hyperlipidemia, level of carotid artery stenosis (asymptomatic or symptomatic) and activity level. The modifiable risk factors are commonly targeted in treatment options to attempt to minimize risk of TIA and stroke. Pathogenesis There are three major mechanisms of ischemia in the brain: embolism traveling to the brain, in situ thrombotic occlusion in the intracranial vessels supplying the parenchyma of the brain, and stenosis of vessels leading to poor perfusion secondary to flow-limiting diameter. Globally, the vessel most commonly affected is the middle cerebral artery. Embolisms can originate from multiple parts of the body. Common mechanisms of stroke and TIA: Diagnosis The initial clinical evaluation of a suspected TIA involves obtaining a history and physical exam (including a neurological exam). History taking includes defining the symptoms and looking for mimicking symptoms as described above. Bystanders can be very helpful in describing the symptoms and giving details about when they started and how long they lasted. The time course (onset, duration, and resolution), precipitating events, and risk factors are particularly important. The definition, and therefore the diagnosis, has changed over time. TIA was classically based on duration of neurological symptoms. The current widely accepted definition is called "tissue-based" because it is based on imaging, not time. The American Heart Association and the American Stroke Association (AHA/ASA) now define TIA as a brief episode of neurological dysfunction with a vascular cause, with clinical symptoms typically lasting less than one hour, and without evidence of significant infarction on imaging. Laboratory workup Laboratory tests should focus on ruling out metabolic conditions that may mimic TIA (e.g. hypoglycemia causing altered mental status), in addition to further evaluating a patients risk factors for ischemic events. All patients should receive a complete blood count with platelet count, blood glucose, basic metabolic panel, prothrombin time/international normalized ratio, and activated partial thromboplastin time as part of their initial workup. These tests help with screening for bleeding or hypercoagulable conditions. Other lab tests, such as a full hypercoagulable state workup or serum drug screening, should be considered based on the clinical situation and factors, such as age of the patient and family history. A fasting lipid panel is also appropriate to thoroughly evaluate the patients risk for atherosclerotic disease and ischemic events in the future. Other lab tests may be indicated based on the history and presentation; such as obtaining inflammatory markers (erythrocyte sedimentation rate and C-reactive protein) to evaluate for giant cell arteritis (which can mimic a TIA) in those presenting with headaches and monocular blindness. Cardiac rhythm monitoring An electrocardiogram is necessary to rule out abnormal heart rhythms, such as atrial fibrillation, that can predispose patients to clot formation and embolic events. Hospitalized patients should be placed on heart rhythm telemetry, which is a continuous form of monitoring that can detect abnormal heart rhythms. Prolonged heart rhythm monitoring (such as with a Holter monitor or implantable heart monitoring) can be considered to rule out arrhythmias like paroxysmal atrial fibrillation that may lead to clot formation and TIAs, however this should be considered if other causes of TIA have not been found. Imaging According to guidelines from the American Heart Association and American Stroke Association Stroke Council, patients with TIA should have head imaging "within 24 hours of symptom onset, preferably with magnetic resonance imaging, including diffusion sequences". MRI is a better imaging modality for TIA than computed tomography (CT), as it is better able to pick up both new and old ischemic lesions than CT. CT, however, is more widely available and can be used particularly to rule out intracranial hemorrhage. Diffusion sequences can help further localize the area of ischemia and can serve as prognostic indicators. Presence of ischemic lesions on diffusion weighted imaging has been correlated with a higher risk of stroke after a TIA.Vessels in the head and neck may also be evaluated to look for atherosclerotic lesions that may benefit from interventions, such as carotid endarterectomy. The vasculature can be evaluated through the following imaging modalities: magnetic resonance angiography (MRA), CT angiography (CTA), and carotid ultrasonography/transcranial doppler ultrasonography. Carotid ultrasonography is often used to screen for carotid artery stenosis, as it is more readily available, is noninvasive, and does not expose the person being evaluated to radiation. However, all of the above imaging methods have variable sensitivities and specificities, making it important to supplement one of the imaging methods with another to help confirm the diagnosis (for example: screen for the disease with ultrasonography, and confirm with CTA). Confirming a diagnosis of carotid artery stenosis is important because the treatment for this condition, carotid endarterectomy, can pose significant risk to the patient, including heart attacks and strokes after the procedure. For this reason, the U.S. Preventive Services Task Force (USPSTF) "recommends against screening for asymptomatic carotid artery stenosis in the general adult population". This recommendation is for asymptomatic patients, so it does not necessarily apply to patients with TIAs as these may in fact be a symptom of underlying carotid artery disease (see "Causes and Pathogenesis" above). Therefore, patients who have had a TIA may opt to have a discussion with their clinician about the risks and benefits of screening for carotid artery stenosis, including the risks of surgical treatment of this condition. Cardiac imaging can be performed if head and neck imaging do not reveal a vascular cause for the patients TIA (such as atherosclerosis of the carotid artery or other major vessels of the head and neck). Echocardiography can be performed to identify patent foramen ovale (PFO), valvular stenosis, and atherosclerosis of the aortic arch that could be sources of clots causing TIAs, with transesophageal echocardiography being more sensitive than transthoracic echocardiography in identifying these lesions. Differential diagnosis Prevention Although there is a lack of robust studies demonstrating the efficacy of lifestyle changes in preventing TIA, many medical professionals recommend them. These include: Avoiding smoking Cutting down on fats to help reduce the amount of plaque buildup Eating a healthy diet including plenty of fruits and vegetables Limiting sodium in the diet, thereby reducing blood pressure Exercising regularly Moderating intake of alcohol, stimulants, sympathomimetics, etc. Maintaining a healthy weightIn addition, it is important to control any underlying medical conditions that may increase the risk of stroke or TIA, including: Hypertension High cholesterol Diabetes mellitus Atrial fibrillation Treatment By definition, TIAs are transient, self-resolving, and do not cause permanent impairment. However, they are associated with an increased risk of subsequent ischemic strokes, which can be permanently disabling. Therefore, management centers on the prevention of future ischemic strokes and addressing any modifiable risk factors. The optimal regimen depends on the underlying cause of the TIA. Lifestyle modification Lifestyle changes have not been shown to reduce the risk of stroke after TIA. While no studies have looked at the optimal diet for secondary prevention of stroke, some observational studies have shown that a Mediterranean diet can reduce stroke risk in patients without cerebrovascular disease. A Mediterranean diet is rich in fruits, vegetables and whole grains, and limited in red meats and sweets. Vitamin supplementation has not been found to be useful in secondary stroke prevention. Antiplatelet medications The antiplatelet medications, aspirin and clopidogrel, are both recommended for secondary prevention of stroke after high-risk TIAs. The clopidogrel can generally be stopped after 10 to 21 days. An exception is TIAs due to blood clots originating from the heart, in which case anticoagulants are generally recommended. After TIA or minor stroke, aspirin therapy has been shown to reduce the short-term risk of recurrent stroke by 60–70%, and the long-term risk of stroke by 13%.The typical therapy may include aspirin alone, a combination of aspirin plus extended-release dipyridamole, or clopidogrel alone. Clopidogrel and aspirin have similar efficacies and side effect profiles. Clopidogrel is more expensive and has a slightly decreased risk of GI bleed. Another antiplatelet, ticlopidine, is rarely used due to increased side effects. Anticoagulant medications Anticoagulants may be started if the TIA is thought to be attributable to atrial fibrillation. Atrial fibrillation is an abnormal heart rhythm that may cause the formation of blood clots that can travel to the brain, resulting in TIAs or ischemic strokes. Atrial fibrillation increases stroke risk by five times, and is thought to cause 10-12% of all ischemic strokes in the US. Anticoagulant therapy can decrease the relative risk of ischemic stroke in those with atrial fibrillation by 67% Warfarin is a common anticoagulant used, but direct acting oral anticoagulants (DOACs), such as apixaban, have been shown to be equally effective while also conferring a lower risk of bleeding. Generally, anticoagulants and antiplatelets are not used in combination, as they result in increased bleeding risk without a decrease in stroke risk. However, combined antiplatelet and anticoagulant therapy may be warranted if the patient has symptomatic coronary artery disease in addition to atrial fibrillation. Sometimes, myocardial infarction ("heart attack") may lead to the formation of a blood clot in one of the chambers of the heart. If this is thought to be the cause of the TIA, people may be temporarily treated with warfarin or other anticoagulant to decrease the risk of future stroke. Blood pressure control Blood pressure control may be indicated after TIA to reduce the risk of ischemic stroke. About 70% of patients with recent ischemic stroke are found to have hypertension, defined as systolic blood pressure (SBP) > 140 mmHg, or diastolic blood pressure (DBP) > 90 mmHg. Until the first half of the 2010s, blood pressure goals have generally been SBP < 140 mmHg and DBP < 90 mmHg. However, newer studies suggest that a goal of SBP <130 mmHg may confer even greater benefit. Blood pressure control is often achieved using diuretics or a combination of diuretics and angiotensin converter enzyme inhibitors, although the optimal treatment regimen depends on the individual.Studies that evaluated the application of Blood pressure‐lowering drugs in people who had a TIA or stroke, concluded that this type of medication helps to reduce the possibility of a recurrent stroke, of a major vascular event and dementia. The effects achieved in stroke recurrence were mainly obtained through the ingestion of angiotensin-converting enzyme (ACE) inhibitor or a diuretic. Cholesterol control There is inconsistent evidence regarding the effect of LDL-cholesterol levels on stroke risk after TIA. Elevated cholesterol may increase ischemic stroke risk while decreasing the risk of hemorrhagic stroke. While its role in stroke prevention is currently unclear, statin therapy has been shown to reduce all-cause mortality and may be recommended after TIA. Diabetes control Diabetes mellitus increases the risk of ischemic stroke by 1.5-3.7 times, and may account for at least 8% of first ischemic strokes. While intensive glucose control can prevent certain complications of diabetes such as kidney damage and retinal damage, there has previously been little evidence that it decreases the risk of stroke or death. However, data from 2017 suggests that metformin, pioglitazone and semaglutide may reduce stroke risk. Surgery If the TIA affects an area that is supplied by the carotid arteries, a carotid ultrasound scan may demonstrate stenosis, or narrowing, of the carotid artery. For people with extra-cranial carotid stenosis, if 70-99% of the carotid artery is clogged, carotid endarterectomy can decrease the five-year risk of ischemic stroke by approximately half. For those with extra-cranial stenosis between 50 and 69%, carotid endarterectomy decreases the 5-year risk of ischemic stroke by about 16%. For those with extra-cranial stenosis less than 50%, carotid endarterectomy does not reduce stroke risk and may, in some cases, increase it. The effectiveness of carotid endarterectomy or carotid artery stenting in reducing stroke risk in people with intra-cranial carotid artery stenosis is currently unknown.In carotid endarterectomy, a surgeon makes an incision in the neck, opens up the carotid artery, and removes the plaque occluding the blood vessel. The artery may then be repaired by adding a graft from another vessel in the body, or a woven patch. In patients who undergo carotid endarterectomy after a TIA or minor stroke, the 30-day risk of death or stroke is 7%.Carotid artery stenting is a less invasive alternative to carotid endarterectomy for people with extra-cranial carotid artery stenosis. In this procedure, the surgeon makes a small cut in the groin and threads a small flexible tube, called a catheter, into the patients carotid artery. A balloon is inflated at the site of stenosis, opening up the clogged artery to allow for increased blood flow to the brain. To keep the vessel open, a small wire mesh coil, called a stent, may be inflated along with the balloon. The stent remains in place, and the balloon is removed. For people with symptomatic carotid stenosis, carotid endarterectomy is associated with fewer perioperative deaths or strokes than carotid artery stenting. Following the procedure, there is no difference in effectiveness if you compare carotid endarterectomy and carotid stenting procedures, however, endarterectomy is often the procedure of choice as it is a safer procedure and is often effective in the longer term for preventing recurrent stroke. For people with asymptomatic carotid stenosis, the increased risk of stroke or death during the stenting procedure compared to an endarterectomy is less certain.People who undergo carotid endarterectomy or carotid artery stenting for stroke prevention are medically managed with antiplatelets, statins, and other interventions as well. Prognosis Without treatment, the risk of an ischemic stroke in the three months after a TIA is about 20% with the greatest risk occurring within two days of the TIA. Other sources cite that 10% of TIAs will develop into a stroke within 90 days, half of which will occur in the first two days following the TIA. Treatment and preventative measures after a TIA (for example treating elevated blood pressure) can reduce the subsequent risk of an ischemic stroke by about 80%. The risk of a stroke occurring after a TIA can be predicted using the ABCD² score. One limitation of the ABCD² score is that it does not reliably predict the level of carotid artery stenosis, which is a major cause of stroke in TIA patients. The patients age is the most reliable risk factor in predicting any level of carotid stenosis in transient ischemic attack. The ABCD2 score is no longer recommended for triage (to decide between outpatient management versus hospital admission) of those with a suspected TIA due to these limitations. Epidemiology With the difficulty in diagnosing a TIA due to its nonspecific symptoms of neurologic dysfunction at presentation and a differential including many mimics, the exact incidence of the disease is unclear. It is currently estimated to have an incidence of approximately 200,000 to 500,000 cases per year in the US according to the American Heart Association. TIA incidence trends similarly to stroke, such that incidence varies with age, gender, and different race/ethnicity populations. Associated risk factors include age greater than or equal to 60, blood pressure greater than or equal to 140 systolic or 90 diastolic, and comorbid diseases, such as diabetes, hypertension, atherosclerosis, and atrial fibrillation. It is thought that approximately 15 to 30 percent of strokes have a preceding TIA episode associated. References == External links ==

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

Can you break down the meaning of the medical term 'Digoxin immune fab' for me?

Digoxin immune fab or digoxin-specific antibody is an antidote for overdose of digoxin. It is made from immunoglobulin fragments from sheep that have already been immunized with a digoxin derivative, digoxindicarboxymethoxylamine (DDMA). Its brand names include Digibind (GlaxoSmithKline) and DigiFab (BTG plc). Medical uses It is used for digoxin toxicity. Digoxin toxicity can emerge during long-term therapy as well as after an overdose. It can occur even when the serum digoxin concentration is within the therapeutic range when one of the following is present: Hemodynamically unstable arrhythmia End organ damage digoxin level > 4 ng/ml if chronic ingestion digoxin level > 10 ng/ml if acute ingestion potassium > 5 mEq/L and symptomaticSide effects of digoxin immune fab may occur: hives difficult breathing swelling of the lips, tongue, face, or throat itching skin redness wheezing cough lightheadedness Contraindications Avoid use in hypokalemia as this drug, while reversing the effects of digitalis, will further reduce serum potassium levels and could precipitate dangerous and even fatal cardiac arrhythmias. The patient must be closely monitored for anaphylactic shock, and anyone allergic to sheep protein, papain, bromelain, or papaya extracts (papain is used to cleave the antibody into Fab and Fc fragments) should not use ovine digoxin immune fab. Because it is relatively new, no drug interaction studies have been performed yet. Pharmacology It works by binding to the digoxin, rendering it unable to bind to its action sites on target cells. The complexes accumulate in the blood and are expelled by the kidney. Regulatory information and clinical studies Case series have reported benefits from anti‐digoxin Fab, but data regarding the response in acute or chronic poisoning are conflicting. Recent observational data support an effect in acute poisoning, but efficacy in chronic poisoning be minimally effective in alleviating cardiac toxicities in chronic digoxin poisoning. Data also support outcomes of acute digoxin poisoning without use of anti‐digoxin Fab. A case series of 147 patients showed that not all cases of acute digoxin overdose require anti‐digoxin Fab, nor should anti‐digoxin Fab dose be calculated based on ingested dose. In contrast, a higher mortality (7.6%) was noted in a case series of acute and chronic digoxin and digitoxin poisoning despite Fab being used first line. Further, a retrospective case‐controlled study of chronic digoxin poisoning did not observe a beneficial effect of anti‐digoxin Fab on mortality. An RCT (n = 66) in yellow oleander poisoning showed an early improvement in cardiac rhythm and hyperkalaemia from anti‐digoxin Fab, prompting early termination of the trial. It was not powered to detect a change in mortality and no deaths were noted. As with all foreign proteins, anaphylaxis, serum sickness or febrile reactions are a source of concern, especially with repeated administration. These reactions appear uncommon for example, in a study of 717 adults where only six patients (0.8%) exhibited any evidence of allergic response. Nevertheless, theoretically, patients previously dependent upon the inotropic effects of digoxin could develop heart failure and hypokalaemia could result within 1–5 hours, owing to intracellular shifts of potassium, as the effects of digoxin are reversed. Patients who require redigitalization must wait for the complexes to be eliminated from the body by the kidneys, this taking 2–3 days with normal renal function. Unfortunately, fab fragments interfere with both fluorescence excitation transfer immunoassays and radioimmunoassays for digoxin. This means that serum drug levels cannot be monitored until the drug-antibody complexes are cleared from the circulation. Intellectual property DigiFab is used as an antidote to treat a life-threatening overdose of digoxin or digitoxin. DigiFab is manufactured and distributed by BTG international Inc. under U.S. License No. 186. DigiFab is a sterile, lyophilized preparation of digoxin-immune ovine Fab (monovalent) immunoglobulin fragments. It is prepared by isolating the immunoglobulin fraction of the ovine serum, digesting it with papain and isolating the digoxin-specific Fab fragments by affinity chromatography. These antibody fragments have a molecular weight of approximately 46,000 Da. Each vial of DigiFab, which will bind approximately 0.5 mg digoxin, contains 40 mg of digoxin immune Fab, 75 mg (approx) of mannitol USP, and 2 mg (approx) sodium acetate USP as a buffering agent. The product contains no preservatives and is intended for intravenous administration. Digibind is manufactured by GlaxoSmithkline, SpA, Parma Italy under US License No. 129. It’s distributed by GSK, Research Triangle park, NC 27709. A patent to use digoxin immunoglobulins C07k16/44 as a regulator of the preeclamptic/eclamptic patients sodium/potassium ATPase activity was approved in 2003 to Charles David Adair under application number WO2004011028A1. Commercial aspects Price increase was reported to range from US $380 to US $750 during 2013 for digoxin-Fab. However, these price increases are not reflective of the United States average AWP for digoxin-Fab as it represents Australian costs converted to US. Prior to 2011, Digibind and DigiFab pricing was US $797 per 38 mg vial and US $786 per 40 mg vial respectively. After GSK discontinued Digibind sale in USA in 2011, the AWP of DigiFab increases by 15% to US $903 per 40 mg vial. AWP of DigiFab has continued to increase as much as 54% occurring in March 2014 to US $2,370 per 40 mg vial. However, the cost may vary depending on wholesaler contractor manufacturer rebates. References External links Drug information online Digibind description

You are a medical lexicon. Explain medical terminology with depth and clarity, making sure the information is both accurate and easy to grasp.

Please help me grasp the concept behind the medical term 'Metabolic syndrome.'

Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndrome is associated with the risk of developing cardiovascular disease and type 2 diabetes. In the U.S., about 25% of the adult population has metabolic syndrome, a proportion increasing with age, particularly among racial and ethnic minorities.Insulin resistance, metabolic syndrome, and prediabetes are closely related to one another and have overlapping aspects. The syndrome is thought to be caused by an underlying disorder of energy utilization and storage. The cause of the syndrome is an area of ongoing medical research. Signs and symptoms The key sign of metabolic syndrome is central obesity, also known as visceral, male-pattern or apple-shaped adiposity. It is characterized by adipose tissue accumulation predominantly around the waist and trunk. Other signs of metabolic syndrome include high blood pressure, decreased fasting serum HDL cholesterol, elevated fasting serum triglyceride level, impaired fasting glucose, insulin resistance, or prediabetes. Associated conditions include hyperuricemia; fatty liver (especially in concurrent obesity) progressing to nonalcoholic fatty liver disease; polycystic ovarian syndrome in women and erectile dysfunction in men; and acanthosis nigricans. Complication Metabolic syndrome can lead to several serious and chronic complications, including type-2 diabetes, cardiovascular diseases, stroke, kidney disease and nonalcoholic fatty liver disease. Causes The mechanisms of the complex pathways of metabolic syndrome are under investigation. The pathophysiology is very complex and has been only partially elucidated. Most people affected by the condition are older, obese, sedentary, and have a degree of insulin resistance. Stress can also be a contributing factor. The most important risk factors are diet (particularly sugar-sweetened beverage consumption), genetics, aging, sedentary behavior or low physical activity, disrupted chronobiology/sleep, mood disorders/psychotropic medication use, and excessive alcohol use. The pathogenic role played in the syndrome by the excessive expansion of adipose tissue occurring under sustained overeating, and its resulting lipotoxicity was reviewed by Vidal-Puig.There is debate regarding whether obesity or insulin resistance is the cause of the metabolic syndrome or if they are consequences of a more far-reaching metabolic derangement. Markers of systemic inflammation, including C-reactive protein, are often increased, as are fibrinogen, interleukin 6, tumor necrosis factor-alpha (TNF-α), and others. Some have pointed to a variety of causes, including increased uric acid levels caused by dietary fructose.Research shows that Western diet habits are a factor in development of metabolic syndrome, with high consumption of food that is not biochemically suited to humans. Weight gain is associated with metabolic syndrome. Rather than total adiposity, the core clinical component of the syndrome is visceral and/or ectopic fat (i.e., fat in organs not designed for fat storage) whereas the principal metabolic abnormality is insulin resistance. The continuous provision of energy via dietary carbohydrate, lipid, and protein fuels, unmatched by physical activity/energy demand, creates a backlog of the products of mitochondrial oxidation, a process associated with progressive mitochondrial dysfunction and insulin resistance. Stress Recent research indicates prolonged chronic stress can contribute to metabolic syndrome by disrupting the hormonal balance of the hypothalamic-pituitary-adrenal axis (HPA-axis). A dysfunctional HPA-axis causes high cortisol levels to circulate, which results in raising glucose and insulin levels, which in turn cause insulin-mediated effects on adipose tissue, ultimately promoting visceral adiposity, insulin resistance, dyslipidemia and hypertension, with direct effects on the bone, causing "low turnover" osteoporosis. HPA-axis dysfunction may explain the reported risk indication of abdominal obesity to cardiovascular disease (CVD), type 2 diabetes and stroke. Psychosocial stress is also linked to heart disease. Obesity Central obesity is a key feature of the syndrome, being both a sign and a cause, in that the increasing adiposity often reflected in high waist circumference may both result from and contribute to insulin resistance. However, despite the importance of obesity, affected people who are of normal weight may also be insulin-resistant and have the syndrome. Sedentary lifestyle Physical inactivity is a predictor of CVD events and related mortality. Many components of metabolic syndrome are associated with a sedentary lifestyle, including increased adipose tissue (predominantly central); reduced HDL cholesterol; and a trend toward increased triglycerides, blood pressure, and glucose in the genetically susceptible. Compared with individuals who watched television or videos or used their computers for less than one hour daily, those who carried out these behaviors for greater than four hours daily have a twofold increased risk of metabolic syndrome. Aging Metabolic syndrome affects 60% of the U.S. population older than age 50. With respect to that demographic, the percentage of women having the syndrome is higher than that of men. The age dependency of the syndromes prevalence is seen in most populations around the world. Diabetes mellitus type 2 The metabolic syndrome quintuples the risk of type 2 diabetes mellitus. Type 2 diabetes is considered a complication of metabolic syndrome. In people with impaired glucose tolerance or impaired fasting glucose, presence of metabolic syndrome doubles the risk of developing type 2 diabetes. It is likely that prediabetes and metabolic syndrome denote the same disorder, defining it by the different sets of biological markers.The presence of metabolic syndrome is associated with a higher prevalence of CVD than found in people with type 2 diabetes or impaired glucose tolerance without the syndrome. Hypoadiponectinemia has been shown to increase insulin resistance and is considered to be a risk factor for developing metabolic syndrome. Coronary heart disease The approximate prevalence of the metabolic syndrome in people with coronary artery disease (CAD) is 50%, with a prevalence of 37% in people with premature coronary artery disease (age 45), particularly in women. With appropriate cardiac rehabilitation and changes in lifestyle (e.g., nutrition, physical activity, weight reduction, and, in some cases, drugs), the prevalence of the syndrome can be reduced. Lipodystrophy Lipodystrophic disorders in general are associated with metabolic syndrome. Both genetic (e.g., Berardinelli-Seip congenital lipodystrophy, Dunnigan familial partial lipodystrophy) and acquired (e.g., HIV-related lipodystrophy in people treated with highly active antiretroviral therapy) forms of lipodystrophy may give rise to severe insulin resistance and many of metabolic syndromes components. Rheumatic diseases There is research that associates comorbidity with rheumatic diseases. Both psoriasis and psoriatic arthritis have been found to be associated with metabolic syndrome. Chronic obstructive pulmonary disease Metabolic syndrome is seen to be a comorbidity in up to 50 percent of those with chronic obstructive pulmonary disease (COPD). It may pre-exist or may be a consequence of the lung pathology of COPD. Pathophysiology It is common for there to be a development of visceral fat, after which the adipocytes (fat cells) of the visceral fat increase plasma levels of TNF-α and alter levels of other substances (e.g., adiponectin, resistin, and PAI-1). TNF-α has been shown to cause the production of inflammatory cytokines and also possibly trigger cell signaling by interaction with a TNF-α receptor that may lead to insulin resistance. An experiment with rats fed a diet with 33% sucrose has been proposed as a model for the development of metabolic syndrome. The sucrose first elevated blood levels of triglycerides, which induced visceral fat and ultimately resulted in insulin resistance. The progression from visceral fat to increased TNF-α to insulin resistance has some parallels to human development of metabolic syndrome. The increase in adipose tissue also increases the number of immune cells, which play a role in inflammation. Chronic inflammation contributes to an increased risk of hypertension, atherosclerosis and diabetes.The involvement of the endocannabinoid system in the development of metabolic syndrome is indisputable. Endocannabinoid overproduction may induce reward system dysfunction and cause executive dysfunctions (e.g., impaired delay discounting), in turn perpetuating unhealthy behaviors. The brain is crucial in development of metabolic syndrome, modulating peripheral carbohydrate and lipid metabolism.Metabolic syndrome can be induced by overfeeding with sucrose or fructose, particularly concomitantly with high-fat diet. The resulting oversupply of omega-6 fatty acids, particularly arachidonic acid (AA), is an important factor in the pathogenesis of metabolic syndrome. Arachidonic acid (with its precursor – linoleic acid) serves as a substrate to the production of inflammatory mediators known as eicosanoids, whereas the arachidonic acid-containing compound diacylglycerol (DAG) is a precursor to the endocannabinoid 2-arachidonoylglycerol (2-AG) while fatty acid amide hydrolase (FAAH) mediates the metabolism of anandamide into arachidonic acid. Anandamide can also be produced from N-acylphosphatidylethanolamine via several pathways. Anandamide and 2-AG can also be hydrolized into arachidonic acid, potentially leading to increased eicosanoid synthesis. Diagnosis A joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity published a guideline to harmonize the definition of the metabolic syndrome. This definition recognizes that the risk associated with a particular waist measurement will differ in different populations. Whether it is better at this time to set the level at which risk starts to increase or at which there is already substantially increased risk will be up to local decision-making groups. However, for international comparisons and to facilitate the etiology, it is critical that a commonly agreed-upon set of criteria be used worldwide, with agreed-upon cut points for different ethnic groups and sexes. There are many people in the world of mixed ethnicity, and in those cases, pragmatic decisions will have to be made. Therefore, an international criterion of overweight may be more appropriate than ethnic specific criteria of abdominal obesity for an anthropometric component of this syndrome which results from an excess lipid storage in adipose tissue, skeletal muscle and liver.The previous definitions of the metabolic syndrome by the International Diabetes Federation (IDF) and the revised National Cholesterol Education Program (NCEP) are very similar, and they identify individuals with a given set of symptoms as having metabolic syndrome. There are two differences, however: the IDF definition states that if body mass index (BMI) is greater than 30 kg/m2, central obesity can be assumed, and waist circumference does not need to be measured. However, this potentially excludes any subject without increased waist circumference if BMI is less than 30. Conversely, the NCEP definition indicates that metabolic syndrome can be diagnosed based on other criteria. Also, the IDF uses geography-specific cut points for waist circumference, while NCEP uses only one set of cut points for waist circumference regardless of geography. IDF The International Diabetes Federation consensus worldwide definition of metabolic syndrome (2006) is: Central obesity (defined as waist circumference# with ethnicity-specific values) AND any two of the following: Raised triglycerides: > 150 mg/dL (1.7 mmol/L), or specific treatment for this lipid abnormality Reduced HDL cholesterol: < 40 mg/dL (1.03 mmol/L) in males, < 50 mg/dL (1.29 mmol/L) in females, or specific treatment for this lipid abnormality Raised blood pressure (BP): systolic BP > 130 or diastolic BP >85 mm Hg, or treatment of previously diagnosed hypertension Raised fasting plasma glucose (FPG): >100 mg/dL (5.6 mmol/L), or previously diagnosed type 2 diabetesIf FPG is >5.6 mmol/L or 100 mg/dL, an oral glucose tolerance test is strongly recommended, but is not necessary to define presence of the syndrome. # If BMI is >30 kg/m2, central obesity can be assumed and waist circumference does not need to be measured WHO The World Health Organization (1999) requires the presence of any one of diabetes mellitus, impaired glucose tolerance, impaired fasting glucose or insulin resistance, AND two of the following: Blood pressure ≥ 140/90 mmHg Dyslipidemia: triglycerides (TG) ≥ 1.695 mmol/L and HDL cholesterol ≤ 0.9 mmol/L (male), ≤ 1.0 mmol/L (female) Central obesity: waist:hip ratio > 0.90 (male); > 0.85 (female), or BMI > 30 kg/m2 Microalbuminuria: urinary albumin excretion ratio ≥ 20 µg/min or albumin:creatinine ratio ≥ 30 mg/g EGIR The European Group for the Study of Insulin Resistance (1999) requires insulin resistance defined as the top 25% of the fasting insulin values among nondiabetic individuals AND two or more of the following: Central obesity: waist circumference ≥ 94 cm or 37 inches (male), ≥ 80 cm or 31.5 inches (female) Dyslipidemia: TG ≥ 2.0 mmol/L and/or HDL-C < 1.0 mmol/L or treated for dyslipidemia Blood pressure ≥ 140/90 mmHg or antihypertensive medication Fasting plasma glucose ≥ 6.1 mmol/L NCEP The U.S. National Cholesterol Education Program Adult Treatment Panel III (2001) requires at least three of the following: Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female) Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dl) Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female) Blood pressure ≥ 130/85 mmHg (or treated for hypertension) Fasting plasma glucose ≥ 6.1 mmol/L (110 mg/dl) American Heart Association There is confusion as to whether, in 2004, the American Heart Association and National Heart, Lung, and Blood Institute intended to create another set of guidelines or simply update the National Cholesterol Education Program definition. Central obesity: waist circumference ≥ 102 cm or 40 inches (male), ≥ 88 cm or 35 inches(female) Dyslipidemia: TG ≥ 1.7 mmol/L (150 mg/dL) Dyslipidemia: HDL-C < 40 mg/dL (male), < 50 mg/dL (female) Blood pressure ≥ 130/85 mmHg (or treated for hypertension) Fasting plasma glucose ≥ 5.6 mmol/L (100 mg/dL), or use of medication for hyperglycemia Other High-sensitivity C-reactive protein has been developed and used as a marker to predict coronary vascular diseases in metabolic syndrome, and it was recently used as a predictor for nonalcoholic fatty liver disease (steatohepatitis) in correlation with serum markers that indicated lipid and glucose metabolism. Fatty liver disease and steatohepatitis can be considered manifestations of metabolic syndrome, indicative of abnormal energy storage as fat in ectopic distribution. Reproductive disorders (such as polycystic ovary syndrome in women of reproductive age), and erectile dysfunction or decreased total testosterone (low testosterone-binding globulin) in men can be attributed to metabolic syndrome. Prevention Various strategies have been proposed to prevent the development of metabolic syndrome. These include increased physical activity (such as walking 30 minutes every day), and a healthy, reduced calorie diet. Many studies support the value of a healthy lifestyle as above. However, one study stated these potentially beneficial measures are effective in only a minority of people, primarily because of a lack of compliance with lifestyle and diet changes. The International Obesity Taskforce states that interventions on a sociopolitical level are required to reduce development of the metabolic syndrome in populations.The Caerphilly Heart Disease Study followed 2,375 male subjects over 20 years and suggested the daily intake of an Imperial pint (~568 mL) of milk or equivalent dairy products more than halved the risk of metabolic syndrome. Some subsequent studies support the authors findings, while others dispute them. A systematic review of four randomized controlled trials said that, in the short term, a paleolithic nutritional pattern improved three of five measurable components of the metabolic syndrome in participants with at least one of the components. Management Medications Generally, the individual disorders that compose the metabolic syndrome are treated separately. Diuretics and ACE inhibitors may be used to treat hypertension. Various cholesterol medications may be useful if LDL cholesterol, triglycerides, and/or HDL cholesterol is abnormal. Diet Dietary carbohydrate restriction reduces blood glucose levels, contributes to weight loss, and reduces the use of several medications that may be prescribed for metabolic syndrome. Epidemiology Approximately 20–25 percent of the worlds adult population has the cluster of risk factors that is metabolic syndrome. In 2000, approximately 32% of U.S. adults had metabolic syndrome. In more recent years that figure has climbed to 34%.In young children, there is no consensus on how to measure metabolic syndrome since age-specific cut points and reference values that would indicate "high risk" have not been well established. A continuous cardiometabolic risk summary score is often used for children instead of a dichotomous measure of metabolic syndrome. History In 1921, Joslin first reported the association of diabetes with hypertension and hyperuricemia. In 1923, Kylin reported additional studies on the above triad. In 1947, Vague observed that upper body obesity appeared to predispose to diabetes, atherosclerosis, gout and calculi. In the late 1950s, the term metabolic syndrome was first used In 1967, Avogadro, Crepaldi and coworkers described six moderately obese people with diabetes, hypercholesterolemia, and marked hypertriglyceridemia, all of which improved when the affected people were put on a hypocaloric, low-carbohydrate diet. In 1977, Haller used the term "metabolic syndrome" for associations of obesity, diabetes mellitus, hyperlipoproteinemia, hyperuricemia, and hepatic steatosis when describing the additive effects of risk factors on atherosclerosis. The same year, Singer used the term for associations of obesity, gout, diabetes mellitus, and hypertension with hyperlipoproteinemia. In 1977 and 1978, Gerald B. Phillips developed the concept that risk factors for myocardial infarction concur to form a "constellation of abnormalities" (i.e., glucose intolerance, hyperinsulinemia, hypercholesterolemia, hypertriglyceridemia, and hypertension) associated not only with heart disease, but also with aging, obesity and other clinical states. He suggested there must be an underlying linking factor, the identification of which could lead to the prevention of cardiovascular disease; he hypothesized that this factor was sex hormones. In 1988, in his Banting lecture, Gerald M. Reaven proposed insulin resistance as the underlying factor and named the constellation of abnormalities syndrome X. Reaven did not include abdominal obesity, which has also been hypothesized as the underlying factor, as part of the condition. See also Metabolic disorder Portal-visceral hypothesis References == External links ==

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What does the medical term 'Thunderclap headache' encompass?

A thunderclap headache is a headache that is severe and has a sudden onset. It is defined as a severe headache that takes seconds to minutes to reach maximum intensity. Although approximately 75% are attributed to "primary" headaches—headache disorder, non-specific headache, idiopathic thunderclap headache, or uncertain headache disorder—the remainder are secondary to other causes, which can include some extremely dangerous acute conditions, as well as infections and other conditions. Usually, further investigations are performed to identify the underlying cause. Signs and symptoms A headache is called "thunderclap headache" if it is severe in character and reaches maximum severity within seconds to minutes of onset. In many cases, there are no other abnormalities, but the various causes of thunderclap headaches may lead to a number of neurological symptoms. Causes Approximately 75% are attributed to "primary" headaches: headache disorder, non-specific headache, idiopathic thunderclap headache or uncertain headache disorder. The remainder are secondary to a number of conditions, including: Subarachnoid hemorrhage (10–25% of all cases of thunderclap headache) Cerebral venous sinus thrombosis Cervical artery dissection Hypertensive emergency (severely raised blood pressure) Spontaneous intracranial hypotension (unexplained low cerebrospinal fluid pressure) Stroke (headache occurs in about 25% of strokes but usually not thunderclap character) Retroclival hematoma (hematoma behind the clivus in the skull, usually due to physical trauma but sometimes spontaneous) Pituitary apoplexy (infarction or hemorrhage of the pituitary gland) Colloid cyst of the third ventricle Meningitis, sinusitis Reversible cerebral vasoconstriction syndrome (previously Call-Fleming syndrome, several subtypes) Primary cough headache, primary exertional headache, and primary sexual headacheThe most important of the secondary causes are subarachnoid hemorrhage, cerebral venous sinus thrombosis, and dissection of an artery in the neck.In subarachnoid hemorrhage, there may be syncope (transient loss of consciousness), seizures, meningism (neck pain and stiffness), visual symptoms, and vomiting. 50–70% of people with subarachnoid hemorrhage have an isolated headache without decreased level of consciousness. The headache typically persists for several days.Cerebral venous sinus thrombosis, thrombosis of the veins of the brain, usually causes a headache that reflects raised intracranial pressure and is therefore made worse by anything that makes the pressure rise further, such as coughing. In 2–10% of cases, the headache is of thunderclap character. In most cases there are other neurological abnormalities, such as seizures and weakness of part of the body, but in 15–30% the headache is the only abnormality.Carotid artery dissection and vertebral artery dissection (together cervical artery dissection), in which a tear forms inside the wall of the blood vessels that supply the brain, often causes pain on the affected side of the head or neck. The pain usually precedes other problems that are caused by impaired blood flow through the artery into the brain; these may include visual symptoms, weakness of part of the body, and other abnormalities depending on the vessel affected. Diagnosis The most important initial investigation is computed tomography of the brain, which is very sensitive for subarachnoid hemorrhage. If this is normal, a lumbar puncture is performed, as a small proportion of SAH is missed on CT and can still be detected as xanthochromia.If both investigations are normal, the specific description of the headache and the presence of other abnormalities may prompt further tests, usually involving magnetic resonance imaging (MRI). Magnetic resonance angiography (MRA) may be useful in identifying problems with the arteries (such as dissection), and magnetic resonance venography (MRV) identifies venous thrombosis. It is not usually necessary to proceed to cerebral angiography, a more precise but invasive investigation of the brains blood vessels, if MRA and MRV are normal. Epidemiology Incidence of thunderclap headache has been estimated at 43 per 100,000 people every year. Approximately 75% are attributed to "primary" headaches: headache disorder, non-specific headache, idiopathic thunderclap headache or uncertain headache disorder. The remainder is attributed to secondary causes: vascular problems, infections and various other conditions. History The importance of severe headaches in the diagnosis of subarachnoid hemorrhage has been known since the 1920s, when London neurologist Charles Symonds described the clinical syndrome. The term "thunderclap headache" was introduced in 1986 in a report by John Day and Neil Raskin, neurologists at the University of California, San Francisco, in a report of a 42-year-old woman who had experienced several sudden headaches and was found to have an aneurysm that had not ruptured. References Further reading Dodick, DW (1 January 2002). "Thunderclap headache". Journal of Neurology, Neurosurgery & Psychiatry. 72 (1): 6–11. doi:10.1136/jnnp.72.1.6. PMC 1737692. PMID 11784817. Ju, Yo-El; Schwedt, Todd (29 March 2010). "Abrupt-Onset Severe Headaches". Seminars in Neurology. 30 (2): 192–200. doi:10.1055/s-0030-1249229. PMC 3558726. PMID 20352589. Ducros, A; Bousser, MG (9 January 2013). "Thunderclap headache". BMJ. 346 (jan08 15): e8557. doi:10.1136/bmj.e8557. PMID 23303883. S2CID 2537784. == External links ==

You are an expert in medical terminology. Explain medical terms in a way that is both precise and easy to understand for non-medical audiences.

Could you please explain the term 'Overlap syndrome' in simple language?

An overlap syndrome is a medical condition which shares features of at least two more widely recognised disorders. Examples of overlap syndromes can be found in many medical specialties such as overlapping connective tissue disorders in rheumatology, and overlapping genetic disorders in cardiology. Rheumatology Examples of overlap syndromes in rheumatology include mixed connective tissue disease and scleromyositis. Diagnosis depends on which diseases the patient shows symptoms and has positive antibodies for in their lab serology. In overlap syndrome, features of the following diseases are found (most common listed): Systemic lupus erythematosus (SLE) Systemic sclerosis Polymyositis Dermatomyositis Rheumatoid arthritis (RA) Sjögrens syndrome Eosinophilic granulomatosis with polyangiitis (EGPA) Autoimmune thyroiditis Antiphospholipid antibody syndromeThe treatment of overlapping connective tissue disorders is mainly based on the use of corticosteroids and immunosuppressants. Biologic drugs, i.e. anti-TNFα or anti-CD20 monoclonal antibodies, have been recently introduced as alternative treatments in refractory cases. There are some concerns with the use of anti-TNF agents in patients with systemic autoimmune diseases due to the risk of triggering disease exacerbations.The term polyangiitis overlap syndrome refers to a systemic vasculitis that shares features with two or more distinct vasculitis syndromes. The most common type of polyangiitis overlap syndrome is microscopic polyangiitis (MPA), which shares features with EGPA, granulomatosis with polyangiitis and panarteritis nodosa. Sometimes polyangiitis overlap syndrome is used as a synonym for MPA. Gastroenterology In gastroenterology, the term overlap syndrome may be used to describe autoimmune liver diseases that combine characteristic features of autoimmune hepatitis, primary biliary cirrhosis and primary sclerosing cholangitis. Cardiology In cardiology, genetic conditions such as Brugada syndrome can share features with related disorders caused by mutations in the same gene. An overlap syndrome can be seen whereby a mutation in the SCN5A gene encoding the cardiac sodium channel causes a reduction in the peak sodium current leading to the typical ECG features of Brugada syndrome, but which simultaneously increases the sustained late sodium current leading to the ECG features of Long QT syndrome type 3. Brugada syndrome can also overlap with arrhythmogenic cardiomyopathy due to certain mutations in the plakophilin gene. See also Autoimmune Mixed connective tissue disease References Further reading The Myositis Association Overlap Syndrome 2011 Conference Presentation == External links ==

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I'm encountering the term 'Cutaneous larva migrans' in medical literature. What's its definition?

Cutaneous larva migrans (abbreviated CLM) is a skin disease in humans, caused by the larvae of various nematode parasites of the hookworm family (Ancylostomatidae). These parasites live in the intestines of dogs, cats, and wild animals and should not be confused with other members of the hookworm family for which humans are definitive hosts, namely Ancylostoma duodenale and Necator americanus. Colloquially called creeping eruption due to its presentation, the disease is also somewhat ambiguously known as "ground itch" or (in some parts of the southern United States) "sandworms", as the larvae like to live in sandy soil. Another vernacular name is plumbers itch. The medical term CLM literally means "wandering larvae in the skin". Symptoms and signs The infection causes a red, intensely pruritic (itchy) eruption, and may look like twirling lesions. The itching can become very painful and if scratched may allow a secondary bacterial infection to develop. Cutaneous larva migrans usually heals spontaneously over weeks to months and has been known to last as long as one year. However, the severity of the symptoms usually causes those infected to seek medical treatment before spontaneous resolution occurs. Following proper treatment, migration of the larvae within the skin is halted and relief of the associated itching can occur in less than 48 hours (reported for thiabendazole).This is separate from the similar cutaneous larva currens which is caused by Strongyloides. Larva currens is also a cause of migratory pruritic eruptions but is marked by 1) migratory speed on the order of inches per hour 2) perianal involvement due to autoinfection from stool and 3) a wide band of urticaria. Cause Hookworm eggs are shed in the infected dog (or other animal) feces to the ground and beach sand, where they then develop over a period of 1–2 weeks into the infectious larval form (filariform larvae). The filariform larvae can burrow through intact skin that comes into contact with soil or sand that is contaminated with feces. Although they are able to infect the deeper tissues of animals (through to the lungs and then the intestinal tract), humans are incidental hosts and the larvae are only able to penetrate the epidermis of the skin and thus create the typical wormlike burrows visible underneath the skin. These parasites apparently lack the collagenase enzymes required to penetrate through the basement membrane deeper into the dermal layers of the skin. Treatment CLM can be treated in a number of different ways: Systemic (oral) agents include albendazole (trade name Albenza) and ivermectin (trade name Stromectol). Another agent which can be applied either topically or taken by mouth is thiabendazole (trade name Mintezol), an anti-helminthic. Topical freezing agents, such as ethylene chloride or liquid nitrogen, applied locally can freeze and kill the larvae, but this method has a high failure rate because the larvae are usually located away from the site of the visible skin trails. Additionally, this is a painful method which can cause blistering and/or ulceration of the skin and it is therefore not recommended. It is recommended to use Benadryl or some anti-itch cream (i.e. Cortizone or Calamine lotion). This will help relieve some of the itch. Wearing shoes in areas where these parasites are known to be endemic offers protection from infection. In general, avoiding exposure of skin to contaminated soil or sand offers the best protection. In some areas dogs have been prohibited from beaches in an attempt to control human infection. Additional images See also Dermatology Intestinal parasite Visceral larva migrans List of migrating cutaneous conditions References External links DermAtlas -1921851750

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Can you demystify the medical term 'Fulvestrant' for me?

Fulvestrant, sold under the brand name Faslodex among others, is a medication used to treat hormone receptor (HR)-positive metastatic breast cancer in postmenopausal women with disease progression as well as HR-positive, HER2-negative advanced breast cancer in combination with palbociclib in women with disease progression after endocrine therapy. It is given by injection into a muscle.Fulvestrant is a selective estrogen receptor degrader (SERD) and was first-in-class to be approved. It works by binding to the estrogen receptor and destabilizing it, causing the cells normal protein degradation processes to destroy it.Fulvestrant was approved for medical use in the United States in 2002. Medical uses Breast cancer Fulvestrant is used for the treatment of hormone receptor positive metastatic breast cancer or locally advanced unresectable disease in postmenopausal women; it is given by injection. A 2017 Cochrane review found it is as safe and effective as first line or second line endocrine therapy.It is also used to treat ER-positive, HER2-negative advanced or metastatic breast cancer in combination with palbociclib in women with disease progression after first-line endocrine therapy.Due to the medications having a chemical structure similar to that of estrogen, it can interact with immunoassays for blood estradiol concentrations and show falsely elevated results. This can improperly lead to discontinuing the treatment. Early puberty Fulvestrant has been used in the treatment of peripheral precocious puberty in girls with McCune–Albright syndrome. Available forms Fulvestrant is provided in a castor oil solution also containing alcohol, benzyl alcohol, and benzyl benzoate. It is supplied at a concentration of 250 mg/5 mL. Contraindications Fulvestrant should not be used in women with kidney failure or who are pregnant. Side effects Very common (occurring in more than 10% of people) adverse effects include nausea, injection site reactions, weakness, and elevated transaminases. Common (between 1% and 10%) adverse effects include urinary tract infections, hypersensitivity reactions, loss of appetite, headache, blood clots in veins, hot flushes, vomiting, diarrhea, elevated bilirubin, rashes, and back pain. In a large clinical trial, the incidence of venous thromboembolism (VTE) with fulvestrant was 0.9%. Pharmacology Pharmacodynamics Fulvestrant is an antiestrogen which acts as an antagonist of the estrogen receptor (ER) and additionally as a selective estrogen receptor degrader (SERD). It works by binding to the estrogen receptor and making it more hydrophobic, which makes the receptor unstable and misfold, which in turn leads normal processes inside the cell to degrade it.In addition to its antiestrogenic activity, fulvestrant is an agonist of the G protein-coupled estrogen receptor (GPER), albeit with relatively low affinity (10–100 nM, relative to 3–6 nM for estradiol). Pharmacokinetics Fulvestrant after an intramuscular injection is slowly absorbed and maximal levels (Cmax) are reached after 5 days on average with a range of 2 to 19 days. The elimination half-life of fulvestrant with intramuscular injection is 40 to 50 days. This is 40 times longer than the half-life of fulvestrant by intravenous injection, indicating that its long half-life with intramuscular injection is due to slow absorption from the injection site. Levels of fulvestrant with 500 mg/month by intramuscular injection (and a single additional 500 mg loading dose on day 15 of therapy) in postmenopausal women with advanced breast cancer were 25.1 ng/mL (25,100 pg/mL) at peak and 28.0 ng/mL (28,000 pg/mL) at trough with a single dose and 28.0 ng/mL (28,000 pg/mL) at peak and 12.2 ng/mL (12,200 pg/mL) at trough after multiple doses at steady state.Fulvestrant does not cross the blood–brain barrier in animals and may not in humans as well. Accordingly, no effects of fulvestrant on brain function have been observed in preclinical or clinical research. Fulvestrant is highly (99%) bound to plasma proteins. It is bound to very low density lipoprotein, low density lipoprotein, and high density lipoprotein, but not to sex hormone-binding globulin.Fulvestrant appears to be metabolized along similar pathways as endogenous steroids; CYP3A4 may be involved, but non-cytochrome P450 routes appear to be more important. It does not inhibit any cytochrome P450 enzymes. Elimination is almost all via feces.Fulvestrant can form colloidal aggregates at certain concentration ranges and this can limit its activity as well as produce bell-shaped concentration–response curves. Chemistry Fulvestrant, also known as 7α-[9-[(4,4,5,5,5-pentafluoropentyl)sulfinyl]nonyl]estradiol, is a synthetic estrane steroid and a derivative of estradiol. An alkyl-sulfinyl moiety was added to the endogenous estrogen receptor ligand.It was discovered through rational drug design, but was selected for further development via phenotypic screening. History Fulvestrant was the first selective estrogen receptor degrader to be approved. It was approved in the United States in 2002 and in Europe in 2004. Society and culture NICE evaluation The U.K. National Institute for Health and Clinical Excellence (NICE) said in 2011 that it found no evidence Faslodex was significantly better than existing treatments, so its widespread use would not be a good use of resources for the countrys National Health Service. The first months treatment of Faslodex, which starts with a loading dose, costs £1,044.82 ($1,666), and subsequent treatments cost £522.41 a month. In the 12 months ending June 2015, the UK price (excluding VAT) of a months supply of anastrozole (Arimidex), which is off patent, cost 89 pence/day, and letrozole (Femara) cost £1.40/day. Patent extension The original patent for Faslodex expired in October 2004. Drugs subject to pre-marketing regulatory review are eligible for patent extension, and for this reason AstraZeneca got an extension of the patent to December 2011. AstraZeneca has filed later patents. A generic version of Faslodex has been approved by the FDA. However, this does not mean that the product will necessarily be commercially available - possibly because of drug patents and/or drug exclusivity. A later patent for Faslodex expires in January 2021. Atossa Genetics has a patent for the administration of fulvestrant into the breast via a microcatheter invented by Susan Love. Research Fulvestrant was studied in endometrial cancer but results were not promising and as of 2016 development for this use was abandoned.Because fulvestrant cannot be given orally, efforts have been made to develop SERD drugs that can be taken by mouth, including brilanestrant and elacestrant. The clinical success of fulvestrant also led to efforts to discover and develop a parallel drug class of selective androgen receptor degraders (SARDs).ZB716, or fulvestrant-3-boronic acid, is an oral prodrug of fulvestrant which is under development. References External links "Fulvestrant". Drug Information Portal. U.S. National Library of Medicine.

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I've encountered the term 'Sertaconazole' while reading about medical topics. What does it refer to exactly?

Sertaconazole, sold under the brand name Ertaczo among others, is an antifungal medication of the Benzothiophene class. It is available as a cream to treat skin infections such as athletes foot. It is also available in a vaginal tablet form. The most popular of these is Gyno-Dermofix. Medical uses In randomized, double-blind, multicentre trials of 3 to 6 weeks duration (n=127-383), a significantly greater number of patients with tinea of the glabrous skin and tinea pedis receiving a topical 2% sertaconazole cream once or twice daily achieved a successful mycological cure compared with recipients of a placebo cream. Side effects Side effects were rarely reported with sertaconazole therapy, but may include contact dermatitis, burning on application site and skin dryness. Pharmacology Pharmacodynamics Sertaconazole has several known mechanisms of action. It is considered fungistatic, fungicidal, antibacterial, antiinflammatory, antitrichomonal, and antipruritic.Like other imidazole antifungals, sertaconazole blocks the synthesis of ergosterol by inhibiting the 14α-demethylase enzyme. Ergosterol is a critical component of the fungal cell membrane. Inhibition of ergosterol synthesis prevents fungal cells from multiplying and impairs hyphae growth. Chemically, sertaconazole contains a benzothiophene ring which makes it unique from other imidazole antifungals. A benzothiophene ring is a sulfur analogue of the indole ring found in the amino acid tryptophan. Tryptophan is found in the fungal membrane in addition to lipids such as ergosterol. The benzothiophene ring in sertaconazole mimics tryptophan and increases the drugs ability to form pores in the fungal cell membrane. If the cell membrane is made sufficiently leaky by these pores the fungal cell will die from loss of ATP and other effects which can include calcium disregulation. These pores are believed to open at about 10 minutes following topical application of sertaconazole. One hour following topical application, approximately 90% of fungal cells die from lack of energy (due to ATP loss) and general loss of homeostasis. Sertaconazole is thought to be the only Benzothiophene antifungal with this mechanism of action. Sertaconazole has also antiinflammatory and antipruritic action. It inhibits the release of proinflammatory cytokines from activated immune cells. It has been shown that sertaconazole activates the p38/COX2/PGE2 pathway. PGE2 can have a variety of important effects in the body including activation of the bodys fever response. Sertaconazole also has antibacterial action. It is hypothesized that the mechanism of action again involves sertaconazoles ability to form pores by mimicking tryptophan. It has also been shown that sertaconazole can kill Trichomonas vaginalis in vitro. The exact mechanism of action is as yet unknown. Sertaconazole also appears to inhibit the dimorphic transformation of Candida albicans into pathogenic fungi. The following fungal organisms, among others, are known to be susceptible to sertaconazole: Candida albicans Epidermophyton floccosum Trichophyton mentagrophytes Trichophyton rubrum Chemistry Sertaconazole contains a stereocenter and consists of two enantiomers. The pharmaceutical drug is a racemate, an equal mixture of the (R)- and (S)-forms. References External links "Sertaconazole". Drug Information Portal. U.S. National Library of Medicine. "Sertaconazole nitrate". Drug Information Portal. U.S. National Library of Medicine.

