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Femoroacetabular impingement	Femoroacetabular impingement (FAI) is a condition involving one or more anatomical abnormalities of the hip joint, which is a ball and socket joint. It is a common cause of hip pain and discomfort in young and middle-aged adults. It occurs when the ball shaped femoral head contacts the acetabulum abnormally or does not permit a normal range of motion in the acetabular socket. Damage can occur to the articular cartilage, or labral cartilage (soft tissue, ring-shaped bumper of the socket), or both. The condition may be symptomatic or asymptomatic. It may cause osteoarthritis of the hip. Treatment options range from conservative management to surgery. Signs and symptoms Pain is the most common complaint in those with FAI. It is experienced in a number of areas, making the diagnosis challenging, but commonly occurs in the groin, upper buttock/lower back, the buttock or beneath the buttock, side of the affected hip and posterior upper leg. Onset of symptoms has been reported to present in both an acute and more gradual manner. The pain is often significant enough to cause a decrease in activity level and movement. Some will also describe decreased range of motion of the affected hip. Another symptom is groin pain associated with activity and no prior history of trauma. Inability to perform activities such as high hip flexion or prolong sitting can also be seen in individuals with FAI. Cause FAI is characterized by abnormal contact between the proximal femur and rim of the acetabulum (hip socket). In most cases, patients present with a deformity in the femoral head, or acetabulum, a poorly positioned femoral-acetabular junction, or any or all of the foregoing. The cause of FAI is currently unknown, but both congenital and acquired etiologies have been put forth. Studies have shown an increased incidence in siblings, suggesting a genetic component. At least one study has also shown a predilection in the white population. It has also been reported to be more common in males. However, there is no concrete evidence to suggest a genetic trait and instead, the most favored theory currently supports that FAI (the cam type in particular) is due to repetitive movements involving the hip (e.g. squatting) in young athletes. Aggravating activities that are commonly reported include repetitive or prolonged squatting, twisting movements of the hip, like pivoting during athletics, getting in and out of cars, and even sitting for prolonged periods. A combination of these factors may also predispose to a form of FAI; predominantly, a marginal developmental hip abnormality together with environmental factors such as recurrent motion of the legs within a supraphysiologic range.Three types of FAI are recognized (see title image). The first involves an excess of bone along the upper surface of the femoral head, known as a cam deformity (abbreviation for camshaft, which the shape of the femoral head and neck resembles). The second is due to an excess of growth of the upper lip of the acetabular cup and is known as a pincer deformity. The third is a combination of the two, generally referred to as mixed. The most common type seen, approximately 70% of the time, is the mixed type. A complicating issue is that some of the radiographic findings of FAI have also been described in asymptomatic subjects.Current literature suggests that the cam type of impingement is associated with the development of hip osteoarthritis. Thus far, no correlation has been seen between the pincer type and development of hip osteoarthritis. Anatomy The hip joint is classified as a ball and socket joint. This type of synovial joint allows for multidirectional movement and rotation. There are two bones that make up the hip joint and create an articulation between the femur and pelvis. This articulation connects the axial skeleton with the lower extremity. The pelvic bone, also known as the innominate bone, is formed by three bones fused together: the ilium, ischium, and pubis. The musculature of the hip is divided into anterior hip muscles and posterior hip muscles. The major nerve supply that runs through the hip joint is the femoral nerve and the sciatic nerve. Diagnosis Clinical evaluation is the first step in diagnosis, but will rarely lead to the diagnosis on its own, due to inconsistent and vague nature of the pain. Childhood and current activity should be inquired about. Physical exam should also involve assessing passive internal rotation of the hip during flexion, as range of motion is reduced in proportion to the size of a cam lesion. Flexing the hip to 90 degrees, adducting, and internally rotating the hip, known as the FADDIR test, should also be performed. It is positive when it causes pain. The FABER test should also be performed, this test involves flexing, abducting, and externally rotating the hip. The FABER test is useful when diagnosing concurrently with a labral pathology and is considered positive if the position elicits pain. Additional non-invasive ways to observe possible FAI is changes in gait that include a lower peak hip extension and internal rotation to compensate for bony growth. X-ray Projectional radiography ("X-ray")is often considered first line for FAI. Anterior-posterior pelvis and a lateral image of the hip in question should be attained. A 45-degree Dunn view is also recommended. Other modalities MRI imaging may follow, particularly if there is no specific evidence on radiographs, producing a three-dimensional reconstruction of the joint for better definition, to evaluate the hip cartilage, or measure hip socket angles (e.g. the alpha-angle as described by Nötzli in 2-D and by Siebenrock in 3-D). MR arthrogram had been used in the past, as it was more sensitive for picking up soft tissue lesions; however, due to improvement in technology, MRI is now considered comparable for picking up such lesions. CT is not usually used due to radiation exposure and no benefit above MRI. It is possible to perform dynamic simulation of hip motion with CT or MRI assisting to establish whether, where, and to what extent, impingement is occurring. The diagnosis is often made in conjunction with a labral tear. Differential Diagnosis Piriformis syndrome or strain Labral tear without FAI Adductor muscle strain Sciatica Athletic pubalgia Gluteus medius/minimus or illiopsoas tendinopathy Stress fracture Femoral head osteonecrosis Other impingements, including anterior inferior iliac spine, ischiofemoral and iliopsoas Loose body in the joint (intra-articular body) Prevention Prevention is currently being investigated. The goal of prevention would be to avoid joint damage and premature hip osteoarthritis. Studies are examining the effectiveness of screening adolescents in school and targeting at-risk individuals for education, physical therapy and decreasing participation in possibly harmful activities/sports as referenced in the epidemiology section. Treatment Treatment of FAI can be divided into those that are non-operative (conservative) and operative. Conservative treatment is often prescribed for those who have not yet received any therapy. Conservative treatment includes physical therapy, avoidance of those activities that produce pain, and nonsteroidal anti-inflammatory drugs. It may also include joint injections with cortisone or hyaluronic acid, particularly for those who wish to avoid surgery.Physical therapy is implemented for the purpose of improving joint mobility, strengthening muscles surrounding the joint, correcting posture, and treating any other muscle or joint deficits that may be exacerbating the condition. A movement analysis may also be performed to identify specific movement patterns that may be causing injury. Studies to demonstrate the effectiveness of physical therapy are currently underway, with no conclusive results to date.Operative treatment is generally recommended to those who continue to have symptoms. It involves the surgical correction of any bony abnormalities causing the impingement and correction of any soft tissue lesions, such as labral tears. The primary aim of surgery is to correct the fit of the femoral head and acetabulum to create a hip socket that reduces contact between the two, allowing a greater range of movement. This includes femoral head sculpting and/or trimming of the acetabular rim.Surgery may be arthroscopic or open. A 2011 study analyzing current surgical methods for management of symptomatic femoral acetabular impingement, suggested that the arthroscopic method had surgical outcomes equal to or better than other methods with a lower rate of major complications when performed by experienced surgeons; consequently, the surgery is now rarely done open.Outcomes of arthroscopic surgery are currently being studied, but have generally been positive. According to a 2019 meta-analysis, the risk of having surgery fail or need to be re-operated on is about 5.5% whereas the complication rate is 1.7%. Additionally, patient reported outcomes show that approximately three to six months post-operative hip arthroscopy is when pain reduction and activities of daily life are improved. For sport function this timeline is about six months to a year. Failure of hip arthroscopy is more likely to fail in older patients, females, or those who have experienced the symptoms of FAI for a long period of time.When performed on elite athletes, most are able to return their previous level of competition. These athletes also have a higher rate of return to sport than recreational and collegiate athletes.Long term, randomized controlled trials evaluating the efficacy of conservative and operative treatments are underway. Epidemiology There has been limited research on the prevalence of FAI among a general population according to a literature review by Algarni. On the other hand, there are many sources that discuss the prevalence of athletes with the condition especially those that are younger and white. Hockey, tennis, soccer, and equestrian are all sports where the prevalence of a femoral neck abnormalities are higher due to the nature of the sport to force athletes into forced, loaded flexion and internal rotation.Cam lesions are more common in males, where pincer lesions are more common in females due to differences in anatomical development of the pelvis. History FAI is a relatively recent discovery. Its original description is credited to orthopedic surgeon Dr. Reinhold Ganz, who first proposed the condition as a cause for hip osteoarthritis in a publication in 2003.While the true diagnosis of FAI can be considered a relatively recent discovery, reports of damage to the femoroaceatabular region date back over a century ago in the orthopedic realm of medicine. It was not until the development of an open surgical dislocation procedure was developed that FAI was discovered as an anatomical difference and cause of osteoarthritis. Orthopedic surgeon Dr. Reinhold Ganz can be credited with this discovery in his 2003 publication that discussed the findings and relation to hip osteoarthritis. Society Notable persons who have had hip impingement: Zach Banner (born 1993), American NFL football offensive tackle for the Pittsburgh Steelers Michelle Kwan, American figure skater Oscar Hiljemark, Swedish footballer Greg Holland, American baseball player Devin Mesoraco, American baseball player Charlie Morton, American baseball player Andy Murray, British tennis player Greg Norman, Australian golfer Alex Rodriguez, American baseball player Isaiah Thomas, American basketball player Notes References Further reading Lewis CL, Sahrmann SA (January 2006). "Acetabular labral tears". Physical Therapy. 86 (1): 110–21. doi:10.1093/ptj/86.1.110. PMID 16386066. External links Femoroacetabular Impingement (FAI) on OrthoInfo IMPAKT-HiP (Investigations of Mobility, Physical Activity, and Knowledge in Hip Pain) Study by the Arthritis Research Centre of Canada
Angioma serpiginosum	Angioma serpiginosum is characterized by minute, copper-colored to bright red angiomatous puncta that have a tendency to become papular.: 592–3 See also Skin lesion List of cutaneous conditions References == External links ==
Tuberculoid leprosy	Tuberculoid leprosy is a form of leprosy characterized by solitary skin lesions that are asymmetrically distributed with few lesions and well demarcated edges. There is also early and marked nerve damage. It tends to heal spontaneously.: 345 Tuberculoid leprosy is characterized by the formation of epithelioid cell granulomas with a large number of epithelioid cells. In this form of leprosy Mycobacterium leprae are either absent from the lesion or occur in very small numbers. This type of leprosy is the most benign and the least contagious. See also Leprosy Skin lesion References == External links ==
Caffeine dependence	Caffeine dependence is the condition of having a substance dependence on caffeine, a commonplace central nervous system stimulant drug which occurs in nature in coffee, tea, yerba mate, cocoa, and other plants. Caffeine is also an additive in many consumer products, including beverages such as caffeinated alcoholic beverages, energy drinks, and colas. Caffeines mechanism of action is somewhat different from that of cocaine and the substituted amphetamines; caffeine blocks adenosine receptors A1 and A2A. Adenosine is a by-product of cellular activity, and stimulation of adenosine receptors produces feelings of tiredness and the need to sleep. Caffeines ability to block these receptors means the levels of the bodys natural stimulants, dopamine and norepinephrine, continue at higher levels. The Diagnostic and Statistical Manual of Mental Disorders describes four caffeine-related disorders including intoxication, withdrawal, anxiety, and sleep. Dependence Mild physical dependence can result from long-term caffeine use. Caffeine addiction, or a pathological and compulsive form of use, has been documented in humans. Addiction vs. Dependence Caffeine use is classified as a dependence, not an addiction. For a drug to be considered addictive, it must activate the brains reward circuit. Caffeine, like addictive drugs, enhances dopamine signaling in the brain (is eugeroic), but not enough to activate the brains reward circuit like addictive substances such as cocaine, morphine, and nicotine. Caffeine dependence forms due to caffeine antagonizing the adenosine A2A receptor, effectively blocking adenosine from the adenosine receptor site. This delays the onset of drowsiness and releases dopamine.Studies have demonstrated that people who take in a minimum of 100 mg of caffeine per day (about the amount in one cup of coffee) can acquire a physical dependence that would trigger withdrawal symptoms that include headaches, muscle pain and stiffness, lethargy, nausea, vomiting, depressed mood, and marked irritability. Professor Roland R. Griffiths, a professor of neurology at Johns Hopkins in Baltimore strongly believes that caffeine withdrawal should be classified as a psychological disorder. His research suggested that withdrawal affects 50% of habitual coffee drinkers, beginning within 12–24 hours after cessation of caffeine intake, and peaking in 20–48 hours, lasting as long as 9 days.Continued exposure to caffeine leads the body to create more adenosine-receptors in the central nervous system, which makes it more sensitive to the effects of adenosine. It reduces the stimulatory effects of caffeine by increasing tolerance, and it increases the withdrawal symptoms of caffeine as the body becomes more sensitive to the effects of adenosine once caffeine intake decreases. Caffeine tolerance develops very quickly. Tolerance to the sleep disruption effects of caffeine were seen after consumption of 400 mg of caffeine 3 times a day for 7 days, whereas complete tolerance was observed after consumption of 300 mg taken 3 times a day for 18 days. Physiological effects When a person becomes caffeine dependent, it can cause a person to suffer different physiological effects which could lead to withdrawal. Symptoms can range from mild to severe that are dependent on the amount of caffeine consumed daily. Tests are still being done to get a better understanding of the effects that occur to someone when they become dependent on different forms of caffeine to make it through the day. Adults Caffeine is consumed by many each day and from this a dependence is formed. For the most part caffeine consumption is safe, but consuming over 400 mg of caffeine has shown adverse physiological and psychological effects; especially in people that have pre-existing conditions. When adults form a dependence on caffeine, it can cause a range of health problems such as headaches, insomnia, dizziness, cardiac issues, hypertension and others. When an adult is dependent on this substance, they must consume a certain amount of caffeine every day to avoid these effects. Pregnancy If pregnant, it is recommended not to consume over 200 mg of caffeine a day (depending on size of person). If a pregnant female consumes high levels of caffeine, it can result in low birth weights due to loss of blood flow to the placenta which could lead to an increase health problems later in that childs life. It can also result in premature labor, reduced fertility, and other reproductive issues. If a female is depended on an excessive amount of caffeine to get them through the day, it is recommended to talk to their healthcare provider to either eliminate the dependency of caffeine or to become less dependent on it. Children and Teenagers It is not recommended for children under the age of 18 to consume several caffeinated drinks according to the American Academy of Pediatrics (AAP). If they were to consume caffeine it is recommended to follow some guidelines so they do not consume too much throughout the day. If they do, they can become dependent on caffeine and without it can suffer many different side effects. These include increase of heart rate and blood pressure, sleep disturbance, mood swings, and acidic problems. Long lasting problems on childrens nervous system and cardiovascular system are currently unknown and studies are still being conducted on it. Tolerance Tolerance levels regarding caffeine typically vary from person to person. Caffeine tolerance occurs when the stimulatory effects of caffeine decrease over time due to regular consumption. According to H.P. Ammon from the National Library of Medicine, caffeine tolerance occurs when the body responds to an intake of caffeine through the up-regulation of adenosine-receptors. References == External links ==
Amebic encephalitis	Amebic encephalitis may refer to: Primary amoebic meningoencephalitis Granulomatous amoebic encephalitis
Christianson syndrome	Christianson syndrome is an X linked syndrome associated with intellectual disability, microcephaly, seizures, ataxia and absent speech. Presentation Onset of symptoms is normally within the first year of life with truncal ataxia and seizures. The head is small (microcephaly). Common facial abnormalities include: Long narrow face Prominent nose Prominent jaw Large ears Open mouth Thick eyebrowsOther common features include: Uncontrolled drooling Abnormal eye movementsThe associated intellectual disability is usually in the profound range. Those affected often have a happy demeanor with frequent smiling and spontaneous laughter. Genetics This condition is caused by mutations in the SLC9A6 gene. This gene is located on the long arm of the X chromosome (Xq26.3). The gene encodes a sodium/hydrogen exchanger located in the endosomes. Mutations in this gene cause a rise in the pH of the endosomes.How this causes the clinical features is not known presently. The inheritance of this condition is X-linked dominant. Diagnosis The diagnosis may be suspected on clinical grounds.It is made by sequencing the SLC9A6 gene. Differential diagnosis Angelman syndrome Spinocerebellar ataxia type 29 Management There is presently no curative treatment. Management is supportive. Epidemiology The prevalence is not known but this is considered to be a rare disease. History This condition was first described in 1999. The causative mutation was discovered in 2008. == References ==
Periungual wart	Periungual warts are warts that cluster around the fingernail or toenail. They appear as thickened, fissured cauliflower-like skin around the nail plate. Periungual warts often cause loss of the cuticle and paronychia. Nail biting increases susceptibility to these warts.Warts of this kind often cause damage to the nail either by lifting the nail from the skin or causing the nail to partially detach. If they extend under the nail, then the patient may suffer pain as a result. Sometimes periungual wart infections resemble the changes that are found in onychomycosis. In worst cases, if the infection causes injury or damage to the nail matrix, deformity in the nail may become permanent. As with other wart types, a number of treatments are available, including laser therapy, cryotherapy, salicylic acid, and other topical treatments. == References ==
Occupational injury	An occupational injury is bodily damage resulting from working. The most common organs involved are the spine, hands, the head, lungs, eyes, skeleton, and skin. Occupational injuries can result from exposure to occupational hazards (physical, chemical, biological, or psychosocial), such as temperature, noise, insect or animal bites, blood-borne pathogens, aerosols, hazardous chemicals, radiation, and occupational burnout.While many prevention methods are set in place, injuries may still occur due to poor ergonomics, manual handling of heavy loads, misuse or failure of equipment, exposure to general hazards, and inadequate safety training. Worldwide It has been estimated that worldwide there are more than 350,000 workplace fatalities and more than 270 million workplace injuries annually. In 2000 there were approximately 2.9 billion workers worldwide. Occupational injuries resulted in the loss of 3.5 years of healthy life for every 1,000 workers. 300,000 of the occupational injuries resulted in a fatality.The most common occupations associated with these hazards vary throughout the world depending on the major industries in a particular country. Overall, the most hazardous occupations are in farming, fishing, and forestry. In more developed countries, construction and manufacturing occupations are associated with high rates of spine, hand, and wrist injuries. By country United States In the United States in 2012, 4,383 workers died from job injuries, 92% of which were men, and nearly 3 million nonfatal workplace injuries & illness were reported which cost businesses a collective loss of $198.2 billion and 60 million workdays. In 2007, 5,488 workers died from job injuries, 92% of which were men, and 49,000 died from work-related injuries. NIOSH estimates that 4 million workers in the U.S. in 2007 sustained non-fatal work related injuries or illnesses.According to data from the National Institute for Occupational Safety and Health (NIOSH) and the Bureau of Labor Statistics, an average of 15 workers die from traumatic injuries each day in the United States, and an additional 200 workers are hospitalized.In a study in the state of Washington, injured workers were followed for 14 years to determine the long term effects of work injury on employment. The work injuries resulted in an average of 1.06 years of lost productivity for each of the 31,588 allowed claims.In 2010, 25% of occupational injuries and illnesses that were not fatal but caused work absences were related to injuries to the upper limb. Dangerous sectors In the U.S. the Bureau of Labor Statistics makes available extensive statistics on workplace accidents and injuries. For example: Common injuries As in the United Kingdom, slips, trips and falls (STF) are common and account for 20-40% of disabling occupational injuries. Often these accidents result in a back injury that can persist to a permanent disability. In the United States, a high risk of back injuries occurs in the health care industry. 25% of reported injuries in health care workers in the state of Pennsylvania are for back pain. Among nurses, the prevalence of lower back pain may be as high as 72% mostly as a result of transferring patients. Some of these injuries can be prevented with the availability of patient lifts, improved worker training, and allocation of more time to perform work procedures. Another common type of injury is carpal tunnel syndrome associated with overuse of the hands and wrists. Studies on a cohort of newly hired workers have thus far identified forceful gripping, repetitive lifting of > 1 kg, and using vibrating power tools as high risk work activities.Additionally, noise exposure in the workplace can cause hearing loss, which accounted for 14% of reported occupational illnesses in 2007. Many initiatives have been created to prevent this common workplace injury. For example, the Buy Quiet program encourages employers to purchase tools and machines that produce less noise and the Safe-In-Sound Award was created to recognize companies and program that excel in the area of hearing loss prevention.Accidental injection or needlestick injuries are a common injury that plague agriculture workers and veterinarians. The majority of these injuries are located to the hands or legs, and can result in mild to severe reactions, including possible hospitalization. Due to the wide variety of biologics used in animal agriculture, needlestick injuries can result in bacterial or fungal infections, lacerations, local inflammation, vaccine/antibiotic reactions, amputations, miscarriage, and death. Due to daily human-animal interactions, livestock related injuries are also a prevalent injury of agriculture workers, and are responsible for the majority of nonfatal worker injuries on dairy farms. Additionally, approximately 30 people die of cattle and horse-related deaths in the United States annually. Employees at risk Perhaps the most important personal factor that predisposes to an increased risk is age. In the United States in 1998 17 million workers were over age 55 and by 2018 this population is expected to more than double. Workers in this age group are more likely to develop lower back pain that may be worsened by work conditions that normally do not affect a younger worker. Older workers are also more likely by be killed in a construction related fall. They are also at higher risk for injury due to age-related hearing loss, visual impairment, and use of multiple prescription medications that has been linked to higher rates of work injuries. In addition to age, other personal risk factors for injury include obesity particularly its associated risk with back injury, and depression.Lack of proper education or training can also predispose an individual to an occupational injury. For example, there is limited needlestick injury awareness among agriculture workers, and there is a need for comprehensive programs to prevent needlestick injuries on livestock operations. Proper animal handling techniques and training, or stockmanship, can also decrease the risk of livestock injury. A handlers timing, positioning, speed, direction of movement, and sounds made will affect the behavior of an animal and consequently the safety of the handler. The agriculture industry has begun to focus more on proper education and training, and has made a variety of resources available to producers. For example, organizations like the Upper Midwest Agriculture Safety and Health Center (UMASH) have a variety of informational fact sheets and training videos easily accessible online. Additionally, organizations like Beef Quality Assurance offers stockmanship training seminars and demonstrations. Regulation In the United States, the Occupational Safety and Health Administration (OSHA) sets and enforces national standards for occupational safety across all sectors. United Kingdom In the UK, a total of 111 fatal injuries happened in a single year. According to the HSE, a total of 111 workers died in work related injuries in the UK during 2019–20. The biggest cause for these fatal injuries was falling from heights that alone was responsible for 29 deaths during the same year. Other causes include injuries from moving vehicles and other objects, and contact with the moving machinery.In the United Kingdom in 2013–2014, 133 people were killed at work. Of those 133 people, 89 were employed, while 44 were self-employed. In 2013–2014, an estimated 629,000 injuries occurred at work. Of these injuries 629,000 injuries, 203,000 led to more than 3 days absence from work. Of these, over 148,000 resulted in them being absent from work for more than 7 days. In the UK, there are workplace injury advice guides online offering support on dealing with occupational injuries. Dangerous sectors Construction: 42 deaths Agriculture: 27 deaths Waste and Recycling: four deaths Other: 60 deathsOf all the workplace accidents that resulted in death, the most common were falls from height, contact with moving machinery and being struck by a vehicle. These types of accidents resulted in over half of all recorded deaths. Common injuries Slips, trips and falls account for over a third of all injuries that happen at work. Incorrect handling of items was the most common cause of injuries that led to absences from work of more than 7 days. In 2010–2011, injuries to the upper limb injuries made up 47% of non-fatal injuries at work in the UK.In all, over 1,900,000 working days were lost in 2013–2014 due to slips, trips and falls. Employees at risk Unsurprisingly, occupation is the biggest influence on the risk of workplace injuries. Workers new to the job are at a much higher risk of injury than more experienced staff, while shift workers and part-time staff also have a greater risk of being injured at work. Employer prosecutions The Health & Safety Executive (HSE) prosecuted 582 cases in 2013–2014, with at least one conviction secured in 547 cases (94%).Local authorities prosecuted a total of 92 cases during the same period, with at least one conviction achieved in 89 cases (97%).A total of 13,790 notices were issued by the HSE and local authorities, with over £16,700,000 issued in fines. Taiwan Traumatic injuries to the upper limbs are the most frequent type of injury at work in Taiwan. In 2010, there were 14,261 occupational injuries recorded in 2010 and 45% of these involved trauma to the upper limbs. Prevention There are many methods of preventing or reducing industrial injuries, including anticipation of problems by risk assessment, safety training, control banding, personal protective equipment safety guards, mechanisms on machinery, and safety barriers. In addition, past problems can be analyzed to find their root causes by using a technique called root cause analysis. A 2013 Cochrane review found low-quality evidence showing that inspections, especially focused inspections, can reduce work-related injuries in the long term. See also Occupational safety and health Occupational disease Occupational exposure banding Safety culture Work accident References External links Census of Fatal Occupational Injuries Charts, 1992-2012 NIOSH Publications on Traumatic Occupational Injury Topics (2008-2009), National Institute for Occupational Safety and Health
Schizoid personality disorder	Schizoid personality disorder (, often abbreviated as SzPD or ScPD) is a personality disorder characterized by a lack of interest in social relationships, a tendency toward a solitary or sheltered lifestyle, secretiveness, emotional coldness, detachment and apathy. Affected individuals may be unable to form intimate attachments to others and simultaneously possess a rich and elaborate but exclusively internal fantasy world. Other associated features include stilted speech, a lack of deriving enjoyment from most activities, feeling as though one is an "observer" rather than a participant in life, an inability to tolerate emotional expectations of others, apparent indifference when praised or criticized, a degree of asexuality, and idiosyncratic moral or political beliefs. Symptoms typically start in late childhood or adolescence.The cause of SzPD is uncertain, but there is some evidence of links and shared genetic risk between SzPD, other cluster A personality disorders (such as schizotypal personality disorder) and schizophrenia. Thus, SzPD is considered to be a "schizophrenia-like personality disorder". It is diagnosed by clinical observation, and it can be very difficult to distinguish SzPD from other mental disorders or conditions (such as autism spectrum disorder, with which it may sometimes overlap).The effectiveness of psychotherapeutic and pharmacological treatments for the disorder has yet to be empirically and systematically investigated. This is largely because people with SzPD rarely seek treatment for their condition. Originally, low doses of atypical antipsychotics were also used to treat some symptoms of SzPD, but their use is no longer recommended. The substituted amphetamine bupropion may be used to treat associated anhedonia. However, it is not general practice to treat SzPD with medications, other than for the short-term treatment of acute co-occurring disorders (e.g. depression). Talk therapies such as cognitive behavioral therapy (CBT) may not be effective, because people with SzPD may have a hard time forming a good working relationship with a therapist.SzPD is a poorly studied disorder, and there is little clinical data on SzPD because it is rarely encountered in clinical settings. Studies have generally reported a prevalence of less than 1%. It is more commonly diagnosed in males than in females. SzPD is linked to negative outcomes, including a significantly compromised quality of life, reduced overall functioning even after 15 years and one of the lowest levels of "life success" of all personality disorders (measured as "status, wealth and successful relationships"). Bullying is particularly common towards schizoid individuals. Suicide may be a running mental theme for schizoid individuals, though they are not likely to actually attempt it. Some symptoms of SzPD (e.g. solitary lifestyle, emotional detachment, loneliness, and impaired communication), however, have been stated as general risk factors for serious suicidal behaviour. Signs and symptoms People with SzPD are often aloof, cold and indifferent, which causes interpersonal difficulty. Most individuals diagnosed with SzPD have trouble establishing personal relationships or expressing their feelings meaningfully. They may remain passive in the face of unfavorable situations. Their communication with other people may be indifferent and terse at times. Schizoid personality types often lack the ability to assess the impact of their own actions in social situations.A person with SzPD may feel suffocated when their personal space is violated and take actions to avoid this feeling. People who have SzPD tend to be happiest when in relationships in which their partner places few emotional or intimate demands on them and does not expect phatic or social niceties. It is not necessarily people they want to avoid, but negative or positive emotional expectations, emotional intimacy and self-disclosure. Therefore, it is possible for individuals with SzPD to form relationships with others based on intellectual, physical, familial, occupational or recreational activities, as long as there is no need for emotional intimacy. Donald Winnicott explains this is because schizoid individuals "prefer to make relationships on their own terms and not in terms of the impulses of other people." Failing to attain that, they prefer isolation. In general, friendship among schizoids is usually limited to one person, often also schizoid, forming what has been called a union of two eccentrics; "within it – the ecstatic cult of personality, outside it – everything is sharply rejected and despised".Although there is the belief people with SzPD are complacent and unaware of their feelings, many recognize their differences from others. Some individuals with SzPD who are in treatment say "life passes them by" or they feel like living inside a shell; they see themselves as "missing the bus" and speak of observing life from a distance.Aaron Beck and his colleagues report that people with SzPD seem comfortable with their aloof lifestyle and consider themselves observers, rather than participants in the world around them. But they also mention that many of their schizoid patients recognize themselves as socially deviant (or even defective) when confronted with the different lives of ordinary people – especially when they read books or see movies focusing on relationships. Even when schizoid individuals may not long for closeness, they can become weary of being "on the outside, looking in". These feelings may lead to depression or depersonalization. If they do, schizoid people often experience feeling "like a robot" or "going through life in a dream".According to Guntrip, Klein and others, people with SzPD may possess a hidden sense of superiority and lack dependence on other peoples opinions. This is very different from the grandiosity seen in narcissistic personality disorder, which is described as "burdened with envy" and with a desire to destroy or put down others. Additionally, schizoids do not go out of their way to achieve social validation.: 60 Unlike the narcissist, the schizoid will often keep their creations private to avoid unwelcome attention or the feeling that their ideas and thoughts are being appropriated by the public.: 174 The related schizotypal personality disorder and schizophrenia are reported to have ties to creative thinking, and it is speculated that the internal fantasy aspect of SzPD may also be reflective of this thinking. Alternatively, there has been an especially large contribution of people with schizoid symptoms to science and theoretical areas of knowledge, including maths, physics, economics, etc. At the same time, people with SzPD are helpless at many practical activities because of their symptoms. Secret schizoids Many schizoid individuals display an engaging, interactive personality, contradicting the observable characteristic emphasized by the DSM-5 and ICD-10 definitions of the schizoid personality. Guntrip (using ideas of Klein, Fairbairn and Winnicott) classifies these individuals as "secret schizoids", who behave with socially available, interested, engaged and involved interaction yet remain emotionally withdrawn and sequestered within the safety of the internal world.: 17 Klein distinguishes between a "classic" SzPD and a "secret" SzPD, which occur "just as often" as each other. Klein cautions one should not misidentify the schizoid person as a result of the patients defensive, compensatory interaction with the external world. He suggests one ask the person what their subjective experience is, to detect the presence of the schizoid refusal of emotional intimacy and preference for objective fact.Frequently, a schizoid individuals social functioning improves, sometimes dramatically, when the individual knows they are an anonymous participant in a real-time conversation or correspondence, e.g. in an online chatroom or message board. It is often the case the individuals online correspondent will report nothing amiss in the individuals engagement and affect. A 2013 study looking at personality disorders and Internet use found that being online more hours per day predicted signs of SzPD. Additionally, SzPD correlated with lower phone call use and fewer Facebook friends.Descriptions of the schizoid personality as "hidden" behind an outward appearance of emotional engagement have been recognized since 1940, with Fairbairns description of "schizoid exhibitionism", in which the schizoid individual is able to express a great deal of feeling and to make what appear to be impressive social contacts yet in reality gives nothing and loses nothing. Because they are "playing a part", their personality is not involved. According to Fairbairn, the person disowns the part they are playing, and the schizoid individual seeks to preserve their personality intact and immune from compromise. The schizoids false persona is based around what those around them define as normal or good behaviour, as a form of compliance.: 143 Further references to the secret schizoid come from Masud Khan, Jeffrey Seinfeld and Philip Manfield, who give a description of an SzPD individual who "enjoys" public speaking engagements but experiences great difficulty in the breaks when audience members would attempt to engage him emotionally. These references expose the problems in relying on outer observable behavior for assessing the presence of personality disorders in certain individuals. Schizoid fantasy A pathological reliance on fantasizing and preoccupation with inner experience is often part of the schizoid withdrawal from the world. Fantasy thus becomes a core component of the self in exile, though fantasizing in schizoid individuals is far more complicated than a means of facilitating withdrawal.: 64 Fantasy is also a relationship with the world and with others by proxy. It is a substitute relationship, but a relationship nonetheless, characterized by idealized, defensive and compensatory mechanisms. This is self-contained and free from the dangers and anxieties associated with emotional connection to real persons and situations. Klein explains it as "an expression of the self struggling to connect to objects, albeit internal objects. Fantasy permits schizoid patients to feel connected, and yet still free from the imprisonment in relationships. In short, in fantasy one can be attached (to internal objects) and still be free." This aspect of schizoid pathology has been generously elaborated in works by R. D. Laing, Donald Winnicott and Ralph Klein.: 64 Sexuality People with SzPD are sometimes sexually apathetic, though they do not typically experience anorgasmia. Their preference to remain alone and detached may cause their need for sex to appear to be less than that of those who do not have SzPD. Sex often causes individuals with SzPD to feel that their personal space is being violated, and they commonly feel that masturbation or sexual abstinence is preferable to the emotional closeness they must tolerate when having sex. Significantly broadening this picture are notable exceptions of SzPD individuals who engage in occasional or even frequent sexual activities with others.Fairbairn notes that schizoids can fear that in a relationship, their needs will weaken and exhaust their partner, so they feel forced to disown them and move to satisfy solely the needs of the partner. The net result of this is a loss of dignity and sense of self within any relationship they enter, eventually leading to intolerable frustration and friction. Appel notes that these fears result in the schizoids negativism, stubbornness and reluctance to love. Thus, a central conflict of the schizoid is between an immense longing for relationships but a deep anxiety and avoidance of relationships, manifested by the choosing of the "lesser evil" of abandoning others.: 100 Individuals with SzPD have long been noted to have an increased rate of unconventional sexual tendencies, though if present, these are rarely acted upon. The schizoid is often labelled asexual or presents with "a lack of sexual identity". Kernberg states that this apparent lack of a sexuality does not represent a lack of sexual definition but rather a combination of several strong fixations to cope with the same conflicts.: 125 People with SzPD are often able to pursue any fantasies with content on the Internet while remaining completely unengaged with the outside world.: 127 Akhtars profile American psychoanalyst Salman Akhtar provided a comprehensive phenomenological profile of SzPD in which classic and contemporary descriptive views are synthesized with psychoanalytic observations. This profile is summarized in the table reproduced below that lists clinical features that involve six areas of psychosocial functioning and are organized by "overt" and "covert" manifestations. "Overt" and "covert" are intended to denote seemingly contradictory aspects that may both simultaneously be present in an individual. These designations do not necessarily imply their conscious or unconscious existence. The covert characteristics are by definition difficult to discern and not immediately apparent. Additionally, the lack of data on the frequency of many of the features makes their relative diagnostic weight difficult to distinguish at this time. However, Akhtar states that his profile has several advantages over the DSM in terms of maintaining historical continuity of the use of the word schizoid, valuing depth and complexity over descriptive oversimplification and helping provide a more meaningful differential diagnosis of SzPD from other personality disorders. Causes Some evidence suggests the cluster A personality disorders have shared genetic and environmental risk factors, and there is an increased prevalence of SzPD in relatives of people with schizophrenia and schizotypal personality disorder. Twin studies with SzPD traits (e.g. low sociability and low warmth) suggest these are inherited. Besides this indirect evidence, the direct heritability estimates of SzPD range from 50 to 59%. To Sula Wolff, who did extensive research and clinical work with children and teenagers with schizoid symptoms, "schizoid personality has a constitutional, probably genetic, basis." The link between SzPD and being underweight may also point to the involvement of biological factors.In general, prenatal caloric malnutrition, premature birth and a low birth weight are risk factors for having a mental disorder and may contribute to the development of SzPD as well. Those who have experienced traumatic brain injury may be also at risk of developing features reflective of SzPD.Other historical researchers had hypothesized excessively perfectionist, unloving or neglectful parenting could play a role. Diagnosis DSM-5 criteria The Diagnostic and Statistical Manual of Mental Disorders is a widely used manual for diagnosing mental disorders. DSM-5 includes SzPD with the same criteria as in DSM-IV. In the DSM-5, SzPD is described as a pervasive pattern of detachment from social relationships and a restricted range of expression of emotions in interpersonal settings, beginning by early adulthood and present in a variety of contexts, as indicated by at least four of the following: Neither desires nor enjoys close relationships, including being part of a family. Almost always chooses solitary activities. Has little, if any, interest in having sexual experiences with another person. Takes pleasure in few, if any, activities. Lacks close friends or confidants other than first-degree relatives. Appears indifferent to the praise or criticism of others. Shows emotional coldness, detachment, or flattened affectivity.According to the DSM, those with SzPD may often be unable to, or will rarely express aggressiveness or hostility, even when provoked directly. These individuals can seem vague or drifting about their goals and their lives may appear directionless. Others view them as indecisive in their actions, self-absorbed, absent-minded and detached from their surroundings. Excessive daydreaming is often present. In cases with severe defects in the capacity to form social relationships, dating and marriage may not be possible. ICD-10 criteria The Classification of Mental and Behavioural Disorders of ICD-10 lists SzPD under (F60.1).The general criteria of personality disorder (F60) should be met first. In addition, at least four of the following criteria must be present: Few, if any, activities provide pleasure. Displays emotional coldness, detachment, or flattened affectivity. Limited capacity to express warm, tender feelings for others as well as anger. Appears indifferent to either praise or criticism from others. Little interest in having sexual experiences with another person (taking into account age). Almost always chooses solitary activities. Excessive preoccupation with fantasy and introspection. Neither desires, nor has, any close friends or confiding relationships (or only one). Marked insensitivity to prevailing social norms and conventions; if these are not followed, this is unintentional. Guntrip criteria Ralph Klein, Clinical Director of the Masterson Institute, delineates the following nine characteristics of the schizoid personality as described by Harry Guntrip:: 13–23 Introversion Withdrawnness Narcissism Self-sufficiency A sense of superiority Loss of affect Loneliness Depersonalization RegressionThe description of Guntrips nine characteristics should clarify some differences between the traditional DSM portrait of SzPD and the traditional informed object relations view. All nine characteristics are consistent. Most, if not all, must be present to diagnose a schizoid disorder. Millons subtypes Theodore Millon restricted the term "schizoid" to those personalities who lack the capacity to form social relationships. He characterizes their way of thinking as being vague and void of thoughts and as sometimes having a "defective perceptual scanning". Because they often do not perceive cues that trigger affective responses, they experience fewer emotional reactions.For Millon, SzPD is distinguished from other personality disorders in that it is "the personality disorder that lacks a personality." He criticizes that this may be due to the current diagnostic criteria: They describe SzPD only by an absence of certain traits, which results in a "deficit syndrome" or "vacuum". Instead of delineating the presence of something, they mention solely what is lacking. Therefore, it is hard to describe and research such a concept.He identified four subtypes of SzPD. Any individual schizoid may exhibit none or one of the following: Differential diagnosis While SzPD shares several symptoms with other mental disorders, there are some important differentiating features: Comorbidity SzPD is often found to be comorbid with at least one of several disorders or pathologies. Sometimes, a person with SzPD may meet criteria for an additional personality disorder; when this happens, it is most often avoidant, schizotypal or paranoid PD. Alexithymia (the inability to identify and describe emotions) is often present in SzPD. Sharon Ekleberry suggests that some people with schizoid personality features may occasionally experience instances of brief reactive psychosis when under stress. Substance use disorder Very little data exists for rates of substance use disorder among people with SzPD, but existing studies suggest they are less likely to have substance abuse problems than the general population. One study found that significantly fewer boys with SzPD had alcohol problems than a control group of non-schizoids. Another study evaluating personality disorder profiles in substance abusers found that substance abusers who showed schizoid symptoms were more likely to abuse one substance rather than many, in contrast to other personality disorders such as borderline, antisocial or histrionic, which were more likely to abuse many.American psychotherapist Sharon Ekleberry states that the impoverished social connections experienced by people with SzPD limit their exposure to the drug culture and that they have limited inclination to learn how to do illegal drugs. Describing them as "highly resistant to influence", she additionally states that even if they could access illegal drugs, they would be disinclined to use them in public or social settings, and because they would be more likely to use alcohol or cannabis alone than for social disinhibition, they would not be particularly vulnerable to negative consequences in early use. Suicide Suicide may be a running theme for schizoid individuals, in part due to the knowledge of the large-scale ostracism that would result if their idiosyncratic views were revealed and their experience that most, if not all people, are unrelatable or have polar opposite reactions to them on societally sensitive issues, though they are not likely to actually attempt it. They might be down and depressed when all possible connections have been cut off, but as long as there is some relationship or even hope for one the risk will be low. The idea of suicide is a driving force against the persons schizoid defenses. Often among people with SzPD, there is a rationally grounded and reasoned position on why they want to die, and this "suicidal construct" takes a stable position in the mind. A mini-review indicates that SzPD or schizoid traits are a major risk factor for both suicide attempts and suicide. Schizoids tend to hide their suicidal thoughts and intentions. Demonstrative suicides or suicide blackmail, as seen in cluster B personality disorders such as borderline, histrionic or antisocial, are extremely rare among schizoid individuals.In cases with schizoid disorder, the characteristics of the premorbidities (emotional coldness, autism, inability to have fun) also affected suicidal behaviour. Their suicides were always genuine in nature, well-planned, and it was only by chance that these patients survived (usually the fatal outcome was prevented by the sudden appearance of others). They denied the existence of suicidal experiences earlier, but argued that in the current circumstances, suicide seemed to them the most appropriate way out. This "suicidal construction" was well-reasoned and took a stable position in the mind. Important in all these cases was the absence of any significant anti-suicidal factors (most were found in a situation of relative social isolation; there were no professional and personal interests). The high ability to introspect in these cases only increased the isolation from reality and made the choice in favour of suicide more reasonable.As in other clinical mental health settings, among suicidal inpatients, individuals with SzPD are not as well-represented as some other groups. A 2011 study on suicidal inpatients at a Moscow hospital found that schizoids were the least common patients, while those with cluster B personality disorders were the most common. Asperger syndrome Several studies have reported an overlap or comorbidity with the autism spectrum disorder Asperger syndrome. Asperger syndrome had traditionally been called "schizoid disorder of childhood", and Eugen Bleuler coined both the terms "autism" and "schizoid" to describe withdrawal to an internal fantasy, against which any influence from outside becomes an intolerable disturbance. In a 2012 study of a sample of 54 young adults with Asperger syndrome, it was found that 26% of them also met criteria for SzPD, the highest comorbidity out of any personality disorder in the sample (the other comorbidities were 19% for obsessive–compulsive personality disorder, 13% for avoidant personality disorder and one female with schizotypal personality disorder). Additionally, twice as many men with Asperger syndrome met criteria for SzPD than women. While 41% of the whole sample were unemployed with no occupation, this rose to 62% for the Aspergers and SzPD comorbid group. Tantam suggested that Asperger syndrome may confer an increased risk of developing SzPD. A 2019 study found that 54% of a group of males aged 11 to 25 with Asperger syndrome showed significant SzPD traits, with 6% meeting full diagnostic criteria for SzPD, compared to 0% of a control.In the 2012 study, it was noted that the DSM may complicate diagnosis by requiring the exclusion of a pervasive developmental disorder (PDD) before establishing a diagnosis of SzPD. The study found that social interaction impairments, stereotyped behaviours and specific interests were more severe in the individuals with Asperger syndrome also fulfilling SzPD criteria, against the notion that social interaction skills are unimpaired in SzPD. The authors believe that substantial subgroup of people with autism spectrum disorder or PDD have clear "schizoid traits" and correspond largely to the "loners" in Lorna Wings classification The autism spectrum (Lancet 1997), described by Sula Wolff. The authors of the 2019 study hypothesised that it is extremely likely that historic cohorts of adults diagnosed with SzPD either also had childhood-onset autistic syndromes or were misdiagnosed. They stressed that further research to clarify overlap and distinctions between these two syndromes was strongly warranted, especially given that high-functioning autism spectrum disorders are now recognised in around 1% of the population. Low weight A study which looked at the body mass index (BMI) of a sample of both male adolescents diagnosed with SzPD and those diagnosed with Asperger syndrome found that the BMI of all patients was significantly below normal. Clinical records indicated abnormal eating behaviour by some patients. Some patients would only eat when alone and refused to eat out. Restrictive diets and fears of disease were also found. It was suggested that the anhedonia of SzPD may also cover eating, leading schizoid individuals to not enjoy it. Alternatively, it was suggested that schizoid individuals may not feel hunger as strongly as others or not respond to it, a certain withdrawal "from themselves". Anti-social conduct Another study looked at rates of anti-social conduct in boys with either SzPD or Asperger syndrome compared with a control group of non-schizoid individuals and found the incidence of anti-social conduct to be the same in both groups. However, the schizoid boys stole significantly less. Upon follow-up in adulthood, out of a matched group of 19 boys with SzPD and 19 boys without, four of the schizoid boys reported having exclusively internal violent fantasies (concerned with Zulu wars, abattoirs, fascists and communists and a collection of knives, respectively), which were pursued entirely by themselves, while the only non-schizoid subject to report a violent fantasy life shared his with a group of young men (dressing up and riding motorcycles as a self-styled "panzer" group).An absent parent or socio-economic disadvantage did not seem to affect the risk of anti-social conduct in schizoid individuals as much as it did in non-schizoid individuals. Absent parents and parental socio-economic disadvantage were also less common in the schizoid group. Controversy The original concept of the schizoid character developed by Ernst Kretschmer in the 1920s comprised an amalgamation of avoidant, schizotypal and schizoid traits. It was not until 1980 and the work of Theodore Millon that led to splitting this concept into three personality disorders (now schizoid, schizotypal and avoidant). This caused debate about whether this was accurate or if these traits were different expressions of a single personality disorder. It has also been argued due to the poor consistency and efficiency of diagnosis due to overlapping traits that SzPD should be removed altogether from the DSM.A 2012 article suggested that two different disorders may better represent SzPD: one affect-constricted disorder (belonging to schizotypal PD) and a seclusive disorder (belonging to avoidant PD). They called for the replacement of the SzPD category from future editions of the DSM by a dimensional model which would allow for the description of schizoid traits on an individual basis.Some critics such as Nancy McWilliams of Rutgers University and Parpottas Panagiotis of European University Cyprus argue that the definition of SzPD is flawed due to cultural bias and that it does not constitute a mental disorder but simply an avoidant attachment style requiring more distant emotional proximity. If that is true, then many of the more problematic reactions these individuals show in social situations may be partly accounted for by the judgements commonly imposed on people with this style. However, impairment is mandatory for any behaviour to be diagnosed as a personality disorder. SzPD seems to satisfy this criterion because it is linked to negative outcomes. These include a significantly compromised quality of life, reduced overall functioning even after 15 years and one of the lowest levels of "life success" of all personality disorders (measured as "status, wealth and successful relationships"). However, determination of what qualify as "impairments" or as "negative outcomes" is itself potentially subject to cultural bias. People with SzPD may not regard a lack of social-status or successful relationships, for example, as a harm. Furthermore, correlation with negative outcomes does not necessarily demonstrate that these outcomes were directly caused by the schizoidal traits. Rather, it may be that these outcomes are the result of discrimination against people with SzPD, who may be viewed as abnormal. Treatment People with SzPD rarely seek treatment for their condition. This issue is found in many personality disorders, which prevents many people with these conditions from seeking treatment: they tend to view their condition as not conflicting with their self-image and their abnormal perceptions and behaviors as rational and appropriate. There are little data on the effectiveness of various treatments on this personality disorder because it is seldom seen in clinical settings. However, those in treatment have the option of medication and psychotherapy. Medication No medications are indicated for directly treating SzPD, but certain medications may reduce the symptoms of SzPD as well as treat co-occurring mental disorders. The symptoms of SzPD mirror the negative symptoms of schizophrenia, such as anhedonia, blunted affect and low energy, and SzPD is thought to be part of the "schizophrenic spectrum" of disorders, which also includes the schizotypal and paranoid personality disorders,
Schizoid personality disorder	and may benefit from the medications indicated for schizophrenia. Originally, low doses of atypical antipsychotics like risperidone or olanzapine were used to alleviate social deficits and blunted affect. However, a 2012 review concluded that atypical antipsychotics were ineffective for treating personality disorders.In contrast, the substituted amphetamine bupropion may be used to treat anhedonia. Likewise, modafinil may be effective in treating some of the negative symptoms of schizophrenia, which are reflected in the symptomatology of SzPD and therefore may help as well. Lamotrigine, SSRIs, TCAs, MAOIs and hydroxyzine may help counter social anxiety in people with SzPD if present, though social anxiety may not be a main concern for the people who have SzPD. However, it is not general practice to treat SzPD with medications, other than for the short-term treatment of acute co-occurring axis I conditions (e.g. depression). Psychotherapy Despite the relative emotional comfort, psychoanalytic therapy of schizoid individuals takes a long time and causes many difficulties. Schizoids are generally poorly involved in psychotherapy due to difficulties in establishing empathic relations with a psychotherapist and low motivation for treatment.Supportive psychotherapy is used in an inpatient or outpatient setting by a trained professional that focuses on areas such as coping skills, improvement of social skills and social interactions, communication and self-esteem issues. People with SzPD may also have a perceptual tendency to miss subtle differences in expression. That causes an inability to pick up hints from the environment because social cues from others that might normally provoke an emotional response are not perceived. That in turn limits their own emotional experience. The perception of varied events only increases their fear for intimacy and limits them in their interpersonal relationships. Their aloofness may limit their opportunities to refine the social skills and behavior necessary to effectively pursue relationships.Besides psychodynamic therapy, cognitive behavioral therapy (CBT) can be used. But because CBT generally begins with identifying the automatic thoughts, one should be aware of the potential hazards that can happen when working with schizoid patients. People with SzPD seem to be distinguished from those with other personality disorders in that they often report having few or no automatic thoughts at all. That poverty of thought may have to do with their apathetic lifestyle. But another possible explanation could be the paucity of emotion many schizoids display, which would influence their thought patterns as well.Socialization groups may help people with SzPD. Educational strategies in which people who have SzPD identify their positive and negative emotions also may be effective. Such identification helps them to learn about their own emotions and the emotions they draw out from others and to feel the common emotions with other people with whom they relate. This can help people with SzPD create empathy with the outside world. Shorter-term treatment The concept of "closer compromise" means that the schizoid patient may be encouraged to experience intermediate positions between the extremes of emotional closeness and permanent exile. A lack of injections of interpersonal reality causes an impoverishment in which the schizoid individuals self-image becomes increasingly empty and volatilized and leads the individual to feel unreal. To create a more adaptive and self-enriching interaction with others in which one "feels real", the patient is encouraged to take risks through greater connection, communication and sharing of ideas, feelings and actions. Closer compromise means that while the patients vulnerability to anxieties is not overcome, it is modified and managed more adaptively. Here, the therapist repeatedly conveys to the patient that anxiety is inevitable but manageable, without any illusion that the vulnerability to such anxiety can be permanently dispensed with. The limiting factor is the point at which the dangers of intimacy become overwhelming and the patient must again retreat. Klein suggests that patients must take the responsibility to place themselves at risk and to take the initiative for following through with treatment suggestions in their personal lives. It is emphasized that these are the therapists impressions and that he or she is not reading the patients mind or imposing an agenda but is simply stating a position that is an extension of the patients therapeutic wish. Finally, the therapist directs attention to the need to employ these actions outside of the therapeutic setting. Longer-term therapy Klein suggests that "working through" is the second longer-term tier of psychotherapeutic work with schizoid patients. Its goals are to change fundamentally the old ways of feeling and thinking and to rid oneself of the vulnerability to those emotions associated with old feelings and thoughts. A new therapeutic operation of "remembering with feeling" that draws on D. W. Winnicotts concepts of false self and true self is called for. The patient must remember with feeling the emergence of his or her false self through childhood and remember the conditions and proscriptions that were imposed on the individuals freedom to experience the self in company with others.Remembering with feeling ultimately leads the patient to understand that he or she had no opportunity to choose from a selection of possible ways of experiencing the self and of relating with others and had few, if any, options other than to develop a schizoid stance toward others. The false self was simply the best way in which the patient could experience the repetitive predictable acknowledgement, affirmation and approval necessary for emotional survival while warding off the effects associated with the abandonment depression.If the goal of shorter-term therapy is for patients to understand that they are not the way they appear to be and can act differently, then the longer-term goal of working through is for patients to understand who and what they are as human beings, what they truly are like and what they truly contain. The goal of working through is not achieved by the patients sudden discovery of a hidden, fully formed talented and creative self living inside, but is a process of slowly freeing oneself from the confinement of abandonment depression in order to uncover a potential. It is a process of experimentation with the spontaneous, nonreactive elements that can be experienced in relationship with others.Working through abandonment depression is a complicated, lengthy and conflicted process that can be an enormously painful experience in terms of what is remembered and what must be felt. It involves mourning and grieving for the loss of the illusion that the patient had adequate support for the emergence of the real self. There is also a mourning for the loss of an identity, the false self, which the person constructed and with which he or she has negotiated much of his or her life. The dismantling of the false self requires relinquishing the only way that the patient has ever known of how to interact with others. This interaction was better than not to have a stable, organized experience of the self, no matter how false, defensive or destructive that identity may be. The dismantling of the false self "leaves the impaired real self with the opportunity to convert its potential and its possibilities into actualities." Working through brings unique rewards, of which the most important element is the growing realization that the individual has a fundamental, internal need for relatedness that may be expressed in a variety of ways. "Only schizoid patients", suggests Klein, "who have worked through the abandonment depression... ultimately will believe that the capacity for relatedness and the wish for relatedness are woven into the structure of their beings, that they are truly part of who the patients are and what they contain as human beings. It is this sense that finally allows the schizoid patient to feel the most intimate sense of being connected with humanity more generally, and with another person more personally. For the schizoid patient, this degree of certainty is the most gratifying revelation, and a profound new organizer of the self experience.": 127 Development and course SzPD can be first apparent in childhood and adolescence with solitariness, poor peer relationships and underachievement in school. This may mark these children as different and make them subject to teasing.Being a personality disorder, which is usually chronic and long-lasting mental conditions, SzPD is not expected to improve with time without treatment; however, much remains unknown because it is rarely encountered in clinical settings. Epidemiology SzPD is uncommon in clinical settings (about 2.2%) and occurs more commonly in males. It is rare compared with other personality disorders, with a prevalence estimated at less than 1% of the general population.Philip Manfield suggests that the "schizoid condition", which roughly includes the DSM schizoid, avoidant and schizotypal personality disorders, is represented by "as many as forty percent of all personality disorders." Manfield adds "This huge discrepancy [from the ten percent reported by therapists for the condition] is probably largely because someone with a schizoid disorder is less likely to seek treatment than someone with other axis-II disorders."A 2008 study assessing personality and mood disorder prevalence among homeless people at New York City drop-in centres reported an SzPD rate of 65% among this sample. The study did not assess homeless people who did not show up at drop-in centres, and the rates of most other personality and mood disorders within the drop-in centres was lower than that of SzPD. The authors noted the limitations of the study, including the higher male-to-female ratio in the sample and the absence of subjects outside the support system or receiving other support (e.g., shelters) as well as the absence of subjects in geographical settings outside New York City, a large city often considered a magnet for disenfranchised people.A University of Colorado Colorado Springs study comparing personality disorders and Myers–Briggs Type Indicator types found that the disorder had a significant correlation with the Introverted (I) and Thinking (T) preferences. History The term "schizoid" was coined in 1908 by Eugen Bleuler to designate a human tendency to direct attention toward ones inner life and away from the external world, a concept akin to introversion in that it was not viewed in terms of psychopathology. Bleuler labeled the exaggeration of this tendency the "schizoid personality". He described these personalities as "comfortably dull and at the same time sensitive, people who in a narrow manner pursue vague purposes".In 1910, August Hoch introduced a very similar concept called the "shut-in" personality. Characteristics of it were reticence, seclusiveness, shyness and a preference for living in fantasy worlds, among others. In 1925, Russian psychiatrist Grunya Sukhareva described a "schizoid psychopathy" in a group of children, resembling todays SzPD and ASD. About a decade later Pyotr Gannushkin also included Schizoids and Dreamers in his detailed typology of personality types.Studies on the schizoid personality have developed along two distinct paths. The "descriptive psychiatry" tradition focuses on overtly observable, behavioral and describable symptoms and finds its clearest exposition in the DSM-5. The dynamic psychiatry tradition includes the exploration of covert or unconscious motivations and character structure as elaborated by classic psychoanalysis and object-relations theory. The descriptive tradition began in 1925 with the description of observable schizoid behaviors by Ernst Kretschmer. He organized those into three groups of characteristics: Unsociability, quietness, reservedness, seriousness and eccentricity. Timidity, shyness with feelings, sensitivity, nervousness, excitability, fondness of nature and books. Pliability, kindliness, honesty, indifference, silence and cold emotional attitudes.These characteristics were the precursors of the DSM-III division of the schizoid character into three distinct personality disorders: schizotypal, avoidant and schizoid. Kretschmer himself, however, did not conceive of separating these behaviors to the point of radical isolation but considered them to be simultaneously present as varying potentials in schizoid individuals. For Kretschmer, the majority of schizoids are not either oversensitive or cold, but they are oversensitive and cold "at the same time" in quite different relative proportions, with a tendency to move along these dimensions from one behavior to the other.The second path, that of dynamic psychiatry, began in 1924 with observations by Eugen Bleuler, who observed that the schizoid person and schizoid pathology were not things to be set apart.: p. 5 Ronald Fairbairns seminal work on the schizoid personality, from which most of what is known today about schizoid phenomena is derived, was presented in 1940. Here, Fairbairn delineated four central schizoid themes: The need to regulate interpersonal distance as a central focus of concern. The ability to mobilize self-preservative defenses and self-reliance. A pervasive tension between the anxiety-laden need for attachment and the defensive need for distance that manifests in observable behavior as indifference. An overvaluation of the inner world at the expense of the outer world.: p. 9 Following Fairbairn, the dynamic psychiatry tradition has continued to produce rich explorations on the schizoid character, most notably from writers Nannarello (1953), Laing (1965), Winnicott (1965), Guntrip (1969), Khan (1974), Akhtar (1987), Seinfeld (1991), Manfield (1992) and Klein (1995). See also Asociality Counterphobic attitude Dissociation (psychology) Hermit Recluse Schizothymia Schizotypy Sluggish cognitive tempo References External links The biological foundations of the schizoid process NY Times article "Like a Fish Needs a Bicycle: For Some People, Intimacy Is Toxic" Psychology Today (2017): The Disappearance of the Schizoid Personality
