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Neurologic examination should assess cognitive and mental abilities, cranial nerve function, motor function, deep tendon reflexes, sensory function, coordination, and gait (if appropriate).Genetic testing
See also
Epilepsy Phenome/Genome Project
References
External links
Bilateral Frontalparietal Polymicrogyria at NIHs Office of Rare Diseases | Hemeralopia (from Greek ημέρα hemera, "day", and αλαός alaos, "blindness") is the inability to see clearly in bright light and is the exact opposite of nyctalopia (night blindness), the inability to see clearly in low light. Hemera was the Greek goddess of day, and Nyx was the goddess of night. However, it has been used in an opposite sense by many non-English-speaking doctors. It can be described as insufficient adaptation to bright light. It is also called "heliophobia" and "day blindness".In hemeralopia, daytime vision gets worse, characterised by photoaversion (dislike/avoidance of light) rather than photophobia (eye discomfort/pain in light), which is typical of inflammations of eye. Nighttime vision largely remains unchanged due to the use of rods as opposed to cones (during the day), which are affected by hemeralopia and in turn degrade the daytime optical response. Hence, many patients feel they see better at dusk than in daytime. Causes
Hemeralopia is known to occur in several ocular conditions. Cone dystrophy and achromatopsia, affecting the cones in the retina, and the anti-epileptic drug trimethadione are typical causes. Adies pupil, which fails to constrict in response to light; aniridia, which is absence of the iris; and albinism, where the iris is defectively pigmented, may also cause this. Central cataracts, due to the lens clouding, disperses the light before it can reach the retina and is a common cause of hemeralopia and photoaversion in the elderly. Cancer-associated retinopathy (CAR), seen when certain cancers incite the production of deleterious antibodies against retinal components, may cause hemeralopia. | 0-1
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Society and culture
Names
Esketamine is the generic name of the drug and its INN and BAN, while esketamine hydrochloride is its BANM. It is also known as S(+)-ketamine, (S)-ketamine, or (–)-ketamine ((-)[+] ketamine) as well as by its developmental code name JNJ-54135419.Esketamine is sold under the brand name Spravato for use as an antidepressant and the brand names Eskesia, Ketanest, Ketanest S, Ketanest-S, Keta-S for use as an anesthetic (veterinary), among others. Availability
Esketamine is marketed as an antidepressant in the United States; and as an anesthetic in the European Union. Legal status
Esketamine is a Schedule III controlled substance in the United States. References
External links
"Esketamine". Drug Information Portal. U.S. National Library of Medicine. "Esketamine hydrochloride". Drug Information Portal. U.S. National Library of Medicine. | Chronic local hypoxia (such as that occurring with overuse of contact lenses) or inflammation may lead to peripheral corneal vascularization, or pannus. Pannus may also develop in diseases of the corneal stem cells, such as aniridia. It is often resolved by peritomy. == References == | 0-1
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Heat stroke or heatstroke, also known as sun stroke, is a severe heat illness that results in a body temperature greater than 40.0 °C (104.0 °F), along with red skin, headache, dizziness, and confusion. Sweating is generally present in exertional heatstroke, but not in classic heatstroke. The start of heat stroke can be sudden or gradual. Heatstroke is a life-threatening condition due to the potential for multi-organ dysfunction, with typical complications including seizures, rhabdomyolysis, or kidney failure.Heat stroke occurs because of high external temperatures and/or physical exertion. It usually occurs under preventable prolonged exposure to extreme environmental or exertional heat. However, certain health conditions can increase the risk of heat stroke, and patients, especially children, with certain genetic predispositions are vulnerable to heatstroke under relatively mild conditions.Preventive measures include drinking sufficient fluids and avoiding excessive heat. Treatment is by rapid physical cooling of the body and supportive care. Recommended methods include spraying the person with water and using a fan, putting the person in ice water, or giving cold intravenous fluids. Adding ice packs around a person is reasonable but does not by itself achieve the fastest possible cooling.Heat stroke results in more than 600 deaths a year in the United States. Rates have increased between 1995 and 2015. Purely exercise-induced heat stroke, though a medical emergency, tends to be self-limiting (the patient stops exercising from cramp or exhaustion) and fewer than 5% of cases are fatal. | Causes
Low sexual desire alone is not equivalent to HSDD because of the requirement in HSDD that the low sexual desire causes marked distress and interpersonal difficulty and because of the requirement that the low desire is not better accounted for by another disorder in the DSM or by a general medical problem. It is therefore difficult to say exactly what causes HSDD. It is easier to describe, instead, some of the causes of low sexual desire.In men, though there are theoretically more types of HSDD/low sexual desire, typically men are only diagnosed with one of three subtypes. Lifelong/generalised: The man has little or no desire for sexual stimulation (with a partner or alone) and never had. Acquired/generalised: The man previously had sexual interest in his present partner, but lacks interest in sexual activity, partnered or solitary. Acquired/situational: The man was previously sexually interested in his present partner but now lacks sexual interest in this partner but has desire for sexual stimulation (i.e. alone or with someone other than his present partner. )Though it can sometimes be difficult to distinguish between these types, they do not necessarily have the same cause. The cause of lifelong/generalized HSDD is unknown. In the case of acquired/generalized low sexual desire, possible causes include various medical/health problems, psychiatric problems, low levels of testosterone or high levels of prolactin. One theory suggests that sexual desire is controlled by a balance between inhibitory and excitatory factors. This is thought to be expressed via neurotransmitters in selective brain areas. | 0-1
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The amount of iron in the sample is then quantified and compared to normal, and evidence of liver damage, especially cirrhosis, is measured microscopically. Formerly, this was the only way to confirm a diagnosis of haemochromatosis, but measures of transferrin and ferritin along with a history are considered adequate in determining the presence of the malady. Risks of biopsy include bruising, bleeding, and infection. Now, when a history and measures of transferrin or ferritin point to haemochromatosis, whether a liver biopsy is still necessary to quantify the amount of accumulated iron is debatable. MRI
MRI-based testing is a noninvasive and accurate alternative to measure liver iron concentrations. Other imaging
Clinically, the disease may be silent, but characteristic radiological features may point to the diagnosis. The increased iron stores in the organs involved, especially in the liver and pancreas, result in characteristic findings on unenhanced CT and a decreased signal intensity in MRI scans. Haemochromatosis arthropathy includes degenerative osteoarthritis and chondrocalcinosis. The distribution of the arthropathy is distinctive, but not unique, frequently affecting the second and third metacarpophalangeal joints of the hand. The arthropathy can, therefore, be an early clue as to the diagnosis of haemochromatosis. Functional testing
Based on the history, a physician might consider specific tests to monitor organ dysfunction, such as an echocardiogram for heart failure, or blood glucose monitoring for patients with haemochromatosis diabetes. | Suspicions were raised after it became obvious to friends and neighbours that Bluey Fletcher was suffering from the same fatal illness that had killed Yvonnes first husband. A police investigation led to the exhumation and testing of Desmond Butlers remains, which showed clear evidence of thallium, and this led to Yvonne being convicted of Butlers murder. She was sentenced to death but the sentence was commuted to life imprisonment after the NSW Government abolished the death penalty; she was eventually released in 1964. At the time of the trial it was reported that this was the first known case in Australia of a person being convicted of murder by administering thallium. The Fletcher case is also notable for the fact that one of the arresting officers was Sydney detective Fred Krahe, who later became notorious for his suspected close involvement with elements of Sydneys organised crime scene and his alleged involvement in the disappearance of social activist Juanita Nielsen. A month later, in October 1952, Bathurst grandmother Ruby Norton was tried for the murder of her daughters fiancé, Allen Williams, who died of thallium poisoning at Cowra Hospital in July 1952. Despite allegations that Norton hated all the men in her family and that she did not want Williams as a son-in-law, Norton was acquitted. In 1953 Sydney woman Veronica Monty, 45, was tried for the attempted murder of her son-in-law, noted Balmain and Australian rugby league player Bob Lulham, who was treated for thallium poisoning in 1952. | 0-1
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This can occur during pregnancy, obesity, cold adaptation, stay in high altitudes, endurance exercise, acute psychosis, and post-traumatic stress disorder.According to newer theories, elevated concentrations of TSH and thyroid hormones in type 2 allostasis result from an up-regulated set point of the feedback loop, which ensues from increased TRH expression in the basolateral amygdala and the paraventricular nucleus of the hypothalamus in response to stress.High-T3 syndrome in thyroid carcinoma may result from autonomous thyroid hormone secretion or overexpression of type 2 deiodinase in cancer cells rather than from type 2 allostasis. Conditions with mixed phenotypes
Psychiatry