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Could you provide a brief overview of 'Epidermolysis bullosa' in a medical context?

Epidermolysis bullosa (EB) is a group of rare medical conditions that result in easy blistering of the skin and mucous membranes. Blisters occur with minor trauma or friction and are painful. Its severity can range from mild to fatal. Inherited EB is a rare disease with a prevalence in the United States of 8.2 per million live births. Those with mild cases may not develop symptoms until they start to crawl or walk. Complications may include esophageal narrowing, squamous cell skin cancer, and the need for amputations. EB is due to a mutation in at least one of 16 different genes. Some types are autosomal dominant while others are autosomal recessive. The underlying mechanism is a defect in attachment between or within the layers of the skin. Loss or diminished function of C7 leads to weakness in the structural architecture of the dermal–epidermal junction (DEJ) and mucosal membranes. There are four main types: epidermolysis bullosa simplex (EBS), dystrophic epidermolysis bullosa (DEB), junctional epidermolysis bullosa (JEB), and Kindler syndrome. The diagnosis is suspected based on symptoms and confirmed by skin biopsy or genetic testing. There is no cure for the condition. Management involves wound care, pain control, controlling infections, nutritional support, and prevention and treatment of complications. About half a million people are affected globally. It occurs equally commonly in males and females. Classification Epidermolysis bullosa refers to a group of disorders that involve the formation of blisters following trivial trauma. Over 300 mutations have been identified in this condition. They have been classified into the following types:: 596 Epidermolysis bullosa simplex Epidermolysis bullosa simplex (EBS) is a form of EB that causes blisters at the site of rubbing. It typically affects the hands and feet, and is typically inherited in an autosomal dominant manner, affecting the keratin genes KRT5 and KRT14. Therefore, there is a failure in keratinization, which affects the integrity and the ability of the skin to resist mechanical stresses. Junctional epidermolysis bullosa Junctional epidermolysis bullosa (JEB) is an inherited disease affecting laminin and collagen. This disease is characterized by blister formation within the lamina lucida of the basement membrane zone: 599  and is inherited in an autosomal recessive manner. It also presents with blisters at the site of friction, especially on the hands and feet, and has variants that can occur in children and adults. Less than one person per million people is estimated to have this form of EB. Dystrophic epidermolysis bullosa Dystrophic epidermolysis bullosa (DEB) is an inherited variant affecting the skin and other organs. DEB is caused by genetic defects (or mutations) within the human COL7A1 gene encoding the protein type VII collagen (collagen VII). DEB-causing mutations can be either autosomal dominant or autosomal recessive. Epidermis bullosa pruriginosa and albopapuloid epidermolysis bullosa (Pasinis disease) are rare subtypes of this disease. Other genetic Epidermolysis bullosa acquisita Acral peeling Pathophysiology The human skin consists of two layers: an outermost layer called the epidermis and a layer underneath called the dermis. In individuals with healthy skin, there are protein anchors between these two layers (Dermo epidermal junction) that prevent them from moving independently from one another (shearing). In people born with EB, the two skin layers lack the protein anchors that hold them together, resulting in extremely fragile skin—even minor mechanical friction (like rubbing or pressure) or trauma will separate the layers of the skin and form blisters and painful sores. EB individuals manifest unremitting skin blistering that evolves into chronic wounds, inflammation, and fibrosis.People with EB have compared the sores with third-degree burns. Furthermore, as a complication of the chronic skin damage, people with EB have an increased risk of malignancies (cancers) of the skin.Virtually any organ lined or covered by epithelium may be injured in inherited EB. External eye, esophagus, upper airway, and genitourinary tract are the epithelial surfaced tissues that are at particular risk. Diagnosis EB can be diagnosed either by a skin (punch) biopsy at the edge of a wound with immunofluorescent mapping, or via blood sample and genetic testing. Treatment The combination of birch bark extract from Betula pendula and Betula pubescens is used to treat epidermolysis bullosa.Research has focused on changing the mixture of keratins produced in the skin. There are 54 known keratin genes—of which 28 belong to the type I intermediate filament genes and 26 to type II—which work as heterodimers. Many of these genes share substantial structural and functional similarity, but they are specialized to cell type and/or conditions under which they are normally produced. If the balance of production could be shifted away from the mutated, dysfunctional keratin gene toward an intact keratin gene, symptoms could be reduced. For example, sulforaphane, a compound found in broccoli, was found to reduce blistering in a mouse model to the point where affected pups could not be identified visually, when injected into pregnant mice (5 μmol/day = 0.9 mg) and applied topically to newborns (1 μmol/day = 0.2 mg in jojoba oil).As of 2008 clinical research at the University of Minnesota has explored allogeneic bone marrow transplantation for RD and junctional EB, treating a two-year-old child who is one of two brothers with EB. A second transplant has also been performed on the childs older brother, and a third transplant is scheduled for a California baby. A clinical trial is planned for 30 subjects. However, the immune suppression that bone marrow transplantation requires causes a risk of serious infections with large scale blisters and skin erosion. Indeed, at least four people have died in the course of either preparation for or institution of bone marrow transplantation for EB, out of only a small group of patients treated so far. The mechanism of action of this therapy is unclear as hematopoietic stem cells are not thought to contribute to epithelial lineages. Rather, it is speculated that cross-correction from tissue-resident graft-derived immune cells contributes to the observed clinical benefit.A pilot study performed in 2015 suggests that systemic granulocyte-colony stimulating factor (G-CSF) may promote increased wound healing in people with dystrophic EB. Transplanting skin derived from genetically modified stem cells onto the wound surfaces has been studied with a report of improvements in one person.A 2017 clinical trial with male RDEB (recessive dystrophic EB) patients conducted successful grafting of type VII gene corrected keratinocytes (COL7A1 gene correction using retrovirus transduction), without any serious adverse effects. Type VII collage formation was observed at the dermis-epidermis junction in significant amounts.A 2020 study demonstrated the safe allogenic grafting of acellular dermal matrix/scaffolds in EB patients without any observed infection or necrosis and instead noted fewer required dressing changes, promoted wound healing, pain reduction, and an overall improvement in the quality of life of the patients. Monitoring The Epidermolysis Bullosa Disease Activity and Scarring index (EBDASI) is a scoring system that objectively quantifies the severity of EB. The EBDASI is a tool for clinicians and patients to monitor the severity of the disease. It has also been designed to evaluate the response to new therapies for the treatment of EB. The EBDASI was developed and validated by Professor Dedee Murrell and her team of students and fellows at the St George Hospital, University of New South Wales, in Sydney, Australia. It was presented at the International Investigative Dermatology congress in Edinburgh in 2013 and a paper-based version was published in the Journal of the American Academy of Dermatology in 2014. Prognosis A 2014 study classified cases into three types—EBS, JEB and DEB—and reviewed their times of death. The first two types tended to die in infancy and the last in early adulthood. In a survey of 11 families affected by the disease, lack of awareness of the disease by both the public and health care providers raised concerns about the care provided. Epidemiology An estimated 20 per million live births are diagnosed with EB, and 9 per million people in the general population have the condition. Of these cases, approximately 92% are EBS, 5% are DEB, 1% are JEB, and 2% are unclassified. Carrier frequency ranges from 1 in 333 for JEB, to 1 in 450 for DEB; the carrier frequency for EBS is presumed to be much higher than JEB or DEB.The disorder occurs in every racial and ethnic group and affects both sexes. Society and culture In 2010, Emma Fogarty, a campaigner for DEBRA Ireland (the EB charity) was awarded a People of the Year Award. Actor Colin Farrell has campaigned with Fogarty on behalf of affected people.In 2014, Pearl Jam lead vocalist Eddie Vedder together with his wife Jill McCormick co-founded the EB Research Partnership, a non-profit organization dedicated to finding a cure for EB. McCormick is childhood friends with Ryan Fullmer, whose son, Michael, was born with EB. Vedder, McCormick, Ryan Fullmer, and his wife, Heather founded Heal EB. In 2014, they merged Heal EB with the Jackson Gabriel Research Foundation to create the EB Research Partnership. The EBRP hosts several annual fundraising events. To date, they have raised $12 million to fund research to find a cure. On March 1, 2019, heavyweight boxer Luis Ortiz was named an honorary ambassador for the EB community by the EB Research Partnership. Ortizs daughter, Lismercedes, was born with EB. Movies The condition was brought to public attention in 2004 in the UK through the Channel 4 documentary The Boy Whose Skin Fell Off, chronicling the life and death of Jonny Kennedy, an Englishman with EB. In the United States, the same could be said of the HBO documentary My Flesh and Blood from 2003. Additionally, the film Butterfly Girl follows Abigail Evans with the disease. In Canada, The Sports Networks award-winning documentary on Jonathan Pitre led to extensive coverage on the boys disease, treatment, and death. Other names Other terms used to describe those affected include "butterfly children" as the skin is fragile as a butterflys wings, "cotton wool babies", or "crystal skin children". References External links GeneReviews/NCBI/UW/NIH entry on Epidermolysis Bullosa Simplex Questions and Answers about Epidermolysis Bullosa - US National Institute of Arthritis and Musculoskeletal and Skin Diseases

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I'm seeking clarification on the medical term 'Acute cerebellar ataxia of childhood.' Could you explain it?

Acute cerebellar ataxia of childhood is a childhood condition characterized by an unsteady gait, most likely secondary to an autoimmune response to infection, drug induced or paraneoplastic. Most common virus causing acute cerebellar ataxia are chickenpox virus and Epstein–Barr virus, leading to a childhood form of post viral cerebellar ataxia. It is a diagnosis of exclusion. Signs and symptoms Acute cerebellar ataxia usually follows 2–3 weeks after an infection. Onset is abrupt. Vomiting may be present at the onset but fever and nuchal rigidity characteristically are absent. Horizontal nystagmus is present in approximately 50% of cases. Truncal ataxia with deterioration of gait Slurred speech and nystagmus Afebrile Cause Possible causes of acute cerebellar ataxia include varicella infection, as well as infection with influenza, Epstein–Barr virus, Coxsackie virus, Echo virus or mycoplasma. Diagnosis Acute Cerebellar ataxia is a diagnosis of exclusion. Urgent CT scan is necessary to rule out cerebellar tumor or hemorrhage as cause of the ataxia; however in acute cerebellar ataxia, the CT will be normal. CSF studies are normal earlier in the course of disease. Later on CSF shows moderate elevation of proteins. Differential diagnosis Brain tumors, including cerebellar astrocytoma, medulloblastoma, neuroblastoma Cerebellar contusion Subdural hematoma Toxins, including ethanol or anticonvulsants Cerebellar infarction or hemorrhage Meningitis Encephalitis Acute disseminated encephalomyelitis Multiple sclerosis Management Supportive treatment is the only intervention for acute cerebellar ataxia of childhood. Symptoms may last as long as 2 or 3 months. Epidemiology Acute cerebellar ataxia is the most common cause of unsteady gait in children. The condition is rare in children older than ten years of age. Most commonly acute cerebellar ataxia affects children between age 2 and 7 years. See also Gluten ataxia References == External links ==

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The term 'Nitrofurantoin' keeps coming up in medical discussions. What does it stand for?

Nitrofurantoin is an antibacterial medication used to treat urinary tract infections, but it is not as effective for kidney infections. It is taken by mouth.Common side effects include nausea, loss of appetite, diarrhea, and headaches. Rarely numbness, lung problems, or liver problems may occur. It should not be used in people with kidney problems. While it appears to be generally safe during pregnancy it should not be used near delivery. While it usually works by slowing bacterial growth, it may result in bacterial death at the high concentrations found in urine.Nitrofurantoin was first sold in 1953. It is on the World Health Organizations List of Essential Medicines. It is available as a generic medication. In 2019, it was the 192nd most commonly prescribed medication in the United States, with more than 2 million prescriptions. Medical uses Current uses include the treatment of uncomplicated urinary tract infections (UTIs) and prophylaxis against UTIs in people prone to recurrent UTIs.Increasing bacterial antibiotic resistance to other commonly used agents, such as trimethoprim/sulfamethoxazole and fluoroquinolones, has led to increased interest in using nitrofurantoin. The efficacy of nitrofurantoin in treating UTIs combined with a low rate of bacterial resistance to this agent makes it one of the first-line agents for treating uncomplicated UTIs as recommended by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.Nitrofurantoin is not recommended for the treatment of pyelonephritis, prostatitis, and intra-abdominal abscess, because of extremely poor tissue penetration and low blood levels. Antibacterial activity Nitrofurantoin has been shown to have good activity against: E. coli Staphylococcus saprophyticus Coagulase negative staphylococci Enterococcus faecalis Staphylococcus aureus Streptococcus agalactiae Citrobacter species Klebsiella species Bacillus subtilis speciesIt is used in the treatment of infections caused by these organisms.Many or all strains of the following genera are resistant to nitrofurantoin: Enterobacter Proteus PseudomonasAntibiotic susceptibility testing should always be performed to further elucidate the resistance profile of the particular strain of bacteria causing infection. Special populations Pregnancy Nitrofurantoin is pregnancy category B in the United States and pregnancy category A in Australia. It is one of the few drugs commonly used in pregnancy to treat UTIs. It however should not be used in late pregnancy due to the potential risk of hemolytic anemia in the newborn. Newborns of women given this drug late in pregnancy had a higher risk of developing neonatal jaundice.Evidence of safety in early pregnancy is mixed as of 2017. The American College of Obstetricians and Gynecologists states that while they can be used in the first trimester other options may be preferred. They remain a first line treatment in the second trimester. A 2015 meta analysis found no increased risk from first trimester use in cohort studies that was a slight increase of malformations in case control studies. Available forms There are two formulations of nitrofurantoin: Macrocrystals - (Macrodantin, Furadantin) – 25, 50, or 100 mg capsules – taken once every 6 hours Monohydrate/macrocrystals - (Macrobid) – 100 mg capsules – taken once every 12 hours or 2 times a day (written on prescriptions as BID, which is the last part of the trade name MacroBID). It is 75% monohydrate and 25% macrocrystals. Contraindications Nitrofurantoin is contraindicated in patients with decreased renal function (CrCl < 60 ml/min) due to systemic accumulation and subtherapeutic levels reached in the urinary tract. However, a retrospective chart review suggests the data for this cutoff are slim and a cutoff of CrCl < 40 ml/min would be more appropriate. Many of the severe side effects of this drug are more common in the elderly and those with renal impairment, as this causes the drug to be retained in the body and reach higher systemic levels. Thus, the drug is not recommended for the elderly population according to 2012 AGS Beers criteria.Nitrofurantoin is also contraindicated in babies up to the age of one month, as they have immature enzyme systems in their red blood cells (glutathione instability), so nitrofurantoin must not be used because it can cause haemolytic anaemia. For the same reason, nitrofurantoin should not be given to pregnant women after 38 weeks of pregnancy. Nitrofurantoin is contraindicated in patients with glucose-6-phosphate dehydrogenase deficiency (G6PD) because of risk of intravascular hemolysis resulting in anemia. Adverse effects The most common side effects with nitrofurantoin are nausea, headache, and flatulence. Less common adverse events (occurring in less than 1% of those taking the drug) include: Gastrointestinal: diarrhea, dyspepsia, abdominal pain, constipation, emesis Neurologic: dizziness, drowsiness, amblyopia Respiratory: acute pulmonary hypersensitivity reaction Allergic: pruritus, urticaria Dermatologic: hair loss Miscellaneous: fever, chills, malaisePatients should be informed that nitrofurantoin colors urine brown; this is completely harmless.Some of the more serious but rare side effects of nitrofurantoin have been a cause of concern. These include pulmonary reactions, hepatotoxicity, and neuropathy. Lung toxicity The pulmonary toxicity caused by nitrofurantoin can be categorized into acute, subacute, and chronic pulmonary reactions. The acute and subacute reactions are thought to be due to a hypersensitivity reaction and often resolve when the drug is discontinued. Acute reactions have been estimated to occur in about one in 5000 women who take the drug. These reactions usually develop 3–8 days after the first dose of nitrofurantoin, but may occur from a few hours to a few weeks after starting the drug. Symptoms include fever, dyspnea, chills, cough, pleuritic chest pain, headache, back pain, and epigastric pain. Chest radiograph will often show unilateral or bilateral infiltrates similar to pulmonary edema. Treatment includes discontinuation of the nitrofurantoin, which should result in symptom improvement within 24 hours.Chronic pulmonary reactions caused by nitrofurantoin include diffuse interstitial pneumonitis, pulmonary fibrosis, or both. This uncommon reaction may occur 1 month to 6 years after starting the drug and is usually related to its total lifetime dose. This reaction manifests with progressive shortness of breath. It is important to recognize nitrofurantoin as possible cause of symptoms and discontinue the drug when the suspicion of pulmonary side effects arises as it can be reversible if the drug is stopped early. Liver toxicity Hepatic reactions, including hepatitis, cholestatic jaundice, chronic active hepatitis, and hepatic necrosis, occur rarely. The onset of chronic active hepatitis may be insidious, and patients should be monitored periodically for changes in biochemical tests that would indicate liver injury. These reactions usually occur after exposure to the drug for more than 6 weeks. If signs of liver failure are observed in a patient taking nitrofurantoin, the drug should be discontinued. Re-challenge with the drug at a later date is not recommended, as the reaction may have a hypersensitivity component and recur when the drug is resumed. Neuropathy Neuropathy is a rare side effect of taking nitrofurantoin. Patients may experience numbness and tingling in a stocking-glove pattern, which may or may not improve upon discontinuation of the drug. Pharmacology Organisms are said to be susceptible to nitrofurantoin if their minimum inhibitory concentration is 32 μg/mL or less. The peak blood concentration of nitrofurantoin following an oral dose of nitrofurantoin 100 mg is less than 1 μg/mL and may be undetectable. Its bioavailability is about 90% and the urinary excretion is 40% tissue penetration is negligible; the drug is well concentrated in the urine: 75% of the dose is rapidly metabolised by the liver, but 25% of the dose is excreted in the urine unchanged, reliably achieving levels of 200 μg/mL or more. In studies of dogs, the majority of urinary excretion is through glomerular filtration with some tubular secretion. There is also tubular absorption which is increased with urine acidification. However the activity of nitrofurantoin is also pH dependent and mean inhibitory concentration rises sharply with increased pH above 6. Nitrofurantoin cannot be used to treat infections other than simple cystitis. At the concentrations achieved in urine (>100 μg/mL), nitrofurantoin is a bactericide. It is bacteriostatic against most susceptible organisms at concentrations less than 32 μg/mL.Nitrofurantoin and the quinolone antibiotics are mutually antagonistic in vitro. It is not known whether this is of clinical significance, but the combination should be avoided.Resistance to nitrofurantoin may be chromosomal or plasmid-mediated and involves inhibition of nitrofuran reductase. Acquired resistance in E. coli continues to be rare. Nitrofurantoin and its metabolites are excreted mainly by the kidneys. In renal impairment, the concentration achieved in urine may be subtherapeutic. Nitrofurantoin should not be used in patients with a creatinine clearance of 60 mL/min or less. However, a retrospective chart review may suggest nitrofurantoin is not contraindicated in this population. Mechanism of action Nitrofurantoin is concentrated in the urine, leading to higher and more effective levels in the urinary tract than in other tissues or compartments. With a 100 mg oral dose, plasma levels are typically less than 1 µg/mL while in the urine it reaches 200 µg/mL.The drug works by damaging bacterial DNA, since its reduced form is highly reactive. This is made possible by the rapid reduction of nitrofurantoin inside the bacterial cell by flavoproteins (nitrofuran reductase) to multiple reactive intermediates that attack ribosomal proteins, DNA, respiration, pyruvate metabolism and other macromolecules within the cell. Nitrofurantoin exerts greater effects on bacterial cells than mammalian cells because bacterial cells activate the drug more rapidly. It is not known which of the actions of nitrofurantoin is primarily responsible for its bactericidal activity. The broad mechanism of action for this drug likely is responsible for the low development of resistance to its effects, as the drug affects many different processes important to the bacterial cell. History Nitrofurantoin has been available for the treatment of lower urinary tract infections (UTIs) since 1953. Society and culture Brand names Nitrofurantoin is marketed under many names in countries worldwide. Animal feed Residues from the breakdown of nitrofuran veterinary antibiotics, including nitrofurantoin, have been found in chicken in Vietnam, China, Brazil, and Thailand. The European Union banned the use of nitrofurans in food producing animals by classifying it in ANNEX IV (list of pharmacologically active substances for which no maximum residue limits can be fixed) of the Council Regulation 2377/90. The Food and Drug Administration (FDA) of the United States has prohibited furaltadone since February 1985 and withdrew the approval for the other nitrofuran drugs (except some topical uses) in January 1992. The topical use of furazolidone and nitrofurazone was prohibited in 2002. Australia prohibited the use of nitrofurans in food production in 1992. Japan did not allocate MRLs for nitrofurans leading to the implementation of a "zero tolerance or no residue standard". In Thailand, the Ministry of Health issued in 2001 Proclamation No. 231 MRL of veterinary drug in food which did not allocate MRL for nitrofurans. The Ministry of Agriculture and Cooperatives had already prohibited importation and use of furazolidone and nitrofurazone in animal feed in 1999 which was extended to all nitrofurans in 2002. Several metabolites of nitrofurans, such as furazolidone, furaltadone and nitrofurazone cause cancer or genetic damage in rats. References External links "Nitrofurantoin". Drug Information Portal. U.S. National Library of Medicine.

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Could you provide a brief overview of 'Boutonneuse fever' in a medical context?

Boutonneuse fever (also called, Mediterranean spotted fever, fièvre boutonneuse, Kenya tick typhus, Indian tick typhus, Marseilles fever, or Astrakhan fever) is a fever as a result of a rickettsial infection caused by the bacterium Rickettsia conorii and transmitted by the dog tick Rhipicephalus sanguineus. Boutonneuse fever can be seen in many places around the world, although it is endemic in countries surrounding the Mediterranean Sea. This disease was first described in Tunisia in 1910 by Conor and Bruch and was named boutonneuse (French for "spotty") due to its papular skin-rash characteristics. Presentation After an incubation period around seven days, the disease manifests abruptly with chills, high fevers, muscular and articular pains, severe headache, and photophobia. The location of the bite forms a black, ulcerous crust (tache noire). Around the fourth day of the illness, a widespread rash appears, first macular and then maculopapular, and sometimes petechial. Diagnosis The diagnosis is made with serologic methods, either the classic Weil–Felix test, (agglutination of Proteus OX strains), ELISA, or immunofluorescence assays in the bioptic material of the primary lesion. The Weil–Felix test demonstrated low sensitivity (33%) in diagnosing acute rickettsial infections and low specificity, with a positive titre of 1:320 seen in 54% of healthy volunteers and 62% of non-rickettsial fever patients. Therefore, the use of the WFT should be discouraged in the diagnosis of acute rickettsial infections. Treatment The illness can be treated with tetracyclines (doxycycline is the preferred treatment), chloramphenicol, macrolides, or fluoroquinolones. See also Rocky Mountain spotted fever References == External links ==

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I'm trying to understand 'Eunuch' within a medical context. Could you shed some light on it?