Cannabis use disorder	Cannabis use disorder (CUD), also known as cannabis addiction or marijuana addiction, is defined in the fifth revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and ICD-10 as the continued use of cannabis despite clinically significant impairment. Signs and symptoms Cannabis use is associated with comorbid mental health problems, such as mood and anxiety disorders, and discontinuing cannabis use is difficult for some users. Psychiatric comorbidities are often present in dependent cannabis users including a range of personality disorders.Based on annual survey data, some high school seniors who report smoking daily (nearly 7%, according to one study) may function at a lower rate in school than students that do not. The sedating and anxiolytic properties of tetrahydrocannabinol (THC) in some users might make the use of cannabis an attempt to self-medicate personality or psychiatric disorders. Dependency Prolonged cannabis use produces both pharmacokinetic changes (how the drug is absorbed, distributed, metabolized, and excreted) and pharmacodynamic changes (how the drug interacts with target cells) to the body. These changes require the user to consume higher doses of the drug to achieve a common desirable effect (known as a higher tolerance), reinforcing the bodys metabolic systems for eliminating the drug more efficiently and further down-regulating cannabinoid receptors in the brain.Cannabis users have shown decreased reactivity to dopamine, suggesting a possible link to a dampening of the reward system of the brain and an increase in negative emotion and addiction severity.Cannabis users can develop tolerance to the effects of THC. Tolerance to the behavioral and psychological effects of THC has been demonstrated in adolescent humans and animals. The mechanisms that create this tolerance to THC are thought to involve changes in cannabinoid receptor function.One study has shown that between 2001–2002 and 2012–2013, the use of marijuana in the US doubled.Cannabis dependence develops in about 9% of users, significantly less than that of heroin, cocaine, alcohol, and prescribed anxiolytics, but slightly higher than that for psilocybin, mescaline, or LSD. Of those who use cannabis daily, 10–20% develop dependence. Withdrawal Cannabis withdrawal symptoms occur in one-half of people in treatment for cannabis use disorders. Symptoms may include dysphoria (anxiety, irritability, depression, restlessness), disturbed sleep, gastrointestinal symptoms, and decreased appetite. It is often paired with rhythmic movement disorder. Most symptoms begin during the first week of abstinence and resolve after a few weeks. About 12% of heavy cannabis users showed cannabis withdrawal as defined by the DSM-5, and this was associated with significant disability as well as mood, anxiety and personality disorders. Cause Cannabis addiction is often due to prolonged and increasing use of the drug. Increasing the strength of the cannabis taken and an increasing use of more effective methods of delivery often increase the progression of cannabis dependency. It can also be caused by being prone to becoming addicted to substances, which can either be genetically or environmentally acquired. Risk factors Certain factors are considered to heighten the risk of developing cannabis dependence and longitudinal studies over a number of years have enabled researchers to track aspects of social and psychological development concurrently with cannabis use. Increasing evidence is being shown for the elevation of associated problems by the frequency and age at which cannabis is used, with young and frequent users being at most risk.The main factors in Australia, for example, related to a heightened risk for developing problems with cannabis use include frequent use at a young age; personal maladjustment; emotional distress; poor parenting; school drop-out; affiliation with drug-using peers; moving away from home at an early age; daily cigarette smoking; and ready access to cannabis. The researchers concluded there is emerging evidence that positive experiences to early cannabis use are a significant predictor of late dependence and that genetic predisposition plays a role in the development of problematic use. High risk groups A number of groups have been identified as being at greater risk of developing cannabis dependence and, in Australia, for example, have been found to include adolescent populations, Aboriginal and Torres Strait Islanders and people with mental health conditions. Adolescents The endocannabinoid system is directly involved in adolescent brain development. Adolescent cannabis users are therefore particularly vulnerable to the potential adverse effects of cannabis use. Adolescent cannabis use is associated with increased cannabis misuse as an adult, issues with memory and concentration, long-term cognitive complications, and poor psychiatric outcomes including social anxiety, suicidality and addiction.There are a lot of reasons why adolescents start a smoking habit. According to a study completed by Bill Sanders, influence from friends, difficult household problems, and experimentation are some of the reasons why this population starts to smoke marijuana. This segment of population seems to be one of the most influenceable group there is. They want to follow the group and look "cool", "hip" and accepted by their friends. This fear of rejection plays a big role in their decision to smoke pot. However it does not seem to be the most important factor. According to a study from Canada, the lack of knowledge about cannabis seems to be the main reason why adolescents start to smoke. The authors observed a high correlation between adolescents that knew about the mental and physical harms of cannabis and their consumption. Of the 1045 young participants in the study, those who could name the least number of negative effects about this drug were usually the ones who were consuming it. They were not isolated cases either. Actually, the study showed that the proportion of teenagers who saw cannabis as a high-risk drug and the ones who thought the contrary was about the same. Pregnancy There is an association between smoking cannabis during pregnancy and low birth weight. Smoking cannabis during pregnancy can lower the amount of oxygen delivered to the developing fetus, which can restrict fetal growth. The active ingredient in cannabis (D9-tetrahydrocannabinol, THC) is fat soluble and can enter into breastmilk during lactation. THC in breastmilk can then subsequently be taken up by a breastfeeding infant, as shown by the presence of THC in the infants feces. However, the evidence for long-term effects of exposure to THC through breastmilk is unclear. Diagnosis Cannabis use disorder is recognized in the fifth version of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5), which also added cannabis withdrawal as a new condition.In the 2013 revision for the DSM-5, DSM-IV abuse and dependence were combined into cannabis use disorder. The legal problems criterion (from cannabis abuse) has been removed, and the craving criterion was newly added, resulting in a total of eleven criteria: hazardous use, social/interpersonal problems, neglected major roles, withdrawal, tolerance, used larger amounts/longer, repeated attempts to quit/control use, much time spent using, physical/psychological problems related to use, activities given up and craving. For a diagnosis of DSM-5 cannabis use disorder, at least two of these criteria need to be present in the last twelve-month period. Additionally, three severity levels have been defined: mild (two or three criteria), moderate (four or five criteria) and severe (six or more criteria) cannabis use disorder.Cannabis use disorder is also recognized in the eleventh revision of the International Classification of Diseases (ICD-11), adding more subdivisions including time intervals of pattern of use (episodic, continuous, or unspecified) and dependence (current, early full remission, sustained partial remission, sustained full remission, or unspecified) compared to the 10th revision.A 2019 meta-analysis found that 34% of people with cannabis-induced psychosis transitioned to schizophrenia. This was found to be comparatively higher than hallucinogens (26%) and amphetamines (22%).To screen for cannabis-related problems, several methods are used. Scales specific to cannabis, which provides the benefit of being cost efficient compared to extensive diagnostic interviews, include the Cannabis Abuse Screening Test (CAST), Cannabis Use Identification Test (CUDIT), and Cannabis Use Problems Identification Test (CUPIT). Scales for general drug use disorders are also used, including the Severity Dependence Scale (SDS), Drug Use Disorder Identification Test (DUDIT), and Alcohol, Smoking, and Substance Involvement Screening Test (ASSIST). However, there are no gold standard and both older and newer scales are still in use. To quantify cannabis use, methods such as Timeline Follow-Back (TLFB) and Cannabis Use Daily (CUD) are used. These methods measure general consumption and not grams of psychoactive substance as the concentration of THC may vary among drug users. Treatment Clinicians differentiate between casual users who have difficulty with drug screens, and daily heavy users, to a chronic user who uses multiple times a day. In the US, as of 2013, cannabis is the most commonly identified illicit substance used by people admitted to treatment facilities. Demand for treatment for cannabis use disorder increased internationally between 1995 and 2002. In the United States, the average adult who seeks treatment has consumed cannabis for over 10 years almost daily and has attempted to quit six or more times.Treatment options for cannabis dependence are far fewer than for opiate or alcohol dependence. Most treatment falls into the categories of psychological or psychotherapeutic, intervention, pharmacological intervention or treatment through peer support and environmental approaches. No medications have been found effective for cannabis dependence, but psychotherapeutic models hold promise. Screening and brief intervention sessions can be given in a variety of settings, particularly at doctors offices, which is of importance as most cannabis users seeking help will do so from their general practitioner rather than a drug treatment service agency.The most commonly accessed forms of treatment in Australia are 12-step programmes, physicians, rehabilitation programmes, and detox services, with inpatient and outpatient services equally accessed. In the EU approximately 20% of all primary admissions and 29% of all new drug clients in 2005, had primary cannabis problems. And in all countries that reported data between 1999 and 2005 the number of people seeking treatment for cannabis use increased. Psychological Psychological intervention includes cognitive behavioral therapy (CBT), motivational enhancement therapy (MET), contingency management (CM), supportive-expressive psychotherapy (SEP), family and systems interventions, and twelve-step programs.Evaluations of Marijuana Anonymous programs, modelled on the 12-step lines of Alcoholics Anonymous and Narcotics Anonymous, have shown small beneficial effects for general drug use reduction. In 2006, the Wisconsin Initiative to Promote Healthy Lifestyles implemented a program that helps primary care physicians identify and address marijuana use problems in patients. Medication As of 2020, there is no single medication that has been proven effective for treating cannabis use disorder; research is focused on three treatment approaches: agonist substitution, antagonist, and modulation of other neurotransmitter systems. More broadly, the goal of medication therapy for cannabis use disorder centers around targeting the stages of the addiction: acute intoxication/binge, withdrawal/negative affect, and preoccupation/anticipation.For the treatment of the withdrawal/negative affect symptom domain of cannabis use disorder, medications may work by alleviating restlessness, irritable or depressed mood, anxiety, and insomnia. Bupropion, which is a norepinephrine–dopamine reuptake inhibitor, has been studied for the treatment of withdrawal with largely poor results. Atomoxetine has also shown poor results, and is as a norepinephrine reuptake inhibitor, though it does increase the release of dopamine through downstream effects in the prefrontal cortex (an area of the brain responsible for planning complex tasks and behavior). Venlafaxine, a serotonin–norepinephrine reuptake inhibitor, has also been studied for cannabis use disorder, with the thought that the serotonergic component may be useful for the depressed mood or anxious dimensions of the withdrawal symptom domain. While venlafaxine has been shown to improve mood for people with cannabis use disorder, a clinical trial in this population actually found worse cannabis abstinence rates compared to placebo. It is worth noting that venlafaxine is sometimes poorly tolerated, and infrequent use or abrupt discontinuation of its use can lead to withdrawal symptoms from the medication itself, including irritability, dysphoria, and insomnia. It is possible that venlafaxine use actually exacerbated cannabis withdrawal symptoms, leading people to use more cannabis than placebo to alleviate their discomfort. Mirtazapine, which increases serotonin and norepinephrine, has also failed to improve abstinence rates in people with cannabis use disorder.People sometimes use cannabis to cope with their anxiety, and cannabis withdrawal can lead to symptoms of anxiety. Buspirone, a serotonin 1A receptor (5-HT1A) agonist, has shown limited efficacy for treating anxiety in people with cannabis use disorder, though there may be better efficacy in males than in females. Fluoxetine, a selective serotonin reuptake inhibitor, has failed to show efficacy in adolescents with both cannabis use disorder and depression. SSRIs are a class of antidepressant drugs that are also used for the treatment of anxiety disorders, such as generalized anxiety disorder. Vilazodone, which has both SSRI and 5-HT1A agonism properties, also failed to increase abstinence rates in people with cannabis use disorder.Studies of divalproex have found no significant benefit, though some studies have found mixed results. Baclofen, a GABA-B receptor agonist and antispasmodic medication, has been found to reduce cravings but without a significant benefit towards preventing relapse or improving sleep. Zolpidem, a GABA-A receptor agonist and "Z-hypnotic" medication, has shown some efficacy in treating insomnia due to cannabis withdrawal, though there is a potential for misuse. Entacapone was well tolerated and decreased cannabis cravings in a trial on a small number of patients. Topiramate, an antiepileptic drug, has shown mixed results in adolescents, reducing the volume of cannabis consumption without significantly increasing abstinence, with somewhat poor tolerability. Gabapentin, an indirect GABA modulator, has shown some preliminary benefit for reducing cravings and cannabis use.The agonist substitution approach is one that draws upon the analogy of the success of nicotine replacement therapy for nicotine addiction. Dronabinol, which is synthetic THC, has shown benefit in reducing cravings and other symptoms of withdrawal, though without preventing relapse or promoting abstinence. Combination therapy with dronabinol and the alpha 2 adrenergic receptor agonist lofexidine have shown mixed results, with possible benefits towards reducing withdrawal symptoms. However, overall, the combination of dronabinol and lofexidine is likely not effective for the treatment of cannabis use disorder. Nabilone, a synthetic THC analogue, has shown benefits in reducing symptoms of withdrawal such as difficulty sleeping, and decreased overall cannabis use. Despite its psychoactive effects, the slower onset of action and longer duration of action of nabilone make it less likely to be abused than cannabis itself, which makes nabilone a promising harm reduction strategy for the treatment of cannabis use disorder. The combination of nabilone and zolpidem has been shown to decrease sleep-related and mood-related symptoms of cannabis withdrawal, in addition to decreasing cannabis use. Nabiximols, a combined THC and cannabidiol (CBD) product that is formulated as an oral (buccal) spray, has been shown to improve withdrawal symptoms without improving abstinence rates. Oral CBD has not shown efficacy in reducing the signs or symptoms of cannabis use, and likely has no benefit in cannabis use withdrawal symptoms. The CB-1 receptor antagonist rimonabant has shown efficacy in reducing the effects of cannabis in users, but with a risk for serious psychiatric side effects.Naltrexone, a mu opioid receptor antagonist, has shown mixed results for cannabis use disorder—both increasing the subjective effects of cannabis when given acutely, but potentially decreasing the overall use of cannabis with chronic administration. N-acetylcysteine (NAC) has shown some limited benefit in decreasing cannabis use in adolescents, though not with adults. Lithium, a mood stabilizer, has shown mixed results for treating symptoms of cannabis withdrawal, but is likely ineffective. Quetiapine, a second-generation antipsychotic, has been shown to treat cannabis withdrawal related insomnia and decreased appetite at the expense of exacerbating cravings. Oxytocin, a neuropeptide that the body produces, has shown some benefit in reducing the use of cannabis when administered intranasally in combination with motivational enhancement therapy sessions, though the treatment effect did not persist between sessions.Finally, CB1 antagonists such as rimonabant have been tested for utility in CUD. These drugs are effective at blocking the subjective effects of cannabis intoxication as well as the somatic components. This is accomplished by preventing THC binding to the CB1 receptor, effectively eliminating the ability to get high. This is similar to how naloxone and naltrexone are used for opiates. CB1 antagonists may also aid in reducing cravings. Worries of psychological side effects that occur over prolonged exposure have led to the discontinuation of the development of many of these compounds, but several are currently entering clinical trials for the treatment of cannabis intoxication.[1] Over-the-counter sedating Antihistamines such as Doxylamine have sedating and anti-emetic effects and may provide short term relief but should only be used within advised dosages. Barriers to treatment Research that looks at barriers to cannabis treatment frequently cites a lack of interest in treatment, lack of motivation and knowledge of treatment facilities, an overall lack of facilities, costs associated with treatment, difficulty meeting program eligibility criteria and transport difficulties. Epidemiology Cannabis is one of the most widely used drugs in the world. In the United States, between 42% and 49% of people have used cannabis, an estimated 9% of those who use cannabis develop dependence. Of Australians aged 14 years and over 34.8% have used cannabis one or more times in their life. In the U.S., cannabis is the most commonly identified illicit substance used by people admitted to treatment facilities. Most of these people were referred there by the criminal justice system. Of admittees 16% either went on their own, or were referred by family or friends.In the European Union (data as available in 2018, information for individual countries was collected between 2012 and 2017), 26.3% of adults aged 15–64 used cannabis at least once in their lives, and 7.2% used cannabis in the last year. The highest prevalence of cannabis use among 15 to 64 years old in the EU was reported in France, with 41.4% having used cannabis at least once in their life, and 2.17% used cannabis daily or almost daily. Among young adults (15–34 years old), 14.1% used cannabis in the last year.Among adolescents (15–16 years old) in a European school based study (ESPAD), 16% of students have used cannabis at least once in their life, and 7% (boys: 8%, girls: 5%) of students had used cannabis in the last 30 days.Globally, 22.1 million people (0.3% of the worlds population) were estimated to have cannabis dependence. Research Medications such as SSRI antidepressants, mixed action antidepressants, bupropion, buspirone and atomoxetine may not be helpful to treat cannabis use disorder, but the evidence is very weak and further research is required. THC preparations, gabapentin, oxytocin, and N-acetylcysteine also require more research to determine if they are effective as the evidence base is weak.Heavy cannabis use has been associated with impaired cognitive functioning, however, its specific details are difficult to elucidate due to the potential use of additional substances of users, and lack of longitudinal studies. See also La Guardia Committee, the first in-depth study into the effects of cannabis. Medical cannabis Quitting smoking References == External links ==
Koebner phenomenon	The Koebner phenomenon or Köbner phenomenon (UK: , US: ), also called the Koebner response or the isomorphic response, attributed to Heinrich Köbner, is the appearance of skin lesions on lines of trauma. The Koebner phenomenon may result from either a linear exposure or irritation. Conditions demonstrating linear lesions after a linear exposure to a causative agent include: molluscum contagiosum, warts and toxicodendron dermatitis (a dermatitis caused by a genus of plants including poison ivy). Warts and molluscum contagiosum lesions can be spread in linear patterns by self-scratching ("auto-inoculation"). Toxicodendron dermatitis lesions are often linear from brushing up against the plant. Causes of the Koebner phenomenon that are secondary to scratching rather than an infective or chemical cause include vitiligo, psoriasis, lichen planus, lichen nitidus, pityriasis rubra pilaris, and keratosis follicularis (Darier disease). Definition The Koebner phenomenon describes skin lesions which appear at the site of injury. It is seen in: Psoriasis Pityriasis rubra pilaris Lichen planus Flat warts Lichen nitidus Vitiligo Lichen sclerosus Elastosis perforans serpiginosa Kaposi sarcoma Necrobiosis lipoidica Lupus Juvenile Idiopathic Arthritis Still disease Cutaneous leishmaniasis Post kala azar dermal leishmaniasisA similar response occurs in pyoderma gangrenosum and Behcets syndrome, and is referred to as pathergy.Rarely Koebner phenomenon has been reported as a mechanism of acute myeloid leukemia dissemination.Warts and molluscum contagiosum are often listed as causing a Koebner reaction, but this is by direct inoculation of viral particles.The linear arrangement of skin lesions in the Koebner phenomenon can be contrasted to both lines of Blaschko and dermatomal distributions. Blaschko lines follow embryotic cell migration patterns and are seen in some mosaic genetic disorders such as incontinentia pigmenti and pigment mosaicism. Dermatomal distributions are lines on the skin surface following the distribution of spinal nerve roots. The rash caused by herpes zoster (Shingles) follows such dermatomal lines. History The Koebner phenomenon was named after the rather eccentric but renowned German dermatologist Heinrich Koebner (1838–1904). Koebner is best known for his work in mycology. His intense nature is illustrated by the following: in a medical meeting, he proudly exhibited on his arms and chest three different fungus infections, which he had self-inoculated, in order to prove the infectiousness of the organisms he was studying. The Koebner phenomenon is the generalized term applied to his discovery that on psoriasis patients, new lesions often appear along lines of trauma. See also Renbök phenomenon References Sources Crissey JT, Parish LC, Holubar KH. Historical Atlas of Dermatology and Dermatologists. New York: The Parthenon Publishing Group, 2002. Paller A, Mancini A. Hurwitz Clinical Pediatric Dermatology. Philadelphia: Elsevier Saunders, 2002.
Parametritis	Parametritis (also known as pelvic cellulitis) is an infection of the parametrium (connective tissue adjacent to the uterus). It is considered a form of pelvic inflammatory disease. References == External links ==
Congenital syphilis	Congenital syphilis is syphilis present in utero and at birth, and occurs when a child is born to a mother with syphilis. Untreated early syphilis infections results in a high risk of poor pregnancy outcomes, including saddle nose, lower extremity abnormalities, miscarriages, premature births, stillbirths, or death in newborns. Some infants with congenital syphilis have symptoms at birth, but many develop symptoms later. Symptoms may include rash, fever, an enlarged liver and spleen, and skeletal abnormalities. Newborns will typically not develop a primary syphilitic chancre but may present with signs of secondary syphilis (i.e. generalized body rash). Often these babies will develop syphilitic rhinitis ("snuffles"), the mucus from which is laden with the T. pallidum bacterium, and therefore highly infectious. If a baby with congenital syphilis is not treated early, damage to the bones, teeth, eyes, ears, and brain can occur. Classification Early This is a subset of cases of congenital syphilis. Newborns may be asymptomatic and are only identified on routine prenatal screening. If not identified and treated, these newborns develop poor feeding and runny nose. By definition, early congenital syphilis occurs in children between 0 and 2 years old. After, they can develop late congenital syphilis. Late Late congenital syphilis is a subset of cases of congenital syphilis. By definition, it occurs in children at or greater than 2 years of age who acquired the infection trans-placentally.Symptoms include: Blunted upper incisor teeth known as Hutchinsons teeth Deafness from auditory nerve disease Frontal bossing (prominence of the brow ridge) Hard palate defect Inflammation of the cornea known as interstitial keratitis Protruding mandible Saber shins Saddle nose (collapse of the bony part of nose) Short maxillae Swollen kneesA frequently-found group of symptoms is Hutchinsons triad, which consists of Hutchinsons teeth (notched incisors), keratitis and deafness and occurs in 63% of cases.Treatment (with penicillin) before the development of late symptoms is essential. Signs and symptoms Abnormal x-rays Anemia Cerebral palsy Du Bois sign, narrowing of the little finger Enlarged liver Enlarged spleen Frontal bossing Sensorineural hearing loss Higouménakis sign, enlargement of the sternal end of clavicle in late congenital syphilis Hutchinsons triad, a set of symptoms consisting of deafness, Hutchinsons teeth (centrally notched, widely spaced peg-shaped upper central incisors), and interstitial keratitis (IK), an inflammation of the cornea which can lead to corneal scarring and potential blindness Hydrocephalus Jaundice Lymph node enlargement Mulberry molars (permanent first molars with multiple poorly developed cusps) Musculoskeletal deformities Petechiae Poorly developed maxillae Pseudoparalysis Rhagades, linear scars at the angles of the mouth and nose result from bacterial infection of skin lesions Snuffles, aka "syphilitic rhinitis", which appears similar to the rhinitis of the common cold, except it is more severe, lasts longer, often involves bloody rhinorrhea, and is often associated with laryngitis Sabre shins Skin rashDeath from congenital syphilis is usually due to bleeding into the lungs. Diagnosis Serological testing is carried out on the mother and the infant. If the neonatal IgG antibody titres are significantly higher than the mothers, then congenital syphilis can be confirmed. Specific IgM in the infant is another method of confirmation. CSF pleocytosis, raised CSF protein level and positive CSF serology suggest neurosyphilis. Treatment If a pregnant mother is identified as being infected with syphilis, treatment can effectively prevent congenital syphilis from developing in the fetus, especially if she is treated before the sixteenth week of pregnancy. The fetus is at greatest risk of contracting syphilis when the mother is in the early stages of infection, but the disease can be passed at any point during pregnancy, even during delivery (if the child had not already contracted it). A woman in the secondary stage of syphilis decreases her fetuss risk of developing congenital syphilis by 98% if she receives treatment before the last month of pregnancy. An affected child can be treated using antibiotics much like an adult; however, any developmental symptoms are likely to be permanent.Kassowitzs law is an empirical observation used in context of congenital syphilis stating that the greater the duration between the infection of the mother and conception, the better the outcome for the infant. Features of a better outcome include less chance of stillbirth and of developing congenital syphilis.The Centers for Disease Control and Prevention recommends treating symptomatic or babies born to an infected mother with unknown treatment status with procaine penicillin G, 50,000 U/kg dose IM a day in a single dose for 10 days. Treatment for these babies can vary on a case-by-case basis. Treatment cannot reverse any deformities, brain, or permanent tissue damage that has already occurred.A Cochrane review found that antibiotics may be effective for serological cure but in general the evidence around the effectiveness of antibiotics for congenital syphilis is uncertain due to the poor methodological quality of the small number of trials that have been conducted. References External links Media related to Congenital syphilis at Wikimedia Commons Images of Congenital Syphilis Manifestations 00655 at CHORUS
Epidermolysis bullosa simplex	Epidermolysis bullosa simplex (EBS) is a disorder resulting from mutations in the genes encoding keratin 5 or keratin 14.: 598 Blister formation of EBS occurs at the dermoepidermal junction. Sometimes EBS is called epidermolytic. Cause Absence of keratin-5,14 since birth. Diagnosis Classification Epidermolysis bullosa simplex may be divided into multiple types: Management No cure for EB Treat symptoms Protect skin, stop blister formation, promote healing Prevent complications Necessary treatment: use oral and topical steroid for healing and prevent complication Maintain cool environment, avoid overheating and decreases friction See also Epidermolysis bullosa List of cutaneous conditions caused by mutations in keratins References Further reading GeneReviews/NCBI/UW/NIH entry on Epidermolysis Bullosa Simplex == External links ==
Glomus tumor	Glomus tumor was also the name formerly (and incorrectly) used for a tumor now called a paraganglioma.A glomus tumor (also known as a "solitary glomus tumor," "solid glomus tumor,") is a rare neoplasm arising from the glomus body and mainly found under the nail, on the fingertip or in the foot.: 670 They account for less than 2% of all soft tissue tumors. The majority of glomus tumors are benign, but they can also show malignant features. Glomus tumors were first described by Hoyer in 1877 while the first complete clinical description was given by Masson in 1924.Histologically, glomus tumors are made up of an afferent arteriole, anastomotic vessel, and collecting venule. Glomus tumors are modified smooth muscle cells that control the thermoregulatory function of dermal glomus bodies. As stated above, these lesions should not be confused with paragangliomas, which were formerly also called glomus tumors in now-antiquated clinical usage. Glomus tumors do not arise from glomus cells, but paragangliomas do. Familial glomangiomas have been associated with a variety of deletions in the GLMN (glomulin) gene, and are inherited in an autosomal dominant manner, with incomplete penetrance. Signs and symptoms Glomus tumors are usually solitary and small lesions. The vast majority are found in the hand, wrist, foot, and under the fingernails.They are often painful, and the pain is reproduced when the lesion is placed in cold water. Multiple tumors are less likely to be painful. These tumors tend to have a bluish discoloration, although a whitish appearance may also be noted. Elevation of the nail bed can occur. In rare cases, the tumors may present in other body areas, such as the gastric antrum or glans penis. Treatment is essentially the same.Malignant glomus tumors, or glomangiosarcomas, are extremely rare and usually represent a locally infiltrative malignancy. However, metastases do occur and are usually fatal. Diagnosis Cancerous glomus tumors are exceedingly rare. Criteria for the diagnosis of malignancy in glomus tumors are: Tumor size of more than 2 centimeters and subfascial or visceral location. Atypical mitotic figures. Marked nuclear atypia and any level of mitotic activity. Pericytes of ZimmermanCancerous glomus tumors have been subdivided into three categories based on their histologic appearance: locally infiltrative glomus tumors (LIGT), glomangiosarcomas arising in benign glomus tumors (GABG), and glomangiosarcomas arising de novo (GADN).A few cases of cancerous glomus tumors have been reported; however, they are usually only locally invasive, and metastases are exceedingly rare. There is one report of widespread metastases of a malignant glomus tumor involving the skin, lungs, jejunum, liver, spleen, and lymph nodes. Another report of a malignant glomus tumor (glomangiosarcoma) with metastases from the skin. A malignant glomus tumor one arose from the kidneys. Differential The probable misdiagnosis of many of these lesions as hemangiomas or venous malformations also makes an accurate assessment of incidence difficult. Treatment Surgical excision is the preferred treatment for benign glomus tumors. Epidemiology The exact rate of glomus tumors is unknown. The multiple variant is rare, accounting for less than 10% of all cases. Sex Solitary glomus tumors, particularly subungual lesions, are more common in females than in males. Multiple lesions are slightly more common in males. Age Solitary glomus tumors are more frequent in adults than in others. Multiple glomus tumors develop 11–15 years earlier than single lesions; about one third of the cases of multiple tumors occur in those younger than 20 years. Congenital glomus tumors are rare; they are plaguelike in appearance and are considered a variant of multiple glomus tumors. See also Coccygeal glomus List of cutaneous conditions Myopericytoma References External links synd/1584 at Who Named It? 00314 at CHORUS
Paroxysmal tachycardia	Paroxysmal tachycardia is a form of tachycardia which begins and ends in an acute (or paroxysmal) manner. It is also known as "Bouveret-Hoffmann syndrome". Cause The cause of this condition is not accurately known, though it is probably of nervous origin and can be aggravated by physical wear and tear. The symptoms are sometimes very alarming but it is not considered in itself dangerous.It has an increased risk of developing in WPW syndrome and LGL syndrome. Diagnosis Classification It can be divided by the origin: supraventricular tachycardia ventricular tachycardia == References ==
Nummular dermatitis	Nummular dermatitis is one of the many forms of dermatitis. it is characterized by round or oval-shaped itchy lesions. The name comes from the Latin word "nummus," which means "coin." Signs and symptoms Nummular dermatitis is characterized by chronic or relapsing itchy coin-sized ovoid-shaped red plaques. They can occur on the trunk, limbs, face, and hands. Causes Many contact sensitizers or irritants are known to cause contact dermatitis superimposed on nummular dermatitis. Studies have implicated nickel, cobalt, chromate, and fragrance as likely culprits. Xerosis, or dehydration of skin is also a likely cause. Infection with Staphylococcus aureus bacteria or Candida albicans may also play a role. Diagnosis Diagnosis of nummular dermatitis is largely via clinical observation. Biopsies are typically not necessary, and cannot be used to rule out other atopic dermatitis or other eczemas. However, patch testing may be employed to rule out irritants (contact dermatitis) as a cause. In children, nummular dermatitis is commonly confused with tinea corporis. Treatment One of the keys to treatment and prevention involves keeping the skin moisturized. Lotions, creams, and bath oils may help prevent an outbreak. If the condition flares up, a common treatment involves the application of topical corticosteroids. Oral antihistamines may help lessen itching. Avoidance of irritants is a common strategy. More severe cases sometimes respond to ultraviolet light treatment. If the condition occurs only during the sun-less winter months then vitamin D supplement might be an effective treatment. Epidemiology The prevalence of nummular dermatitis in the United States is approximately 2 per 1,000. It is considered a disease of adulthood, for it is rare in children. See also List of cutaneous conditions Sulzberger–Garbe syndrome References == External links ==
Achilles tendinitis	Achilles tendinitis, also known as achilles tendinopathy, occurs when the Achilles tendon, found at the back of the ankle, becomes sore. Achilles tendinopathy is accompanied by alterations in the tendons structure and mechanical properties. The most common symptoms are pain and swelling around the affected tendon. The pain is typically worse at the start of exercise and decreases thereafter. Stiffness of the ankle may also be present. Onset is generally gradual.It commonly occurs as a result of overuse such as running. Other risk factors include trauma, a lifestyle that includes little exercise, high-heel shoes, rheumatoid arthritis, and medications of the fluoroquinolone or steroid class. Diagnosis is generally based on symptoms and examination.There are several simple actions that individuals can take to prevent or reduce tendinitis. Though commonly used, some of these actions have limited or no scientific evidence to support them, namely pre-exercise stretching. Strengthening calf muscles, avoiding over-training, and selecting more appropriate footwear are more well-regarded options. Running mechanics can be improved with simple exercises that will help runners avoid achilles injury. Treatment typically involves rest, ice, non-steroidal antiinflammatory agents (NSAIDs), and physical therapy. In those whose symptoms last more than six months despite other treatments, surgery may be considered. Achilles tendinitis is relatively common. Signs and symptoms Symptoms can vary from an ache or pain and swelling to the local area of the ankles, or a burning that surrounds the whole joint. With this condition, the pain is usually worse during and after activity, and the tendon and joint area can become stiffer the following day as swelling impinges on the movement of the tendon. Many patients report stressful situations in their lives in correlation with the beginnings of pain which may contribute to the symptoms.Achilles tendon injuries can be separated into insertional tendinopathy (20%–25% of the injuries), midportion tendinopathy (55%–65%), and proximal musculotendinous junction (9%–25%) injuries, according to the location of pain. Cause Achilles tendinitis is a common injury, particularly in sports that involve lunging and jumping. It is also a known side effect of fluoroquinolone antibiotics such as ciprofloxacin, as are other types of tendinitis.Swelling in a region of micro-damage or partial tear can be detected visually or by touch. Increased water content and disorganized collagen matrix in tendon lesions may be detected by ultrasonography or magnetic resonance imaging.Achilles tendinitis is thought to have physiological, mechanical, or extrinsic (i.e. footwear or training) causes. Physiologically, the Achilles tendon is subject to poor blood supply through the synovial sheaths that surround it. This lack of blood supply can lead to the degradation of collagen fibers and inflammation. Tightness in the calf muscles has also been known to be involved in the onset of Achilles tendinitis.During the loading phase of the running and walking cycle, the ankle and foot naturally pronate and supinate by approximately 5 degrees. Excessive pronation of the foot (over 5 degrees) in the subtalar joint is a type of mechanical mechanism that can lead to tendinitis.An overuse injury refers to repeated stress and strain, which is likely the case in endurance runners. Overuse can simply mean an increase in running, jumping or plyometric exercise intensity too soon. Another consideration would be the use of improper or worn-down footwear, which lack the necessary support to maintain the foot in the natural/normal pronation. Pathophysiology The Achilles tendon is the extension of the calf muscle and attaches to the heel bone. It causes the foot to extend (plantar flexion) when those muscles contract.The Achilles tendon does not have good blood supply or cell activity, so this injury can be slow to heal. The tendon receives nutrients from the tendon sheath or paratendon. When an injury occurs to the tendon, cells from surrounding structures migrate into the tendon to assist in repair. Some of these cells come from blood vessels that enter the tendon to provide direct blood flow to increase healing. With the blood vessels come nerve fibers. Researchers including Alfredson and his team in Sweden believe these nerve fibers to be the cause of the pain - they injected local anaesthetic around the vessels and this decreased significantly the pain from the Achilles tendon. Diagnosis Achilles tendinitis is usually diagnosed from a medical history, and physical examination of the tendon. Projectional radiography shows calcification deposits within the tendon at its calcaneal insertion in approximately 60 percent of cases. Magnetic resonance imaging (MRI) can determine the extent of tendon degeneration, and may show differential diagnoses such as bursitis. Prevention Performing consistent physical activity will improve the elasticity and strength of the tendon, which will assist in resisting the forces that are applied.While stretching before beginning an exercise session is often recommended evidence to support this practice is limited. Prevention of recurrence includes following appropriate exercise habits and wearing low-heeled shoes. In the case of incorrect foot alignment, orthotics can be used to properly position the feet. Footwear that is specialized to provide shock-absorption can be utilized to defend the longevity of the tendon. Achilles tendon injuries can be the result of exceeding the tendons capabilities for loading, therefore it is important to gradually adapt to exercise if someone is inexperienced, sedentary, or is an athlete who is not progressing at a steady rate.Eccentric strengthening exercises of the gastrocnemius and soleus muscles are utilized to improve the tensile strength of the tendon and lengthen the musculotendinous junction, decreasing the amount of strain experienced with ankle joint movements. This eccentric training method is especially important for individuals with chronic Achilles tendinosis which is classified as the degeneration of collagen fibers. These involve repetitions of slowly lowering the body while standing on the affected leg, using the opposite arm and foot to assist in repeating the cycle, and starting with the heel in a hyperextended position. (Hyperextension is typically achieved by balancing the forefoot on the edge of a step, a thick book, or a barbell weight so that the point of the heel is a couple of inches above the forefoot.) Treatment Treatment typically involves rest, ice, non-steroidal antiinflammatory agents (NSAIDs), and physical therapy. A heel lift or orthotics may also be helpful, but evidence on both heel lifts and orthotics is limited. Foam rolling may increase range of motion, but there is only weak evidence for the direct treatment of stiffness. Other treatments include: An eccentric exercise routine designed to strengthen the tendon. Application of a boot or cast. Injections The evidence to support injection therapies is poor. This includes corticosteroid injections. These can also increase the risk of tendon rupture. Autologous blood injections - results have not been highly encouraging and there is little evidence for their use. Procedures Tentative evidence supports the use of extracorporeal shockwave therapy. Epidemiology The prevalence of Achilles tendinitis varies among different ages and groups of people. Achilles tendinitis is most commonly found in individuals aged 30–40 Runners are susceptible, as well as anyone participating in sports, and men aged 30–39.Risk factors include participating in a sport or activity that involves running, jumping, bounding, and change of speed. Although Achilles tendinitis is mostly likely to occur in runners, it also is more likely in participants in basketball, volleyball, dancing, gymnastics and other athletic activities. Other risk factors include gender, age, improper stretching, and overuse. Another risk factor is any congenital condition in which an individuals legs rotate abnormally, which in turn causes the lower extremities to overstretch and contract; this puts stress on the Achilles tendon and will eventually cause Achilles tendinitis. References == External links ==
Vesicoureteral reflux	Vesicoureteral reflux (VUR), also known as vesicoureteric reflux, is a condition in which urine flows retrograde, or backward, from the bladder into one or both ureters and then to the renal calyx or kidneys. Urine normally travels in one direction (forward, or anterograde) from the kidneys to the bladder via the ureters, with a 1-way valve at the vesicoureteral (ureteral-bladder) junction preventing backflow. The valve is formed by oblique tunneling of the distal ureter through the wall of the bladder, creating a short length of ureter (1–2 cm) that can be compressed as the bladder fills. Reflux occurs if the ureter enters the bladder without sufficient tunneling, i.e., too "end-on". Signs and symptoms Most children with vesicoureteral reflux are asymptomatic. Vesicoureteral reflux may be diagnosed as a result of further evaluation of dilation of the kidney or ureters draining urine from the kidney while in utero as well as when a sibling has VUR (though routine testing in either circumstance is controversial). Reflux also increases risk of acute bladder and kidney infections, so testing for reflux may be performed after a child has one or more infections. In infants, the signs and symptoms of a urinary tract infection may include only fever and lethargy, with poor appetite and sometimes foul-smelling urine, while older children typically present with discomfort or pain with urination and frequent urination. Causes In healthy individuals the ureters enter the urinary bladder obliquely and run submucosally for some distance. This, in addition to the ureters muscular attachments, helps secure and support them posteriorly. Together these features produce a valvelike effect that occludes the ureteric opening during storage and voiding of urine. In people with VUR, failure of this mechanism occurs, with resultant backward (retrograde) flow of urine. Primary VUR Insufficient submucosal length of the ureter relative to its diameter causes inadequacy of the valvular mechanism. This is precipitated by a congenital defect or lack of longitudinal muscle of the portion of the ureter within the bladder resulting in an ureterovesicular junction (UVJ) abnormality. Secondary VUR In this category the ureters valvular mechanism is initially intact and healthy but becomes overwhelmed by increased bladder pressures associated with obstruction, which distorts the ureterovesicular junction. The obstructions may be anatomical or functional. Secondary VUR can be further divided into anatomical and functional groups. Anatomical Posterior urethral valves; urethral or meatal stenosis. These causes are treated surgically when possible. Functional Bladder instability, neurogenic bladder and non-neurogenic bladder. Bladder infections may cause reflux due to the elevated pressures associated with inflammation.Resolution of functional VUR will usually occur if the precipitating cause is treated and resolved. Medical and/or surgical treatment may be indicated. Diagnosis The following procedures may be used to diagnose VUR: Cystography Fluoroscopic voiding cystourethrogram (VCUG) Abdominal ultrasound Technetium-99m Dimercaptosuccunic Acid (DMSA) ScintigraphyAn abdominal ultrasound might suggest the presence of VUR if ureteral dilatation is present; however, in many circumstances of VUR of low to moderate, even high severity, the sonogram may be completely normal, thus providing insufficient utility as a single diagnostic test in the evaluation of children suspected of having VUR, such as those presenting with prenatal hydronephrosis or urinary tract infection (UTI).VCUG is the method of choice for grading and initial workup, while RNC is preferred for subsequent evaluations as there is less exposure to radiation. A high index of suspicion should be attached to any case where a child presents with a urinary tract infection, and anatomical causes should be excluded. A VCUG and abdominal ultrasound should be performed in these cases DMSA scintigraphy is used for the evaluation of the parenchymal damage, which is seen as cortical scars. After the first febrile UTI, the diagnostic role of an initial scintigraphy for detecting the damage before the VCUG was investigated and it was suggested that VCUG can be omitted in children who has no cortical scars and urinary tract dilatation.Early diagnosis in children is crucial as studies have shown that the children with VUR who present with a UTI and associated acute pyelonephritis are more likely to develop permanent renal cortical scarring than those children without VUR, with an odds ratio of 2.8. Thus VUR not only increases the frequency of UTIs, but also the risk of damage to upper urinary structures and end-stage renal disease. Severity Vesicoureteral reflux (VUR) is graded according to severity. Grade I – reflux into non-dilated ureter Grade II – reflux into the renal pelvis and calyces without dilatation Grade III – mild/moderate dilatation of the ureter, renal pelvis and calyces with minimal blunting of the fornices Grade IV – dilation of the renal pelvis and calyces with moderate ureteral tortuosity Grade V – gross dilatation of the ureter, pelvis and calyces; ureteral tortuosity; loss of papillary impressionsThe younger the patient and the lower the grade at presentation the higher the chance of spontaneous resolution. Approximately 85% of grade I & II VUR cases will resolve spontaneously. Approximately 50% of grade III cases and a lower percentage of higher grades will also resolve spontaneously. Treatment The goal of treatment is to minimize infections, as it is infections that cause renal scarring and not the vesicoureteral reflux. Minimizing infections is primarily done by prophylactic antibiotics in newborns and infants who are not potty trained. However, in children who are older, physicians and parents should focus on bowel and bladder management. Children who hold their bladder or who are constipated have a greater number of infections than children who void on a regular schedule. When medical management fails to prevent recurrent urinary tract infections, or if the kidneys show progressive renal scarring then surgical interventions may be necessary. Medical management is recommended in children with Grade I-III VUR as most cases will resolve spontaneously. A trial of medical treatment is indicated in patients with Grade IV VUR especially in younger patients or those with unilateral disease. Of the patients with Grade V VUR only infants are trialled on a medical approach before surgery is indicated, in older patients surgery is the only option. Endoscopic injection Endoscopic injection involves applying a gel around the ureteral opening to create a valve function and stop urine from flowing back up the ureter. The gel consists of two types of sugar-based molecules called dextranomer and hyaluronic acid. Trade names for this combination include Deflux and Zuidex. Both constituents are well known from previous uses in medicine. They are also biocompatible, which means that they do not cause significant reactions within the body. In fact, hyaluronic acid is produced and found naturally within the body. Medical treatment Medical treatment entails low dose antibiotic prophylaxis until resolution of VUR occurs. Antibiotics are administered nightly at half the normal therapeutic dose. The specific antibiotics used differ with the age of the patient and include: Amoxicillin or ampicillin – infants younger than 6 weeks Trimethoprim-sulfamethoxazole (co-trimoxazole) – 6 weeks to 2 monthsAfter 2 months the following antibiotics are suitable: Nitrofurantoin {5–7 mg/kg/24hrs} Nalidixic acid Bactrim Trimethoprim CephalosporinsUrine cultures are performed 3 monthly to exclude breakthrough infection. Annual radiological investigations are likewise indicated. Good perineal hygiene, and timed and double voiding are also important aspects of medical treatment. Bladder dysfunction is treated with the administration of anticholinergics. Surgical management A surgical approach is necessary in cases where a breakthrough infection results despite prophylaxis, or there is non-compliance with the prophylaxis. Similarly if the VUR is severe (Grade IV & V), there are pyelonephritic changes or congenital abnormalities. Other reasons necessitating surgical intervention are failure of renal growth, formation of new scars, renal deterioration and VUR in girls approaching puberty. There are four types of surgical procedure available for the treatment of VUR: endoscopic (STING/HIT procedures); laparoscopic; robotic-assisted laparoscopic; and open procedures (Cohen procedure, Leadbetter-Politano procedure, Lich-Gregoir technique). Laparoscopic and robotic-assisted laparoscopic procedures are often imitation of classical open procedures in laparoscopic or robotic-assisted laparoscopic environments. Surveillance The American Urological Association recommends ongoing monitoring of children with VUR until the abnormality resolves or is no longer clinically significant. The recommendations are for annual evaluation of blood pressure, height, weight, analysis of the urine, and kidney ultrasound. Epidemiology It has been estimated that VUR is present in more than 10% of the population. Younger children are more prone to VUR because of the relative shortness of the submucosal ureters. This susceptibility decreases with age as the length of the ureters increases as the children grow. In children under the age of 1 year with a urinary tract infection, 70% will have VUR. This number decreases to 15% by the age of 12. Although VUR is more common in males antenatally, in later life there is a definite female preponderance with 85% of cases being female. History As early as the time of Graeco-Roman physician and anatomist Galen described the urinary tract and noted that there were specific mechanisms to prevent the reflux of urine. References == External links ==
Cellulitis	Cellulitis is a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of the area of redness are generally not sharp and the skin may be swollen. While the redness often turns white when pressure is applied, this is not always the case. The area of infection is usually painful. Lymphatic vessels may occasionally be involved, and the person may have a fever and feel tired.The legs and face are the most common sites involved, although cellulitis can occur on any part of the body. The leg is typically affected following a break in the skin. Other risk factors include obesity, leg swelling, and old age. For facial infections, a break in the skin beforehand is not usually the case. The bacteria most commonly involved are streptococci and Staphylococcus aureus. In contrast to cellulitis, erysipelas is a bacterial infection involving the more superficial layers of the skin, present with an area of redness with well-defined edges, and more often is associated with a fever. The diagnosis is usually based on the presenting signs and symptoms, while a cell culture is rarely possible. Before making a diagnosis, more serious infections such as an underlying bone infection or necrotizing fasciitis should be ruled out.Treatment is typically with antibiotics taken by mouth, such as cephalexin, amoxicillin or cloxacillin. Those who are allergic to penicillin may be prescribed erythromycin or clindamycin instead. When methicillin-resistant S. aureus (MRSA) is a concern, doxycycline or trimethoprim/sulfamethoxazole may, in addition, be recommended. There is concern related to the presence of pus or previous MRSA infections. Elevating the infected area may be useful, as may pain killers.Potential complications include abscess formation. Around 95% of people are better after 7 to 10 days of treatment. Those with diabetes, however, often have worse outcomes. Cellulitis occurred in about 21.2 million people in 2015. In the United States about 2 of every 1,000 people per year have a case affecting the lower leg. Cellulitis in 2015 resulted in about 16,900 deaths worldwide. In the United Kingdom, cellulitis was the reason for 1.6% of admissions to a hospital. Signs and symptoms The typical signs and symptoms of cellulitis are an area that is red, hot, and painful. The photos shown here are of mild to moderate cases and are not representative of the earlier stages of the condition. Complications Potential complications may include abscess formation, fasciitis, and sepsis. Causes Cellulitis is caused by bacteria that enter and infect the tissue through breaks in the skin. Group A Streptococcus and Staphylococcus are the most common causes of the infection and may be found on the skin as normal flora in healthy individuals.About 80% of cases of Ludwigs angina, or cellulitis of the submandibular space, are caused by dental infections. Mixed infections, due to both aerobes and anaerobes, are commonly associated with this type of cellulitis. Typically, this includes alpha-hemolytic streptococci, staphylococci, and bacteroides groups.Predisposing conditions for cellulitis include an insect or spider bite, blistering, an animal bite, tattoos, pruritic (itchy) skin rash, recent surgery, athletes foot, dry skin, eczema, injecting drugs (especially subcutaneous or intramuscular injection or where an attempted intravenous injection "misses" or blows the vein), pregnancy, diabetes, and obesity, which can affect circulation, as well as burns and boils, although debate exists as to whether minor foot lesions contribute. Occurrences of cellulitis may also be associated with the rare condition hidradenitis suppurativa or dissecting cellulitis.The appearance of the skin assists a doctor in determining a diagnosis. A doctor may also suggest blood tests, a wound culture, or other tests to help rule out a blood clot deep in the veins of the legs. Cellulitis in the lower leg is characterized by signs and symptoms similar to those of a deep vein thrombosis, such as warmth, pain, and swelling (inflammation). Reddened skin or rash may signal a deeper, more serious infection of the inner layers of skin. Once below the skin, the bacteria can spread rapidly, entering the lymph nodes and the bloodstream and spreading throughout the body. This can result in influenza-like symptoms with a high temperature and sweating or feeling very cold with shaking, as the affected person cannot get warm.In rare cases, the infection can spread to the deep layer of tissue called the fascial lining. Necrotizing fasciitis, also called by the media "flesh-eating bacteria", is an example of a deep-layer infection. It is a medical emergency. Risk factors The elderly and those with a weakened immune system are especially vulnerable to contracting cellulitis. Diabetics are more susceptible to cellulitis than the general population because of impairment of the immune system; they are especially prone to cellulitis in the feet, because the disease causes impairment of blood circulation in the legs, leading to diabetic foot or foot ulcers. Poor control of blood glucose levels allows bacteria to grow more rapidly in the affected tissue and facilitates rapid progression if the infection enters the bloodstream. Neural degeneration in diabetes means these ulcers may not be painful, thus often become infected. Those who have had poliomyelitis are also prone because of circulatory problems, especially in the legs.Immunosuppressive drugs, and other illnesses or infections that weaken the immune system, are also factors that make infection more likely. Chickenpox and shingles often result in blisters that break open, providing a gap in the skin through which bacteria can enter. Lymphedema, which causes swelling on the arms and/or legs, can also put an individual at risk. Diseases that affect blood circulation in the legs and feet, such as chronic venous insufficiency and varicose veins, are also risk factors for cellulitis.Cellulitis is also common among dense populations sharing hygiene facilities and common living quarters, such as military installations, college dormitories, nursing homes, oil platforms, and homeless shelters. Diagnosis Cellulitis is most often a clinical diagnosis, readily identified in many people by history and physical examination alone, with rapidly spreading areas of cutaneous swelling, redness, and heat, occasionally associated with inflammation of regional lymph nodes. While classically distinguished as a separate entity from erysipelas by spreading more deeply to involve the subcutaneous tissues, many clinicians may classify erysipelas as cellulitis. Both are often treated similarly, but cellulitis associated with furuncles, carbuncles, or abscesses is usually caused by S. aureus, which may affect treatment decisions, especially antibiotic selection. Skin aspiration of nonpurulent cellulitis, usually caused by streptococcal organisms, is rarely helpful for diagnosis, and blood cultures are positive in fewer than 5% of all cases.It is important to evaluate for co-existent abscess, as this finding usually requires surgical drainage as opposed to antibiotic therapy alone. Physicians clinical assessment for abscess may be limited, especially in cases with extensive overlying induration, but use of bedside ultrasonography performed by an experienced practitioner readily discriminates between abscess and cellulitis and may change management in up to 56% of cases. Use of ultrasound for abscess identification may also be indicated in cases of antibiotic failure. Cellulitis has a characteristic "cobblestoned" appearance indicative of subcutaneous edema without a defined hypoechoic, heterogeneous fluid collection that would indicate abscess. Differential diagnosis Other conditions that may mimic cellulitis include deep vein thrombosis, which can be diagnosed with a compression leg ultrasound, and stasis dermatitis, which is inflammation of the skin from poor blood flow. Signs of a more severe infection such as necrotizing fasciitis or gas gangrene that would require prompt surgical intervention include purple bullae, skin sloughing, subcutaneous edema, and systemic toxicity. Misdiagnosis can occur in up to 30% of people with suspected lower-extremity cellulitis, leading to 50,000 to 130,000 unnecessary hospitalization and $195 to $515 million in avoidable healthcare spending annually in the United States. Evaluation by dermatologists for cases of suspected cellulitis has been shown to reduce misdiagnosis rates and improve patient outcomes.Associated musculoskeletal findings are sometimes reported. When it occurs with acne conglobata, hidradenitis suppurativa, and pilonidal cysts, the syndrome is referred to as the follicular occlusion triad or tetrad.Lyme disease can be misdiagnosed as cellulitis. The characteristic bullseye rash does not always appear in Lyme disease (the rash may not have a central or ring-like clearing, or not appear at all). Factors supportive of Lyme include recent outdoor activities where Lyme is common and rash at an unusual site for cellulitis, such as armpit, groin, or behind the knee. Lyme can also result in long-term neurologic complications. The standard treatment for cellulitis, cephalexin, is not useful in Lyme disease. When it is unclear which one is present, the IDSA recommends treatment with cefuroxime axetil or amoxicillin/clavulanic acid, as these are effective against both infections. Prevention In those who have previously had cellulitis, the use of antibiotics may help prevent future episodes. This is recommended by CREST for those who have had more than two episodes. A 2017 meta-analysis found a benefit of preventative antibiotics for recurrent cellulitis in the lower limbs, but the preventative effects appear to diminish after stopping antibiotic therapy. Treatment Antibiotics are usually prescribed, with the agent selected based on suspected organism and presence or absence of purulence, although the best treatment choice is unclear. If an abscess is also present, surgical drainage is usually indicated, with antibiotics often prescribed for co-existent cellulitis, especially if extensive. Pain relief is also often prescribed, but excessive pain should always be investigated, as it is a symptom of necrotizing fasciitis. Elevation of the affected area is often recommended.Steroids may speed recovery in those on antibiotics. Antibiotics Antibiotics choices depend on regional availability, but a penicillinase-resistant semisynthetic penicillin or a first-generation cephalosporin is currently recommended for cellulitis without abscess. A course of antibiotics is not effective in between 6 and 37% of cases. Epidemiology Cellulitis in 2015 resulted in about 16,900 deaths worldwide, up from 12,600 in 2005.Cellulitis is a common global health burden, with more than 650,000 admissions per year in the United States alone. In the United States, an estimated 14.5 million cases annually of cellulitis account for $3.7 billion in ambulatory care costs alone. The majority of cases of cellulitis are nonculturable and therefore the causative bacteria are unknown. In the 15% of cellulitis cases in which organisms are identified, most are due to β-hemolytic Streptococcus and Staphylococcus aureus. Other animals Horses may acquire cellulitis, usually secondarily to a wound (which can be extremely small and superficial) or to a deep-tissue infection, such as an abscess or infected bone, tendon sheath or joint. Cellulitis from a superficial wound usually creates less lameness (grade 1–2 of 5) than that caused by septic arthritis (grade 4–5). The horse exhibits inflammatory edema, which is hot, painful swelling. This swelling differs from stocking up in that the horse does not display symmetrical swelling in two or four legs, but in only one leg. This swelling begins near the source of infection, but eventually continues down the leg. In some cases, the swelling also travels distally. Treatment includes cleaning the wound and caring for it properly, the administration of NSAIDs, such as phenylbutazone, cold hosing, applying a sweat wrap or a poultice, and mild exercise. See also Haemophilus influenzae cellulitis Helicobacter cellulitis Tuberculous cellulitis References Further reading Stevens, DL; Bisno, AL; Chambers, HF; Dellinger, EP; Goldstein, EJ; Gorbach, SL; Hirschmann, JV; Kaplan, SL; Montoya, JG; Wade, JC (15 July 2014). "Practice guidelines for the diagnosis and management of skin and soft tissue infections: 2014 update by the infectious diseases society of America". Clinical Infectious Diseases. 59 (2): 147–59. doi:10.1093/cid/ciu296. PMID 24947530. External links "Cellulitis". MedlinePlus. U.S. National Library of Medicine.