Stress suppresses TSH, and alterations in thyroid hormone levels may arise in psychiatric illness. In major depressive disorder, an NTIS-like phenotype may be observed, with reduced T3 and increased rT3. T4 may be elevated, and TSH is usually normal, although TSHs normal circadian rhythm may be disrupted. Bipolar 1 and PTSD can exemplify an anti-NTIS phenotype, with upregulation of the HPT axis and increased T3. This may also occur during acute schizophrenic episodes. Exercise
After exercise, a transient increase occurs in TSH, T4, and T3, but this is thought to be due to increased blood concentration as a result of dehydration. The effects normalize after rest. After long-term heavy strain, levels of thyroid hormones decrease. This is exacerbated by other stressors such as undernutrition and lack of sleep, such as in a military training setting. During endurance exercise, before exhaustion, elevated thyroid hormone levels may happen due to increased expected energy demand (type 2 allostatic load). | Classical phenotype (type 1 thyroid allostasis)
Causes
Causes of classical euthyroid sick syndrome include a number of acute and chronic conditions, including pneumonia, fasting, starvation, anorexia nervosa, sepsis, trauma, cardiopulmonary bypass, malignancy, stress, heart failure, hypothermia, myocardial infarction, kidney failure, cirrhosis, diabetic ketoacidosis, surgery, infection, brain injury, shock, cancer, and HIV.Outside the hospital setting, euthyroid sick syndrome (nonthyroidal illness syndrome - NTIS) has been assumed closely related with a series of chronic diseases, such as inflammatory bowel disease, chronic fatigue syndrome, and autoimmune diseases.Additionally, an NTIS-like phenotype can be present in major depressive disorder, as well as overexercise. Pathophysiology
In critical illness, the activity of different deiodinases is altered. Humoral and neuronal inputs at the level of the hypothalamus may adjust the set point of thyroid homeostasis. This may play an important role in the pathogenesis of the central component of thyroid allostasis in critical illness, tumors, uremia and starvation (TACITUS). In addition, both illness and medication (e.g. salicylates and heparin) may impair plasma protein binding of thyroid hormones, resulting in reduced levels of total hormones, while free hormone concentrations may be temporarily elevated.Euthyroid sick syndrome probably represents an overlap of an allostatic response with pathologic reactions and drug interferences. Allostatic overload may result in wasting syndrome and myxedema coma. Thyroid storm, though, represents allostatic failure, where the organism is unable to develop NTIS in the situation of thyrotoxicosis. Deiodinases
Three primary deiodinases are responsible for thyroid hormone conversion and breakdown. | 11
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Depersonalization-derealization disorder (DPDR, DPD) is a mental disorder in which the person has persistent or recurrent feelings of depersonalization or derealization. Depersonalization is described as feeling disconnected or detached from ones self. Individuals may report feeling as if they are an outside observer of their own thoughts or body, and often report feeling a loss of control over their thoughts or actions. Derealization is described as detachment from ones surroundings. Individuals experiencing derealization may report perceiving the world around them as foggy, dreamlike/surreal, or visually distorted.Depersonalization-derealization disorder is thought to be caused largely by interpersonal trauma such as childhood abuse. Adverse early childhood experiences, specifically emotional abuse and neglect have been linked to the development of depersonalization symptoms. Triggers may include significant stress, panic attacks, and drug use. Those who do have this disorder could be in a depersonalized state for as long as a regular panic attack lasts. However, in some certain situations this state of mind could last either hours, days, and possibly even weeks at a time.Diagnostic criteria for depersonalization-derealization disorder includes persistent or recurrent feelings of detachment from ones mental or bodily processes or from ones surroundings. A diagnosis is made when the dissociation is persistent and interferes with the social or occupational functions of daily life.While depersonalization-derealization disorder was once considered rare, lifetime experiences with it occur in about 1–2% of the general population. The chronic form of the disorder has a reported prevalence of 0.8 to 1.9%. | Anatomical differences are common and can be congenital. In some women, cervical incompetence or cervical insufficiency occurs with the inability of the cervix to stay closed during the entire pregnancy. It does not cause first trimester miscarriages. In the second trimester, it is associated with an increased risk of miscarriage. It is identified after a premature birth has occurred at about 16–18 weeks into the pregnancy. During the second trimester, major trauma can result in a miscarriage. Smoking
Tobacco (cigarette) smokers have an increased risk of miscarriage. There is an increased risk regardless of which parent smokes, though the risk is higher when the gestational mother smokes. Morning sickness
Nausea and vomiting of pregnancy (NVP, or morning sickness) is associated with a decreased risk. Several possible causes have been suggested for morning sickness but there is still no agreement. NVP may represent a defense mechanism which discourages the mothers ingestion of foods that are harmful to the fetus; according to this model, a lower frequency of miscarriage would be an expected consequence of the different food choices made by women experiencing NVP. Chemicals and occupational exposure
Chemical and occupational exposures may have some effect in pregnancy outcomes. A cause and effect relationship almost can never be established. Those chemicals that are implicated in increasing the risk for miscarriage are DDT, lead, formaldehyde, arsenic, benzene and ethylene oxide. Video display terminals and ultrasound have not been found to have an effect on the rates of miscarriage. | 0-1
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Aortic dissection (AD) occurs when an injury to the innermost layer of the aorta allows blood to flow between the layers of the aortic wall, forcing the layers apart. In most cases, this is associated with a sudden onset of severe chest or back pain, often described as "tearing" in character. Also, vomiting, sweating, and lightheadedness may occur. Other symptoms may result from decreased blood supply to other organs, such as stroke, lower extremity ischemia, or mesenteric ischemia. Aortic dissection can quickly lead to death from insufficient blood flow to the heart or complete rupture of the aorta.AD is more common in those with a history of high blood pressure; a number of connective tissue diseases that affect blood vessel wall strength including Marfan syndrome and Ehlers–Danlos syndrome; a bicuspid aortic valve; and previous heart surgery. Major trauma, smoking, cocaine use, pregnancy, a thoracic aortic aneurysm, inflammation of arteries, and abnormal lipid levels are also associated with an increased risk. The diagnosis is suspected based on symptoms with medical imaging, such as computed tomography, magnetic resonance imaging, or ultrasound used to confirm and further evaluate the dissection. The two main types are Stanford type A, which involves the first part of the aorta, and type B, which does not.Prevention is by blood pressure control and smoking cessation. Management of AD depends on the part of the aorta involved. Dissections that involve the first part of the aorta (adjacent to the heart) usually require surgery. | Pachydermodactyly is a superficial dermal fibromatosis that presents as a poorly circumscribed symmetric, infiltrative, asymptomatic soft-tissue hypertrophy of the proximal fingers, typically sparing the thumbs and fifth fingers and rarely extending proximally to the wrists or occurring distally. : 990
See also
Skin lesion
References
External links
A Case of Pachydermodactyly | 0-1
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A hydrosalpinx is a condition that occurs when a Fallopian tube is blocked and fills with serous or clear fluid near the ovary (distal to the uterus). The blocked tube may become substantially distended giving the tube a characteristic sausage-like or retort-like shape. The condition is often bilateral and the affected tubes may reach several centimeters in diameter. The blocked tubes cause infertility. A Fallopian tube filled with blood is a hematosalpinx, and with pus a pyosalpinx.Hydrosalpinx is a composite of the Greek words ὕδωρ (hydōr – "water") and σάλπιγξ (sálpinx – "trumpet"); its plural is hydrosalpinges. Signs and symptoms
Symptoms can vary. Some patients have lower often recurring abdominal pain or pelvic pain, while others may be asymptomatic. As tubal function is impeded, infertility is a common symptom. Patients who are not trying to get pregnant and have no pain, may go undetected. Endometriosis, ruptured appendicitis, and abdominal surgery sometimes are associated with the problem. As a reaction to injury, the body rushes inflammatory cells into the area, and inflammation and later healing result in loss of the fimbria and closure of the tube. These infections usually affect both Fallopian tubes, and although a hydrosalpinx can be one-sided, the other tube on the opposite side is often abnormal. By the time it is detected, the tubal fluid usually is sterile, and does not contain an active infection. (Not symptoms)
Cause
The major cause for distal tubal occlusion is pelvic inflammatory disease, usually as a consequence of an ascending infection by chlamydia or gonorrhea. | During an infertility work-up a hysterosalpingogram, an X-ray procedure that uses a contrast agent to image the Fallopian tubes, shows the retort-like shape of the distended tubes and the absence of spillage of the dye into the peritoneum. If, however, there is a tubal occlusion at the utero-tubal junction, a hydrosalpinx may go undetected. When a hydrosalpinx is detected by a hysterosalpingogram it is prudent to administer antibiotics to reduce the risk of reactivation of an inflammatory process. When laparoscopy is performed, the surgeon may note the distended tubes, identify the occlusion, and may also find associated adhesions affecting the pelvic organs. Laparoscopy not only allows for the diagnosis of hydrosalpinx, but also presents a platform for intervention (see management). Prevention