A eunuch ( YOO-nək) is a man who has been castrated. Throughout history, castration often served a specific social function.The earliest records for intentional castration to produce eunuchs are from the Sumerian city of Lagash in the 2nd millennium BCE. Over the millennia since, they have performed a wide variety of functions in many different cultures: courtiers or equivalent domestics, for espionage or clandestine operations, castrato singers, concubines, or sexual partners, religious specialists, soldiers, royal guards, government officials, and guardians of women or harem servants. Eunuchs would usually be servants or slaves who had been castrated to make them less threatening servants of a royal court where physical access to the ruler could wield great influence. Seemingly lowly domestic functions—such as making the rulers bed, bathing him, cutting his hair, carrying him in his litter, or even relaying messages—could, in theory, give a eunuch "the rulers ear" and impart de facto power on the formally humble but trusted servant. Similar instances are reflected in the humble origins and etymology of many high offices. Eunuchs supposedly did not generally have loyalties to the military, the aristocracy, or a family of their own (having neither offspring nor in-laws, at the very least). They were thus seen as more trustworthy and less interested in establishing a private "dynasty". Because their condition usually lowered their social status, they could also be easily replaced or killed without repercussion. In cultures that had both harems and eunuchs, eunuchs were sometimes used as harem servants. Etymology Eunuch comes from the Ancient Greek word εὐνοῦχος (eunoukhos), first attested in a fragment of Hipponax, the 6th century BCE comic poet and prolific inventor of compound words. The acerbic poet describes a particular lover of fine food having "consumed his estate dining lavishly and at leisure every day on tuna and garlic-honey cheese paté like a Lampsacene eunoukhos."The earliest surviving etymology of the word is from late antiquity. The 5th century (CE) Etymologicon by Orion of Thebes offers two alternative origins for the word eunuch: first, to tēn eunēn ekhein, "guarding the bed", a derivation inferred from eunuchs established role at the time as "bedchamber attendants" in the imperial palace, and second, to eu tou nou ekhein, "being good with respect to the mind", which Orion explains based on their "being deprived of intercourse (esterēmenou tou misgesthai), the things that the ancients used to call irrational (anoēta, literally: mindless)". Orions second option reflects well-established idioms in Ancient Greek, as shown by entries for transl. grc – transl. noos, eunoos and ekhein in Liddell and Scotts Greek-English Lexicon, while the first option is not listed as an idiom under eunē in that standard reference work. However, the first option was cited by the late 9th century Byzantine emperor Leo VI in his New Constitution 98 banning the marriage of eunuchs, in which he noted eunuchs reputation as trustworthy guardians of the marriage bed (eunē) and claimed that the very word eunuch attested to this kind of employment. The emperor also goes further than Orion by attributing eunuchs lack of male-female intercourse specifically to castration, which he said was performed with the intention "that they will no longer do the things that males do, or at least to extinguish whatever has to do with desire for the female sex". The 11th century Byzantine monk Nikon of the Black Mountain, opting instead for Orions second alternative, stated that the word came from eunoein (eu "good" + nous "mind"), thus meaning "to be well-minded, well-inclined, well-disposed or favorable", but unlike Orion he argued that this was due to the trust that certain jealous and suspicious foreign rulers placed in the loyalty of their eunuchized servants. Theophylact of Ohrid in a dialogue In Defence of Eunuchs also stated that the origin of the word was from eupnoeic and ekhein, "to have, hold", since they were always "well-disposed" toward the master who "held" or owned them. The 12th century Etymologicum Magnum (s.v. eunoukhos) essentially repeats the entry from Orion, but stands by the first option, while attributing the second option to what "some say". In the late 12th century, Eustathius of Thessalonica (Commentaries on Homer 1256.30, 1643.16) offered an original derivation of the word from eunis + okheuein, "deprived of mating". In translations of the Bible into modern European languages, such as the Luther Bible or the King James Bible, the word eunuchs as found in the Latin Vulgate is usually rendered as an officer, official or chamberlain, consistent with the idea that the original meaning of eunuch was bed-keeper (Orions first option). Modern religious scholars have been disinclined to assume that the courts of Israel and Judah included castrated men, even though the original translation of the Bible into Greek used the word eunoukhos. The early 17th-century scholar and theologian Gerardus Vossius therefore explains that the word originally designated an office, and he affirms the view that it was derived from eunē and ekhein (i.e. "bed-keeper"). He says the word came to be applied to castrated men in general because such men were the usual holders of that office. Still, Vossius notes the alternative etymologies offered by Eustathius ("deprived of mating") and others ("having the mind in a good state"), calling these analyses "quite subtle". Then, after having previously declared that eunuch designated an office (i.e., not a personal characteristic), Vossius ultimately sums up his argument in a different way, saying that the word "originally signified continent men" to whom the care of women was entrusted, and later came to refer to castration because "among foreigners" that role was performed "by those with mutilated bodies". Modern etymologists have followed Orions first option. In an influential 1925 essay on the word eunuch and related terms, Ernst Maass suggested that Eustathiuss derivation "can or must be laid to rest", and he affirmed the derivation from eunē and ekhein ("guardian of the bed"), without mentioning the other derivation from eunoos and ekhein ("having a well-disposed state of mind"). In Latin, the words eunuchus, spado (Greek: σπάδων spadon), and castratus were used to denote eunuchs. By region and epoch Ancient Middle East The four-thousand-year-old Egyptian Execration Texts threaten enemies in Nubia and Asia, specifically referencing "all males, all eunuchs, all women."Castration was sometimes punitive; under Assyrian law, homosexual acts were punishable by castration. Eunuchs were familiar figures in the Assyrian Empire (ca. 850 until 622 BCE) and in the court of the Egyptian Pharaohs (down to the Lagid dynasty known as Ptolemies, ending with Cleopatra VII, 30 BCE). Eunuchs sometimes were used as regents for underage heirs to the throne, as it seems to be the case for the Neo-Hittite state of Carchemish. Political eunuchism became a fully established institution among the Achamenide Persians. Eunuchs held powerful positions in the Achaemenide court. The eunuch Bagoas (not to be confused with Alexanders Bagoas) was the Vizier of Artaxerxes III and Artaxerxes IV, and was the primary power behind the throne during their reigns, until he was killed by Darius III.Marmon (1995) writes "Mamluk biographies of the eunuchs often praise their appearance with adjectives such as jamil (beautiful), wasim (handsome), and ahsan (the best, most beautiful) or akmal (the most perfect)." Ancient Greece, Rome and Byzantium The practice was also well established in other Mediterranean areas among the Greeks and Romans, although a role as court functionary does not arise until Byzantine times. The Galli or Priests of Cybele were eunuchs. In the late period of the Roman Empire, after the adoption of the oriental royal court model by the Emperors Diocletian (r. 284-305) and Constantine (r. 306–337), emperors were surrounded by eunuchs for such functions as bathing, haircutting, dressing, and bureaucratic functions, in effect acting as a shield between the emperor and his administrators from physical contact, thus enjoying great influence in the imperial court (see Eusebius and Eutropius). Julian (r. 361–363) released the eunuchs from their service because he felt they were overpaid, and he subsequently realized how much they had contributed to palace operations.The Roman poet Martial rails against a woman who has sex with partially castrated eunuchs (those whose testicles were removed or rendered inactive only) in the bitter epigram (VI, 67): "Do you ask, Panychus, why your Caelia only consorts with eunuchs? Caelia wants the flowers of marriage – not the fruits." It is up for debate whether this passage is representative of any sort of widely practiced behavior, however. At the Byzantine imperial court, there were a great number of eunuchs employed in domestic and administrative functions, actually organized as a separate hierarchy, following a parallel career of their own. Archieunuchs—each in charge of a group of eunuchs—were among the principal officers in Constantinople, under the emperors. Under Justinian in the 6th century, the eunuch Narses functioned as a successful general in a number of campaigns. Advantages of eunuchs were that they prevented offices from becoming hereditary, allowing appointments to be made on merit; they were more dedicated to their jobs, not being distracted by family obligations; and they were ineligible for the throne, and for that reason thought by emperors to be safe. Those who had been deprived not only of their testicles but also their penises were known in Greek as carzimasia, and were highly prized.By the last centuries of the Empire, the number of roles reserved for eunuchs had reduced, and their use may have been all but over.Following the Byzantine tradition, eunuchs had important tasks at the court of the Norman Kingdom of Sicily during the middle 12th century. One of them, Philip of Mahdia, has been admiratus admiratorum, and another one, Ahmed es-Sikeli, was prime minister. China In China, castration included removal of the penis as well as the testicles (see emasculation). Both organs were cut off with a knife at the same time.Eunuchs existed in China from about 4,000 years ago, were imperial servants by 3,000 years ago, and were common as civil servants by the time of the Qin dynasty. From those ancient times until the Sui dynasty, castration was both a traditional punishment (one of the Five Punishments) and a means of gaining employment in the Imperial service. Certain eunuchs, such as the Ming dynasty official Zheng He, gained immense power that occasionally superseded that of even the Grand Secretaries. Self-castration was a common practice, although it was not always performed completely, which led to it being made illegal. It is said that the justification for the employment of eunuchs as high-ranking civil servants was that, since they were incapable of having children, they would not be tempted to seize power and start a dynasty. In many cases, eunuchs were considered more reliable than the scholar-officials. As a symbolic assignment of heavenly authority to the palace system, a constellation of stars was designated as the Emperors, and, to the west of it, four stars were identified as his "eunuchs."The tension between eunuchs in the service of the emperor and virtuous Confucian officials is a familiar theme in Chinese history. In his History of Government, Samuel Finer points out that reality was not always that clear-cut. There were instances of very capable eunuchs who were valuable advisers to their emperor, and the resistance of the "virtuous" officials often stemmed from jealousy on their part. Ray Huang argues that in reality, eunuchs represented the personal will of the Emperor, while the officials represented the alternative political will of the bureaucracy. The clash between them would thus have been a clash of ideologies or political agenda.The number of eunuchs in Imperial employ fell to 470 by 1912, when the practice of using them ceased. The last Imperial eunuch, Sun Yaoting, died in December 1996. Korea The eunuchs of Korea, called Naesi (내시, 內侍), were officials to the king and other royalty in traditional Korean society. The first recorded appearance of a Korean eunuch was in Goryeosa ("History of Goryeo"), a compilation about the Goryeo Dynasty period. In 1392, with the founding of the Joseon Dynasty, the Naesi system was revised, and the department was renamed the "Department of Naesi" (내시부, 內侍府).The Naesi system included two ranks, those of Sangseon (상선, 尙膳, "Chief of Naesi"), who held the official title of senior second rank, and Naegwan (내관, 內官, "Common official naesi"), both of which held rank as officers. 140 naesi in total served the palace in Joseon Dynasty period. They also took the exam on Confucianism every month. The naesi system was repealed in 1894 following Gabo reform. During the Yuan dynasty, eunuchs became a desirable commodity for tributes.Eunuchs were the only males outside the royal family allowed to stay inside the palace overnight. Court records going back to 1392 indicate that the average lifespan of eunuchs was 70.0 ± 1.76 years, which was 14.4–19.1 years longer than the lifespan of non-castrated men of similar socioeconomic status. Vietnam The Vietnamese adopted the eunuch system and castration techniques from China. Records show that the Vietnamese performed castration in a painful procedure by removing the entire genitalia with both penis and testicles being cut off with a sharp knife or metal blade. The procedure was agonizing since the entire penis was cut off. The young mans thighs and abdomen would be tied and others would pin him down on a table. The genitals would be washed with pepper water and then cut off. A tube would be then inserted into the urethra to allow urination during healing. Many Vietnamese eunuchs were products of self castration to gain access to the palaces and power. In other cases they might be paid to become eunuchs. They served in many capacities, from supervising public works, to investigating crimes, to reading public proclamations. Thailand In Siam (modern Thailand) Indian Muslims from the Coromandel Coast served as eunuchs in the Thai palace and court. The Thai at times asked eunuchs from China to visit the court in Thailand and advise them on court ritual since they held them in high regard. Burma Sir Henry Yule saw many Muslims serving as eunuchs in the Konbaung Dynasty of Burma (modern Myanmar) while on a diplomatic mission. Arabian Peninsula For several centuries, Muslim Eunuchs were tasked with honored roles in Medina and Mecca. They are thought to have been instituted in their role there by Salah ad-Deen Ayubi, but perhaps earlier. Their tasks included caring for the Prophet Muhammad’s tomb, maintaining borders between males and females where needed, and keeping order in the sacred spaces. They were highly respected in their time and remained there throughout the Ottoman Empire’s control of the area and afterward. In the present day, it is reported that only a few remain. Ottoman Empire In the Ottoman Empire, eunuchs were typically slaves imported from outside their domains. A fair proportion of male slaves were imported as eunuchs. The Ottoman court harem—within the Topkapı Palace (1465–1853) and later the Dolmabahçe Palace (1853–1909) in Istanbul—was under the administration of the eunuchs. These were of two categories: black eunuchs and white eunuchs. Black eunuchs were African slaves who served the concubines and officials in the Harem together with chamber maidens of low rank. The white eunuchs were European slaves from the Balkans or the Caucasus, either purchased in the slave markets or taken as boys from Christian families in the Balkans who were unable to pay the Jizya tax. They served the recruits at the Palace School and were from 1582 prohibited from entering the Harem. An important figure in the Ottoman court was the Chief Black Eunuch (Kızlar Ağası or Dar al-Saada Ağası). In control of both the Harem and a net of spies among the black eunuchs, the Chief Eunuch was involved in almost every palace intrigue and thereby could gain power over either the sultan or one of his viziers, ministers, or other court officials. One of the most powerful Chief Eunuchs was Beshir Agha in the 1730s, who played a crucial role in establishing the Ottoman version of Hanafi Islam throughout the Empire by founding libraries and schools. Coptic involvement In the 14th century, the Muslim Egyptian religious scholar Taj-al-Din Abu Nasr Abdal-Wahhab al-Subki discussed eunuchs in his book Kitab Muid al-Niam wa Mubid al-Niqam (Arabic: كتاب معيد النعم ومبيد النقم), a title that has been translated as Book of the Guide to [Divine] Benefits and Averting of [Divine] Vengeance and also as Book of Tutor of Graces and Annihilator of Misfortunes. In a chapter dedicated to eunuchs, Al-Subki made "the clear implication that eunuchness is itself an office," Shaun Marmon explained, adding that al-Subki had specified occupational subgroups for the tawashiya [eunuchs]: the zimam watched over women, and the muqaddam al-mamalik over adolescent boys.Edmund Andrews of Northwestern University, in an 1898 article called "Oriental Eunuchs" in the American Journal of Medicine, refers to Coptic priests in "Abou Gerhè in Upper Egypt" castrating slave boys. Coptic castration of slaves was discussed by Peter Charles Remondino, in his book History of Circumcision from the Earliest Times to the Present, published in 1900. He refers to the "Abou-Gerghè" monastery in a place he calls "Mount Ghebel-Eter". He adds details not mentioned by Andrews such as the insertion of bamboo into the victim. Bamboo was used with Chinese eunuchs. Andrews states his information is derived from an earlier work, Les Femmes, les eunuques, et les guerriers du Soudan, published by a French explorer, Count Raoul du Bisson, in 1868, though this detail does not appear in Du Bissons book.Remondinos claims were repeated in similar form by Henry G. Spooner in 1919, in the American Journal of Urology and Sexology. Spooner, an associate of William J. Robinson, referred to the monastery as "Abou Gerbe in Upper Egypt".According to Remondino, Spooner, and several later sources, the Coptic priests sliced the penis and testicles off Nubian or Abyssinian slave boys around the age of eight. The boys were captured from Abyssinia and other areas in Sudan like Darfur and Kordofan, then brought into Sudan and Egypt. During the operation, the Coptic clergyman chained the boys to tables, then, after slicing off their sexual organs, stuck a piece of bamboo into the urethra and submerged them in neck-high sand under the sun. The survival rate was ten percent. Slave traders made especially large profits off eunuchs from this region.However, neither "Abou Gerbe", as an actual monastery, nor "Mount Ghebel Eter", as an actual location, are known. Additionally, the cited references from Andrews, Remondino and Spooner appear circular, originating in tales told by a single French explorer. The later cited sources simply copy the earlier ones. Further, the 90% mortality rate seems economically improbable, given that it would require that markets paid at least 15 times the value of an uncastrated slave boy for a eunuch slave boy. A modern peer-reviewed source reports survival in Chinese court castrations of children at 33%, which is quite low, but nevertheless far higher than reported by Remondino. The same source reports later adult castrations as having a survival rate of 98%. Consequently, the accounts of castration by Coptic monks reported above, along with the 90% mortality figure, should be treated with considerable skepticism. Fatimid Caliphate In the Shii Fatimid Empire (909CE - 1171CE) eunuchs played major roles in the politics of the caliphates court, as well as holding a certain level of sacredness due to their association with the Fatimid imam-caliph. The eunuchs of the empire were normally purchased from slave auctions and belonged to a variety of Arab and non-Arab minority groups, though in many other cases they were brought from various noble families in the empire, which gave these individuals special connections to the Caliph. However, a system that employed foreign slaves, from multiple ethic & multi-linguistic groups were preferred and often quoted as "ideal servants". With imams normally ruling over a majority non-Shii population the court eunuchs served an important role of being ambassadors of the Imam-Caliph. They would use their own loyalty and fervor toward both the Shii sect and the imam-caliph himself amongst the common people of the empire to increase love for Fatimid rule. This was effective due to the mixed heritages of the eunuchs which gave them an ethnic and/or cultural common ground with the people they spoke with. Not just due to their inability to produce offspring, which made them less of a threat politically, but also in the fact that they had no choice but to dedicate their lives to their masters. Politically speaking the eunuchs often were placed into positions of significant power in one of four sectors; the service of the female members of the court, the service of the male members of the court, administrative and clerical positions, and military service. This is seen during the Fatimid occupation of Cairo. Here eunuchs had at some point held the position of shurta and hisba who controlled the military garrison and the markets respectively; the two most important positions in the city besides the magistrate himself. The wide net of eunuchs across all elements of the court made them quite unique in the political realm, As only they could deal with both men and women. However the most important role of Fatimid Eunuchs was in their direct service to the Imam-Caliphs as chamberlains, treasurers, governors, and attendants. Here they held a great amount of political and spiritual sway in both the noble realm and the commoner population. For instance in 946 AD the Imam-Caliph al-Qaim died resulting in a power vacuum causing a large familial conflict. This conflict only came to an end due to the Court Eunuch al-Jawdhar informing the possible heirs that al-Qaim had bequeathed his title to his son al-Mansur. Al-Jawdhar was the sole person told about this by al-Qiam as the hujja, which in the Shii sect of Islam is the chosen individual that imams are able to inform about their line of succession. This was one of the most sacred positions in the sect as they were seen as great wells of religious knowledge and law. There were several other eunuchs of high regard in Fatimid history, mainly being Abul-Fadi Rifq al-Khadim and Abul-Futuh Barjawan al-Ustadh. Rifq was a black African eunuch general served as governor of the Damascus until he led an army of 30,000 men in a campaign to expand Fatimid control northeast to the city of Aleppo, Syria. He was noted for being able to unite a diverse group of black Africans, Arabs, Bedouins, Berbers, and Turks into one coherent fight force which was able to successfully combat the Mirdasids, Bedouins, and Byzantines. Barjawan was a European eunuch during late Fatimid rule who gained power through his military and political savvy which brought peace between them and the Byzantine empire. Moreover, he squashed revolts in the Libya and the Levant. Given his reputation and power in the court and military he took the reigns of the caliphate from his then student al-Hakim bi-Amr Allah; then ruled as the de facto Regent 997 CE. His usurpation of power from the caliph resulted in his assassination in 1000 CE on the orders of al-Hakim. Algiers In the 16th century, an Englishman, Samson Rowlie, was captured and castrated to serve the Ottoman governor in Algiers. Indian subcontinent (Central Asian Muslim conquerors) Eunuchs in Indian sultanates (before the Mughals) Eunuchs were frequently employed in Imperial palaces by Muslim rulers as servants for female royalty, as guards of the royal harem, and as sexual mates for the nobles. Some of them attained high-status positions in society. An early example of such a high-ranking eunuch was Malik Kafur. Eunuchs in Imperial palaces were organized in a hierarchy, often with a senior or Chief Eunuch (Urdu: Khwaja Saras), directing junior eunuchs below him. Eunuchs were highly valued for their strength and trustworthiness, allowing them to live amongst women with fewer worries. This enabled eunuchs to serve as messengers, watchmen, attendants and guards for palaces. Often, eunuchs also doubled as part of the Kings court of advisers. The hijra of South Asia Hijra, a Hindi term traditionally translated into English as "eunuch", actually refers to what modern Westerners would call transgender women and effeminate homosexual men (although some of them reportedly identify as belonging to a third sex). The history of this third sex is mentioned in the Ancient Indian Kama Sutra, which refers to people of a "third sex" (triteeyaprakrti). Some of them undergo ritual castration, but the majority do not. They usually dress in saris (traditional garb worn by women in India) or shalwar kameez (traditional garb worn by women in South Asia) and wear heavy make-up. They typically live on the margins of society and face discrimination. Hijra tend to have few options for earning a wage, with many turning to sex work and others performing ritualistic songs and dances. They are integral to several Hindu ceremonies, such as dance programs at marriage ceremonies. They may also earn a living by going uninvited to large ceremonies such as weddings, births, new shop openings and other major family events, and singing until they are paid or given gifts to go away. The ceremony is supposed to bring good luck and fertility, while the curse of an unappeased hijra is feared by many. Hijra often engage in prostitution and begging to earn money, with begging typically accompanied by singing and dancing. Some Indian provincial officials have used the assistance of hijras to collect taxes in the same fashion—they knock on the doors of shopkeepers, while dancing and singing, embarrassing them into paying. Recently, hijras have started to found organizations to improve their social condition and fight discrimination, such as the Shemale Foundation Pakistan. Religious castration Castration as part of religious practice, and eunuchs occupying religious roles, have been established prior to classical antiquity. Archaeological finds at Çatalhöyük in Anatolia indicate worship of a Magna Mater figure, a forerunner of the goddess Cybele found in later Anatolia and other parts of the near East. Later Roman followers of Cybele were called Galli, who practiced ritual self-castration, known as sanguinaria. Eunuch priests also figured prominently in the Atargatis cult in Syria during the first centuries AD.The practice of religious castration continued into the Christian era, with members of the early church practicing celibacy (including castration) for religious purposes, although the extent and even the existence of this practice among Christians is subject to debate. The early theologian Origen found evidence of the practice in Matthew 19:10–12: "His disciples said to him, If such is the case of a man with his wife, it is better not to marry. But he said to them, Not everyone can accept this teaching, but only those to whom it is given. For there are eunuchs who have been so from birth, and there are eunuchs who have been made eunuchs by others, and there are eunuchs who have made themselves eunuchs for the sake of the kingdom of heaven. Let anyone accept this who can." (NRSV) Tertullian, a 2nd-century Church Father, described Jesus himself and Paul of Tarsus as spadones, which is translated as "eunuchs" in some contexts. Quoting from the cited book: "Tertullian takes spado to mean virgin". The meaning of spado in late antiquity can be interpreted as a metaphor for celibacy. Tertullian even goes so far with the metaphor as to say St. Paul had been "castrated".Eunuch priests have served various goddesses from India for many centuries. Similar phenomena are exemplified by some modern Indian communities of the hijra, which are associated with a deity and with certain rituals and festivals – notably the devotees of Yellammadevi, or jogappas, who are not castrated, and the Ali of southern India, of whom at least some are.The 18th-century Russian Skoptzy (скопцы) sect was an example of a castration cult, where its members regarded castration as a way of renouncing the sins of the flesh. Several members of the 20th-century Heavens Gate cult were found to have been castrated, apparently voluntarily and for the same reasons. In the Bible [6] Wherefore they are no more twain, but one flesh. What therefore God hath joined together, let not man put asunder. [7] They say unto him, Why did Moses then command to give a writing of divorcement, and to put her away? [8] He saith unto them, Moses because of the hardness of your hearts suffered you to put away your wives: but from the beginning it was not so. [9] And I say unto you, Whosoever shall put away his wife, except [it be] for fornication, and shall marry another, committeth adultery: and whoso marrieth her which is put away doth commit adultery. [10] His disciples say unto him, If the case of the man be so with [his] wife, it is not good to marry. [11] But he said unto them, All [men] cannot receive this saying, save [they] to whom it is given. [12] For there are some eunuchs, which were so born from [their] mothers womb: and there are some eunuchs, which were made eunuchs of men: and there be eunuchs, which have made themselves eunuchs for the kingdom of heavens sake. He that is able to receive [it], let him receive [it]. The reference to "eunuchs" in Matthew 19:12 has yielded various interpretations. Eunuchs are mentioned many times in the Bible, such as in the Book of Isaiah (56:4) using the word סריס (saris). Although the Ancient Hebrews did not practice castration, eunuchs were common in other cultures featured in the Bible, such as ancient Egypt, Babylonia, the Persian Empire, and ancient Rome. In the Book of Esther, servants of the harem of Ahasuerus, such as Hegai and Shashgaz, as well as other servants such as Hatach, Harbonah, Bigthan, and Teresh, are referred to as sarisim. Being exposed to the consorts of the king, they would likely have been castrated. There is some confusion regarding eunuchs in Old Testament passages, since the Hebrew word for eunuch, saris (סריס), could also refer to other servants and officials who had not been castrated but served in similar capacities.One of the earliest converts to Christianity was an Ethiopian eunuch who was a high court official of Candace, the Queen of Ethiopia, but was already a eunuch at the time of conversion (Acts 8:27–39). Non-castrated eunuchs The term eunuch has sometimes figuratively been used for a wide range of men who were seen to be physically unable to procreate. Hippocrates describes the Scythians as being afflicted with high rates of erectile dysfunction and thus "the most eunuchoid of all nations" (Airs Waters Places 22). In the Charlton T. Lewis, Charles Short, A Latin Dictionary, the term literally used for impotent males is spado but may also be used for eunuchs. Some men have falsified the status of their castration to gain entrance into the palace. Chinese eunuch Lao Ai for instance, became the lover of the mother of Qin Shi Huang, who bore him two sons, before Lao Ai and his sons were executed after participating in a rebellion against Qin Shi Huang. Castrato singers Eunuchs castrated before puberty were also valued and trained in several cultures for their exceptional voices, which retained a childlike and other-worldly flexibility and treble pitch (a high-pitched voice). Such eunuchs were known as castrati. As women were sometimes forbidden to sing in Church, their place was taken by castrati. Castrati became very popular in 18th century opera seria. The practice, known as castratism, remained popular until the 18th century and was known into the 19th century. The last famous Italian castrato, Giovanni Velluti, died in 1861. The sole existing sound recording of a castrato singer documents the voice of Alessandro Moreschi, the last eunuch in the Sistine Chapel choir, who died in 1922. This Italian practice of castrating young males to maintain their soprano voices was ended by Pope Leo XIII (1878). In popular culture Notable eunuchs In chronological order. First millennium BCE Mutakkil-Marduk (8th century BCE): Assyrian chief eunuch, eponym of the year 798 BCE in an Assyrian eponym chronicle. Yariri (8th century BCE): regent of Neo-Hittite Carchemish thought likely to be a eunuch. Sin-shumu-lishir (7th century BCE): Assyrian eunuch who attempted to usurp power in the Neo-Assyrian Empire. Aspamistres or Mithridates (5th century BCE): bodyguard of Xerxes I of Persia, and (with Artabanus) his murderer. Artoxares: an envoy of Artaxerxes I and Darius II of Persia. Bagoas (4th century BCE): prime minister of king Artaxerxes III of Persia, and his assassin (Bagoas is an old Persian word meaning eunuch). Bagoas (4th century BCE): a favorite of Alexander the Great. Influential in changing Alexanders attitude toward Persians and therefore in the kings policy decision to try to integrate the conquered peoples fully into his Empire as loyal subjects. He thereby paved the way for the relative success of Alexanders Seleucid successors and greatly enhanced the diffusion of Greek culture to the East. Batis (4th century BCE): resisted Alexander the Great at the Siege of Gaza. Philetaerus (4th/3rd century BCE): founder of the Attalid dynasty of Pergamum Zhao Gao (died 210 BCE): favourite of Qin Shihuangdi, who plotted against Li Si. Sima Qian (old romanization Ssu-ma Chien; 2nd/1st century BCE): the first person to have practiced modern historiography – gathering and analyzing both primary and secondary sources to write his monumental history of the Chinese Empire. Ganymedes (1st century BCE): highly capable adviser and general of Cleopatra VIIs sister and rival, Princess Arsinoe. Unsuccessfully attacked Julius Caesar three times at Alexandria. Pothinus (1st century BCE): regent for pharaoh Ptolemy XII. First millennium CE Sporus (died 69): an attractive Roman boy who was castrated by, and later married to, Emperor Nero. Unidentified "Ethiopian eunuch" (1st century AD), from the Kingdom of Kush in modern-day Sudan, described in the Acts of the Apostles (chapter 8). Philip the Evangelist, one of the original seven deacons, is directed by the Holy Spirit to catch up to the eunuchs chariot and hears him reading from the Book of Isaiah (chapter 53). Philip explained that the section prophesies Jesus crucifixion, which Philip described to the eunuch. The eunuch was baptized shortly thereafter. Halotus (c. 20–30 CE – c. 70–80 CE), servant to the Roman Emperor Claudius and suspected of poisoning him. Cai Lun (c. 50–62–121): Former attribution to Lun as the inventor of paper has been rescinded following discovery of many earlier manuscripts written on paper. It is now highly questionable if he was directly involved in making paper. Zhang Rang: head of the infamous "10 Changshi" (ten attendants) of the Eastern Han dynasty. Huang Hao: eunuch in the state of Shu; also appears in the Romance of the Three Kingdoms. Cen Hun (died 280): eunuch in the state of Wu during the Three Kingdoms Period. Origen (c. 185–c. 253): early Christian theologian, allegedly castrated himself based on his reading of the Gospel of Matthew 19:12 ("For there are eunuchs, who were born so from their mothers womb: and there are eunuchs, who were made so by men: and there are eunuchs, who have made themselves eunuchs for the kingdom of heaven. He that can take, let him take it."). Despite the fact that the early Christian theologian Tertullian wrote that Jesus was a eunuch, there is no corroboration in any other early source. (The Skoptsy did, however, believe it to be true.) Chusdazat (died 344): He served King Shapur II, who killed him for declaring his Christian identity. Dorotheus of Tyre (255–362): A bishop who attended the Council of Nicaea, was exiled by Diocletian and Julian, and was martyred. Eutropius (died 399): only eunuch known to have attained the highly distinguished office of Roman Consul. Chrysaphius (died 450): chief minister of Eastern Roman Emperor Theodosius II, architect of imperial policy towards the Huns. Narses (478–573): general of Byzantine emperor Justinian I, responsible for destroying the Ostrogoths in 552 at the Battle of Taginae in Italy and reconquering Rome for the empire. Solomon (480s/490s–544): general and governor of Africa under Justinian I. Gao Lishi (684–762): a loyal and trusted friend of Tang emperor Xuanzong. Li Fuguo (704–762): Tang eunuch who began another era of eunuch rule. Yu Chaoen (722–770): Tang eunuch who began his career as army supervisor. Staurakios (died 800): chief associate and minister of the Byzantine empress Irene of Athens. Ignatius of Constantinople (799–877): twice Patriarch of Constantinople during troubled political times (847–858 and 867–877). First absolutely unquestioned eunuch saint, recognized by both the Orthodox and Roman Churches. (There are a great many early saints who were probably eunuchs, though few either as influential nor unquestioned as to their castration.) Yazaman al-Khadim (died 891): Emir of Tarsus and successful commander in the wars against the Byzantine Empire. Munis al-Khadim (845/846–933/934): Commander-in-chief of the Abbasid armies between 908 and his death. Joseph Bringas (died 965): chief minister of the Byzantine Empire under Romanos II (959–963). Second millennium CE Jia Xian (c. 1010–c. 1070): Chinese mathematician; invented the Jia Xian triangle for the calculation of square roots and cube roots. Ly Thuong Kiet (1019–1105): general during the Lý Dynasty in Vietnam. Penned what is considered the first Vietnamese declaration of independence. Regarded as a Vietnamese national hero. Pierre Abélard (1079–1142): French scholastic philosopher and theologian. Forcibly castrated by his girlfriends uncle while in bed. Lulu al-Yaya (died 1117): Regent of the Seljuk sultanate of Aleppo. Malik Kafur (fl. 1296–1316): a eunuch slave who became a general in the army of Alauddin Khalji, ruler of the Delhi sultanate. Zheng He (1371–1433): famous admiral who led huge Chinese fleets of exploration around the Indian Ocean. Yishiha (15th century): admiral in charge of expeditions down the Amur River under the Yongle and Xuande Emperors. Wu Rui (15th century): a Chinese eunuch in Lê Dynasty Annam (Vietnam). Gang Bing (died 1410): patron saint of eunuchs in China who castrated himself to demonstrate his loyalty to the Yongle Emperor. Wang Zhen (died 1449): first Ming eunuch with much power; see Tumu Crisis. Kim Cheo Seon (1421–1505): one of the most famous eunuchs in Korean Joseon Dynasty, ably served kings in the Joseon dynasty. His life is the subject of a historical drama in South Korea. Liu Jin (1451–1510): corrupt eunuch official of the Ming dynasty and de facto emperor, member of the Eight Tigers. Judar Pasha (1562–1606): a Spanish eunuch who became the head of the Moroccan invasion force into the Songhai Empire. Wei Zhongxian (1568–1627): eunuch of the Ming dynasty, considered the most powerful eunuch in Chinese history. Senesino (1686–1758): Italian contralto castrato singer. Farinelli (1705–1782): Italian soprano castrato singer. Giusto Fernando Tenducci (c. 1736–1790): Italian soprano castrato singer. Mohammad Khan Qajar (1742–1797): chief of the Qajar tribe. He became the King/Shah of Persia in 1794 and established the Qajar dynasty. Lê Văn Duyệt (c. 1763–1832): Vietnamese eunuch, military strategist and government official (not a true eunuch, he was born a hermaphrodite). Thomas P. "Boston" Corbett (b. 1832; presumed dead 1894): killer of John Wilkes Booth, the assassin of Abraham Lincoln, who castrated himself to avoid temptation from prostitutes. Li Lianying (1848–1911): a despotic eunuch of the Qing dynasty. Alessandro Moreschi (1858–1922): Italian castrato singer, the only one to make recordings. Xin Xiuming (1878–1959): Entered Emperor Puyis service in 1902; left palace service in 1911; became abbot of the Taoist temple at the Babaoshan Revolutionary Cemetery by 1930; wrote memoir Eunuchs Recollection (老太监的回忆). Sun Yaoting (1902–1996): last surviving imperial eunuch of Chinese history. See also The dictionary definition of eunuch at Wiktionary Nullo (body modification) References & bibliography Citations Further reading Further listening In Our Time: The Eunuch. Presenter: Melvyn Bragg. Interviewed Guests: Karen Radner, Professor of Ancient Near Eastern History at University College London; Shaun Tougher, Reader in Ancient History at Cardiff University; Michael Hoeckelmann, British Academy Postdoctoral Fellow in the Department of History at Kings College London. Producer: Thomas Morris. Broadcaster: BBC Radio 4. Date: 26 February 2015 External links "38 rare pictures of eunuchs during Qing Dynasty". China Underground. "Born Eunuchs". Well.com. "Eunuchs in Pharaonic Egypt". well.com. "The Ancient Roman and Talmudic Definition of Natural Eunuchs". well.com. "The Eunuch Archive". eunuch.org. "The Perfect Servant: Eunuchs and the Social Construction of Gender in Byzantium". Archived from the original on 29 December 2007 – via Find Articles.