Neuromyotonia	Neuromyotonia (NMT) is a form of peripheral nerve hyperexcitability that causes spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin. NMT along with Morvans syndrome are the most severe types in the Peripheral Nerve Hyperexciteability spectrum. Example of two more common and less severe syndromes in the spectrum are Cramp Fasciculation Syndrome and Benign Fasciculation Syndrome. NMT can have both hereditary and acquired (non- inherited) forms. The prevalence of NMT is unknown. Signs and symptoms NMT is a diverse disorder. As a result of muscular hyperactivity, patients may present with muscle cramps, stiffness, myotonia-like symptoms (slow relaxation), associated walking difficulties, hyperhidrosis (excessive sweating), myokymia (quivering of a muscle), fasciculations (muscle twitching), fatigue, exercise intolerance, myoclonic jerks and other related symptoms. The symptoms (especially the stiffness and fasciculations) are most prominent in the calves, legs, trunk, and sometimes the face and neck, but can also affect other body parts. NMT symptoms may fluctuate in severity and frequency. Symptoms range from mere inconvenience to debilitating. At least a third of people also experience sensory symptoms. Causes The three causes of NMT are: Acquired Paraneoplastic HereditaryThe acquired form is the most common, accounting for up to 80 percent of all cases and is suspected to be autoimmune-mediated, which is usually caused by antibodies against the neuromuscular junction. The exact cause is unknown. However, autoreactive antibodies can be detected in a variety of peripheral (e.g. myasthenia gravis, Lambert-Eaton myasthenic syndrome) and central nervous system (e.g. paraneoplastic cerebellar degeneration, paraneoplastic limbic encephalitis) disorders. Their causative role has been established in some of these diseases but not all. Neuromyotonia is considered to be one of these with accumulating evidence for autoimmune origin over the last few years. Autoimmune neuromyotonia is typically caused by antibodies that bind to potassium channels on the motor nerve resulting in continuous/hyper-excitability. Onset is typically seen between the ages of 15–60, with most experiencing symptoms before the age of 40. Some neuromyotonia cases do not only improve after plasma exchange but they may also have antibodies in their serum samples against voltage-gated potassium channels. Moreover, these antibodies have been demonstrated to reduce potassium channel function in neuronal cell lines. Diagnosis Diagnosis is clinical and initially consists of ruling out more common conditions, disorders, and diseases, and usually begins at the general practitioner level. A doctor may conduct a basic neurological exam, including coordination, strength, reflexes, sensation, etc. A doctor may also run a series of tests that include blood work and MRIs. From there, a patient is likely to be referred to a neurologist or a neuromuscular specialist. The neurologist or specialist may run a series of more specialized tests, including needle electromyography EMG/ and nerve conduction studies (NCS) (these are the most important tests), chest CT (to rule out paraneoplastic) and specific blood work looking for voltage-gated potassium channel antibodies, acetylcholine receptor antibody, and serum immunofixation, TSH, ANA ESR, EEG etc. Neuromyotonia is characterized electromyographically by doublet, triplet or multiplet single unit discharges that have a high, irregular intraburst frequency. Fibrillation potentials and fasciculations are often also present with electromyography.Because the condition is so rare, it can often be years before a correct diagnosis is made. NMT is not fatal and many of the symptoms can be controlled. However, because NMT mimics some symptoms of motor neuron disease (ALS) and other more severe diseases, which may be fatal, there can often be significant anxiety until a diagnosis is made. In some rare cases, acquired neuromyotonia has been misdiagnosed as amyotrophic lateral sclerosis (ALS) particularly if fasciculations may be evident in the absence of other clinical features of ALS. However, fasciculations are rarely the first sign of ALS as the hallmark sign is weakness. Similarly, multiple sclerosis has been the initial misdiagnosis in some NMT patients. In order to get an accurate diagnosis see a trained neuromuscular specialist. People diagnosed with Benign Fasciculation Syndrome or Enhanced Physiological Tremor may experience similar symptoms as NMT, although it is unclear today whether BFS or EPT are weak forms of NMT. Types There are three main types of NMT: Chronic Monophasic (symptoms that resolve within several years of onset; postinfection, postallergic) Relapsing Remitting Peripheral nerve hyperexcitability Neuromyotonia is a type of peripheral nerve hyperexcitability. Peripheral nerve hyperexcitability is an umbrella diagnosis that includes (in order of severity of symptoms from least severe to most severe) benign fasciculation syndrome, cramp fasciculation syndrome, neuromyotonia and morvans syndrome. Some doctors will only give the diagnosis of peripheral nerve hyperexcitability as the differences between the three are largely a matter of the severity of the symptoms and can be subjective. However, some objective EMG criteria have been established to help distinguish between the three. Moreover, the generic use of the term peripheral nerve hyperexcitability syndromes to describe the aforementioned conditions is recommended and endorsed by several prominent researchers and practitioners in the field. Treatments There is no known cure for neuromyotonia, but the condition is treatable. Anticonvulsants, including phenytoin and carbamazepine, usually provide significant relief from the stiffness, muscle spasms, and pain associated with neuromyotonia. Plasma exchange and IVIg treatment may provide short-term relief for patients with some forms of the acquired disorder. It is speculated that the plasma exchange causes an interference with the function of the voltage-dependent potassium channels, one of the underlying issues of hyper-excitability in autoimmune neuromyotonia. Botox injections also provide short-term relief. Immunosuppressants such as Prednisone may provide long term relief for patients with some forms of the acquired disorder. Prognosis The long-term prognosis is uncertain, and has mostly to do with the underlying cause; i.e. autoimmune, paraneoplastic, etc. However, in recent years increased understanding of the basic mechanisms of NMT and autoimmunity has led to the development of novel treatment strategies. NMT disorders are now amenable to treatment and their prognoses are good. Many patients respond well to treatment, which usually provide significant relief of symptoms. Some cases of spontaneous remission have been noted, including Isaacs original two patients when followed up 14 years later. While NMT symptoms may fluctuate, they generally dont deteriorate into anything more serious, and with the correct treatment the symptoms are manageable. A very small proportion of cases with NMT may develop central nervous system findings in their clinical course, causing a disorder called Morvans syndrome, and they may also have antibodies against potassium channels in their serum samples. Sleep disorder is only one of a variety of clinical conditions observed in Morvans syndrome cases ranging from confusion and memory loss to hallucinations and delusions. However, this is a separate disorder. Some studies have linked NMT with certain types of cancers, mostly lung and thymus, suggesting that NMT may be paraneoplastic in some cases. In these cases, the underlying cancer will determine prognosis. However, most examples of NMT are autoimmune and not associated with cancer. References == External links ==
Developmental verbal dyspraxia	Developmental verbal dyspraxia (DVD), also known as childhood apraxia of speech (CAS) and developmental apraxia of speech (DAS), is a condition in which children have problems saying sounds, syllables and words. This is not because of muscle weakness or paralysis. The brain has problems planning to move the body parts (e.g., lips, jaw, tongue) needed for speech. The child knows what they want to say, but their brain has difficulty coordinating the muscle movements necessary to say those words.The exact cause of this disorder is usually unknown. Many observations suggest a genetic cause of DVD, as many with the disorder have a family history of communication disorders. The gene FOXP2 has been implicated in many studies of the condition, and when this is the cause, the condition is inherited in an autosomal dominant manner, however roughly 75% of these cases are de novo.There is no cure for DVD, but with appropriate, intensive intervention, people with this motor speech disorder can improve significantly. Presentation "Childhood apraxia of speech (CAS) is a neurological childhood (pediatric) speech sound disorder in which the precision and consistency of movements underlying speech are impaired in the absence of neuromuscular deficits (e.g., abnormal reflexes, abnormal tone). CAS may occur as a result of known neurological impairment, in association with complex neurobehavioral disorders of known or unknown origin, or as an idiopathic neurogenic speech sound disorder. The core impairment in planning and/or programming spatiotemporal parameters of movement sequences results in errors in speech sound production and prosody." American Speech-Language-Hearing Association (ASHA) Ad Hoc Committee on Apraxia of Speech in Children (2007) There are three significant features that differentiate DVD/CAS from other childhood speech sound disorders. These features are: "Inconsistent errors on consonants and vowels in repeated productions of syllables and words Lengthened coarticulatory transitions between sounds and syllables Inappropriate prosody, especially in the realization of lexical or phrasal stress"Even though DVD/CAS is a developmental disorder, it will not simply disappear when children grow older. Children with this disorder do not follow typical patterns of language acquisition and will need treatment in order to make progress. Causes DVD/CAS is a motor disorder, which means that the problem is located in the brain and its signals, and not in the mouth. In most cases, the cause is unknown. Possible causes include genetic syndromes and disorders.Recent research has focused on the significance of the FOXP2 gene in both species and individual development. Research regarding the KE family, where half the members of the extended family, over three generations, exhibited heritable developmental verbal dyspraxia, were found to have a defective copy of the FOXP2 gene. and further studies suggest that the FOXP2 gene as well as other genetic issues could explain DVD/CAS. including 16p11.2 microdeletion syndrome.New research suggests a role for the sodium channel SCN3A in the development of the perisylvian areas, which maintain key language circuits- Broca and Wernicke Area. Patients with mutations in SCN3A had oral-motor speech disorders.Birth/prenatal injuries, as well as stroke, can also be causes of DVD/CAS. Furthermore, DVD/CAS can occur as a secondary characteristic to a variety of other conditions. These include autism, some forms of epilepsy, fragile X syndrome, galactosemia and chromosome translocations involving duplications or deletions. Diagnosis Developmental verbal dyspraxia can be diagnosed by a speech language pathologist (SLP) through specific exams that measure oral mechanisms of speech. The oral mechanisms exam involves tasks such as pursing lips, blowing, licking lips, elevating the tongue, and also involves an examination of the mouth. A complete exam also involves observation of the patient eating and talking. Tests such as the Kaufman Speech Praxis test, a more formal examination, are also used in diagnosis. A differential diagnosis of DVD/CAS is often not possible for children under the age of two years old. Even when children are between 2–3 years, a clear diagnosis cannot always occur, because at this age, they may still be unable to focus on, or cooperate with, diagnostic testing. Management There is no cure for DVD/CAS, but with appropriate, intensive intervention, people with the disorder can improve significantly.DVD/CAS requires various forms of therapy which varies with the individual needs of the patient. Typically, treatment involves one-on-one therapy with a speech language pathologist (SLP). In children with DVD/CAS, consistency is a key element in treatment. Consistency in the form of communication, as well as the development and use of oral communication are extremely important in aiding a childs speech learning process.Many therapy approaches are not supported by thorough evidence; however, the aspects of treatment that do seem to be agreed upon are the following: Treatment needs to be intense and highly individualized, with about 3–5 therapy sessions each week A maximum of 30 minutes per session is best for young children Principles of motor learning theory and intense speech-motor practice seem to be the most effective Non-speech oral motor therapy is not necessary or sufficient A multi-sensory approach to therapy may be beneficial: using sign language, pictures, tactile cues, visual prompts, and augmentative and alternative communication (AAC) can be helpful.Although these aspects of treatment are supported by much clinical documentation, they lack evidence from systematic research studies. In ASHAs position statement on DVD/CAS, ASHA states there is a critical need for collaborative, interdisciplinary, and programmatic research on the neural substrates, behavioral correlates, and treatment options for DVD/CAS. Integral stimulation One technique that is frequently used to treat DVD/CAS is integral stimulation. Integral stimulation is based on cognitive motor learning, focusing on the cognitive motor planning needed for the complex motor task of speech. It is often referred to as the "watch me, listen, do as I do" approach and is founded on a multi-step hierarchy of strategies for treatment. This hierarchy of strategies allows the clinician to alter treatment depending upon the needs of the child. It uses various modalities of presentation, emphasizing the auditory and visual modes. Experts suggest that extensive practice and experience with the new material is key, so hundreds of target stimuli should be elicited in a single session. Furthermore, distributed (shorter, but more frequent) and random treatment, which mix target and non-target utterances, produces greater overall learning.The six steps of the hierarchy upon which integral stimulation therapy for children is loosely organized are: "The child watches and listens and simultaneously produces the stimulus with the clinician. The clinician models, then the child repeats the stimulus while the clinician simultaneously mouths it. The clinician models and provides cues and the child repeats. The clinician models and the child repeats with no cues provided. The clinician elicits the stimulus without modeling, such as by asking a question, with the child responding spontaneously. The child produces stimuli in less-directed situations with clinician encouragement, such as in role-play or games". Integrated phonological approach Another treatment strategy that has been shown to have positive effects is an integrated phonological approach. This approach "incorporates targeted speech production practice into phonological awareness activities and uses letters and phonological cues to prompt speech production". McNeill, Gillon, & Dodd studied 12 children ages 4–7 with DVD/CAS who were treated with this approach two times a week for two six-week blocks of time (separated by a six-week withdrawal block). They found positive effects for most of the children in the areas of speech production, phonological awareness, word decoding, letter knowledge, and spelling. These results show that it is clinically productive to target speech production, phonological awareness, letter knowledge, spelling, and reading all at once. This is particularly important since children with DVD/CAS often have continuous problems with reading and spelling, even if their production of speech improves. See also Apraxia Apraxia of speech Developmental coordination disorder Dysarthria FOXP2 and human evolution KE family Origin of speech Speech and language impairment References == External links ==
Gastroenteritis	Gastroenteritis, also known as infectious diarrhea and gastro, is inflammation of the gastrointestinal tract including the stomach and intestine. Symptoms may include diarrhea, vomiting, and abdominal pain. Fever, lack of energy, and dehydration may also occur. This typically lasts less than two weeks. It is not related to influenza, even though in the U.S. it is sometimes called the "stomach flu".Gastroenteritis is usually caused by viruses, gut bacteria, parasites, and fungi can also cause gastroenteritis. In children, rotavirus is the most common cause of severe disease. In adults, norovirus and Campylobacter are common causes. Eating improperly prepared food, drinking contaminated water or close contact with a person who is infected can spread the disease. Treatment is generally the same with or without a definitive diagnosis, so testing to confirm is usually not needed.For young children in impoverished countries, prevention includes hand washing with soap, drinking clean water, breastfeeding babies instead of using formula, and proper disposal of human waste. The rotavirus vaccine is recommended as a prevention for children. Treatment involves getting enough fluids. For mild or moderate cases, this can typically be achieved by drinking oral rehydration solution (a combination of water, salts and sugar). In those who are breastfed, continued breastfeeding is recommended. For more severe cases, intravenous fluids may be needed. Fluids may also be given by a nasogastric tube. Zinc supplementation is recommended in children. Antibiotics are generally not needed. However, antibiotics are recommended for young children with a fever and bloody diarrhea.In 2015, there were two billion cases of gastroenteritis, resulting in 1.3 million deaths globally. Children and those in the developing world are affected the most. In 2011, there were about 1.7 billion cases, resulting in about 700,000 deaths of children under the age of five. In the developing world, children less than two years of age frequently get six or more infections a year. It is less common in adults, partly due to the development of immunity. Signs and symptoms Gastroenteritis usually involves both diarrhea and vomiting. Sometimes, only one or the other is present. This may be accompanied by abdominal cramps. Signs and symptoms usually begin 12–72 hours after contracting the infectious agent. If due to a virus, the condition usually resolves within one week. Some viral infections also involve fever, fatigue, headache and muscle pain. If the stool is bloody, the cause is less likely to be viral and more likely to be bacterial. Some bacterial infections cause severe abdominal pain and may persist for several weeks.Children infected with rotavirus usually make a full recovery within three to eight days. However, in poor countries treatment for severe infections is often out of reach and persistent diarrhea is common. Dehydration is a common complication of diarrhea. Severe dehydration in children may be recognized if the skin color and position returns slowly when pressed. This is called "prolonged capillary refill" and "poor skin turgor". Abnormal breathing is another sign of severe dehydration. Repeat infections are typically seen in areas with poor sanitation, and malnutrition. Stunted growth and long-term cognitive delays can result.Reactive arthritis occurs in 1% of people following infections with Campylobacter species. Guillain–Barré syndrome occurs in 0.1%. Hemolytic uremic syndrome (HUS) may occur due to infection with Shiga toxin-producing Escherichia coli or Shigella species. HUS causes low platelet counts, poor kidney function, and low red blood cell count (due to their breakdown). Children are more predisposed to getting HUS than adults. Some viral infections may produce benign infantile seizures. Cause Viruses (particularly rotavirus (in children) and norovirus (in adults)) and the bacteria Escherichia coli and Campylobacter species are the primary causes of gastroenteritis. There are, however, many other infectious agents that can cause this syndrome including parasites and fungus. Non-infectious causes are seen on occasion, but they are less likely than a viral or bacterial cause. Risk of infection is higher in children due to their lack of immunity. Children are also at higher risk because they are less likely to practice good hygiene habits. Children living in areas without easy access to water and soap are especially vulnerable. Viral Rotaviruses, noroviruses, adenoviruses, and astroviruses are known to cause viral gastroenteritis. Rotavirus is the most common cause of gastroenteritis in children, and produces similar rates in both the developed and developing world. Viruses cause about 70% of episodes of infectious diarrhea in the pediatric age group. Rotavirus is a less common cause in adults due to acquired immunity. Norovirus is the cause in about 18% of all cases. Generally speaking, viral gastroenteritis accounts for 21–40% of the cases of infectious diarrhea in developed countries.Norovirus is the leading cause of gastroenteritis among adults in America accounting for about 90% of viral gastroenteritis outbreaks. These localized epidemics typically occur when groups of people spend time proximate to each other, such as on cruise ships, in hospitals, or in restaurants. People may remain infectious even after their diarrhea has ended. Norovirus is the cause of about 10% of cases in children. Bacterial In some countries, Campylobacter jejuni is the primary cause of bacterial gastroenteritis, with half of these cases associated with exposure to poultry. In children, bacteria are the cause in about 15% of cases, with the most common types being Escherichia coli, Salmonella, Shigella, and Campylobacter species. If food becomes contaminated with bacteria and remains at room temperature for a period of several hours, the bacteria multiply and increase the risk of infection in those who consume the food. Some foods commonly associated with illness include raw or undercooked meat, poultry, seafood, and eggs; raw sprouts; unpasteurized milk and soft cheeses; and fruit and vegetable juices. In the developing world, especially sub-Saharan Africa and Asia, cholera is a common cause of gastroenteritis. This infection is usually transmitted by contaminated water or food.Toxigenic Clostridium difficile is an important cause of diarrhea that occurs more often in the elderly. Infants can carry these bacteria without developing symptoms. It is a common cause of diarrhea in those who are hospitalized and is frequently associated with antibiotic use. Staphylococcus aureus infectious diarrhea may also occur in those who have used antibiotics. Acute "travelers diarrhea" is usually a type of bacterial gastroenteritis, while the persistent form is usually parasitic. Acid-suppressing medication appears to increase the risk of significant infection after exposure to a number of organisms, including Clostridium difficile, Salmonella, and Campylobacter species. The risk is greater in those taking proton pump inhibitors than with H2 antagonists. Parasitic A number of parasites can cause gastroenteritis. Giardia lamblia is most common, but Entamoeba histolytica, Cryptosporidium spp., and other species have also been implicated. As a group, these agents comprise about 10% of cases in children. Giardia occurs more commonly in the developing world, but this type of illness can occur nearly everywhere. It occurs more commonly in persons who have traveled to areas with high prevalence, children who attend day care, men who have sex with men, and following disasters. Transmission Transmission may occur from drinking contaminated water or when people share personal objects. Water quality typically worsens during the rainy season and outbreaks are more common at this time. In areas with four seasons, infections are more common in the winter. Worldwide, bottle-feeding of babies with improperly sanitized bottles is a significant cause. Transmission rates are also related to poor hygiene, (especially among children), in crowded households, and in those with poor nutritional status. Adults who have developed immunities might still carry certain organisms without exhibiting symptoms. Thus, adults can become natural reservoirs of certain diseases. While some agents (such as Shigella) only occur in primates, others (such as Giardia) may occur in a wide variety of animals. Non-infectious There are a number of non-infectious causes of inflammation of the gastrointestinal tract. Some of the more common include medications (like NSAIDs), certain foods such as lactose (in those who are intolerant), and gluten (in those with celiac disease). Crohns disease is also a non-infectious source of (often severe) gastroenteritis. Disease secondary to toxins may also occur. Some food-related conditions associated with nausea, vomiting, and diarrhea include: ciguatera poisoning due to consumption of contaminated predatory fish, scombroid associated with the consumption of certain types of spoiled fish, tetrodotoxin poisoning from the consumption of puffer fish among others, and botulism typically due to improperly preserved food.In the United States, rates of emergency department use for noninfectious gastroenteritis dropped 30% from 2006 until 2011. Of the twenty most common conditions seen in the emergency department, rates of noninfectious gastroenteritis had the largest decrease in visits in that time period. Pathophysiology Gastroenteritis is defined as vomiting or diarrhea due to inflammation of the small or large bowel, often due to infection. The changes in the small bowel are typically noninflammatory, while the ones in the large bowel are inflammatory. The number of pathogens required to cause an infection varies from as few as one (for Cryptosporidium) to as many as 108 (for Vibrio cholerae). Diagnosis Gastroenteritis is typically diagnosed clinically, based on a persons signs and symptoms. Determining the exact cause is usually not needed as it does not alter the management of the condition.However, stool cultures should be performed in those with blood in the stool, those who might have been exposed to food poisoning, and those who have recently traveled to the developing world. It may also be appropriate in children younger than 5, old people, and those with poor immune function. Diagnostic testing may also be done for surveillance. As hypoglycemia occurs in approximately 10% of infants and young children, measuring serum glucose in this population is recommended. Electrolytes and kidney function should also be checked when there is a concern about severe dehydration. Dehydration A determination of whether or not the person has dehydration is an important part of the assessment, with dehydration typically divided into mild (3–5%), moderate (6–9%), and severe (≥10%) cases. In children, the most accurate signs of moderate or severe dehydration are a prolonged capillary refill, poor skin turgor, and abnormal breathing. Other useful findings (when used in combination) include sunken eyes, decreased activity, a lack of tears, and a dry mouth. A normal urinary output and oral fluid intake is reassuring. Laboratory testing is of little clinical benefit in determining the degree of dehydration. Thus the use of urine testing or ultrasounds is generally not needed. Differential diagnosis Other potential causes of signs and symptoms that mimic those seen in gastroenteritis that need to be ruled out include appendicitis, volvulus, inflammatory bowel disease, urinary tract infections, and diabetes mellitus. Pancreatic insufficiency, short bowel syndrome, Whipples disease, coeliac disease, and laxative abuse should also be considered. The differential diagnosis can be complicated somewhat if the person exhibits only vomiting or diarrhea (rather than both).Appendicitis may present with vomiting, abdominal pain, and a small amount of diarrhea in up to 33% of cases. This is in contrast to the large amount of diarrhea that is typical of gastroenteritis. Infections of the lungs or urinary tract in children may also cause vomiting or diarrhea. Classical diabetic ketoacidosis (DKA) presents with abdominal pain, nausea, and vomiting, but without diarrhea. One study found that 17% of children with DKA were initially diagnosed as having gastroenteritis. Prevention Water, sanitation, hygiene A supply of easily accessible uncontaminated water and good sanitation practices are important for reducing rates of infection and clinically significant gastroenteritis. Personal hygiene measures (such as hand washing with soap) have been found to decrease rates of gastroenteritis in both the developing and developed world by as much as 30%. Alcohol-based gels may also be effective. Food or drink that is thought to be contaminated should be avoided.Breastfeeding is important, especially in places with poor hygiene, as is improvement of hygiene generally. Breast milk reduces both the frequency of infections and their duration. Vaccination Due to both its effectiveness and safety, in 2009 the World Health Organization recommended that the rotavirus vaccine be offered to all children globally. Two commercial rotavirus vaccines exist and several more are in development. In Africa and Asia these vaccines reduced severe disease among infants and countries that have put in place national immunization programs have seen a decline in the rates and severity of disease. This vaccine may also prevent illness in non-vaccinated children by reducing the number of circulating infections. Since 2000, the implementation of a rotavirus vaccination program in the United States has substantially decreased the number of cases of diarrhea by as much as 80 percent. The first dose of vaccine should be given to infants between 6 and 15 weeks of age. The oral cholera vaccine has been found to be 50–60% effective over two years.There are a number of vaccines against gastroenteritis in development. For example, vaccines against Shigella and enterotoxigenic Escherichia coli (ETEC), which are two of the leading bacterial causes of gastroenteritis worldwide. Management Gastroenteritis is usually an acute and self-limiting disease that does not require medication. The preferred treatment in those with mild to moderate dehydration is oral rehydration therapy (ORT). For children at risk of dehydration from vomiting, taking a single dose of the anti vomiting medication metoclopramide or ondansetron, may be helpful, and butylscopolamine is useful in treating abdominal pain. Rehydration The primary treatment of gastroenteritis in both children and adults is rehydration. This is preferably achieved by drinking rehydration solution, although intravenous delivery may be required if there is a decreased level of consciousness or if dehydration is severe. Drinking replacement therapy products made with complex carbohydrates (i.e. those made from wheat or rice) may be superior to those based on simple sugars. Drinks especially high in simple sugars, such as soft drinks and fruit juices, are not recommended in children under five years of age as they may increase diarrhea. Plain water may be used if more specific ORT preparations are unavailable or the person is not willing to drink them. A nasogastric tube can be used in young children to administer fluids if warranted. In those who require intravenous fluids, one to four hours worth is often sufficient. Dietary It is recommended that breast-fed infants continue to be nursed in the usual fashion, and that formula-fed infants continue their formula immediately after rehydration with ORT. Lactose-free or lactose-reduced formulas usually are not necessary. Children should continue their usual diet during episodes of diarrhea with the exception that foods high in simple sugars should be avoided. The BRAT diet (bananas, rice, applesauce, toast and tea) is no longer recommended, as it contains insufficient nutrients and has no benefit over normal feeding.A Cochrane Review from 2020 concludes that probiotics make little or no difference to people who have diarrhea lasting 2 days or longer and that there is no proof that they reduce its duration. They may be useful in preventing and treating antibiotic associated diarrhea. Fermented milk products (such as yogurt) are similarly beneficial. Zinc supplementation appears to be effective in both treating and preventing diarrhea among children in the developing world. Antiemetics Antiemetic medications may be helpful for treating vomiting in children. Ondansetron has some utility, with a single dose being associated with less need for intravenous fluids, fewer hospitalizations, and decreased vomiting. Metoclopramide might also be helpful. However, the use of ondansetron might possibly be linked to an increased rate of return to hospital in children. The intravenous preparation of ondansetron may be given orally if clinical judgment warrants. Dimenhydrinate, while reducing vomiting, does not appear to have a significant clinical benefit. Antibiotics Antibiotics are not usually used for gastroenteritis, although they are sometimes recommended if symptoms are particularly severe or if a susceptible bacterial cause is isolated or suspected. If antibiotics are to be employed, a macrolide (such as azithromycin) is preferred over a fluoroquinolone due to higher rates of resistance to the latter. Pseudomembranous colitis, usually caused by antibiotic use, is managed by discontinuing the causative agent and treating it with either metronidazole or vancomycin. Bacteria and protozoans that are amenable to treatment include Shigella Salmonella typhi, and Giardia species. In those with Giardia species or Entamoeba histolytica, tinidazole treatment is recommended and superior to metronidazole. The World Health Organization (WHO) recommends the use of antibiotics in young children who have both bloody diarrhea and fever. Antimotility agents Antimotility medication has a theoretical risk of causing complications, and although clinical experience has shown this to be unlikely, these drugs are discouraged in people with bloody diarrhea or diarrhea that is complicated by fever. Loperamide, an opioid analogue, is commonly used for the symptomatic treatment of diarrhea. Loperamide is not recommended in children, however, as it may cross the immature blood–brain barrier and cause toxicity. Bismuth subsalicylate, an insoluble complex of trivalent bismuth and salicylate, can be used in mild to moderate cases, but salicylate toxicity is theoretically possible. Epidemiology It is estimated that there were two billion cases of gastroenteritis that resulted in 1.3 million deaths globally in 2015. Children and those in the developing world are most commonly affected. As of 2011, in those younger than five, there were about 1.7 billion cases resulting in 0.7 million deaths, with most of these occurring in the worlds poorest nations. More than 450,000 of these fatalities are due to rotavirus in children under five years of age. Cholera causes about three to five million cases of disease and kills approximately 100,000 people yearly. In the developing world, children less than two years of age frequently get six or more infections a year that result in significant gastroenteritis. It is less common in adults, partly due to the development of acquired immunity.In 1980, gastroenteritis from all causes caused 4.6 million deaths in children, with the majority occurring in the developing world. Death rates were reduced significantly (to approximately 1.5 million deaths annually) by 2000, largely due to the introduction and widespread use of oral rehydration therapy. In the US, infections causing gastroenteritis are the second most common infection (after the common cold), and they result in between 200 and 375 million cases of acute diarrhea and approximately ten thousand deaths annually, with 150 to 300 of these deaths in children less than five years of age. Society and culture Gastroenteritis is associated with many colloquial names, including "Montezumas revenge", "Delhi belly", "la turista", and "back door sprint", among others. It has played a role in many military campaigns and is believed to be the origin of the term "no guts no glory".Gastroenteritis is the main reason for 3.7 million visits to physicians a year in the United States and 3 million visits in France. In the United States gastroenteritis as a whole is believed to result in costs of US$23 billion per year with that due to rotavirus alone resulting in estimated costs of US$1 billion a year. Terminology The first usage of "gastroenteritis" was in 1825. Before this time it was commonly known as typhoid fever or "cholera morbus", among others, or less specifically as "griping of the guts", "surfeit", "flux", "colic", "bowel complaint", or any one of a number of other archaic names for acute diarrhea. Cholera morbus is a historical term that was used to refer to gastroenteritis rather than specifically cholera. Other animals Many of the same agents cause gastroenteritis in cats and dogs as in humans. The most common organisms are Campylobacter, Clostridium difficile, Clostridium perfringens, and Salmonella. A large number of toxic plants may also cause symptoms.Some agents are more specific to a certain species. Transmissible gastroenteritis coronavirus (TGEV) occurs in pigs resulting in vomiting, diarrhea, and dehydration. It is believed to be introduced to pigs by wild birds and there is no specific treatment available. It is not transmissible to humans. See also Enterocolitis References Notes Dolin, Raphael; Mandell, Gerald L.; Bennett, John E., eds. (2010). Mandell, Douglas, and Bennetts principles and practice of infectious diseases (7th ed.). Philadelphia: Churchill Livingstone/Elsevier. ISBN 978-0-443-06839-3. External links Diarrhoea and Vomiting Caused by Gastroenteritis: Diagnosis, Assessment and Management in Children Younger than 5 Years – NICE Clinical Guidelines, No. 84. "Gastroenteritis". MedlinePlus. U.S. National Library of Medicine.
Sialolithiasis	Sialolithiasis (also termed salivary calculi, or salivary stones) is a crystallopathy where a calcified mass or sialolith forms within a salivary gland, usually in the duct of the submandibular gland (also termed "Whartons duct"). Less commonly the parotid gland or rarely the sublingual gland or a minor salivary gland may develop salivary stones. The usual symptoms are pain and swelling of the affected salivary gland, both of which get worse when salivary flow is stimulated, e.g. with the sight, thought, smell or taste of food, or with hunger or chewing. This is often termed "mealtime syndrome". Inflammation or infection of the gland may develop as a result. Sialolithiasis may also develop because of the presence of existing chronic infection of the glands, dehydration (e.g. use of phenothiazines), Sjögrens syndrome and/or increased local levels of calcium, but in many instances the cause is idiopathic (unknown). The condition is usually managed by removing the stone, and several different techniques are available. Rarely, removal of the submandibular gland may become necessary in cases of recurrent stone formation. Sialolithiasis is common, accounting for about 50% of all disease occurring in the major salivary glands and causing symptoms in about 0.45% of the general population. Persons aged 30–60 and males are more likely to develop sialolithiasis. Classification The term is derived from the Greek words sialon (saliva) and lithos (stone), and the Greek -iasis meaning "process" or "morbid condition". A calculus (plural calculi) is a hard, stone-like concretion that forms within an organ or duct inside the body. They are usually made from mineral salts, and other types of calculi include tonsiloliths (tonsil stones) and renal calculi (kidney stones). Sialolithiasis refers to the formation of calculi within a salivary gland. If a calculus forms in the duct that drains the saliva from a salivary gland into the mouth, then saliva will be trapped in the gland. This may cause painful swelling and inflammation of the gland. Inflammation of a salivary gland is termed sialadenitis. Inflammation associated with blockage of the duct is sometimes termed "obstructive sialadenitis". Because saliva is stimulated to flow more with the thought, sight or smell of food, or with chewing, pain and swelling will often get suddenly worse just before and during a meal ("peri-prandial"), and then slowly decrease after eating, this is termed meal time syndrome. However, calculi are not the only reasons that a salivary gland may become blocked and give rise to the meal time syndrome. Obstructive salivary gland disease, or obstructive sialadenitis, may also occur due to fibromucinous plugs, duct stenosis, foreign bodies, anatomic variations, or malformations of the duct system leading to a mechanical obstruction associated with stasis of saliva in the duct.Salivary stones may be divided according to which gland they form in. About 85% of stones occur in the submandibular gland, and 5–10% occur in the parotid gland. In about 0–5% of cases, the sublingual gland or a minor salivary gland is affected. When minor glands are rarely involved, caliculi are more likely in the minor glands of the buccal mucosa and the maxillary labial mucosa. Submandibular stones are further classified as anterior or posterior in relation to an imaginary transverse line drawn between the mandibular first molar teeth. Stones may be radiopaque, i.e. they will show up on conventional radiographs, or radiolucent, where they not be visible on radiographs (although some of their effects on the gland may still be visible). They may also symptomatic or asymptomatic, according to whether they cause any problems or not. Signs and symptoms Signs and symptoms are variable and depend largely upon whether the obstruction of the duct is complete or partial, and how much resultant pressure is created within the gland. The development of infection in the gland also influences the signs and symptoms. Pain, which is intermittent, and may suddenly get worse before mealtimes, and then slowly get better (partial obstruction). Swelling of the gland, also usually intermittent, often suddenly appearing or increasing before mealtimes, and then slowly going down (partial obstruction). Tenderness of the involved gland. Palpable hard lump, if the stone is located near the end of the duct. If the stone is near the submandibular duct orifice, the lump may be felt under the tongue. Lack of saliva coming from the duct (total obstruction). Erythema (redness) of the floor of the mouth (infection). Pus discharging from the duct (infection). Cervical lymphadenitis (infection). Bad breath.Rarely, when stones form in the minor salivary glands, there is usually only slight local swelling in the form of a small nodule and tenderness. Causes There are thought to be a series of stages that lead to the formation of a calculus (lithogenesis). Initially, factors such as abnormalities in calcium metabolism, dehydration, reduced salivary flow rate, altered acidity (pH) of saliva caused by oropharyngeal infections, and altered solubility of crystalloids, leading to precipitation of mineral salts, are involved. Other sources state that no systemic abnormality of calcium or phosphate metabolism is responsible.The next stage involves the formation of a nidus which is successively layered with organic and inorganic material, eventually forming a calcified mass. In about 15-20% of cases the sialolith will not be sufficiently calcified to appear radiopaque on a radiograph, and will therefore be difficult to detect. Other sources suggest a retrograde theory of lithogenesis, where food debris, bacteria or foreign bodies from the mouth enter the ducts of a salivary gland and are trapped by abnormalities in the sphincter mechanism of the duct opening (the papilla), which are reported in 90% of cases. Fragments of bacteria from salivary calculi were reported to be Streptococci species which are part of the normal oral microbiota and are present in dental plaque.Stone formation occurs most commonly in the submandibular gland for several reasons. The concentration of calcium in saliva produced by the submandibular gland is twice that of the saliva produced by the parotid gland. The submandibular gland saliva is also relatively alkaline and mucous. The submandibular duct (Whartons duct) is long, meaning that saliva secretions must travel further before being discharged into the mouth. The duct possesses two bends, the first at the posterior border of the mylohyoid muscle and the second near the duct orifice. The flow of saliva from the submandibular gland is often against gravity due to variations in the location of the duct orifice. The orifice itself is smaller than that of the parotid. These factors all promote slowing and stasis of saliva in the submandibular duct, making the formation of an obstruction with subsequent calcification more likely. Salivary calculi sometimes are associated with other salivary diseases, e.g. sialoliths occur in two thirds of cases of chronic sialadenitis, although obstructive sialadenitis is often a consequence of sialolithiasis. Gout may also cause salivary stones, although in this case they are composed of uric acid crystals rather than the normal composition of salivary stones. Diagnosis Diagnosis is usually made by characteristic history and physical examination. Diagnosis can be confirmed by x-ray (80% of salivary gland calculi are visible on x-ray), by sialogram, or by ultrasound. Treatment Some current treatment options are: Non-invasive: For small stones, hydration, moist heat therapy, NSAIDs (nonsteroidal anti-inflammatory drugs) occasionally, and having the patient take any food or beverage that is bitter and/or sour. Sucking on citrus fruits, such as a lemon or orange, may increase salivation and promote spontaneous expulsion of stones within the size range of 2–10 mm. Some stones may be massaged out by a specialist. Shock wave therapy (Extracorporeal shock wave lithotripsy). Minimally invasive: Sialendoscopy Surgical: An ENT or oral/maxillofacial surgeon may cannulate the duct to remove the stone (sialectomy). A surgeon may make a small incision near the stone to remove it. In some cases when stones continually reoccur the offending salivary duct is removed. Supporting treatment: To prevent infection while the stone is lodged in the duct, antibiotics are sometimes used. Epidemiology The prevalence of salivary stones in the general population is about 1.2% according to post mortem studies, but the prevalence of salivary stones which cause symptoms is about 0.45% in the general population. Sialolithiasis accounts for about 50% of all disease occurring in major salivary glands, and for about 66% of all obstructive salivary gland diseases. Salivary gland stones are twice as common in males as in females. The most common age range in which they occur is between 30 and 60, and they are uncommon in children. References == External links ==
Epilepsia partialis continua	Epilepsia partialis continua is a rare type of brain disorder in which a patient experiences recurrent motor epileptic seizures that are focal (hands and face), and recur every few seconds or minutes for extended periods (days to years). It is sometimes called Kozhevnikovs epilepsia named after Russian psychiatrist Aleksei Yakovlevich Kozhevnikov who first described this type of epilepsy. Signs and symptoms During these seizures, there is repetitive focal myoclonus or Jacksonian march. After a seizure has subsided, Todds phenomenon may be observed, which includes transient unilateral weakness. Causes There are numerous causes for this kind of seizure and they differ depending somewhat on the age at which the seizures begin. Epilepsy most often occurs at the extremes of life – in childhood or in very old age – but can develop at any time throughout ones life. Although these seizures are usually due to large, acute brain lesions resulting from strokes in adults and focal cortical inflammatory processes in children (Rasmussens encephalitis), possibly caused by chronic viral infections, edema, or autoimmune processes. They are very medication and therapy-resistant, and the primary therapeutic goal is to stop secondary generalization. There are also many other reasons why these seizures occur. For example, they could be due to genetics, infections, or problems with brain development. Commonly the cause is unknown. Genetic background determines such features as height, eye color, and potential to develop certain diseases like diabetes, but it also determines all the chemicals and structures that make up the brain, therefore playing a role in epilepsia partialis continua. The chemicals and structures that make up the brain have similarities across different people, but they vary in certain enzymes and receptors. These variations are not usually enough to cause a problem, but occasionally they do. For example, if a person has a mutation in a gene that creates the sodium channel (a part of the neuron required for firing) it makes it easier for neuronal firing to get out of control. An infection of the brain (encephalitis) can also be a contributing factor. Although this sort of infection is uncommon it can be due to a virus, bacterium, or (very rarely) fungus. If a seizure happens during the infection itself, the person most likely doesnt have epilepsy but has "symptomatic seizures" or seizures occurring because of a known injury to the brain. Once the infection is stopped the seizures will stop. Another more common infection is "meningitis", infection of the membranes surrounding the brain. Since this infection does not directly involve the brain it might not appear as a possible cause of epilepsy, but has been shown that meningitis can cause epilepsy, which would give rise to the possibility of developing epilepsy partialis continua. These infections are most likely to result in epilepsy when they occur at an early age. Problems with brain development can also be a factor. The brain undergoes a complicated process during development in which neurons are born and must travel to the surface of the brain. Here they wind up carefully placed in six distinct layers of the cerebral cortex. Throughout the brain, the placement of these neurons is normally quite precise. If this system doesnt work exactly right, neurons can develop outside their appropriate areas. If this happens then the firing or circuitry of the brain is not right, and an abnormal, epileptic circuit can result. Treatment Identification of the underlying cause plays an important role in treatment. Brain abscesses or tumors can be—at least temporarily or partially, if not fully and permanently—surgically treated and chemotherapy and/or radiotherapy is given to the patient. If seizures do continue, various anticonvulsant medication regimens that can be tolerated by the patient can be tested and if need be, administered, either orally, or in emergency conditions such as status epilepticus after tonic-clonic (grand mal) seizures, intravenously. If stroke or other similar, transient disorders occur (cerebrovascular accident, or transient ischemic attack, TIA), then neurological imaging of the affected lobes or hemispheres of the brain can be performed (CT, MRI, PET, etc.) and, if not absolutely contraindicated, antithrombolytic therapy might be given if it can be tolerated due to the seizures; if a hemorrhagic stroke has occurred and surgery can be performed to cauterize the vessel or otherwise stop the bleeding, it will be attempted if it can be done safely. References == External links ==
Greig cephalopolysyndactyly syndrome	Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux). Presentation The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures and developmental delay. Pathophysiology Greig cephalopolysyndactyly syndrome is a chromosomal condition related to chromosome 7. Mutations in the GLI3 gene cause Greig cephalopolysyndactyly syndrome. The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth.Different genetic changes involving the Gli3 gene can cause Greig cephalopolysyndactyly syndrome. In some cases, the condition results from a chromosomal abnormality, such as a large deletion or translocation of genetic material, in the region of chromosome 7 that contains the GLI3 gene. In other cases, a mutation in the GLI3 gene itself is responsible for the disorder. Each of these genetic changes prevents one copy of the gene in each cell from producing any functional protein. It remains unclear how a reduced amount of this protein disrupts early development and causes the characteristic features of Greig cephalopolysyndactyly syndrome.This condition is inherited in an autosomal dominant pattern, which means the defective gene is located on an autosome, and only one copy of the defective GLI3 gene is sufficient to cause the disorder. In cases of dominant inheritance, an affected person inherits the genetic mutation or chromosomal abnormality from one affected parent.Rare instances of this disorder are sporadic, and occur in people with no history of the condition in their family. Diagnosis The disease is not easily definable. The main form of diagnosis is presumptive, if the person has the usual triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, macrocephaly, and hypertelorism. However, a definitive diagnosis can be made if there is a phenotype that is caused by a Gcps and a Gli3 gene mutation. It can also be made if the person has a family member or relative with the disease. Possibly, antenatal ultrasound can detect macrocephaly, and a high-resolution ultrasound can detect polydactyly and syndactyly. There are a lot of differential diagnoses, including over 100 syndromes and disorders that can cause polydactyly. However, there are a few diseases with an overlap that is significant. These diseases include: acrocallosal syndrome, carpenter syndrome, and Gorlin syndrome. Management The main treatment is surgery to fix the abnormalities in the limbs, like syndactyly. It is less important to repair the feet surgically, as it can cause complications, and it is not aesthetically important compared to the hands. If there is polydactyly with an extra digit that is fully functional, then the digit can stay. Some people may have intellectual disability, though this condition usually causes only mild impairment. Developmental assistance and early specialist intervention should be offered in the case of intellectual disability. People should be tested as an individual and be given proper assistance. Prognosis The outlook is usually good in the usual case of GCPS. Mostly, the biggest problem associated with the condition in mild intellectual impairment. Eponym The condition is named for David Middleton Greig FRSE. References External links Greig cephalopolysyndactyly syndrome at NLM Genetics Home Reference GeneReview/NIH/UW entry on Greig Cephalopolysyndactyly Syndrome
Iridodialysis	Iridodialysis is a localized separation or tearing away of the iris from its attachment to the ciliary body. Symptoms and signs Those with small iridodialyses may be asymptomatic and require no treatment, but those with larger dialyses may have corectopia or polycoria and experience monocular diplopia, glare, or photophobia. Iridodialyses often accompany angle recession and may cause glaucoma or hyphema. Hypotony may also occur. Complications Those with traumatic iridodialyses (particularly by blunt trauma) are at high risk for angle recession, which may cause glaucoma. This is typically seen about 100 days after the injury, and as such is sometimes called "100-day glaucoma". Medical or surgical treatment to control the IOP may be required if glaucoma is present. Soft, opaque contact lenses may be used to improve cosmesis and reduce the perception of double vision. Causes Iridodialyses are usually caused by blunt trauma to the eye, but may also be caused by penetrating eye injuries. An iridodialysis may be an iatrogenic complication of any intraocular surgery and at one time they were created intentionally as part of intracapsular cataract extraction. Iridodialyses have been reported to have occurred from boxing, airbag deployments, high-pressure water jets, elastic bungee cords, bottle caps opened under pressure, water balloons, fireworks, and various types of balls. Treatment Iridodialysis causing an associated hyphema has to be carefully managed, and recurrent bleeds should be prevented by strict avoidance of all sporting activities. Management typically involves observation and bed rest. Red blood cells may decrease the outflow of aqueous humor, therefore the eye pressure should be kept low by giving oral acetazolamide (a diuretic given to reduce intraoccular pressure). Accidental trauma during sleep should be prevented by patching with an eye shield during night time. Avoid giving aspirin, heparin/warfarin and observe daily for resolution or progression. A large hyphema may require careful anterior chamber washout. Rebleeds may require additional intervention and therapy. Later, surgical repair may be considered for larger avulsions causing significant double vision, cosmesis or glare symptoms. Surgical repair is usually done by 10-0 prolene suture taking the base of iris avulsion and suturing it to the scleral spur and ciliary body junction. See also Eye injury References == External links ==
Fibromatosis colli	Fibromatosis colli (FMC), also termed sternocleidomastoid tumor of infancy, pseudotumor of infancy, and infancy sternocleidomastoid pseudotumor, is an uncommon (incidence: 0.4%-1.3% of live births), congenital tumor in one of the two sternocleidomastoid neck muscles although rare cases have presented with a FMC tumor in both sternocleidomastoid muscles. A tumor is here defined as a growth of tissue that is not coordinated with the normal surrounding tissue and persists in growing even if the original trigger for its growth is removed. FMC tumors are benign growths that may cause disfigurements but are not cancers and do not metastasize (i.e. spread) to distant tissues.As judged by microscopic cytology analyses, fibromatosis colli tumors consist of spindle-shaped fibroblasts (i.e. the most common cell type in connective tissue) located in a background of collagen fibers, decomposing skeletal muscle fibers, and, in some cases, regenerating skeletal muscle fibers. The fibroblasts have a completely normal appearance with no evidence suggesting that they are malignant. The World Health Organization, 2020, classified fibromatosis colli as in the category of benign fibroblastic and myofibroblastic tumors.In the majority of cases, FMC tumors decrease in size and completely resolve by the newborns second year. If left untreated, however, a significant percentage of cases progress to, and are the most frequent cause of, congenital muscular torticollis, i.e. an abnormal, asymmetrical head or neck position commonly called wry neck. Untreated FMC tumors may also progress to facial asymmetry, plagiocephaly (i.e. flattened head), permanent loss of neck mobility, scoliosis (i.e. sidewise curvature of the spine), or other structural disfigurements that result from compensatory mechanisms. Presentation FMC tumors most commonly present as slow-growing, firm, mobile, nontender, spindle-shaped masses in the lower two-thirds of the sternocleidomastoid muscle of infants within 8 weeks (average: 24 days) of delivery. At diagnosis, these infants heads may tilt toward the side with the mass while their chins tilt to the opposite, uninvolved side. This tilting is due to sternocleidomastoid muscle contracture. FMC tumors are more common in males and the right sternocleidomastoid muscle although very rare cases present with bilateral tumors. Untreated, the masses may continue to grow for weeks after birth but then stabilize, start regressing after 4–8 months of life, and over the ensuing 1–2 years typically fully resolve. In three studies, >25%, >50% and >80% of these infants have had difficult deliveries such as a breech birth, delivery requiring forceps, primigravida birth (i.e. mothers first child), prolonged, difficult labor, or delivery by Caesarean section. From 6-20% of newborns with fibromatosis colli also present with other congenital lesions such as hip dysplasia or, less commonly, facial asymmetry. Pathology Microscopic histopathological analyses of biopsied FMC tumor tissues typically find benign-appearing, spindle-shaped fibroblasts, decomposing skeletal muscle fibers, and, in some cases, regenerating skeletal muscle fibers in a collagen fiber-containing background. If necessary, these tumors are typically diagnosed by microscopic examination of fine-needle aspiration samples rather than the more invasive approach of tumor biopsy sampling. The asperates show scant to moderately cellular, scattered, oval-shaped to spindle-shaped fibroblasts, naked nuclei (i.e. cell nuclei virtually devoid of other cell elements such as the cytoplasm), wisps of collagen, atrophic, degenerating muscle fibers, regenerating muscle fibers, and intact skeletal muscle cells containing multiple nuclei. There is no evidence of inflammation, hemorrhage, cell necrosis, or rapidly dividing and/or proliferating cells. Etiology It has been postulated that the FMC tumor mass itself is a remnant of a hematoma caused by tissue injury occurring during delivery. However, there are no features of hematomas (e.g. hemosiderin released by dying red blood cells) in theses lesions at diagnosis and no evidence of trauma (e.g. overlying skin changes or discolorations) at birth in infants who later present with FMC tumors. It has also been suggested that venous outflow obstruction occurring in the fetus while in the uterus or during delivery leads to degeneration of sternocleidomastoid muscle fibers and subsequent fibrosis of the damaged areas. Finally, it has been suggested that an injury due to poor fetal head positioning in the uterus produces a compartment syndrome-like pressure-induced injury to the sternocleidomastoid muscle that results in muscle cell death followed by tissue fibrosis and the usual pathology of FMC tumors. Diagnosis The recommended first step after clinically detecting a sternocleidomastoid mass in a newborn infant is Doppler ultrasonography combined with duplex ultrasonography. This method commonly reveals diagnostic (up to 100% sensitivity rates) findings of diffuse or focal enlargement of sternocleidomastoid muscle that has no cysts or other ultrasonography-detected abnormalities. If these imaging findings are not diagnostic, magnetic resonance imaging may clarify the diagnosis. If the findings still remain unclear, microscopic examination of fine needle asperates taken from the tumor will, when combined with the imaging findings, the lesion’s natural history, and its clinical presentation, likely confirm the diagnosis of FMC in virtually all cases. Treatment and prognosis Prompt diagnosis and treatment of FMS is crucial for avoiding the impairments that may follow long-term mal-positioning of infants head such as permanent facial asymmetry, flattened head, loss of neck mobility, and scoliosis. About 95% of infants with minimal limitations in their heads mobility show improvements in this mobility after 4 weeks of an active home stimulation program (i.e. observation, massage, and active and passive stretching) while ~91% of infants with more severe movement limitations show good results after 3 sessions of targeted physiotherapy over a 3–4 month period. The recommended treatment for infants who show no improvements in mobility after 1 year of physical therapy or who initially present at >12 months of age is surgical tenotomy (i.e. cutting) of one of the tendons on the involved sternocleidomastoid muscle. Tenotomy may use the open surgical (i.e. cutting of skin) approach or endoscopic (i.e. percutaneous) approach. The overall prognosis of FMS tumors is good using these treatment measures.Infants presenting with FMS should be examined for the presence of hip dysplasia. See also Skin lesion == References ==
Open fracture	An open fracture, also called a compound fracture, is a type of bone fracture in orthopedics that is frequently caused by high energy trauma. It is a bone fracture associated with a break in the skin continuity which can cause complications such as infection, malunion, and nonunion. Gustilo open fracture classification is the most commonly used method to classify open fractures, to guide treatment and to predict clinical outcomes. Advanced trauma life support is the first line of action in dealing with open fractures and to rule out other life-threatening condition in cases of trauma. Cephalosporins are generally the first line of antibiotics. The antibiotics are continued for 24 hours to minimize the risk of infections. Therapeutic irrigation, wound debridement, early wound closure and bone fixation are the main management of open fractures. All these actions aimed to reduce the risk of infections. Causes Open fractures can occur due to direct impacts such as high-energy physical forces (trauma), motor vehicular accidents, firearms, and falls from height. Indirect mechanisms include twisting (torsional injuries) and falling from a standing position. These mechanisms are usually associated with substantial degloving of the soft-tissues, but can also have a subtler appearance with a small poke hole and accumulation of clotted blood in the tissues. Depending on the nature of the trauma, it can cause different types of fractures: Common fractures Result from significant trauma to the bone. This trauma can come from a variety of forces – a direct blow, axial loading, angular forces, torque, or a mixture of these. Pathological fractures Result from minor trauma to diseased bone. These preexisting processes include metastatic lesions, bone cysts, advanced osteoporosis, etc. Fracture-dislocations Severe injury in which both fracture and dislocation take place simultaneously. Gunshot wounds Caused by high-speed projectiles, they cause damage as they go through the tissue, through secondary shock wave and cavitation. Diagnosis The initial evaluation for open fractures is to rule out any other life-threatening injuries. Advanced Trauma Life Support (ATLS) is the initial protocol to rule out such injuries. Once the patient is stabilised, orthopedic injuries can be evaluated. Mechanism of injury is important to know the amount energy that is transferred to the patient and the level of contamination. Every limb should be exposed to evaluate any other hidden injuries. Characteristics of the wound should be noted in detail. Neurology and the vascular status of the affected limb are important to rule out any nerve or blood vessels injuries. High index of suspicion of compartment syndrome should be maintained for leg and forearm fractures.There are a number of classification systems attempting to categorise open fractures such as Gustilo open fracture classification, Tscherne classification, and Müller AO Classification of fractures. However, Gustilo open fracture classification is the most commonly used classification system. Gustilo system grades the fracture according to energy of injury, soft tissue damage, level of contamination, and comminution of fractures. The higher the grade, the worse the outcome of the fracture. However, Gustilo system is not without its limitations. The system has limited interobserver reliability at 50% to 60%. The size of injury on the skin surface does not necessarily reflect the extent of deep underlying soft tissue injury. Therefore, the true grading of Gustilo can only be done in operating theatre. Management Acute management Urgent interventions, including therapeutic irrigation and wound debridement, are often necessary to clean the area of injury and minimize the risk of infection. Other risks of delayed intervention include long-term complications, such as deep infection, vascular compromise and complete limb loss. After wound irrigation, dry or wet gauze should be applied to the wound to prevent bacterial contamination. Taking photographs of the wound can help to reduce the need of multiple examinations by different doctors, which could be painful. Limb should be reduced and placed in a well-padded splint for immobilization of fractures. Pulses should be documented before and after reduction.Wound cultures are positive in 22% of pre-debridement cultures and 60% of post-debridement cultures of infected cases. Therefore, pre-operative cultures no longer recommended. The value of post-operative cultures is unknown. Tetanus prophylaxis is routinely given to enhance immune response against Clostridium tetani. Anti-tetanus immunoglobulin is only indicated for those with highly contaminated wounds with uncertain vaccination history. Single intramuscular dose of 3000 to 5000 units of tetanus immunoglobulin is given to provide immediate immunity.Another important clinical decision during acute management of open fractures involves the effort to avoid preventable amputations, where functional salvage of the limb is clearly desirable. Care must be taken to ensure this decision is not solely based on an injury severity tool score, but rather a decision made following a full discussion of options between doctors and the person, along with their family and care team. Antibiotics Administration of antibiotics as soon as possible is necessary to reduce the risk of infection. However, antibiotics may not provide necessary benefits in open finger fractures and low velocity firearms injury. First generation cephalosporin (cefazolin) is recommended as first line antibiotics for the treatment of open fractures. The antibiotic is useful against gram positive cocci and gram negative rods such as Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae. To extend the coverage of antibiotics against more bacteria in Type III Gustilo fractures, combination of first generation cephalosporin and aminoglycoside (gentamicin or tobramycin) or a third generation cephalosporin is recommended to cover against nosocomial gram negative bacilli such as Pseudomonas aeruginosa. Adding penicillin to cover for gas gangrene caused by anaerobic bacteria Clostridium perfringens is a controversial practice. Studies has shown that such practice may not be necessary as the standard antibiotic regimen is enough to cover for Clostridial infections. Antibiotic impregnated devices such as tobramycin impregnated Poly(methyl methacrylate) (PMMA) beads and antibiotic bone cement are helpful in reducing rates of infection. The use of absorbable carriers with implant coatings at the time of surgical fixation is also an effective means of delivering local antibiotics.There has been no agreement on the optimal duration of antibiotics. Studies has shown that there is no additional benefits of risk of infection when giving antibiotics for one day, when compared to giving antibiotics for three days or five days. However, at present, there is only low to moderate evidence for this and more research is needed. Some authors recommended that antibiotics to be given for three doses for Gustilo Grade I fractures, for one day after wound closure in Grade II fractures, three days in Grade IIIA fractures, and three days after wound closure for Grade IIIB and IIIC. Wound irrigation There has been no agreement for the optimal solution for wound irrigation. Studies found out that there is no difference in infection rates by using normal saline or other various forms of water (distilled, boiled, or tap). There is also no difference in infection rates when using normal saline with castile soap compared with normal saline together with bacitracin in irrigating wounds. Studies also have shown that there is no difference in infection rates using low pressure pulse lavage (LPPL) when compared to high pressure pulse lavage (HPPL) in irrigating wounds. Optimal amount of fluid for irrigation also has not been established. It is recommended that the amount of irrigation solution to be determined by the severity of the fracture, with 3 litres for type I fractures, 6 litres for type II fractures, and 9 litres for type III fractures. Wound debridement The purpose of wound debridement is to remove all contaminated and non-viable tissues including skin, subcutaneous fat, muscles and bones. Viability of bones and soft tissues are determined by their capacity to bleed. Meanwhile, the viability of muscles is determined by colour, contractility, consistency, and their capacity to bleed. The optimal timing of performing wound debridement and closure is debated and dependent on the severity of the injury, resources and antibiotics available, and individual needs. Debridement time can vary from 6 to 72 hours, and closure time can be immediate (less than 72 hours) or delayed (72 hours to up to 3 months). There is no difference in infection rates for performing surgery within 6 hours of injury when compared to until 72 hours after injury. Surgical management Early fracture immobilisation and fixation helps to prevent further soft tissue injury and promotes wound and bone healing. This is especially important in the treatment of intraarticular fractures where early fixation allows early joint motion to prevent joint stiffness. Fracture management depends on the persons overall well-being, fracture pattern and location, and the extent of soft tissue injury. Both reamed and unreamed intramedullary nailing are accepted surgical treatments for open tibial fracture. Both techniques have similar rates of postoperative healing, postoperative infection, implant failure and compartment syndrome. Unreamed intramedullary nailing is advantageous because it has a lower incidence of superficial infection and malunion compared to external fixation. However, unreamed intramedullary nailing can result in high rates of hardware failure if a persons weight bearing after surgery is not closely controlled. Compared to external fixation, unreamed intramedullary nailing has similar rates of deep infection, delayed union and nonunion following surgery. For open tibial fractures in children, there is an increasing trend of using orthopedic cast rather than external fixation. Bone grafting is also helpful in fracture repair. However, internal fixation using plates and screws is not recommended as it increase the rate of infection. Amputation is a last resort intervention, and is determined by factors such as tissue viability and coverage, infection, and the extent of damage to the vascular system. Wound management Early wound closure is recommended to reduce the rates hospital-acquired infection. For Grade I and II fractures, wound can be healed by secondary intention or through primary closure. There is conflicting evident to suggest the effectiveness of Negative-pressure wound therapy (vacuum dressing), with several sources citing a decreased risk in infection, and others suggesting no proven benefit. Epidemiology Crush injuries are the most common form of injuries, followed by falls from standing height, and road traffic accidents. Open fractures tend to occur more often in males than females at the ratio of 7 to 3 and the age of onset of 40.8 and 56 years respectively. In terms of anatomy location, fractures of finger phalanges are the most common one at the rate of 14 per 100,000 people per year in the general population, followed by fracture of tibia at 3.4 per 100,000 population per year, and distal radius fracture at 2.4 per 100,000 population per year. Infection rates for Gustilo Grade I fractures is 1.4%, followed by 3.6% for Grade II fractures, 22.7% for Grade IIIA fractures, and 10 to 50% of Grade IIIB and IIIC fractures. History Before the 1850s, surgeons usually amputated the limbs for those with open fractures, as it was associated with severe sepsis and gangrene which can be life-threatening. It was only until the 20th century, when Joseph Lister adopted the aseptic technique in surgeries, that the rate of death from open fractures reduced from 50% to 9%. == References ==
Vibratory angioedema	Vibratory angioedema is a form of physical urticaria that may be an inherited autosomal dominant trait, or may be acquired after prolonged exposure to occupational vibration.: 155 See also Urticaria Skin lesion List of cutaneous conditions == References ==
Familial nasal acilia	Familial nasal acilia is a rare congenital defect which is characterized by the complete absence of cilia on the epithelial cells of the respiratory tract. Symptoms are common within ones family and start as soon as one is born, with signs such as respiratory distress, dyspnea, lobar atelectasis, bronchiectasis and neo-natal pneumonia. Other symptoms that occur later in life include chronic moist coughing, chronic sinusitis, chronic otitis media, chronic rhinitis, and recurrence of upper and lower respiratory tract infections.Exact prevalence is unknown, OrphaNet estimates this condition to affect less than 1 out of every million people worldwide. R Soferman et al. described this disorder to be "autosomal recessive". == References ==
Idiopathic pneumonia syndrome	Idiopathic pneumonia syndrome is a set of pneumonia-like symptoms that occur with no sign of infection in the lung. Idiopathic pneumonia syndrome is a serious condition that can occur after a stem cell transplant. It occurs between 2.2 and 15 percent of hematopoietic stem cell transplants. The incubation period ranges between 4 and 106 days, but mostly is about 22 days from transplant. Symptoms The symptoms are like pneumonia, and include fever, chills, coughing, and breathing problems. Lack of oxygen may also occur. Risk factors Risk factors for IPS can be old age, graft vs host disease, multi organ failure, and multiple organ failure. Diagnosis Treatment Treatment is only supportive, with steroids showing no effect. The need for mechanical ventilation is indicative of a poor prognosis. Steroids are often used, though often without effect. References Idiopathic pneumonia syndrome entry in the public domain NCI Dictionary of Cancer Terms This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms".