As pelvic inflammatory disease is the major cause of hydrosalpinx formation, steps to reduce sexually transmitted disease will reduce incidence of hydrosalpinx. Also, as hydrosalpinx is a sequel to a pelvic infection, adequate and early antibiotic treatment of a pelvic infection is called for. Management
For most of the past century patients with tubal infertility due to hydrosalpinx underwent tubal corrective surgery to open up the distally occluded end of the tubes (salpingostomy) and remove adhesions (adhesiolysis). Unfortunately, pregnancy rates tended to be low as the infection process often had permanently damaged the tubes, and in many cases hydrosalpinges and adhesions formed again. Further, ectopic pregnancy is a typical complication. Surgical interventions can be done by laparotomy or laparoscopy. | 11
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Symptoms are due to spinal cord damage and include pain, decreased sensation of touch, weakness, and loss of muscle tissue. The diagnosis is confirmed with a spinal CT, myelogram or MRI of the spinal cord. The cavity may be reduced by surgical decompression.Furthermore, evidence also suggests that impact injuries to the thorax area highly correlate with the occurrence of a cervical-located syrinx. Treatment
Surgery
Treating syringomyelia sometimes requires surgery. Surgery involving the spinal cord carries certain risks, and as with any medical treatment, the potential benefits have to be weighed against the possible complications. On the other hand, delaying treatment can increase the risk of permanent damage. Evaluation of the condition is necessary because syringomyelia can remain stationary for long periods of time, and in some cases progress rapidly.The main goal of surgical intervention is to correct the condition which led to the formation of the syrinx. Draining the syrinx can also help, by preventing it from becoming worse, but the symptoms the syrinx has already caused may not go away.In cases involving an Arnold–Chiari malformation, the main goal of surgery is to provide more space for the cerebellum at the base of the skull and upper cervical spine, without entering the brain or spinal cord. This often causes the syrinx to shrink or disappear over time, as the normal flow of cerebrospinal fluid is restored. If syringomyelia is caused by a tumor, removing the tumor – if possible – is the treatment of choice.Most patients’ symptoms stabilize or have a modest improvement following surgery. | Vascular myelopathy (vascular disease of the spinal cord) refers to an abnormality of the spinal cord in regard to its blood supply. The blood supply is complicated and supplied by two major vessel groups: the posterior spinal arteries and the anterior spinal arteries—of which the Artery of Adamkiewicz is the largest. Both the posterior and anterior spinal arteries run the entire length of the spinal cord and receive anastomotic (conjoined) vessels in many places. The anterior spinal artery has a less efficient supply of blood and is therefore more susceptible to vascular disease. Whilst atherosclerosis of spinal arteries is rare, necrosis (death of tissue) in the anterior artery can be caused by disease in vessels originating from the segmental arteries such as atheroma (arterial wall swelling) or aortic dissection (a tear in the aorta). Spinal cord infarction
Anterior spinal artery syndrome
Anterior spinal artery syndrome is necrosis of tissue in the anterior spinal artery or its branches. It is characterised by pain which radiates at onset and sudden quadraplegia (paralysis of all four limbs) or paraplegia (paralysis of the lower body). Within days, flaccid limbs become spastic and hyporeflexia (underactive nerve responses) turns into hyperreflexia (overactive nerve responses) and extensor plantar nerve responses. Sensory loss to pain and temperature also occurs up to the level of damage on the spinal cord, as damage to different areas will affect different parts of the body.In diagnosis, other causes of abrupt paralysis should be excluded such as cord compression, transverse myelitis (inflammation of the spinal cord) and Guillain–Barré syndrome. | 0-1
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Nikki may refer to:
Arts and entertainment
Fictional characters
Nikki (Barbie), a fashion doll in the Barbie toy line
Nikki (comics), a Marvel Comics character
Nikki and Paulo, from the TV series Lost
Nikki, the mascot of Swapnote
Nikki, the main character from Dork Diaries
Music
Nikki (album), by Nikki Yanofsky, 2010
Nikki, an album by Quruli, 2005
"Nikki" (song), by Forever the Sickest Kids, 2013
"Nikki", a song by Logic from Under Pressure, 2014
"Nikki", an instrumental composition by Burt Bacharach
Other media
Nikki (DC Thomson), a 1980s girls comic
Nikki (TV series), a 2000s American series starring Nikki Cox
Nikki, Wild Dog of the North, a 1961 Walt Disney film
People
Nikki (given name), including a list of people with the name
Singers
Nikki (singer), Japanese-American singer
Nikki (Malaysian singer), Nikki Palikat (born 1985), a finalist in the first season of Malaysian Idol
Nigar Jamal (born 1980) or Nikki, English-Azerbaijani singer
Other uses
Nikki (drug), marketing name of a birth control pill
Nikki, Benin, a city, arrondissement and commune
See also
Nicci (disambiguation)
Nicki (disambiguation)
Nicky (disambiguation)
Nickey (disambiguation)
Nickie (disambiguation)
Nique (disambiguation)
All pages with titles beginning with Nikki
All pages with titles containing Nikki
Nikii Daas
NikkieTutorials
Nikky Finney
Nikky
Niky | Other confounding conditions contributing to ORS are thick and profuse pelvic adhesions, inflammation, bleeding after surgery (peri-operative bleeding), and ovaries which are retroperitoneal, can all contribute to the unintentional preservation of ovarian fragments. Risks
The risk of ovarian remnant (ORS) is increased by incomplete removal of the ovary at the time of oophorectomy. Surgical factors that contribute to incomplete removal include those that limit surgical exposure of the ovary, or compromise surgical technique. Factors may include:
adhesions – these can limit visualization of the ovary and may also cause it to adhere to surrounding tissues. Adhesions are often present due to preexisting conditions and/or prior surgeries. In the majority of cases reported since 2007, endometriosis was the most common indication for the initial oophorectomy in patients who subsequently had ORS. Endometriosis increases the risk for functional ovarian tissue being embedded into adjacent structures, making complete excision of tissue challenging. Anatomic variations - unusual location of ovarian tissue, for example
Intraoperative bleeding
Poor surgical technique – this may include failure to obtain adequate exposure or restore adequate anatomy, or imprecise choice of incision siteOvarian remnant (ORS) may first be considered in women who have undergone oophorectomy and have suggestive symptoms, the presence of a mass, or evidence of persistent ovarian function (by symptoms or laboratory testing). A history of oophorectomy is required, by definition, to make the diagnosis. Notes regarding the indication for the procedure and the procedure itself should be reviewed and may include prior abdominal or pelvic surgery, endometriosis, and/or poor surgical visualization. | 0-1
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Progressive bulbar palsy (PBP) is a medical condition. It belongs to a group of disorders known as motor neuron diseases. PBP is a disease that attacks the nerves supplying the bulbar muscles. These disorders are characterized by the degeneration of motor neurons in the cerebral cortex, spinal cord, brain stem, and pyramidal tracts. This specifically involves the glossopharyngeal nerve (IX), vagus nerve (X), and hypoglossal nerve (XII).This disorder should not be confused with pseudobulbar palsy or progressive spinal muscular atrophy. The term infantile progressive bulbar palsy is used to describe progressive bulbar palsy in children. The ICD-11 lists progressive bulbar palsy as a variant of amyotrophic lateral sclerosis (ALS). Signs and symptoms
Prognosis for PBP patients is poor. Progressive bulbar palsy symptoms can include progressive difficulty with talking and swallowing. Patients can also exhibit reduced gag reflexes, weak palatal movements, fasciculations, and weak movement of the facial muscles and tongue. In advanced cases of PBP, patients may be unable to protrude their tongue or manipulate food in their mouth.Patients with early cases of PBP have difficulty with pronunciations, particularly lateral consonants (linguals) and velars, and may show problems with drooling saliva. If the corticobulbar tract is affected a pseudobulbar affect with emotional changes may occur. Because PBP patients have such difficulty swallowing, food and saliva can be inhaled into the lungs. This can cause gagging and choking, and it increases the risk of pneumonia. | The authors, however, cited a study in younger patients who at a 3.5-year follow-up showed no memory impairments and speculated that certain memory functions take longer to recover from chronic benzodiazepine use and further improvements in elderly peoples cognitive function may occur beyond 52 weeks after withdrawal. The reason it took 24 weeks for improvements to be seen after cessation of benzodiazepine use was due to the time it takes the brain to adapt to the benzodiazepine-free environment.At 24 weeks, significant improvements were found, including accuracy of information processing improved, but a decline was seen in those who remained on benzodiazepines. Further improvements were noted at the 52-week follow-up, indicating ongoing improvements with benzodiazepine abstinence. Younger people on benzodiazepines also experience cognitive deterioration in visual-spatial memory but are not as vulnerable as the elderly to the cognitive effects. Improved reaction times were noted at 52 weeks in elderly patients free from benzodiazepines. This is an important function in the elderly, especially if they drive a car due to the increased risk of road traffic accidents in benzodiazepine users. At the 24-week follow-up, 80% of people had successfully withdrawn from benzodiazepines. Part of the success was attributed to the placebo method used for part of the trial which broke the psychological dependence on benzodiazepines when the elderly patients realised they had completed their gradual reduction several weeks previously and had only been taking placebo tablets. | 0-1