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

Could you offer a clear explanation of the term 'Flumazenil' as used in the medical field?

Flumazenil (also known as flumazepil, code name Ro 15-1788) is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines (particularly in cases of overdose), through competitive inhibition. It was first characterized in 1981, and was first marketed in 1987 by Hoffmann-La Roche under the trade name Anexate. However, it did not receive FDA approval until December 20, 1991. The developer lost its exclusive patent rights in 2008; so at present, generic formulations of this drug are available. Intravenous flumazenil is primarily used to treat benzodiazepine overdoses and to help reverse anesthesia. Administration of flumazenil by sublingual lozenge and topical cream has also been tested. Medical uses Flumazenil benefits patients who become excessively drowsy after use of benzodiazepines for either diagnostic or therapeutic procedures.The drug has been used as an antidote in the treatment of benzodiazepine overdoses. It reverses the effects of benzodiazepines by competitive inhibition at the benzodiazepine (BZ) recognition site on the GABA/benzodiazepine receptor complex. There are many complications that must be taken into consideration when used in the acute care setting. These include lowered seizure threshold, agitation, and anxiousness. Flumazenils short half-life requires multiple doses. Because of the potential risks of withdrawal symptoms and the drugs short half-life, patients must be carefully monitorered to prevent recurrence of overdose symptoms or adverse side effects. Flumazenil is also sometimes used after surgery to reverse the sedative effects of benzodiazepines. This is similar to naloxones application to reverse the effect of opiates and opioids following surgery. Administration of the drug requires careful monitoring by an anesthesiologist due to potential side effects and serious risks associated with over-administeration. Likewise, post-surgical monitoring is also necessary because flumazenil can mask the apparent metabolization ("wearing off") of the drug after removal of patient life-support and monitoring equipment. Flumazenil has been effectively used to treat overdoses of non-benzodiazepine hypnotics, such as zolpidem, zaleplon and zopiclone (also known as "Z-drugs").It may also be effective in reducing excessive daytime sleepiness while improving vigilance in primary hypersomnias, such as idiopathic hypersomnia.The drug has also been used in hepatic encephalopathy. It may have beneficial short‐term effects in people with cirrhosis, but there is no evidence for long-term benefits.The onset of action is rapid, and effects are usually seen within one to two minutes. The peak effect is seen at six to ten minutes. The recommended dose for adults is 200 μg every 1–2 minutes until the effect is seen, up to a maximum of 3 mg per hour. It is available as a clear, colourless solution for intravenous injection, containing 500 μg in 5 mL. Many benzodiazepines (including midazolam) have longer half-lives than flumazenil. Therefore, in cases of overdose, repeat doses of flumazenil may be required to prevent recurrent symptoms once the initial dose of flumazenil wears off. It is hepatically metabolised to inactive compounds which are excreted in the urine. Individuals who are physically dependent on benzodiazepines may experience benzodiazepine withdrawal symptoms, including seizure, upon rapid administration of flumazenil. It is not recommended for routine use in those with a decreased level of consciousness.In terms of drug enforcement initiatives, diversion control programs and required post-marketing surveillance of adverse events, orders for flumazenil may trigger a prescription audit to the search for benzodiazepine misuse and for clinically significant adverse reactions related to their use. PET radioligand Radiolabeled with the radioactive isotope carbon-11, flumazenil may be used as a radioligand in neuroimaging with positron emission tomography to visualize the distribution of GABAA receptors in the human brain. Treatment for benzodiazepine dependence & tolerance Epileptic patients who have become tolerant to the anti-seizure effects of the benzodiazepine clonazepam became seizure-free for several days after treatment with 1.5 mg of flumazenil. Similarly, patients who were dependent on high doses of benzodiazepines (median dosage 333 mg diazepam-equivalent) were able to be stabilised on a low dose of clonazepam after 7–8 days of treatment with flumazenil.Flumazenil has been tested against placebo in benzo-dependent subjects. Results showed that typical benzodiazepine withdrawal effects were reversed with few to no symptoms. Flumazenil was also shown to produce significantly fewer withdrawal symptoms than saline in a randomized, placebo-controlled study with benzodiazepine-dependent subjects. Additionally, relapse rates were much lower during subsequent follow-up.In vitro studies of tissue cultured cell lines have shown that chronic treatment with flumazenil enhanced the benzodiazepine binding site where such receptors have become more numerous and uncoupling/down-regulation of GABAA has been reversed. After long-term exposure to benzodiazepines, GABAA receptors become down-regulated and uncoupled. Growth of new receptors and recoupling after prolonged flumazenil exposure has also been observed. It is thought this may be due to increased synthesis of receptor proteins.Flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4–266 weeks. This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms. Low-dose, slow subcutaneous flumazenil administration is a safe procedure for patients withdrawing from long-term, high-dose benzodiazepine dependency. It has a low risk of seizures even amongst those who have experienced convulsions when previously attempting benzodiazepine withdrawal.In Italy, the gold standard for treatment of high-dose benzodiazepine dependency is 8–10 days of low-dose, slowly infused flumazenil. One addiction treatment centre in Italy has used flumazenil to treat over 300 patients who were dependent on high doses of benzodiazepines (up to 70 times higher than conventionally prescribed) with physicians being among the clinics most common patients. Clinical pharmacology Flumazenil, an imidazobenzodiazepine derivative, antagonizes the actions of benzodiazepines on the central nervous system. Flumazenil competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex. It also exhibits weak partial agonism of GABAA receptor complexes that contain α6-type monomers; the clinical relevance of this is unknown.Flumazenil does not antagonize all of the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, and most anesthetics) and does not reverse the effects of opioids. It will however antagonize the action of non-benzodiazepine z-drugs, such as zolpidem and zopiclone, because they act via the benzodiazepine site of the GABA receptor - it has been used to successfully treat z-drug overdose. Pharmacodynamics Intravenous flumazenil has been shown to antagonize sedation, impairment of recall, psychomotor impairment and ventilatory depression produced by benzodiazepines in healthy human volunteers. The duration and degree of reversal of sedative benzodiazepine effects are related to the dose and plasma concentrations of flumazenil. Availability Flumazenil is sold under a wide variety of brand names worldwide like Anexate, Lanexat, Mazicon, Romazicon. In India it is manufactured by Roche Bangladesh Pharmaceuticals and USAN Pharmaceuticals. See also Benzodiazepine overdose Benzodiazepine Bretazenil Imidazenil Ro15-4513 GABAA receptor negative allosteric modulators References Other Romazicon product information, Roche USA External links Media related to Flumazenil at Wikimedia Commons Flumazenil drug label/data at Daily Med from U.S. National Library of Medicine, National Institutes of Health.

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Bismuth subsalicylate'?

Bismuth subsalicylate, sold generically as pink bismuth and under the brand names Pepto-Bismol and BisBacter, is an antacid elixir medication used to treat temporary discomforts of the stomach and gastrointestinal tract, such as nausea, heartburn, indigestion, upset stomach, and diarrhea. Bismuth subsalicylate has the empirical chemical formula of C7H5BiO4, and it is a colloidal substance obtained by hydrolysis of bismuth salicylate (Bi(C6H4(OH)CO2)3). Medical uses As a derivative of salicylic acid, bismuth subsalicylate displays anti-inflammatory and bactericidal action. It also acts as an antacid. Adverse effects There are some adverse effects. It can cause a black tongue and black stools in some users of the drug when it combines with trace amounts of sulfur in saliva and the colon to form bismuth sulfide. Bismuth sulfide is a highly insoluble black salt, and the discoloration seen is temporary and harmless. Long-term use (greater than six weeks) may lead to accumulation and toxicity. Some of the risks of salicylism can apply to the use of bismuth subsalicylate.Children should not take medication with bismuth subsalicylate while recovering from influenza or chicken pox, as epidemiologic evidence points to an association between the use of salicylate-containing medications during certain viral infections and the onset of Reye syndrome. For the same reason, it is typically recommended that nursing mothers not use medication containing bismuth subsalicylate because small amounts of the medication are excreted in human breast milk, and these pose a theoretical risk of Reyes syndrome to nursing children.Salicylates are very toxic to cats, and thus bismuth subsalicylate should not be administered to cats.The British National Formulary does not recommend bismuth-containing antacids (unless chelated), cautioning that absorbed bismuth can be neurotoxic, causing encephalopathy, and that such antacids tend to be constipating. Drug interactions There is an increased risk of bleeding when using bismuth subsalicylate and anticoagulation therapy, like Coumadin (Warfarin) Mechanism of action Bismuth subsalicylate is used as an antacid and antidiarrheal, and to treat some other gastrointestinal symptoms, such as nausea. The means by which this occurs is still not well documented. It is thought to be some combination of the following: Stimulation of absorption of fluids and electrolytes by the intestinal wall (antisecretory action) As a salicylate, reducing inflammation/irritation of stomach and intestinal lining through inhibition of prostaglandin G/H synthase 1/2 Reduction in hypermotility of the stomach Inhibits adhesion and filmogenesis by Escherichia coli Bactericidal action of a number of its subcomponents, including salicylic acid Bactericidal action via a so-called oligodynamic effect in which small amounts of heavy metals such as bismuth damage many different bacteria species. Weak antacid propertiesIn vitro and in vivo data have shown that bismuth subsalicylate hydrolyzes in the gut to bismuth oxychloride and salicylic acid and less commonly bismuth hydroxide. In the stomach, this is likely an acid-catalyzed hydrolysis. The salicylic acid is absorbed and therapeutical concentrations of salicylic acid can be found in blood after bismuth subsalicylate administration. Bismuth oxychloride and bismuth hydroxide are both believed to have bactericidal effects, as is salicylic acid for enterotoxigenic E. coli a common cause of "travelers diarrhea."Organobismuth compounds have historically been used in growth media for selective isolation of microorganisms. Such salts have been shown to inhibit proliferation of Helicobacter pylori, other enteric bacteria, and some fungi. Structure Despite its common usage and commercial significance, the exact structure of the pharmaceutical long remained undetermined, but was revealed, through the use of advanced electron crystallography techniques, to be a layered coordination polymer with the formula BiO(C7H5O3). In the structure, both the carboxylate and phenol groups of the salicylate coordinate towards the bismuth cations. The determination of bismuth subsalicylate had long been hindered due to the small particle size as well as defects within the structure, arising from variations in the stacking arrangement of the bismuth subsalicylate layers, which could be observed as part of the structural investigation. History While bismuth salts were in use in Europe by the late 1700s, the combination of bismuth subsalicylate and zinc salts for astringency with salol (phenyl salicylate) appears to have begun in the US in the early 1900s as a remedy for life-threatening diarrhea in infants with cholera. At first sold directly to physicians, it was first marketed as Bismosal in 1918.Pepto-Bismol began being sold in 1900 or 1901 by a doctor in New York. It was originally sold as a remedy for infant diarrhea by Norwich Pharmacal Company under the name "Bismosal: Mixture Cholera Infantum". It was renamed Pepto-Bismol in 1919. Norwich Eaton Pharmaceuticals was acquired by Procter and Gamble in 1982.As of 1946 and 1959, Canadian advertisements placed by Norwich show the product as Pepto-Besmal both in graphic and text.Pepto-Bismol is an over-the-counter drug currently produced by the Procter & Gamble company in the United States, Canada and the United Kingdom. Pepto-Bismol is made in chewable tablets and swallowable caplets, but it is best known for its original formula, which is a thick liquid. This original formula is a medium pink in color, with a teaberry (methyl salicylate) flavor.Generic bismuth subsalicylate, and other branded versions of the drug, are widely available in pill and liquid form. References External links Andrews PC, Deacon GB, Forsyth CM, Junk PC, Kumar I, Maguire M (August 2006). "Towards a structural understanding of the anti-ulcer and anti-gastritis drug bismuth subsalicylate". Angewandte Chemie. 45 (34): 5638–42. doi:10.1002/anie.200600469. PMID 16865763.

You are a medical interpreter. Your duty is to translate medical terms into easily digestible information, maintaining accuracy and detail.

I'm looking for a concise explanation of the medical term 'Porokeratotic eccrine ostial and dermal duct nevus.'

Porokeratotic eccrine ostial and dermal duct nevus is a skin lesion that resembles a comedonal nevus, but it occurs on the palms and soles where pilosebaceous follicles are normally absent. It is probably transmitted by paradominant transmission. See also Prominent inferior labial artery List of cutaneous conditions == References ==

You are a facilitator of medical knowledge. Provide thorough and accessible explanations of medical terms, catering to both specialists and non-specialists.

I'm not familiar with the medical term 'Vitreomacular adhesion.' Could you provide some insights?

Vitreomacular adhesion (VMA) is a human medical condition where the vitreous gel (or simply vitreous, AKA vitreous humour) of the human eye adheres to the retina in an abnormally strong manner. As the eye ages, it is common for the vitreous to separate from the retina. But if this separation is not complete, i.e. there is still an adhesion, this can create pulling forces on the retina that may result in subsequent loss or distortion of vision. The adhesion in of itself is not dangerous, but the resulting pathological vitreomacular traction (VMT) can cause severe ocular damage. The current standard of care for treating these adhesions is pars plana vitrectomy (PPV), which involves surgically removing the vitreous from the eye. A biological agent for non-invasive treatment of adhesions called ocriplasmin has been approved by the FDA on October 17, 2012. Symptom and signs Traction caused by VMA is the underlying pathology of an eye disease called symptomatic VMA. There is evidence that symptomatic VMA can contribute to the development of several well-known eye disorders, such as macular hole and macular pucker, that can cause visual impairment, including blindness. It may also be associated with age-related macular degeneration (AMD), diabetic macular edema (DME), retinal vein occlusion, and diabetic retinopathy (DR). Pathology Over time, it is common for the vitreous within the human eye to liquify and collapse in processes known as syneresis and synchisis respectively. This creates fluid-filled areas that can combine to form pockets of vitreous gel that are mostly liquid with very small concentrations of collagen. If these liquid pockets are close enough to the interface between the vitreous gel and the retina, they can cause complete separation of the vitreous from the retina in a normally occurring process in older humans called posterior vitreous detachment (PVD). PVD in of itself is not dangerous and a natural process.If the separation of the vitreous from the retina is not complete, areas of focal attachment or adhesions can occur, i.e. a VMA. The pulling forces or traction from this adhesion on the retinal surface can sometimes cause edema within the retina, damage to retinal blood vessels causing bleeding, or damage to the optic nerve causing disruption in the nerve signals sent to the brain for visual processing. It is important to note that while the VMA itself is not dangerous, the resultant pulling on the retina called vitreomacular traction (VMT) causes the above damage. The size and strength of the VMA determine the variety of resulting pathologies or symptoms.VMA can also lead to the development of VMT/traction-related complications such as macular puckers and macular holes leading to distorted vision or metamorphopsia; epiretinal membrane; tractional macular oedema; myopic macular retinoschisis; visual impairment; blindness. The incidence of VMA is reported as high as 84% for patients with macular hole, 100% for patients with vitreomacular traction syndrome, and 56% in idiopathic epimacular membrane. Diagnosis Careful eye examination by an ophthalmologist or optometrist is critical for diagnosing symptomatic VMA. Imaging technologies such as optical coherence tomography (OCT) have significantly improved the accuracy of diagnosing symptomatic VMA. Treatment A new FDA approved drug was released on the market late 2013. Jetrea (Brand name) or Ocriplasmin (Generic name) is the first drug of its kind used to treat vitreomacular adhesion.Mechanism of Action: Ocriplasmin is a truncated human plasmin with proteolytic activity against protein components of the vitreous body and vitreoretinal interface. It dissolves the protein matrix responsible for the vitreomacular adhesion. Adverse drug reactions: Decreased vision, potential for lens subluxation, dyschromatopsia (yellow vision), eye pain, floaters, blurred vision. New Drug comparison Rating gave Jetea a 5 indicating an important advance. Previously, no recommended treatment was available for the patient with mild symptomatic VMA. In symptomatic VMA patients with more significant vision loss, the standard of care is pars plana vitrectomy (PPV), which involves surgically removing the vitreous from the eye, thereby surgically releasing the symptomatic VMA. In other words, vitrectomy induces PVD to release the traction/adhesion on the retina. An estimated 850,000 vitrectomy procedures are performed globally on an annual basis with 250,000 in the United States alone. A standard PPV procedure can lead to serious complications including small-gauge PPV. Complications can include retinal detachment, retinal tears, endophthalmitis, and postoperative cataract formation. Additionally, PPV may result in incomplete separation, and it may potentially leave a nidus for vasoactive and vasoproliferative substances, or it may induce development of fibrovascular membranes. As with any invasive surgical procedure, PPV introduces trauma to the vitreous and surrounding tissue.There are data showing that nonsurgical induction of PVD using ocriplasmin (a recombinant protease with activity against fibronectin and laminin) can offer the benefits of successful PVD while eliminating the risks associated with a surgical procedure, i.e. vitrectomy. Pharmacologic vitreolysis is an improvement over invasive surgery as it induces complete separation, creates a more physiologic state of the vitreomacular interface, prevents the development of fibrovascular membranes, is less traumatic to the vitreous, and is potentially prophylactic. As of 2012, ThromboGenics is still developing the ocriplasmin biological agent. Ocriplasmin is approved recently under the name Jetrea for use in the United States by the FDA.view.An experimental test of injections of perfluoropropane (C3F8) on 15 symptomatic eyes of 14 patients showed that vitreomacular traction resolved in 6 eyes within 1 month and resolved in 3 more eyes within 6 months. A systematic review found high-certainty evidence that Ocriplasmin compared to no treatment increases the chance of resolution and improves vision in people with symptomatic VMA. Ocriplasmin probably reduces the need for surgery but there were more adverse events in eyes treated with ocriplasmin compared to control. References == External links ==

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I'm trying to expand my medical knowledge. Can you elucidate the term 'Somapacitan'?

Somapacitan, sold under the brand name Sogroya, is a growth hormone medication. Somapacitan is a human growth hormone analog. Somapacitan-beco is produced in Escherichia coli by recombinant DNA technology.The most common side effects include: back pain, joint paint, indigestion, a sleep disorder, dizziness, tonsillitis, swelling in the arms or lower legs, vomiting, adrenal insufficiency, hypertension, increase in blood creatine phosphokinase (a type of enzyme), weight increase, and anemia.It was approved for medical use in the United States in August 2020, and in the European Union in March 2021.Somapacitan is the first human growth hormone (hGH) therapy that adults only take once a week by injection under the skin; other FDA-approved hGH formulations for adults with growth hormone deficiency must be administered daily. It contains a small non-covalent moiety that reversibly binds to serum albumin which slows down elimination. Medical uses Somapacitan is indicated for replacement of endogenous growth hormone in adults with growth hormone deficiency (GHD).GHD is a condition when the body doesnt produce enough growth hormone on its own. Growth hormone regulates many functions in the body including accumulation of fat in the trunk or central area of the body that can be associated with serious medical issues. Contraindications Somapacitan should not be used in people with active malignancy, any stage of diabetic eye disease in which high blood sugar levels cause damage to blood vessels in the retina, acute critical illness, or those with acute respiratory failure, because of the increased risk of mortality with use of pharmacologic doses of somapacitan in critically ill individuals without growth hormone deficiency. History Somapacitan was evaluated in a randomized, double-blind, placebo-controlled trial (NCT02229851) in 300 participants with growth hormone deficiency who had never received growth hormone treatment or had stopped treatment with other growth hormone formulations at least three months before the study. Participants were randomly assigned to receive injections of weekly somapacitan, weekly placebo (inactive treatment), or daily somatropin, an FDA-approved growth hormone. The effectiveness of somapacitan was determined by the percentage change of truncal fat, the fat that is accumulated in the trunk or central area of the body that is regulated by growth hormone and can be associated with serious medical issues. The trial was conducted at 92 sites in 16 countries: the United States, Australia, Germany, India, Japan, Latvia, Lithuania, Malaysia, Poland, Romania, Russian Fed, South Africa, Sweden, Turkey, Ukraine and the United Kingdom.Adult participants were assigned at random to weekly Sogroya or placebo injections for 34 weeks. Neither the participants nor the investigators knew which treatment was given until the end of the trial. One additional group of participants with GHD received daily injections of somatotropin (an approved treatment for GHD). At the end of the 34-week treatment period, truncal fat decreased by 1.06%, on average, among participants taking weekly somapacitan while it increased among participants taking the placebo by 0.47%. In the daily somatropin group, truncal fat decreased by 2.23%. Participants in the weekly somapacitan and daily somatropin groups had similar improvements in other clinical endpoints. Society and culture Legal status Somapacitan was approved for medical use in the United States in August 2020. The U.S. Food and Drug Administration (FDA) granted the approval of Sogroya to Novo Nordisk, Inc.On 28 January 2021, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Sogroya, intended for the treatment of growth hormone deficiency in adults. The applicant for this medicinal product is Novo Nordisk A/S. Somapacitan was approved for medical use in the European Union in March 2021. See also Growth hormone therapy References External links "Somapacitan". Drug Information Portal. U.S. National Library of Medicine. Clinical trial number NCT02229851 for "Trial to Compare the Efficacy and Safety of NNC0195-0092 (Somapacitan) With Placebo and Norditropin FlexPro (Somatropin) in Adults With Growth Hormone Deficiency. (REAL 1)" at ClinicalTrials.gov

You function as a medical informant. Please provide in-depth yet accessible descriptions of medical terms, suitable for a broad audience.