Inguinal lymphadenopathy	Inguinal lymphadenopathy causes swollen lymph nodes in the groin area. It can be a symptom of infective or neoplastic processes. Infective aetiologies include Tuberculosis, HIV, non-specific or reactive lymphadenopathy to recent lower limb infection or groin infections. Another notable infectious cause is Lymphogranuloma venereum, which is a sexually transmitted infection of the lymphatic system. Neoplastic aetiologies include lymphoma, leukaemia and metastatic disease from primary tumours in the lower limb, external genitalia or perianal region and melanoma. References Ferrer R (October 1998). "Lymphadenopathy: differential diagnosis and evaluation". Am Fam Physician. 58 (6): 1313–20. PMID 9803196. Further reading Principles and Practice of Infectious Diseases. Elsevier Health Sciences. 2014. ISBN 9781455748013. Retrieved 21 December 2017.
Hypoparathyroidism	Hypoparathyroidism is decreased function of the parathyroid glands with underproduction of parathyroid hormone (PTH). This can lead to low levels of calcium in the blood, often causing cramping and twitching of muscles or tetany (involuntary muscle contraction), and several other symptoms. It is a very rare disease. The condition can be inherited, but it is also encountered after thyroid or parathyroid gland surgery, and it can be caused by immune system-related damage as well as a number of rarer causes. The diagnosis is made with blood tests, and other investigations such as genetic testing depending on the results. The primary treatment of hypoparathyroidism is calcium and vitamin D supplementation. Calcium replacement or vitamin D can ameliorate the symptoms but can increase the risk of kidney stones and chronic kidney disease. Additionally, injectable medications such as recombinant human parathyroid hormone or teriparatide may be given by injection to replace the missing hormone. Signs and symptoms The main symptoms of hypoparathyroidism are the result of the low blood calcium level, which interferes with normal muscle contraction and nerve conduction. As a result, people with hypoparathyroidism can experience paresthesia, an unpleasant tingling sensation around the mouth and in the hands and feet, as well as muscle cramps and severe spasms known as "tetany" that affect the hands and feet. Many also report a number of subjective symptoms such as fatigue, headaches, bone pain and insomnia. Crampy abdominal pain may occur. Physical examination of someone with hypocalcemia may show tetany, but it is also possible to provoke tetany of the facial muscles by tapping on the facial nerve (a phenomenon known as Chvosteks sign) or by using the cuff of a sphygmomanometer to temporarily obstruct the blood flow to the arm (a phenomenon known as Trousseaus sign of latent tetany).A number of medical emergencies can arise in people with low calcium levels. These are seizures, severe irregularities in the normal heart beat, as well as spasm of the upper part of the airways or the smaller airways known as the bronchi (both potentially causing respiratory failure). Related conditions Causes Hypoparathyroidism can have the following causes: Removal of, or trauma to, the parathyroid glands due to thyroid surgery (thyroidectomy), parathyroid surgery (parathyroidectomy) or other surgical interventions in the central part of the neck (such as operations on the larynx and/or pharynx) is a recognized cause. It is the most common cause of hypoparathyroidism. Although surgeons generally make attempts to spare normal parathyroid glands at surgery, inadvertent injury to the glands or their blood supply is still common. When this happens, the parathyroids may cease functioning. This is usually temporary but occasionally long term (permanent). Kenny-Caffey Syndrome Autoimmune invasion and destruction is the most common non-surgical cause. It can occur as part of autoimmune polyendocrine syndromes. Hemochromatosis can lead to iron accumulation and consequent dysfunction of a number of endocrine organs, including the parathyroids. Absence or dysfunction of the parathyroid glands is one of the components of chromosome 22q11 microdeletion syndrome (other names: DiGeorge syndrome, Schprintzen syndrome, velocardiofacial syndrome). Magnesium deficiency A defect in the calcium receptor leads to a rare congenital form of the disease Idiopathic (of unknown cause) Occasionally due to other hereditary causes (e.g. Barakat syndrome (HDR syndrome) a genetic development disorder resulting in hypoparathyroidism, sensorineural deafness, and kidney disease) Mechanism The parathyroid glands are so named because they are usually located behind the thyroid gland in the neck. They arise during fetal development from structures known as the third and fourth pharyngeal pouch. The glands, usually four in number, contain the parathyroid chief cells that sense the level of calcium in the blood through the calcium-sensing receptor and secrete parathyroid hormone. Magnesium is required for PTH secretion. Under normal circumstances, the parathyroids secrete PTH to maintain a calcium level within normal limits, as calcium is required for adequate muscle and nerve function (including the autonomic nervous system). PTH acts on several organs to increase calcium levels. It increases calcium absorption in the bowel, while in the kidney it prevents calcium excretion and increases phosphate release and in bone it increases calcium through bone resorption. Diagnosis Diagnosis is by measurement of calcium, serum albumin (for correction) and PTH in blood. If necessary, measuring cAMP (cyclic AMP) in the urine after an intravenous dose of PTH can help in the distinction between hypoparathyroidism and other causes.Differential diagnoses are: Pseudohypoparathyroidism (normal PTH levels but tissue insensitivity to the hormone, associated with intellectual disability and skeletal deformities) and pseudopseudohypoparathyroidism. Vitamin D deficiency or hereditary insensitivity to this vitamin (X-linked dominant). Malabsorption Kidney disease Medication: steroids, diuretics, some antiepileptics.Other tests include ECG for abnormal heart rhythms, and measurement of blood magnesium levels. Treatment Severe hypocalcaemia, a potentially life-threatening condition, is treated as soon as possible with intravenous calcium (e.g. as calcium gluconate). Generally, a central venous catheter is recommended, as the calcium can irritate peripheral veins and cause phlebitis. In the event of a life-threatening attack of low calcium levels or tetany (prolonged muscle contractions), calcium is administered by intravenous (IV) infusion. Precautions are taken to prevent seizures or larynx spasms. The heart is monitored for abnormal rhythms until the person is stable. When the life-threatening attack has been controlled, treatment continues with medicine taken by mouth as often as four times a day.Long-term treatment of hypoparathyroidism is with vitamin D analogs and calcium supplementation, but may be ineffective in some due to potential renal damage. The N-terminal fragment of parathyroid hormone (PTH 1-34) has full biological activity. The use of pump delivery of synthetic PTH 1-34 provides the closest approach to physiologic PTH replacement therapy. Injections of recombinant human parathyroid hormone are available as treatment in those with low blood calcium levels. See also Hyperparathyroidism References == External links ==
White sponge nevus	White sponge nevus (WSN) is an autosomal dominant condition of the oral mucosa (the mucous membrane lining of the mouth). It is caused by a mutations in certain genes coding for keratin, which causes a defect in the normal process of keratinization of the mucosa. This results in lesions which are thick, white and velvety on the inside of the cheeks within the mouth. Usually, these lesions are present from birth or develop during childhood. The condition is entirely harmless, and no treatment is required. Signs and symptoms It presents itself in the mouth, most frequently as a thick, bilateral, symmetrical white plaques with a spongy, corrugated or velvety texture. Most usually, the lesions are on the buccal mucosa, but sometimes on the labial mucosa, alveolar ridge, floor of the mouth, ventral surface of the tongue or soft palate. The gingival margin and dorsum of the tongue are almost never affected. Less commonly, sites outside the mouth are affected, including the nasal, esophageal, laryngeal, anal and genital mucosae. It usually is present from birth, or develops during childhood. Rarely, the lesions may develop during adolescence. Apart from the appearance of the affected areas, there are usually no other signs or symptoms. Pathophysiology WSN is caused by a mutation of the keratin 4 or keratin 13 genes, located respectively at human chromosomes 12q13 and 17q21-q22. The condition is inherited in an autosomal dominant manner. This indicates that the defective gene responsible for a disorder is located on an autosome (chromosomes 12 and 17 are autosomes), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. Diagnosis Differential diagnosis It is often mistaken for leukoplakia.The differential diagnosis also includes hyperplastic candidiasis and frictional keratosis Classification The ICD-10 lists WSN under "other congenital malformations of mouth". It could be classified as a skin condition, or more precisely as a genodermatosis (a genetically determined skin disorder). Treatment There is no treatment, but because this is a benign condition with no serious clinical complications, prognosis is excellent. See also Oral melanosis List of cutaneous conditions caused by mutations in keratins Hereditary benign intraepithelial dyskeratosis References External links White sponge nevus of cannon; Leukokeratosis, hereditary mucosal at NIHs Office of Rare Diseases
Brain herniation	Brain herniation is a potentially deadly side effect of very high pressure within the skull that occurs when a part of the brain is squeezed across structures within the skull. The brain can shift across such structures as the falx cerebri, the tentorium cerebelli, and even through the foramen magnum (the hole in the base of the skull through which the spinal cord connects with the brain). Herniation can be caused by a number of factors that cause a mass effect and increase intracranial pressure (ICP): these include traumatic brain injury, intracranial hemorrhage, or brain tumor.Herniation can also occur in the absence of high ICP when mass lesions such as hematomas occur at the borders of brain compartments. In such cases local pressure is increased at the place where the herniation occurs, but this pressure is not transmitted to the rest of the brain, and therefore does not register as an increase in ICP.Because herniation puts extreme pressure on parts of the brain and thereby cuts off the blood supply to various parts of the brain, it is often fatal. Therefore, extreme measures are taken in hospital settings to prevent the condition by reducing intracranial pressure, or decompressing (draining) a hematoma which is putting local pressure on a part of the brain. Signs and symptoms Brain herniation frequently presents with abnormal posturing, a characteristic positioning of the limbs indicative of severe brain damage. These patients have a lowered level of consciousness, with Glasgow Coma Scores of three to five. One or both pupils may be dilated and fail to constrict in response to light. Vomiting can also occur due to compression of the vomiting center in the medulla oblongata. Severe headaches and seizures as a result of increased intracranial pressure are not uncommon. Cardiovascular and pulmonary symptoms may also be present as the brain loses function, but might also be associated with bleeding. They can include: hypertension, respiratory depression, arrhythmia and in severe cases cardiac arrest. Causes Causes of brain herniation include: Brain edema Hematoma Stroke Tumour Infection Classification The tentorium is an extension of the dura mater that separates the cerebellum from the cerebrum. There are two major classes of herniation: supratentorial and infratentorial. Supratentorial refers to herniation of structures normally found above the tentorial notch, and infratentorial refers to structures normally found below it. Supratentorial herniation1) Uncal (transtentorial) 2) Central 3) Cingulate (subfalcine/transfalcine) 4) Transcalvarial 5) Tectal (posterior) Infratentorial herniation6) Upward (upward cerebellar or upward transtentorial) 7) Tonsillar (downward cerebellar) Uncal herniation In uncal herniation, a common subtype of transtentorial herniation, the innermost part of the temporal lobe, the uncus, can be squeezed so much that it moves towards the tentorium and puts pressure on the brainstem, most notably the midbrain. The tentorium is a structure within the skull formed by the dura mater of the meninges. Tissue may be stripped from the cerebral cortex in a process called decortication.The uncus can squeeze the oculomotor nerve (a.k.a. CN III), which may affect the parasympathetic input to the eye on the side of the affected nerve, causing the pupil of the affected eye to dilate and fail to constrict in response to light as it should. Pupillary dilation often precedes the somatic motor effects of CN III compression called oculomotor nerve palsy or third nerve palsy. This palsy presents as deviation of the eye to a "down and out" position due to loss of innervation to all ocular motility muscles except for the lateral rectus (innervated by abducens nerve (a.k.a. CN VI) and the superior oblique (innervated by trochlear nerve a.k.a. CN IV). The symptoms occur in this order because the parasympathetic fibers surround the motor fibers of CN III and are hence compressed first.Compression of the ipsilateral posterior cerebral artery will result in ischemia of the ipsilateral primary visual cortex and contralateral visual field deficits in both eyes (contralateral homonymous hemianopsia). Another important finding is a false localizing sign, the so-called Kernohans notch, which results from compression of the contralateral cerebral crus containing descending corticospinal and some corticobulbar tract fibers. This leads to Ipsilateral hemiparesis in reference to the herniation and contralateral hemiparesis with reference to the cerebral crus.With increasing pressure and progression of the hernia there will be distortion of the brainstem leading to Duret hemorrhages (tearing of small vessels in the parenchyma) in the median and paramedian zones of the mesencephalon and pons. The rupture of these vessels leads to linear or flamed shaped hemorrhages. The disrupted brainstem can lead to decorticate posture, respiratory center depression and death. Other possibilities resulting from brain stem distortion include lethargy, slow heart rate, and pupil dilation.Uncal herniation may advance to central herniation. The sliding uncus syndrome represents uncal herniation without alteration in the level of consciousness and other sequelae mentioned above. Central herniation In central herniation, the diencephalon and parts of the temporal lobes of both of the cerebral hemispheres are squeezed through a notch in the tentorium cerebelli. Transtentorial herniation can occur when the brain moves either up or down across the tentorium, called ascending and descending transtentorial herniation respectively; however descending herniation is much more common. Downward herniation can stretch branches of the basilar artery (pontine arteries), causing them to tear and bleed, known as a Duret hemorrhage. The result is usually fatal. Other symptoms of this type of herniation include small, fixed pupils with paralysis of upward eye movement giving the characteristic appearance of "sunset eyes". Also found in these patients, often as a terminal complication is the development of diabetes insipidus due to the compression of the pituitary stalk. Radiographically, downward herniation is characterized by obliteration of the suprasellar cistern from temporal lobe herniation into the tentorial hiatus with associated compression on the cerebral peduncles. Upwards herniation, on the other hand, can be radiographically characterized by obliteration of the quadrigeminal cistern. Intracranial hypotension syndrome has been known to mimic downwards transtentorial herniation. Cingulate herniation In cingulate or subfalcine herniation, the most common type, the innermost part of the frontal lobe is scraped under part of the falx cerebri, the dura mater at the top of the head between the two hemispheres of the brain. Cingulate herniation can be caused when one hemisphere swells and pushes the cingulate gyrus by the falx cerebri. This does not put as much pressure on the brainstem as the other types of herniation, but it may interfere with blood vessels in the frontal lobes that are close to the site of injury (anterior cerebral artery), or it may progress to central herniation. Interference with the blood supply can cause dangerous increases in ICP that can lead to more dangerous forms of herniation. Symptoms for cingulate herniation are not well defined. Usually occurring in addition to uncal herniation, cingulate herniation may present with abnormal posturing and coma. Cingulate herniation is frequently believed to be a precursor to other types of herniation. Transcalvarial herniation In transcalvarial herniation, the brain squeezes through a fracture or a surgical site in the skull. Also called "external herniation", this type of herniation may occur during craniectomy, surgery in which a flap of skull is removed, the protruding brain region preventing the piece of skull from being replaced during the operation. Upward herniation Increased pressure in the posterior fossa can cause the cerebellum to move up through the tentorial opening in upward, or cerebellar herniation. The midbrain is pushed through the tentorial notch upward. This is also known as ascending transtentorial herniation since it occurs across the tentorium cerebelli. Tonsillar herniation In tonsillar herniation, also called downward cerebellar herniation, transforaminal herniation, or "coning", the cerebellar tonsils move downward through the foramen magnum possibly causing compression of the lower brainstem and upper cervical spinal cord as they pass through the foramen magnum. Increased pressure on the brainstem can result in dysfunction of the centers in the brain responsible for controlling respiratory and cardiac function. The most common signs are intractable headache, head tilt, and neck stiffness due to tonsillar impaction. The level of consciousness may decrease and also give rise to flaccid paralysis. Blood pressure instability is also evident in these patients.Congenital tonsillar herniation of the cerebellum is also known as a Chiari malformation (CM), or previously an Arnold-Chiari malformation (ACM). There are four types of Chiari malformation, and they represent very different disease processes with different symptoms and prognosis. These conditions can be found in asymptomatic patients as an incidental finding, or can be so severe as to be life-threatening. This condition is now being diagnosed more frequently by radiologists, as more patients undergo MRI scans of their heads, especially upright MRI, which is more than twice as sensitive for detecting this condition. Cerebellar tonsillar ectopia (CTE) is a term used by radiologists to describe cerebellar tonsils that are "low lying" but that do not meet the radiographic criteria for definition as a Chiari malformation. The currently accepted radiographic definition for a Chiari malformation is that cerebellar tonsils lie at least 5mm below the level of the foramen magnum. Some clinicians have reported that some patients appear to experience symptoms consistent with a Chiari malformation without radiographic evidence of tonsillar herniation. Sometimes these patients are described as having a Chiari [type] 0. There are many suspected causes of tonsillar herniation including: decreased or malformed posterior fossa (the lower, back part of the skull) not providing enough room for the cerebellum; hydrocephalus or abnormal CSF volume pushing the tonsils out; or dural tension pulling the brain caudally. Connective tissue disorders, such as Ehlers Danlos syndrome, can be associated. For further evaluation of tonsillar herniation, CINE flow studies are used. This type of MRI examines flow of CSF at the cranio-cervical joint. For persons experiencing symptoms but without clear MRI evidence, especially if the symptoms are better in the supine position and worse upon standing/upright, an upright MRI may be useful. Treatment Treatment involves removal of the etiologic mass and decompressive craniectomy. Brain herniation can cause severe disability or death. In fact, when herniation is visible on a CT scan, the prognosis for a meaningful recovery of neurological function is poor. The patient may become paralyzed on the same side as the lesion causing the pressure, or damage to parts of the brain caused by herniation may cause paralysis on the side opposite the lesion. Damage to the midbrain, which contains the reticular activating network which regulates consciousness, will result in coma. Damage to the cardio-respiratory centers in the medulla oblongata will cause respiratory arrest and (secondarily) cardiac arrest. Investigation is underway regarding the use of neuroprotective agents during the prolonged post-traumatic period of brain hypersensitivity associated with the syndrome. See also Second-impact syndrome References == External links ==
Thanatophoric dysplasia	Thanatophoric dysplasia is a severe skeletal disorder characterized by a disproportionately small ribcage, extremely short limbs and folds of extra skin on the arms and legs. Symptoms and signs Infants with this condition have disproportionately short arms and legs with extra folds of skin. Other signs of the disorder include a narrow chest, small ribs, underdeveloped lungs, and an enlarged head with a large forehead and prominent, wide-spaced eyes. Thanatophoric dysplasia is a lethal skeletal dysplasia divided into two subtypes. Type I is characterized by extreme rhizomelia, bowed long bones, narrow thorax, a relatively large head, normal trunk length and absent cloverleaf skull. The spine shows platyspondyly, the cranium has a short base, and, frequently, the foramen magnum is decreased in size. The forehead is prominent, and hypertelorism and a saddle nose may be present. Hands and feet are normal, but fingers are short. Type II is characterized by short, straight long bones and cloverleaf skull. It presents with typical telephone-handle shaped long bones and H-shaped vertebrae. Causes It can be associated with missense mutations in fibroblast growth factor receptor-3. It is inherited in an autosomal dominant manner. Diagnosis Classification Infants with type 1 thanatophoric dysplasia also have curved thigh bones, flattened bones of the spine (platyspondyly) and shortened thoracic ribs. Note: Prenatal ultra-sound images of the ribs sometimes appear asymmetrical when in fact they are not. In certain cases, this has caused a misdiagnosis of Osteogenisis Imperfecta (OI) type II.An unusual head shape called kleeblattschädel ("cloverleaf skull") can be seen with type 2 thanatophoric dysplasia. Prognosis The term thanatophoric is Greek for "death bearing". Children with this condition are usually stillborn or die shortly after birth from respiratory failure. A small number have survived into childhood, and a very few beyond. Survivors have difficulty breathing on their own and require respiratory support such as high flow oxygen through a canula or ventilator support via tracheostomy. There may also be evidence of spinal stenosis and seizures. The oldest known living TD survivor as of 2013 was a 29-year-old woman. One man lived to be 26 years old. Another man lived to age 20. It was reported in 1998 that a 21 year old man with the condition lives in the United States, while two children with TD aged 10 and 12, a boy and a girl, were known in Germany. There was also a 6-year-old boy living with TD and two 1-year old boys. As of 2021 Christopher Álvarez, 24, is a Colombian living with TD in New York City. Incidence This condition affects about 1 in 60,000 births. References External links GeneReview/NCBI/NIH/UW entry on Thanatophoric Dysplasia Thanatophoric dysplasia at NLM Genetics Home Reference
Retinal vasculitis	Retinal vasculitis is inflammation of the vascular branches of the retinal artery, caused either by primary ocular disease processes, or as a specific presentation of any systemic form of vasculitis such as Behçets disease, sarcoidosis, multiple sclerosis, or any form of systemic necrotizing vasculitis such as temporal arteritis, polyarteritis nodosa, and granulomatosis with polyangiitis, or due to lupus erythematosus, or rheumatoid arthritis. Eales disease, pars planitis, birdshot retinochoroidopathy (autoimmune bilateral posterior uveitis), and Fuchs heterochromic iridocyclitis (FHI) can also cause retinal vasculitis. Infectious pathogens such as Mycobacterium tuberculosis, visceral larva migrans (Toxocara canis & Toxocara cati) can also cause retinal vasculitis. Symptoms Retinal vasculitis presents as painless, decrease of visual acuity (blurry vision), visual floaters, scotomas (dark spot in vision), decreased ability to distinguish colors, and metamorphopsia (distortion of images such as linear images). Diseases associated with retinal vasculitis Diagnosis Retinal vasculitis is very rare as the only presenting symptom. Often, there is sufficient systemic evidence to help the physician decide between any one of the aforementioned possible systemic diseases. For those patients who present with only vasculitis of the retinal vessels, great investigative effort (Chest X-ray, blood test, urinary analysis, vascular biopsy, ophthalmology assessment, etc.) should be undertaken to ensure that a systemic disease is not the hidden culprit. Findings Ophthalmic examination may reveal neovascularization (creation of new vessels in the retina), retinal vessel narrowing, retinal vessel cuffing, retinal hemorrhage, or possible vitritis (inflammation of the vitreous body) or choroiditis (inflammation of the choroid). Treatment Intravitreal administration of corticosteroid and immunosuppressants in a case non infectious retinal vasculitis Antimicrobial therapy is required in the case of infectious retinal vasculitis Sources == External links ==
Macronychia	Macronychia is a genus of satellite flies in the family Sarcophagidae. There are at least 20 described species in Macronychia. Species These 21 species belong to the genus Macronychia: Data sources: i = ITIS, c = Catalogue of Life, g = GBIF, b = Bugguide.net References == Further reading ==
Neisseria gonorrhoeae	Neisseria gonorrhoeae, also known as gonococcus (singular), or gonococci (plural), is a species of Gram-negative diplococci bacteria isolated by Albert Neisser in 1879. It causes the sexually transmitted genitourinary infection gonorrhea as well as other forms of gonococcal disease including disseminated gonococcemia, septic arthritis, and gonococcal ophthalmia neonatorum. It is oxidase positive and aerobic, and it survives phagocytosis and grows inside neutrophils. Culturing it requires carbon dioxide supplementation and enriched agar (chocolate agar) with various antibiotics (Thayer–Martin). It exhibits antigenic variation through genetic recombination of its pili and surface proteins that interact with the immune system.Sexual transmission is through vaginal, anal, or oral sex. Sexual transmission may be prevented through the use of barrier protection. Perinatal transmission may occur during childbirth, and may be prevented by antibiotic treatment of the mother before birth and the application of antibiotic eye gel on the eyes of the newborn. After an episode of gonococcal infection, infected persons do not develop immunity to future infections. Reinfection is possible due to N. gonorrhoeaes ability to evade the immune system by varying its surface proteins.N. gonorrhoeae can cause infection of the genitals, throat, and eyes. Asymptomatic infection is common in males and females. Untreated infection may spread to the rest of the body (disseminated gonorrhea infection), especially the joints (septic arthritis). Untreated infection in women may cause pelvic inflammatory disease and possible infertility due to the resulting scarring. Diagnosis is through culture, Gram stain, or nucleic acid tests, such as polymerase chain reaction, of a urine sample, urethral swab, or cervical swab. Chlamydia co-testing and testing for other STIs is recommended due to high rates of co-infection. Microbiology Neisseria species are fastidious, Gram-negative cocci that require nutrient supplementation to grow in laboratory cultures. Neisseria spp. are facultatively intracellular and typically appear in pairs (diplococci), resembling the shape of coffee beans. Neisseria is non-spore-forming, capable of moving using twitching motility, and an obligate aerobe (requires oxygen to grow). Of the 11 species of Neisseria that colonize humans, only two are pathogens. N. gonorrhoeae is the causative agent of gonorrhea and N. meningitidis is one cause of bacterial meningitis. Culture and identification N. gonorrhoeae is usually isolated on Thayer–Martin agar (or VPN) agar in an atmosphere enriched with 3-7% carbon dioxide. Thayer–Martin agar is a chocolate agar plate (heated blood agar) containing nutrients and antimicrobials (vancomycin, colistin, nystatin, and trimethoprim). This agar preparation facilitates the growth of Neisseria species while inhibiting the growth of contaminating bacteria and fungi. Martin Lewis and New York City agar are other types of selective chocolate agar commonly used for Neisseria growth. N. gonorrhoeae is oxidase positive (possessing cytochrome c oxidase) and catalase positive (able to convert hydrogen peroxide to oxygen). When incubated with the carbohydrates lactose, maltose, sucrose, and glucose, N. gonorrhoeae will oxidize only the glucose. Surface molecules On its surface, N. gonorrhoeae bears hair-like pili, surface proteins with various functions, and sugars called lipooligosaccharides. The pili mediate adherence, movement, and DNA exchange. The Opa proteins interact with the immune system, as do the porins. Lipooligosaccharide (LOS) is an endotoxin that provokes an immune response. All are antigenic and all exhibit antigenic variation (see below). The pili exhibit the most variation. The pili, Opa proteins, porins, and even the LOS have mechanisms to inhibit the immune response, making asymptomatic infection possible.Dynamic polymeric protein filaments called type IV pili allow N. gonorrhoeae to adhere to and move along surfaces. To enter the host the bacteria uses the pili to adhere to and penetrate mucosal surfaces. The pili are a necessary virulence factor for N. gonorrhoeae; without them, the bacterium is unable to cause infection. To move, individual bacteria use their pili like a grappling hook: first, they are extended from the cell surface and attach to a substrate. Subsequent pilus retraction drags the cell forward. The resulting movement is referred to as twitching motility. N. gonorrhoeae is able to pull 100,000 times its own weight, and the pili used to do so are amongst the strongest biological motors known to date, exerting one nanonewton. The PilF and PilT ATPase proteins are responsible for powering the extension and retraction of the type IV pilus, respectively. The adhesive functions of the gonococcal pilus play a role in microcolony aggregation and biofilm formation. Surface proteins called Opa proteins can be used to bind to receptors on immune cells and prevent an immune response. At least 12 Opa proteins are known and the many permutations of surface proteins make recognizing N. gonorrhoeae and mounting a defense by immune cells more difficult.Lipooligosaccharide (LOS) is a low-weight version of lipopolysaccharide present on the surfaces of most other Gram-negative bacteria. It is a sugar (saccharide) side chain attached to lipid A (thus "lipo-") in the outer membrane coating the cell wall of the bacteria. The root "oligo" refers to the fact that it is a few sugars shorter than the typical lipopolysaccharide. As an endotoxin, LOS provokes inflammation. The shedding of LOS by the bacteria is responsible for local injury in, for example, pelvic inflammatory disease. Although its main function is as an endotoxin, LOS may disguise itself with host sialic acid and block initiation of the complement cascade. Antigenic variation N. gonorrhoeae evades the immune system through a process called antigenic variation. This process allows N. gonorrhoeae to recombine its genes and alter the antigenic determinants (sites where antibodies bind), such as the Type IV pili, that adorn its surface. Simply stated, the chemical composition of molecules is changed due to changes at the genetic level. N. gonorrhoeae is able to vary the composition of its pili, and LOS; of these, the pili exhibit the most antigenic variation due to chromosomal rearrangement. The PilS gene is an example of this ability to rearrange as its combination with the PilE gene is estimated to produce over 100 variants of the PilE protein. These changes allow for adjustment to the differences in the local environment at the site of infection, evasion of recognition by targeted antibodies, and contribute to the lack of an effective vaccine.In addition to the ability to rearrange the genes it already has, it is also naturally competent to acquire new DNA (via plasmids), via its type IV pilus, specifically proteins Pil Q and Pil T. These processes allow N. gonorrhoeae to acquire/spread new genes, disguise itself with different surface proteins, and prevent the development of immunological memory – an ability which has led to antibiotic resistance and has also impeded vaccine development. Phase variation Phase variation is similar to antigenic variation, but instead of changes at the genetic level altering the composition of molecules, these genetic changes result in the turning on or off of a gene. Phase variation most often arises from a frameshift in the expressed gene. The Opacity, or Opa, proteins of N. gonorrhoeae rely strictly on phase variation. Every time the bacteria replicate, they may switch multiple Opa proteins on or off through slipped-strand mispairing. That is, the bacteria introduce frameshift mutations that bring genes in or out of frame. The result is that different Opa genes are translated every time. Pili are varied by antigenic variation, but also phase variation. Frameshifts occur in both the pilE and pilC genes, effectively turning off the expression of pili in situations when they are not needed, such as after colonization when N. gonorrhoeae survives within cells as opposed to on their surfaces. Survival of gonococci After gonococci invade and transcytose the host epithelial cells, they land in the submucosa, where neutrophils promptly consume them. The pili and Opa proteins on the surface may interfere with phagocytosis, but most gonococci end up in neutrophils. The exudates from infected individuals contain many neutrophils with ingested gonococci. Neutrophils release an oxidative burst of reactive oxygen species in their phagosomes to kill the gonococci. However, a significant fraction of the gonococci can resist killing through the action of their catalase which breaks down reactive oxygen species and is able to reproduce within the neutrophil phagosomes.Stohl and Seifert showed that the bacterial RecA protein, which mediates repair of DNA damage, plays an important role in gonococcal survival. Michod et al. have suggested that N. gonorrhoeae may replace DNA damaged in neutrophil phagosomes with DNA from neighboring gonococci. The process in which recipient gonococci integrate DNA from neighboring gonococci into their genome is called transformation. Genome The genomes of several strains of N. gonorrhoeae have been sequenced. Most of them are about 2.1 Mb in size and encode 2,100 to 2,600 proteins (although most seem to be in the lower range). For instance, strain NCCP11945 consists of one circular chromosome (2,232,025 bp) encoding 2,662 predicted open reading frames (ORFs) and one plasmid (4,153 bp) encoding 12 predicted ORFs. The estimated coding density over the entire genome is 87%, and the average G+C content is 52.4%, values that are similar to those of strain FA1090. The NCCP11945 genome encodes 54 tRNAs and four copies of 16S-23S-5S rRNA operons. Horizontal gene transfer In 2011, researchers at Northwestern University found evidence of a human DNA fragment in a N. gonorrhoeae genome, the first example of horizontal gene transfer from humans to a bacterial pathogen. Disease Symptoms of infection with N. gonorrhoeae differ depending on the site of infection and many infections are asymptomatic independent of sex. In symptomatic men, the primary symptom of genitourinary infection is urethritis – burning with urination (dysuria), increased urge to urinate, and a pus-like (purulent) discharge from the penis. The discharge may be foul smelling. If untreated, scarring of the urethra may result in difficulty urinating. Infection may spread from the urethra in the penis to nearby structures, including the testicles (epididymitis/orchitis), or to the prostate (prostatitis). Men who have had a gonorrhea infection have a significantly increased risk of having prostate cancer. In symptomatic women, the primary symptoms of genitourinary infection are increased vaginal discharge, burning with urination (dysuria), increased urge to urinate, pain with intercourse, or menstrual abnormalities. Pelvic inflammatory disease results if N. gonorrhoeae ascends into the pelvic peritoneum (via the cervix, endometrium, and fallopian tubes). The resulting inflammation and scarring of the fallopian tubes can lead to infertility and increased risk of ectopic pregnancy. Pelvic inflammatory disease develops in 10 to 20% of the females infected with N. gonorrhoeae. It is important to note that depending on the route of transmission, N. gonorrhoeae may cause infection of the throat (pharyngitis) or infection of the anus/rectum (proctitis).In perinatal infection, the primary manifestation is infection of the eye (neonatal conjunctivitis or ophthalmia neonatorum) when the newborn is exposed to N. gonorrhoeae in the birth canal. The eye infection can lead to corneal scarring or perforation, ultimately resulting in blindness. If the newborn is exposed during birth, conjunctivitis occurs within 2–5 days after birth and is severe. Gonococcal ophthalmia neonatorum, once common in newborns, is prevented by the application of erythromycin (antibiotic) gel to the eyes of babies at birth as a public health measure. Silver nitrate is no longer used in the United States.Disseminated gonococcal infections can occur when N. gonorrhoeae enters the bloodstream, often spreading to the joints and causing a rash (dermatitis-arthritis syndrome). Dermatitis-arthritis syndrome results in joint pain (arthritis), tendon inflammation (tenosynovitis), and painless non-pruritic (non-itchy) dermatitis. Disseminated infection and pelvic inflammatory disease in women tend to begin after menses due to reflux during menses, facilitating spread. In rare cases, disseminated infection may cause infection of the meninges of the brain and spinal cord (meningitis) or infection of the heart valves (endocarditis). Transmission N. gonorrhoeae is transmitted through vaginal, oral, or anal sex; nonsexual transmission is unlikely in adult infection. It can also be transmitted to the newborn during passage through the birth canal if the mother has untreated genitourinary infection. Given the high rate of asymptomatic infection, all pregnant women should be tested for gonorrhea infection. However, communal baths, towels or fabric, rectal thermometers and caregivers hands have been implicated as means of transmission in the pediatric setting. Kissing has also been implicated as a theoretical means of transmission in the gay male population, based on a newer study.Traditionally, the bacterium was thought to move attached to spermatozoa, but this hypothesis did not explain female to male transmission of the disease. A recent study suggests that rather than "surf" on wiggling sperm, N. gonorrhoeae bacteria use pili to anchor onto proteins in the sperm and move through coital liquid. Infection For N. gonorrhoeae, the first step after successful transmission is adherence to the epithelial cells found at the mucosal site that is infected. The bacterium relies on type IV pili that attach and retract, pulling N. gonorrhoeae toward the epithelial membrane where its surface proteins, such as opacity proteins, can interact directly. After adherence, N. gonorrhoeae replicates itself and forms microcolonies. While colonizing, N. gonorrhoeae has the potential to transcytose across the epithelial barrier and work its way in to the bloodstream. During growth and colonization, N. gonorrhoeae stimulates the release of cytokines and chemokines from host immune cells that are pro-inflammatory. These pro-inflammatory molecules result in the recruitment of macrophages and neutrophils. These phagocytic cells typically take in foreign pathogens and destroy them, but N. gonorrhoeae has evolved many mechanisms that allow it to survive within these immune cells and thwart the attempts at elimination. Prevention Transmission is reduced by using latex barriers (e.g. condoms or dental dams) during sex and by limiting sexual partners. Condoms and dental dams should be used during oral and anal sex, as well. Spermicides, vaginal foams, and douches are not effective for prevention of transmission. Treatment The current treatment recommended by the CDC is an injected single dose of ceftriaxone (a third-generation cephalosporin). Sexual partners (defined by the CDC as sexual contact within the past 60 days) should also be notified, tested, and treated. It is important that if symptoms persist after receiving treatment of N. gonorrhoeae infection, a reevaluation should be pursued. Antibiotic resistance Antibiotic resistance in gonorrhea has been noted beginning in the 1940s. Gonorrhea was treated with penicillin, but doses had to be progressively increased to remain effective. By the 1970s, penicillin- and tetracycline-resistant gonorrhea emerged in the Pacific Basin. These resistant strains then spread to Hawaii, California, the rest of the United States, Australia and Europe. Fluoroquinolones were the next line of defense, but soon resistance to this antibiotic emerged, as well. Since 2007, standard treatment has been third-generation cephalosporins, such as ceftriaxone, which are considered to be our "last line of defense".Recently, a high-level ceftriaxone-resistant strain of gonorrhea called H041 was discovered in Japan. Lab tests found it to be resistant to high concentrations of ceftriaxone, as well as most of the other antibiotics tested. Within N. gonorrhoeae, genes exist that confer resistance to every single antibiotic used to cure gonorrhea, but thus far they do not coexist within a single gonococcus. However, because of N. gonorrhoeaes high affinity for horizontal gene transfer, antibiotic-resistant gonorrhea is seen as an emerging public health threat. Serum resistance As a Gram negative bacteria, N. gonorrhoeae requires defense mechanisms to protect itself against the complement system (or complement cascade), whose components are found with human serum. There are three different pathways that activate this system however, they all result in the activation of complement protein 3 (C3). A cleaved portion of this protein, C3b, is deposited on pathogenic surfaces and results in opsonization as well as the downstream activation of the membrane attack complex. N. gonorrhoeae has several mechanisms to avoid this action. As a whole, these mechanisms are referred to as serum resistance. History Name origin Neisseria gonorrhoeae is named for Albert Neisser, who isolated it as the causative agent of the disease gonorrhea in 1878. Galen (130 AD) coined the term "gonorrhea" from the Greek gonos which means "seed" and rhoe which means "flow". Thus, gonorrhea means "flow of seed", a description referring to the white penile discharge, assumed to be semen, seen in male infection. Discovery In 1878, Albert Neisser isolated and visualized N. gonorrhoeae diplococci in samples of pus from 35 men and women with the classic symptoms of genitourinary infection with gonorrhea – two of whom also had infections of the eyes. In 1882, Leistikow and Loeffler were able to grow the organism in culture. Then in 1883, Max Bockhart proved conclusively that the bacterium isolated by Albert Neisser was the causative agent of the disease known as gonorrhea by inoculating the penis of a healthy man with the bacteria. The man developed the classic symptoms of gonorrhea days after, satisfying the last of Kochs postulates. Until this point, researchers debated whether syphilis and gonorrhea were manifestations of the same disease or two distinct entities. One such 18th-century researcher, John Hunter, tried to settle the debate in 1767 by inoculating a man with pus taken from a patient with gonorrhea. He erroneously concluded that both syphilis and gonorrhea were indeed the same disease when the man developed the copper-colored rash that is classic for syphilis. Although many sources repeat that Hunter inoculated himself, others have argued that it was in fact another man. After Hunters experiment other scientists sought to disprove his conclusions by inoculating other male physicians, medical students, and incarcerated men with gonorrheal pus, who all developed the burning and discharge of gonorrhea. One researcher, Ricord, took the initiative to perform 667 inoculations of gonorrheal pus on patients of a mental hospital, with zero cases of syphilis. Notably, the advent of penicillin in the 1940s made effective treatments for gonorrhea available. See also Neisseria meningitidis References External links Type strain of Neisseria gonorrhoeae at BacDive – the Bacterial Diversity Metadatabase
Cheilitis	Cheilitis is a medical condition characterized by inflammation of the lips. The inflammation may include the perioral skin (the skin around the mouth), the vermilion border, or the labial mucosa. The skin and the vermilion border are more commonly involved, as the mucosa is less affected by inflammatory and allergic reactions.Cheilitis is a general term, and there are many recognized types and different causes. According to its onset and course, cheilitis can be either acute or chronic. Most cheilitis is caused by exogenous factors such as dryness (chapping) and acute sun exposure. Allergic tests may identify allergens that cause cheilitis. Chapped lips Chapped lips (also known as cheilitis simplex or common cheilitis) is characterized by the cracking, fissuring, and peeling of the skin of the lips, and is one of the most common types of cheilitis. While both lips may be affected, the lower lip is the most common site. There may also be burning or the formation of large, painful cracks when the lips are stretched. Chronic cheilitis simplex can progress to crusting and bleeding. Counterintuitively, constant licking of the lips causes drying and irritation, and eventually the mucosa splits or cracks. The lips have a greater tendency to dry out in cold, dry weather. Digestive enzymes present in the saliva may also irritate the lips, and the evaporation of the water in saliva saps moisture from them. Some children have a habit of sucking and chewing on the lower lip, producing a combination of cheilitis and a sharply demarcated perioral erythema.Treatment is usually successful with barrier lubricants, such as lip salve or Vaseline. Medical grade (USP) lanolin accelerates repair of the lips, and is used in some lip repair products. Sometimes the term "cheilitis simplex" is used interchangeably with cheilitis in general; however, exfoliative cheilitis is also sometimes stated to be the equivalent of chapped lips. Actinic cheilitis Also termed "solar cheilosis", actinic cheilitis is the result of chronic over-exposure to ultraviolet radiation in sunlight. It usually occurs on the lower lip, which is dry, scaling, and wrinkled grey-white in appearance. It is especially common in people with light skin types who live in sunny climates (e.g., Australians of European ancestry), and in persons who spend a lot of time outdoors. There is a small risk that actinic cheilitis can develop into squamous cell carcinoma in the long term, but lip cancer is usually noticed early and hence has a good prognosis compared to oral cancer generally. Angular cheilitis Angular cheilitis (angular stomatitis, also known as cheilosis) is inflammation of one or both of the corners (angles) of the mouth. It is a fairly common condition, and often affects elderly people. There are many possible causes, including nutritional deficiencies (iron, B vitamins, folate), contact allergies, infections (Candida albicans, Staphylococcus aureus or β-hemolytic streptococci) and edentulism (often with overclosure of the mouth and concomitant denture-related stomatitis), and others. Eczematous cheilitis Also termed "lip dermatitis", eczematous cheilitis is a diverse group of disorders which often have an unknown cause. Chronic eczematous reactions account for the majority of chronic cheilitis cases.It is divided into endogenous (due to an inherent characteristic of the individual), and exogenous (where it is caused by an external agent). The main cause of endogenous eczematous cheilitis is atopic cheilitis (atopic dermatitis), and the main causes of exogenous eczematous cheilitis is irritant contact cheilitis (e.g., caused by a lip-licking habit) and allergic contact cheilitis. The latter is characterized by a dryness, fissuring, edema, and crusting. It affects females more commonly than males, in a ratio of about 9:1. The most common causes of allergic contact cheilitis is lip cosmetics, including lipsticks and lip balm, followed by toothpastes. A lipstick allergy can be difficult to diagnose in some cases as it is possible that cheilitis can develop without the person even wearing lipstick. Instead, small exposure such as kissing someone who is wearing lipstick is enough to cause the condition.Allergy to Balsam of Peru can manifest as cheilitis. Allergies to metal, wood, or other components can cause cheilitis reactions in musicians, especially players of woodwind and brass instruments, e.g., the so-called "clarinetists cheilitis", or "flutists cheilitis". "Pigmented contact cheilitis" is one type of allergic cheilitis in which a brown-black discoloration of the lips develops. Patch testing is used to identify the substance triggering allergic contact cheilitis. Infectious cheilitis Infectious cheilitis refers to cheilitis caused by infectious disease. The terms "Candidal cheilitis" and "bacterial cheilitis" are sometimes used, denoting the involvement of Candida organisms and bacterial species respectively. The term "cheilocandidiasis" describes exfoliative (flaking) lesions of the lips and the skin around the lips, and is caused by a superficial candidal infection due to chronic lip licking. Impetigo (caused by Streptococcus pyogenes and/or Staphylococcus aureus), can manifest as an exfoliative cheilitis-like appearance.Herpes labialis (cold sore) is a common cause of infectious cheilitis. A lesion caused by recurrence of a latent herpes simplex infection can occur in the corner of the mouth, and be mistaken for other causes of angular cheilitis. In fact this is herpes labialis, and is sometimes termed "angular herpes simplex". Granulomatous cheilitis Orofacial granulomatosis is enlargement of lips due to the formation of non-caseating granulomatous inflammation, which obstruct lymphatic drainage of the orofacial soft tissues, causing lymphedema. Essentially, granulomatous cheilitis refers to the lip swelling that accompanies this condition. "Median cheilitis" may be seen, which is fissuring in the midline of the lips due to the enlargement of the lips. Angular cheilitis may also be associated with orofacial granulomatosis. A related condition is Melkersson–Rosenthal syndrome, a triad of facial palsy, chronic lip edema, and fissured tongue. "Mieschers cheilitis", and "granulomatous macrocheilitis", are synonyms of granulomatous cheilitis. Drug-related cheilitis Common causes of drug-related cheilitis include Etretinate, Indinavir, Protease inhibitors, Vitamin A and Isotretinoin (a retinoid drug). Uncommon causes include Atorvastatin, Busulphan, Clofazimine, Clomipramine, Cyancobalamin, Gold, Methyldopa, Psoralens, Streptomycin, Sulfasalazine and Tetracycline. A condition called "drug-induced ulcer of the lip" is described as being characterized by painful or tender, well-defined ulcerations of the lip without induration. It is the result of oral administration of drugs, and the condition resolves when the drugs are stopped. Exfoliative cheilitis Also termed "cheilitis exfoliativa" or "tic de levres", is an uncommon inflammatory condition of the vermilion zone of the lips, which become painful and crusted. There is continuous production and desquamation (shedding) of thick, brown scales of keratin. The keratin layer of the epidermis of the lips experiences a faster growth and death rate than normal and desquamates. When these scales are removed, a lip of normal appearance is revealed beneath, although there may be associated erythema and edema. The condition has not yet been attributed to any particular cause. Rarely are infections to blame. In some individuals, there is an association with stress, anxiety, depression or personality disorders. In one report, 87% of individuals had some form of psychiatric disturbance, and 47% had thyroid dysfunction, which in turn can cause psychiatric conditions like depression.Some cases of exfoliative cheilitis are thought to represent factitious damage, termed "factitious cheilitis" or "artifactual cheilitis", and are related to repetitive lip picking or licking habits. This appears as crusting and ulceration caused by repetitive chewing and sucking of the lips. Some consider habitual lip licking or picking to be a form of nervous tic. This habit is sometimes termed perlèche (derived from the French word pourlècher meaning "to lick ones lips"). Factitious cheilitis is significantly more common in young females.Exfoliative cheilitis has also been linked to HIV/AIDS. Management consists mostly of keeping the lips moist and the application of topical corticosteroids ranging from hydrocortisone to clobetasol. There have also been reports of using topical tacrolimus ointment. Cheilitis glandularis Chelitis glandularis is a rare inflammatory condition of the minor salivary glands, usually in the lower lip, which appears swollen and everted. There may also be ulceration, crusting, abscesses, and sinus tracts. It is an acquired disorder, but the cause is uncertain. Suspected causes include sunlight, tobacco, syphilis, poor oral hygiene and genetic factors. The openings of the minor salivary gland ducts become inflamed and dilated, and there may be mucopurulent discharge from the ducts. A previous classification suggested dividing cheilitis into 3 types based on severity, with the later stages involving secondary infection with bacteria, and increased ulceration, suppuration and swelling: Type 1, Simple; Type 2, Superficial suppurative ("Baelzs disease"); and Type 3, Deep suppurative ("cheilitis glandularis epostemetosa"). Cheilitis glandularis usually occurs in middle-aged and elderly males, and it carries a risk of malignant transformation to squamous cell carcinoma (18% to 35%). Preventative treatment such as vermilionectomy ("lip shave") is therefore the treatment of choice. Plasma cell cheilitis Plasma cell cheilitis is a very rare presentation of a condition which more usually occurs on the gingiva (termed "plasma cell gingivitis") or sometimes the tongue. Plasma cell cheilitis appears as well defined, infiltrated, dark red plaque with a superficial lacquer-like glazing. Plasma cell cheilitis usually involves the lower lip. The lips appear dry, atrophic and fissured. Angular cheilitis is sometimes also present. Other causes Lupus erythematosus, sometimes termed "lupus cheilitis" Crohns disease (angular cheilitis) "Nutritional cheilitis", e.g. pyridoxine (vitamin B6) deficiency Lichen planus Pemphigoid Xerostomia References External links Media related to Cheilitis at Wikimedia Commons
Ossification of the posterior longitudinal ligament	Ossification of the posterior longitudinal ligament (OPLL) is a process of fibrosis, calcification, and ossification of the posterior longitudinal ligament of the spine, that may involve the spinal dura. Once considered a disorder unique to people of Asian heritage, it is now recognized as an uncommon disorder in a variety of patients with myelopathy. Causes The causes of OPLL are unknown. However, genetic and environmental factors appear to play a role in pathogenesis. OPLL may also be associated with diffuse idiopathic skeletal hyperostosis Diagnosis Myeolography, including post-myelographic CT is likely the most effective imaging study an accurate diagnosis. Treatment Surgical management options include extensive cervical laminectomy with or without an additional posterior arthrodesis, anterior decompression and arthrodesis, and posterior cervical laminoplasty. Treatment decisions can be made based on a grading systems devised by Hirabayashi et al., supplemented by the Nurick myelopathy classification system. Prognosis Most patients suffer from only mild symptoms. Symptoms typically last approximately 13 months. Of patients without myelopathy at initial presentation, only 29% of them will develop myelopathy within 30 years. Epidemiology The age range of patients with OPLL is from 32 to 81 years (mean = 53), with a male predominance. Prevalence is higher in those of Japanese or Asian ancestry (2-3.5%) and rarer in other racial groups (0.16%). Schizophrenia patients in Japan may have as high as 20% incidence. References == External links ==
Hypertrophic scar	A hypertrophic scar is a cutaneous condition characterized by deposits of excessive amounts of collagen which gives rise to a raised scar, but not to the degree observed with keloids. Like keloids, they form most often at the sites of pimples, body piercings, cuts and burns. They often contain nerves and blood vessels. They generally develop after thermal or traumatic injury that involves the deep layers of the dermis and express high levels of TGF-β. Cause Mechanical tension on a wound has been identified as a leading cause for hypertrophic scar formation.When a normal wound heals, the body produces new collagen fibers at a rate which balances the breakdown of old collagen. Hypertrophic scars are red and thick and may be itchy or painful. They do not extend beyond the boundary of the original wound, but may continue to thicken for up to six months. Hypertrophic scars usually improve over one or two years, but may cause distress due to their appearance or the intensity of the itching; they can also restrict movement if they are located close to a joint.Some people have an inherited tendency to hypertrophic scarring, for example, those with Ehlers–Danlos syndrome. Prevention It is not possible to completely prevent hypertrophic scars, so those with a history of them should inform their doctor or surgeon if they need surgery. Management A 2021 systematic review brought together evidence from different studies that investigated using silicone gel sheeting to treat hypertrophic scars. 13 studies with a total of 468 participants were reviewed in total. Many different treatments were included but it was uncertain whether silicone gel sheets were more effective than most of these. Silicone gel sheets may improve the appearance of scars slightly compared with applying onion extract, and may reduce pain compared with no treatment with silicone gel sheets or pressure garments.A 2022 systematic review included multiple studies on laser therapy for treating hypertrophic scars. There was not enough evidence for the review authors to determine if laser therapy was more effective than other treatments. They were also unable to conclude if laser therapy leads to more harm than benefits compared with no treatment or different kinds of treatment.Scar therapies, such as cryosurgery, may speed up the healing process from a hypertrophic scar to a flatter, paler one.Early hypertrophic scars should be treated with applied pressure and massage in the first 1.5–3 months. If necessary, silicone therapy should be applied later. Ongoing hypertrophy may be treated with corticosteroids injections. Surgical revision may be considered after 1 year. See also Keloid List of cutaneous conditions == References ==
Familial dysalbuminemic hyperthyroxinemia	Familial dysalbuminemic hyperthyroxinemia is a type of hyperthyroxinemia associated with mutations in the human serum albumin gene. The term was introduced in 1982. References == External links ==
Neutrophilia	Neutrophilia (also called neutrophil leukocytosis or occasionally neutrocytosis) is leukocytosis of neutrophils, that is, a high number of neutrophils in the blood. Because neutrophils are the main type of granulocytes, mentions of granulocytosis often overlap in meaning with neutrophilia. The opposite of neutrophilia is neutropenia. Causes Neutrophils are the primary white blood cells that respond to a bacterial infection, so the most common cause of neutrophilia is a bacterial infection, especially pyogenic infections.Neutrophils are also increased in any acute inflammation, so will be raised after a heart attack, other infarct or burns.Some drugs, such as prednisone, have the same effect as cortisol and adrenaline (epinephrine), causing marginated neutrophils to enter the blood stream.A neutrophilia might also be the result of a malignancy. Chronic myelogenous leukemia (CML or chronic myeloid leukaemia) is a disease where the blood cells proliferate out of control. These cells may be neutrophils. Neutrophilia can also be caused by appendicitis and splenectomy.Primary neutrophilia can additionally be a result of leukocyte adhesion deficiency. "Left shift" A "left shift" refers to the presence of increased proportions of younger, less well differentiated neutrophils and neutrophil-precursor cells in the blood. This generally reflects early or premature release of myeloid cells from the bone marrow, the site where neutrophils are generated. A severe neutrophilia with left shift is referred to as a leukemoid reaction. The leukocyte alkaline phosphatase (LAP) score, which refers to the amount of alkaline phosphatase per neutrophil, will increase. In a severe infection, toxic granulation changes happen to the neutrophils.This can resemble Pelger-Huet anomaly. See also Absolute neutrophil count References == External links ==
Facial eczema	Facial eczema is a mycotoxic disease that affects the liver of several animals, mainly sheep and cattle, but can also infect other ungulates. It is caused by ingesting sporidesmins released by the fungus Pithomyces chartarum. Its visible symptoms are characterized by red skin that turns black and crusty before peeling off, as well as inflammation that can cause swelling of the udder, teats, ears and face. The disease is not always visible. Other symptoms include weight loss, weakness and death. P. chartarum It grows mostly in New Zealand but also occurs in Australia, France, South Africa, and South America. The fungus grows on dead plants, especially on perennial ryegrass near the ground (25mm height). It most commonly grows between January and May, as it requires warm, humid conditions, as well as moisture at ground level. Areas of spore growth can include urine patches and areas sheltered by hedges. The fungus grows in clusters and is normally invisible to human eye. It produces millions of spores with the toxic substance sporidesmin. Fresh spores are particularly toxic. Contaminated pasture loses its toxicity after 2 weeks. Pathophysiology The incubation period is 7-20 days after poison intake. Sporidesmin is hepatotoxic and leads to hepatogenous photosensitization and phylloerythrin accumulation in the bloodstream. It damages the bile ducts and then the liver. The worst case is liver necrosis. This causes – as a secondary effect – photosensitization, this means the inflammation of unpigmented areas and exposed skin (ears, teat, face) and photodynamic dermatitis. Only 5% of affected animals show the respective clinical signs. Symptoms Sheep Infected sheep experience sunburn at face, ears, teats and vulva. It is the primary symptom of the poisoning caused by sporidesmin. The sunburn is caused by the fact that the lower tissue is swollen. The skin gets crusty, dark and then peels,. making it susceptible to infection. Other symptoms include dullness, weakness, inappetence, and ill-thrift. An affection of the liver results in jaundice. In a worst-case, the sheep die. Cattle Infected cattle suffer from sunburn. Dark pigmented skin is often affected. Cattle produce less milk. Jaundice is possible and death after some months. Treatment Convalescence can take a long time, but some animals may not get healthy. External therapy is possible to treat the sunburn. Animals could be protected by the intake of zinc. Zinc reacts with sporidesmin to create a metallic complex, so that the poison can be eliminated from the body. Prevention and control If animals are sunburned, they should be placed in the stable to protect them from sunlight. Infected cattle should no longer be used in milk production.Reduce flock density (0.45 hectare/ 15 cows or 100 sheep)GGT (enzyme) is released by the damaged liver over the course of this disease and can be tested to indicate disease severity. == References ==
Cyclosporiasis	Cyclosporiasis is a disease caused by infection with Cyclospora cayetanensis, a pathogenic protozoan transmitted by feces or feces-contaminated food and water. Outbreaks have been reported due to contaminated fruits and vegetables. It is not spread from person to person, but can be a hazard for travelers as a cause of diarrhea. Cause Cyclosporiasis primarily affects humans and other primates. When an oocyst of Cyclospora cayetanensis enters the small intestine, it invades the mucosa, where it incubates for about one week. After incubation, the infected person begins to experience severe watery diarrhea, bloating, fever, stomach cramps, and muscle aches.The parasite particularly affects the jejunum of the small intestine. Of nine patients in Nepal who were diagnosed with cyclosporiasis, all had inflammation of the lamina propria along with an increase of plasma in the lamina propria. Oocysts were also observed in duodenal aspirates.Oocysts are often present in the environment as a result of using contaminated water or human feces as fertilizer. Diagnosis Diagnosis can be difficult due to the lack of recognizable oocysts in the feces. PCR-based DNA tests and acid-fast staining can help with identification. Prevention There is no vaccine to prevent cyclosporiasis in humans at present, but one is available for reduction of fetal losses in sheep. Treatment The infection is often treated with trimethoprim/sulfamethoxazole, also known as Bactrim or co-trimoxazole, because traditional anti-protozoal drugs are not sufficient. To prevent transmission, food should be cooked thoroughly and drinking water from streams should be avoided. Epidemiology The first recorded cases of cyclosporiasis in humans were as recent as 1977, 1978, and 1979. They were reported by Ashford, a British parasitologist who discovered three cases while working in Papua New Guinea. Ashford found that the parasite had very late sporulation, from 8–11 days, making the illness difficult to diagnose. When examining feces, the unsporulated oocysts can easily be mistaken for fungal spores, and thus can be easily overlooked.In 2007, Indian researchers published a case report that found an association between Cyclospora infection and Bells palsy. This was the first reported case of Bell’s palsy following chronic Cyclospora infection. In addition to other extra-intestinal reports, cyclosporiasis might be involved in either reversible neuronal damage or other unknown mechanisms to lead to Guillain-Barré syndrome or Bells palsy. In 2010, a report of Cyclospora transmission via swimming in the Kathmandu Valley was published in the Journal of Institute of Medicine. The researchers found that openly defecated human stool samples around the swimmers living quarters and near the swimming pool were positive for Cyclospora. However, they did not find the parasite in dog stool, bird stool, cattle dung, vegetable samples, or water samples. They concluded that pool water contaminated via environmental pollution might have caused the infection, as the parasite can resist chlorination in water.Cyclosporiasis infections have been well reported in Nepal. In one study, Tirth Raj Ghimire, Purna Nath Mishra, and Jeevan Bahadur Sherchan collected samples of vegetables, sewage, and water from ponds, rivers, wells, and municipal taps in the Kathmandu Valley from 2002 to 2004. They found Cyclospora in radish, cauliflower, cabbage, and mustard leaves, as well as sewage and river water. This first epidemiological study determined the seasonal character of cyclosporiasis outbreaks in Nepal during the rainy season, from May to September. Cyclosporiasis in AIDS patients At the beginning of the AIDS epidemic in the early 1980s, cyclosporiasis was identified as one of the most important opportunistic infections among AIDS patients.In 2005, Ghimire and Mishra reported a case of cyclosporiasis in a patient with low hemoglobin and suggested that this coccidian might be involved in reducing hemoglobin due to lack of immune system. In 2006, their groups published a paper about the role of cyclosporiasis in HIV/AIDS patients and non-HIV/AIDS patients in the Kathmandu Valley.In 2008, Indian researchers published a report about the epidemiology of Cyclospora in HIV/AIDS patients in Kathmandu. They examined samples of soil, river water, sewage, chicken stool, dog stool, and stool in the streets, and found them positive for Cyclospora. They also evaluated several risk factors for cyclosporiasis in AIDS patients. Outbreaks Although it was initially thought that Cyclospora was confined to tropical and subtropical regions, occurrences of cyclosporiasis are becoming more frequent in North America. According to the Centers for Disease Control and Prevention, there have been 11 documented cyclosporiasis outbreaks in the U.S. and Canada since the 1990s. The CDC also recorded 1,110 laboratory-confirmed sporadic instances of cyclosporiasis.Between June and August 2013, multiple independent outbreaks of the disease in the U.S. sickened at least 631 people across 25 states. Investigations later identified a bagged salad mixture as the cause of an outbreak in Iowa and Nebraska.In 2015, the CDC was notified of 546 persons with confirmed cyclosporiasis infection across 31 states. Cluster investigations in Texas, where the greatest number of infections was reported, indicated that contaminated cilantro was the culprit.During July 21–August 8, 2017, the Texas Department of State Health Services (DSHS) was notified of 20 cases of cyclosporiasis among persons who dined at a Mediterranean-style restaurant chain (chain A) in the Houston area.On July 31, 2018, the United States Department of Agriculture (USDA) issued a public health alert for certain beef, pork and poultry salad and wrap products potentially contaminated with Cyclospora. The contamination came from the chopped romaine lettuce used in these products. In June 2020, the CDC and other regulatory bodies began investigating an outbreak of Cyclosporiasis in the Midwestern United States linked to bagged salad mix. On June 27, 2020, Fresh Express announced a voluntary recall of over 91 Fresh Express and private label salad products. References External links Cyclosporiasis at Centers for Disease Control & Prevention Cyclospora Infection at MayoClinic.com