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Exacerbations in bronchiectasis present as a worsening of cough, increasing sputum volume or thickened consistency lasting at least 48 hours, worsening shortness of breath (breathlessness), worsening exercise intolerance, increased fatigue or malaise and the development of hemoptysis.People often report frequent bouts of "bronchitis" requiring therapy with repeated courses of antibiotics. People with bronchiectasis may have bad breath from active infection. On examination, crepitations and expiratory rhonchi may be heard with auscultation. Nail clubbing is a rare symptom.The complications of bronchiectasis include serious health conditions, such as respiratory failure and atelectasis:
collapse or closure of a lung. Respiratory failure occurs when not enough oxygen passes from the lungs into the blood. Atelectasis occur when one or more segments of the lungs collapse or do not inflate properly. Other pulmonary complications include lung abscess and empyema. Cardiovascular complications include cor pulmonale, in which there is enlargement and failure of the right side of the heart as a result of disease of the lungs. Causes
There are many causes that can induce or contribute to the development of bronchiectasis. The frequency of these different causes varies with geographic location. Cystic fibrosis is identified as a cause in up to half of cases. Bronchiectasis without CF is known as non-CF bronchiectasis. Historically, about half of all case of non-CF bronchiectasis were found to be idiopathic, or without a known cause. However, more recent studies with a more thorough diagnostic work-up have found an etiology in 60 to 90% of patients. | Other autoimmune diseases such as ulcerative colitis and Crohns disease also have an association with bronchiectasis. Additionally, graft-versus-host disease in patients who have undergone stem cell transplantation can lead to bronchiectasis as well. Lung injury
Bronchiectasis could be caused by: inhalation of ammonia and other toxic gases, chronic pulmonary aspiration of stomach acid from esophageal reflux, or a hiatal hernia. Congenital
Bronchiectasis may result from congenital disorders that affect cilia motility or ion transport. A common genetic cause is cystic fibrosis, which affects chloride ion transport. Another genetic cause is primary ciliary dyskinesia, a rare disorder that leads to immotility of cilia and can lead to situs inversus. When situs inversus is accompanied by chronic sinusitis and bronchiectasis, this is known as Kartageners syndrome. Other rare genetic causes include Youngs syndrome and Williams-Campbell syndrome. Tracheobronchomegaly, or Mournier-Kuhn syndrome is a rare condition characterized by significant tracheobronchial dilation and recurrent lower respiratory tract infections. Individuals with alpha 1-antitrypsin deficiency have been found to be particularly susceptible to bronchiectasis, due to the loss of inhibition to enzyme elastase which cleaves elastin. This decreases the ability of the alveoli to return to normal shape during expiration. Cigarette smoking
A causal role for tobacco smoke in bronchiectasis has not been demonstrated. Nonetheless, tobacco smoking can worsen pulmonary function and accelerate the progression of disease that is already present. | 11
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As acetaldehyde is one of the major causes of the symptoms of a "hangover", this produces immediate and severe negative reaction to alcohol intake. About 5 to 10 minutes after alcohol intake, the patient may experience the effects of a severe hangover for a period of 30 minutes up to several hours. Symptoms include flushing of the skin, accelerated heart rate, shortness of breath, nausea, vomiting, throbbing headache, visual disturbance, mental confusion, postural syncope, and circulatory collapse.Disulfiram should not be taken if alcohol has been consumed in the last 12 hours. There is no tolerance to disulfiram: the longer it is taken, the stronger its effects. As disulfiram is absorbed slowly through the digestive tract and eliminated slowly by the body, the effects may last for up to two weeks after the initial intake; consequently, medical ethics dictate that patients must be fully informed about the disulfiram-alcohol reaction.Disulfiram does not reduce alcohol cravings, so a major problem associated with this drug is extremely poor compliance. Methods to improve compliance include subdermal implants, which release the drug continuously over a period of up to 12 weeks, and supervised administration practices, for example, having the drug regularly administered by ones spouse.Although disulfiram remained the most common pharmaceutical treatment of alcohol abuse until the end of the 20th century, today it is often replaced or accompanied with newer drugs, primarily the combination of naltrexone and acamprosate, which directly attempt to address physiological processes in the brain associated with alcohol abuse. | Male adrenoleukodystrophy phenotypes
Female adrenoleukodystrophy phenotypes
Genetics
ALD is caused by mutations in ABCD1, located at Xq28 and demonstrates X-linked recessive inheritance. The gene ABCD1 encodes a peroxisomal membrane transporter which is responsible for transporting very long chain fatty acid substrate into the peroxisomes for degradation. Mutations in this gene that interfere with this process cause this syndrome.Males with an ABCD1 mutation are hemizygous, as they only have a single X chromosome. Female carriers will typically avoid the most severe manifestations of the disease, but often become symptomatic later in life. Although the detection of an ABCD1 mutation identifies an individual who is affected with a form of ALD, there is no genotype–phenotype correlation. Within a family, there will often be several different phenotypes, despite the presence of the same causative mutation. In one case, a family with six affected members displayed five different phenotypes. There are no common mutations that cause ALD, most are private or familial. Almost 600 different mutations have been identified, approximately half are missense mutations, one quarter are frameshifts, with in-frame deletions and splicing defects making up the remainder. The incidence of new mutations in ALD (those occurring spontaneously, rather than being inherited from a carrier parent) is estimated at 4.1%, with the possibility that these are due to germline mosaicism. Pathogenesis
The exact cause for the varied collection of symptoms found in the different ALD phenotypes is not clear. The white matter of the brain, the Leydig cells of the testes and the adrenal cortex are the most severely affected systems. | 0-1
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Nasal mucosa, particularly in the region of middle meatus becomes swollen due to collection of extracellular fluid. This extracellular fluid collection causes polyp formation and protrusion into the nasal cavity or sinuses. Polyps which are sessile in the beginning become pedunculated due to gravity.In people with nasal polyps due to aspirin or NSAID sensitivity, the underlying mechanism is due to disorders in the metabolism of arachidonic acid. Exposure to cycloxygenase inhibitors such as aspirin and NSAIDs leads to shunting of products through the lipoxygenase pathway leading to an increased production of products that cause inflammation. In the airway, these inflammatory products lead to symptoms of asthma such as wheezing as well as nasal polyp formation. Diagnosis
Nasal polyps can be seen on physical examination inside of the nose and are often detected during the evaluation of symptoms. On examination, a polyp will appear as a visible mass in the nostril. Some polyps may be seen with anterior rhinoscopy (looking in the nose with a nasal speculum and a light), but frequently, they are farther back in the nose and must be seen by nasal endoscopy. Nasal endoscopy involves passing a small, rigid camera with a light source into the nose. An image is projected onto a screen in the office so the doctor can examine the nasal passages and sinuses in greater detail. | The procedure is not generally painful, but the person can be given a spray decongestant and local anesthetic to minimize discomfort.Attempts have been made to develop scoring systems to determine the severity of nasal polyps. Proposed staging systems take into account the extent of polyps seen on endoscopic exam and the number of sinuses affected on CT imaging. This staging system is only partially validated, but in the future, may be useful for communicating the severity of disease, assessing treatment response, and planning treatment. Types
There are two primary types of nasal polyps: ethmoidal and antrochoanal. Ethmoidal polyps arise from the ethmoid sinuses and extend through the middle meatus into the nasal cavity. Antrochoanal polyps usually arise in the maxillary sinus and extend into the nasopharynx and represent only 4–6% of all nasal polyps.However, antrochoanal polyps are more common in children comprising one-third of all polyps in this population. Ethmoidal polyps are usually smaller and multiple while antrochoanal polyps are usually single and larger. CT scan
CT scan can show the full extent of the polyp, which may not be fully appreciated with physical examination alone. Imaging is also required for planning surgical treatment. On a CT scan, a nasal polyp generally has an attenuation of 10–18 Hounsfield units, which is similar to that of mucus. Nasal polyps may have calcification. Histology
On histologic examination, nasal polyps consist of hyperplastic edematous (excess fluid) connective tissue with some seromucous glands and cells representing inflammation (mostly neutrophils and eosinophils). Polyps have virtually no neurons. | 11
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Nadolols inhibition of beta-1 receptors in the heart and kidney leads to its effects on lowering blood pressure. The drug impairs AV node conduction and decreases sinus rate. Nadolol may also increase plasma triglycerides and decrease HDL-cholesterol levels. Chemistry
Nadolol is a mixture of stereoisomers. It is polar and hydrophilic, with low lipid solubility. References
External links