I'm not familiar with the medical term 'Intrauterine growth restriction.' Could you provide some insights?

Intrauterine growth restriction (IUGR), or fetal growth restriction, refers to poor growth of a fetus while in the womb during pregnancy. IUGR is defined by clinical features of malnutrition and evidence of reduced growth regardless of an infants birth weight percentile. The causes of IUGR are broad and may involve maternal, fetal, or placental complications.At least 60% of the 4 million neonatal deaths that occur worldwide every year are associated with low birth weight (LBW), caused by intrauterine growth restriction (IUGR), preterm delivery, and genetic abnormalities, demonstrating that under-nutrition is already a leading health problem at birth. Intrauterine growth restriction can result in a baby being small for gestational age (SGA), which is most commonly defined as a weight below the 10th percentile for the gestational age. At the end of pregnancy, it can result in a low birth weight. Types There are two major categories of IUGR: pseudo IUGR and true IUGRWith pseudo IUGR, the fetus has a birth weight below the tenth percentile for the corresponding gestational age but has a normal ponderal index, subcutaneous fat deposition, and body proportion. Pseudo IUGR occurs due to uneventful intrauterine course and can be rectified by proper postnatal care and nutrition. Such babies are also called small for gestational age.True IUGR occurs due to pathological conditions which may be either fetal or maternal in origin. In addition to low body weight they have abnormal ponderal index, body disproportion, and low subcutaneous fat deposition. There are two types-symmetrical and asymmetrical. Some conditions are associated with both symmetrical and asymmetrical growth restriction. Asymmetrical Asymmetrical IUGR accounts for 70-80% of all IUGR cases. In asymmetrical IUGR, there is decreased oxygen or nutrient supply to the fetus during the third trimester of pregnancy due to placental insufficiency. This type of IUGR is sometimes called "head sparing" because brain growth is typically less affected, resulting in a relatively normal head circumference in these children. Because of decreased oxygen supply to the fetus, blood is diverted to the vital organs, such as the brain and heart. As a result, blood flow to other organs - including liver, muscle, and fat - is decreased. This causes abdominal circumference in these children to be decreased.A lack of subcutaneous fat leads to a thin and small body out of proportion with the liver. Normally at birth the brain of the fetus is 3 times the weight of its liver. In IUGR, it becomes 5-6 times. In these cases, the embryo/fetus has grown normally for the first two trimesters but encounters difficulties in the third, sometimes secondary to complications such as pre-eclampsia. Other symptoms than the disproportion include dry, peeling skin and an overly-thin umbilical cord. The baby is at increased risk of hypoxia and hypoglycemia. This type of IUGR is most commonly caused by extrinsic factors that affect the fetus at later gestational ages. Specific causes include: Chronic high blood pressure Severe malnutrition Genetic mutations, Ehlers–Danlos syndrome Symmetrical Symmetrical IUGR is commonly known as global growth restriction, and indicates that the fetus has developed slowly throughout the duration of the pregnancy and was thus affected from a very early stage. The head circumference of such a newborn is in proportion to the rest of the body. Since most neurons are developed by the 18th week of gestation, the fetus with symmetrical IUGR is more likely to have permanent neurological sequelae. Common causes include: Early intrauterine infections, such as cytomegalovirus, rubella or toxoplasmosis Chromosomal abnormalities Anemia Maternal substance use (prenatal alcohol use can result in Fetal alcohol syndrome) Causes IUGR is caused by a variety of factors; these can be fetal, maternal, placental or genetic factors. Maternal Pre-pregnancy weight and nutritional status Poor weight gain during pregnancy Malnutrition Anemia Substance use: smoking, alcohol, drugs including marijuana or cocaine Medication: warfarin, steroids, anticonvulsants Inter-pregnancy interval of less than 6 months Assisted reproductive technologies Pre-gestational diabetes Gestational diabetes Pulmonary disease Cardiovascular disease Kidney disease Hypertension Celiac disease increases the risk of intrauterine growth restriction by an odds ratio of approximately 2.48 Subclinical hypothyroidism Blood clotting disorder/disease (e.g., Factor V Leiden) Uteroplacental Preeclampsia Multiple gestation Uterine malformations Placental insufficiency Fetal Chromosomal abnormalities Vertically transmitted infections: TORCH, Malaria, congenital HIV infection, Syphilis Erythroblastosis fetalis Congenital abnormalities Genetic Placental genes Maternal genes: Endothelin-1 over-expression, Leptin under-expression Fetal genes Pathophysiology If the cause of IUGR is extrinsic to the fetus (parental or uteroplacental), transfer of oxygen and nutrients to the fetus is decreased. This causes a reduction in the fetus’ stores of glycogen and lipids. This often leads to hypoglycemia at birth. Polycythemia can occur secondary to increased erythropoietin production caused by the chronic hypoxemia. Hypothermia, thrombocytopenia, leukopenia, hypocalcemia, and bleeding in the lungs are often results of IUGR.Infants with IUGR are at increased risk of perinatal asphyxia due to chronic hypoxia, usually associated with placental insufficiency, placental abruption, or a umbilical cord accident. This chronic hypoxia also places IUGR infants at elevated risk of persistent pulmonary hypertension of the newborn, which can impair an infants blood oxygenation and transition to postnatal circulation.If the cause of IUGR is intrinsic to the fetus, growth is restricted due to genetic factors or as a sequela of infection. IUGR is associated with a wide range of short- and long-term neurodevelopmental disorders. Cardiovascular In IUGR, there is an increase in vascular resistance in the placental circulation, causing an increase in cardiac afterload. There is also increased vasoconstriction of the arteries in the periphery, which occurs in response to chronic hypoxia in order to preserve adequate blood flow to the fetus vital organs. This prolonged vasoconstriction leads to remodeling and stiffening of the arteries, which also contributes to the increase in cardiac afterload. Therefore, the fetal heart must work harder to contract during each heartbeat, which leads to an increase in wall stress and cardiac hypertrophy. These changes in the fetal heart lead to increased long-term risk of hypertension, atherosclerosis, cardiovascular disease, and stroke. Pulmonary Normal lung development is interrupted in fetuses with IUGR, which increases their risk for respiratory compromise and impaired lung function later in life. Preterm infants with IUGR are more likely to have bronchopulmonary dysplasia (BPD), a chronic lung disease that is thought to be associated with prolonged use of mechanical ventilation. Neurological IUGR is associated with long-term motor deficits and cognitive impairment. In order to adapt to the chronic hypoxia associated with placental insufficiency, blood flow is redirected to the brain to try to preserve brain growth and development as much as possible. Even though this is thought to be protective, fetuses with IUGR who have undergone this brain-sparing adaptation have worse neurological outcomes compared with those who have not undergone this adaptation.Magnetic resonance imaging (MRI) can detect changes in volume and structural development of infants with IUGR compared with those whose growth is appropriate for gestational age (AGA). But MRI is not easily accessible for all patients.White matter effects – In postpartum studies of infants, it was shown that there was a decrease of the fractal dimension of the white matter in IUGR infants at one year corrected age. This was compared to at term and preterm infants at one year adjusted corrected age.Grey matter effects – Grey matter was also shown to be decreased in infants with IUGR at one year corrected age.Children with IUGR are often found to exhibit brain reorganization including neural circuitry. Reorganization has been linked to learning and memory differences between children born at term and those born with IUGR.Studies have shown that children born with IUGR had lower IQ. They also exhibit other deficits that point to frontal lobe dysfunction.IUGR infants with brain-sparing show accelerated maturation of the hippocampus which is responsible for memory. This accelerated maturation can often lead to uncharacteristic development that may compromise other networks and lead to memory and learning deficiencies. Management Mothers whose fetus is diagnosed with intrauterine growth restriction can be managed with several monitoring and delivery methods. It is currently recommended that any fetus that has growth restriction and additional structural abnormalities should be evaluated with genetic testing. In addition to evaluating the fetal growth velocity, the fetus should primarily be monitored by ultrasonography every 3–4 weeks. An additional monitoring technique is an Doppler velocimetry. Doppler velocimetry is useful in monitoring blood flow through the uterine and umbilical arteries, and may indicate signs of uteroplacental insufficiency. This method may also detect blood vessels, specifically the ductus venosus and middle cerebral arteries, which are not developing properly or may not adapt well after birth. Monitoring via Doppler velocimetry has been shown to decrease the risk of morbidity and mortality before and after parturition among IUGR patients. Standard fetal surveillance via nonstress tests and/or biophysical profile scoring is also recommended. Bed rest has not been found to improve outcomes and is not typically recommended. There is currently a lack of evidence supporting any dietary or supplemental changes that may prevent the development of IUGR.The optimal timing of delivery for a fetus with IUGR is unknown. However, the timing of delivery is currently based on the cause of IUGR and parameters collected from the umbilical artery doppler. Some of these include: pulsatility index, resistance index, and end-diastolic velocities, which are measurements of the fetal circulation. Fetuses with an anticipated delivery before 34 weeks gestation are recommended to receive corticosteroids to facilitate fetal maturation. Anticipated births before 32 weeks should receive magnesium sulfate to protect development of the fetal brain. Outcomes Postnatal complications After correcting for several factors such as low gestational parental weight, it is estimated that only around 3% of pregnancies are affected by true IUGR. 20% of stillborn infants exhibit IUGR. Perinatal mortality rates are 4-8 times higher for infants with IUGR, and morbidity is present in 50% of surviving infants. Common causes of mortality in fetuses/infants with IUGR include: severe placental insufficiency and chronic hypoxia, congenital malformations, congenital infections, placental abruption, cord accidents, cord prolapse, placental infarcts, and severe perinatal depression.IUGR is more common in preterm infants than in full term (37–40 weeks gestation) infants, and its frequency decreases with increasing gestational age. Relative to premature infants who do not exhibit IUGR, premature infants with IUGR are more likely to have adverse neonatal outcomes, including respiratory distress syndrome, intraventricular hemorrhage, and necrotizing enterocolitis. This association with prematurity suggests utility of screening for IUGR as a potential risk factor for preterm labor.Feeding intolerance, hypothermia, hypoglycemia, and hyperglycemia are all common in infants in the postnatal period, indicating the need to closely manage these patients temperature and nutrition. Furthermore, rapid metabolic and physiologic changes in the first few days after birth can yield susceptibility to hypocalcemia, polycythemia, immunologic compromise, and renal dysfunction. Long-term consequences According to the theory of thrifty phenotype, intrauterine growth restriction triggers epigenetic responses in the fetus that are otherwise activated in times of chronic food shortage. If the offspring actually develops in an environment where food is readily accessible, it may be more prone to metabolic disorders, such as obesity and type II diabetes.Infants with IUGR may continue to show signs of abnormal growth throughout childhood. Infants with asymmetric IUGR (head-sparing) typically have more robust catch-up postnatal growth, as compared with infants with symmetric IUGR, who may remain small throughout life. The majority of catch-up growth occurs in the first 6 months of life, but can continue throughout the first two years. Approximately 10% of infants who are small for gestational age due to IUGR will still have short stature in late childhood.Infants with IUGR are also at elevated risk for neurodevelopmental abnormalities, including motor delay and cognitive impairments. Low IQ in adulthood may occur in up to one third of infants born small for gestational age due to IUGR. Infants who fail to display adequate catch-up growth in the first few years of life may exhibit worse outcomes.Catch-up growth can alter fat distribution in children diagnosed with IUGR as infants and increase risk of metabolic syndrome. Infants with IUGR may be susceptible to long-term dysfunction of several endocrine processes, including growth hormone signaling, the hypothalamic-pituitary-adrenal axis, and puberty. Renal dysfunction, disrupted lung development, and impaired bone metabolism are also associated with IUGR. Animals In sheep, intrauterine growth restriction can be caused by heat stress in early to mid pregnancy. The effect is attributed to reduced placental development causing reduced fetal growth. Hormonal effects appear implicated in the reduced placental development. Although early reduction of placental development is not accompanied by concurrent reduction of fetal growth; it tends to limit fetal growth later in gestation. Normally, ovine placental mass increases until about day 70 of gestation, but high demand on the placenta for fetal growth occurs later. (For example, research results suggest that a normal average singleton Suffolk x Targhee sheep fetus has a mass of about 0.15 kg at day 70, and growth rates of about 31 g/day at day 80, 129 g/day at day 120 and 199 g/day at day 140 of gestation, reaching a mass of about 6.21 kg at day 140, a few days before parturition.) In adolescent ewes (i.e. ewe hoggets), overfeeding during pregnancy can also cause intrauterine growth restriction, by altering nutrient partitioning between dam and conceptus. Fetal growth restriction in adolescent ewes overnourished during early to mid pregnancy is not avoided by switching to lower nutrient intake after day 90 of gestation; whereas such switching at day 50 does result in greater placental growth and enhanced pregnancy outcome. Practical implications include the importance of estimating a threshold for "overnutrition" in management of pregnant ewe hoggets. In a study of Romney and Coopworth ewe hoggets bred to Perendale rams, feeding to approximate a conceptus-free live mass gain of 0.15 kg/day (i.e. in addition to conceptus mass), commencing 13 days after the midpoint of a synchronized breeding period, yielded no reduction in lamb birth mass, where compared with feeding treatments yielding conceptus-free live mass gains of about 0 and 0.075 kg/day. In both of the above models of IUGR in sheep, the absolute magnitude of uterine blood flow is reduced. Evidence of substantial reduction of placental glucose transport capacity has been observed in pregnant ewes that had been heat-stressed during placental development. See also Runt Interspecific pregnancy can cause this in animals References == External links ==

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Can you break down the meaning of the medical term 'Ketonuria' for me?

Ketonuria is a medical condition in which ketone bodies are present in the urine. It is seen in conditions in which the body produces excess ketones as an indication that it is using an alternative source of energy. It is seen during starvation or more commonly in type 1 diabetes mellitus. Production of ketone bodies is a normal response to a shortage of glucose, meant to provide an alternate source of fuel from fatty acids. Pathophysiology Ketones are metabolic end-products of fatty acid metabolism. In healthy individuals, ketones are formed in the liver and are completely metabolized so that only negligible amounts appear in the urine. However, when carbohydrates are unavailable or unable to be used as an energy source, fat becomes the predominant body fuel instead of carbohydrates and excessive amounts of ketones are formed as a metabolic byproduct. Higher levels of ketones in the urine indicate that the body is using fat as the major source of energy. Ketone bodies that commonly appear in the urine when fats are burned for energy are acetoacetate and beta-hydroxybutyric acid. Acetone is also produced and is expired by the lungs. Normally, the urine should not contain a noticeable concentration of ketones to give a positive reading. As with tests for glucose, acetoacetate can be tested by a dipstick or by a lab. The results are reported as small, moderate, or large amounts of acetoacetate. A small amount of acetoacetate is a value under 20 mg/dL; a moderate amount is a value of 30–40 mg/dL, and a finding of 80 mg/dL or greater is reported as a large amount. One 2010 study admits that though ketonurias relation to general metabolic health is ill-understood, there is a positive relationship between the presence of ketonuria after fasting and positive metabolic health. Causes Metabolic abnormalities such as diabetes, renal glycosuria, or glycogen storage disease. Dietary conditions such as starvation, fasting, low-carbohydrate diets, prolonged vomiting, and anorexia including caused by hyperemesis gravidarum. Conditions in which metabolism is increased, such as hyperthyroidism, fever, pregnancy or lactation.In non-diabetic persons, ketonuria may occur during acute illness or severe stress. Approximately 15% of hospitalized patients may have ketonuria, even though they do not have diabetes. In a diabetic patient, ketone bodies in the urine suggest that the patient is not adequately controlled and that adjustments of medication, diet, or both should be made promptly. In the non diabetic patient, ketonuria reflects a reduced carbohydrate metabolism and an increased fat metabolism. Diagnosis A wide variety of companies manufacture ketone screening strips. A strip consists of a thin piece of plastic film slightly larger than a matchstick, with a reagent pad on one end that is either dipped into a urine sample or passed through the stream while the user is voiding. The pad is allowed to react for an exact, specified amount of time (it is recommended to use a stopwatch to time this exactly and disregard any resultant colour change after the specified time); its resulting colour is then compared to a graded shade chart indicating a detection range from negative presence of ketones up to a significant quantity. In severe diabetic ketoacidosis, the dipstix reaction based on sodium nitroprusside may underestimate the level of ketone bodies in the blood. It is sensitive to acetoacetate only, and the ratio of beta-hydroxybutyric to acetoacetate is shifted from a normal value of around 1:1 up to around 10:1 under severely ketoacetotic conditions, due to a changing redox milieu in the liver. Measuring acetoacetate alone will thus underestimate the accompanying beta-hydroxybutyrate if the standard conversion factor is applied. Screening Screening for ketonuria is done frequently for acutely ill patients, presurgical patients, and pregnant women. Any diabetic patient who has elevated levels of blood and urine glucose should be tested for urinary ketones. In addition, when diabetic treatment is being switched from insulin to oral hypoglycemic agents, the patients urine should be monitored for ketonuria. The development of ketonuria within 24 hours after insulin withdrawal usually indicates a poor response to the oral hypoglycemic agents. Diabetic patients should have their urine tested regularly for glucose and ketones, particularly when acute infection or other illness develops. In conditions associated with acidosis, urinary ketones are tested to assess the severity of acidosis and to monitor treatment response. Urine ketones appear before there is any significant increase in blood ketones; therefore, urine ketone measurement is especially helpful in emergency situations. References External links National Institute of Health (NIH) webpage on Ketonuria

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I need a basic explanation for the medical term 'Vascular dementia.'

Vascular dementia (VaD) is dementia caused by problems in the supply of blood to the brain, typically a series of minor strokes, leading to worsening cognitive abilities, the decline occurring piecemeal. The term refers to a syndrome consisting of a complex interaction of cerebrovascular disease and risk factors that lead to changes in brain structures due to strokes and lesions, resulting in changes in cognition. The temporal relationship between a stroke and cognitive deficits is needed to make the diagnosis. Signs and symptoms Differentiating dementia syndromes can be challenging, due to the frequently overlapping clinical features and related underlying pathology. In particular, Alzheimers disease often co-occurs with vascular dementia.People with vascular dementia present with progressive cognitive impairment, acutely or sub-acutely as in mild cognitive impairment, frequently step-wise, after multiple cerebrovascular events (strokes). Some people may appear to improve between events and decline after further silent strokes. A rapidly deteriorating condition may lead to death from a stroke, heart disease, or infection.The disease is described as both a mental disorder and behavioural disorder within the International Classification of Diseases. Signs and symptoms are cognitive, motor, behavioral, and for a significant proportion of patients, also affective. These changes typically occur over a period of 5–10 years. Signs are typically the same as in other dementias, but mainly include cognitive decline and memory impairment of sufficient severity as to interfere with activities of daily living, sometimes with presence of focal neurologic signs, and evidence of features consistent with cerebrovascular disease on brain imaging (CT or MRI). The neurologic signs localizing to certain areas of the brain that can be observed are hemiparesis, bradykinesia, hyperreflexia, extensor plantar reflexes, ataxia, pseudobulbar palsy, as well as gait problems and swallowing difficulties. People have patchy deficits in terms of cognitive testing. They tend to have better free recall and fewer recall intrusions when compared with patients with Alzheimers disease. In the more severely affected patients, or patients affected by infarcts in Wernickes or Brocas areas, specific problems with speaking called dysarthria and aphasias may be present.In small vessel disease, the frontal lobes are often affected. Consequently, patients with vascular dementia tend to perform worse than their Alzheimers disease counterparts in frontal lobe tasks, such as verbal fluency, and may present with frontal lobe problems: apathy, abulia (lack of will or initiative), problems with attention, orientation, and urinary incontinence. They tend to exhibit more perseverative behavior. VaD patients may also present with general slowing of processing ability, difficulty shifting sets, and impairment in abstract thinking. Apathy early in the disease is more suggestive of vascular dementia.Rare genetic disorders that cause vascular lesions in the brain have other presentation patterns. As a rule, they tend to occur earlier in life and have a more aggressive course. In addition, infectious disorders, such as syphilis, can cause arterial damage, strokes, and bacterial inflammation of the brain. Causes Vascular dementia can be caused by ischemic or hemorrhagic infarcts affecting multiple brain areas, including the anterior cerebral artery territory, the parietal lobes, or the cingulate gyrus. On rare occasion, infarcts in the hippocampus or thalamus are the cause of dementia. A history of stroke increases the risk of developing dementia by around 70%, and recent stroke increases the risk by around 120%. Brain vascular lesions can also be the result of diffuse cerebrovascular disease, such as small vessel disease.Risk factors for vascular dementia include age, hypertension, smoking, hypercholesterolemia, diabetes mellitus, cardiovascular disease, and cerebrovascular disease. Other risk factors include geographic origin, genetic predisposition, and prior strokes.Vascular dementia can sometimes be triggered by cerebral amyloid angiopathy, which involves accumulation of beta amyloid plaques in the walls of the cerebral arteries, leading to breakdown and rupture of the vessels. Since amyloid plaques are a characteristic feature of Alzheimers disease, vascular dementia may occur as a consequence. Cerebral amyloid angiopathy can, however, appear in people with no prior dementia condition. Amyloid beta accumulation is often present in cognitively normal elderly people.Two reviews of 2018 and 2019 found potentially an association between celiac disease and vascular dementia. Diagnosis Several specific diagnostic criteria can be used to diagnose vascular dementia, including the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) criteria, the International Classification of Diseases, Tenth Edition (ICD-10) criteria, the National Institute of Neurological Disorders and Stroke criteria, Association Internationale pour la Recherche et lEnseignement en Neurosciences (NINDS-AIREN) criteria, the Alzheimers Disease Diagnostic and Treatment Center criteria, and the Hachinski Ischemic Score (after Vladimir Hachinski).The recommended investigations for cognitive impairment include: blood tests (for anemia, vitamin deficiency, thyrotoxicosis, infection, etc.), chest X-Ray, ECG, and neuroimaging, preferably a scan with a functional or metabolic sensitivity beyond a simple CT or MRI. When available as a diagnostic tool, single photon emission computed tomography (SPECT) and positron emission tomography (PET) neuroimaging may be used to confirm a diagnosis of multi-infarct dementia in conjunction with evaluations involving mental status examination. In a person already having dementia, SPECT appears to be superior in differentiating multi-infarct dementia from Alzheimers disease, compared to the usual mental testing and medical history analysis. Advances have led to the proposal of new diagnostic criteria.The screening blood tests typically include full blood count, liver function tests, thyroid function tests, lipid profile, erythrocyte sedimentation rate, C reactive protein, syphilis serology, calcium serum level, fasting glucose, urea, electrolytes, vitamin B-12, and folate. In selected patients, HIV serology and certain autoantibody testing may be done.Mixed dementia is diagnosed when people have evidence of Alzheimers disease and cerebrovascular disease, either clinically or based on neuro-imaging evidence of ischemic lesions. Pathology Gross examination of the brain may reveal noticeable lesions and damage to blood vessels. Accumulation of various substances such as lipid deposits and clotted blood appear on microscopic views. The white matter is most affected, with noticeable atrophy (tissue loss), in addition to calcification of the arteries. Microinfarcts may also be present in the gray matter (cerebral cortex), sometimes in large numbers. Although atheroma of the major cerebral arteries is typical in vascular dementia, smaller vessels and arterioles are mainly affected. Prevention Early detection and accurate diagnosis are important, as vascular dementia is at least partially preventable. Ischemic changes in the brain are irreversible, but the patient with vascular dementia can demonstrate periods of stability or even mild improvement. Since stroke is an essential part of vascular dementia, the goal is to prevent new strokes. This is attempted through reduction of stroke risk factors, such as high blood pressure, high blood lipid levels, atrial fibrillation, or diabetes mellitus. Meta-analyses have found that medications for high blood pressure are effective at prevention of pre-stroke dementia, which means that high blood pressure treatment should be started early. These medications include angiotensin converting enzyme inhibitors, diuretics, calcium channel blockers, sympathetic nerve inhibitors, angiotensin II receptor antagonists or adrenergic antagonists. Elevated lipid levels, including HDL, were found to increase risk of vascular dementia. However, six large recent reviews showed that therapy with statin drugs was ineffective in treatment or prevention of this dementia. Aspirin is a medication that is commonly prescribed for prevention of strokes and heart attacks; it is also frequently given to patients with dementia. However, its efficacy in slowing progression of dementia or improving cognition has not been supported by studies. Smoking cessation and Mediterranean diet have not been found to help patients with cognitive impairment; physical activity was consistently the most effective method of preventing cognitive decline. Treatment Currently, there are no medications that have been approved specifically for prevention or treatment of vascular dementia. The use of medications for treatment of Alzheimers dementia, such as cholinesterase inhibitors and memantine, has shown small improvement of cognition in vascular dementia. This is most likely due to the drugs actions on co-existing AD-related pathology. Multiple studies found a small benefit in VaD treatment with: memantine, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist; cholinesterase inhibitors galantamine, donepezil, rivastigmine; Studies have been proposed to evaluate whether an extract of Ginkgo biloba EGb761 improves cognition, daily activities, and quality of life in treating vascular dementia.In those with celiac disease or non-celiac gluten sensitivity, a strict gluten-free diet may relieve symptoms of mild cognitive impairment. It should be started as soon as possible. There is no evidence that a gluten free diet is useful against advanced dementia. People with no digestive symptoms are less likely to receive early diagnosis and treatment.General management of dementia includes referral to community services, aid with judgment and decision-making regarding legal and ethical issues (e.g., driving, capacity, advance directives), and consideration of caregiver stress. Behavioral and affective symptoms deserve special consideration in this patient group. These problems tend to resist conventional psychopharmacological treatment, and often lead to hospital admission and placement in permanent care. Prognosis Many studies have been conducted to determine average survival of patients with dementia. The studies were frequently small and limited, which caused contradictory results in the connection of mortality to the type of dementia and the patients gender. A very large study conducted in Netherlands in 2015 found that the one-year mortality was three to four times higher in patients after their first referral to a day clinic for dementia, when compared to the general population. If the patient was hospitalized for dementia, the mortality was even higher than in patients hospitalized for cardiovascular disease. Vascular dementia was found to have either comparable or worse survival rates when compared to Alzheimers Disease; another very large 2014 Swedish study found that the prognosis for VaD patients was worse for male and older patients.Unlike Alzheimers disease, which weakens the patient, causing them to succumb to bacterial infections like pneumonia, vascular dementia can be a direct cause of death due to the possibility of a fatal interruption in the brains blood supply. Epidemiology Vascular dementia is the second-most-common form of dementia after Alzheimers disease (AD) in older adults. The prevalence of the illness is 1.5% in Western countries and approximately 2.2% in Japan. It accounts for 50% of all dementias in Japan, 20% to 40% in Europe and 15% in Latin America. 25% of stroke patients develop new-onset dementia within one year of their stroke. One study found that in the United States, the prevalence of vascular dementia in all people over the age of 71 is 2.43%, and another found that the prevalence of the dementias doubles with every 5.1 years of age. The incidence peaks between the fourth and the seventh decades of life and 80% of patients have a history of hypertension.A recent meta-analysis identified 36 studies of prevalent stroke (1.9 million participants) and 12 studies of incident stroke (1.3 million participants). For prevalent stroke, the pooled hazard ratio for all-cause dementia was 1.69 (95% confidence interval: 1.49–1.92; P < .00001; I2 = 87%). For incident stroke, the pooled risk ratio was 2.18 (95% confidence interval: 1.90–2.50; P < .00001; I2 = 88%). Study characteristics did not modify these associations, with the exception of sex, which explained 50.2% of between-study heterogeneity for prevalent stroke. These results confirm that stroke is a strong, independent, and potentially modifiable risk factor for all-cause dementia. See also Binswangers disease Cerebrovascular accident References External links Multi-Infarct Dementia Fact Sheet at ninds.nih.gov American Academy of Neurology (December 21, 2007). "Walking and Moderate Exercise Help Prevent Dementia". ScienceDaily. Retrieved December 21, 2007, from https://www.sciencedaily.com/releases/2007/12/071219202948.htm

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Can you break down the meaning of the medical term 'Follicular cyst of ovary' for me?