Progressive outer retinal necrosis	Progressive outer retinal necrosis (PORN) syndrome is a form of chorio-retinitis, an infection in the retina, the back of the eye. The disease is most commonly caused by the Varicella zoster virus and is found almost exclusively in patients with HIV/AIDS (acquired immunodeficiency syndrome). Progressive outer retinal necrosis is the second most common opportunistic retinal infection in North America among people with AIDS. The reason this disease process is considered opportunistic is precisely because it only presents in patients with AIDS, a disease that attacks and weakens the immune system, making space for other infections, like Varicella zoster virus (VZV) and Herpes simplex virus (HSV), to attack the body. The syndrome, PORN, falls under the umbrella of Necrotizing Herpetic Retinopathy, along with Acute Retinal Necrosis (ARN). Although fairly similar processes, the two forms of retinopathy have different presenting symptoms. Acute Retinal Necrosis, or ARN, is damage more central in the retinal portion of the eye with dead or necrotic areas well defined. ARN also presents with inflammation within the eye and is often painful. Progressive outer retinal necrosis (PORN) is a chorioretinitis presenting with multiple lesions in the peripheral retina. Unlike ARN, this disease process has no signs of intraocular inflammation, the hallmark feature, or vascular involvement. Presentation (Signs and Symptoms) The presentation of the disease is dependent on the patients AIDS prognosis. If the immune system has been significantly weakened by AIDS, a patient will likely present with worse and faster progressing PORN. Commonly presenting symptoms of PORN include: Blurry vision Acute onset bilateral visual loss OR painless progressive visual loss Decreased vision with pain Floaters Headaches Diagnosis The diagnosis of Progressive outer retinal necrosis (PORN) syndrome is made primarily through history and physical exam. A patients medical history of AIDS increases the likelihood of PORN as the diagnosis. An eye exam will show specific hallmark features, including opacified lesions in the peripheral retina without inflammation. There are medical tests that can aid in diagnosing the severity of the disease process, however are not necessary for initial diagnosis. Imaging studies: may help diagnose the extent of retinal involvement Optical coherence tomography (OCT): this test allows ophthalmologists to look at outer and inner layers of the retina Fundus autofluorescence: shows areas of unhealthy cells in the retina Blood work: the labs can show how immuno-compromised an individual is Vitreous Tap: Analysis of the fluid in the eye can show the causative organism, such as VZV.Other possible diseases to consider when a patient presents with symptoms similar to PORN include: CMV retinitis, ARN, Syphilitic retinitis, Toxoplasma retinochoroiditis, tuberculosis, toxocariasis, fungal or bacterial endophthalmitis Inflammatory: Sarcoidosis, Behcets, other retinal vasculitides, Neoplastic: intraocular lymphoma, leukemia, metastasis. Prognosis If left untreated, PORN syndrome can become bilateral, affecting both eyes. The retina can also atrophy, or decay, over time as the blood supply decreases. This leads to retinal detachment, a process where the retina breaks off the back of the eye. Retinal detachments are considered surgical emergencies, as they can lead to blindness if not promptly fixed. Treatment When AIDS first became a diagnosis, ophthalmologists began seeing patients with infectious processes such as Progressive outer retinal necrosis (PORN). With the use of HAART (3 drug regimen standard) treatment for HIV/AIDS in the 1990s, the presentation of these chorioretinitis diseases became less severe and less frequent.Treatment for Necrotizing Herpetic Retinopathy, including ARN and PORN, includes the anti-viral medications Ganciclovir and Foscarnet. These medications are given as intra-vitreal injections (injected into the fluid of the eye). This treatment has shown success in reversing the disease process and improving vision to an extent. See also Cytomegalovirus retinitis List of systemic diseases with ocular manifestations == References ==
Prune belly syndrome	Prune belly syndrome is a rare, genetic birth defect affecting about 1 in 40,000 births. About 97% of those affected are male. Prune belly syndrome is a congenital disorder of the urinary system, characterized by a triad of symptoms. The syndrome is named for the mass of wrinkled skin that is often (but not always) present on the abdomen of those with the disorder. Signs and symptoms Prune-belly triad consists of signs such as: Cryptorchidism, abdominal wall defects and genitourinary defects: A partial or complete lack of abdominal wall muscles. There may be wrinkly folds of skin covering the abdomen. Cryptorchidism (undescended testicles) in males Urinary tract abnormality such as unusually large ureters, distended bladder, accumulation and backflow of urine from the bladder to the ureters and the kidneys (vesicoureteral reflux)Other signs include: Frequent urinary tract infections due to the inability to properly expel urine. Ventricular septal defect Malrotation of the gut Club foot Later in life, a common symptom is post-ejaculatory discomfort. Most likely a bladder spasm, it lasts about two hours. Musculoskeletal abnormalities include pectus excavatum, scoliosis, and congenital joint dislocations including the hip. Diagnosis of prune belly syndrome necessitates a thorough orthopaedic evaluation because of the high prevalence of associated musculoskeletal abnormalities. Pulmonary hypoplasia, pneumonia, and atelectasis involving lung lobes Complications Prune belly syndrome can result in distention and enlargement of internal organs such as the bladder and intestines. Surgery is often required but will not return the organs to a normal size. Bladder reductions have shown that the bladder will again stretch to its previous size due to lack of muscle. Complications may also arise from enlarged/malformed kidneys, which may result in kidney failure and the childs going on dialysis or requiring a kidney transplant. Many individuals with prune belly syndrome have good physical and mental health, despite all the concerns. With proper treatment, however, a longer, healthier life is possible. Diagnosis Prune belly syndrome can be diagnosed via ultrasound while a child is still in-utero. An abnormally large abdominal cavity resembling that of an obese person is the key indicator, as the abdomen swells with the pressure of accumulated urine.In young children, frequent urinary tract infections often herald prune belly syndrome, as they are normally uncommon. If a problem is suspected, doctors can perform blood tests to check renal function. Another study that may suggest the syndrome is a voiding cystourethrogram.PBS is far more common in males. Autosomal recessive inheritance has been suggested in some cases. A homozygous mutation in the muscarinic cholinergic receptor-3 gene (CHRM3) on chromosome 1q43 was reported in one family. Treatment The type of treatment, like that of most disorders, depends on the severity of the symptoms. One option is to perform a vesicostomy, which allows the bladder to drain through a small hole in the abdomen, thus helping to prevent urinary tract infections. Similarly, consistent self-catheterization, often several times per day, can be an effective approach to preventing infections. A more drastic procedure is a surgical "remodeling" of the abdominal wall and urinary tract. Boys often need to undergo an orchiopexy to move the testes to their proper place in the scrotum. References External links The Journal of Bone & Joint Surgery \| Article
Eosinophilic gastroenteritis	Eosinophilic gastroenteritis (EG or EGE) is a rare and heterogeneous condition characterized by patchy or diffuse eosinophilic infiltration of gastrointestinal (GI) tissue, first described by Kaijser in 1937. Presentation may vary depending on location as well as depth and extent of bowel wall involvement and usually runs a chronic relapsing course. It can be classified into mucosal, muscular and serosal types based on the depth of involvement. Any part of the GI tract can be affected, and isolated biliary tract involvement has also been reported. The stomach is the organ most commonly affected, followed by the small intestine and the colon. Signs and symptoms EG typically presents with a combination of chronic nonspecific GI symptoms which include abdominal pain, diarrhea, occasional nausea and vomiting, weight loss and abdominal distension. Approximately 80% have symptoms for several years; a high degree of clinical suspicion is often required to establish the diagnosis, as the disease is extremely rare. It doesnt come all of a sudden but takes about 3–4 years to develop depending upon the age of the patient. Occasionally, the disease may manifest itself as an acute abdomen or bowel obstruction. Mucosal EG (25–100%) is the most common variety, which presents with features of malabsorption and protein losing enteropathy. Failure to thrive and anaemia may also be present. Lower gastrointestinal bleeding may imply colonic involvement. Muscular EG (13–70%) present with obstruction of gastric outlet or small intestine; sometimes as an obstructing caecal mass or intussusception. Subserosal EG (4.5% to 9% in Japan and 13% in the US) presents with ascites which is usually exudative in nature, abundant peripheral eosinophilia, and has favourable responses to corticosteroids. Other documented features are cholangitis, pancreatitis, eosinophilic splenitis, acute appendicitis and giant refractory duodenal ulcer. Pathophysiology Peripheral blood eosinophilia and elevated serum IgE are usual but not universal. The damage to the gastrointestinal tract wall is caused by eosinophilic infiltration and degranulation.As a part of host defense mechanism, eosinophils are normally present in gastrointestinal mucosa, though the finding in deeper tissue is almost always pathologic. What triggers such dense infiltration in EG is not clear. It is possible that different pathogenetic mechanisms of disease is involved in several subgroups of patients. Food allergy and variable IgE response to food substances has been observed in some patients which implies role of hypersensitive response in pathogenesis. Many patients indeed have history of other atopic conditions like eczema, asthma, etc.Eosinophil recruitment into inflammatory tissue is a complex process, regulated by a number of inflammatory cytokines. In EG cytokines IL-3, IL-5 and granulocyte macrophage colony stimulating factor (GM-CSF) may be behind the recruitment and activation. They have been observed immunohistochemically in diseased intestinal wall. In addition eotaxin has been shown to have an integral role in regulating the homing of eosinophils into the lamina propria of stomach and small intestine. In the allergic subtype of disease, it is thought that food allergens cross the intestinal mucosa and trigger an inflammatory response that includes mast cell degranulation and recruitment of eosinophils. Diagnosis Talley et al. suggested 3 diagnostic criteria which are still widely used: the presence of gastrointestinal symptoms, histological demonstration of eosinophilic infiltration in one or more areas of the gastrointestinal tract or presence of high eosinophil count in ascitic fluid (latter usually indicates subserosal variety), no evidence of parasitic or extraintestinal disease.Hypereosinophilia, the hallmark of allergic response, may be absent in up to 20% of patients, but hypoalbuminaemia and other abnormalities suggestive of malabsorption may be present. CT scans may show nodular and irregular thickening of the folds in the distal stomach and proximal small bowel, but these findings can also be present in other conditions like Crohns disease and lymphoma.The endoscopic appearance in eosinophilic gastroenteritis is nonspecific; it includes erythematous, friable, nodular, and occasional ulcerative changes. Sometimes diffuse inflammation results in complete loss of villi, involvement of multiple layers, submucosal oedema and fibrosis.Definitive diagnosis involves histological evidence of eosinophilic infiltration in biopsy slides. Microscopy reveals >20 eosinophils per high power field. Infiltration is often patchy, can be missed and laparoscopic full thickness biopsy may be required. Radio isotope scan using technetium (99mTc) exametazime-labeled leukocyte SPECT may be useful in assessing the extent of disease and response to treatment but has little value in diagnosis, as the scan does not help differentiating EG from other causes of inflammation.When eosinophilic gastroenteritis is observed in association with eosinophilic infiltration of other organ systems, the diagnosis of idiopathic hypereosinophilic syndrome should be considered. Management Corticosteroids are the mainstay of therapy with a 90% response rate in some studies. Appropriate duration of steroid treatment is unknown and relapse often necessitates long term treatment. Various steroid sparing agents e.g. sodium cromoglycate (a stabilizer of mast cell membranes), ketotifen (an antihistamine), and montelukast (a selective, competitive leukotriene receptor antagonist) have been proposed, centering on an allergic hypothesis, with mixed results. Oral budesonide (an oral steroid) can be useful in treatment, as well. An elimination diet may be successful if a limited number of food allergies are identified.In a randomized clinical trial, lirentelimab was found to improve eosinophil counts and symptoms in individuals with eosinophilic gastritis and duodenitis. Epidemiology Epidemiology may differ between studies, as number of cases are small, with approximately 300 EG cases reported in published literature. EG can present at any age and across all races, with a slightly higher incidence in males. Earlier studies showed higher incidence in the third to fifth decades of life. Other gastrointestinal conditions associated with allergy Eosinophilic esophagitis Eosinophilic ascites Coeliac disease Protein losing enteropathy from intolerance to cows milk protein Infantile formula protein intolerance See also Aeroallergen Allergy Gastroenteritis Malabsorption References == External links ==
Intestinal neuronal dysplasia	Intestinal neuronal dysplasia (IND) is an inherited disease of the intestine that affects one in 3000 children and adults. The intestine uses peristalsis to push its contents toward the anus; IND sufferers have a problem with the motor neurons that lead to the intestine, inhibiting this process and thus preventing digestion. It can often be confused for Hirschsprungs disease, as both have similar symptoms. Presentation IND can be grouped into NID A and NID B, with the "A" form affecting the sympathetic innervation, and the "B" version affecting the parasympathetic innervation. In 2002 Martucciello and colleagues published the first analysis of associated anomalies in IND population is an important clinical approach to investigate possible pathogenetic correlations. Two recessive syndromes were identified (3 families). The first was characterized by NID B, intestinal malrotation, and congenital short bowel, the second by NID B, short stature, mental retardation, and facial dysmorphism. In this study, gastrointestinal anomalies accounted for 67.4% of all associated disorders. These data suggest a strong correlation between IND and intestinal development. Diagnosis Treatment Conservative treatment involves the long term use of laxatives and enemas, and has limited success. Dietary changes in order to control the disease are ineffective and high fiber diets often worsen the symptoms in children. As a last resort, surgical treatment (internal sphincter myectomy or colon resection) is used. In extreme cases, the only effective cure is a complete transplant of the affected parts. Society A famous case of IND is that of Adele Chapman, who had a triple transplant of the small intestine, pancreas and liver, the first of its kind in the UK; therefore the official charity of IND is the Adele Chapman Foundation. References == External links ==
Metabolic myopathy	Metabolic myopathies are myopathies that result from defects in biochemical metabolism that primarily affect muscle. They are generally genetic defects that interfere with muscles ability to create energy. At the cellular level, metabolic myopathies lack some kind of enzyme that prevent the chemical reactions necessary to create adenosine triphosphate (ATP). This prevents the muscle cells from being able to function properly and disrupts communication between joints and bones. Some people with a metabolic myopathy never develop symptoms due to the bodys ability to produce enough ATP through alternative pathways. In the event more ATP is needed from the affected pathway, the lack of it becomes an issue and symptoms develop. People with a metabolic myopathy often experience symptoms such as progressive muscle weakness, fatigue, pain and cramping after exercise, and considerable breakdown of muscle tissue. The degree of symptoms varies greatly from person to person and is dependent on the severity of enzymatic defect. In extreme cases it can lead to Rhabdomyolysis. Types Metabolic myopathies are generally caused by an inherited genetic mutation. This mutation has an autosomal recessive inheritance pattern making it fairly rare to inherit, but it can also be caused by a random genetic mutation. Metabolic myopathies are named after the pathway in which the defective enzyme or a lack of enzymes is present. This causes the underproduction of adenosine triphosphate (ATP) and affects the muscles in different parts of the body. The three main categories of diseases are listed below: Glycogen storage diseases- defect in sugar metabolism Lipid storage disorder- defect in fat processing Mitochondrial myopathy- defect in mitochondrial enzyme Diagnosis The symptoms of a metabolic myopathy can be easily confused with the symptoms of another disease. In most cases, a Muscle biopsy is necessary for an accurate diagnosis of the cause of muscle weakness. A blood test can be done under normal circumstances to test for genetic differences and signs of tissue breakdown, or with an added cardio portion that can indicate if muscle breakdown is occurring. An electromyography is sometimes taken in order to rule out other disorders if the cause of fatigue is unknown. Differentiating between different types of metabolic myopathies can be difficult due to the similar symptoms of each type such as Myoglobinuria and exercise intolerance. It has to be determined whether the patient has fixed or exercise induced manifestations, and if exercise related what kind of exercise, before extensive exercise related lab testing is done to determine the underlying cause. Treatment Metabolic Myopathies have varying levels of symptoms, being most severe when developed during infancy. Those who do not develop a form of a metabolic myopathy until they are in their young adult or adult life tend to have more treatable symptoms that can be helped with a change in diet and exercise. Depending on what enzyme is affected, a high-protein or low-fat diet may be recommended along with mild exercise. It is important for people with metabolic myopathies to consult with their doctors for a treatment plan in order to prevent acute muscle breakdowns while exercising that lead to the release of muscle proteins into the bloodstream that can cause kidney damage. References External links Metabolic Myopathies - eMedicine
Ornithine translocase deficiency	Ornithine translocase deficiency, also called hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome, is a rare autosomal recessive urea cycle disorder affecting the enzyme ornithine translocase, which causes ammonia to accumulate in the blood, a condition called hyperammonemia. Ammonia, which is formed when proteins are broken down in the body, is toxic if the levels become too high. The nervous system is especially sensitive to the effects of excess ammonia. Pathophysiology Mutations in SLC25A15 cause ornithine translocase deficiency. Ornithine translocase deficiency belongs to a class of metabolic disorders referred to as urea cycle disorders. The urea cycle is a sequence of reactions that occurs in liver cells. This cycle processes excess nitrogen, generated when protein is used by the body, to make a compound called urea that is excreted by the kidneys. The SLC25A15 gene provides instructions for making a protein called a mitochondrial ornithine transporter. This protein is needed to move a molecule called ornithine within the mitochondria (the energy-producing centers in cells). Specifically, this protein transports ornithine across the inner membrane of mitochondria to the region called the mitochondrial matrix, where it participates in the urea cycle. Mutations in the SLC25A15 gene result in a mitochondrial ornithine transporter that is unstable or the wrong shape, and which cannot bring ornithine to the mitochondrial matrix. This failure of ornithine transport causes an interruption of the urea cycle and the accumulation of ammonia, resulting in the signs and symptoms of ornithine translocase deficiency.This disorder is inherited in an autosomal recessive pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - are required to be born with the disorder. The parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder. Diagnosis Clinical findings in HHH syndrome are non-specific. If the disorder is suspected, laboratory testing can provide diagnostic information. Plasma amino acid analysis will show elevated ornithine levels, and urine amino acids will detect homocitrulline. Orotic acid may also be elevated. Ammonia levels can be variably elevated. If these findings are present, molecular testing may provide additional confirmatory information. Treatment Treatments include discontinuation of protein intake, intravenous infusion of glucose and, as needed, infusion of supplemental arginine and the ammonia removal drugs, sodium phenylacetate and sodium benzoate. See also Ornithine transcarbamylase deficiency Inborn errors of metabolism Ornithine aminotransferase deficiency (gyrate atrophy of the choroid and retina) References Charles Scriver, Beaudet, A.L., Valle, D., Sly, W.S., Vogelstein, B., Childs, B., Kinzler, K.W. (accessed 2007). New York: McGraw-Hill. Summaries of 255 chapters, full text through many universities. There is also the OMMBID blog. Further reading Ornithine translocase deficiency at NLM Genetics Home Reference == External links ==
Central diabetes insipidus	Central diabetes insipidus, also called neurogenic diabetes insipidus, is a type of diabetes insipidus due to a lack of vasopressin (ADH) production in the brain. Vasopressin acts to increase the volume of blood (intravascularly), and decrease the volume of urine produced. Therefore, a lack of it causes increased urine production and volume depletion. It is also known as neurohypophyseal diabetes insipidus, referring to the posterior pituitary (neurohypophysis), which is supplied by the hypothalamus in the brain. This condition has only polyuria in common with diabetes. Although not mutually exclusive, with most typical cases, the name diabetes insipidus is a misleading misnomer. A better name might be "hypothalamic-neurohypophyseal ADH deficiency". Signs and symptoms Increased thirst, polyuria and dehydration with metabolic encephalopathy. Causes Unknown In at least 25% of cases (the most commonly occurring classification), neurogenic diabetes insipidus is of unknown cause, meaning that the lack of vasopressin production arose from an unknown cause. It is also due to damage of the hypothalamus, pituitary stalk, posterior pituitary, and can arise from head trauma. Acquired The lack of vasopressin production usually results from some sort of damage to the pituitary gland. It may be due to damage to the brain caused by: Benign suprasellar tumors (20% of cases) Infections (encephalitis, tuberculosis, etc.) Trauma (17% of cases) or neurosurgery (9% of cases) Non-infectious granuloma (sarcoidosis, Langerhans cell histiocytosis etc.) Leukaemia Autoimmune - associated with thyroiditis Other rare causes which include hemochromatosis and histiocytosis.Vasopressin is released by the posterior pituitary, but unlike most other pituitary hormones, vasopressin is produced in the hypothalamus. Neurogenic diabetes insipidus can be a failure of production at the hypothalamus, or a failure of release at the pituitary. Genetic The most rare form of central DI is familial neurogenic diabetes insipidus. This form of DI is due to an inherited mutation of the arginine vasopressin-neurophysin II (AVP-NPII) gene, inherited in an autosomal dominant manner. At one point, only 45 families worldwide were known to possess this genetic trait. It is now more widely recognized, although the precise number of people affected with this form of DI is unknown at the present time.There is also an X-linked familial form.Wolfram Syndrome (also called DIDMOAD) is characterised by DI, diabetes mellitus, sensorineural deafness, and optic atrophy. Diagnosis In many respects, the diagnosis of central diabetes insipidus begins as a diagnosis of exclusion. Specifically, other more common causes of polyuria and polydipsia are ruled out. Common rule outs include: diabetes mellitus, chronic kidney disease, hypokalemia, hypercalcemia, and psychogenic polydipsia. Once these conditions have been ruled out a water deprivation test is employed to confirm the diagnosis of CDI. Treatment The disorder is treated with vasopressin analogs such as desmopressin. Nonetheless, many times desmopressin alone is not enough to bring under control all the symptoms, and another intervention must be implemented. See also Fluid deprivation test References == External links ==
Gastritis	Gastritis is inflammation of the lining of the stomach. It may occur as a short episode or may be of a long duration. There may be no symptoms but, when symptoms are present, the most common is upper abdominal pain (see dyspepsia). Other possible symptoms include nausea and vomiting, bloating, loss of appetite and heartburn. Complications may include stomach bleeding, stomach ulcers, and stomach tumors. When due to autoimmune problems, low red blood cells due to not enough vitamin B12 may occur, a condition known as pernicious anemia.Common causes include infection with Helicobacter pylori and use of nonsteroidal anti-inflammatory drugs (NSAIDs). Less common causes include alcohol, smoking, cocaine, severe illness, autoimmune problems, radiation therapy and Crohns disease. Endoscopy, a type of X-ray known as an upper gastrointestinal series, blood tests, and stool tests may help with diagnosis. The symptoms of gastritis may be a presentation of a myocardial infarction. Other conditions with similar symptoms include inflammation of the pancreas, gallbladder problems, and peptic ulcer disease.Prevention is by avoiding things that cause the disease. Treatment includes medications such as antacids, H2 blockers, or proton pump inhibitors. During an acute attack drinking viscous lidocaine may help. If gastritis is due to NSAIDs these may be stopped. If H. pylori is present it may be treated with a combination of antibiotics such as amoxicillin and clarithromycin. For those with pernicious anemia, vitamin B12 supplements are recommended either by mouth or by injection. People are usually advised to avoid foods that bother them.Gastritis is believed to affect about half of people worldwide. In 2013 there were approximately 90 million new cases of the condition. As people get older the disease becomes more common. It, along with a similar condition in the first part of the intestines known as duodenitis, resulted in 50,000 deaths in 2015. H. pylori was first discovered in 1981 by Barry Marshall and Robin Warren. Signs and symptoms Many people with gastritis experience no symptoms at all. However, upper central abdominal pain is the most common symptom; the pain may be dull, vague, burning, aching, gnawing, sore, or sharp. Pain is usually located in the upper central portion of the abdomen, but it may occur anywhere from the upper left portion of the abdomen around to the back. Other signs and symptoms may include the following: Nausea Vomiting (may be clear, green or yellow, blood-streaked or completely bloody depending on the severity of the stomach inflammation) Belching (does not usually relieve stomach pain if present) Bloating Early satiety Loss of appetite Unexplained weight loss Causes There are two categories of gastritis depending on the cause of the disease. There is erosive gastritis, for which the common causes are stress, alcohol, some drugs, such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs), and Crohns disease. And, there is non-erosive gastritis, for which the most common cause is a Helicobacter pylori infection. Helicobacter pylori Helicobacter pylori colonizes the stomachs of more than half of the worlds population, and the infection continues to play a key role in the pathogenesis of a number of gastroduodenal diseases. Colonization of the gastric mucosa with Helicobacter pylori results in the development of chronic gastritis in infected individuals and, in a subset of patients, chronic gastritis progresses to complications (e.g., ulcer disease, stomach cancers, and some distinct extragastric disorders). However, more than 80% of individuals infected with the bacterium are asymptomatic and it has been postulated that it may play an important role in the natural stomach ecology. Critical illness Gastritis may also develop after major surgery or traumatic injury ("Cushing ulcer"), burns ("Curling ulcer"), or severe infections. Gastritis may also occur in those who have had weight loss surgery resulting in the banding or reconstruction of the digestive tract. Diet Evidence does not support a role for specific foods, including spicy foods and coffee, in the development of peptic ulcers. People are usually advised to avoid foods that bother them. There is little specific advice on diet published by authoritative sources. The website of the National Health Service of the United Kingdom advises "avoiding foods that can irritate the stomach, such as spicy, acidic or fried foods", and suggests that "you may want to talk to a GP about this". Pathophysiology Acute Acute erosive gastritis typically involves discrete foci of surface necrosis due to damage to mucosal defenses. NSAIDs inhibit cyclooxygenase-1, or COX-1, an enzyme responsible for the biosynthesis of eicosanoids in the stomach, which increases the possibility of peptic ulcers forming. Also, NSAIDs, such as aspirin, reduce a substance that protects the stomach called prostaglandin. These drugs used in a short period are not typically dangerous. However, regular use can lead to gastritis. Additionally, severe physiologic stress ("stress ulcers") from sepsis, hypoxia, trauma, or surgery is also a common etiology for acute erosive gastritis. This form of gastritis can occur in more than 5% of hospitalized patients.Also, note that alcohol consumption does not cause chronic gastritis. It does, however, erode the mucosal lining of the stomach; low doses of alcohol stimulate hydrochloric acid secretion. High doses of alcohol do not stimulate secretion of acid. Chronic Chronic gastritis refers to a wide range of problems of the gastric tissues. The immune system makes proteins and antibodies that fight infections in the body to maintain a homeostatic condition. In some disorders the body targets the stomach as if it were a foreign protein or pathogen; it makes antibodies against, severely damages, and may even destroy the stomach or its lining. In some cases bile, normally used to aid digestion in the small intestine, will enter through the pyloric valve of the stomach if it has been removed during surgery or does not work properly, also leading to gastritis. Gastritis may also be caused by other medical conditions, including HIV/AIDS, Crohns disease, certain connective tissue disorders, and liver or kidney failure. Since 1992, chronic gastritis lesions are classified according to the Sydney system. Metaplasia Mucous gland metaplasia, the reversible replacement of differentiated cells, occurs in the setting of severe damage of the gastric glands, which then waste away (atrophic gastritis) and are progressively replaced by mucous glands. Gastric ulcers may develop; it is unclear if they are the causes or the consequences. Intestinal metaplasia typically begins in response to chronic mucosal injury in the antrum and may extend to the body. Gastric mucosa cells change to resemble intestinal mucosa and may even assume absorptive characteristics. Intestinal metaplasia is classified histologically as complete or incomplete. With complete metaplasia, gastric mucosa is completely transformed into small-bowel mucosa, both histologically and functionally, with the ability to absorb nutrients and secrete peptides. In incomplete metaplasia, the epithelium assumes a histologic appearance closer to that of the large intestine and frequently exhibits dysplasia. Diagnosis Often, a diagnosis can be made based on patients description of their symptoms. Other methods which may be used to verify gastritis include: Blood tests: Blood cell count Presence of H. pylori Liver, kidney, gallbladder, or pancreas functions Urinalysis Stool sample, to look for blood in the stool X-rays Endoscopy, to check for stomach lining inflammation and mucous erosion Stomach biopsy, to test for gastritis and other conditionsThe OLGA staging frame of chronic gastritis on histopathology. Atrophy is scored as the percentage of atrophic glands and scored on a four-tiered scale. No atrophy (0%) = score 0; mild atrophy (1–30%) = score 1; moderate atrophy (31–60%) = score 2; 9 severe atrophy (>60%) = score 3. These scores (0–3) are used in the OLGA staging assessment in each 10 compartment: Treatment Antacids are a common treatment for mild to medium gastritis. When antacids do not provide enough relief, medications such as H2 blockers and proton-pump inhibitors that help reduce the amount of acid are often prescribed.Cytoprotective agents are designed to help protect the tissues that line the stomach and small intestine. They include the medications sucralfate and misoprostol. If NSAIDs are being taken regularly, one of these medications to protect the stomach may also be taken. Another cytoprotective agent is bismuth subsalicylateSeveral regimens are used to treat H. pylori infection. Most use a combination of two antibiotics and a proton pump inhibitor. Sometimes bismuth is added to the regimen. History In 1,000 A.D, Avicenna first gave the description of stomach cancer. In 1728, German physician Georg Ernst Stahl first coined the term "gastritis". Italian anatomical pathologist Giovanni Battista Morgagni further described the characteristics of gastric inflammation. He described the characteristics of erosive or ulcerative gastritis and erosive gastritis. Between 1808 and 1831, French physician François-Joseph-Victor Broussais gathered information from the autopsies of dead French soldiers. He described chronic gastritis as "Gastritide" and erroneously believed that gastritis was the cause of ascites, typhoid fever, and meningitis. In 1854, Charles Handfield Jones and Wilson Fox described the microscopic changes of stomach inner lining in gastritis which existed in diffuse and segmental forms. In 1855, Baron Carl von Rokitansky first described hypertrophic gastritis. In 1859, British physician, William Brinton first described about acute, subacute, and chronic gastritis. In 1870, Samuel Fenwick noted that pernicious anemia causes glandular atrophy in gastritis. German surgeon Georg Ernst Konjetzny noticed that both gastric ulcer and gastric cancer are the results of gastric inflammation. Shields Warren and Willam A. Meissner described the intestinal metaplasia of the stomach as a feature of chronic gastritis. See also Gastroenteritis Esophagitis References Further reading == External links ==
Urticarial vasculitis	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 ==
Pancreatic fistula	A pancreatic fistula is an abnormal communication between the pancreas and other organs due to leakage of pancreatic secretions from damaged pancreatic ducts. An external pancreatic fistula is one that communicates with the skin, and is also known as a pancreaticocutaneous fistula, whereas an internal pancreatic fistula communicates with other internal organs or spaces. Pancreatic fistulas can be caused by pancreatic disease, trauma, or surgery. Signs and symptoms Marked recent weight loss is a major clinical manifestation, and unresponsiveness of the ascites to diuretics is an additional diagnostic clue. Pathogenesis Internal pancreatic fistulas are most commonly caused by disruption of the pancreatic duct due to chronic pancreatitis. The chronic pancreatitis is usually alcoholic in origin in adults, and traumatic in origin in children. They may also be caused by leakage from a pancreatic pseudocyst. Anterior disruption of a pseudocyst or a pancreatic duct leads to leakage of pancreatic secretions into the free peritoneal cavity, leading to pancreatic ascites. If the duct is disrupted posteriorly, the secretions leak through the retroperitoneum into the mediastinum via the aortic or esophageal hiatus. Once in the mediastinum, the secretions can either be contained in a mediastinal pseudocyst, lead to enzymatic mediastinitis, or, more commonly, leak through the pleura to enter the chest and form a chronic pancreatic pleural effusion. Diagnosis Pleural or ascitic fluid should be sent for analysis. An elevated amylase level, usually > 1,000 IU/L, with protein levels over 3.0 g/dL is diagnostic. Serum amylase is often elevated as well, due to enzyme diffusion across the peritoneal or pleural surface. Contrast-enhanced computed tomography and endoscopic retrograde cholangiopancreatography (ERCP) may also assist in diagnosis, with the latter an essential component of treatment. Types External An external pancreatic fistula is an abnormal communication between the pancreas (actually pancreatic duct) and the exterior of the body via the abdominal wall. Loss of bicarbonate-rich pancreatic fluid via a pancreatic fistula can result in a hyperchloraemic or normal anion gap metabolic acidosis. Loss of a small volume of fluid will not cause a problem but an acidosis is common if the volume of pancreatic fluid lost from the body is large. Internal First described by Smith (1953), and elaborated upon by Cameron et al. (1976), internal pancreatic fistulas can result in pancreatic ascites, mediastinital pseudocysts, enzymatic mediastinitis, or pancreatic pleural effusions, depending on the flow of pancreatic secretions from a disrupted pancreatic duct or leakage from a pseudocyst. Treatment The production of pancreatic enzymes is suppressed by restricting the patients oral intake of food patient in conjunction with the use of long-acting somatostatin analogues. The patients nutrition is maintained by total parenteral nutrition. This treatment is continued for 2–3 weeks, and the patient is observed for improvement. If no improvement is seen, the patient may receive endoscopic or surgical treatment. If surgical treatment is followed, an ERCP is needed to identify the site of the leak. Fistulectomy is done in which the involved part of the pancreas is also removed. References Bibliography == External links ==
Histidinemia	Histidinemia is a rare autosomal recessive metabolic disorder caused by a deficiency of the enzyme histidase. Histidase is needed for the metabolism of the amino acid histidine. Although originally thought to be linked to multiple developmental disorders histidinemia is now accepted as a relatively benign disorder, leading to a reduction in the prevalence of neonatal screening procedures. Presentation Histidinemia is considered benign as most patients remain asymptomatic, early correlational evidence from the first decade of histidinemia research lead to the theory that histidinemia was associated with multiple developmental symptoms including hyperactivity, speech impediment, developmental delay, learning difficulties, and sometimes mental retardation. However, these claims were later deemed coincidental as a large subpopulation of infants that tested positive for histidinemia were found to have normal IQ and speech characteristics; as such histidinemia has since been reclassified as a benign inborn error of metabolism. Molecular mechanism Histidinemia occurs as the result of an inborn error of metabolism that may result in either an inactive or a severely reduced histidine ammonia-lyase (HAL) enzyme activity. The gene that encodes for HAL spans a roughly 25 kb and consists of 21 exons located at the 12q22-q24.1 position of human chromosome 12. There are eight mutations currently associated with autosomal recessive histidinemia, that include: four missense mutations, two exonic polymorphisms and two intronic polymorphisms. Diagnosis Histidenemia is characterized by increased levels of histidine, histamine and imidazole in blood, urine and cerebrospinal fluid. This also results in decreased levels of the metabolite urocanic acid in blood, urine, and skin cells. In Japan, neonatal screening was previously performed on infants within one month of birth; infants demonstrating a blood histidine level of 6 mg/dl or more underwent careful testing as suspected histidinemia cases. A typical characteristic of histidinemia is an increase in the blood histidine levels from normal levels (70–120 μM) to an elevated level (290–1420 μM). Further testing includes: observing histidine as well as imidazolepyruvic acid metabolites in the urine. However, neonatal urine testing has been discontinued in most places, with the exception of Quebec. Treatment It has been suggested that a possible method of treatment for histidinemia is through the adoption of a diet that is low in histidine intake. However, the requirement for such dietary restrictions is typically unnecessary for 99% of all cases of histidinemia. Prevalence Histidinemia is a rare autosomal recessive disorder. However, histidinemia is considered the most prevalent inborn error of metabolism with a reported incidence of 1:8600 (Quebec); 1:180,000 (New York) and 1:9600 (Japan); and an average of 1:12,000 observed in the neonatal screening of over 20 million newborns. See also Prolinemia Sarcosinemia Tyrosinemia References == External links ==
Hepatosplenomegaly	Hepatosplenomegaly (commonly abbreviated HSM) is the simultaneous enlargement of both the liver (hepatomegaly) and the spleen (splenomegaly). Hepatosplenomegaly can occur as the result of acute viral hepatitis, infectious mononucleosis, and histoplasmosis or it can be the sign of a serious and life-threatening lysosomal storage disease. Systemic venous hypertension can also increase the risk for developing hepatosplenomegaly, which may be seen in those patients with right-sided heart failure. Common causes Rare disorders Lipoproteinlipase deficiency Multiple sulfatase deficiency Osteopetrosis Adult-onset Stills disease (AOSD) References == External links ==
Benzodiazepine dependence	Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, however, the continued use seems to be associated with the avoidance of unpleasant withdrawal reaction rather than from the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, without the described dependence behavior.Addiction consists of people misusing or craving the drug not to relieve withdrawal symptoms, but to experience its euphoric or intoxicating effects. It is necessary to distinguish between addiction to and abuse of benzodiazepines and physical dependence on them. The increased GABA inhibition on the neural systems caused by benzodiazepines is counteracted by the bodys development of tolerance to the drugs effects; the development of tolerance occurs as a result of neuroadaptations, which result in decreased GABA activity and increased excitability of the glutamate system; these adaptations occur as a result of the body trying to overcome the central nervous system depressant effects of the drug to restore homeostasis. When benzodiazepines are stopped, these neuroadaptations are "unmasked" leading to hyper-excitability of the nervous system and the appearance of withdrawal symptoms.Therapeutic dose dependence is the largest category of people dependent on benzodiazepines. These individuals typically do not escalate their doses to high levels and generally use their medication as intended by their prescriber. Smaller groups include patients escalating their dosage to higher levels and drug misusers as well. Tolerance develops within days or weeks to the anticonvulsant, hypnotic, muscle relaxant and after 4 months there is little evidence that benzodiazepines retain their anxiolytic properties. Some authors, however, disagree and feel that benzodiazepines retain their anxiolytic properties. Long-term benzodiazepine treatment may remain necessary in certain clinical conditions.Numbers of benzodiazepine prescriptions have been declining, due primarily to concerns of dependence. In the short term, benzodiazepines can be effective drugs for acute anxiety or insomnia. With longer-term use, other therapies, both pharmacological and psychotherapeutic, become more effective. This is in part due to the greater effectiveness over time of other forms of therapy, and also due to the eventual development of pharmacological benzodiazepine tolerance. Signs and symptoms The signs and symptoms of benzodiazepine dependence include feeling unable to cope without the drug, unsuccessful attempts to cut down or stop benzodiazepine use, tolerance to the effects of benzodiazepines, and withdrawal symptoms when not taking the drug. Some withdrawal symptoms that may appear include anxiety, depressed mood, depersonalisation, derealisation, sleep disturbance, hypersensitivity to touch and pain, tremor, shakiness, muscular aches, pains, twitches, and headache. Benzodiazepine dependence and withdrawal have been associated with suicide and self-harming behaviors, especially in young people. The Department of Health substance misuse guidelines recommend monitoring for mood disorder in those dependent on or withdrawing from benzodiazepines.Benzodiazepine dependence is a frequent complication for those prescribed for or using for longer than four weeks, with physical dependence and withdrawal symptoms being the most common problem, but also occasionally drug-seeking behavior. Withdrawal symptoms include anxiety, perceptual disturbances, distortion of all the senses, dysphoria, and, in rare cases, psychosis and epileptic seizures. Elderly Long-term use and benzodiazepine dependence is a serious problem in the elderly. Failure to treat benzodiazepine dependence in the elderly can cause serious medical complications. The elderly have less cognitive reserve and are more sensitive to the short (e.g., in between dose withdrawal) and protracted withdrawal effects of benzodiazepines, as well as the side-effects both from short-term and long-term use. This can lead to excessive contact with their doctor. Research has found that withdrawing elderly people from benzodiazepines leads to a significant reduction in doctor visits per year, it is presumed, due to an elimination of drug side-effects and withdrawal effects.Tobacco and alcohol are the most common substances that elderly individuals develop dependence on or misuse. The next-most-common substance that elderly people develop a drug dependence to or misuse is benzodiazepines. Drug-induced cognitive problems can have serious consequences for elderly people and can lead to confusional states and "pseudo-dementia". About 10% of elderly patients referred to memory clinics actually have a drug-induced cause that most often is benzodiazepines. Benzodiazepines have also been linked to an increased risk of road traffic accidents and falls in the elderly. The long-term effects of benzodiazepines are still not fully understood. Long-term benzodiazepine use is associated with attentional and visuospatial functional impairments. Withdrawal from benzodiazepines can lead to improved alertness and decreased forgetfulness in the elderly. Withdrawal led to statistically significant improvements in memory function and performance-related skills in those having withdrawn successfully from benzodiazepines, whereas those having remained on benzodiazepines experienced worsening symptoms. People having withdrawn from benzodiazepines also felt their sleep was more refreshing, making statements such as "I feel sharper when I wake up" or "I feel better, more awake", or "It used to take me an hour to fully wake up." This suggests that benzodiazepines may actually make insomnia worse in the elderly. Cause Tolerance occurs to the muscle-relaxant, anticonvulsant, and sleep-inducing effects of benzodiazepines, and upon cessation a benzodiazepine withdrawal syndrome occurs. This can lead to benzodiazepines being taken for longer than originally intended, as people continue to take the drugs over a long period of time to suppress withdrawal symptoms. Some people use benzodiazepines at very high doses and devote a lot of time to doing so, satisfying the diagnostic criteria in DSM V for substance use disorder. Another group of people include those on low to moderate therapeutic doses of benzodiazepines who do not use their benzodiazepines differently than recommended by their prescriber but develop a physical tolerance and benzodiazepine dependence. A considerable number of individuals using benzodiazepines for insomnia escalate their dosage, sometimes above therapeutically-prescribed dose levels. Tolerance to the anxiolytic effect of benzodiazepines has been clearly demonstrated in rats. In humans, there is little evidence that benzodiazepines retain their anti-anxiety effects beyond four months of continuous treatment; there is evidence that suggests that long-term use of benzodiazepines may actually worsen anxiety, which in turn may lead to dosage escalation, with one study finding 25% of patients escalated their dosage. Some authors, however, consider benzodiazepines to be effective long-term; however, it is more likely that the drugs are acting to prevent rebound anxiety withdrawal effects which can be mistaken as continued drug efficacy. Tolerance to the anticonvulsant and muscle-relaxing effects of benzodiazepines occurs within a few weeks in most patients. Risk factors The risk factors for benzodiazepine dependence are long-term use beyond four weeks, use of high doses, use of potent short-acting benzodiazepines, dependent personalities, and proclivity for substance use. Use of short-acting benzodiazepines leads to repeated withdrawal effects that are alleviated by the next dose, which reinforce in the individual the dependence. A physical dependence develops more quickly with higher potency benzodiazepines such as alprazolam (Xanax) than with lower potency benzodiazepines such as chlordiazepoxide (Librium).Symptom severity is worse with the use of high doses, or with benzodiazepines of high potency or short half-life. Other cross-tolerant sedative hypnotics, such as barbiturates or alcohol, increase the risk of benzodiazepine dependence. Similar to opioids use for pain, therapeutic use of benzodiazepines rarely leads to a substance use disorder. Mechanism Tolerance and physical dependence Tolerance develops rapidly to the sleep-inducing effects of benzodiazepines. The anticonvulsant and muscle-relaxant effects last for a few weeks before tolerance develops in most individuals. Tolerance results in a desensitization of GABA receptors and an increased sensitization of the excitatory neurotransmitter system, such as NMDA glutamate receptors. These changes occur as a result of the body trying to overcome the drugs effects. Other changes that occur are the reduction of the number of GABA receptors (downregulation) as well as possibly long-term changes in gene transcription coding of brain cells. The differing speed at which tolerance occurs to the therapeutic effects of benzodiazepines can be explained by the speed of changes in the range of neurotransmitter systems and subsystems that are altered by chronic benzodiazepine use. The various neurotransmitter systems and subsystems may reverse tolerance at different speeds, thus explaining the prolonged nature of some withdrawal symptoms. As a result of a physical dependence that develops due to tolerance, a characteristic benzodiazepine withdrawal syndrome often occurs after removal of the drug or a reduction in dosage. Changes in the expression of neuropeptides such as corticotropin-releasing hormone and neuropeptide Y may play a role in benzodiazepine dependence. Individuals taking daily benzodiazepine drugs have a reduced sensitivity to further additional doses of benzodiazepines. Tolerance to benzodiazepines can be demonstrated by injecting diazepam into long-term users. In normal subjects, increases in growth hormone occurs, whereas, in benzodiazepine-tolerant individuals, this effect is blunted.Animal studies have shown that repeated withdrawal from benzodiazepines leads to increasingly severe withdrawal symptoms, including an increased risk of seizures; this phenomenon is known as kindling. Kindling phenomena are well established for repeated ethanol (alcohol) withdrawal; alcohol has a very similar mechanism of tolerance and withdrawal to benzodiazepines, involving the GABAA, NMDA, and AMPA receptors.The shift of benzodiazepine receptors to an inverse agonist state after chronic treatment leads the brain to be more sensitive to excitatory drugs or stimuli. Excessive glutamate activity can result in excitotoxicity, which may result in neurodegeneration. The glutamate receptor subtype NMDA is well known for its role in causing excito-neurotoxicity. The glutamate receptor subtype AMPA is believed to play an important role in neuronal kindling as well as excitotoxicity during withdrawal from alcohol as well as benzodiazepines. It is highly possible that NMDA receptors are involved in the tolerance to some effects of benzodiazepines.Animal studies have found that glutamergic changes as a result of benzodiazepine use are responsible for a delayed withdrawal syndrome, which in mice peaks 3 days after cessation of benzodiazepines. This was demonstrated by the ability to avoid the withdrawal syndrome by the administration of AMPA antagonists. It is believed that different glutamate subreceptors, e.g., NMDA and AMPA, are responsible for different stages/time points of the withdrawal syndrome. NMDA receptors are upregulated in the brain as a result of benzodiazepine tolerance. AMPA receptors are also involved in benzodiazepine tolerance and withdrawal. A decrease in benzodiazepine binding sites in the brain may also occur as part of benzodiazepine tolerance. Cross tolerance Benzodiazepines share a similar mechanism of action with various sedative compounds that act by enhancing the GABAA receptor. Cross tolerance means that one drug will alleviate the withdrawal effects of another. It also means that tolerance of one drug will result in tolerance of another similarly-acting drug. Benzodiazepines are often used for this reason to detoxify alcohol-dependent patients and can have life-saving properties in preventing or treating severe life-threatening withdrawal syndromes from alcohol, such as delirium tremens. However, although benzodiazepines can be very useful in the acute detoxification of alcoholics, benzodiazepines in themselves act as positive reinforcers in alcoholics, by increasing the desire for alcohol. Low doses of benzodiazepines were found to significantly increase the level of alcohol consumed in alcoholics. Alcoholics dependent on benzodiazepines should not be abruptly withdrawn but be very slowly withdrawn from benzodiazepines, as over-rapid withdrawal is likely to produce severe anxiety or panic, which is well known for being a relapse risk factor in recovering alcoholics.There is cross tolerance between alcohol, the benzodiazepines, the barbiturates, the nonbenzodiazepine drugs, and corticosteroids, which all act by enhancing the GABAA receptors function via modulating the chloride ion channel function of the GABAA receptor.Neuroactive steroids, e.g., progesterone and its active metabolite allopregnanolone, are positive modulators of the GABAA receptor and are cross tolerant with benzodiazepines. The active metabolite of progesterone has been found to enhance the binding of benzodiazepines to the benzodiazepine binding sites on the GABAA receptor. The cross-tolerance between GABAA receptor positive modulators, including benzodiazepines, occurs because of the similar mechanism of action and the subunit changes that occur from chronic use from one or more of these compounds in expressed receptor isoforms. Abrupt withdrawal from any of these compounds, e.g., barbiturates, benzodiazepines, alcohol, corticosteroids, neuroactive steroids, and nonbenzodiazepines, precipitate similar withdrawal effects characterized by central nervous system hyper-excitability, resulting in symptoms such as increased seizure susceptibility and anxiety. While many of the neuroactive steroids do not produce full tolerance to their therapeutic effects, cross-tolerance to benzodiazepines still occurs as had been demonstrated between the neuroactive steroid ganaxolone and diazepam. Alterations of levels of neuroactive steroids in the body during the menstrual cycle, menopause, pregnancy, and stressful circumstances can lead to a reduction in the effectiveness of benzodiazepines and a reduced therapeutic effect. During withdrawal of neuroactive steroids, benzodiazepines become less effective. Physiology of withdrawal Withdrawal symptoms are a normal response in individuals having chronically used benzodiazepines, and an adverse effect and result of drug tolerance. Symptoms typically emerge when dosage of the drug is reduced. GABA is the second-most-common neurotransmitter in the central nervous system (the most common being glutamate) and by far the most abundant inhibitory neurotransmitter; roughly one-quarter to one-third of synapses use GABA. The use of benzodiazepines has a profound effect on almost every aspect of brain and body function, either directly or indirectly.Benzodiazepines cause a decrease in norepinephrine (noradrenaline), serotonin, acetylcholine, and dopamine. These neurotransmitters are needed for normal memory, mood, muscle tone and coordination, emotional responses, endocrine gland secretions, heart rate, and blood pressure control. With chronic benzodiazepine use, tolerance develops rapidly to most of its effects, so that, when benzodiazepines are withdrawn, various neurotransmitter systems go into overdrive due to the lack of inhibitory GABA-ergic activity. Withdrawal symptoms then emerge as a result, and persist until the nervous system physically reverses the adaptions (physical dependence) that have occurred in the CNS.Withdrawal symptoms typically consist of a mirror image of the drugs effects: Sedative effects and suppression of REM and SWS stages of sleep can be replaced by insomnia, nightmares, and hypnogogic hallucinations; its antianxiety effects are replaced with anxiety and panic; muscle-relaxant effects are replaced with muscular spasms or cramps; and anticonvulsant effects are replaced with seizures, especially in cold turkey or overly-rapid withdrawal.Benzodiazepine withdrawal represents in part excitotoxicity to brain neurons. Rebound activity of the hypothalamic-pituitary-adrenocortical axis also plays an important role in the severity of benzodiazepine withdrawal. Tolerance and the resultant withdrawal syndrome may be due to alterations in gene expression, which results in long-term changes in the function of the GABAergic neuronal system.During withdrawal from full or partial agonists, changes occur in benzodiazepine receptor with upregulation of some receptor subtypes and downregulation of other receptor subtypes. Withdrawal Long-term use of benzodiazepines leads to increasing physical and mental health problems, and as a result, discontinuation is recommended for many long-term users. The withdrawal syndrome from benzodiazepines can range from a mild and short-lasting syndrome to a prolonged and severe syndrome. Withdrawal symptoms can lead to continued use of benzodiazepines for many years, long after the original reason for taking benzodiazepines has passed. Many patients know that the benzodiazepines no longer work for them but are unable to discontinue benzodiazepines because of withdrawal symptoms.Withdrawal symptoms can emerge despite slow reduction but can be reduced by a slower rate of withdrawal. As a result, withdrawal rates have been recommended to be customized to each individual patient. The time needed to withdrawal can vary from a couple of months to a year or more and often depends on length of use, dosage taken, lifestyle, health, and social and environmental stress factors.Diazepam is often recommended due to its long elimination half-life and also because of its availability in low potency doses. The non-benzodiazepine Z drugs such as zolpidem, zaleplon, and zopiclone should not be used as a replacement for benzodiazepines, as they have a similar mechanism of action and can induce a similar dependence. The pharmacological mechanism of benzodiazepine tolerance and dependence is the internalization (removal) of receptor site in the brain and changes in gene transcription codes in the brain.With long-term use and during withdrawal of benzodiazepines, treatment-emergent depression and emotional blunting may emerge and sometimes also suicidal ideation. There is evidence that the higher the dose used the more likely it is benzodiazepine use will induce these feelings. Reducing the dose or discontinuing benzodiazepines may be indicated in such cases. Withdrawal symptoms can persist for quite some time after discontinuing benzodiazepines. Some common protracted withdrawal symptoms include anxiety, depression, insomnia, and physical symptoms such as gastrointestinal, neurologic, and musculoskeletal effects. The protracted withdrawal state may still occur despite slow titration of dosage. It is believed that the protracted withdrawal effects are due to persisting neuroadaptations. Diagnosis For a diagnosis of benzodiazepine dependence to be made, the ICD-10 requires that at least 3 of the below criteria are met and that they have been present for at least a month, or, if less than a month, that they appeared repeatedly during a 12-month period. Behavioral, cognitive, and physiological phenomena that are associated with the repeated use and that typically include a strong desire to take the drug. Difficulty controlling use Continued use despite harmful consequences Preference given to drug use rather than to other activities and obligations Increased tolerance to effects of the drug and sometimes a physical withdrawal state.These diagnostic criteria are good for research purposes, but, in everyday clinical practice, they should be interpreted according to clinical judgement. In clinical practice, benzodiazepine dependence should be suspected in those having used benzodiazepines for longer than a month, in particular, if they are from a high-risk group. The main factors associated with an increased incidence of benzodiazepine dependence include: Dose Duration Concomitant use of antidepressantsBenzodiazepine dependence should be suspected also in individuals having substance use disorders including alcohol, and should be suspected in individuals obtaining their own supplies of benzodiazepines. Benzodiazepine dependence is almost certain in individuals who are members of a tranquilizer self-help group.Research has found that about 40 percent of people with a diagnosis of benzodiazepine dependence are not aware that they are dependent on benzodiazepines, whereas about 11 percent of people judged not to be dependent believe that they are. When assessing a person for benzodiazepine dependence, asking specific questions rather than questions based on concepts is recommended by experts as the best approach of getting a more accurate diagnosis. For example, asking persons if they "think about the medication at times of the day other than when they take the drug" would provide a more meaningful answer than asking "do you think you are psychologically dependent?". The Benzodiazepine Dependence Self Report Questionnaire is one questionnaire used to assess and diagnose benzodiazepine dependence. Definition Benzodiazepine dependence is the condition resulting from repeated use of benzodiazepine drugs. It can include both a physical dependence as well as a psychological dependence and is typified by a withdrawal syndrome upon a fall in blood plasma levels of benzodiazepines, e.g., during dose reduction or abrupt withdrawal. Prevention Due to the risk of developing tolerance, dependence, and adverse health effects, such as cognitive impairment, benzodiazepines are indicated for short-term use only - a few weeks, followed by a gradual dose reduction. The Committee on the Review of Medicines (UK) The Committee on the Review of Medicines carried out a review into benzodiazepines due to significant concerns of tolerance, drug dependence, benzodiazepine withdrawal problems, and other adverse effects and published the results in the British Medical Journal in March 1980. The committee found that benzodiazepines do not have any antidepressant or analgesic properties and are, therefore, unsuitable treatments for conditions such as depression, tension headaches, and dysmenorrhea. Benzodiazepines are also not beneficial in the treatment of psychosis. The committee also recommended against benzodiazepines for use in the treatment of anxiety or insomnia in children.The committee was in agreement with the Institute of Medicine (USA) and the conclusions of a study carried out by the White House Office of Drug Policy and the National Institute on Drug Abuse (USA) that there is little evidence that long-term use of benzodiazepine hypnotics are beneficial in the treatment of insomnia due to the development of tolerance. Benzodiazepines tend to lose their sleep-promoting properties within 3–14 days of continuous use, and, in the treatment of anxiety, the committee found that there was little convincing evidence that benzodiazepines retains efficacy in the treatment of anxiety after 4 months of continuous use due to the development of tolerance.The committee found that the regular use of benzodiazepines causes the development of dependence characterized by tolerance to the therapeutic effects of benzodiazepines and the development of the benzodiazepine withdrawal syndrome including symptoms such as anxiety, apprehension, tremors, insomnia, nausea, and vomiting upon cessation of benzodiazepine use. Withdrawal symptoms tend to develop within 24 hours upon cessation of short-acting benzodiazepines, and 3–10 days after cessation of longer-acting benzodiazepines. Withdrawal effects could even occur after treatment lasting only 2 weeks at therapeutic dose levels; however, withdrawal effects tend to occur with habitual use beyond 2 weeks and are more likely the higher the dose. The withdrawal symptoms may appear to be similar to the original condition.The committee recommended that all benzodiazepine treatment be withdrawn gradually and recommended that benzodiazepine treatment be used only in carefully selected patients and that therapy be limited to short-term use only. It was noted in the review that alcohol can potentiate the central nervous system-depressant effects of benzodiazepines and should be avoided. The central nervous system-depressant effects of benzodiazepines may make driving or operating machinery dangerous, and the elderly are more prone to these adverse effects. High single doses or repeated low doses have been reported to produce hypotonia, poor sucking, and hypothermia in the neonate, and irregularities in the fetal heart. The committee recommended that benzodiazepines be avoided in lactation.The committee recommended that withdrawal from benzodiazepines be gradual, as abrupt withdrawal from high doses of benzodiazepines may cause confusion, toxic psychosis, convulsions, or a condition resembling delirium tremens. Abrupt withdrawal from lower doses may cause depression, nervousness, rebound insomnia, irritability, sweating, and diarrhea. Treatment Benzodiazepines are regarded as a highly addictive drug class. A psychological and physical dependence can develop in as short as a few weeks but may take years to develop in other individuals. Patients wanting to withdraw from benzodiazepines typically receive little advice or support, and such withdrawal should be by small increments over a period of months.Benzodiazepines are usually prescribed only short-term, as there is little justification for their prescribing long-term. Some doctors however, disagree and believe long-term use beyond 4 weeks is sometimes justified, although there is little data to support this viewpoint. Such viewpoints are a minority in the medical literature.There is no evidence that "drug holidays" or periods of abstinence reduced the risk of dependence; there is evidence from animal studies that such an approach does not prevent dependence from happening. Use of short-acting benzodiazepines is associated with interdose withdrawal symptoms. Kindling has clinical relevance with regard to benzodiazepines; for example, there is an increasing shift to use of benzodiazepines with a shorter half-life and intermittent use, which can result in interdose withdrawal and rebound effects. Cognitive behavioral therapy Cognitive behavioral therapy has been found to be more effective for the long-term management of insomnia than sedative hypnotic drugs. No formal withdrawal programs for benzodiazepines exists with local providers in the UK. Meta-analysis of published data on psychological treatments for insomnia show a success rate between 70 and 80%. A large-scale trial utilizing cognitive behavioral therapy in chronic users of sedative hypnotics including nitrazepam, temazepam, and zopiclone found CBT to be a significantly more effective long-term treatment for chronic insomnia than sedative hypnotic drugs. Persisting improvements in sleep quality, sleep onset latency, increased total sleep, improvements in sleep efficiency, significant improvements in vitality, physical and mental health at 3-, 6-, and 12-month follow-ups were found in those receiving CBT. A marked reduction in total sedative hypnotic drug use was found in those receiving CBT, with 33% reporting zero hypnotic drug use. Age has been found not to be a barrier to successful outcome of CBT. It was concluded that CBT for the management of chronic insomnia is a flexible, practical, and cost-effective treatment, and it was also concluded that CBT leads to a reduction of benzodiazepine drug intake in a significant number of patients.Chronic use of hypnotic medications is not recommended due to their adverse effects on health and the risk of dependence. A gradual taper is usual clinical course in getting people off of benzodiazepines, but, even with gradual reduction, a large proportion of people fail to stop taking benzodiazepines. The elderly are particularly sensitive to the adverse effects of hypnotic medications. A clinical trial in elderly people dependent on benzodiazepine hypnotics showed that the addition of CBT to a gradual benzodiazepine reduction program increased the success rate of discontinuing benzodiazepine hypnotic drugs from 38% to 77% and at the 12-month follow-up from 24% to 70%. The paper concluded that CBT is an effective tool for reducing hypnotic use in the elderly and reducing the adverse health effects that are associated with hypnotics such as drug dependence, cognitive impairments, and increased road traffic accidents.A study of patients undergoing benzodiazepine withdrawal who had a diagnosis of generalized anxiety disorder showed that those having received CBT had a very high success rate of discontinuing benzodiazepines compared to those not having receive CBT. This success rate was maintained at the 12-month follow-up. Furthermore, it