"Nadolol". Drug Information Portal. U.S. National Library of Medicine. | Central banks still hold historical gold reserves as a store of value although the level has generally been declining. The largest gold depository in the world is that of the U.S. Federal Reserve Bank in New York, which holds about 3% of the gold known to exist and accounted for today, as does the similarly laden U.S. Bullion Depository at Fort Knox. In 2005 the World Gold Council estimated total global gold supply to be 3,859 tonnes and demand to be 3,754 tonnes, giving a surplus of 105 tonnes.After 15 August 1971 Nixon shock, the price began to greatly increase, and between 1968 and 2000 the price of gold ranged widely, from a high of $850 per troy ounce ($27.33/g) on 21 January 1980, to a low of $252.90 per troy ounce ($8.13/g) on 21 June 1999 (London Gold Fixing). Prices increased rapidly from 2001, but the 1980 high was not exceeded until 3 January 2008, when a new maximum of $865.35 per troy ounce was set. Another record price was set on 17 March 2008, at $1023.50 per troy ounce ($32.91/g).In late 2009, gold markets experienced renewed momentum upwards due to increased demand and a weakening US dollar. On 2 December 2009, gold reached a new high closing at $1,217.23. Gold further rallied hitting new highs in May 2010 after the European Union debt crisis prompted further purchase of gold as a safe asset. | 0-1
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Skipping over a few mathematical steps the probability of electron transfer can be calculated (albeit quite difficult) using the following formula
With
J
{\displaystyle J}
being the electronic coupling constant describing the interaction between the two states (reactants and products) and
g
(
t
)
{\displaystyle g(t)}
being the line shape function. Taking the classical limit of this expression, meaning
ℏ
ω
≪
k
T
{\displaystyle \hbar \omega \ll kT}
, and making some substitution an expression is obtained very similar to the classically derived formula, as expected. | The term γ inside the logarithm is the activity and x is the ratio of the ion to the total composition of the electrode. The novel term Ω is the partial molar volume of the ion in the host and σ corresponds to the mean stress felt by the system. The result of this equation is that diffusion, which is dependent on chemical potential, gets impacted by the added stress and, therefore changes the battery’s performance. Furthermore, mechanical stresses may also impact the electrode’s solid-electrolyte-interphase layer. The interface which regulates the ion and charge transfer and can be degraded by stress. Thus, more ions in the solution will be consumed to reform it, diminishing the overall efficiency of the system. Other anodes and cathodes
In a vacuum tube or a semiconductor having polarity (diodes, electrolytic capacitors) the anode is the positive (+) electrode and the cathode the negative (−). The electrons enter the device through the cathode and exit the device through the anode. Many devices have other electrodes to control operation, e.g., base, gate, control grid. In a three-electrode cell, a counter electrode, also called an auxiliary electrode, is used only to make a connection to the electrolyte so that a current can be applied to the working electrode. The counter electrode is usually made of an inert material, such as a noble metal or graphite, to keep it from dissolving. Welding electrodes
In arc welding, an electrode is used to conduct current through a workpiece to fuse two pieces together. | 11
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About 120 mutations are associated with this condition and OCRL gene which is associated with oculocerebrorenal syndrome
Diagnosis
Diagnosis of oculocerebrorenal syndrome can be done via genetic testing Among the different investigations that can de done are:
Urinalysis
MRI
Blood test
Treatment
In terms of treatment of oculocerebrorenal syndrome for those individuals who are affected by this condition includes the following:
Glaucoma control (via medication)
Nasogastric tube feeding
Physical therapy
Clomipramine
Potassium citrate
Epidemiology
Because oculocerebrorenal syndrome is an X-linked recessive condition, the disease develops mostly in men with very rare occurrences in women, while women are carriers of the disease; it has an estimated prevalence of 1 in 500,000 people. History
It was first described in 1952 by American paediatrician Charles Upton Lowe (August 24, 1921 – February 9, 2012) and colleagues at the Massachusetts General Hospital in Boston. Because of the three major organ systems involved (eyes, brain and kidney), it is known as oculocerebrorenal syndrome. See also
List of congenital disorders
References
Further reading
Bökenkamp, Arend; Ludwig, Michael (1 January 2016). "The oculocerebrorenal syndrome of Lowe: an update". Pediatric Nephrology (Berlin, Germany). 31 (12): 2201–2212. doi:10.1007/s00467-016-3343-3. ISSN 0931-041X. PMC 5118406. PMID 27011217. == External links == | However, other thyroid diseases such as multinodular goitre, Hashimoto thyroiditis, thyroid adenoma, and thyroid carcinoma also retains the radiotracer because of high metabolic nature of these diseases. Thus, the final diagnosis always requires pathological examination of the tissue in question. Treatment
Parathyroid carcinoma is sometimes diagnosed during surgery for primary hyperparathyroidism. If the surgeon suspects carcinoma based on severity or invasion of surrounding tissues by a firm parathyroid tumor, aggressive excision is performed, including the thyroid and surrounding tissues as necessary.Agents such as calcimimetics (for example, cinacalcet) are used to mimic calcium and are able to activate the parathyroid calcium-sensing receptor (making the parathyroid gland "think" we have more calcium than we actually do), therefore lowering the calcium level, in an attempt to decrease the hypercalcemia. References
External links
Parathyroid cancer entry in the public domain NCI Dictionary of Cancer Terms
Parathyroid Carcinoma (Medscape eMedicine)
Cancer Management Handbook: Thyroid and Parathyroid Cancers
This article incorporates public domain material from the U.S. National Cancer Institute document: "Dictionary of Cancer Terms". | 0-1
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Radiology
Chest radiographs of patients with PAM usually reveal bilateral diffuse micronodular calcifications, producing a "sandstorm” appearance that first involves the inferior portions and then the middle and upper portions of the lungs. High-resolution computed tomography
The most common findings on HRCT are diffuse hyperdense ground-glass attenuation and subpleural linear calcifications, often most predominant in the inferior and posterior portions of the lungs. Additionally, the medial aspects of the lungs appear to be more heavily involved than the lateral aspects. Ground-glass opacities, probably due to small calculi in the air space, are the most common finding in children and in patients with early-stage PAM. Magnetic resonance imaging
On magnetic resonance imaging (MRI), the calcific lesions usually show hypointensity or a signal void on T1- and T2-weighted images. Pulmonary function studies
Pulmonary function tests, arterial blood gases, ventilation perfusion relationships, and O2 diffusing capacity are normal in the initial stages of PAM. As the disease progresses, pulmonary function tests reveal typical features of a restrictive defect with reduced forced vital capacity (FVC) and elevated forced expiratory volume in FEV1/FVC. Treatment
To date, no treatment has been proven to effectively reverse or prevent the progression of PAM. Lung transplantation is an option for end stage disease, but is typically only recommended as a last resort when quality of life is significantly impaired.Etidronate is a bisphosphonate and can reduce the formation of calcium hydroxyapatite crystals. It has led to clinical and radiological improvements in few cases. Epidemiology
Since the disease was first described in 1918, over 500 case reports have appeared in the literature. | Nonbacterial thrombotic endocarditis (NBTE) is a form of endocarditis in which small sterile vegetations are deposited on the valve leaflets. Formerly known as marantic endocarditis, which comes from the Greek marantikos, meaning "wasting away". The term "marantic endocarditis" is still sometimes used to emphasize the association with a wasting state such as cancer. Risk factors
Marantic vegetations are often associated with previous rheumatic fever. Other risk factors include:
hypercoagulable states
malignant cancers, especially mucin-producing adenocarcinomas (most commonly associated with pancreatic adenocarcinomas)
systemic lupus erythematosus: Referred to as Libman-Sacks endocarditis
trauma (e.g., catheters)
Valve predilection
The disease affects the valves with following predilection: mitral valve > aortic valve > tricuspid valve > pulmonary valve
Histopathology
Grossly, vegetations form along lines of valve closure and are generally symmetric with a smooth or verrucoid (warty) texture. Histologically, lesions are composed of fibrin (eosinophilic) and platelets but, unlike bacterial etiologies, contain little evidence of PMNs, microorganisms or inflammation. Diagnosis
Due to the non-invasive nature of NBTE, clinical examination may or may not reveal a new murmur. An embolic stroke may be the first feature to suggest diagnosis of NBTE. An echocardiograph may be used to further assess for valvular lesions. References
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Ecallantide (trade name Kalbitor) is a drug used for the treatment of hereditary angioedema (HAE) and in the prevention of blood loss in cardiothoracic surgery. It is an inhibitor of the protein kallikrein and a 60-amino acid polypeptide which was developed from a Kunitz domain through phage display to mimic antibodies inhibiting kallikrein. Medical uses
Angioedema
On November 27, 2009, ecallantide was approved by the FDA for the treatment of acute attacks of hereditary angioedema for persons over 16 years of age. A single dose requires three separate injections, which are given under the skin.Ecallantide does not appear to be efficacious for the treatment of angioedema due to ACE inhibitors. Adverse effects
The most common adverse effects are headache, nausea, fatigue and diarrhea. Less common, but observed in more than 5% of patients in clinical trials, are respiratory tract infections, fever, vomiting, itching and upper abdominal pain. Up to 4% of patients showed anaphylaxis, which led to a black box warning in the US. Interactions
As of 2011, no interaction studies have been conducted. Mechanism of action
HAE is caused by a mutation of the C1-inhibitor gene. Defective or missing C1-inhibitor permits activation of kallikrein, a protease that is responsible for liberating bradykinin from its precursor kininogen. An excess of bradykinin leads to fluid leakage from blood vessels, causing swelling of tissues typical of HAE. Ecallantide suppresses this pathogenetic mechanism by selectively and reversibly inhibiting the activity of plasma kallikrein. Ecallantides inhibitory constant (Ki) for kallikrein is 25 picoMolar, indicating high affinity. | See also