The follicular cyst of the ovary is a type of functional simple cyst, and is the most common type of ovarian cyst. Signs and symptoms Its rupture can create sharp, severe pain on the side of the ovary on which the cyst appears. This sharp pain (sometimes called mittelschmerz) occurs in the middle of the menstrual cycle, during ovulation. About a fourth of women with this type of cyst experience pain.Usually, these cysts produce no symptoms and disappear by themselves within a few months. Pathophysiology This type can form when ovulation doesnt occur, and a follicle doesnt rupture or release its egg but instead grows until it becomes a cyst, or when a mature follicle involutes (collapses on itself). It usually forms during ovulation, and can grow to about 7 cm in diameter. It is thin-walled, lined by one or more layers of granulosa cell, and filled with clear fluid. Diagnosis Ultrasound is the primary tool used to document the follicular cyst. A doctor monitors these to make sure they disappear, and looks at treatment options if they do not. References == External links ==

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Could you please explain the term 'Necrotizing fasciitis' in simple language?

Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the bodys soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or purple skin in the affected area, severe pain, fever, and vomiting. The most commonly affected areas are the limbs and perineum.Typically, the infection enters the body through a break in the skin such as a cut or burn. Risk factors include poor immune function such as from diabetes or cancer, obesity, alcoholism, intravenous drug use, and peripheral artery disease. It does not typically spread between people. The disease is classified into four types, depending on the infecting organism. Between 55 and 80% of cases involve more than one type of bacteria. Methicillin-resistant Staphylococcus aureus (MRSA) is involved in up to a third of cases. Medical imaging is often helpful to confirm the diagnosis.Necrotizing fasciitis may be prevented with proper wound care and handwashing. It is usually treated with surgery to remove the infected tissue, and intravenous antibiotics. Often, a combination of antibiotics is used, such as penicillin G, clindamycin, IV vancomycin, and gentamicin. Delays in surgery are associated with a much higher risk of death. Despite high-quality treatment, the risk of death is between 25 and 35%.Necrotizing fasciitis occurs in about 0.4 people per 100,000 per year in the U.S., and about 1 per 100,000 in Western Europe. Both sexes are affected equally. It becomes more common among older people and is rare in children. It has been described at least since the time of Hippocrates. The term "necrotizing fasciitis" first came into use in 1952. Signs and symptoms Symptoms may include fever, swelling, and complaints of excessive pain. The initial skin changes are similar to cellulitis or abscess, thus making the diagnosis at early stages difficult. Hardening of the skin and soft tissue and swelling beyond the area of skin changes are commonly present in those with early necrotizing changes. The redness and swelling usually blend into surrounding normal tissues. The overlying skin may appear shiny and tense. Other signs which are more suggestive of necrotizing changes (but present in later stages in 7 to 44% of the cases) are: formation of bullae, bleeding into the skin which is present before skin necrosis (skin turning from red to purple and black due to thrombosis of blood vessels), presence of gas in tissues, and reduced or absent sensation over the skin (due to the necrosis of the underlying nerves). Rapid progression to shock despite antibiotic therapy is another indication of necrotizing fasciitis. Necrotizing changes affecting the groin are known as Fournier gangrene.However, those who are immunocompromised (have cancer, use corticosteroid, on radiotherapy, chemotherapy, HIV/AIDS, or prior organ or bone marrow transplantation) may not show typical symptoms. Immunocompromised persons also have twice the risk of death from necrotizing infections, so higher suspicion should be maintained in this group. Cause Risk factors More than 70% of cases are recorded in people with at least one of these clinical situations: immunosuppression, diabetes, alcoholism/drug abuse/smoking, malignancies, and chronic systemic diseases. For reasons that are unclear, it occasionally occurs in people with an apparently normal general condition.Necrotizing fasciitis can occur at any part of the body, but it is more commonly seen at the extremities, perineum, and genitals. Only a few of such cases arise from the chest and abdomen. Trauma is the usual cause of the infection, such as from intravenous drug injection, insulin injection, animal and insect bites, catheter insertion over the skin, or a fistula connecting skin to the internal body organs. Skin infections such as abscess and ulcers can also complicate necrotizing fasciitis. Spreading of infection through blood has been suggested for those with streptococcal pharyngitis. For infection of the perineum and genitals (Fournier gangrene), trauma, surgery, urinary tract infection, stones, and Bartholin gland abscess are the usual causes.The risk of developing necrotizing fasciitis from a wound can be reduced by good wound care and handwashing. Bacteria Types of soft-tissue necrotizing infection can be divided into four classes according to the types of bacteria infecting the soft tissue. This classification system was first described by Giuliano and his colleagues in 1977.Type I infection: This is the most common type of infection, and accounts for 70 to 80% of cases. It is caused by a mixture of bacterial types, usually in abdominal or groin areas. This type of infection is usually caused by various species of Gram-positive cocci, (Staphylococcus aureus, Streptococcus pyogenes, and enterococci), Gram-negative rods, (Escherichia coli, Pseudomonas aeruginosa), and anaerobes, (Bacteroides and Clostridium species). Populations of those affected are typically older with medical comorbidities such as diabetes mellitus, obesity, and immunodeficiency. Usually, trauma is not the cause of such infections. Previous history of abscess infection or gut perforation with bacterial translocation may be elicited. Clostridial infection accounts for 10% of type I infection. Clostridium species involved are Clostridium perfringens, Clostridium septicum, and Clostridium sordellii, which typically cause gas gangrene (also known as myonecrosis). Clostridium perfringens produces two deadly toxins: alpha-toxin and theta-toxin. Alpha-toxin causes excessive platelet aggregation which blocks blood vessels and deprives the vital organs of oxygen supply. This creates an acidic, oxygen-deficient environment for the proliferation of bacteria. When alpha-toxin is absorbed by soft tissues, it can inhibit the migration of white blood cells from blood vessels into the soft tissue, thus impairing phagocyte function. The two toxins together can cause destruction of red blood cells in blood vessels, damage to the integrity of the blood vessels, and suppression of heart function.Clostridium sordellii can also produce two major toxins: all known virulent strains produce the essential virulence factor lethal toxin (TcsL), and a number also produce haemorrhagic toxin (TcsH). TcsL and TcsH are both members of the large clostridial cytotoxin (LCC) family. The key Clostridium septicum virulence factor is a pore-forming toxin called alpha-toxin, though it is unrelated to the Clostridium perfringens alpha-toxin. Myonecrotic infections caused by these clostridial species commonly occur in injecting heroin users. Those with clostridial infections typically have severe pain at the wound site, where the wound typically drains foul-smelling blood mixed with serum (serosanguinous discharge). Shock can progress rapidly after initial injury or infection, and once the state of shock is established, the chance of dying exceeds 50%. Another bacterium associated with similar rapid disease progression is group A streptococcal infection (mostly Streptococcus pyogenes). Meanwhile, other bacterial infections require two or more days to become symptomatic.Type II infection: This infection accounts for 20 to 30% of cases, mainly involving the extremities. This mainly involves Streptococcus pyogenes bacteria, alone or in combination with staphylococcal infections. Both types of bacteria can progress rapidly and manifest as toxic shock syndrome. Streptococcus species produce M protein, which acts as a superantigen, stimulating a massive systemic immune response which is not effective against the bacterial antigen, precipitating shock. Type II infection more commonly affects young, healthy adults with a history of injury.Type III infection: Vibrio vulnificus, a bacterium found in saltwater, is a rare cause of this infection, which occurs through a break in the skin. Disease progression is similar to type II but sometimes with little visible skin changes.Type IV infection: Some authors have described the type IV infection as fungal in nature. Diagnosis Early diagnosis is difficult, as the disease often looks early on like a simple superficial skin infection. While a number of laboratory and imaging modalities can raise the suspicion for necrotizing fasciitis, none can rule it out. The gold standard for diagnosis is a surgical exploration in a setting of high suspicion. When in doubt, a small incision can be made into the affected tissue, and if a finger easily separates the tissue along the fascial plane, the diagnosis is confirmed and an extensive debridement should be performed. Medical imaging Imaging has a limited role in the diagnosis of necrotizing fasciitis. The time delay in performing imaging is a major concern. Plain radiography may show subcutaneous emphysema (gas in the subcutaneous tissue), which is strongly suggestive of necrotizing changes, but it is not sensitive enough to detect all the cases, because necrotizing skin infections caused by bacteria other than clostridial infections usually do not show subcutaneous emphysema. If the diagnosis is still in doubt, computed tomography (CT) scans and magnetic resonance imaging (MRI) are more sensitive modalities than plain radiography. However, both the CT scan and MRI are not sensitive enough to rule out necrotizing changes completely. CT scan may show fascial thickening, edema, subcutaneous gas, and abscess formation. In MRI, when fluid collection with deep fascia involvement occurs, thickening or enhancement with contrast injection, necrotizing fasciitis should be strongly suspected. Meanwhile, ultrasonography can show superficial abscess formation, but is not sensitive enough to diagnose necrotizing fasciitis. CT scan is able to detect about 80% of cases, while MRI may pick up slightly more. Scoring system A white blood cell count greater than 15,000 cells/mm3 and serum sodium level less than 135 mmol/L have a sensitivity of 90% in detecting the necrotizing soft tissue infection. It also has a 99% chance of ruling out necrotizing changes if the values have shown otherwise. Various scoring systems are being developed to determine the likelihood of getting necrotizing fasciitis, but a scoring system developed by Wong and colleagues in 2004 is the most commonly used. It is the laboratory risk indicator for necrotizing fasciitis (LRINEC) score, which can be used to stratify by risk those people having signs of severe cellulitis or abscess to determine the likelihood of necrotizing fasciitis being present. It uses six laboratory values: C-reactive protein, total white blood cell count, hemoglobin, sodium, creatinine, and blood glucose. A score of 6 or more indicates that necrotizing fasciitis should be seriously considered. The scoring criteria are: CRP (mg/L) ≥150: 4 points WBC count (×103/mm3) <15: 0 points 15–25: 1 point >25: 2 points Hemoglobin (g/dL) >13.5: 0 points 11–13.5: 1 point <11: 2 points Sodium (mmol/L) <135: 2 points Creatinine (umol/L) >141: 2 points Glucose (mmol/L) >10: 1 pointHowever, the scoring system has not been validated. The values would be falsely positive if any other inflammatory conditions are present. Therefore, the values derived from this scoring system should be interpreted with caution. About 10% of patients with necrotizing fasciitis in the original study still had a LRINEC score <6. A validation study showed that patients with a LRINEC score ≥6 have a higher rate of both death and amputation. Prevention Necrotizing fasciitis can be partly prevented by good wound care and handwashing. Treatment Surgical debridement (cutting away affected tissue) is the mainstay of treatment for necrotizing fasciitis. Early medical treatment is often presumptive; thus, antibiotics should be started as soon as this condition is suspected. Tissue cultures (rather than wound swabs) are taken to determine appropriate antibiotic coverage, and antibiotics may be changed in light of results. Besides blood pressure control and hydration, support should be initiated for those with unstable vital signs and low urine output. Surgery Aggressive wound debridement should be performed early, usually as soon as the diagnosis of necrotizing soft tissue infection (NSTI) is made. Surgical incisions often extend beyond the areas of induration (the hardened tissue) to remove the damaged blood vessels that are responsible for the induration. However, cellulitic soft tissues are sometimes spared from debridement for later skin coverage of the wound. More than one operation may be used to remove additional necrotic tissue. In some cases when an extremity is affected by a NSTI, amputation may be the surgical treatment of choice. After the wound debridement, adequate dressings should be applied to prevent exposure of bones, tendons, and cartilage so that such structures do not dry out and to promote wound healing.For necrotizing infection of the perineal area (Fourniers gangrene), wound debridement and wound care in this area can be difficult because of the excretory products that often render this area dirty and affect the wound-healing process. Therefore, regular dressing changes with a fecal management system can help to keep the wound at the perineal area clean. Sometimes, colostomy may be necessary to divert the excretory products to keep the wound at the perineal area clean. Antibiotics Empiric antibiotics are usually initiated as soon as the diagnosis of NSTI has been made, and then later changed to culture-guided antibiotic therapy. In the case of NSTIs, empiric antibiotics are broad-spectrum, covering gram-positive (including MRSA), gram-negative, and anaerobic bacteria.While studies have compared moxifloxacin (a fluoroquinolone) and amoxicillin-clavulanate (a penicillin) and evaluated appropriate duration of treatment (varying from 7 to 21 days), no definitive conclusions on the efficacy of treatment, ideal duration of treatment, or the adverse effects could be made due to poor-quality evidence. Add-on therapy Hyperbaric oxygen: While human and animal studies have shown that high oxygen tension in tissues helps to reduce edema, stimulate fibroblast growth, increase the killing ability of white blood cells, inhibit bacterial toxin release, and increase antibiotic efficacy, no high-quality trials have been shown to support or refute the use of hyperbaric oxygen therapy in patients with NSTIs. Intravenous immunoglobulin (IVIG): No clear difference between using IVIG and placebo has been shown in the treatment of NSTIs, and one study showed serious adverse effects with IVIG use, including acute kidney injury, allergic reactions, aseptic meningitis syndrome, haemolytic anaemia, thrombi, and transmissible agents. AB103: One study assessed the efficacy of a new type of treatment that affects the immune response, called AB103. The study showed no difference in mortality with use of this therapy, but it is difficult to draw definitive conclusions due to low-quality evidence. Supportive therapy: Supportive therapy, often including intravenous hydration, wound care, anticoagulants to prevent thromboembolic events, pain control, etc. should always be provided to patients when appropriate. Epidemiology Necrotizing fasciitis affects about 0.4 in every 100,000 people per year in the United States. About 1,000 cases of necrotizing fasciitis occur per year in the United States, but the rates have been increasing. This could be due to increasing awareness of this condition, leading to increased reporting, or bacterial virulence or increasing bacterial resistance against antibiotics. In some areas of the world, it is as common as one in every 100,000 people.Higher rates of necrotizing fasciitis are seen in those with obesity or diabetes, and those who are immunocompromised or alcoholic, or have peripheral artery disease. However, the disease may also occur in young, healthy adults with no underlying illnesses. NSAIDs may increase the rates of necrotizing infections due to the modification of immune response in the body, because NSAIDs inhibit the cycloxygenase-1 and cycloxygenase-2 enzymes which are important in producing thromboxane and prostaglandin E2. Prostaglandin has been responsible for fever, inflammation, and pain. The inhibition of prostaglandin E2 production reduces inflammatory response and leukocyte adhesion, and thus reduces immune response against bacterial invasion, giving rise to soft-tissue infection. History In the fifth century BCE, Hippocrates described necrotizing soft tissue infection as a disease where those affected would have "erysipelas all over the body while the cause was only a trivial accident. Bones, flesh, and sinew (cord, tendon, or nerve) would fall off from the body and there were many deaths". The first English description for necrotizing soft-tissue infection was by British surgeon Leonard Gillespie and British physicians Gilbert Blaine and Thomas Trotter in the 18th century. At that time, necrotizing soft-tissue infections were known variously as "phagedaenic ulcer" (ulceration that spreads and destroys surrounding tissue), "gangrenous phagedena", "gangrenous ulcer", "malignant ulcer", "putrid ulcer", "fulminating gangrene", "necrotizing erysipelas", "gangrenous erysipelas", "crepitant cellulitis", "gangrenous cellulitis", "Meleney cellulitis", "necrotizing synergistic cellulitis", "hemolytic streptococcal gangrene", "progressive bacterial synergistic gangrene", "necrotizing abscess", "galloping gangrene", or "hospital gangrene". Later, "hospital gangrene" became more commonly used. In 1871 Confederate States Army surgeon Joseph Jones reported 2,642 cases of hospital gangrene with a mortality rate of 46%. In 1883, Dr Jean-Alfred Fournier described the necrotizing infection of the perineum and scrotum, now called Fournier gangrene. The term "necrotizing fasciitis" was first coined by Wilson in 1952. Its definition has become broader, to include not only infection of fascia, but also other soft-tissue infection. Despite being disfavored by the medical community, the term "galloping gangrene" is frequently used in sensationalistic news media to refer to outbreaks of necrotizing fasciitis. Society and culture Notable cases 1994 Lucien Bouchard, former premier of Québec, Canada, who was infected while leader of the federal official opposition Bloc Québécois party, lost a leg to the illness. 1994 A cluster of cases occurred in Gloucestershire, in the west of England. Of five confirmed and one probable infection, two died. The cases were believed to be connected. The first two had acquired the Streptococcus pyogenes bacteria during surgery; the remaining four were community-acquired. The cases generated much newspaper coverage, with lurid headlines such as "Flesh Eating Bug Ate My Face". 1997 Ken Kendrick, former agent and partial owner of the San Diego Padres and Arizona Diamondbacks, contracted the disease. He had seven surgeries in a little more than a week and later fully recovered. 2004 Don Rickles, American stand-up comedian, actor, and author, known especially for his insult comedy, contracted the disease in his left leg. He had six operations and later recovered. The condition confined him in his later years to performing comedy from a chair. 2004 Eric Allin Cornell, winner of the 2001 Nobel Prize in Physics, lost his left arm and shoulder to the disease. 2005 Alexandru Marin, an experimental particle physicist, professor at MIT, Boston University, and Harvard University, and researcher at CERN and JINR, died from the disease. 2006 Alan Coren, British writer and satirist, announced in his Christmas column for The Times that his long absence as a columnist had been caused by his contracting the disease while on holiday in France. 2009 R. W. Johnson, British journalist and historian, contracted the disease in March after injuring his foot while swimming. His leg was amputated above the knee. 2011 Jeff Hanneman, guitarist for the thrash metal band Slayer, contracted the disease. He died of liver failure two years later, on May 2, 2013, and it was speculated that his infection was the cause of death. However, on May 9, 2013, the official cause of death was announced as alcohol-related cirrhosis. Hanneman and his family had apparently been unaware of the extent of the condition until shortly before his death. 2011 Peter Watts, Canadian science-fiction author, contracted the disease. On his blog, Watts reported, "Im told I was a few hours away from being dead...If there was ever a disease fit for a science-fiction writer, flesh-eating disease has got to be it. This...spread across my leg as fast as a Star Trek space disease in time-lapse." 2014 Daniel Gildenlöw, Swedish singer and songwriter for the band Pain of Salvation, spent several months in a hospital after being diagnosed with necrotizing fasciitis on his back in early 2014. After recovering, he wrote the album In the Passing Light of Day, a concept album about his experience during the hospitalization. 2015 Edgar Savisaar, Estonian politician, had his right leg amputated. He got the disease during a trip to Thailand. 2018 Alex Smith, an American football quarterback for the Washington Football Team of the National Football League (NFL), contracted the disease after being injured during a game. He suffered an open compound fracture in his lower leg, which became infected. Smith narrowly avoided amputation, and eventually returned to playing professional football in October 2020. Smiths injury and recovery is the subject of the ESPN documentary "E60 Presents: Project 11". See also Capnocytophaga canimorsus Gangrene Mucormycosis, a rare fungal infection that can resemble necrotizing fasciitis (See type IV NF listing above) Noma (disease) Toxic shock syndrome Vibrio vulnificus References External links Necrotizing fasciitis at Curlie LRINEC Score Online

You function as a medical explainer. Your task is to convey the meanings of medical terms in a detailed, yet easy-to-understand manner.

I'm curious about the meaning of the medical term 'Hair bleaching.' Can you give me some insights?

Hair bleaching, is the practice of lightening the hair color mainly for cosmetic purposes using bleaching agents. Bleaching can be done alone, combined with a toner, or as a step for further hair coloring. The most common commercial bleaching agents in use are hydrogen peroxide and persulfate salts, but historically other agents such as sulfuric acid, wood ash, lye and hypochlorite bleach were used. Hair can also become bleached unintentionally, such as through sun exposure. History During the early years of the Roman Empire, blond hair was associated with prostitutes. The preference changed to bleaching the hair blond when Greek culture, which practiced bleaching, reached Rome, and was reinforced when the legions that conquered Gaul returned with blond slaves. Sherrow also states that Roman women tried to lighten their hair, but the substances often caused hair loss, so they resorted to wigs made from the captives hair. The bleaching agent used by the Roman women was composed of a solution of ashes from burnt nuts or plants.Diodorus Siculus, a 1st century BC Greek historian, described in detail how Celtic people bleached their hair: "Their aspect is terrifying... They are very tall in stature, with rippling muscles under clear white skin. Their hair is blond, but not naturally so: they bleach it, to this day, artificially, washing it in lime and combing it back from their foreheads. They look like wood-demons, their hair thick and shaggy like a horses mane. Some of them are clean-shaven, but others—especially those of high rank—shave their cheeks but leave a moustache that covers the whole mouth...".During the medieval period, Spanish women preferred to dye their hair black, yet by the time of the Renaissance in the 16th century the fashion (imported from Italy) was to bleach their hair blond or dye it red. Between the Renaissance and the Enlightenment, a number of dangerous hair bleaching methods remained widely practiced, including the use of sulfuric acid, which was an accepted form of hair coloring around the 1600s, and laying out in the sun with hair covered in lye a century later.In Sir Hugh Plats 1602 work Delightes for Ladies the use of oil of vitriol (sulfuric acid) to bleach black hair to chestnut is described as: "Take one part of lead calcined with Sulphur, and one part of quicklime: temper them somewhat thin with water: lay it upon the hair, chafing it well in, and let it dry one quarter of an hour or thereasbouts; the wash the same off with fair water divers times: and lastly with sope and water, and it will be a very natural hair-colour. The longer it lyeth upon the haire, the browner it groweth, This coloureth not the flesh at all, and yet it lasteth very long in the hair." Modern history Howard Hughes 1931 movie Platinum Blonde starring Jean Harlow is noted to have popularized platinum blonde hair color in the US. After the movies success Hughess team established a chain of "Platinum Blonde clubs" in several cities and offered a $10,000 prize that would go to any hairdresser who could copy Harlows shade. Though Harlow denied her hair was bleached, the platinum blonde color was reportedly achieved with a weekly application of ammonia, Clorox bleach, and Lux soap flakes. This process weakened and damaged Harlows naturally ash-blonde hair.During the 1930s Lawrence M. Gelb advanced the formulas of the bleaching products. In 1950 Clairol, the company Gelb founded with wife Jane Clair, introduced the first one-step hair dye product that lightened hair, which became a huge success with the masses. Bleaching process Using bleaching agents Melanin pigments, which give hair a darker color, can be broken down with oxidation. Most commercial bleaching formulas contain hydrogen peroxide and persulfate salts, which under alkaline conditions created by ammonia or monoethanolamine can bleach the hair. Persulfate salts, in combination with hydrogen peroxide or alone, is known for its ability to degrade organics, after activation with heat, transition metals, ultraviolet light, or other means that produce the sulfate radical. Without activation, the persulfate anion is known to react with some organic chemicals, although with slow kinetics. When melanin is oxidized, oxygen gas is released. Products for bleaching ones hair at home usually contain a 6% solution of hydrogen peroxide, while products for use in a hair salon can contain up to 9%. Hair bleaching products can damage hair and cause severe burns to the scalp when applied incorrectly or left on too long.Industrial bleaches that work by reduction (such as sodium hydrosulphite) react with a chromophore, the part of the molecule responsible for its color and decrease the number of carbon-oxygen bonds in it, making it uncoloured. This process might be reversed to a certain extent by oxygen in the air, such as yellowing of bleached paper if kept exposed to air. In contrast hydrogen peroxide chemically alters the chromophore so that it increases the number of carbon-oxygen bonds. Due to the relative absence of reducing agents in the environment, chromophores cannot restore themselves as seen in reduction-based bleaches.Bleaching the hair is a gradual process and different colors could be achieved dependent on the original hair color, application time, and strength of the product used. Applied on black hair, the hair will change its color to brown, red, orange, orange-yellow, yellow, and finally pale yellow. Toner Toning is a common practice after bleaching to mask the undesirable red and orange tones of "brassy" hair using a toner dye. Through toning, the yellow hue of fully bleached hair can be removed to achieve platinum blond hair. The appropriate color of the toner depends on the color of the bleached hair; e.g. to remove the yellow tones a violet toner dye will be needed, but to neutralize red and orange hues a green and blue toner would be more suitable. Tinted shampoos can also be used to tone hair. Sun exposure Excessive exposure to the sun is the most common cause of structural damage of the hair shaft. Photochemical hair damage encompasses hair protein degradation and loss, as well as hair pigment deterioration Photobleaching is common among people with European ancestry. Around 72 percent of customers who agreed to be involved in a study and have European ancestry reported in a recent 23andMe research that the sun lightens their hair. The company also have identified 48 genetic markers that may influence hair photobleaching. Medical significance Drug testing methods using hair samples are found to be disrupted by chemical hair treatments including bleaching. According to a 2019 study bleaching has caused strong chemical degradation on cannabinoids in hair, while permanent colorings in single applications had only negligible effects on cannabinoids. A 2021 study found similar results for methamphetamine concentrations in hair.Persulfate containing products may produce a variety of cutaneous and respiratory responses, such as allergic eczematous contact dermatitis, irritant dermatitis, localized edema, generalized urticaria, rhinitis, asthma, and syncope. References Further reading Robbins, Clarence R. (2006-05-26). Chemical and Physical Behavior of Human Hair. Springer Science & Business Media. ISBN 978-0-387-21695-9.

You are a guide to medical language. Please provide in-depth and understandable explanations of medical terms, highlighting their significance in healthcare.

I'm seeking clarification on the medical term 'Miglitol.' Could you explain it?