Benzodiazepine dependence	was found that, in patients having discontinued benzodiazepines, they no longer met the diagnosis of general anxiety disorder, and that the number of patients no longer meeting the diagnosis of general anxiety disorder was higher in the group having received CBT. Thus, CBT can be an effective tool to add to a gradual benzodiazepine dosage reduction program leading to improved and sustained mental health benefits (Disputed). Letter to patients Sending a letter to patients warning of the adverse effects of long-term use of benzodiazepines and recommending dosage reduction has been found to be successful and a cost-effective strategy in reducing benzodiazepine consumption in general practice. Within a year of the letters going out, there was found to be a 17% fall in the number of benzodiazepines being prescribed, with 5% of patients having totally discontinued benzodiazepines. A study in the Netherlands reported a higher success rate by sending a letter to patients who are benzodiazepine-dependent. The results of the Dutch study reported 11.3% of patients discontinuing benzodiazepines completely within a year. Flumazenil Flumazenil delivered via slow subcutaneous infusion represents a safe procedure for those 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. Epidemiology Research studies have come to different conclusions on the number of therapeutic dose users who develop a physical dependence and withdrawal syndrome. Researches estimate 20-100% (thats a wide range) of patients, taking benzodiazepines at therapeutic dosages for the long term, are physically dependent and will experience withdrawal symptoms.Benzodiazepines can be addictive and induce dependence even at low doses, with 23% becoming addicted within 3 months of use. Benzodiazepine addiction is considered a public health problem. Approximately 68.5% of prescriptions of benzodiazepines originate from local health centers, with psychiatry and general hospitals accounting for 10% each. A survey of general practitioners reported that the reason for initiating benzodiazepines was due to an empathy for the patients suffering and a lack of other therapeutic options rather than patients demanding them. However, long-term use was more commonly at the insistence of the patient, it is presumed, because physical dependence or addiction had developed.Approximately twice as many women as men are prescribed benzodiazepines. It is believed that this is largely because men typically turned to alcohol to cope with stress and women to prescription drugs. Biased perception of women by male doctors may also play a role in increased prescribing rates to women; however, increased anxiety features in women does not account for the wide gap alone between men and women.Based on findings in the US from the Treatment Episode Data Set (TEDS), an annual compilation of patient characteristics in substance use disorder treatment facilities in the United States, admissions due to "primary tranquilizer" (including, but not limited to, benzodiazepine-type) drug use increased 79% from 1992 to 2002.A study published in the British Journal of General Practice in July 2017 found that in a sample taken from a survey conducted in 2014–2015 in Bradford a mean of 0.69% of registered patients had been prescribed benzodiazepines for more than a year. This would suggest that there were around 300,000 long-term users of diazepine in the UK. History Previously, physical dependence on benzodiazepines was largely thought to occur only in people on high-therapeutic-dose ranges. Low- or normal-dose dependence was not suspected until the 1970s, and it was not until the early 1980s that it was confirmed. Low-dose dependence has now been clearly demonstrated in both animal studies and human studies, and is a recognized clinical disadvantage of benzodiazepines. Severe withdrawal syndromes can occur from these low doses of benzodiazepines even after gradual dose reduction. An estimated 30–45% of chronic low-dose benzodiazepine users are dependent and it has been recommended that benzodiazepines even at low dosage be prescribed for a maximum of 7–14 days to avoid dependence. As a result, the global trend is toward strict regulations for the prescription of benzodiazepines due to this risk of low-dose dependence.Some controversy remains, however, in the medical literature as to the exact nature of low-dose dependence and the difficulty in getting patients to discontinue their benzodiazepines, with some papers attributing the problem to predominantly drug-seeking behavior and drug craving, whereas other papers having found the opposite, attributing the problem to a problem of physical dependence with drug-seeking and craving not being typical of low-dose benzodiazepine users. Society and culture Misuse and addiction Benzodiazepines are one of the largest classes of illicitly used substances; they are classed as schedule IV controlled drugs because of their recognized medical uses. Across the world the most frequently diverted and non-medically used benzodiazepines include temazepam, diazepam, nimetazepam, nitrazepam, triazolam, flunitrazepam, midazolam, and in the United States alprazolam, clonazepam, and lorazepam. Benzodiazepines can cause serious addiction problems. A survey of doctors in Senegal found that many doctors feel that their training and knowledge of benzodiazepines is, in general, poor; a study in Dakar found that almost one-fifth of doctors ignored prescribing guidelines regarding short-term use of benzodiazepines, and almost three-quarters of doctors regarded their training and knowledge of benzodiazepines to be inadequate. More training regarding benzodiazepines has been recommended for doctors. Due to the serious concerns of addiction, national governments were recommended to urgently seek to raise knowledge via training about the addictive nature of benzodiazepines and appropriate prescribing of benzodiazepines.A six-year study on 51 Vietnam veterans who had a substance use disorder related mainly to stimulants (11 people), opiates (26 people), or benzodiazepines (14 people) was carried out to assess psychiatric symptoms related to the specific substances. After six years, people who used opiates had little change in psychiatric symptomatology; five of the people who used stimulants developed psychosis, and eight of the people who used benzodiazepine developed depression. Therefore, long-term benzodiazepine use and dependence seems to carry a negative effect on mental health, with a significant risk of causing depression. Benzodiazepines are also sometimes taken intra-nasally when not recommended for use this way by their prescriber.In the elderly, alcohol and benzodiazepines are the most commonly used addictive substances, and the elderly population is more susceptible to benzodiazepine withdrawal syndrome and delirium than are younger patients. See also Long-term effects of benzodiazepines Alcohol withdrawal syndrome Long-term effects of alcohol consumption SSRI discontinuation syndrome Drug related crime References External links Benzodiazepine dependence at Curlie
Gamma globulin	Gamma globulins are a class of globulins, identified by their position after serum protein electrophoresis. The most significant gamma globulins are immunoglobulins (antibodies), although some immunoglobulins are not gamma globulins, and some gamma globulins are not immunoglobulins. Use as medical treatment Gamma globulin injections are usually given in an attempt to temporarily boost a patients immunity against disease. Injections are most commonly used on patients having been exposed to hepatitis A or measles, or to make a kidney donor and a recipient compatible regardless of blood type or tissue match. Injections are also used to boost immunity in patients unable to produce gamma globulins naturally because of an immune deficiency, such as X-linked agammaglobulinemia and hyper IgM syndrome. Such injections are less common in modern medical practice than they were previously, and injections of gamma globulin previously recommended for travelers have largely been replaced by the use of hepatitis A vaccine. Gamma globulin infusions are also used to treat some immunological diseases, such as idiopathic thrombocytopenia purpura (ITP), a disease in which the platelets are being attacked by antibodies, leading to seriously low platelet counts. It appears that gamma globulin causes the spleen to ignore the antibody-tagged platelets, thus allowing them to survive and function. Another theory on how gamma globulin administration works in autoimmune disease is by overloading the mechanisms that degrade gamma globulins. Overloading the degradation mechanism causes the harmful gamma globulins to have a much shorter half of the life in sera. Intravenous immunoglobulin (IVIG) may be used in Kawasaki disease. In 1953, gamma globulin was shown to prevent paralytic polio.Being a product derived from bone marrow and lymph gland cells, gamma globulin injections, along with blood transfusions and intravenous drug use, can pass hepatitis C to their recipients. Once hepatitis C was identified in 1989, blood banks began screening all blood donors for the presence of the virus in their bloodstream. However, since hepatitis C is known to have been present since at least the 1940s, a gamma globulin shot received prior to the early 1990s put the recipient at risk of being infected. Intravenous gamma globulin was FDA-approved in 2004 to reduce antibodies in a patient with kidney failure to allow that person to accept a kidney from a donor with a different blood type (ABO-incompatible), or who is an unacceptable tissue match. Stanley Jordan at Cedars-Sinai Medical Center in Los Angeles pioneered this treatment. Pathology An excess is known as hypergammaglobulinemia. A deficiency is known as hypogammaglobulinemia. A disease of gamma globulins is called a "gammopathy" (for example, in monoclonal gammopathy of undetermined significance). References External links gamma-Globulins at the US National Library of Medicine Medical Subject Headings (MeSH)
Carbamate poisoning	Carbamate poisoning is poisoning due to exposure to carbamates. Carbamates are typically used as pesticides; however, some also have medical uses. Symptoms may be similar to organophosphate poisoning. == References ==
Bednars aphthae	Bednars aphthae is a type of oral ulceration (mouth ulcers) which occurs in infants. The lesions are located on the palate and are caused by trauma. No treatment is required since the lesions heal within a few days.The condition was first described in 1850, by the Austrian physician Alois Bednar (1816-1888). References == External links ==
Upington disease	Upington disease is an extremely rare autosomal dominant malformation disorder. It has only one published source claiming its existence in three generations of one family from South Africa. Presentation The disease is characterized by Perthes-like pelvic anomalies (premature closure of the capital femoral epiphyses and widened femoral necks with flattened femoral heads), enchondromata and ecchondromata. Genetics Upington disease is inherited in an autosomal dominant manner. This means the defective gene is located on an autosome, and one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder. Management Eponym The name Upington refers to the city in the Northern Cape Province, South Africa, from where the family originates. References == External links ==
Juvenile xanthogranuloma	Juvenile xanthogranuloma is a form of histiocytosis, classified as "non-Langerhans cell histiocytosis", or more specifically, "type 2".It is a rare skin disorder that primarily affects children under one year of age but can also be found in older children and adults. It was first described in 1905 by Adamson. In 5% to 17% of people, the disorder is present at birth, but the median age of onset is two years. JXG is a benign idiopathic cutaneous granulomatous tumor and the most common form of non-Langerhans cell histiocytosis (non-LHC). The lesions appear as orange-red macules or papules and are usually located on the face, neck, and upper trunk. They may also appear at the groin, scrotum, penis, clitoris, toenail, palms, soles, lips, lungs, bone, heart, and gastrointestinal tract more rarely. JXG usually manifests with multiple lesions on the head and neck in cases with children under six months of age. The condition usually resolves spontaneously over one to five years. A biopsy of the lesion is critical to confirm the diagnosis. Ocular JXG manifests in up to 10% of people with JXG and may affect their vision. The presence of JXG in the eye can cause spontaneous hyphema, secondary glaucoma or even blindness. It is most often seen in the iris but may be found on the eyelid, corneoscleral limbus, conjunctiva, orbit, retina, choroid, disc, or optic nerve. Of patients with ocular JXG, 92% are younger than the age of two. Although cutaneous JXG usually disappear spontaneously, ocular lesions rarely improve spontaneously and require treatment. Treatments that have been used include surgical excision, intralesional steroid injection, cryotherapy, and low dose radiotherapy. In the case of a resistant or reoccurring lesion, chemotherapy has been used as a treatment. Ocular JXG is usually unilateral and presents with a tumor, a red eye with signs of uveitis, unilateral glaucoma, spontaneous hyphema or heterochromia iridis. Diagnosing and treating the patient as early as possible contributes to the most positive visual outcome. Histiocytic disorders like JXG are identified by the cells that make them up. Immunohistochemical analysis is used to discern the immunoreactivity to certain antibodies in these analyses. JXG is a non-LHC disorder which is a varied group of disorders defined by the accumulation of histiocytes that do not meet criteria to be diagnosed as Langerhans cells. JXG is not metastatic and may be present with lipid deposits. JXG is often accompanied with other disorders such as neurofibromatosis type one and juvenile chronic myelogenous leukemia. Juvenile variety xanthogranuloma can be distinguished from xanthoma by the spread of the lesion and the lack of lipid abnormalities. Other similar diagnoses include molluscum contagiosum, hemangioma and neurofibroma. See also Non-X histiocytoses List of cutaneous conditions References == External links ==
Bat ear	Bat ear may refer to: Protruding ear, an abnormally protruding human ear A shape of dog ear; see Canine terminology The ear of a bat, used for echolocation The ear of a nocturnal insect, primarily used to detect calls from insectivorous bats See also Bat-eared fox
Syphilid	A syphilid is any of the cutaneous and mucous membrane lesions characteristic of secondary and tertiary syphilis.It appears about 10 weeks after infection. Patient may present with prodromal symptoms such as fever, acratia, myalgia arthralgia, headache, anorexia. Its eruption pattern is macular, papular, follicular papules, or pustule, symmetrical, generalized and dense, round or oval in shape, and is red copper in color. See also Id reactions List of cutaneous conditions == References ==
Ethylmalonic encephalopathy	Ethylmalonic encephalopathy (EE) is a rare autosomal recessive inborn error of metabolism. Patients affected with EE are typically identified shortly after birth, with symptoms including diarrhea, petechiae and seizures. The genetic defect in EE is thought to involve an impairment in the degradation of sulfide intermediates in the body. Hydrogen sulfide then builds up to toxic levels. EE was initially described in 1994. Most cases of EE have been described in individuals of Mediterranean or Arabic origin. Signs and symptoms Neurologic signs and symptoms include progressively delayed development, weak muscle tone (hypotonia), seizures, and abnormal movements. The bodys network of blood vessels is also affected. Children with this disorder may experience rashes of tiny red spots (petechiae) caused by bleeding under the skin and blue discoloration in the hands and feet due to reduced oxygen in the blood (acrocyanosis). Chronic diarrhea is another common feature of ethylmalonic encephalopathy. EE is often identified by urine organic acid analysis, the excretion of ethylmalonic acid, methylsuccinic acid, isobutyrylglycine and isovalerylglucine. Patients will also often have elevated thiosulphate concentration in their urine.The signs and symptoms of ethylmalonic encephalopathy are apparent at birth or begin in the first few months of life. Problems with the nervous system typically worsen over time, and most affected individuals survive only into early childhood. A few children with a milder, chronic form of this disorder have been reported, and there can be considerable phenotypic variation, even within families. The life expectancy of individuals with EE is less than ten years. Pathophysiology Mutations in the ETHE1 gene cause ethylmalonic encephalopathy. The ETHE1 gene makes an enzyme that plays an important role in energy production. It is active in mitochondria, which are the energy-producing centers within cells. Little is known about its exact function, however. Mutations in the ETHE1 gene lead to the production of a defective version of the enzyme or prevents the enzyme from being made. A lack of the ETHE1 enzyme impairs the ability to make energy in mitochondria. Additionally, a loss of this enzyme allows potentially toxic compounds, including ethylmalonic acid and lactic acid, to build up in the body. Excess amounts of these compounds can be detected in urine. It remains unclear how a loss of the ETHE1 enzyme leads to progressive brain dysfunction and the other features of ethylmalonic encephalopathy. Ethylmalonic encephalopathy is an autosomal recessive disorder, which means the defective gene is located on an autosome, and both parents must carry one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are usually not affected by the disorder. Diagnosis Treatment References External links Ethylmalonic encephalopathy at NLM Genetics Home Reference
Femoral hernia	Femoral hernias occur just below the inguinal ligament, when abdominal contents pass through a naturally occurring weakness in the abdominal wall called the femoral canal. Femoral hernias are a relatively uncommon type, accounting for only 3% of all hernias. While femoral hernias can occur in both males and females, almost all develop in women due to the increased width of the female pelvis. Femoral hernias are more common in adults than in children. Those that do occur in children are more likely to be associated with a connective tissue disorder or with conditions that increase intra-abdominal pressure. Seventy percent of pediatric cases of femoral hernias occur in infants under the age of one. Definitions A hernia is caused by the protrusion of a viscus (in the case of groin hernias, an intra-abdominal organ) through a weakness in the abdominal wall. This weakness may be inherent, as in the case of inguinal, femoral and umbilical hernias. On the other hand, the weakness may be caused by previous surgical incision through the muscles and fascia in the area; this is termed an incisional hernia. A femoral hernia may be either reducible or irreducible, and each type can also present as obstructed and/or strangulated.A reducible femoral hernia occurs when a femoral hernia can be pushed back into the abdominal cavity, either spontaneously or with manipulation. However, it is more likely to occur spontaneously. This is the most common type of femoral hernia and is usually painless. An irreducible femoral hernia occurs when a femoral hernia cannot be completely reduced, typically due to adhesions between the hernia and the hernial sac. This can cause pain and a feeling of illness. An obstructed femoral hernia occurs when a part of the intestine involved in the hernia becomes twisted, kinked, or constricted, causing an intestinal obstruction. A strangulated femoral hernia occurs when a constriction of the hernia limits or completely obstructs blood supply to part of the bowel involved in the hernia. Strangulation can occur in all hernias, but is more common in femoral and inguinal hernias due to their narrow "weaknesses" in the abdominal wall. Nausea, vomiting, and severe abdominal pain are characteristics of a strangulated hernia. This is a medical emergency as the loss of blood supply to the bowel can result in necrosis (tissue death) followed by gangrene (tissue decay). This is a life-threatening condition requiring immediate surgery.The term incarcerated femoral hernia is sometimes used, but may have different meanings to different authors and physicians. For example: "Sometimes the hernia can get stuck in the canal and is called an irreducible or incarcerated femoral hernia." "The term incarcerated is sometimes used to describe an [obstructed] hernia that is irreducible but not strangulated. Thus, an irreducible, obstructed hernia can also be called an incarcerated one." "Incarcerated hernia is a hernia that cannot be reduced. These may lead to bowel obstruction but are not associated with vascular compromise."A hernia can be described as reducible if the contents within the sac can be pushed back through the defect into the peritoneal cavity, whereas with an incarcerated hernia, the contents are stuck in the hernia sac. However, the term incarcerated seems to always imply that the femoral hernia is at least irreducible. Signs and symptoms Femoral hernias typically present as a groin lump or bulge, which may differ in size during the day, based on internal pressure variations of the intestine. This lump is typically retort shaped. The bulge or lump is typically smaller or may disappear completely in the prone position.They may or may not be associated with pain. Often, they present with a varying degree of complication ranging from irreducibility through intestinal obstruction to frank gangrene of contained bowel. The incidence of strangulation in femoral hernias is high. A femoral hernia has often been found to be the cause of unexplained small bowel obstruction. The cough impulse is often absent and is not relied on solely when making a diagnosis of femoral hernia. The lump is more globular than the pear-shaped lump of the inguinal hernia. The bulk of a femoral hernia lies below an imaginary line drawn between the anterior superior iliac spine and the pubic tubercle (which essentially represents the inguinal ligament) whereas an inguinal hernia starts above this line. Nonetheless, it is often impossible to distinguish the two preoperatively. Anatomy The femoral canal is located below the inguinal ligament on the lateral aspect of the pubic tubercle. It is bounded by the inguinal ligament anteriorly, pectineal ligament posteriorly, lacunar ligament medially, and the femoral vein laterally. It normally contains a few lymphatics, loose areolar tissue, and occasionally a lymph node called Cloquets node. The function of this canal appears to be to allow the femoral vein to expand when necessary to accommodate increased venous return from the leg during periods of activity. Diagnosis The diagnosis is largely a clinical one, generally done by physical examination of the groin. However, in obese patients, imaging in the form of ultrasound, CT, or MRI may aid in the diagnosis. For example, an abdominal X-ray showing small bowel obstruction in a female patient with a painful groin lump needs no further investigation. Several other conditions have a similar presentation and must be considered when forming the diagnosis: inguinal hernia, an enlarged femoral lymph node, aneurysm of the femoral artery, dilation of the saphenous vein, athletic pubalgia, and an abscess of the psoas. Classification Several subtypes of femoral hernia have been described. Management Femoral hernias, like most other hernias, usually need operative intervention. This should ideally be done as an elective (non-emergency) procedure. However, because of the high incidence of complications, femoral hernias often need emergency surgery. Surgery Some surgeons choose to perform "key-hole" or laparoscopic surgery (also called minimally invasive surgery) rather than conventional "open" surgery. With minimally invasive surgery, one or more small incisions are made that allow the surgeon to use a surgical camera and small tools to repair the hernia.Either open or minimally invasive surgery may be performed under general or regional anesthesia, depending on the extent of the intervention needed. Three approaches have been described for open surgery: Lockwood’s infra-inguinal approach Lotheissen‘s trans-inguinal approach McEvedy’s high approachThe infra-inguinal approach is the preferred method for elective repair. The trans-inguinal approach involves dissecting through the inguinal canal and carries the risk of weakening the inguinal canal. McEvedy’s approach is preferred in the emergency setting when strangulation is suspected. This allows better access to and visualization of the bowel for possible resection. In any approach, care should be taken to avoid injury to the urinary bladder which is often a part of the medial part of the hernial sac. Repair is either performed by suturing the inguinal ligament to the pectineal ligament using strong non-absorbable sutures or by placing a mesh plug in the femoral ring. With either technique care should be taken to avoid any pressure on the femoral vein. Postoperative outcome Patients undergoing elective surgical repair do very well and may be able to go home the same day. However, emergency repair carries a greater morbidity and mortality rate and this is directly proportional to the degree of bowel compromise. Epidemiology Femoral hernias are more common in multiparous females, which results from elevated intra-abdominal pressure that dilates the femoral vein and in turn stretches femoral ring. Such constant pressure causes preperitoneal fat to insinuate in the femoral ring, a consequence of which is development of a femoral peritoneal sac. References External links Surgery Encyclopaedia
Cluttons joints	Cluttons joints is a term describing the finding of symmetrical joint swelling seen in patients with congenital syphilis. It most commonly affects the knees, presenting with synovitis and joint effusions (collections of fluid within the joint capsules) lasting up to a year. It has also been reported affecting the ankles, elbows, wrists and fingers. It is usually painless, although pain in the absence of trauma can occur in a few cases. There is usually no disability associated with the joint swelling, and recovery is usually complete. It occurs between 5 and 20 years of age in both sexes.The condition was described in 1886 by Henry Hugh Clutton in The Lancet. == References ==
Sialodochitis	Sialodochitis (also termed ductal sialadenitis), is inflammation of the duct system of a salivary gland. This is compared to sialadenitis, which is inflammation of the gland parenchyma.Sialodochitis may be associated with salivary duct strictures and salivary stones.It is common in both the parotid glands and submandibular glands.The treatment is as for sialadenitis. Diagnosis It may appear on a CT scan or MRI scan as enhancement and dilation of the duct (sialectasis).On sialography, it may appear as segments of duct dilation and stenosis. This is sometimes termed the sausage link appearance. Sialodochitis fibrinosa This is a rare condition, probably caused by an allergic reaction, in which there is sudden swelling of the salivary glands. It is associated with other allergic conditions such as asthma, urticaria, allergic rhinitis and food allergy. == References ==
Hypopyon	Hypopyon is a medical condition involving inflammatory cells in the anterior chamber of the eye. It is an exudate rich in white blood cells, seen in the anterior chamber, usually accompanied by redness of the conjunctiva and the underlying episclera. It is a sign of inflammation of the anterior uvea and iris, i.e. iritis, which is a form of anterior uveitis. The exudate settles at the dependent aspect of the eye due to gravity. It can be sterile (in bacterial corneal ulcer) or not sterile (fungal corneal ulcer). Differential diagnosis Hypopyon can be present in a corneal ulcer. It can occur as a result of Behçets disease, endophthalmitis, panuveitis/panophthalmitis, or adverse reactions to some drugs (such as rifabutin).Hypopyon is also known as sterile pus because it occurs due to the release of toxins and not by the actual invasion of pathogens. The toxins secreted by the pathogens mediate the outpouring of leukocytes that settle in the anterior chamber of the eye. An inverse hypopyon is different from a standard hypopyon. Inverse hypopyon is seen after a pars plana vitrectomy with an insertion of silicone oil (as a replacement of the vitreous humour that has been removed in the operation; the silicone oil maintains internal tamponade). When the silicone oil emulsifies, it seeps into the anterior chamber and settles at the top of the anterior chamber. This is in contrast to hypopyon resulting from toxins where the leukocytes settle at the bottom of the anterior chamber. This is due to the effect of gravity, hence the name inverse hypopyon. Treatment A hypopyon should not be drained, because it offers protection against the invading pathogen due to the presence of white blood cells, although long-standing hypopyon can cause close-angle glaucoma and anterior synechiae.Intravitreal antibiotics can be used if endophthalmitis is suspected. See also Hyphema Uveitis References == External links ==
Kleine–Levin syndrome	Kleine–Levin syndrome (KLS) is a rare disorder characterized by persistent episodic hypersomnia and cognitive or mood changes. Many patients also experience hyperphagia, hypersexuality and other symptoms. Patients generally experience recurrent episodes of the condition for more than a decade and may return at a later age. Individual episodes generally last more than a week, sometimes lasting for months. The condition greatly affects the personal, professional, and social lives of those with KLS. The severity of symptoms and the course of the syndrome vary between those with KLS. Patients commonly have about 20 episodes over about a decade. Several months generally elapse between episodes. The onset of the condition usually follows a viral infection; several different viruses have been observed to trigger KLS. It is generally only diagnosed after similar conditions have been excluded; MRI, CT scans, lumbar puncture, and toxicology tests are used to rule out other possibilities. The syndromes mechanism is not known, but the thalamus is thought to possibly play a role. SPECT has shown thalamic hypoperfusion of patients during episodes. KLS is very rare, occurring at a rate of 1 in 1 million, which limits research into genetic factors. The condition primarily affects adolescent males, though females can also be affected and the age of onset varies. There is no known cure, and there is little evidence supporting drug treatment. Lithium has been reported to have limited effects in case reports, decreasing the length of episodes and duration between them in some patients. Stimulants have been shown to promote wakefulness during episodes, but they do not counteract cognitive symptoms or decrease the duration of episodes. The condition is named after Willi Kleine and Max Levin, who described cases of the disease in the early 20th century. It was added to the International Classification of Sleep Disorders in 1990. Symptoms Patients with Kleine–Levin syndrome (KLS) experience recurring episodes of prolonged sleep (hypersomnia). In most cases, patients sleep 15 to 21 hours a day during episodes. Excessive appetite (hyperphagia) and unusual cravings are present in half to two thirds of cases. About half of patients, mainly male patients, experience dramatically increased sexual urges (hypersexuality). Several other symptoms usually accompany the syndrome, including marked changes in mood and cognitive ability. Derealization and severe apathy are present in at least 80 percent of cases. About one third of patients experience hallucinations or delusions. Depression and anxiety occur less commonly; one study found them in about 25 percent of patients. Individuals usually cannot remember what happened during episodes. Repetitive behaviors and headaches are commonly reported. Some patients act very childlike during episodes, and communication skills and coordination sometimes worsen.Sleep studies of KLS show varying results based on the amount of time the patient is observed. Slow wave sleep is often reduced at the beginning of episodes, and REM sleep is reduced near the end. Conversely, REM sleep is often normal at the beginning, and slow wave sleep is often normal by the conclusion. Stage two non-rapid eye movement sleep is often interrupted during KLS. Studies also show that stage one and three non-rapid eye movement sleep become more efficient when the episodes end. The Multiple Sleep Latency Test has yielded inconsistent results when given to KLS patients. In many cases, hours are spent in a withdrawn sleep-like state while awake during episodes. Most sleep studies have been performed while subject is near the end of their episodes. Some patients experience brief insomnia and become very happy and talkative after the episode ends.The first time a patient experiences KLS, it usually occurs along with symptoms that are similar to those of the flu or encephalitis. In at least 75 percent of cases, symptoms occur after an airway infection or a fever. Viruses observed before the development of the condition include Epstein–Barr virus, varicella zoster virus, herpes zoster virus, influenza A virus subtypes, and adenovirus. Several days after symptoms first occur, patients become very tired. In cases that occur after an infection, KLS usually starts within three to five days for teenagers and fewer for children. In other cases, alcohol consumption, head injury, or international travel precede symptoms. Lifestyle habits, such as stress, alcohol abuse and lack of sleep and stress, have also been proposed as possible triggers. First episodes of KLS are preceded by a clear event in about 90 percent of cases. Recurrences generally do not have clear triggers; only about 15 percent have a precipitating event.The condition generally disrupts the social lives and academic or professional obligations of those with KLS. Some patients also gain weight during episodes. The most severe cases cause a long-term impact on mood and cognitive attention. In rare cases, patients experience long-term memory problems.In patients with KLS, MRI and CT scans show normal brain morphology. When SPECT is performed, hypoperfusion can often be observed in the brain, particularly in the thalamic and frontotemporal areas. The hypoperfusion is significantly diminished between episodes. Serum biology, c-reactive proteins and leptins, the hormonal pituitary axis, and protein in the cerebral spinal fluid (CSF) are normal in KLS patients. Cause It is not known what causes KLS, but several mechanisms have been proposed. One possible explanation is hypothalamic or circadian dysfunction. The thalamus probably plays a role in the out-of-control sleeping, and patients with diencephalic–hypothalamic dysfunction caused by tumors experience symptoms similar to those of KLS patients. Specifically, the medial temporal regions of the thalamus may be involved, although examinations of KLS patients have not consistently found abnormalities in this area. The temporal lobe also appears to play a role in the condition, possibly causing cognitive difficulties. The apathy and disinhibition found in some with KLS suggest that the condition may include frontal lobe dysfunction as well. The involvement of the thalamus, temporal lobe, and frontal lobe of the brain suggests that there is a multifocal, localized encephalopathy. There are also persistent subclinical abnormalities in some with KLS.Another possible explanation concerns the metabolism of serotonin and dopamine. An imbalance in the neurotransmitter pathways of these chemicals could play a role. Viral infections have also been suggested as a possible cause. Evidence for their role includes lesions found in autopsies. CSF samples from KLS patients indicate that the condition has a different cause than influenza-associated encephalopathy. Triggers of KLS may also affect the blood-brain barrier, which could play a role in the condition. There is limited evidence of what role hypocretin may play, although it often influences hypersomnia.Androgen might (indirectly) block melatonin receptors, possibly by means of vasodilation, and cause cholinergic abnormalities in some cases of Kleine–Levin syndrome.Because KLS occurs at a much higher rate in Jews and in some families, it is likely that there is some genetic component in addition to environmental factors. Genetic studies hold promise for understanding the disease, but they have yielded inconsistent results and few patients are available for testing.Epilepsy and depression do not appear to cause KLS. The conditions rapid onset after infections indicates that the immune system is not to blame.One study has suggested a link to the gene LMOD3 on chromosome 3. Diagnosis KLS can be diagnosed when there is confusion, apathy, or derealization in addition to frequent bouts of extreme tiredness and prolonged sleep. The earliest it can be diagnosed is the second episode, this is not common. The condition is generally treated as a diagnosis of exclusion. Because KLS is rare, other conditions with similar symptoms are usually considered first.MRIs can determine if the symptoms are caused by certain brain disorders, stroke, and multiple sclerosis. Lumbar puncture can determine if encephalitis is the cause. KLS must be differentiated from substance abuse by toxicology tests. The use of electroencephalography (EEG) can exclude temporal status epilepticus from consideration. EEGs are normal in about 70% of KLS patients, but background slowing may sometimes be detected. In addition, low-frequency high-amplitude waves can be observed during waking hours.Initially, KLS appears similar to bipolar depression. Patients with frontal-lobe syndromes and Klüver–Bucy syndrome also display similar symptoms, but these conditions can be differentiated by the presence of brain lesions. KLS should also be distinguished from very rare cases of menstruation-caused hypersomnia. Prevention Lithium is the only drug that appears to have a preventive effect. In two studies of more than 100 patients, lithium helped prevent recurrence of symptoms in 20% to 40% of cases. The recommended blood level of lithium for KLS patients is 0.8–1.2 mEq/ml. It is not known if other mood stabilizers have an effect on the condition. Anti-depressants do not prevent recurrence. Treatment Several drug therapies have been used on patients with KLS, but none of them have been subject to randomized controlled trials. A 2016 Cochrane Review concluded that "No evidence indicates that pharmacological treatment for Kleine–Levin syndrome is effective and safe".In several cases, stimulants, including modafinil, have been reported to have a limited effect on patients, often alleviating sleepiness. They can cause behavioral problems, but they may pose fewer issues if used in older patients with mild symptoms. In some case reports, lithium has been reported to decrease the length of episodes and the severity of their symptoms and to increase the time between episodes. It has been reported to be effective in about 25 to 60 percent of cases. Its use carries the risk of side effects in the thyroid or kidneys. Antipsychotics and benzodiazepines can help alleviate psychotic and anxiety related symptoms, respectively. Carbamazepine has been reported to be less effective than lithium but more effective than some drugs in its class. Electroconvulsive therapy is not effective and worsens symptoms.KLS patients generally do not need to be admitted to hospitals. It is recommended that caregivers reassure them and encourage them to maintain sleep hygiene. It may also be necessary for patients to be prevented from putting themselves in dangerous situations, such as driving. Prognosis The frequency of KLS episodes can vary from attacks one week in length occurring twice a year to dozens of episodes that follow each other in close succession. The median duration of KLS episodes is about ten days, but some last several weeks or months. A study of 108 patients found an average of 19 episodes over the duration of the disease. Another study found a median of 3.5 months between episodes. Outside of episodes, there is no disturbance in patients sleep patterns and they are generally asymptomatic. Patients do not experience the same symptoms in each episode.About 80 percent of patients are adolescents when they first experience KLS. On some occasions though, its first occurrence comes in childhood or adulthood. In most adolescent-onset patients, symptoms cease by the time they are 30 years old. A French study of 108 patients found a median duration of 13 years, but a review of 186 cases found a median duration of 8 years. Unusually young or old patients and those who experience hypersexuality tend to have a more severe course. Patients who initially have frequent attacks generally see the disease cease earlier than others. The condition spontaneously resolves, and the patient is considered to be cured if there have been no symptoms for six years. Epidemiology Population-based studies of KLS have not been performed. Its prevalence is about 1 case per million people. In France, KLS has a prevalence of 1.5 per million people. It occurs most frequently among Jews in the US and Israel. First-degree relatives of people who have the syndrome are much more likely than the general population to have it, although only in about one percent of cases do family members contract it. About 70 to 90 percent of patients are male. Patients with the syndrome are more likely than the general population to have genetic disorders, and about a third of people with the syndrome encountered some form of birth difficulty. In a study of 186 older patients, about ten percent had preexisting psychiatric issues. One study found that about ten percent of patients had a neurological condition before KLS developed. The condition does not appear to occur most frequently in one season. History In 1815, there was a report of a young man who showed excessive appetite and prolonged sleep after experiencing a fever; this may have been an early description of the condition. Another case with similar symptoms was described by Brierre de Boismont in 1862.Five patients with symptoms of persistent sleepiness were described in detail in 1925 by Willi Kleine, a neurologist from Frankfurt. This report was followed four years later by details of a similar case by New York-based psychiatrist Max Levin. In 1935, Levin published information about several more cases, including one described by Kleine. Levin noted that some patients displayed an intense appetite in addition to their persistent tiredness. MacDonald Critchley, who first wrote about the condition in 1942, described 11 cases he had examined and reviewed 15 other published cases in a 1962 publication. In the report, which included patients he had examined in the Royal Navy during World War II, he observed that irritability and depersonalization often occurred while patients were awake. He named the condition Kleine–Levin syndrome and noted four common traits: hypersexuality, adolescent onset, spontaneous resolution, and compulsive eating. He believed that the condition only affected males, but later studies showed some female patients. In the 1970s, several psychoanalytic and psychodynamic explanations for the condition were proposed. In 1980, a Hawaiian–Caucasian family was found in which nine family members had the condition.Diagnostic criteria for KLS was established by Schmidt in 1990, and the International Classification of Sleep Disorders further refined them. KLS is classified as a sleep disorder, specifically one of recurrent hypersomnia. Before 2005, hyperphagia and hypersexuality were thought to occur in all cases. That was changed with the guidelines published that year, which noted that they did not always occur. References Bibliography Arnulf, Isabelle; Rico, Thomas; Mignot, Emmanuel (2012). "Diagnosis, Disease Course, and Management of Patients with Kleine-Levin Syndrome". The Lancet Neurology. 11 (10): 918–28. doi:10.1016/S1474-4422(12)70187-4. PMID 22995695. S2CID 7636103. Arnulf, Isabelle; Zeitzer, J. M.; Farber, N.; Mignot, Emmanuel (2005). "Kleine–Levin Syndrome: a Systematic Review of 186 Cases in the Literature". Brain. 128 (12): 2763–76. doi:10.1093/brain/awh620. PMID 16230322. Billiard, Michel; Jaussent, Isabelle; Dauvilliers, Yves; Besset, Alain (2011). "Recurrent Hypersomnia: a Review of 339 Cases". Sleep Medicine Reviews. 15 (4): 247–57. doi:10.1016/j.smrv.2010.08.001. PMID 20970360. Frenette, Eric; Kushida, Clete (2009). "Primary Hypersomnias of Central Origin". Seminars in Neurology. 29 (4): 354–67. doi:10.1055/s-0029-1237114. PMID 19742411. Gupta, Ravi; Lahan, Vivekananda; Srivastava, Malini (2011). "Kleine-Levin Syndrome and Idiopathic Hypersomnia: Spectrum Disorders". Indian Journal of Psychological Medicine. 33 (2): 194–98. doi:10.4103/0253-7176.92048. PMC 3271500. PMID 22345850. Huang, Yu-Shu; Lakkis, Clair; Guilleminault, Christian (2010). "Kleine-Levin Syndrome: Current Status". Medical Clinics of North America. 94 (3): 557–62. doi:10.1016/j.mcna.2010.02.011. PMID 20451032. Kodaira, Minori; Yamamoto, Kanji (2012). "First Attack of Kleine-Levin Syndrome Triggered by Influenza B Mimicking Influenza-associated Encephalopathy". Internal Medicine. 51 (12): 1605–8. doi:10.2169/internalmedicine.51.7051. PMID 22728499. Mignot, Emmanuel (2012). "A Practical Guide to the Therapy of Narcolepsy and Hypersomnia Syndromes". Neurotherapeutics. 9 (4): 739–52. doi:10.1007/s13311-012-0150-9. PMC 3480574. PMID 23065655. Oliveira, Marcio; Conti, Cristiane; Prado, Gilmar (2016) [2013]. "Pharmacological Treatment for Kleine-Levin Syndrome". Cochrane Database of Systematic Reviews. 5 (5): CD006685. doi:10.1002/14651858.CD006685.pub4. PMC 7386458. PMID 27153153. Pearce, J. M. (2008). "Kleine–Levin Syndrome: History and Brief Review". European Neurology. 60 (4): 212–4. doi:10.1159/000148694. PMID 18667831. Ramdurg, Santosh (2010). "Kleine–Levin Syndrome: Etiology, Diagnosis, and Treatment". Annals of Indian Academy of Neurology. 13 (4): 241–6. doi:10.4103/0972-2327.74185. PMC 3021925. PMID 21264130. External links kleine_levin at NINDS Story of young man with Kleine–Levin syndrome at The New York Times
Dysbaric osteonecrosis	Dysbaric osteonecrosis or DON is a form of avascular necrosis where there is death of a portion of the bone that is thought to be caused by nitrogen embolism (blockage of the blood vessels by a bubble of nitrogen coming out of solution) in divers. Although the definitive pathologic process is poorly understood, there are several hypotheses: Intra- or extravascular nitrogen in bones, "nitrogen embolism". Osmotic gas effects due to intramedullary pressure effects. fat embolism hemoconcentration and increased coagulability. Presentation The lesion begins as a localised area of infarction, usually without symptoms. Early identification of lesions by radiography is not possible, but over time areas of radiographic opacity develop in association with the damaged bone. Symptomatic lesions usually involve joint surfaces, and fracture where attempted healing occurs. This process takes place over months to years and eventually causes disabling arthritis, particularly of the femoral head (hip).Dysbaric osteonecrosis lesions are typically bilateral and usually occur at both ends of the femur and at the proximal end of the humerus. Symptoms are usually only present when a joint surface is involved, which typically does not occur until a long time after the causative exposure to a hyperbaric environment. The initial damage is attributed to the formation of bubbles, and one episode can be sufficient, however incidence is sporadic and generally associated with relatively long periods of hyperbaric exposure, and aetiology is uncertain. Diagnosis The diagnosis is made by x-ray/MRI appearance and has five juxta-articular classifications and forehead, neck, and shaft classifications indicating early radiological signs.Early on there is flattening of articular surfaces, thinning of cartilage with osteophyte (spur) formation. In juxta-articular lesions without symptoms, there is dead bone and marrow separated from living bone by a line of dense collagen. Microscopic cysts form, fill with necrotic material and there is massive necrosis with replacement by cancellous bone with collapse of the lesions.The following staging system is sometimes useful when managing lesions. Stage 0 - Intravascular coagulation Stage 1 - Dead bone without repair Stage 2 - Dead bone with repair but without collapse Stage 3 - Dead bone with repair and with collapse Stage 4 - Secondary degenerative arthritisIn a study of bone lesions in 281 compressed air workers done by Walder in 1969, 29% of the lesions were in the humeral head (shoulder), 16% in the femoral head (hip), 40% in the lower end of the femur (lower thigh at the knee) and 15% in the upper tibia (knee below the knee cap). Worsening of the condition from continued decompression in an asymptomatic x-ray finding may occur. Prevention Prevention is a more successful strategy than treatment. By using the most conservative decompression schedule reasonably practicable, and by minimizing the number of major decompression exposures, the risk of DON may be reduced. Prompt treatment of any symptoms of decompression sickness (DCS) with recompression and hyperbaric oxygen also reduce the risk of subsequent DON. Treatment Treatment is difficult, often requiring a joint replacement. Spontaneous improvement occasionally happens and some juxta-articular lesions do not progress to collapse. Other treatments include immobilization and osteotomy of the femur. Cancellous bone grafts are of little help. Prognosis If the diver has not been exposed to excessive depth and decompression and presents as DON, there may be a predisposition for the condition. Diving should be restricted to shallow depths. Divers who have suffered from DON are at increased risk of future fracture of a juxta-articular lesion during a dive, and may face complications with future joint replacements. Because of the young age of the population normally affected, little data is available regarding joint replacement complications.There is the potential for worsening of DON for any diving where there might be a need for decompression, experimental or helium diving. Physically stressful diving should probably be restricted, both in sport diving and work diving due to the possibility of unnecessary stress to the joint. Any diving should be less than 40 feet/12 meters. These risks are affected by the degree of disability and by the type of lesion (juxta-articular or shaft). Prevalence Dysbaric osteonecrosis is a significant occupational hazard, occurring in 50% of commercial Japanese divers, 65% of Hawaiian fishermen and 16% of commercial and caisson divers in the UK. Its relationship to compressed air is strong in that it may follow a single exposure to compressed air, may occur with no history of DCS but is usually associated with significant compressed air exposure. The distribution of lesions differs with the type of exposure - the juxta-articular lesions being more common in caisson workers than in divers. There is a definite relationship between length of time exposed to extreme depths and the percentage of divers with bone lesions. Evidence does not suggest that dysbaric osteonecrosis is a significant risk in recreational scuba diving. References External links ScubaDocs Dysbaric Osteonecrosis page Rubicon Research Repository
Hypopituitarism	Hypopituitarism is the decreased (hypo) secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is known as selective hypopituitarism. If there is decreased secretion of most or all pituitary hormones, the term panhypopituitarism (pan meaning "all") is used.The signs and symptoms of hypopituitarism vary, depending on which hormones are undersecreted and on the underlying cause of the abnormality. The diagnosis of hypopituitarism is made by blood tests, but often specific scans and other investigations are needed to find the underlying cause, such as tumors of the pituitary, and the ideal treatment. Most hormones controlled by the secretions of the pituitary can be replaced by tablets or injections. Hypopituitarism is a rare disease, but may be significantly underdiagnosed in people with previous traumatic brain injury. The first description of the condition was made in 1914 by the German physician Dr Morris Simmonds. Signs and symptoms The hormones of the pituitary have different actions in the body, and the symptoms of hypopituitarism therefore depend on which hormone is deficient. The symptoms may be subtle and are often initially attributed to other causes. In most of the cases, three or more hormones are deficient. The most common problem is insufficiency of follicle-stimulating hormone (FSH) and/or luteinizing hormone (LH) leading to sex hormone abnormalities. Growth hormone deficiency is more common in people with an underlying tumor than those with other causes.Sometimes, there are additional symptoms that arise from the underlying cause; for instance, if the hypopituitarism is due to a growth hormone-producing tumor, there may be symptoms of acromegaly (enlargement of the hands and feet, coarse facial features), and if the tumor extends to the optic nerve or optic chiasm, there may be visual field defects. Headaches may also accompany pituitary tumors, as well as pituitary apoplexy (infarction or haemorrhage of a pituitary tumor) and lymphocytic hypophysitis (autoimmune inflammation of the pituitary). Apoplexy, in addition to sudden headaches and rapidly worsening visual loss, may also be associated with double vision that results from compression of the nerves in the adjacent cavernous sinus that control the eye muscles.Pituitary failure results in many changes in the skin, hair and nails as a result of the absence of pituitary hormone action on these sites. Complications Several hormone deficiencies associated with hypopituitarism may lead to secondary diseases. For instance, growth hormone deficiency is associated with obesity, raised cholesterol and the metabolic syndrome, and estradiol deficiency may lead to osteoporosis. While effective treatment of the underlying hormone deficiencies may improve these risks, it is often necessary to treat them directly. Anterior pituitary Deficiency of all anterior pituitary hormones is more common than individual hormone deficiency. Deficiency of luteinizing hormone (LH) and follicle-stimulating hormone (FSH), together referred to as the gonadotropins, leads to different symptoms in men and women. Women experience oligo- or amenorrhea (infrequent/light or absent menstrual periods respectively) and infertility. Men lose facial, scrotal and trunk hair, as well as have decreased muscle mass and anemia. Both sexes may experience a decrease in libido and loss of sexual function, and have an increased risk of osteoporosis (bone fragility). Lack of LH/FSH in children is associated with delayed puberty.Growth hormone (GH) deficiency leads to a decrease in muscle mass, central obesity (increase in body fat around the waist) and impaired attention and memory. Children experience growth retardation and short stature.Adrenocorticotropic hormone (ACTH) deficiency leads to adrenal insufficiency, a lack of production of glucocorticoids such as cortisol by the adrenal gland. If the problem is chronic, symptoms consist of fatigue, weight loss, failure to thrive (in children), delayed puberty (in adolescents), hypoglycemia (low blood sugar levels), anemia and hyponatremia (low sodium levels). If the onset is abrupt, collapse, shock and vomiting may occur. ACTH deficiency is highly similar to primary Addisons disease, which is cortisol deficiency as the result of direct damage to the adrenal glands; the latter form, however, often leads to hyperpigmentation of the skin, which does not occur in ACTH deficiency.Thyroid-stimulating hormone (TSH) deficiency leads to hypothyroidism (lack of production of thyroxine (T4) and triiodothyronine (T3) in the thyroid). Typical symptoms are tiredness, intolerance to cold, constipation, weight gain, hair loss and slowed thinking, as well as a slowed heart rate and low blood pressure. In children, hypothyroidism leads to delayed growth and in extreme inborn forms to a syndrome called cretinism.Prolactin (PRL) plays a role in breastfeeding, and inability to breastfeed may point at abnormally low prolactin levels. Posterior pituitary Antidiuretic hormone (ADH) deficiency leads to the syndrome of diabetes insipidus (unrelated to diabetes mellitus): inability to concentrate the urine, leading to polyuria (production of large amounts of clear urine) that is low in solutes, dehydration and—in compensation—extreme thirst and constant need to drink (polydipsia), as well as hypernatremia (high sodium levels in the blood). ADH deficiency may be masked if there is ACTH deficiency, with symptoms only appearing when cortisol has been replaced.Oxytocin (OXT) deficiency generally causes few symptoms, however may lead to abnormal social developments due to its complex role as a social neuropeptide. Causes Pathophysiology The pituitary gland is located at the base of the brain, and intimately connected with the hypothalamus. It consists of two lobes: the posterior pituitary, which consists of nervous tissue branching out of the hypothalamus, and the anterior pituitary, which consists of hormone-producing epithelium. The posterior pituitary secretes antidiuretic hormone, which regulates osmolarity of the blood, and oxytocin, which causes contractions of the uterus in childbirth and participates in breastfeeding.The pituitary develops in the third week of embryogenesis from interactions between the diencephalon part of the brain and the nasal cavity. The brain cells secrete FGF-8, Wnt5a and BMP-4, and the oral cavity BMP-2. Together, these cellular signals stimulate a group of cells from the oral cavity to form Rathkes pouch, which becomes independent of the nasal cavity and develops into the anterior pituitary; this process includes the suppression of production of a protein called Sonic hedgehog by the cells of Rathkes pouch. The cells then differentiate further into the various hormone-producing cells of the pituitary. This requires particular transcription factors that induce the expression of particular genes. Some of these transcription factors have been found to be deficient in some forms of rare combined pituitary hormone deficiencies (CPHD) in childhood. These are HESX1, PROP1, POU1F1, LHX3, LHX4, TBX19, SOX2 and SOX3. Each transcription factor acts in particular groups of cells. Therefore, various genetic mutations are associated with specific hormone deficiencies. For instance, POU1F1 (also known as Pit-1) mutations cause specific deficiencies in growth hormone, prolactin and TSH. In addition to the pituitary, some of the transcription factors are also required for the development of other organs; some of these mutations are therefore also associated with specific birth defects. Most of the hormones in the anterior pituitary are each part of an axis that is regulated by the hypothalamus. The hypothalamus secretes a number of releasing hormones, often according to a circadian rhythm, into blood vessels that supply the anterior pituitary; most of these are stimulatory (thyrotropin-releasing hormone, corticotropin-releasing hormone, gonadotropin-releasing hormone and growth hormone-releasing hormone), apart from dopamine, which suppresses prolactin production. In response to the releasing hormone rate, the anterior pituitary produces its hormones (TSH, ACTH, LH, FSH, GH) which in turn stimulate effector hormone glands in the body, while prolactin (PRL) acts directly on the breast gland. Once the effector glands produce sufficient hormones (thyroxine, cortisol, estradiol or testosterone and IGF-1), both the hypothalamus and the pituitary cells sense their abundance and reduce their secretion of stimulating hormones. The hormones of the posterior pituitary are produced in the hypothalamus and are carried by nerve endings to the posterior lobe; their feedback system is therefore located in the hypothalamus, but damage to the nerve endings would still lead to a deficiency in hormone release.Unless the pituitary damage is being caused by a tumor that overproduces a particular hormone, it is the lack of pituitary hormones that leads to the symptoms described above, and an excess of a particular hormone would indicate the presence of a tumor. The exception to this rule is prolactin: if a tumor compresses the pituitary stalk, a decreased blood supply means that the lactotrope cells, which produce prolactin, are not receiving dopamine and therefore produce excess prolactin. Hence, mild elevations in prolactin are attributed to stalk compression. Very high prolactin levels, though, point more strongly towards a prolactinoma (prolactin-secreting tumor). Diagnosis The diagnosis of hypopituitarism is made on blood tests. Two types of blood tests are used to confirm the presence of a hormone deficiency: basal levels, where blood samples are taken–usually in the morning–without any form of stimulation, and dynamic tests, where blood tests are taken after the injection of a stimulating substance. Measurement of ACTH and growth hormone usually requires dynamic testing, whereas the other hormones (LH/FSH, prolactin, TSH) can typically be tested with basal levels. There is no adequate direct test for ADH levels, but ADH deficiency can be confirmed indirectly; oxytocin levels are not routinely measured.Generally, the finding of a combination of a low pituitary hormone together with a low hormone from the effector gland is indicative of hypopituitarism. Occasionally, the pituitary hormone may be normal but the effector gland hormone decreased; in this case, the pituitary is not responding appropriately to effector hormone changes, and the combination of findings is still suggestive of hypopituitarism. Basal tests Levels of LH/FSH may be suppressed by a raised prolactin level, and are therefore not interpretable unless prolactin is low or normal. In men, the combination of low LH and FSH in combination with a low testosterone confirms LH/FSH deficiency; a high testosterone would indicate a source elsewhere in the body (such as a testosterone-secreting tumor). In women, the diagnosis of LH/FSH deficiency depends on whether the woman has been through the menopause. Before the menopause, abnormal menstrual periods together with low estradiol and LH/FSH levels confirm a pituitary problem; after the menopause (when LH/FSH levels are normally elevated and the ovaries produce less estradiol), inappropriately low LH/FSH alone is sufficient. Stimulation tests with GnRH are possible, but their use is not encouraged.For TSH, basal measurements are usually sufficient, as well as measurements of thyroxine to ensure that the pituitary is not simply suppressing TSH production in response to hyperthyroidism (an overactive thyroid gland). A stimulation test with thyrotropin-releasing hormone (TRH) is not regarded as useful. Prolactin can be measured by basal level, and is required for the interpretation of LH and FSH results in addition to the confirmation of hypopituitarism or diagnosis of a prolactin-secreting tumor. Stimulation tests Growth hormone deficiency is almost certain if all other pituitary tests are also abnormal, and insulin-like growth factor 1 (IGF-1) levels are decreased. If this is not the case, IGF-1 levels are poorly predictive of the presence of GH deficiency; stimulation testing with the insulin tolerance test is then required. This is performed by administering insulin to lower the blood sugar to a level below 2.2 mmol/L. Once this occurs, growth hormone levels are measured. If they are low despite the stimulatory effect of the low blood sugars, growth hormone deficiency is confirmed. The test is not without risks, especially in those prone to seizures or are known to have heart disease, and causes the unpleasant symptoms of hypoglycemia. Alternative tests (such as the growth hormone releasing hormone stimulation test) are less useful, although a stimulation test with arginine may be used for diagnosis, especially in situations where an insulin tolerance test is thought to be too dangerous. If GH deficiency is suspected, and all other pituitary hormones are normal, two different stimulation tests are needed for confirmation.If morning cortisol levels are over 500 nmol/L, ACTH deficiency is unlikely, whereas a level less than 100 is indicative. Levels between 100 and 500 require a stimulation test. This, too, is done with the insulin tolerance test. A cortisol level above 500 after achieving a low blood