Icatibant, another drug for the treatment of HAE
== References == | 11
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In contrast, reticular reflex myoclonus occurs spontaneously to stimuli applied to distal limbs. Spinal myoclonus is caused by defects in spinal organization or connections, and peripheral myoclonus has symptoms of rhythmic jerks due to a neuron-the most common being the hemifacial spasm. Dystonia
Dystonia is a response to simultaneous contraction of agonist and antagonist muscles seen as twisting and contorting that affect posture and stance. Other symptoms can include tremors and muscle spasms due to various interactions of muscle, contractions and movement. Dystonia can be either primary or secondary with the latter being more common. Primary dystonia or "pure" dystonia is only physiological in origin. Secondary dystonia has multiple origins that are physiological, pathological or neurological. Myoclonus dystonia
Myoclonus dystonia includes the rapid contractions of myoclonus alongside the abnormal postures classified under dystonia, as well as neurological and psychiatric issues. This disease typically begins during childhood with symptoms of myoclonus and slight dystonia, most commonly cervical dystonia or writers cramp. Dystonia symptoms tend to not get exaggerated over the course of the disease and is rarely the only associated symptom, while the myoclonus symptoms can become more severe. Psychiatric issues are clinically diagnosed with the aforementioned symptoms and include depression, anxiety, personality disorders and addiction. Obsessive-compulsive disorder is associated with myoclonus dystonia as both have been found to have a commonality on chromosome 7 in various studies.Neurological symptoms are relatively common in those with myoclonus dystonia. Any neurological abnormalities will not normally be present in those affected at a young age. | In one hospital in Buenos Aires, the Ricardo Gutiérrez Childrens hospital, the disease accounted for 14% of their inpatient respiratory population from 1993 to 2002. As such, much of the information about post-infectious bronchiolitis obliterans has come from research out of South America. The most significant risk factors for the disease are infection with adenovirus and the need for ventilator support. In contrast with another cause of bronchiolitis obliterans in children, Stevens Johnsons syndrome, post-infectious bronchiolitis obliterans tends to be a chronic but non-progressive disease. The disease can have varying impact on children and their quality of life, which has been studied by lung function tests, as well as their exercise tolerance. Children with lower lung function based on their pulmonary function testing, have lower exercise tolerance, which compounds the impact of the disease on cardiovascular function as they are not able to maintain age appropriate aerobic fitness. This ultimately affects their activities of daily living (ADLs) and their quality of life going forward. Burn pits
A form of constrictive bronchiolitis is starting to present in Iraq and Afghanistan veterans. It has been attributed to veterans being exposed to trash burn pits. Veterans present with shortness of breath and other asthma-like symptoms. The only way to diagnose this condition is by doing a lung biopsy as chest X-rays and CT scans come back as normal. | 0-1
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Ciprofloxacin/dexamethasone (Ciprodex) is an antibiotic/steroid combination medication. It contains the synthetic broad-spectrum antibacterial agent, ciprofloxacin hydrochloride (0.3%), combined with the anti-inflammatory corticosteroid, dexamethasone (0.1%), in a sterile, preserved suspension for otic use. Ciprofloxacin, a fluoroquinolone antibiotic, has shown in vitro activity against many Gram-positive and Gram-negative bacteria including Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Pseudomonas aeruginosa. Dexamethasone acts as an anti-inflammatory corticosteroid. Medical uses
Ciprodex is indicated for use in the treatment of acute otitis media and acute otitis externa (swimmers ear) in people aged six months and older. Mechanism of action
Ciprofloxacin functions as a bactericide by interfering with DNA gyrase, an enzyme with a key role in the synthesis of bacterial DNA. Dexamethasone is used in combination in order to aid in the reducing inflammatory responses that often accompany bacterial infection. Clinical trials
In clinical trials, the median time to cessation of ear pain in Ciprodex was five days in a sample population of 909 participants. However, the clinical trial failed to demonstrate any significant benefit of using the combination of active ingredients in Ciprodex over ciprofloxacin alone, in regards to ear pain. Ciprodex was superior to ciprofloxacin in regards to time to cessation of otorrhea. Phase I
The most reported adverse effects of phase I studies included headache, rhinitis, pain, dyspepsia, and dysmenorrhea. Investigators did not believe that any of these were directly treatment-related, as many of these events are considered symptoms or manifestations of the underlying illness. | Symptoms result from the release of histamine and other active substances by mast cells, and consist of redness (mainly due to vasodilation of the peripheral small blood vessels), swelling of the conjunctiva, itching, and increased production of tears. Bacterial
Bacterial conjunctivitis causes the rapid onset of conjunctival redness, swelling of the eyelid, and a sticky discharge. Typically, symptoms develop first in one eye, but may spread to the other eye within 2–5 days. Conjunctivitis due to common pus-producing bacteria causes marked grittiness or irritation and a stringy, opaque, greyish or yellowish discharge that may cause the lids to stick together, especially after sleep. Severe crusting of the infected eye and the surrounding skin may also occur. The gritty or scratchy feeling is sometimes localized enough that patients may insist that they have a foreign body in the eye.Common bacteria responsible for nonacute bacterial conjunctivitis are Staphylococcus, Streptococcus, and Haemophilus species. Less commonly, Chlamydia spp. may be the cause. Bacteria such as Chlamydia trachomatis or Moraxella spp. can cause a nonexudative but persistent conjunctivitis without much redness. Bacterial conjunctivitis may cause the production of membranes or pseudomembranes that cover the conjunctiva. Pseudomembranes consist of a combination of inflammatory cells and exudates and adhere loosely to the conjunctiva, while true membranes are more tightly adherent and cannot be easily peeled away. Cases of bacterial conjunctivitis that involve the production of membranes or pseudomembranes are associated with Neisseria gonorrhoeae, β-hemolytic streptococci, and Corynebacterium diphtheriae. C. diphtheriae causes membrane formation in conjunctiva of unimmunized children. | 0-1
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The FDA has issued several letters warning manufacturers and suppliers of colon hydrotherapy equipment about making false claims of effectiveness, safety issues, and quality control violations. History
The concept of autointoxication, the idea that food enters the intestine and rots, provides a rationale for colon cleansing. The ancient Egyptians believed that toxins formed as a result of decomposition within the intestines, and moved from there into the circulatory system, causing fever and the development of pus. The Ancient Greeks adopted and expanded the idea, applying their belief in the four humours. In the 19th century, studies in biochemistry and microbiology seemed to support the autointoxication hypothesis, and mainstream physicians promoted the idea. Daly notes that, historically, "purging was one of the few procedures that a physician could perform with visible, often impressive results and without immediate or obvious dangers".Ilya Ilyich Mechnikov (1845-1916) became the strongest supporter of the idea of colon cleansing; he thought that toxins could shorten the lifespan. Over time, the concept broadened to autointoxication, which supposes that the body cannot fully dispose of its waste products and toxins, which then accumulate in the intestine. In some cases, the concept led to radical surgeries to remove the colon for unrelated symptoms.Autointoxication enjoyed some favor in the medical community in the late 19th and early 20th centuries, but clinicians discarded it as advances in science failed to support its claims. | Treatment
Treatment of gastric outlet obstruction depends on the cause, but is usually either surgical or medical. Medication
In most people with peptic ulcer disease, the oedema will usually settle with conservative management with nasogastric suction, replacement of fluids and electrolytes and proton pump inhibitors. Surgery
Surgery is indicated in cases of gastric outlet obstruction in which there is significant obstruction and in cases where medical therapy has failed. Endoscopic balloon therapy may be attempted as an alternative to surgery, with balloon dilation reporting success rates of 76% after repeat dilatons. The operation usually performed is an antrectomy, the removal of the antral portion of the stomach. Other surgical approaches include: vagotomy, the severing of the vagus nerve, the Billroth I, a procedure which involves anastomosing the duodenum to the distal stomach, or a bilateral truncal vagotomy with gastrojejunostomy. References
External links
Gastric outlet obstruction due to duodenal tuberculosis | 0-1
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In particular, they tend to make more saccades per line than persons with normal stereo vision, and to have a reduced reading speed, especially when reading a text with small font size.Strabismic amblyopia is treated by clarifying the visual image with glasses, or encouraging use of the amblyopic eye with an eyepatch over the dominant eye or pharmacologic penalization of the better eye. Penalization usually consists of applying atropine drops to temporarily paralyze the accommodation reflex, leading to the blurring of vision in the good eye. It also dilates the pupil. This helps to prevent the bullying and teasing associated with wearing a patch, although sometimes application of the eye drops is challenging. The ocular alignment itself may be treated with surgical or nonsurgical methods, depending on the type and severity of the strabismus. Refractive