Miglitol is an oral anti-diabetic drug that acts by inhibiting the ability of the patient to break down complex carbohydrates into glucose. It is primarily used in diabetes mellitus type 2 for establishing greater glycemic control by preventing the digestion of carbohydrates (such as disaccharides, oligosaccharides, and polysaccharides) into monosaccharides which can be absorbed by the body.Miglitol, and other structurally-related iminosugars, inhibit glycoside hydrolase enzymes called alpha-glucosidases. Since miglitol works by preventing digestion of carbohydrates, it lowers the degree of postprandial hyperglycemia. It must be taken at the start of main meals to have maximal effect. Its effect will depend on the amount of non-monosaccharide carbohydrates in a persons diet. In contrast to acarbose (another alpha-glucosidase inhibitor), miglitol is systemically absorbed; however, it is not metabolized and is excreted by the kidneys. See also Alpha-glucosidase inhibitor Miglustat Voglibose == References ==

You act as a mediator between medical professionals and the public. Provide comprehensive explanations of medical terms, ensuring they are both precise and easily understood.

I'm looking for a concise explanation of the medical term 'Congenital cytomegalovirus infection.'

Congenital cytomegalovirus (CMV) infection refers to a condition where cytomegalovirus is transmitted in the prenatal period. CMV is a member of the virus family herpesviridae and is the most common intrauterine infection.Human cytomegalovirus is one of the vertically transmitted infections that lead to congenital abnormalities. Others include toxoplasmosis, rubella, herpes simplex, and syphilis. Presentation For infants who are infected by their mothers before birth, two potential adverse scenarios exist: Generalized infection may occur in the infant, and can cause complications such as low birth weight, microcephaly, seizures, petechial rash similar to the "blueberry muffin" rash of congenital rubella syndrome, and moderate hepatosplenomegaly (with jaundice). Though severe cases can be fatal, with supportive treatment most infants with CMV disease will survive. However, from 80% to 90% will have complications within the first few years of life that may include hearing loss, vision impairment, and varying degrees of learning disability. Another 5% to 10% of infants who are infected but without symptoms at birth will subsequently have varying degrees of hearing and mental or coordination problems. CMV is the most common cause of non-genetic sensorineural hearing loss in children. The onset of hearing loss can occur at any point during childhood, although commonly within the first decade. It is progressive and can affect both ears. The earlier the mother contracts the virus during pregnancy the more severe the effects are on the fetus, similarly the incidence of SNHL is dependent on which trimester of pregnancy CMV is contracted. The virus accounts for 20% of sensorineural hearing loss in children.These risks appear to be almost exclusively associated with women who previously have not been infected with CMV and who are having their first infection with the virus during pregnancy. There appears to be little risk of CMV-related complications for women who have been infected at least 6 months prior to conception. For this group, which makes up 50% to 80% of the women of child-bearing age, the rate of newborn CMV infection is 1%, and these infants appear to have no significant illness or abnormalities.The virus can also be transmitted to the infant at delivery from contact with genital secretions or later in infancy through breast milk. However, these infections usually result in little or no clinical illness in the infant. CMV can also be transferred through blood transfusions and close contact with large groups of children.To summarise, during a pregnancy when a woman who has never had CMV infection becomes infected with CMV, there is a risk that after birth the infant may have CMV-related complications, the most common of which are associated with hearing loss, visual impairment, or diminished mental and motor capabilities. On the other hand, healthy infants and children who acquire CMV after birth have few, if any, symptoms or complications. However, infants born preterm and infected with CMV after birth (especially via breastmilk) may experience cognitive and motor impairments later in life.Symptoms associated with CMV, such as hearing loss, can result in further developmental delay. A delay in general speech and language development is more common in children with CMV. Children with symptomatic CMV have been found to have a greater incidence of long-term neurological and neurodevelopmental complications than children with fetal alcohol syndrome or down syndrome.Congenital cytomegalovirus infection can be an important cause of intraventricular hemorrhage and neonatal encephalopathy. Diagnosis CMV Testing People infected with CMV develop antibodies to it, initially IgM later IgG indicating current infection and immunity respectively. The virus can be diagnosed through viral isolation, or using blood, urine, or saliva samples.When infected with CMV, most women have no symptoms, but some may have symptoms resembling mononucleosis. Women who develop a mononucleosis-like illness during pregnancy should consult their medical provider.The Centers for Disease Control and Prevention (CDC) does not recommend routine maternal screening for CMV infection during pregnancy because there is no test that can definitively rule out primary CMV infection during pregnancy. Women who are concerned about CMV infection during pregnancy should practice CMV prevention measures. Considering that the CMV virus is present in saliva, urine, tears, blood, mucus, and other bodily fluids, frequent hand washing with soap and water is important after contact with diapers or oral secretions, especially with a child who is in daycare or interacting with other young children on a regular basis.A diagnosis of congenital CMV infection can be made if the virus is found in an infants urine, saliva, blood, or other body tissues during the first week after birth. Antibody tests cannot be used to diagnose congenital CMV; a diagnosis can only be made if the virus is detected during the first week of life. Congenital CMV cannot be diagnosed if the infant is tested more than one week after birth.Visually healthy infants are not routinely tested for CMV infection although only 10–20% will show signs of infection at birth though up to 80% may go onto show signs of prenatal infection in later life. If a pregnant woman finds out that she has become infected with CMV for the first time during her pregnancy, she should have her infant tested for CMV as soon as possible after birth.Treatment for CMV infection should start at 1 month of age and should occur for 6 months. The options for treatment are intravenous ganciclovir and oral valganciclovir. After diagnosis, it is important to further investigate any possible evidence of end-organ disease and symptoms through blood tests, imaging, ophthalmology tests, and hearing tests. Prevention Recommendations for pregnant women with regard to CMV infection: Throughout the pregnancy, practice good personal hygiene, especially handwashing with soap and water, after contact with diapers or oral secretions (particularly with a child who is in day care). Sharing of food, eating and drinking utensils, and contact with toddlers saliva should be avoided. Women who develop a mononucleosis-like illness during pregnancy should be evaluated for CMV infection and counseled about the possible risks to the unborn child. Laboratory testing for antibody to CMV can be performed to determine if a woman has already had CMV infection. Recovery of CMV from the cervix or urine of women at or before the time of delivery does not warrant a cesarean section. The demonstrated benefits of breast-feeding outweigh the minimal risk of acquiring CMV from the breast-feeding mother. There is no need to either screen for CMV or exclude CMV-excreting children from schools or institutions because the virus is frequently found in many healthy children and adults.Treatment with hyperimmune globulin in mothers with primary CMV infection has been shown to be effective in preventing congenital disease in several studies. One study did not show significant decrease in the risk of congenital cytomegalovirus infection. Childcare Most healthy people working with infants and children face no special risk from CMV infection. However, for women of child-bearing age who previously have not been infected with CMV, there is a potential risk to the developing unborn child (the risk is described above in the Pregnancy section). Contact with children who are in day care, where CMV infection is commonly transmitted among young children (particularly toddlers), may be a source of exposure to CMV. Since CMV is transmitted through contact with infected body fluids, including urine and saliva, child care providers (meaning day care workers, special education teachers, as well as mothers) should be educated about the risks of CMV infection and the precautions they can take. Day care workers appear to be at a greater risk than hospital and other health care providers, and this may be due in part to the increased emphasis on personal hygiene in the health care setting.Recommendations for individuals providing care for infants and children: Employees should be educated concerning CMV, its transmission, and hygienic practices, such as handwashing, which minimize the risk of infection. Susceptible nonpregnant women working with infants and children should not routinely be transferred to other work situations. Pregnant women working with infants and children should be informed of the risk of acquiring CMV infection and the possible effects on the unborn child. Routine laboratory testing for CMV antibody in female workers is not specifically recommended due to its high occurrence, but can be performed to determine their immune status. Epidemiology Worldwide, approximately 1 in 100 to 500 babies are born with congenital CMV. Approximately 1 in 3000 will show symptoms and 1 in 7000 will die. Congenital HCMV infection occurs when the mother has a primary infection (or reactivation) during pregnancy. Due to the lower seroprevalence of HCMV in industrialized countries and higher socioeconomic groups, congenital infections are actually less common in poorer communities, where more women of child-bearing age are already seropositive. In industrialized countries up to 8% of HCMV seronegative mothers contract primary HCMV infection during pregnancy, of which roughly 50% will transmit to the fetus. Between 10 and 15% of infected fetuses are then born with symptoms, which may include pneumonia, gastrointestinal, retinal and neurological disease. 10-15% of asymptomatic babies will develop long term neurological effects. SNHL is found in 35% of children with CMV, cognitive deficits have been found in 66% of children with CMV, and death occurs in 4% of children. HCMV infection occurs in roughly 1% of all neonates with those who are not congenitally infected contracting the infection possibly through breast milk. Other sources of neonatal infection are bodily fluids which are known to contain high titres in shedding individuals: saliva (<107copies/ml) and urine (<105copies/ml ) seem common routes of transmission. The incidence of primary CMV infection in pregnant women in the United States varies from 1% to 3%. Healthy pregnant women are not at special risk for disease from CMV infection. When infected with CMV, most women have no symptoms and very few have a disease resembling infectious mononucleosis. It is their developing fetuses that may be at risk for congenital CMV disease. CMV remains the most important cause of congenital viral infection in the United States. HCMV is the most common cause of congenital infection in humans and intrauterine primary infections are more common than other well-known infections and syndromes, including Down Syndrome, Fetal Alcohol Syndrome, Spina Bifida, and Pediatric HIV/AIDS. References External links Cytomegalovirus (CMV)—NHS Choices CMV: Congenital CMV Infection—CDC

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

Can you break down the meaning of the medical term 'Cangrelor' for me?

Cangrelor, sold under the brand name Kengreal in the United States, CANREAL in India ( MSN Labs ) and Kengrexal in the European Union) is a P2Y12 inhibitor FDA approved as of June 2015 as an antiplatelet drug for intravenous application. Some P2Y12 inhibitors are used clinically as effective inhibitors of adenosine diphosphate-mediated platelet activation and aggregation. Unlike clopidogrel (Plavix), which is a prodrug, cangrelor is an active drug not requiring metabolic conversion. Poor interim results led to the abandonment of the two CHAMPION clinical trials in mid-2009. The BRIDGE study, for short term use prior to surgery, continues. The CHAMPION PHOENIX trial was a randomized study of over 11,000 patients published in 2013. It found usefulness of cangrelor in patients getting cardiac stents. Compared with clopidogrel given around the time of stenting, intravenous ADP-receptor blockade with cangrelor significantly reduced the rate of stent thrombosis and myocardial infarction. Reviewers have questioned the methodology of the trial. Medical use According to recent phase 3 randomized trials, a cangrelor–clopidogrel combination is safe and has been found to be more effective than standard clopidogrel treatment at reducing ischemic events in the heart, without increasing major bleeding in the treatment of stenotic coronary arteries. The advantages of this drug combination are most prominent in patients with myocardial infarction.Available antiplatelet drugs have delayed onset and offset of action. Since cangrelors effects are immediate and quickly reversed, it is a more desirable drug for elective treatment of stenotic coronary arteries, high risk acute coronary syndromes treated with immediate coronary stenting, and for bridging those surgery patients who require P2Y12 inhibition.Current evidence regarding cangrelor therapy is limited by the lack studies assessing cangrelor administration in conjunction with either prasugrel or ticagrelor.Recently, its been approved for adult patients undergoing percutaneous coronary intervention (PCI). Pharmacology Cangrelor is a high-affinity, reversible inhibitor of P2Y12 receptors that causes almost complete inhibition of ADP-induced platelet aggregate. It is a modified ATP derivative stable to enzymatic degradation. It does not require metabolic conversion to an active metabolite. This allows cangrelors immediate effect after infusion, and the therapeutic effects can be maintained with continuous infusion. The pharmacokinetics of cangrelor has allowed it to rapidly achieve steady-state concentrations with a clearance of 50 L/h and a half-life of 2.6 to 3.3 minutes. Cessation of its administration is associated with rapid removal, and normal platelet function is restored within 1 hour. Adverse effects Despite fewer bleeding events during cardiac surgery, cangrelor carries the risk of potential autoimmune reactions manifesting as breathlessness. Potential mechanisms for dyspnea following cangrelor treatment include: repeated binding and unbinding cycles, impaired platelet turnover, and lung sequestration or apoptosis of overloaded destructive platelets. The dyspnea risks following cangrelor treatment, suggest a common mechanism linking transfusion-related acute lung injury, dyspnea, and reversible platelet inhibition.The risk of breathlessness after intravenous cangrelor is smaller when compared with other reversible platelet P2Y12 receptor inhibitors, however, it is still significantly higher when compared to irreversible oral antiplatelet drugs or intravenous glycoprotein IIb/IIIa inhibitors; which do not increase the incidence of breathlessness at all. References External links "Cangrelor". Drug Information Portal. U.S. National Library of Medicine. "Cangrelor tetrasodium". Drug Information Portal. U.S. National Library of Medicine.

You act as a bridge between medical jargon and everyday language. Explain medical terms in a manner that is comprehensive yet approachable for non-experts.

I'm encountering the term 'Myelomalacia' in medical literature. What's its definition?

Myelomalacia is a pathological term referring to the softening of the spinal cord. Possible causes of myelomalacia include cervical myelopathy, hemorrhagic infarction, or acute injury, such as that caused by intervertebral disc extrusion.In advanced stages, this disorder causes flaccid paraplegia (impairment of motor function in lower extremities), total areflexia (below normal or absence of reflexes) of the pelvic limbs and anus, loss of deep pain perception caudal (toward the coccyx, or tail) to the site of spinal cord injury, muscular atrophy (wasting away of muscle tissue), depressed mental state, and respiratory difficulty due to intercostal (muscles that run between the ribs) and diaphragmatic paralysis. Gradual cranial migration of the neurological deficits (problems relating to the nervous system), is known as ascending syndrome and is said to be a typical feature of diffuse myelomalacia. Although clinical signs of myelomalacia are observed within the onset (start) of paraplegia, sometimes they may become evident only in the post-operative period, or even days after the onset of paraplegia. Death from myelomalacia may occur as a result of respiratory paralysis when the ascending lesion (abnormal damaged tissue) reaches the motor nuclei of the phrenic nerves (nerves between the C3-C5 region of the spine) in the cervical (neck) region. Classification Myelomalacia affects the neurological functions in the spinal cord. Once breached, the ramification of the damage directly affects the motor functions of the body. Because the central nervous system is affected, the condition is classified under the neurological field of study. Spinal Cord Injury When myelomalacia occurs, the damage done to the spinal cord may range from minimal to extensive. The spinal cord and the brain work together, making them the key components of the central nervous system. Damage to this system affects specific functions of the body, primarily relating to the function of muscles. The areas most commonly injured include the cervical vertebrae (C1-C7), and the lumbar spine (L1-L5). Symptoms The onset of myelomalacia may be so subtle that it is overlooked. Depending on the extent of the spinal cord injury, the symptoms may vary. In some cases, the symptom may be as common as hypertension. Though every case is different, several cases reported loss of motor functions in the extremities, areflexia or sudden jerks of the limbs, loss of pain perception, or even paralysis; all of which are possible indicators of a damaged and softened spinal cord. In the most severe cases, paralysis of the respiratory system manifests in death. Cause The most common way the disorder occurs is from a result of hemorrhaging (bleeding within) or inadequate blood supply to the spinal cord, making it weak and susceptible to damage.Because myelomalacia involves a damaged spinal cord, it may occur in any individual. Those most at risk are the geriatric population due to weaker bone density. Once the spinal injury has occurred, one of two things may happen. Firstly, hemorrhaging within the spinal cord may cause compression, which damages the spinal cord even further. Another consequence of myelomalacia is improper circulation of blood to the area damaged, resulting in further damage to the spinal cord. Sport Athletes Due to extensive physical contact and activity, many athletes become victim to myelomalacia. Any accidents or injuries attained during athletic competition to the spinal cord may result in myelomalacia. Accounts of awkward landing on the ground or being hit intensively have attested to spinal cord injury. Geriatric With the growth in the elderly population of humans, there has been a rise to myelomalacia. Because the human body begins to deteriorate with age, and because human population is living many years longer, there has been a growth in cases of myelomalacia. As the bones in the body begin to weaken in a process known as osteopenia, the body is more vulnerable to damage. A simple fall may damage the spinal cord and myelomalacia may soon ensue. Diagnosing There are two tests that can provide a definite diagnosis of myelomalacia; magnetic resonance imaging (MRI), or myelography. Diffuse hyperintensity on T2-weighted imaging, and hypointensity on T1-weighted imaging of the spinal cord can be an indication of the onset or progression of myelomalacia Treatment There is no known treatment to reverse nerve damage due to myelomalacia. In some cases, surgery to alleviate the injury to the area may slow or stop further damage. As motor function degenerates, muscle spasticity and atrophy may occur. Medications such as NSAIDs and gabapentinoids may be prescribed to reduce swelling of the spinal cord, pain, and spasticity.Research is underway to consider the potential of stem cells for treatment of neurodegenerative diseases. There are, however, no approved stem cell therapies for myelomalacia. See also == References ==

You are a conduit for medical education. Your task is to offer detailed explanations of medical terms, ensuring they are understandable and precise.

I've come across the term 'Stenosis of pulmonary artery' in a medical context, but I'm not sure what it means. Can you clarify?

Stenosis of the pulmonary artery is a condition where the pulmonary artery is subject to an abnormal constriction (or stenosis). Peripheral pulmonary artery stenosis may occur as an isolated event or in association with Alagille syndrome, Berardinelli-Seip congenital lipodystrophy type 1, Costello syndrome, Keutel syndrome, nasodigitoacoustic syndrome (Keipert syndrome), Noonan syndrome or Williams syndrome.It should not be confused with a pulmonary valve stenosis, which is in the heart, but can have similar hemodynamic effects. Both stenosis of the pulmonary artery and pulmonary valve stenosis are causes of pulmonic stenosis.In some cases it is treated with surgery. References == External links ==

You are an assistant in medical learning. Your role is to clarify medical terminology, ensuring the information is both accurate and accessible.

What is the significance of the term 'Cyanocobalamin' in the medical field?

Cyanocobalamin is a form of vitamin B12 used to treat vitamin B12 deficiency except in the presence of cyanide toxicity. The deficiency may occur in pernicious anemia, following surgical removal of the stomach, with fish tapeworm, or due to bowel cancer. It is less preferred than hydroxocobalamin for treating vitamin B12 deficiency. It is used by mouth, by injection into a muscle, or as a nasal spray.Cyanocobalamin is generally well tolerated. Minor side effects may include diarrhea and itchiness. Serious side effects may include anaphylaxis, low blood potassium, and heart failure. Use is not recommended in those who are allergic to cobalt or have Lebers disease. Vitamin B12 is an essential nutrient meaning that it cannot be made by the body but is required for life.Cyanocobalamin was first manufactured in the 1940s. It is available as a generic medication and over the counter. In 2019, it was the 155th most commonly prescribed medication in the United States, with more than 4 million prescriptions. Medical use Cyanocobalamin is usually prescribed after surgical removal of part or all of the stomach or intestine to ensure adequate serum levels of vitamin B12. It is also used to treat pernicious anemia, vitamin B12 deficiency (due to low intake from food or inability to absorb due to genetic or other factors), thyrotoxicosis, hemorrhage, malignancy, liver disease and kidney disease. Cyanocobalamin injections are often prescribed to gastric bypass patients who have had part of their small intestine bypassed, making it difficult for B12 to be acquired via food or vitamins. Cyanocobalamin is also used to perform the Schilling test to check ability to absorb vitamin B12.Cyanocobalamin is also produced in the body (and then excreted via urine) after intravenous hydroxycobalamin is used to treat cyanide poisoning. Side effects Possible side effects of cyanocobalamin injection include allergic reactions such as hives, difficult breathing; redness of the face; swelling of the arms, hands, feet, ankles or lower legs; extreme thirst; and diarrhea. Less-serious side effects may include headache, dizziness, leg pain, itching, or rash.Treatment of megaloblastic anemia with concurrent vitamin B12 deficiency using B12 vitamers (including cyanocobalamin), creates the possibility of hypokalemia due to increased erythropoiesis (red blood cell production) and consequent cellular uptake of potassium upon anemia resolution. When treated with cyanocobalamin, patients with Lebers disease may develop serious optic atrophy, possibly leading to blindness. Chemistry Vitamin B12 is the "generic descriptor" name for any vitamers of vitamin B12. Animals, including humans, can convert cyanocobalamin to any one of the active vitamin B12 compounds.Cyanocobalamin is one of the most widely manufactured vitamers in the vitamin B12 family (the family of chemicals that function as B12 when put into the body), because cyanocobalamin is the most air-stable of the B12 forms. It is the easiest to crystallize and therefore easiest to purify after it is produced by bacterial fermentation. It can be obtained as dark red crystals or as an amorphous red powder. Cyanocobalamin is hygroscopic in the anhydrous form, and sparingly soluble in water (1:80). It is stable to autoclaving for short periods at 121 °C (250 °F). The vitamin B12 coenzymes are unstable in light. After consumption the cyanide ligand is replaced by other groups (adenosyl, methyl) to produce the biologically active forms. The cyanide is converted to thiocyanate and excreted by the kidney. Chemical reactions In the cobalamins, cobalt normally exists in the trivalent state, Co(III). However, under reducing conditions, the cobalt center is reduced to Co(II) or even Co(I), which are usually denoted as B12r and B12s, for reduced and super reduced, respectively. B12r and B12s can be prepared from cyanocobalamin by controlled potential reduction, or chemical reduction using sodium borohydride in alkaline solution, zinc in acetic acid, or by the action of thiols. Both B12r and B12s are stable indefinitely under oxygen-free conditions. B12r appears orange-brown in solution, while B12s appears bluish-green under natural daylight, and purple under artificial light.B12s is one of the most nucleophilic species known in aqueous solution. This property allows the convenient preparation of cobalamin analogs with different substituents, via nucleophilic attack on alkyl halides and vinyl halides.For example, cyanocobalamin can be converted to its analog cobalamins via reduction to B12s, followed by the addition of the corresponding alkyl halides, acyl halides, alkene or alkyne. Steric hindrance is the major limiting factor in the synthesis of the B12 coenzyme analogs. For example, no reaction occurs between neopentyl chloride and B12s, whereas the secondary alkyl halide analogs are too unstable to be isolated. This effect may be due to the strong coordination between benzimidazole and the central cobalt atom, pulling it down into the plane of the corrin ring. The trans effect determines the polarizability of the Co–C bond so formed. However, once the benzimidazole is detached from cobalt by quaternization with methyl iodide, it is replaced by H2O or hydroxyl ions. Various secondary alkyl halides are then readily attacked by the modified B12s to give the corresponding stable cobalamin analogs. The products are usually extracted and purified by phenol-methylene chloride extraction or by column chromatography.Cobalamin analogs prepared by this method include the naturally occurring coenzymes methylcobalamin and cobamamide, and other cobalamins that do not occur naturally, such as vinylcobalamin, carboxymethylcobalamin and cyclohexylcobalamin. This reaction is under review for use as a catalyst for chemical dehalogenation, organic reagent and photosensitized catalyst systems. Production Cyanocobalamin is commercially prepared by bacterial fermentation. Fermentation by a variety of microorganisms yields a mixture of methylcobalamin, hydroxocobalamin and adenosylcobalamin. These compounds are converted to cyanocobalamin by addition of potassium cyanide in the presence of sodium nitrite and heat. Since multiple species of Propionibacterium produce no exotoxins or endotoxins and have been granted GRAS status (generally regarded as safe) by the United States Food and Drug Administration, they are the preferred bacterial fermentation organisms for vitamin B12 production.Historically, the physiological form was initially thought to be cyanocobalamin. This was because hydroxocobalamin produced by bacteria was changed to cyanocobalamin during purification in activated charcoal columns after separation from the bacterial cultures (because cyanide is naturally present in activated charcoal). Cyanocobalamin is the form in most pharmaceutical preparations because adding cyanide stabilizes the molecule.The total world production of vitamin B12, by four companies (the French Sanofi-Aventis and three Chinese companies) in 2008 was 35 tonnes. Metabolism The two bioactive forms of vitamin B12 are methylcobalamin in cytosol and adenosylcobalamin in mitochondria. Multivitamins often contain cyanocobalamin, which is presumably converted to bioactive forms in the body. Both methylcobalamin and adenosylcobalamin are commercially available as supplement pills. The MMACHC gene product catalyzes the decyanation of cyanocobalamin as well as the dealkylation of alkylcobalamins including methylcobalamin and adenosylcobalamin. This function has also been attributed to cobalamin reductases. The MMACHC gene product and cobalamin reductases enable the interconversion of cyano- and alkylcobalamins.Cyanocobalamin is added to fortify nutrition, including baby milk powder, breakfast cereals and energy drinks for humans, also animal feed for poultry, swine and fish. Vitamin B12 becomes inactive due to hydrogen cyanide and nitric oxide in cigarette smoke. Vitamin B12 also becomes inactive due to nitrous oxide N2O commonly known as laughing gas, used for anaesthesia and as a recreational drug. Vitamin B12 becomes inactive due to microwaving or other forms of heating. In the cytosol Methylcobalamin and 5-methyltetrahydrofolate are needed by methionine synthase in the methionine cycle to transfer a methyl group from 5-methyltetrahydrofolate to homocysteine, thereby generating tetrahydrofolate (THF) and methionine, which is used to make SAMe. SAMe is the universal methyl donor and is used for DNA methylation and to make phospholipid membranes, choline, sphingomyelin, acetylcholine, and other neurotransmitters. In mitochondria The enzymes that use B12 as a built-in cofactor are methylmalonyl-CoA mutase (PDB 4REQ) and methionine synthase (PDB 1Q8J).The metabolism of propionyl-CoA occurs in the mitochondria and requires Vitamin B12 (as adenosylcobalamin) to make succinyl-CoA. When the conversion of propionyl-CoA to succinyl-CoA in the mitochondria fails due to Vitamin B12 deficiency, elevated blood levels of methylmalonic acid (MMA) occur. Thus, elevated blood levels of homocysteine and MMA may both be indicators of vitamin B12 deficiency. Adenosylcobalamin is needed as cofactor in methylmalonyl-CoA mutase—MUT enzyme. Processing of cholesterol and protein gives propionyl-CoA that is converted to methylmalonyl-CoA, which is used by MUT enzyme to make succinyl-CoA. Vitamin B12 is needed to prevent anemia, since making porphyrin and heme in mitochondria for producing hemoglobin in red blood cells depends on succinyl-CoA made by vitamin B12. Absorption and transport Inadequate absorption of vitamin B12 may be related to coeliac disease. Intestinal absorption of vitamin B12 requires successively three different protein molecules: haptocorrin, intrinsic factor and transcobalamin II. See also Methylcobalamin Hydroxocobalamin Adenosylcobalamin Cobalamin biosynthesis References External links "Cyanocobalamin". Drug Information Portal. U.S. National Library of Medicine.