sugar rules out ACTH deficiency, while lower levels confirm the diagnosis. A similar stimulation test using corticotropin-releasing hormone (CRH) is not sensitive enough for the purposes of the investigation. If the insulin tolerance test yields an abnormal result, a further test measuring the response of the adrenal glands to synthetic ACTH (the ACTH stimulation test) can be performed to confirm the diagnosis. Stimulation testing with metyrapone is an alternative. Some suggest that an ACTH stimulation test is sufficient as first-line investigation, and that an insulin tolerance test is only needed if the ACTH test is equivocal. The insulin tolerance test is discouraged in children. None of the tests for ACTH deficiency are perfect, and further tests after a period of time may be needed if initial results are not conclusive.Symptoms of diabetes insipidus should prompt a formal fluid deprivation test to assess the bodys response to dehydration, which normally causes concentration of the urine and increasing osmolarity of the blood. If these parameters are unchanged, desmopressin (an ADH analogue) is administered. If the urine then becomes concentrated and the blood osmolarity falls, there is a lack of ADH due to lack of pituitary function ("cranial diabetes insipidus"). In contrast, there is no change if the kidneys are unresponsive to ADH due to a different problem ("nephrogenic diabetes insipidus"). Further investigations If one of these tests shows a deficiency of hormones produced by the pituitary, magnetic resonance imaging (MRI) scan of the pituitary is the first step in identifying an underlying cause. MRI may show various tumors and may assist in delineating other causes. Tumors smaller than 1 cm are referred to as microadenomas, and larger lesions are called macroadenomas. Computed tomography with radiocontrast may be used if MRI is not available. Formal visual field testing by perimetry is recommended, as this would show evidence of optic nerve compression by a tumor.Other tests that may assist in the diagnosis of hypopituitarism, especially if no tumor is found on the MRI scan, are ferritin (elevated in hemochromatosis), angiotensin converting enzyme (ACE) levels (often elevated in sarcoidosis), and human chorionic gonadotropin (often elevated in tumor of germ cell origin). If a genetic cause is suspected, genetic testing may be performed. Treatment Treatment of hypopituitarism is threefold: removing the underlying cause, treating the hormone deficiencies, and addressing any other repercussions that arise from the hormone deficiencies. Underlying cause Pituitary tumors require treatment when they are causing specific symptoms, such as headaches, visual field defects or excessive hormone secretion. Transsphenoidal surgery (removal of the tumor by an operation through the nose and the sphenoidal sinuses) may, apart from addressing symptoms related to the tumor, also improve pituitary function, although the gland is sometimes damaged further as a result of the surgery. When the tumor is removed by craniotomy (opening the skull), recovery is less likely–but sometimes this is the only suitable way to approach the tumor. After surgery, it may take some time for hormone levels to change significantly. Retesting the pituitary hormone levels is therefore performed 2 to 3 months later.Prolactinomas may respond to dopamine agonist treatment–medication that mimics the action of dopamine on the lactrotrope cells, usually bromocriptine or cabergoline. This approach may improve pituitary hormone secretion in more than half the cases, and make supplementary treatment unnecessary.Other specific underlying causes are treated as normally. For example, hemochromatosis is treated by venesection, the regular removal of a fixed amount of blood. Eventually, this decreases the iron levels in the body and improves the function of the organs in which iron has accumulated. Hormone replacement Most pituitary hormones can be replaced indirectly by administering the products of the effector glands: hydrocortisone (cortisol) for adrenal insufficiency, levothyroxine for hypothyroidism, testosterone for male hypogonadism, and estradiol for female hypogonadism (usually with a progestogen to inhibit unwanted effects on the uterus). Growth hormone is available in synthetic form, but needs to be administered parenterally (by injection). Antidiuretic hormone can be replaced by desmopressin (DDAVP) tablets or nose spray. Generally, the lowest dose of the replacement medication is used to restore wellbeing and correct the deranged results, as excessive doses would cause side-effects or complications. Those requiring hydrocortisone are usually instructed to increase their dose in physically stressful events such as injury, hospitalization and dental work as these are times when the normal supplementary dose may be inadequate, putting the patient at risk of adrenal crisis.Long-term follow up by specialists in endocrinology is generally needed for people with known hypopituitarism. Apart from ensuring the right treatment is being used and at the right doses, this also provides an opportunity to deal with new symptoms and to address complications of treatment.Difficult situations arise in deficiencies of the hypothalamus-pituitary-gonadal axis in people (both men and women) who experience infertility; infertility in hypopituitarism may be treated with subcutaneous infusions of FSH, human chorionic gonadotropin–which mimics the action of LH–and occasionally GnRH. Prognosis Several studies have shown that hypopituitarism is associated with an increased risk of cardiovascular disease and some also an increased risk of death of about 50% to 150% the normal population. It has been difficult to establish which hormone deficiency is responsible for this risk, as almost all patients studied had growth hormone deficiency. The studies also do not answer the question as to whether the hypopituitarism itself causes the increased mortality, or whether some of the risk is to be attributed to the treatments, some of which (such as sex hormone supplementation) have a recognized adverse effect on cardiovascular risk.The largest study to date followed over a thousand people for eight years; it showed an 87% increased risk of death compared to the normal population. Predictors of higher risk were: female sex, absence of treatment for sex hormone deficiency, younger age at the time of diagnosis, and a diagnosis of craniopharyngioma. Apart from cardiovascular disease, this study also showed an increased risk of death from lung disease.Quality of life may be significantly reduced, even in those people on optimum medical therapy. Many report both physical and psychological problems. It is likely that the commonly used replacement therapies do not completely mimic the natural hormone levels in the body. Health costs remain about double those of the normal population.Hypopituitarism is usually permanent. It requires lifelong treatment with one or more medicines. Epidemiology There is only one study that has measured the prevalence (total number of cases in a population) and incidence (annual number of new cases) of hypopituitarism. This study was conducted in Northern Spain and used hospital records in a well-defined population. The study showed that 45.5 people out of 100,000 had been diagnosed with hypopituitarism, with 4.2 new cases per year. 61% were due to tumors of the pituitary gland, 9% due to other types of lesions, and 19% due to other causes; in 11% no cause could be identified.Recent studies have shown that people with a previous traumatic brain injury, spontaneous subarachnoid hemorrhage (a type of stroke) or radiation therapy involving the head have a higher risk of hypopituitarism. After traumatic brain injury, as much as a quarter have persistent pituitary hormone deficiencies. Many of these people may have subtle or non-specific symptoms that are not linked to pituitary problems but attributed to their previous condition. It is therefore possible that many cases of hypopituitarism remain undiagnosed, and that the annual incidence would rise to 31 per 100,000 annually if people from these risk groups were to be tested. History The pituitary was known to the ancients, such as Galen, and various theories were proposed about its role in the body, but major clues as to the actual function of the gland were not advanced until the late 19th century, when acromegaly due to pituitary tumors was described. The first known report of hypopituitarism was made by the German physician and pathologist Dr Morris Simmonds. He described the condition on autopsy in a 46-year-old woman who had had severe puerperal fever eleven years earlier, and subsequently had amenorrhea, weakness, signs of rapid aging, and anemia. The pituitary gland was very small and there were few remnants of both the anterior and the posterior pituitary. The eponym Simmonds syndrome is used infrequently for acquired hypopituitarism, especially when cachexia (general ill health and malnutrition) predominates. Most of the classic causes of hypopituitarism were described in the 20th century; the early 21st century saw the recognition of how common hypopituitarism could be in previous head injury victims.Until the 1950s, the diagnosis of pituitary disease remained based on clinical features and visual field examination, sometimes aided by pneumoencephalography and X-ray tomography. Nevertheless, the field of pituitary surgery developed during this time. The major breakthrough in diagnosis came with the discovery of radioimmunoassay by Rosalyn Yalow and Solomon Berson in the late 1950s. This allowed the direct measurement of the hormones of the pituitary, which as a result of their low concentrations in blood had previously been hard to measure. Stimulation tests were developed in the 1960s, and in 1973 the triple bolus test was introduced, a test that combined stimulation testing with insulin, GnRH and TRH. Imaging of the pituitary, and therefore identification of tumors and other structural causes, improved radically with the introduction of computed tomography in the late 1970s and magnetic resonance imaging in the 1980s. Popular culture The scenario of the movie Orphan by Jaume Collet-Serra in 2009, is entirely based on the antagonist, a 33-year-old Estonian serial killer named Leena Klammer; who has a form of hypopituitarism that also causes her to have proportional dwarfism, making her look like a 9-year-old child named Esther. In 2014, into the french TV show "Profilage", the storyline of the episode "Poupée russe" (Season 5, Episode 2) is also based on the theme of a similar illness. References External links Hypopituitarism at Curlie
Weaver syndrome	Weaver syndrome is a rare autosomal dominant genetic disorder associated with rapid growth beginning in the prenatal period and continuing through the toddler and youth years. It is characterized by advanced osseous maturation and distinctive craniofacial, skeletal and neurological abnormalities. It is similar to Sotos syndrome and is classified as an overgrowth syndrome. Its genetic cause was identified in 2011 as mutations in the EZH2 gene. Forty-eight cases had been documented and confirmed as of December 2013, and its prevalence is estimated to be similar to that of Sotos syndrome, around 1 in 15,000. It was first described by American physician David Weaver in 1974. Signs and symptoms Children with Weaver syndrome tend to look similar and have distinctive physical and craniofacial characteristics, which may include several, but not all, of the following features: Other features may include loose skin, thin deep-set nails, thin hair, short ribs, limited elbow and knee extension, camptodactyly, and a coarse, low-pitched voice. Delayed development of motor skills such as sitting, standing, and walking are commonly exhibited in early childhood. Patients with Weaver syndrome typically have mild intellectual disability with poor coordination and balance. They also have some neurological abnormalities such as speech delay, epilepsy, intellectual disability, hypotonia or hypertonia, and behavioral problems. Cause The cause for Weaver syndrome was identified in 2011 as autosomal dominant mutations in the EZH2 gene on chromosome 7q36. EZH2 (Enhancer of Zeste, Drosophila, homolog 2) is the second histone methyltransferase associated with human overgrowth. It encodes the catalytic component of the PRC2 protein complex (Polycomb Repressive Complex 2), which regulates chromatin structure and gene expression, and has been found to repress transcription. EZH2 also has critical roles in stem cell maintenance and cell lineage determination, such as osteogenesis, myogenesis, lymphopoiesis and hematopoiesis. It can also be associated with mutations in the histone methyltransferase NSD1 gene on chromosome 5q35. The functions of NSD1 are not clearly known, but it is thought to act as a factor in influencing transcription, which contains domains involved in chromatin-mediated regulation during development.Most cases are found to be sporadic, with no family history of the syndrome, although there have been a few cases in families where autosomal dominant inheritance has been reported. Diagnosis Differential diagnosis Weaver syndrome and Sotos syndrome are often mistaken for one another due to their significant phenotypic overlap and similarities. Clinical features shared by both syndromes include overgrowth in early development, advanced bone age, developmental delay, and prominent macrocephaly. Mutations in the NSD1 gene may also be another cause for confusion. The NSD1 gene provides instructions for making a protein that is involved in normal growth and development. Deletions and mutations in the NSD1 gene is a common cause for patients with Sotos syndrome and in some cases for Weaver syndrome as well.Features distinguishing Weaver syndrome from Sotos syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep-set nails, retrognathia with a prominent chin crease, increased prenatal growth, and a carpal bone age that is greatly advanced compared to metacarpal and phalangeal bone age. Treatment There is no cure available for Weaver syndrome. However, with multidisciplinary management such as neurological, pediatric, orthopedic and psychomotor care and genetic counseling, symptoms can be managed. Surgery may be used to correct any skeletal issues. Physical and occupational therapy are considered an option to help with muscle tone. Also, speech therapy is often recommended for speech related problems. Prognosis With appropriate treatment and management, patients with Weaver syndrome appear to do well, both physically and intellectually, throughout their life and have a normal lifespan. Their adult height can reach 7-8 feet. Epidemiology The incidence of Weaver syndrome is uncertain, as the causative mutation was only identified in 2011. As of December 2013, 48 cases of Weaver syndrome had been documented and confirmed. In 2012, the South West Thames Regional Genetic Service at St Georges Hospital in London, based on their detection rate among a cohort of patients within their Childhood Overgrowth Study, estimated a prevalence rate similar to that of Sotos syndrome, around 1 in 15,000. History The condition was first described by American physician David Weaver in 1974. See also Beckwith–Wiedemann syndrome Perlman syndrome Sotos syndrome References == External links ==
Trichothiodystrophy	Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into tricho – "hair", thio – "sulphur", and dystrophy – "wasting away" or literally "bad nourishment". TTD is associated with a range of symptoms connected with organs of the ectoderm and neuroectoderm. TTD may be subclassified into four syndromes: Approximately half of all patients with trichothiodystrophy have photosensitivity, which divides the classification into syndromes with or without photosensitivity; BIDS and PBIDS, and IBIDS and PIBIDS. Modern covering usage is TTD-P (photosensitive), and TTD. Presentation Features of TTD can include photosensitivity, icthyosis, brittle hair and nails, intellectual impairment, decreased fertility and short stature. A more subtle feature associated with this syndrome is a "tiger tail" banding pattern in hair shafts, seen in microscopy under polarized light. The acronyms PIBIDS, IBIDS, BIDS and PBIDS give the initials of the words involved. BIDS syndrome, also called Amish brittle hair brain syndrome and hair-brain syndrome, is an autosomal recessive inherited disease. It is nonphotosensitive. BIDS is characterized by brittle hair, intellectual impairment, decreased fertility, and short stature.: 501 There is a photosensitive syndrome, PBIDS.BIDS is associated with the gene MPLKIP (TTDN1). IBIDS syndrome, following the acronym from ichthyosis, brittle hair and nails, intellectual impairment and short stature, is the Tay syndrome or sulfur-deficient brittle hair syndrome, first described by Tay in 1971. (Chong Hai Tay was the Singaporean doctor who was the first doctor in South East Asia to have a disease named after him.) Tay syndrome should not be confused with the Tay–Sachs disease.: 485 It is an autosomal recessive congenital disease.: 501 In some cases, it can be diagnosed prenatally. IBIDS syndrome is nonphotosensitive. Cause The photosensitive form is referred to as PIBIDS, and is associated with ERCC2 and ERCC3. Photosensitive forms All photosensitive TTD syndromes have defects in the nucleotide excision repair (NER) pathway, which is a vital DNA repair system that removes many kinds of DNA lesions. This defect is not present in the nonphotosensitive TTDs. These type of defects can result in other rare autosomal recessive diseases like xeroderma pigmentosum and Cockayne syndrome. DNA repair Currently, mutations in four genes are recognized as causing the TTD phenotype, namely TTDN1, XPB, XPD and TTDA. Individuals with defects in XPB, XPD and TTDA are photosensitive, whereas those with a defect in TTDN1 are not. The three genes, XPB, XPD and TTDA, encode protein components of the multi-subunit transcription/repair factor IIH (TFIIH). This complex factor is an important decision maker in NER that opens the DNA double helix after damage is initially recognized. NER is a multi-step pathway that removes a variety of different DNA damages that alter normal base pairing, including both UV-induced damages and bulky chemical adducts. Features of premature aging often occur in individuals with mutational defects in genes specifying protein components of the NER pathway, including those with TTD (see DNA damage theory of aging). Diagnosis Treatment See also Skin lesion List of cutaneous conditions References External links NIH document on Tay syndrome
Herpesviral meningitis	Herpesviral meningitis is meningitis associated with herpes simplex virus (HSV).HSV-2 is the most common cause of Mollarets meningitis, a type of recurrent viral meningitis. This condition was first described in 1944 by French neurologist Pierre Mollaret. Recurrences usually last a few days or a few weeks, and resolve without treatment. They may recur weekly or monthly for approximately 5 years following primary infection. Diagnosis Although DNA analysis techniques such as polymerase chain reaction can be used to look for DNA of herpesviruses in spinal fluid or blood, the results may be negative, even in cases where other definitive symptoms exist. Treatment See also Herpesviral encephalitis References == External links ==
Acropachy	Acropachy is a dermopathy associated with Graves disease. It is characterized by soft-tissue swelling of the hands and clubbing of the fingers. Radiographic imaging of affected extremities typically demonstrates periostitis, most commonly the metacarpal bones. The exact cause is unknown, but it is thought to be caused by stimulating auto-antibodies that are implicated in the pathophysiology of Graves thyrotoxicosis. There is no effective treatment for acropachy. Since it is closely associated with Graves disease, it is associated with other manifestations of Graves disease, such as Graves ophthalmopathy and thyroid dermopathy.Hereditary acropachy (also known as "isolated congenital nail clubbing") may be associated with HPGD. See also Periosteal reaction References External links Radiopaedia.org: Thyroid acropachy
Non-gonococcal urethritis	Nongonococcal urethritis (NGU) is an inflammation of the urethra that is not caused by gonorrheal infection. For treatment purposes, doctors usually classify infectious urethritis in two categories: gonococcal urethritis, caused by gonorrhea, and nongonococcal urethritis (NGU). Symptoms and signs The symptoms of urethritis can include pain or a burning sensation upon urination (dysuria), a white/cloudy discharge and a feeling that one needs to pass urine frequently. For men, the signs and symptoms are discharge from the penis, burning or pain when urinating, itching, irritation, or tenderness. In women, the signs and symptoms are discharge from vagina, burning or pain when urinating, anal or oral infections, abdominal pain, or abnormal vaginal bleeding, which may be an indication that the infection has progressed to Pelvic Inflammatory Disease. NGU is transmitted by touching the mouth, penis, vagina or anus by penis, vagina or anus of a person who has NGU. NGU is more common in men than women. Men may have a discharge (strange liquid) from the penis, pain when urinating, and itching, irritation or tenderness around the opening of the penis. Women might not have any symptoms and may not know they have NGU until severe problems occur. Women might have discharge from the vagina, burning or pain when urinating, pain in the abdominal (stomach) area, or bleeding from the vagina that is not from a monthly period. (This may be an sign that NGU has become worse and turned into Pelvic Inflammatory Disease, or PID). Causes There are many causes of NGU. This is in part due to the large variety of organisms living in the urinary tract. Ureaplasma urealyticum and Mycoplasma genitalium are some of the culprits. NGU is also associated with reactive arthritis, in which the triad of arthritis, conjunctivitis, and urethritis is seen. Bacterial The most common bacterial cause of NGU is Chlamydia trachomatis, but it can also be caused by Ureaplasma urealyticum, Haemophilus vaginalis, Mycoplasma genitalium, Mycoplasma hominis, Neisseria meningitidis, Gardnerella vaginalis, Acinetobacter lwoffii, Acinetobacter calcoaceticus, and E.coli. Viral Herpes simplex virus, Adenovirus, Cytomegalovirus Fungi Candida Albicans Parasitic Parasitic causes include Trichomonas vaginalis (rare). Noninfectious Urethritis can be caused by mechanical injury (from a urinary catheter or a cystoscope), or by an irritating chemical (antiseptics or some spermicides). Diagnosis It has been easy to test for the presence of gonorrhea by viewing a Gram stain of the urethral discharge under a microscope: The causative organism is distinctive in appearance; however, this works only with men because other non-pathogenic gram-negative microbes are present as normal flora of the vagina in women. Thus, one of the major causes of urethritis can be identified (in men) by a simple common test, and the distinction between gonococcal and non-gonococcal urethritis arose for this reason. Non-gonococcal urethritis (NGU) is diagnosed if a person with urethritis has no signs of gonorrhea bacteria on laboratory tests. The most frequent cause of NGU (23%-55% of cases) is C. trachomatis. Non-specific urethritis In the United Kingdom, NGU is more often called non-specific urethritis; "non-specific" is a medical term meaning "specific cause has not been identified", and in this case refers to the detection of urethritis, and the testing for but found negative of gonorrhea. In this sense, the most likely cause of NSU is a chlamydia infection. However, the term NSU is sometimes distinguished and used to mean that both gonorrhea and chlamydia have been ruled out. Thus, depending on the sense, chlamydia can either be the most likely cause or have been ruled out, and frequently detected organisms are Ureaplasma urealyticum and Mycoplasma hominis. Treatment Treatment is based on the prescription and use of the proper antibiotics depending on the strain of the ureaplasma.Because of its multi-causative nature, initial treatment strategies involve using a broad range antibiotic that is effective against chlamydia (such as doxycycline). It is imperative that both the patient and any sexual contacts be treated. Women infected with the organisms that cause NGU may develop pelvic inflammatory disease. If symptoms persist, follow-up with a urologist may be necessary to identify the cause. According to a study, tinidazole used with doxycycline or azithromycin may cure NGU better than when doxycycline or azithromycin is used alone.If left untreated, complications include epididymitis and infertility. Consistent and correct use of latex condoms during sexual activity greatly reduces the likelihood of infection. See also Bacterial vaginosis References == External links ==
Contracture	In pathology, a contracture is a permanent shortening of a muscle or joint. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spastic cerebral palsy, but can also be due to the congenital abnormal development of muscles and connective tissue in the womb. Contractures develop when normally elastic tissues such as muscles or tendons are replaced by inelastic tissues (fibrosis). This results in the shortening and hardening of these tissues, ultimately causing rigidity, joint deformities and a total loss of movement around the joint. Most of the physical therapy, occupational therapy and other exercise regimens targeted towards people with spasticity focuses on trying to prevent contractures from happening in the first place. However, research on sustained traction of connective tissue in approaches such as adaptive yoga has demonstrated that contracture can be reduced, at the same time that tendency toward spasticity is addressed. Contractures can also be due to ischemia (restriction of blood flow) leading to the death of muscle tissue, as in Volkmanns contracture. They can also be caused by excessive myofibroblast and matrix metalloproteinase accumulation in wound margins following injury. See also Arthrogryposis Burn scar contracture Capsular contracture Clubfoot Dupuytrens contracture Freeman–Sheldon syndrome Marden–Walker syndrome Muscle contracture References == External links ==
Geniculate ganglionitis	Geniculate ganglionitis or geniculate neuralgia (GN), also called nervus intermedius neuralgia, Ramsay Hunt syndrome, or Hunts neuralgia, is a rare disorder characterized by severe paroxysmal neuralgic pain deep in the ear, that may spread to the ear canal, outer ear, mastoid or eye regions. GN may also occur in combination with trigeminal or glossopharyngeal neuralgia.The pain of GN is sharp, shooting or burning and can last for hours. Painful attacks can be triggered by cold, noise, swallowing or touch, but triggers are usually unique to the sufferer. Other related symptoms that may be experienced include increased salivation, bitter taste, tinnitus and vertigo. GN is rare, and only limited data is available regarding the incidence, prevalence, and risk factors associated with this condition. Middle-aged adults, however, seem to be predominantly affected, women more than men. Cause GN may be caused by compression of somatic sensory branch of cranial nerve VII which goes through the nervus intermedius. In sufferers of GN, signals sent along these nerves are altered and interpreted by the geniculate ganglion (a structure in the brain) as GN pain. GN may also develop following herpes zoster oticus (Ramsay Hunt syndrome), where cold sores occur on the ear drum or ear. This may also be associated with facial paresis (weakness), tinnitus, vertigo and deafness. Disorders of lacrimation, salivation and/or taste sometimes accompany the pain. There is a common association with herpes zoster. Diagnosis Diagnostic criteria:A. Pain paroxysms of intermittent occurrence, lasting for seconds or minutes, in the depth of the ear B. Presence of a trigger area in the posterior wall of the auditory canal C. Not attributed to another disorder Treatment Pharmacological A trial of the anticonvulsant drug carbamazepine is common for patients diagnosed with GN. For patients who do not tolerate or respond to carbamazepine, alternative drugs include oxcarbazepine, gabapentin, phenytoin, lamotrigine, and baclofen. In addition, tricyclics (e.g., amitriptyline) and pregabalin are useful in other types of neuropathic pain. Surgical A variety of surgeries have been performed including microvascular decompression (MVD) of the fifth, ninth, and tenth nerves; as well as partial cutting of the nervus intermedius, geniculate ganglion, chorda tympani and/or the ninth and tenth cranial nerves. References == External links ==
Glucuronosyltransferase	Uridine 5-diphospho-glucuronosyltransferase (UDP-glucuronosyltransferase, UGT) is a microsomal glycosyltransferase (EC 2.4.1.17) that catalyzes the transfer of the glucuronic acid component of UDP-glucuronic acid to a small hydrophobic molecule. This is a glucuronidation reaction.Alternative names: glucuronyltransferase UDP-glucuronyl transferase UDP-GT Function Glucuronosyltransferases are responsible for the process of glucuronidation, a major part of phase II metabolism. Arguably the most important of the Phase II (conjugative) enzymes, UGTs have been the subject of increasing scientific inquiry since the mid-to-late 1990s. The reaction catalyzed by the UGT enzyme involves the addition of a glucuronic acid moiety to xenobiotics and is the most important pathway for the human bodys elimination of the most frequently prescribed drugs. It is also the major pathway for foreign chemical (dietary, environmental, pharmaceutical) removal for most drugs, dietary substances, toxins and endogenous substances. UGT is present in humans, other animals, plants, and bacteria. Famously, UGT enzymes are not present in the genus Felis, and this accounts for a number of unusual toxicities in the cat family. The glucuronidation reaction consists of the transfer of the glucuronosyl group from uridine 5-diphospho-glucuronic acid (UDPGA) to substrate molecules that contain oxygen, nitrogen, sulfur or carboxyl functional groups. The resulting glucuronide is more polar (e.g. hydrophilic) and more easily excreted than the substrate molecule. The product solubility in blood is increased allowing it to be eliminated from the body by the kidneys. Diseases A deficiency in the bilirubin specific form of glucuronosyltransferase is thought to be the cause of Gilberts syndrome, which is characterized by unconjugated hyperbilirubinemia. It is also associated with Crigler–Najjar syndrome, a more serious disorder where the enzymes activity is either completely absent (Crigler–Najjar syndrome type I) or less than 10% of normal (type II). Infants may have a developmental deficiency in UDP-glucuronyl transferase, and are unable to hepatically metabolize the antibiotic drug chloramphenicol which requires glucuronidation. This leads to a condition known as gray baby syndrome. Causes Causes of unconjugated hyperbilirubinemia are divided into three main categories, namely, excessive bilirubin synthesis, liver bilirubin uptake malfunction, and bilirubin conjugation compromise.As to excessive bilirubin synthesis, both intravascular hemolysis and extravascular hemolysis can involve in the pathophysiology. Additionally, dyserythropoiesis and extravasation of blood into tissues such as angioedema and edema can also lead to indirect hyperbilirubinemia, along with heart failure, medication-induced, ethinyl estradiol, chronic hepatitis, and cirrhosis that are, otherwise, attributed to hepatic bilirubin mal-uptake and bilirubin conjugation compromise, respectively. Genes Human genes which encode UGT enzymes include: B3GAT1, B3GAT2, B3GAT3 UGT1A1, UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10 UGT2A1, UGT2A2, UGT2A3, UGT2B4, UGT2B7, UGT2B10, UGT2B11, UGT2B15, UGT2B17, UGT2B28 References External links Glucuronosyltransferase at the US National Library of Medicine Medical Subject Headings (MeSH)
Tachycardia-induced cardiomyopathy	Tachycardia-induced cardiomyopathy (TIC) is a disease where prolonged tachycardia (a fast heart rate) or arrhythmia (an irregular heart rhythm) causes an impairment of the myocardium (heart muscle), which can result in heart failure. People with TIC may have symptoms associated with heart failure (e.g. shortness of breath or ankle swelling) and/or symptoms related to the tachycardia or arrhythmia (e.g. palpitations). Though atrial fibrillation is the most common cause of TIC, several tachycardias and arrhythmias have been associated with the disease.There are no formal diagnostic criteria for TIC. Thus, TIC is typically diagnosed when (1) tests have excluded other causes of cardiomyopathy and (2) there is improvement in myocardial function after treatment of the tachycardia or arrhythmia. Treatment of TIC can involve treating the heart failure as well as the tachycardia or arrhythmia. TIC has a good prognosis with treatment, with most people recovering some to all of their heart function.The number of cases that occur is unclear. TIC has been reported in all age groups. Signs and symptoms People with TIC most often present with symptoms of congestive heart failure and/or symptoms related to their irregular heart rhythm. Symptoms of congestive heart failure can include shortness of breath, ankle swelling, fatigue, and weight gain. Symptoms of an irregular heart rhythm can include palpitations and chest discomfort.The timecourse of TIC is most well-studied in experiments on animals. Researchers have found that animals began to exhibit abnormal changes in blood flow after just one day of an artificially generated fast heart rate (designed to simulate a tachyarrythmia). As their TIC progresses, these animals will have worsening heart function (e.g.: reduced cardiac output and reduced ejection fraction) for 3–5 weeks. The worsened heart function then persists at a stable state until the heart rate is returned to normal. With normal heart rates, these animals begin to demonstrate improving heart function at 1–2 days, and even complete recovery of ejection fraction at 1 month.Human studies of the timecourse of TIC are not as robust as animal studies, though current studies suggest that the majority of people with TIC will recover a significant degree of heart function over months to years. Causes TIC has been associated with supraventricular tachycardia (SVT), ventricular tachycardia (VT), frequent premature ventricular contractions (PVCs), rapid atrial and ventricular pacing, and left bundle branch block. The types of SVT associated with TIC include atrial fibrillation, atrial flutter, incessant atrial tachycardia, permanent junctional reciprocating tachycardia, atrioventricular reciprocating tachycardia, and atrioventricular nodal reentry tachycardia. Atrial fibrillation is the most common and well-studied etiology of TIC. Diagnosis There are no specific diagnostic criteria for TIC, and it can be difficult to diagnose for a number of reasons. First, in patients presenting with both tachycardia and cardiomyopathy, it can be difficult to distinguish which is the causative agent. Additionally, it can occur in patients with or without underlying structural heart disease. Previously normal left ventricular ejection fraction or left ventricular systolic dysfunction out of proportion to a patient’s underlying cardiac disease can be important clues to possible TIC. The diagnosis of TIC is made after excluding other causes of cardiomyopathy and observing resolution of the left ventricular systolic dysfunction with treatment of the tachycardia.Specific tests that can be used in the diagnosis and monitoring of TIC include: electrocardiography (EKG) Continuous cardiac rhythm monitoring (e.g. Holter monitor) echocardiography Radionuclide imaging Endomyocardial biopsy Cardiac magnetic resonance imaging (CMR) N-terminal pro-B-type natriuretic peptide (NT-pro BNP)Cardiac rhythm monitors can be used to diagnose tachyarrhythmias. The most common modality used is an EKG. A continuous rhythm monitor such as a Holter monitor can be used to characterize the frequency of a tachyarrhythmia over a longer period of time. Additionally, some patients may not present to the clinical setting in an abnormal rhythm, and continuous rhythm monitor can be useful to determine if an arrhythmia is present over a longer duration of time.To assess cardiac structure and function, echocardiography is the most commonly available and utilized modality. In addition to decreased left ventricular ejection fraction, studies indicate that patients with TIC may have a smaller left ventricular end-diastolic dimension compared to patients with idiopathic dilated cardiomyopathy. Radionuclide imaging can be used as a non-invasive test to detect myocardial ischemia. Cardiac MRI has also been used to evaluate patients with possible TIC. Late-gadolinium enhancement on cardiac MRI indicates the presence of fibrosis and scarring, and may be evidence of cardiomyopathy not due to tachycardia. A decline in serial NT-pro BNP with control of tachyarrhythmia indicates reversibility of the cardiomyopathy, which would also suggest TIC.People with TIC display distinct changes in endomyocardial biopsies. TIC is associated with the infiltration of CD68+ macrophages into the myocardium while CD3+ T-cells are very rare. Furthermore, patients with TIC display significant fibrosis due to collagen deposition. The distribution of mitochondria has found to be altered as well, with an enrichment at the intercalated discs (EMID-sign).TIC is likely underdiagnosed due to attribution of the tachyarrhythmia to the cardiomyopathy. Poor control of the tachyarrhythmia can result in worsening of heart failure symptoms and cardiomyopathy. Therefore, it is important to aggressively treat the tachyarrhythmia and monitor patients for resolution of left ventricular systolic dysfunction in cases of suspected TIC. Treatment Treatment of TIC involves treating both the tachyarrhythmia and the heart failure with the goal of adequate rate control or restoration of the normal heart rhythm (aka. normal sinus rhythm) to reverse the cardiomyopathy. The treatment of the tachyarrhythmia depends on the specific arrhythmia, but possible treatment modalities include rate control, rhythm control with antiarrhythmic agents and cardioversion, radiofrequency (RF) catheter ablation, or AV node ablation with permanent pacemaker implantation.For TIC due to atrial fibrillation, rate control, rhythm control, and RF catheter ablation can be effective to control the tachyarrhythmia and improve left ventricular systolic function. For TIC due to atrial flutter, rate control is often difficult to achieve, and RF catheter ablation has a relatively high success rate with a low risk of complications. In patients with TIC due to other types of SVT, RF catheter ablation is recommended as a first-line treatment. In patients with TIC due to VT or PVCs, both antiarrhythmics and RF catheter ablation can be used. However, the options for antiarrhythmic agents are limited because certain agents can be proarrhythmic in the setting of myocardial dysfunction in TIC. Therefore, RF catheter ablation is often a safe and effective choice for treatment VT and PVCs causing TIC. In cases where other treatment strategies fail, AV node ablation with permanent pacemaker implantation can also be used to treat the tachyarrhythmia.The treatment of heart failure commonly involves neurohormonal blockade with beta-blockers and angiotensin convertase inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) along with symptomatic management with diuretics. Beta-blockers and ACE inhibitors can inhibit and potentially reverse the negative cardiac remodeling, which refers to structural changes in the heart, that occurs in TIC. However, the need to continue these agents after treatment of the tacharrhythmia and resolution of left ventricular systolic dysfunction remains controversial. Prognosis The prognosis for TIC after treatment of the underlying tachyarrhythmia is generally good. Studies show that left ventricular function often improves within 1 month of treatment of the tachyarrhythmia, and normalization of the left ventricular ejection fraction occurs in the majority of patients by 3 to 4 months. In some patients however, recovery of this function can take greater than 1 year or be incomplete. In addition, despite improvement in the left ventricular ejection fraction, studies have demonstrated that patients with prior TIC continue to demonstrate signs of negative cardiac remodeling including increased left ventricular end-systolic dimension, end-systolic volume, and end-diastolic volume. Additionally, recurrence of the tachyarrhythmia in patients with a history of TIC has been associated with a rapid decline in left ventricular ejection fraction and more severe cardiomyopathy that their prior presentation, which may be a result of the negative cardiac remodeling. There have also been cases of sudden death in patients with a history of TIC, which may be associated with worse baseline left ventricular dysfunction. Given these risks, routine monitoring with clinic visits, ECG, and echocardiography is recommended. Epidemiology The true incidence of TIC is unclear. Some studies have noted the incidence of TIC in adults with irregular heart rhythms to range from 8% to 34%. Other studies of patients with atrial fibrillation and left ventricular dysfunction estimate that 25–50% of these study participants have some degree of TIC. TIC has been reported in all age groups. See also Cardiomyopathy Congestive heart failure References == External links ==
Myocardial rupture	Myocardial rupture is a laceration of the ventricles or atria of the heart, of the interatrial or interventricular septum, or of the papillary muscles. It is most commonly seen as a serious sequela of an acute myocardial infarction (heart attack). It can also be caused by trauma. Signs and symptoms Symptoms of myocardial rupture are recurrent or persistent chest pain, syncope, and distension of jugular vein. Sudden death caused by a myocardial rupture is sometimes preceded by no symptoms. Causes The most common cause of myocardial rupture is a recent myocardial infarction, with the rupture typically occurring three to five days after infarction. Other causes of rupture include cardiac trauma, endocarditis (infection of the heart), cardiac tumors, infiltrative diseases of the heart, and aortic dissection.Risk factors for rupture after an acute myocardial infarction include female gender, advanced age of the individual, first ischemic event, and a low body mass index. Other presenting signs associated with myocardial rupture include a pericardial friction rub, sluggish flow in the coronary artery after it is opened i.e. revascularized with an angioplasty, the left anterior descending artery being often the cause of the acute MI, and delay of revascularization greater than 2 hours. Diagnosis Due to the acute hemodynamic deterioration associated with myocardial rupture, the diagnosis is generally made based on physical examination, changes in the vital signs, and clinical suspicion. The diagnosis can be confirmed with echocardiography. The diagnosis is ultimately made at autopsy. Classification Myocardial ruptures can be classified as one of three types. Type I myocardial rupture is an abrupt slit-like tear that generally occurs within 24 hours of an acute myocardial infarction. Type II is an erosion of the infarcted myocardium, which is suggestive of a slow tear of the dead myocardium. Type II ruptures typically occur more than 24 hours after the infarction occurred. Type III ruptures are characterized by early aneurysm formation and subsequent rupture of the aneurysm.Another method for classifying myocardial ruptures is by the anatomical portion of the heart that has ruptured. By far the most dramatic is rupture of the free wall of the left or right ventricles, as this is associated with immediate hemodynamic collapse and death secondary to acute pericardial tamponade. Rupture of the interventricular septum will cause a ventricular septal defect. Rupture of a papillary muscle will cause acute mitral regurgitation.The rupture will most often occur near the edge of the necrotic myocardium where it abuts healthy (but hyperemic) myocardium where the inflammatory response is at its greatest. Further, the rupture will occur in an area of greatest shear stress. Within the left ventricle, these areas are adjacent to both anterior and posterior papillary muscles (regardless of whether the papillary muscle is involved in the infarction).Left ventricular free wall rupture almost always results in hemopericardium (the exception being in the scenario where the patient has had prior open heart surgery and has obliterative fibrous pericardial adhesions; these would prevent egress of blood) and pericardial tamponade. An accumulation of as little as 75 ml of blood, acquired acutely in a patient without pre-existing pericardial effusion, is sufficient to produce tamponade (wherein the ventricles are incapable of filling and are thus incapable of producing adequate stroke volume). Treatment The treatment for myocardial rupture is supportive in the immediate setting and surgical correction of the rupture, if feasible. A certain small percentage of individuals do not seek medical attention in the acute setting and survive to see the physician days or weeks later. In this setting, it may be reasonable to treat the rupture medically and delay or avoid surgery completely, depending on the individuals comorbid medical issues. Prognosis The prognosis of myocardial rupture is dependent on a number of factors, including which portion of the myocardium is involved in the rupture. In one case series, if myocardial rupture involved the free wall of the left ventricle, the mortality rate was 100.0%. The chances of survival rise dramatically if the patient: 1. has a witnessed initial event; 2. seeks early medical attention; 3. has an accurate diagnosis by the emergentologist; and 4. happens to be at a facility that has a cardiac surgery service (by whom a quick repair of the rupture can be attempted). Even if the individual survives the initial hemodynamic sequelae of the rupture, the 30‑day mortality is still significantly higher than if rupture did not occur. Incidence The incidence of myocardial rupture has decreased in the era of urgent revascularization and aggressive pharmacological therapy for the treatment of an acute myocardial infarction. However, the decrease in the incidence of myocardial rupture is not uniform; there is a slight increase in the incidence of rupture if thrombolytic agents are used to abort a myocardial infarction. On the other hand, if primary percutaneous coronary intervention is performed to abort the infarction, the incidence of rupture is significantly lowered. The incidence of myocardial rupture if PCI is performed in the setting of an acute myocardial infarction is about 1 percent. References == External links ==
Ulnar–mammary syndrome	Ulnar–mammary syndrome or Schinzel syndrome is a cutaneous condition characterized by nipple and breast hypoplasia or aplasia. Features of UMS can be mild to severe and can vary significantly from person to person, even within the same family. The main features of UMS include upper limb defects (including abnormal or incomplete development of the fingers and forearm), underdevelopment of the apocrine and mammary glands (leading to absent breast development and the inability to produce breast milk), and various genital abnormalities. Other signs and symptoms may include hormonal deficiencies, delayed puberty (particularly in males), dental problems and obesity. People with UMS may have distinct facial features, including a wide face tapering to a prominent chin, and a broad nose. Genetics It has been associated with TBX3. This gene is located on the long arm of chromosome 12 (12q24.21).Another gene that has been associated with this condition is SYNM. This gene is located on the long arm of chromosome 15 (15q26.3). See also Carvajal syndrome List of cutaneous conditions References == External links ==
Lichen striatus	Lichen striatus is a rare skin condition that is seen primarily in children, most frequently appearing ages 5–15.: 226–27 It consists of a self-limiting eruption of small, scaly papules. Symptoms Lichen striatus impacts the skin and nails. It is seen as an unbroken or disrupted, linear band consisting of small tan, pink or flesh colored papules. The papules could be smooth, flat topped or scaly. The band of lichen striatus varies from a few millimeters to 1-- 2 cm wide and extends from a few centimeters to the complete length of the extremity. By and large, the papules are unilateral and single on an extremity along the lines of Blaschko. Itching is an accompanying function of the disorder. Diagnosis Diagnosis is based on observing the appearance of the lesions. Management It is self-limiting condition 1.reassurance 2.steroid cream for local application 3.moisturiser lotion See also Lichen planus List of cutaneous conditions References External links New England Journal of Medicine - Images of the Week
Xeroderma pigmentosum	Xeroderma pigmentosum (XP) is a genetic disorder in which there is a decreased ability to repair DNA damage such as that caused by ultraviolet (UV) light. Symptoms may include a severe sunburn after only a few minutes in the sun, freckling in sun exposed areas, dry skin and changes in skin pigmentation. Nervous system problems, such as hearing loss, poor coordination, loss of intellectual function and seizures, may also occur. Complications include a high risk of skin cancer, with about half having skin cancer by age 10 without preventive efforts, and cataracts. There may be a higher risk of other cancers such as brain cancers.XP is autosomal recessive, with mutations in at least nine specific genes able to result in the condition. Normally, the damage to DNA which occurs in skin cells from exposure to UV light is repaired by nucleotide excision repair. In people with xeroderma pigmentosum, this damage is not repaired. As more abnormalities form in DNA, cells malfunction and eventually become cancerous or die. Diagnosis is typically suspected based on symptoms and confirmed by genetic testing.There is no cure for XP. Treatment involves completely avoiding the sun. This includes protective clothing, sunscreen and dark sunglasses when out in the sun. Retinoid creams may help decrease the risk of skin cancer. Vitamin D supplementation is generally required. If skin cancer occurs, it is treated in the usual way. The life expectancy of those with the condition is about 30 years less than normal.The disease affects about 1 in 100,000 worldwide. By region, it affects about 1 in 370 in India, 1 in 20,000 in Japan, 1 in 250,000 people in the United States and 1 in 430,000 in Europe. It occurs equally commonly in males and females. Xeroderma pigmentosum was first described in the 1870s by Moritz Kaposi. In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristic dry, pigmented skin. Individuals with the disease have been referred to as "children of the night" or "moon children". Signs and symptoms Signs and symptoms of xeroderma pigmentosum may include: Severe sunburn when exposed to only small amounts of sunlight. These often occur during a childs first exposure to sunlight. Development of many freckles at an early age Rough-surfaced growths (solar keratoses), and skin cancers Eyes that are painfully sensitive to the sun and may easily become irritated, bloodshot and clouded Blistering or freckling on minimum sun exposure Telangiectasia (spider veins) Limited growth of hair on chest and legs Scaly skin Xeroderma (dry skin) Irregular dark spots on the skin Corneal ulcerations Genetics One of the most frequent defects in xeroderma pigmentosum is an autosomal recessive genetic defect in which nucleotide excision repair (NER) enzymes are mutated, leading to a reduction in or elimination of NER. If left unchecked, damage caused by ultraviolet light can cause mutations in individual cells DNA. The causes of the neurological abnormalities are poorly understood and are not connected with exposure to ultraviolet light. The most current theories suggest that oxidative DNA damage is generated during normal metabolism in the central nervous system, and that some types of this damage must be repaired by NER.Since DNA repair is under genetic control, it can mutate. Many genetic disorders such as xeroderma pigmentosum (XP; MIM 278700) are caused by mutations in genes that repair damaged DNA. XP affects the mechanism that repairs UV damage in skin cell DNA. Those affected with the autosomal recessive disorder XP are extremely sensitive to UV light produced by the sun and develop pigmented spots, tumors, and skin cancer with minimal exposure. Individuals with XP are about 1,000 times more likely to develop skin cancer than individuals without the disorder.The molecular defects in XP cells result in a greatly elevated induction of mutations in sun-exposed skin of affected individuals. This increased mutation frequency probably accounts for the pigmentation changes and the skin cancers. Examination of mutations in the p53 gene in tumors from XP patients reveal p53 mutations characteristic of UV exposure in the majority of tumors As with all genetic disorders, genetic counseling and psychological support is appropriate for the families to discuss probability of occurrence in future pregnancies, feelings of isolation and concern about career prospects. There is no cure for xeroderma pigmentosum. The most common fate for individuals with XP is early death from cancer. XP repair proteins The XPA protein acts during NER as a scaffold for assembly of other DNA repair proteins at sites of DNA damage to ensure appropriate excision of the damage.The XPB (ERCC3) protein is employed in unwinding the DNA double helix after DNA damage is initially recognized. Mutations in the XPB(ERCC3) gene can lead to XP or XP combined with Cockayne syndrome.The XPC protein forms a complex with RAD23B protein to form the initial damage recognition factor in global genomic nucleotide excision repair (GG-NER). This complex recognizes a wide variety of damages that thermodynamically destabilize DNA duplexes.The XPD (ERCC2) protein, in combination with the XPB helicase-containing transcription/repair complex TFIIH, is employed in unwinding the DNA duplex after damage is initially recognized. Mutations in the XPD(ERCC2) gene cause a variety of syndromes; XP, trichothiodystrophy (TTD), or a combination of XP and Cockayne syndrome (XPCS). Both trichothiodystrophy and Cockayne syndrome display features of premature aging, suggesting an association between deficient DNA repair and premature aging (see DNA damage theory of aging). XPE is a heterodimeric protein composed of two subunits. The larger subunit DDB1 primarily functions as a core component of CUL4A- and CUL4B-based E3 ubiquitin ligase complexes. Substrates that are ubiquitinnated by these complexes include proteins employed in DNA repair.The XPF (ERCC4) protein together with the ERCC1 protein forms a complex usually designated ERCC1-XPF. This complex separates the DNA helix for a short distance on either side of the site of damage. It then acts as an endonuclease to incise the damaged DNA strand on the 5 side of the damaged site. Mutant cells with deficient ERCC1-XPF are not only defective in NER, but also in the repair of double-strand breaks and inter-strand crosslinks. The XPG protein is an endonuclease that incises DNA during NER at the 3 side of the damaged nucleotide. Mutations in the XPG (ERCC5) gene can lead to XP alone, or in combination with Cockayne syndrome (CS), or in combination with infantile lethal cerebro-oculo-facio-skeletal syndrome. Diagnosis Types There are seven complementation groups, plus one variant form: Treatment There is no cure for the disorder; all treatment is symptomatic or preventive. Symptoms can be avoided or controlled by completely avoiding exposure to sunlight, either by staying indoors or wearing protective clothing and using sunscreen when outdoors. Keratosis can also be treated by using cryotherapy or fluorouracil. In more severe cases of XP, even minuscule amounts of UV light, for example, from covered windows or fluorescent bulbs, can be very dangerous and trigger symptoms.On September 10, 2020, Clinuvel Pharmaceuticals announced that it was investigating the use of its FDA-approved flagship drug Scenesse as a potential treatment to increase pain-free light exposure for patients with xeroderma pigmentosum. Prognosis The average life expectancy of an individual with any type of XP and no neurological symptoms is approximately 37 years, and 29 years if neurological symptoms are present.In the United States, the probability for individuals with the disorder to survive until 40 years of age may be as high as 70% if they have never been exposed to sunlight in their life.In India, many patients with XP die at an early age from skin cancers. However, if a person is diagnosed early, does not have severe neurological symptoms, and takes precautionary measures to completely avoid any exposure to UV light and sunlight, they may be able to survive until middle age. History Xeroderma pigmentosum was first described in 1874 by Hebra and Moritz Kaposi. In 1882, Kaposi coined the term xeroderma pigmentosum for the condition, referring to its characteristic dry, pigmented skin.The 1968 paper about XP by James Cleaver demonstrated the link between UV-induced DNA damage, faulty DNA repair and cancer. Culture Because people with XP need to strictly avoid sunlight, but can go outside at night, they have been called children of the dark, children of the night, and vampire children. These terms can be considered derogatory.XP has been a plot element in several fictional works. One of the common themes in films about XP is whether teens with XP will risk sun exposure in pursuit of a romantic partner.Film series like Children of Darkness, a German silent-drama film which was released in two parts in the year of 1921 and 1922 respectively, was among some of the initially popular movies that was made about XP. Other films, like the 1964 American drama film Della, starring Joan Crawford, Paul Burke, Charles Bickford and Diane Baker, directed by Robert Gist, which was originally produced by Four Star Television as a television pilot for a proposed NBC series named Royal Bay, was also based on this skin disease. The Dark Side of the Sun, a 1988 American-Yugoslavian drama film, was directed by Božidar Nikolić and stars Brad Pitt for his first ever leading role as a young man in search of a cure for his disorder. The Others (2001 film), a 2001 American psychological horror film starring Nicole Kidman, features two children, Anne and Nicholas, who must avoid all sunlight because of a rare disease characterized by photosensitivity. A CBS television movie aired in 1994, Children of the Dark, was based on the story of the real-life couple Jim and Kim Harrison, whose two daughters have XP.Lurlene McDaniels young adult book How I Do Love Thee features the story "Night Vision", in which the protagonist, leukemia survivor Brett, falls in love with a girl named Shayla that has XP. Christopher Snow, the protagonist of Dean Koontzs Moonlight Bay Trilogy, has XP and therefore must live most of his life during the night. The first two entries of the trilogy, Fear Nothing and Seize the Night, were both published in 1998. The final entry in the trilogy, tentatively titled Ride the Storm, has yet to be published as of August 2020.The 2011 French drama film The Moon Child is based on a 13-year-old child with XP, which prevents him from exposing himself to daylight. The 2012 documentary Sun Kissed explores the XP problem on the Navajo Indian Reservation, and links it to the genetic legacy of the Long Walk of the Navajo, when the Navajo people were forced to move to a new location.The 2018 romance film Midnight Sun, based on a 2006 Japanese film, A Song to the Sun, tells the story of a girl named Katie Price with XP and the impact of her sickness on her life and relationships, following the story of Prices accidental exposure to sunlight and subsequent neurological degeneration. Research directions Research into XP has had two main results: better understanding the disease itself, and also better understanding the normal biological mechanisms involved in DNA repair. Research into XP has produced insights that have been translated into treatments and prevention for cancer. See also DeSanctis–Cacchione syndrome Genetic disorder Biogerontology Cockayne syndrome List of cutaneous conditions List of cutaneous conditions associated with increased risk of nonmelanoma skin cancer Photophobia Senescence References External links GeneReviews/NCBI/NIH/UW entry on xeroderma pigmentosum
Palatine uvula	The palatine uvula, usually referred to as simply the uvula, is a conic projection from the back edge of the middle of the soft palate, composed of connective tissue containing a number of racemose glands, and some muscular fibers. It also contains many serous glands, which produce thin saliva. It is only found in human beings. Structure Muscle The muscular part of the uvula (Latin: musculus uvulae) shortens and broadens the uvula. This changes the contour of the posterior part of the soft palate. This change in contour allows the soft palate to adapt closely to the posterior pharyngeal wall to help close the nasopharynx during swallowing.Its muscles are controlled by the pharyngeal branch of the vagus nerve. Variation A bifid or bifurcated uvula is a split or cleft uvula. Newborns with cleft palate often also have a split uvula. The bifid uvula results from incomplete fusion of the palatine shelves but it is considered only a slight form of clefting. Bifid uvulas have less muscle in them than a normal uvula, which may cause recurring problems with middle ear infections. While swallowing, the soft palate is pushed backwards, preventing food and drink from entering the nasal cavity. If the soft palate cannot touch the back of the throat while swallowing, food and drink can enter the nasal cavity. Splitting of the uvula occurs infrequently but is the most common form of mouth and nose area cleavage among newborns. Bifid uvula occurs in about 2% of the general population, although some populations may have a high incidence, such as Native Americans who have a 10% rate.Bifid uvula is a common symptom of the rare genetic syndrome Loeys–Dietz syndrome, which is associated with an increased risk of aortic aneurysm. Function During swallowing, the soft palate and the uvula move together to close off the nasopharynx, and prevent food from entering the nasal cavity. It has also been proposed that the abundant amount of thin saliva produced by the uvula serves to keep the throat well lubricated.It has a function in speech as well. In many languages, a range of consonant sounds, known as uvular consonants, are articulated by creating a constriction of airflow between the uvula and the back of the tongue. The voiced uvular trill, written [ʀ] in the International Phonetic Alphabet, is one example; it is used in French, Arabic and Hebrew, among other languages. Due to the large amount of saliva produced from glands in the uvula that are absent in other mammals, it has been suggested that the uvula is an accessory speech organ.Stimulation of the uvula also causes the gag reflex to initiate. This is often a problem for people with uvula piercings, and a common method of inducing vomiting. Clinical significance Inflammation At times, the mucous membrane around the uvula may swell, causing the uvula to expand 3–5 times its normal size. This condition is known as uvulitis. When the uvula touches the throat or tongue, it can cause sensations like gagging or choking, although there is no foreign matter present. This can cause problems with breathing, talking, and eating. There are many theories about what causes the uvula to swell, including dehydration (e.g. from arid weather); excessive smoking or other inhaled irritants; snoring; allergic reaction; or a viral or bacterial infection. An aphthous ulcer which has formed on the uvula can also cause swelling and discomfort.If the swelling is caused by dehydration, drinking fluids may improve the condition. If the cause is a bacterial infection, gargling salt water may help. However, it can also be a sign of other problems. Some people with a history of recurring uvulitis carry an epinephrine autoinjector to counteract symptoms of an attack. A swollen uvula is not normally life-threatening and subsides in a short time, typically within a day. Snoring and sleep apnea The uvula can also contribute to snoring or heavy breathing during sleep; having an elongated uvula can cause vibrations that lead to snoring. In some cases this can lead to sleep apnea, which may be treated by removal of the uvula or part of it if necessary, an operation known as uvulopalatopharyngoplasty (commonly referred to as UPPP, or UP3). However, this operation can also cause sleep apnea if scar tissue forms and the airspace in the velopharynx is decreased. The success of UPPP as a treatment for sleep apnea is unknown, but some research has shown 40–60% effectiveness in reducing symptoms. Typically apnea subsides for the short term, but returns over the medium to long term, and sometimes is worse than it was before the UPPP. Velopharyngeal insufficiency In a small number of people, the uvula does not close properly against the back of the throat, causing a condition known as velopharyngeal insufficiency. This causes "nasal" (or more properly "hyper-nasal") speech, where extra air comes down the nose, and the speaker is unable to say certain consonants, such as pronouncing b like m. Nasal regurgitation During swallowing, the soft palate and the uvula move superiorly to close off the nasopharynx, preventing food from entering the nasal cavity. When this process fails, the result is called nasal regurgitation. It is common in people with VPI, the myositides, and neuromuscular disease. Regurgitation of fluids in this way may also occur if a particularly high volume of liquid is regurgitated, or during vigorous coughing, for example being caused by the accidental inhalation of water. Due to the action of coughing preventing the uvula from blocking the nasopharynx, liquid may be expelled back through the nose. Society and culture In some parts of Africa, including Ethiopia and Eritrea, the uvula or a section of it is ritually removed by a traditional healer. In this case, the uvula may be noticeably shortened. It is not thought to contribute to velopharyngeal inadequacy, except in cases where the tonsils have also been removed. History Etymology In Latin, ūvula means "little grape", the diminutive form of ūva "grape" (of unknown origin). A swollen uvula was called ūva. See also Uvula (disambiguation) Tonsil Epiglottis References External links MedlinePlus Encyclopedia: 001257 - Uvulitis
Bacillary dysentery	Bacillary dysentery is a type of dysentery, and is a severe form of shigellosis. Bacillary dysentery is associated with species of bacteria from the family Enterobacteriaceae. The term is usually restricted to Shigella infections.Shigellosis is caused by one of several types of Shigella bacteria. Three species are associated with bacillary dysentery: Shigella sonnei, Shigella flexneri and Shigella dysenteriae. A study in China indicated that Shigella flexneri 2a was the most common serotype.Salmonellosis caused by Salmonella enterica (serovar Typhimurium) has also been described as a cause of bacillary dysentery, though this definition is less common. It is sometimes listed as an explicit differential diagnosis of bacillary dysentery, as opposed to a cause.Bacillary dysentery should not be confused with diarrhea caused by other bacterial infections. One characteristic of bacillary dysentery is blood in stool, which is the result of invasion of the mucosa by the pathogen. History The Bacteria causing Shigellosis is named after "Shiga" a Japanese researcher who discovered the bacteria in 1897 Pathogenesis Transmission is fecal-oral and is remarkable for the small number of organisms that may cause disease (10 ingested organisms cause illness in 10% of volunteers, and 500 organisms cause disease in 50% of volunteers). Shigella bacteria invade the intestinal mucosal cells but do not usually go beyond the lamina propria. Dysentery is caused when the bacteria escape the epithelial cell phagolysosome, multiply within the cytoplasm, and destroy host cells. Shiga toxin causes hemorrhagic colitis and hemolytic-uremic syndrome by damaging endothelial cells in the microvasculature of the colon and the glomeruli, respectively. In addition, chronic arthritis secondary to S. flexneri infection, called reactive arthritis, may be caused by a bacterial antigen; the occurrence of this syndrome is strongly linked to HLA-B27 genotype, but the immunologic basis of this reaction is not understood. Diagnosis Specimen: Fresh stool is collected. Culture: Specimen is inoculated on selective media like MacConkeys agar, DCA, XLD agar. Selenite F broth(0.4%) is used as enrichment medium which permits the rapid growth of enteric pathogens while inhibiting the growth of normal flora like E. coli for 6–8 hours. Subculture is done on the solid media from selenite F broth. All the solid media are incubated at 37 degrees for 24 hours. Cultural characteristics: Colorless (NLF) colonies appear on MacConkeys agar which are further confirmed by gram staining, hanging drop preparation and biochemical reactions. Treatment Dysentery is initially managed by maintaining fluid intake using oral rehydration therapy. If this treatment cannot be adequately maintained due to vomiting or the profuseness of diarrhea, hospital admission may be required for intravenous fluid replacement. Ideally, no antimicrobial therapy should be administered until microbiological microscopy and culture studies have established the specific infection involved. When laboratory services are not available, it may be necessary to administer a combination of drugs, including an amoebicidal drug to kill the parasite and an antibiotic to treat any associated bacterial infection. Anyone with bloody diarrhea needs immediate medical help. Treatment often starts with an oral rehydrating solution—water mixed with salt and carbohydrates—to prevent dehydration. (Emergency relief services often distribute inexpensive packets of sugars and mineral salts that can be mixed with clean water and used to restore lifesaving fluids in dehydrated children gravely ill from dysentery.) If Shigella is suspected and it is not too severe, the doctor may recommend letting it run its course—usually less than a week. The patient will be advised to replace fluids lost through diarrhea. If the infection is severe, the doctor may prescribe antibiotics, such as ciprofloxacin or TMP-SMX (Bactrim). Unfortunately, many strains of Shigella are becoming resistant to common antibiotics, and effective medications are often in short supply in developing countries. If necessary, a doctor may have to reserve antibiotics for those at highest risk for death, including young children, people over 50, and anyone suffering from dehydration or malnutrition. No vaccine is available. There are several Shigella vaccine candidates in various stages of development that could reduce the incidence of dysentery in endemic countries, as well as in travelers with travelers diarrhea. References == External links ==