Refractive amblyopia may result from anisometropia (unequal refractive error between the two eyes). Anisometropia exists when there is a difference in the power between the two eyes. The eye which provides the brain with a clearer image typically becomes the dominant eye. The image in the other eye is blurred, which results in abnormal development of one half of the visual system. Refractive amblyopia is usually less severe than strabismic amblyopia and is commonly missed by primary care physicians because of its less dramatic appearance and lack of obvious physical manifestation, such as with strabismus. | When an infected mosquito pierces a persons skin to take a blood meal, sporozoites in the mosquitos saliva enter the bloodstream and migrate to the liver where they infect hepatocytes, multiplying asexually and asymptomatically for a period of 8–30 days.After a potential dormant period in the liver, these organisms differentiate to yield thousands of merozoites, which, following rupture of their host cells, escape into the blood and infect red blood cells to begin the erythrocytic stage of the life cycle. The parasite escapes from the liver undetected by wrapping itself in the cell membrane of the infected host liver cell.Within the red blood cells, the parasites multiply further, again asexually, periodically breaking out of their host cells to invade fresh red blood cells. Several such amplification cycles occur. Thus, classical descriptions of waves of fever arise from simultaneous waves of merozoites escaping and infecting red blood cells.Some P. vivax sporozoites do not immediately develop into exoerythrocytic-phase merozoites, but instead, produce hypnozoites that remain dormant for periods ranging from several months (7–10 months is typical) to several years. After a period of dormancy, they reactivate and produce merozoites. Hypnozoites are responsible for long incubation and late relapses in P. vivax infections, although their existence in P. ovale is uncertain.The parasite is relatively protected from attack by the bodys immune system because for most of its human life cycle it resides within the liver and blood cells and is relatively invisible to immune surveillance. However, circulating infected blood cells are destroyed in the spleen. | 0-1
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spinipalpusm, Dermacentor andersoni, and D. variabilis
Endemic to: North America and eastern Russia
Colorado tick fever
Organism: Colorado tick fever virus (CTF), a coltivirus from the Reoviridae
Vector: Dermacentor andersoni
Region: US (West)
Crimean-Congo hemorrhagic fever
Organism: CCHF virus, a nairovirus, from the Bunyaviridae
Vector: Hyalomma marginatum, Rhipicephalus bursa
Region: Southern part of Asia, Northern Africa, Southern Europe
Severe febrile illnessOrganism: Heartland virus, a phlebovirus, from the Bunyaviridae
Vector: Lone star tick (Amblyomma americanum)
Region: Missouri and Tennessee, United States
Severe febrile illness, headaches, coma in 1/3 patientsOrganism: tentatively Alongshan virus, jingmenvirus group in the flavivirus family
Vector: tick (likely Ixodes persulcatus, Ixodes ricinus), mosquitoes
Region: Inner Mongolia but potentially more widespread
Protozoan
Babesiosis
Organism: Babesia microti, Theileria equi
Vector: Ixodes scapularis (deer tick), I. pacificus (western black-legged tick)
Region (US): Northeast, West Coast
Cytauxzoonosis
Organism: Cytauxzoon felis
Vector: Amblyomma americanum (Lone star tick)
Region (US): South, Southeast
Toxin
Tick paralysis
Cause: Toxin
Vector (US): Dermacentor andersoni (Rocky Mountain wood tick), D. variabilis (American dog tick or wood tick)
Region (US): D. andersoni: East, D. variabilis: East, West coast
Vector (Australia): Ixodes holocyclus (Australian paralysis tick)
Region (Australia): East
Allergies
Alpha-gal allergy - Alpha-gal syndrome is likely caused by a hypersensitivity reaction to the Alpha-gal (Galactose-alpha-1,3-galactose) sugar molecule introduced by ticks while feeding on a human host. The immune reaction can leave people with an allergy to red meat and other mammalian derived products. | Poikiloderma of Civatte is a cutaneous condition and refers to reticulated red to red-brown skin patches with telangiectasias. It is identifiable as a reddish-brown discoloration on the side of the neck, usually on both sides. It is more common in lighter-skinned individuals, in females rather than in males and more often affects middle-aged to elderly women. This disease is basically a change of the skin due to dilation of the blood vessels in the neck. "Civatte" was the French dermatologist who first identified it in the 1920s. See also
Cutis rhomboidalis nuchae
List of cutaneous conditions
Poikiloderma
Poikiloderma vasculare atrophicans
References
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Cholera is now no longer considered a pressing health threat in Europe and North America due to filtering and chlorination of water supplies, but it still strongly affects populations in developing countries. In the past, vessels flew a yellow quarantine flag if any crew members or passengers had cholera. No one aboard a vessel flying a yellow flag would be allowed ashore for an extended period, typically 30 to 40 days.Historically many different claimed remedies have existed in folklore. Many of the older remedies were based on the miasma theory, that the disease was transmitted by bad air. Some believed that abdominal chilling made one more susceptible, and flannel and cholera belts were included in army kits. In the 1854–1855 outbreak in Naples, homeopathic camphor was used according to Hahnemann. T. J. Ritters Mothers Remedies book lists tomato syrup as a home remedy from northern America. Elecampane was recommended in the United Kingdom, according to William Thomas Fernie. The first effective human vaccine was developed in 1885, and the first effective antibiotic was developed in 1948. Cholera cases are much less frequent in developed countries where governments have helped to establish water sanitation practices and effective medical treatments. In the 19th century the United States, for example, had a severe cholera problem similar to those in some developing countries. | Any individual, even a healthy adult in middle age, can undergo a severe case, and each persons case should be measured by the loss of fluids, preferably in consultation with a professional health care provider.The cystic fibrosis genetic mutation known as delta-F508 in humans has been said to maintain a selective heterozygous advantage: heterozygous carriers of the mutation (who are not affected by cystic fibrosis) are more resistant to V. cholerae infections. In this model, the genetic deficiency in the cystic fibrosis transmembrane conductance regulator channel proteins interferes with bacteria binding to the intestinal epithelium, thus reducing the effects of an infection. Mechanism
When consumed, most bacteria do not survive the acidic conditions of the human stomach. The few surviving bacteria conserve their energy and stored nutrients during the passage through the stomach by shutting down protein production. When the surviving bacteria exit the stomach and reach the small intestine, they must propel themselves through the thick mucus that lines the small intestine to reach the intestinal walls where they can attach and thrive.Once the cholera bacteria reach the intestinal wall, they no longer need the flagella to move. The bacteria stop producing the protein flagellin to conserve energy and nutrients by changing the mix of proteins that they express in response to the changed chemical surroundings. On reaching the intestinal wall, V. cholerae start producing the toxic proteins that give the infected person a watery diarrhea. | 11
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Central pontine myelinolysis is a neurological condition involving severe damage to the myelin sheath of nerve cells in the pons (an area of the brainstem). It is predominately iatrogenic (treatment-induced), and is characterized by acute paralysis, dysphagia (difficulty swallowing), dysarthria (difficulty speaking), and other neurological symptoms. Central pontine myelinolysis was first described as a disorder in 1959. The original paper described four cases with fatal outcomes, and the findings on autopsy. The disease was described as a disease of alcoholics and malnutrition. Central pontine indicated the site of the lesion and myelinolysis was used to emphasise that myelin was affected. The authors intentionally avoided the term demyelination to describe the condition, in order to differentiate this condition from multiple sclerosis and other neuroinflammatory disorders.Since this original description, demyelination in other areas of the central nervous system associated with osmotic stress has been described outside the pons (extrapontine). Osmotic demyelination syndrome is the term used for both central pontine myelinolysis and extrapontine myelinolysis.Central pontine myelinolysis, and osmotic demyelination syndrome, present most commonly as a complication of treatment of patients with profound hyponatremia (low sodium), which can result from a varied spectrum of conditions, based on different mechanisms. It occurs as a consequence of a rapid rise in serum tonicity following treatment in individuals with chronic, severe hyponatremia who have made intracellular adaptations to the prevailing hypotonicity. Signs and symptoms
Symptoms depend on the regions of the brain involved. | The favourable factors contributing to the good outcome in central pontine myelinolysis without hyponatremia were: concurrent treatment of all electrolyte disturbances, early intensive care unit involvement at the advent of respiratory complications, early introduction of feeding including thiamine supplements with close monitoring of the electrolyte changes and input.Research has led to improved outcomes. Animal studies suggest that inositol reduces the severity of osmotic demyelination syndrome if given before attempting to correct chronic hyponatraemia. Further study is required before using inositol in humans for this purpose. Prognosis