Sadomasochism	Sadomasochism ( SAY-doh-MASS-ə-kiz-əm) is the giving and receiving of pleasure from acts involving the receipt or infliction of pain or humiliation. Practitioners of sadomasochism may seek sexual pleasure from their acts. While the terms sadist and masochist refer respectively to one who enjoys giving and receiving pain, some practitioners of sadomasochism may switch between activity and passivity.The abbreviation S&M is commonly used for Sadomasochism (or Sadism & Masochism), although the initialisms S-M, SM, or S/M are also used, particularly by practitioners. Sadomasochism is not considered a clinical paraphilia unless such practices lead to clinically significant distress or impairment for a diagnosis. Similarly, sexual sadism within the context of mutual consent, generally known under the heading BDSM, is distinguished from non-consensual acts of sexual violence or aggression. Definition and etymology The word sadomasochism is a portmanteau of the words sadism () and masochism. The two words incorporated into this compound, "sadism" and "masochism", were originally derived from the names of two authors. The term "sadism" has its origin in the name of the Marquis de Sade (1740–1814), who not only practised sexual sadism, but also wrote novels about these practices, of which the best known is Justine. "Masochism" is named after Leopold von Sacher-Masoch (1836–1895), who wrote novels expressing his masochistic fantasies. These terms were first selected for identifying human behavioural phenomena and for the classification of psychological illnesses or deviant behaviour. The German psychiatrist Richard von Krafft-Ebing introduced the terms "Sadism" and "Masochism" into medical terminology in his work Neue Forschungen auf dem Gebiet der Psychopathia sexualis ("New research in the area of Psychopathology of Sex") in 1890. In 1905, Sigmund Freud described sadism and masochism in his Drei Abhandlungen zur Sexualtheorie ("Three papers on Sexual Theory") as stemming from aberrant psychological development from early childhood. He also laid the groundwork for the widely accepted medical perspective on the subject in the following decades. This led to the first compound usage of the terminology in Sado-Masochism (Loureiroian "Sado-Masochismus") by the Viennese Psychoanalyst Isidor Isaak Sadger in his work Über den sado-masochistischen Komplex ("Regarding the sadomasochistic complex") in 1913.In the later 20th century, BDSM activists have protested against these ideas, because, they argue, they are based on the philosophies of the two psychiatrists, Freud and Krafft-Ebing, whose theories were built on the assumption of psychopathology and their observations of psychiatric patients. The DSM nomenclature referring to sexual psychopathology has been criticized as lacking scientific veracity, and advocates of sadomasochism have sought to separate themselves from psychiatric theory by the adoption of the term BDSM instead of the common psychological abbreviation, "S&M". However, the term BDSM also includes B&D (bondage and discipline), D/s (dominance and submission), and S&M (sadism and masochism). The terms bondage and discipline usually refer to the use of either physical or psychological restraint or punishment, and sometimes involves sexual role playing, including the use of costumes. In contrast to frameworks seeking to explain sadomasochism through psychological, psychoanalytic, medical, or forensic approaches, which seek to categorize behavior and desires, and find a root cause, Romana Byrne suggests that such practices can be seen as examples of "aesthetic sexuality", in which a founding physiological or psychological impulse is irrelevant. Rather, according to Byrne, sadism and masochism may be practiced through choice and deliberation, driven by certain aesthetic goals tied to style, pleasure, and identity, which in certain circumstances, she claims can be compared with the creation of art. Psychology Historical perspective Sadomasochism, or the use of pain as a sexual stimulant has been practiced since ancient times with some scholars suggesting that it is an integral part of human culture. There are even those who propose that it is already present among nonhuman primate and primitive human communities before emerging in ancient Egyptian, Indian, Oriental, and Arab cultures. One of the oldest surviving narratives that cited its practice was an Egyptian love song, sung by a man expressing a desire to be subjugated by a woman so he could experience pleasure as she treats him like a slave. The Roman historian Juvenal also described a case of a woman who submitted herself to the whipping and beating of the followers of Pan.The modern conceptualization of sadomasochism stemmed from the terms sadism and masochism introduced to the medical field by German psychiatrist Richard von Krafft-Ebing in his 1886 compilation of case studies Psychopathia Sexualis. Pain and physical violence are not essential in Krafft-Ebings conception, and he defined "masochism" (German Masochismus) entirely in terms of control. Sigmund Freud, a psychoanalyst and a contemporary of Krafft-Ebing, noted that both were often found in the same individuals, and combined the two into a single dichotomous entity known as "sadomasochism" (German Sadomasochismus, often abbreviated as S&M or S/M). This observation is commonly verified in both literature and practice; many practitioners, both sadists and masochists, define themselves as switches and "switchable" — capable of taking and deriving pleasure in either role. However, French philosopher Gilles Deleuze argued that the concurrence of sadism and masochism proposed in Freuds model is the result of "careless reasoning," and should not be taken for granted.Freud introduced the terms "primary" and "secondary" masochism. Though this idea has come under a number of interpretations, in a primary masochism the masochist undergoes a complete, rather than partial, rejection by the model or courted object (or sadist), possibly involving the model taking a rival as a preferred mate. This complete rejection is related to the death drive (Todestrieb) in Freuds psychoanalysis. In a secondary masochism, by contrast, the masochist experiences a less serious, more feigned rejection and punishment by the model. Secondary masochism, in other words, is the relatively casual version, more akin to a charade, and most commentators are quick to point out its contrivedness.Rejection is not desired by a primary masochist in quite the same sense as the feigned rejection occurring within a mutually consensual relationship—or even where the masochist happens to be the one having actual initiative power. In Things Hidden Since the Foundation of the World, René Girard attempts to resuscitate and reinterpret Freuds distinction of primary and secondary masochism, in connection with his own philosophy.Both Krafft-Ebing and Freud assumed that sadism in men resulted from the distortion of the aggressive component of the male sexual instinct. Masochism in men, however, was seen as a more significant aberration, contrary to the nature of male sexuality. Freud doubted that masochism in men was ever a primary tendency, and speculated that it may exist only as a transformation of sadism. Sadomasochism in women received comparatively little discussion, as it was believed that it occurred primarily in men. Both also assumed that masochism was so inherent to female sexuality that it would be difficult to distinguish as a separate inclination. Havelock Ellis, in Studies in the Psychology of Sex, argued that there is no clear distinction between the aspects of sadism and masochism, and that they may be regarded as complementary emotional states. He also made the important point that sadomasochism is concerned only with pain in regard to sexual pleasure, and not in regard to cruelty, as Freud had suggested. In other words, the sadomasochist generally desires that the pain be inflicted or received in love, not in abuse, for the pleasure of either one or both participants. This mutual pleasure may even be essential for the satisfaction of those involved. Here, Ellis touches upon the often paradoxical nature of widely reported consensual S&M practices. It is described as not simply pain to initiate pleasure, but violence—"or the simulation of involuntary violent acts"—said to express love. This irony is highly evident in the observation by many, that not only are popularly practiced sadomasochistic activities usually performed at the express request of the masochist, but that it is often the designated masochist who may direct such activities, through subtle emotional cues perceived or mutually understood and consensually recognized by the designated sadistIn his essay Coldness and Cruelty, (originally Présentation de Sacher-Masoch, 1967) Gilles Deleuze rejects the term "sadomasochism" as artificial, especially in the context of the quintessentially modern masochistic work, Sacher-Masochs Venus In Furs. Deleuzes counterargument is that the tendency toward masochism is based on intensified desire brought on or enhanced by the acting out of frustration at the delay of gratification. Taken to its extreme, an intolerably indefinite delay is rewarded by punitive perpetual delay, manifested as unwavering coldness. The masochist derives pleasure from, as Deleuze puts it, the "Contract": the process by which he can control another individual and turn the individual into someone cold and callous. The sadist, in contrast, derives pleasure from the "Law": the unavoidable power that places one person below another. The sadist attempts to destroy the ego in an effort to unify the id and super-ego, in effect gratifying the most base desires the sadist can express while ignoring or completely suppressing the will of the ego, or of the conscience. Thus, Deleuze attempts to argue that masochism and sadism arise from such different impulses that the combination of the two terms is meaningless and misleading. A masochists perception of their own self-subjugating sadistic desires and capacities are treated by Deleuze as reactions to prior experience of sadistic objectification. (For example, in terms of psychology, compulsively defensive appeasement of pathological guilt feelings as opposed to the volition of a strong free will.) The epilogue of Venus In Furs shows the character of Severin has become embittered by his experiment in the alleged control of masochism, and advocates instead the domination of women.Before Deleuze, however, Sartre had presented his own theory of sadism and masochism, at which Deleuzes deconstructive argument, which took away the symmetry of the two roles, was probably directed. Because the pleasure or power in looking at the victim figures prominently in sadism and masochism, Sartre was able to link these phenomena to his famous philosophy of the "Look of the Other". Sartre argued that masochism is an attempt by the "For-itself" (consciousness) to reduce itself to nothing, becoming an object that is drowned out by the "abyss of the Others subjectivity". By this Sartre means that, given that the "For-itself" desires to attain a point of view in which it is both subject and object, one possible strategy is to gather and intensify every feeling and posture in which the self appears as an object to be rejected, tested, and humiliated; and in this way the For-itself strives toward a point of view in which there is only one subjectivity in the relationship, which would be both that of the abuser and the abused. Conversely, Sartre held sadism to be the effort to annihilate the subjectivity of the victim. That means that the sadist is exhilarated by the emotional distress of the victim because they seek a subjectivity that views the victim as both subject and object.This argument may appear stronger if it is understood that this "Look of the Other" theory is either only an aspect of the faculties of desire, or somehow its primary faculty. This does not account for the turn that Deleuze took for his own theory of these matters, but the premise of "desire as Look" is associated with theoretical distinctions always detracted by Deleuze, in what he regarded as its essential error to recognize "desire as lack"—which he identified in the philosophical temperament of Plato, Socrates, and Lacan. For Deleuze, insofar as desire is a lack it is reducible to the "Look".Finally, after Deleuze, René Girard included his account of sadomasochism in Things Hidden Since the Foundation of The World (1978), making the chapter on masochism a coherent part of his theory of mimetic desire. In this view of sadomasochism, the violence of the practices is an expression of a peripheral rivalry that has developed around the actual love-object. There is clearly a similarity to Deleuze, since both in the violence surrounding the memory of mimetic crisis and its avoidance, and in the resistance to affection that is focused on by Deleuze, there is an understanding of the value of the love object in terms of the processes of its valuation, acquisition and the test it imposes on the suitor. Modern psychology There are a number of reasons commonly given for why a sadomasochist finds the practice of S&M enjoyable, and the answer is largely dependent on the individual. For some, taking on a role of compliance or helplessness offers a form of therapeutic escape; from the stresses of life, from responsibility, or from guilt. For others, being under the power of a strong, controlling presence may evoke the feelings of safety and protection associated with childhood. They likewise may derive satisfaction from earning the approval of that figure (see: Servitude (BDSM)). A sadist, on the other hand, may enjoy the feeling of power and authority that comes from playing the dominant role, or receive pleasure vicariously through the suffering of the masochist. It is poorly understood, though, what ultimately connects these emotional experiences to sexual gratification, or how that connection initially forms. Dr. Joseph Merlino, author and psychiatry adviser to the New York Daily News, said in an interview that a sadomasochistic relationship, as long as it is consensual, is not a psychological problem: Its a problem only if it is getting that individual into difficulties, if he or she is not happy with it, or its causing problems in their personal or professional lives. If its not, Im not seeing that as a problem. But assuming that it did, what I would wonder about is what is his or her biology that would cause a tendency toward a problem, and dynamically, what were the experiences this individual had that led him or her toward one of the ends of the spectrum. It is usually agreed on by psychologists that experiences during early sexual development can have a profound effect on the character of sexuality later in life. Sadomasochistic desires, however, seem to form at a variety of ages. Some individuals report having had them before puberty, while others do not discover them until well into adulthood. According to one study, the majority of male sadomasochists (53%) developed their interest before the age of 15, while the majority of females (78%) developed their interest afterwards (Breslow, Evans, and Langley 1985). The prevalence of sadomasochism within the general population is unknown. Despite female sadists being less visible than males, some surveys have resulted in comparable amounts of sadistic fantasies between females and males. The results of such studies indicate that ones sex may not be the determining factor for a preference towards sadism. Medical and forensic classification Medical categorization BDSM Medical opinion of sadomasochistic activities has changed over time. The classification of sadism and masochism in the Diagnostic and Statistical Manual of Mental Disorders (DSM) has always been separate; sadism was included in the DSM-I in 1952, while masochism was added in the DSM-II in 1968. Contemporary psychology continues to identify sadism and masochism separately, and categorizes them as either practised as a life style, or as a medical condition.The current version of the American Psychiatric Associations manual, DSM-5, excludes consensual BDSM from diagnosis as a disorder when the sexual interests cause no harm or distress. Sexual sadism disorder however, listed within the DSM-5, is where arousal patterns involving consenting and non‐consenting others are not distinguished ICD On 18 June 2018, the WHO (World Health Organization) published ICD-11, and Sadomasochism, together with Fetishism and Transvestic Fetishism, are now removed as psychiatric diagnoses. Moreover, discrimination of fetish- and BDSM individuals is considered inconsistent with human rights principles endorsed by the United Nations and The World Health Organization.The classifications of sexual disorders reflect contemporary sexual norms and have moved from a model of pathologization or criminalization of non-reproductive sexual behaviors to a model which reflects sexual well-being and pathologizes the absence or limitation of consent in sexual relations.The ICD-11 classification, contrary to ICD-10 and DSM-5, clearly distinguishes consensual sadomasochistic behaviours (BDSM) that do not involve inherent harm to self or others, from harmful violence on non‐consenting persons (Coercive sexual sadism disorder).In this regard, "ICD-11 go further than the changes made for DSM-5 … in the removal of disorders diagnosed based on consenting behaviors that are not in and of themselves associated with distress or functional impairment."In Europe, an organization called ReviseF65 has worked to remove sadomasochism from the ICD. On commission from the WHO ICD-11 Working Group on Sexual Disorders and Sexual Health, ReviseF65 in 2009 and 2011 delivered reports documenting that sadomasochism and sexual violence are two different phenomena. The report concluded that the Sadomasochism diagnosis were outdated, non scientific, and stigmatizing. In 1995, Denmark became the first European Union country to have completely removed sadomasochism from its national classification of diseases. This was followed by Sweden in 2009, Norway in 2010, Finland in 2011 and Iceland in 2015."Based on advances in research and clinical practice, and major shifts in social attitudes and in relevant policies, laws, and human rights standards", the World Health Organization (18 June 2018) removed Fetishism, Transvestic Fetishism and Sadomasochism as psychiatric diagnoses.The ICD-11 classification consider Sadomasochism as a variant in sexual arousal and private behavior without appreciable public health impact and for which treatment is neither indicated nor sought."Further the ICD-11 guidelines "respect the rights of individuals whose atypical sexual behavior is consensual and not harmful."WHOs ICD-11 Working Group admits that psychiatric diagnoses have been used to harass, silence, or imprison sadomasochists. Labeling them as such may create harm, convey social judgment, and exacerbate existing stigma and violence to individuals so labeled.According to ICD-11, psychiatric diagnoses can no longer be used to discriminate against BDSM people and fetishists.Recent surveys on the spread of BDSM fantasies and practices show strong variations in the range of their results. Nonetheless, researchers assume that 5 to 25 percent of the population practices sexual behavior related to pain or dominance and submission. The population with related fantasies is believed to be even larger. Forensic classification According to Anil Aggrawal, in forensic science, levels of sexual sadism and masochism are classified as follows: Sexual masochists: Class I: Bothered by, but not seeking out, fantasies. May be preponderantly sadists with minimal masochistic tendencies or non-sadomasochistic with minimal masochistic tendencies Class II: Equal mix of sadistic and masochistic tendencies. Like to receive pain but also like to be dominant partner (in this case, sadists). Sexual orgasm is achieved without pain or humiliation. Class III: Masochists with minimal to no sadistic tendencies. Preference for pain or humiliation (which facilitates orgasm), but not necessary to orgasm. Capable of romantic attachment. Class IV: Exclusive masochists (i.e. cannot form typical romantic relationships, cannot achieve orgasm without pain or humiliation).Sexual sadists: Class I: Bothered by sexual fantasies but do not act on them. Class II: Act on sadistic urges with consenting sexual partners (masochists or otherwise). Categorization as leptosadism is outdated. Class III: Act on sadistic urges with non-consenting victims, but do not seriously injure or kill. May coincide with sadistic rapists. Class IV: Only act with non-consenting victims and will seriously injure or kill them.The difference between I–II and III–IV is consent. BDSM The term BDSM is commonly used to describe consensual activities that contain sadistic and masochistic elements. Masochists tend to be very specific about the types of pain they enjoy, preferring some and disliking others. Many behaviors such as spanking, tickling, and love-bites contain elements of sadomasochism. Even if both parties legally consent to such acts this may not be accepted as a defense against criminal charges. Very few jurisdictions will permit consent as a legitimate defense if serious bodily injuries are caused. It has been argued that in many countries, the law disregards the sexual nature of sadomasochism - or the fact that participants enter these relationships voluntarily because they enjoy the experience. Instead, the criminal justice system focuses on what it views as dangerous or violent behavior. What this essentially means is that instead of attempting to understand and accommodate for voluntary sadomasochism, the law typically views these incidences as cases of assault. This can be seen with the well-known case in Great Britain, where 15 men were trialed for a range of offences relating to sadomasochism. Samois, the earliest known lesbian S/M organization in the United States, was founded in San Francisco in 1978.Harsh acts of S&M may include consensual torture of the sensitive parts of body, such as cock and ball torture for males, and breast torture and pussy torture for females. Acts common for both genders may include ass torture (ex. using speculum), face torture (ex. nose torture), etc. In extreme cases, sadism and masochism can include fantasies, sexual urges or behavior which cause observably significant distress or impairment in social, occupational, or other important areas of functioning, to the point that they can be considered part of a mental disorder. However, this is widely considered to be rare, as psychiatrists now regard such behaviors as clinically aberrant only if they are identifiable as symptoms or associated with other problems such as personality disorder or neurosis. There is some controversy in the psychology professions regarding a personality disorder referred to alternately as "self-defeating personality disorder" or "masochistic personality disorder", where masochistic behavior may not be in relation to other diagnosed mental disease. Ernulf and Innala (1995) observed discussions among individuals with such interests, one of whom described the goal of hyperdominance.The Fifty Shades trilogy is a series of very popular erotic romance novels by E. L. James which involve S/M. These have been criticized for their inaccurate and harmful depiction of S/M. Their film adaptations have been similarly criticized. Other A table in Larry Townsends The Leathermans Handbook II (the 1983 second edition; the 1972 first edition did not include this list) which is generally considered authoritative states that a black handkerchief is a symbol for sadomasochism in the handkerchief code, which is employed usually among gay male casual-sex seekers or BDSM practitioners in the United States, Canada, Australia and Europe. Wearing the handkerchief on the left indicates the top, dominant, or active partner; right the bottom, submissive, or passive partner. However, negotiation with a prospective partner remains important because, as Townsend noted, people may wear hankies of any color "only because the idea of the hankie turns them on" or "may not even know what it means". In popular culture In Bollywood film Housefull, BDSM is displayed between Akshay Kumar and Jiah Khan during the song "I Dont Know What To Do". See also References Footnotes Bibliography
Hypnic headache	Hypnic headaches are benign primary headaches that affect the elderly, with an average age of onset at 63 ± 11 years. They are moderate, throbbing, bilateral or unilateral headaches that wake the sufferer from sleep once or multiple times a night. They typically begin a few hours after sleep begins and can last from 15–180 min. There is normally no nausea, photophobia, phonophobia or autonomic symptoms associated with the headache. They commonly occur at the same time every night possibly linking the headaches with circadian rhythm, but polysomnography has recently revealed that the onset of hypnic headaches may be associated with REM sleep. Diagnosis For diagnosis of hypnic headache syndrome, headaches should occur at least 15 times per month for at least one month. Included in the differential diagnosis of a new onset nighttime headaches in the elderly is drug withdrawal, temporal arteritis, Sleep apnea, oxygen desaturation, Pheochromocytoma, intracranial causes, primary and secondary neoplasms, communicating hydrocephalus, subdural hematoma, vascular lesions, migraines, cluster headaches, chronic paroxysmal hemicrania, headaches due to bruxism, and hypnic headache. All other causes must be ruled out before the diagnosis of hypnic headache can be made. Treatments Lithium carbonate 200–600 mg at bedtime is an effective treatment for most patients but for those that can not tolerate Lithium, Verapamil, indomethacin, melatonin or methysergide may be tried. Two patients have also responded to flunarizine 5 mg. It has also been shown that 1–2 cups of coffee or 100–200 mg of caffeine before bed can prevent hypnic headaches. A recent review of 348 cases available in the literature has been recently published. References == External links ==
Prolapse	In medicine, prolapse is a condition in which organs fall down or slip out of place. It is used for organs protruding through the vagina, rectum, or for the misalignment of the valves of the heart. A spinal disc herniation is also sometimes called "disc prolapse". Prolapse means "to fall out of place", from the Latin prolabi meaning "to fall out". Relating to the uterus, prolapse condition results in an inferior extension of the organ into the vagina, caused by weakened pelvic muscles. Humans Heart valve prolapse The main type of prolapse of heart valves in humans is mitral valve prolapse (MVP), which is a valvular heart disease characterized by the displacement of an abnormally thickened mitral valve leaflet into the left atrium during systole. Tricuspid valve prolapse can cause tricuspid regurgitation. Rectal prolapse Rectal prolapse is a condition in which part of the wall or the entire wall of the rectum falls out of place. Rectal prolapse can be a medical emergency. In some cases, the rectum may protrude. Symptoms of a rectal prolapse may be: Leakage of stool Bleeding, anal pain, itching, irritation Tissue that protrudes from the rectumA surgeon may operate through the abdomen to secure part of the large intestine or rectum to the inside of the abdominal cavity (rectopexy). Sometimes the surgeon removes the affected part of the intestine. Surgery also can be done through the perineum (the area between the genitals and the anus) to remove the prolapsing tissue. Surgery is most often successful for people who still have some control over their bowel movements. If the anal sphincter is damaged, surgery may correct the prolapse but not be able to completely correct fecal incontinence (lack of control of bowel movements). Fecal incontinence can both potentially improve or deteriorate after prolapse surgery. If the lining has fallen out of the anus and is around 7 cm or less, it should eventually retract back inside naturally, though the retraction can take up to four days. Female genital prolapse Uterine prolapse (or Pelvic organ prolapse) occurs when the female pelvic organs fall from their normal position, into or through the vagina. Occurring in women of all ages, it is more common as women age, particularly in those who have delivered large babies or had exceedingly long pushing phases of labor. Smoking, obesity, connective tissue disorders, upper respiratory disorders‚ and repetitive strain injuries can all increase prolapse risk. Minor prolapse can be treated with exercises to strengthen the pelvic floor muscles (pelvic physiotherapy); more serious prolapse, e.g., complete procidentia, requires pessary use or reconstructive surgical treatment. Reconstructive pelvic prolapse surgery may be done without resorting to complete hysterectomy by hysteropexy, the resuspension of the prolapsed uterus. Traditional gynecologic practice favors removal of the uterus or ovaries (or both) at the time of prolapse surgery, and one estimate states that of the 600,000 hysterectomies performed in the United States every year, 13 percent are for prolapse. However, there is concern that many of these hysterectomies may be unnecessary and that hysteropexy would suffice as a treatment instead. Pelvic floor prolapse The rectum or urinary bladder may prolapse as a result of changes in the integrity of connective tissue in the posterior or anterior vaginal walls, respectively, resulting in pelvic floor prolapse. Symptoms may include a feeling of pressure in the pelvis, or the visible protrusion of organs from the vagina. Prolapse is almost never painful, but the change in position of organs may cause urinary or bowel symptoms. Pessaries are a treatment option for pelvic organ prolapse. Umbilical cord prolapse Umbilical cord prolapse occurs when the umbilical cord comes out of the uterus with or before the presenting part of the fetus. It is a relatively rare condition and occurs in fewer than 1% of pregnancies. Cord prolapse is more common in women who have had rupture of their amniotic sac. Other risk factors include maternal or fetal factors that prevent the fetus from occupying a normal position in the maternal pelvis, such as abnormal fetal lie, too much amniotic fluid, or a premature or small fetus. The concern with cord prolapse is that pressure on the cord from the fetus will cause cord compression that compromises blood flow to the fetus. Whenever there is a sudden decrease in fetal heart rate or abnormal fetal heart tracing, umbilical cord prolapse should be considered. Due to the possibility for fetal death and other complications, umbilical cord prolapse is considered an obstetric emergency during pregnancy or labor. Current management guidelines focus on quick delivery, which usually entails a cesarean section. With appropriate management, the majority of cases have good neonatal outcomes. Other species Reptiles Genital prolapse has been reported in snakes and turtles. Birds Oviduct prolapse is an often fatal condition in birds. When an egg is laid, the vagina everts through the cloaca to deliver the egg. Large eggs and avian obesity are contributors to this condition. Immediate veterinary assistance is paramount to the survival of a bird with prolapse. Even with immediate medical intervention the chances for survival are usually uncertain. Untreated birds will begin to tear at the injury site, and other flockmates will begin to cannibalize the prolapse area, a behaviour commonly known as pickout. Cattle Prolapsed uterus in cattle, particularly dairy cattle, generally occurs in the first 12 hours post-calving. Frequent causes are hypocalcemia combined with irritation of the birth canal, causing straining. Replacement of the protrusion, which can range from the size of a softball to the hanging of the entire uterus down below the hocks, is performed with the cow in sternal recumbency, an epidural injection, and hindlimbs frogged rearwards to allow the pelvis to tip forward, easing replacement. Careful washing and cleaning prior to replacement is important as is ensuring that the horns are completely everted once inside the cow. Often a Buhner suture is placed in the vulva to prevent subsequent reprolapse. Another type of reproductive prolapse in cattle is so-called bovine vaginal prolapse. Sheep Same as in cows. Pigs Rectal prolapse is a condition routinely identified in pigs on farms and at slaughterhouses. If not reduced quickly, prolapses in pigs become necrotic and infected, and risk being cannibalized by other pen mates. If the latter happens it normally results in death of the animal by sepsis, shock or faecal peritonitis. Horses and mules Rectal prolapse occurring in horse and mule would be better termed anal prolapse, as it only involves mucous membrane moving posteriorly to form a circular protrusion outside the anus The condition is not painful. In mares after parturition, it is described as a 10 to 60 mm mucous protrusion.In young mules and foals, anal prolapse occurs with a frequency similar to that of Gasterophilus haemorrhoidalis. In extensive breeding conditions, the disease is only recognized after some days, leading to intense edema of prolapsed tissues and necrosis of the mucous membrane. Early cases in should be treated with the application of hygroscopic substances like powdered sugar followed by purse-string suturing. When prolapsed tissues are edematous and necrotic, amputation is performed. The prognosis is fair as the removed tissues do not contain any important organs or large blood vessels. References External links Media related to Pelvic prolapses at Wikimedia Commons
Perianal cellulitis	Perianal cellulitis, also known as perianitis or perianal streptococcal dermatitis, is a bacterial infection affecting the lower layers of the skin (cellulitis) around the anus. It presents as bright redness in the skin and can be accompanied by pain, difficulty defecating, itching, and bleeding. This disease is considered a complicated skin and soft tissue infection (cSSTI) because of the involvement of the deeper soft tissues.Perianal cellulitis is most commonly caused by group A beta-hemolytic streptococcus bacteria (Streptococcus pyogenes), which resides normally ("in small numbers") in the human throat and on the human skin. Other less common causes may include infection with group B beta-hemolytic streptococci (Streptococcus agalactiae), a bacteria found in the human vagina of some, or Staphylococcus aureus, a common component of the bacterial community in the human nose and/or skin.Perianal cellulitis occurs mainly in male children between six months and 10 years of age, however, there are documented cases of perianal cellulitis in adults as well. Oral antibiotics are the first line treatment for perianal cellulitis and may be used in combination with topical antibiotics. Since the infection occurs within the deeper layers of skin, using a topical treatment by itself may not be effective. In about 20% of cases, recurrence of perianal streptococcal dermatitis infection occurs within 3.5 months. Routine hygiene practices should also be encouraged in children and adults in order to reduce the risk of recurrent infection. Signs and symptoms Perianal cellulitis manifests as multiple symptoms that are inconsistent with a systemic disease. The most notable feature is a very distinct redness around the anus, and other signs of inflammation which can include swelling and itching at the site. Other associated symptoms with perianal cellulitis include pain when defecating and bleeding. These symptoms can often be confused with other skin conditions, such as diaper rash, eczema, psoriasis, hemorrhoids, and more. These symptoms can cause extreme discomfort, especially in diaper-wearing infants, and serious complications can arise if left untreated. In about 10% of cases, balanitis or vulvovaginitis can develop concomitantly. In even rarer instances, tonsillopharyngitis can develop concomitantly as well.Complications most often occur when perianal cellulitis remains undiagnosed and untreated for an extended period of time. In cases where perianal cellulitis is left untreated, it can cause more serious symptoms such as abscess formation and rheumatic fever. Additionally, untreated perianal cellulitis poses a risk of transmission to other people, such as caretakers or family members. Perianal cellulitis can also cause post-streptococcal nephritis, which should be monitored with urinalysis to assess kidney function. Diagnosis The diagnosis of perianal cellulitis is made either through a rapid strep test or by swabbing the affected areas for a bacterial culture indicating infection by group A β-hemolytic streptococci. In order to confirm diagnosis of perianal streptococcal dermatitis, the anus and genitalia require examination followed by bacterial swabbing of the exudate from the affected area is preferred. The swabs will be sent for microbiological analysis of the culture to confirm the growth of group A β-hemolytic streptococci. "The time to diagnosis of perianal streptococcal dermatitis is ≥3 weeks in 65% of cases." Because perianal cellulitis is commonly misdiagnosed, it is imperative that the proper diagnosing procedures are followed when encountering these symptoms, as delayed detection can result in severe complications.Within the pediatric population, it is common for the management of rashes to occur under the collaboration of an inter-professional team. Due to the diverse causes of rashes in the pediatric population, it may be necessary to refer pediatric patients to a pediatrician or a dermatologist to prevent misdiagnosis of perianal streptococcal dermatitis. Across the different disciplines of care, nurses have an opportunity to provide education on proper hygiene techniques to reduce the risk of recurrent infection. Pharmacists can provide patient and caretaker counseling on the selected medication therapy and improve medication adherence. By working together as an inter-professional team, all types of clinicians can improve patient health outcomes by raising awareness and reducing both time to diagnosis and the rate of recurrence of perianal streptococcal dermatitis infection. Differential diagnosis Due to the non-specific presentation of the symptoms of perianal streptococcal dermatitis, it is frequently misdiagnosed by clinicians. To reach the correct diagnosis of perianal streptococcal dermatitis often ranges from weeks to months and can extend to even longer. During this time, the patient can undergo treatment for a variety of differential diagnoses. Perianal streptococcal dermatitis imitates other common diseases in the anal region and therefore can be mistaken for "candidiasis, irritant diaper dermatitis, pinworm infestation, chronic inflammatory bowel disease, seborrheic dermatitis, or even sexual abuse." The delay in diagnosis of perianal streptococcal dermatitis can result in prolonged discomfort and additional symptoms of constipation, anal discharge or oozing, and anal fissures. Pathophysiology Causes In most cases of perianal streptococcal dermatitis in children, swab cultures indicate that infection is caused by the bacteria Streptococcus pyogenes, more specifically classified as group A beta-hemolytic streptococci (GAS). There have been reported cases, however, that have found perianal streptococcal cellulitis infections to be caused by group B beta-hemolytic streptococci (GBS) and, in rare cases, other groups of beta-hemolytic streptococci or Staphylococcus aureus. It is important to note, however, that in the rare adult cases of perianal streptococcal cellulitis that have been identified, the most common cause is by beta-hemolytic streptococci from group B specified as Streptococcus agalactiae. Streptococci are gram-positive bacteria that grow in chains, but they have no motility and do not generate spores. Group A streptococci and Group B streptococci are the two most common strains that are associated with pediatric cases. Infections caused by Group A streptococci are generally more mild than infections caused by Group B streptococci. The most common Group A streptococcus infections can range from strep throat to pneumonia to cellulitis. Group B streptococcus is more commonly found in the gastrointestinal and genital tracts, and can also be transmitted vertically from mother to child during vaginal labor. These newborn cases of infection often manifest as sepsis, pneumonia, and meningitis, among other presentations.Based on cases studied of children with perianal streptococcal dermatitis, there has been a pattern of perianal infection occurring after being diagnosed with previous streptococcal infections (i.e. "strep throat"). It is believed that bacteria from these infections may be introduced to the skin of the perianal region after touching the nose or mouth and then proceeding to use the toilet or touching the area for any other reason.While perianal streptococcal dermatitis is a treatable condition, there are serious consequences that may arise if left undiagnosed and/or untreated in patients with an infection. Failure to properly diagnose and treat perianal streptococcal dermatitis may lead to more serious infections that could result in injury or death. Mechanism Upon the initial exposure of Streptococcus pyogenes (group A beta-hemolytic streptocci) bacteria to the skin surrounding the perianal region, the bacteria adheres to the skins surface with filaments on its cell wall surface called adhesins. An adhesin found in group A beta-hemolytic streptococci of particular importance is called the M protein, which utilizes complex mechanisms to recognize various receptors on human cell types for attachment. After attachment, colonization of Streptococcus pyogenes occurs and the bacteria release many toxins that are responsible for the manifestation of symptoms of perianal cellulitis such as inflammation, fever, and itching. Secretion of hyaluronidase, also known as "spreading factor", encourages the Streptococcus pyogenes bacterium to spread more easily throughout the lower layers of skin tissue (subcutaneous tissue). As the streptococci continue to colonize, the formation of a biofilm may arise and its protective properties may make it more difficult to treat the infection with antibiotics.In cases of perianal cellulitis infections that are not treated properly, group A beta-hemolytic streptococci may cross into the bloodstream through the epithelium of the perianal area to cause serious infections such as necrotizing fasciitis or toxic shock syndrome. The group A beta-hemolytic streptococci bacteria that enter the bloodstream are able to cause serious infections by overpowering natural immune responses and allowing bacteria to rapidly multiply to cause harm to the body. Treatment After the diagnosis of perianal streptococcal dermatitis has been confirmed, the most successful treatment regimens utilize a combination of topical and systemic antibiotics. Oral antibiotics are the recommended first-line treatment for perianal streptococcal dermatitis. Perianal streptococcal dermatitis does not resolve on its own. The treatment of choice for oral antibiotics include "penicillin V, azithromycin, clarithromycin, clindamycin, erythromycin, penicillinase-resistant penicillin, or cephalosporins." Oral antibiotics work best in combination with a topical antibiotic such as mupirocin, or an antiseptic such as chlorhexidine. Due to the affect that perianal streptococcal dermatitis has on the deeper layers of the skin, topical antimicrobial therapy alone appears to be poorly effective. Treatment duration ranges from 14 to 21 days and treatment success is determined by clinical examination and post-treatment swabbing of the affected area to confirm that the infection is no longer present. Prevention & Recurrence There is little data that currently exists on the prevention of perianal cellulitis. However, "approximately one-third of people with cellulitis suffer recurrent episodes and the only proven strategy for preventing this is long-term, low-dose oral penicillin." Performing post-treatment swabbing and confirming eradication of group A β-hemolytic streptococci infection reduces the chance of perianal streptococcal dermatitis recurrence. In about 20% of cases, recurrence of perianal streptococcal dermatitis infection occurs within 3.5 months. In the case of perianal cellulitis, maintaining the dryness of the site and addressing the infection with topical antifungal ointment is sufficient to prevent recurrent infection for a duration between 3 and 6 weeks. Potential risk factors for perianal streptococcal dermatitis include: poor living conditions, atopic dermatitis, and malnutrition. Routine hygiene practices should also be encouraged in children and adults in order to reduce the risk of recurrent infection. Prescribed antibiotic regimens should also be adhered to until completion, so as to avoid the risk of developing a multi-resistant strain of infection in the future.Proper screening measures should be followed as perianal cellulitis continues to be severely underdiagnosed. Perianal cellulitis is often misdiagnosed as other skin conditions, such as diaper rash (in infants), eczema, psoriasis, hemorrhoids, and more. Epidemiology The incidence of perianal streptococcal dermatitis in the pediatric population has not been determined. It is believed that the lack of data is due to the difficulty clinicians face recognizing perianal streptococcal dermatitis. Perianal streptococcal dermatitis most commonly affects children between 6 months and 10 years old, with males being more commonly affected than females. Results from a systematic literature review further supports this as a majority of childhood cases of perianal streptococcal cellulitis occurred in males younger than 7 years old.While traditionally thought to be a disease specific to children, there have been case reports of perianal streptococcal dermatitis in adults. Etymology The term perianal is made up of two components, peri- (Greek prefix meaning "about" or "around") and anal ("related to, or involving the anus"). Cellulitis describes a bacterial infection affecting the lower layers of the skin.Historically, perianal cellulitis may be referred to as perianal streptococcal dermatitis. However, perianal cellulitis is best understood to be a cellulitis, an infection of the inner layers of skin, rather than a dermatitis, which implies an irritation of the outermost layers of skin (the epidermis). See also List of cutaneous conditions CDC List of Group A Streptococcal Diseases References == External links ==
Ectopic ureter	Ectopic ureter (or ureteral ectopia) is a medical condition where the ureter, rather than terminating at the urinary bladder, terminates at a different site. In males this site is usually the urethra, in females this is usually the urethra or vagina. It can be associated with renal dysplasia, frequent urinary tract infections, and urinary incontinence (usually continuous drip incontinence). Ectopic ureters are found in 1 of every 2000–4000 patients, and can be difficult to diagnose, but are most often seen on CT scans.Ectopic ureter is commonly a result of a duplicated renal collecting system, a duplex kidney with 2 ureters. In this case, usually one ureter drains correctly to the bladder, with the duplicated ureter presenting as ectopic.The embryology that explains the pathology of an ectopic ureter is a cephalad origin of the ureteral bud on the mesonephric duct. With an abnormally long common excretory duct, the ureter never becomes incorporated into the bladder, and, therefore, remains ectopic. In the female, the most common locations of an ectopic ureter are the bladder neck, urethra, or Gartners duct which lies between the urethra and the anterior vaginal wall. See also Ectopia (disambiguation) References == External links ==
Glycogen storage disease type III	Glycogen storage disease type III (GSD III) is an autosomal recessive metabolic disorder and inborn error of metabolism (specifically of carbohydrates) characterized by a deficiency in glycogen debranching enzymes. It is also known as Coris disease in honor of the 1947 Nobel laureates Carl Cori and Gerty Cori. Other names include Forbes disease in honor of clinician Gilbert Burnett Forbes (1915–2003), an American physician who further described the features of the disorder, or limit dextrinosis, due to the limit dextrin-like structures in cytosol. Limit dextrin is the remaining polymer produced after hydrolysis of glycogen. Without glycogen debranching enzymes to further convert these branched glycogen polymers to glucose, limit dextrinosis abnormally accumulates in the cytoplasm.Glycogen is a molecule the body uses to store carbohydrate energy. Symptoms of GSD-III are caused by a deficiency of the enzyme amylo-1,6 glucosidase, or debrancher enzyme. This causes excess amounts of an abnormal glycogen to be deposited in the liver, muscles and, in some cases, the heart. Signs and symptoms Glycogen storage disease type III presents during infancy with hypoglycemia and failure to thrive. Clinical examination usually reveals hepatomegaly. Muscular disease, including hypotonia and cardiomyopathy, usually occurs later. The liver pathology typically regresses as the individual enter adolescence, as does splenomegaly, should the individual so develop it. Genetics In regards to genetics glycogen storage disease type III is inherited in an autosomal recessive pattern (which means both parents need be a carrier), and occurs in about 1 of every 100,000 live births. The highest incidence of glycogen storage disease type III is in the Faroe Islands where it occurs in 1 out of every 3,600 births, probably due to a founder effect. There seem to be two mutations in exon 3 (c.17_18delAG) being one of them, which are linked to the subtype IIIb.The amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase gene and mutations to it, are at the root of this condition. The gene is responsible for creating glycogen debranching enzyme, which in turn helps in glycogen decomposition. Diagnosis In terms of the diagnosis for glycogen storage disease type III, the following tests/exams are carried out to determine if the individual has the condition: Biopsy (muscle or liver) CBC Ultrasound DNA mutation analysis (helps ascertain GSD III subtype) Differential diagnosis The differential diagnosis of glycogen storage disease type III includes GSD I, GSD IX and GSD VI. This however does not mean other glycogen storage diseases should not be distinguished as well. Classification Clinical manifestations of glycogen storage disease type III are divided into four classes: GSD IIIa, is the most common, (along with GSD IIIb) and which clinically includes muscle and liver involvement GSD IIIb, which clinically has liver involvement but no muscle involvement GSD IIIc which clinically affects liver and muscle. GSD IV affects liver only (not muscle) Treatment Treatment for glycogen storage disease type III may involve a high-protein diet, in order to facilitate gluconeogenesis. Additionally the individual may need: IV glucose (if oral route is inadvisable) Nutritional specialist Vitamin D (for osteoporosis/secondary complication) Hepatic transplant (if complication occurs) References Further reading Mayorandan, Sebene; Meyer, Uta; Hartmann, Hans; Das, Anibh Martin (1 January 2014). "Glycogen storage disease type III: modified Atkins diet improves myopathy". Orphanet Journal of Rare Diseases. 9: 196. doi:10.1186/s13023-014-0196-3. ISSN 1750-1172. PMC 4302571. PMID 25431232. Sentner, Christiaan P.; Hoogeveen, Irene J.; Weinstein, David A.; Santer, René; Murphy, Elaine; McKiernan, Patrick J.; Steuerwald, Ulrike; Beauchamp, Nicholas J.; Taybert, Joanna; Laforêt, Pascal; Petit, François M.; Hubert, Aurélie; Labrune, Philippe; Smit, G. Peter A.; Derks, Terry G. J. (22 April 2016). "Glycogen storage disease type III: diagnosis, genotype, management, clinical course and outcome". Journal of Inherited Metabolic Disease. 39 (5): 697–704. doi:10.1007/s10545-016-9932-2. ISSN 0141-8955. PMC 4987401. PMID 27106217. External links Media related to Glycogen storage disease type III at Wikimedia Commons
Cavernous hemangioma	Cavernous hemangioma, also called cavernous angioma, venous malformation, or cavernoma, is a type of venous malformation due to endothelial dysmorphogenesis from a lesion which is present at birth. A cavernoma in the brain is called a cerebral cavernous malformation or CCM. Despite its designation of a hemangioma, a cavernous hemangioma is not a tumor as it does not display endothelial hyperplasia. The abnormal tissue causes a slowing of blood flow through the cavities, or "caverns". The blood vessels do not form the necessary junctions with surrounding cells, and the structural support from the smooth muscle is hindered, causing leakage into the surrounding tissue. It is the leakage of blood, referred to as hemorrhage, that causes a variety of symptoms known to be associated with the condition. Symptoms People with this condition in the brain may or may not experience symptoms. Some complications of the condition are life-threatening or cause major disruptions to normal functioning. Dangerous seizures due to compression of the brain, bleeding inside the brain tissue, vision problems, difficulty with speaking or using words, memory loss, ataxia, or hydrocephalus can occur. Less serious symptoms may include headaches and weakness or numbness in the arms or legs, though these symptoms alone do not indicate a person has the condition. In the eye, it may cause disruption or damage to the extraocular muscles and optic nerve which may manifest as double vision, progressive proptosis, decreased visual acuity, or other vision changes. It can lead to partial or complete blindness. When the condition occurs in the liver it usually does not cause symptoms, but some may experience pain in the upper right abdomen, a feeling of fullness after eating only a small amount of food, decreased appetite, nausea, or vomiting. Presentation Cavernous hemangiomas can arise nearly anywhere in the body where there are blood vessels. They are sometimes described as resembling raspberries because of the appearance of bubble-like caverns. Unlike capillary hemangiomas, cavernous ones can be life-threatening and do not regress. Causes Most cases of cavernomas are thought to be congenital; however they can develop over the course of a lifetime. While there is no definitive cause, research suggests that genetic mutations result in the condition. Congenital hemangiomas that appear on the skin are known as either vascular or red birthmarks. Familial cerebral cavernous malformations are known to occur. The mutations may be inherited in an autosomal dominant fashion or occur sporadically. Overall, familial disease is thought to be responsible for one-third to one-half of cases. In the US, approximately 50% of Hispanic patients with cerebral cavernous malformations have a familial form. In contrast, the familiar form of the condition accounts for only 10 to 20% of cases in Caucasians. The reason for this difference is not presently known. Several genes – K-Rev interaction trapped 1 (ССМ1), Malcavernin (CCM2) and Programmed cell death protein 10 (ССМ3) – have been identified as having mutations thought to be related to these lesions. These genes are located at 7q21.2 (chromosome 7 long arm), 7p13 (chromosome 7 short arm) and 3q25.2-q27 (chromosome 3 long arm) respectively. These lesions are further discussed in the Online Mendelian Inheritance in Man site – the reference numbers are OMIM 116860, OMIM 603284 and OMIM 603285 respectively. Variations Cerebral cavernomas Cavernous hemangiomas located in the brain or spinal cord are referred to as cerebral cavernomas or more usually as cerebral cavernous malformations (CCMs), and can be found in the white matter, but often abut the cerebral cortex. When they contact the cortex, they can represent a potential seizure focus for the patient. Unlike other cavernous hemangiomas, there is no tissue within the malformation and its borders are not encapsulated. Therefore, they can change in size and number over time. Liver cavernous hemangioma Cavernous hemangiomas are erroneously called the most common benign tumors of the liver. Usually one malformation exists, but multiple lesions can occur in the left or right lobe of the liver in 40% of patients. Their sizes can range from a few millimeters to 20 centimetres. Those over 5 cm are often referred to as giant hemangiomas. These lesions are better classified as venous malformations. Eye cavernous hemangioma In the eye, it is known as orbital cavernous hemangioma and is found in women more frequently than men, most commonly between the ages of 20–40. This neoplasm is usually located within the muscle cone, which is lateral to the optic nerve. It is not usually treated unless the patient is symptomatic. Visual impairment happens when the optic nerve is compressed or the extraocular muscles are surrounded. Mechanism There are several known causes for cavernous hemangiomas, but some cases are still unknown. Radiation treatment used for other medical conditions has been suggested to cause cavernous malformation in some patients. Hemangioma tumors are a result of rapid proliferation of endothelial cells and pericytic hyperplasia, or the enlargement of tissue as a result of abnormal cell division pericytes. The pathogenesis of hemangioma is still not understood. It has been suggested that growth factors and hormonal influences contribute to the abnormal cell proliferation. Cavernous liver hemangiomas are more commonly diagnosed in women who have been pregnant. As a result of this, it is believed that estrogen levels may play a role in the incidence of liver cavernomas. Genetic studies show that specific gene mutations or deletions are causes for the disease. The genes identified for cerebral cavernous hemangiomas (or malformations), are CCM1 (also KRIT1), CCM2 (also MGC4607, malcavernin) and CCM3 (also PDCD10). The loss of function of these genes is believed to be responsible for cerebral cavernous malformations. Furthermore, it is also believed that a "second hit mutation" is necessary for the onset of the disease. This means that having a mutation in one of the two genes present on a chromosome is not enough to cause the cavernous malformation, but mutation of both alleles would cause the malformation. Additionally, research on hemangiomas in general has shown that loss of heterozygosity is common in tissue where hemangioma develops. This would confirm that more than a single allele mutation is needed for the abnormal cell proliferation. KRIT1 has been shown to act as a transcription factor in the development of arterial blood vessels in mice. CCM2 has overlapping structure with CCM1 (KRIT1) and acts as a scaffolding protein when expressed. Both genes are involved with MAP3K3 and thus appear to be a part of the same pathway. CCM2 has been shown to cause embryonic death in mice. Lastly, the CCM3 gene has been shown to have similar expression to CCM1 and CCM2, suggesting a link in its functionality. Currently, no experiments have determined its exact function. The lack of function of these genes in control of a proliferative signaling pathway would result in uncontrolled proliferation and the development of a tumor. In 2018, it was theorized that proliferation of endothelial cells with dysfunctional tight junctions, that are under increased endothelial stress from elevated venous pressure provides the pathophysiological basis for cavernous hemangioma development. Diagnosis Gradient-Echo T2WI magnetic resonance imaging (MRI) is most sensitive method for diagnosing cavernous hemangiomas. MRI is such a powerful tool for diagnosis, it has led to an increase in diagnosis of cavernous hemangiomas since the technologys advent in the 1980s. The radiographic appearance is most commonly described as "popcorn" or "mulberry"-shaped. Computed tomography (CT) scanning is not a sensitive or specific method for diagnosing cavernous hemangiomas. Angiography is typically not necessary, unless it is required to rule out other diagnoses. Additionally, biopsies can be obtained from tumor tissue for examination under a microscope. It is essential to diagnose cavernous hemangioma because treatments for these lesions are less aggressive than that of cancerous tumors, such as angiosarcoma. However, since MRI appearance is practically pathognomonic, biopsy is rarely needed for verification.On ultrasound, cavernous haemangiomas in liver appeared as homogenous, hyperechoic lesions with posterior acoustic enhancement. On CT or MRI scans, it shows peripheral globular/nodular enhancement in the arterial phase, with portions of attenuation of enhancing areas. In the portal venous phase, it shows progressive centripetal enhancement. In delayed phase, it shows retention of contrast. It shows a high signal on T2 weighted images. Treatment Asymptomatic lesions may not require treatment but may need to be monitored for any change in the size. A change in size of lesions in the nose, lips, or eyelids can be treated with steroid drugs to slow its progress. Steroids can be taken orally or injected directly into the tumor. Applying pressure to the tumor can also be used to minimize swelling at the site of the hemangioma. A procedure that uses small particles to close off the blood supply is known as sclerotherapy. This allows for tumor shrinkage and less pain. It is possible for the tumor to regrow its blood supply after the procedure has been done. If the lesion caused by the cavernous hemangioma is destroying healthy tissue around it or if the patient is experiencing major symptoms, then surgery can be used to remove the cavernoma piecemeal. A common complication of the surgery is hemorrhage and the loss of blood. There is also the possibility of the hemangioma reoccurring after its removal. Additionally, the risk of a stroke or death is also possible.Treatments for cerebral cavernous hemangiomas include radiosurgery or microsurgery. The treatment approach depends on the site, size and symptoms present, as well as the history of hemorrhage from the lesion. Microsurgery is generally preferred if the cerebral cavernous hemangioma is superficial in the central nervous system, or the risk of damage to surrounding tissue from irradiation is too high. Additionally, a large hemorrhage with deterioration of the patient or intractable symptoms (such as seizures or coma) are further indications for microsurgical intervention. Gamma-knife radiation is the favored mechanism of radiosurgery. It provides a precise radiation dose to the cerebral cavernous hemangioma while relatively sparing the surrounding tissue. These treatment approaches for cavernous hemangiomas in other regions of the body have limited research. Prognosis A few studies have worked on providing details related to the outlook of disease progression. Two studies show that each year 0.5% of people who have never had bleeding from their brain cavernoma, but had symptoms of seizures, were affected by bleeding. In contrast, patients who have had bleeding from their brain cavernoma in the past had a higher risk of being affected by subsequent bleeding. The statistics for this are very broad, ranging from 4–23% a year. Additional studies suggest that women and patients under the age of 40 are at higher risk of bleeding, but similar conducted studies did not reach the same conclusion. However, when cavernous hemangiomas are completely excised, there is very little risk of growth or rebleeding. In terms of life expectancy, not enough data has been collected on patients with this malformation in order to provide a representative statistical analysis. Epidemiology The true incidence of cavernous hemangiomas is difficult to estimate because they are frequently misdiagnosed as other venous malformations. Cavernous hemangiomas of the brain and spinal cord (cerebral cavernous hemangiomas (malformations) (CCM)), can appear at all ages but usually occur in the third to fourth decade of a persons life with no sexual preference. In fact, CCM is present in 0.5% of the population. However, approximately 40% of those with malformations have symptoms. Asymptomatic individuals are usually individuals that developed the malformation sporadically, while symptomatic individuals usually have inherited the genetic mutation. The majority of diagnoses of CCM are in adults; however, 25% of cases of CCM are children. Approximately 5% of adults have liver hemangiomas in the United States, but most are asymptomatic. Liver hemangiomas usually occur between the ages of 30–50 and more commonly in women. Cases of infantile liver cavernomas are extremely rare. Cavernous hemangioma of the eye is more prevalent in women than men and between the ages of 20–40. Research In the treatment of a brain cavernous hemangioma, neurosurgery is usually the treatment chosen. Research needs to be conducted on the efficacy of treatment with stereotactic radiation therapy, especially on the long-term. However, radiotherapy is still being studied as a form of treatment if neurosurgery is too dangerous due to the location of the cavernoma. Genetic researchers are still working on determining the cause of the illness and the mechanism behind blood vessel formation. Clinical trials are being conducted to better assess when it is appropriate to treat a patient with this malformation and with what treatment method. Additionally, long-term studies are being conducted because there is no information related to the long-term outlook of patients with cavernoma. An existing registry known as The International Cavernous Angioma Patient Registry collects information from patients diagnosed with cavernoma in order to facilitate discovery of non-invasive treatments. References Further reading External Links Alliance to Cure Cavernous Malformation [1]"It is our mission to inform, support, and mobilize those affected by cavernous angioma and drive research for better treatments and a cure. We do this by developing and executing strategic, creative, high-return interventions as a model for rare diseases." Cavernoma Alliance UK, "Mission: To work to find a cure for cavernoma, improving treatment and supporting those affected by cavernoma along the way."
Adiposogenital dystrophy	Adiposogenital dystrophy is a condition that may be caused by tertiary hypogonadism originating from decreased levels in GnRH. Low levels of GnRH has been associated with defects of the feeding centers of the hypothalamus, leading to an increased consumption of food and thus caloric intake. Presentation It is characterized by: Obesity Growth delays and delayed sexual development, atrophy or hypoplasia of the gonads, and altered secondary sex characteristics, Headaches Problems with vision polyuria, polydipsia.It is usually associated with tumors of the hypothalamus, causing increased appetite and depressed secretion of gonadotropin. It seems to affect males mostly.Many overweight children may appear to have the disorder because of the concurrence of obesity and retarded sexual development; these children have no endocrine disturbances, however, and they mature normally after delayed puberty. Diagnosis Laboratory analysis of the urine from children with Froehlich syndrome typically reveals low levels of pituitary hormones, and that finding may suggest the presence of a lesion on the pituitary. Additional tests are needed before a definite diagnosis of Froehlich syndrome may be made. Treatment Pituitary extracts may be administered to replace the missing hormones (hormonal replacement therapy) in patients with Froehlich syndrome. Tumors of the hypothalamus should be surgically removed if possible. Appetite may be very difficult to manage, although weight control depends on this. References == External links ==

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