Though traditionally the prognosis is considered poor, a good functional recovery is possible. All patients at risk of developing refeeding syndrome should have their electrolytes closely monitored, including sodium, potassium, magnesium, glucose and phosphate. Recent data indicate that the prognosis of critically ill patients may even be better than what is generally considered, despite severe initial clinical manifestations and a tendency by the intensivists to underestimate a possible favorable evolution. While some patients die, most survive and of the survivors, approximately one-third recover; one-third are disabled but are able to live independently; one-third are severely disabled. Permanent disabilities range from minor tremors and ataxia to signs of severe brain damage, such as spastic quadriparesis and locked-in syndrome. Some improvements may be seen over the course of the first several months after the condition stabilizes.The degree of recovery depends on the extent of the original axonal damage. References
External links
MedPix Images of Osmotic Myelinolysis | 11
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Problem gambling or ludomania is repetitive gambling behavior despite harm and negative consequences. Problem gambling may be diagnosed as a mental disorder according to DSM-5 if certain diagnostic criteria are met. Pathological gambling is a common disorder that is associated with both social and family costs. The DSM-5 has re-classified the condition as an addictive disorder, with those affected exhibiting many similarities to those who have substance addictions. The term gambling addiction has long been used in the recovery movement. Pathological gambling was long considered by the American Psychiatric Association to be an impulse-control disorder rather than an addiction. However, data suggest a closer relationship between pathological gambling and substance use disorders than exists between PG and obsessive-compulsive disorder, largely because the behaviors in problem gambling and most primary substance use disorders (i.e. those not resulting from a desire to "self-medicate" for another condition such as depression) seek to activate the brains reward mechanisms while the behaviors characterizing obsessive-compulsive disorder are prompted by overactive and misplaced signals from the brains fear mechanisms.Problem gambling is an addictive behavior with a high comorbidity with alcohol problems. A common tendency shared by people who have a gambling addiction is impulsivity. Signs and symptoms
Research by governments in Australia led to a universal definition for that country which appears to be the only research-based definition not to use diagnostic criteria: "Problem gambling is characterized by many difficulties in limiting money and/or time spent on gambling which leads to adverse consequences for the gambler, others, or for the community." | Transient hypogammaglobulinemia of infancy is a form of hypogammaglobulinemia appearing after birth, leading to a reduction in the level of IgG, and also sometimes IgA and IgM. (The ratios of immunoglobulins vary rapidly in all infants, and the term dysgammaglobulinemia, although theoretically applicable, is not usually used in this context.) It can result in increased infections, but it can also present without symptoms. Pathophysiology
Normally, a newborns immunoglobulins come from the mother during pregnancy and wane after birth until 3-6 months of age, when the infant begins to start to produce their own IgG. However, in transient hypogammaglobulinemia of infancy, the IgG synthesis is delayed, and the hypogammaglobulinemia is prolonged beyond age 6 months. See also
List of cutaneous conditions
References
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Society and culture
Legal status
On 16 December 2021, and on 24 February 2022, the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) adopted a positive opinion, recommending the granting of a marketing authorization for the medicinal product Padcev, intended for the treatment of adults with urothelial cancer. The applicant for this medicinal product is Astellas Pharma Europe B.V. Enfortumab vedotin was approved for medical use in the European Union in April 2022. Names
Enfortumab vedotin is the international nonproprietary name (INN), and the United States Adopted Name (USAN). References
External links
"Enfortumab vedotin". Drug Information Portal. U.S. National Library of Medicine. | doi:10.1007/s002640050218. PMC 3619716. PMID 9651775. Jebson, Peter J. L.; Engber, William D. (1997). "Radial tunnel syndrome: Long-term results of surgical decompression". The Journal of Hand Surgery. 22 (5): 889–96. doi:10.1016/S0363-5023(97)80086-X. PMID 9330150. Sarris, Ioannis K.; Papadimitriou, Nikolaos G.; Sotereanos, Dean G. (2002). "Radial Tunnel Syndrome". Techniques in Hand and Upper Extremity Surgery. 6 (4): 209–212. doi:10.1097/00130911-200212000-00010. PMID 16520604. == External links == | 0-1
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By 2005, lenalidomide, a chemotherapy drug, was recognized to be effective in MDS patients with the 5q- syndrome, and in December 2005, the US FDA approved the drug for this indication. Patients with isolated 5q-, low IPSS risk, and transfusion dependence respond best to lenalidomide. Typically, prognosis for these patients is favorable, with a 63-month median survival. Lenalidomide has dual action, by lowering the malignant clone number in patients with 5q-, and by inducing better differentiation of healthy erythroid cells, as seen in patients without 5q deletion. Splicing factor mutations
Mutations in splicing factors have been found in 40–80% of cases with myelodysplastic syndrome, particularly in those with ringed sideroblasts. IDH1 and IDH2 mutations
Mutations in the genes encoding for isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) occur in 10–20% of patients with myelodysplastic syndrome, and confer a worsened prognosis in low-risk MDS. Because the incidence of IDH1/2 mutations increases as the disease malignancy increases, these findings together suggest that IDH1/2 mutations are important drivers of progression of MDS to a more malignant disease state. GATA2 deficiency
GATA2 deficiency is a group of disorders caused by a defect, familial, or sporadic inactivating mutations, in one of the two GATA2 genes. These autosomal dominant mutations cause a reduction in the cellular levels of the genes product, GATA2. The GATA2 protein is a transcription factor critical for the embryonic development, maintenance, and functionality of blood-forming, lymph-forming, and other tissue-forming stem cells. | Chronic malabsorptive diarrhea leads to the poor absorption of fat, causing steatorrhea (fatty, offensive-smelling stool), flatulence, and abdominal distension. Protein-losing enteropathy may also occur, causing depletion of albumin, a blood protein, which may lead to peripheral edema caused by the lowered oncotic pressures.Hyperpigmentation of the skin occurs in almost half; some also have skin nodules. Various eye problems, such as uveitis, may occur; this is typically associated with deteriorating vision and pain in the affected eye. Endocarditis (infection of the heart valve) has been reported in a small number of cases, sometimes in people with no other symptoms of Whipples disease; this is typically noticed as breathlessness and leg swelling due to fluid accumulation as the heart is unable to pump fluid through the body.Of those affected by Whipples disease, 10–40% have problems related to the involvement of the brain; the symptoms relate to the part of the brain that is affected. The most common problems are dementia, memory loss, confusion, and decreased level of consciousness. Eye-movement disturbances and myorhythmia (rapidly repetitive movements of the muscles) of the face, together referred to as oculomasticatory myorhythmia, are highly characteristic for Whipples disease. Weakness and poor coordination of part of the body, headaches, seizures, and a number of more uncommon neurological features are present in some cases. Mechanism
T. whipplei is one of the Actinomycetes, and is a distant relative of the Mycobacterium avium complex, explaining in part why Whipples disease is similar to the diseases caused by MAC bacteria. | 0-1
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But in Guinea all Fulani women responding to a survey in 2012 said they had experienced FGM, against 12 percent of the Fulani in Chad, while in Nigeria the Fulani are the only large ethnic group in the country not to practise it. Reasons
Support from women
Dahabo Musa, a Somali woman, described infibulation in a 1988 poem as the "three feminine sorrows": the procedure itself, the wedding night when the woman is cut open, then childbirth when she is cut again. Despite the evident suffering, it is women who organize all forms of FGM. Anthropologist Rose Oldfield Hayes wrote in 1975 that educated Sudanese men who did not want their daughters to be infibulated (preferring clitoridectomy) would find the girls had been sewn up after the grandmothers arranged a visit to relatives. Gerry Mackie has compared the practice to footbinding. Like FGM, footbinding was carried out on young girls, nearly universal where practised, tied to ideas about honour, chastity, and appropriate marriage, and "supported and transmitted" by women. FGM practitioners see the procedures as marking not only ethnic boundaries but also gender differences. According to this view, male circumcision defeminizes men while FGM demasculinizes women. Fuambai Ahmadu, an anthropologist and member of the Kono people of Sierra Leone, who in 1992 underwent clitoridectomy as an adult during a Sande society initiation, argued in 2000 that it is a male-centred assumption that the clitoris is important to female sexuality. African female symbolism revolves instead around the concept of the womb. | Sycosis vulgaris is a cutaneous condition characterized by a chronic infection of the chin or bearded region. : 252 The irritation is caused by a deep infection of hair follicles, often by species of Staphylococcus or Propionibacterium bacteria. Asymptomatic or painful and tender erythematous papules and pustules may form around coarse hair in the beard (sycosis barbae) or the back of the neck (sycosis nuchae). See also
Folliculitis
List of cutaneous conditions
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Peliosis hepatis can be associated with peliosis of the spleen, as well as bacillary angiomatosis of the skin in HIV patients. Trench fever
Trench fever, also known as five-day fever or quintan fever, is the initial manifestation of B. quintana infection. Clinical manifestations range from asymptomatic infection to severe illness. Classical presentations include a febrile illness of acute onset, headache, dizziness, and shin pain. Chronic infection manifestations include attacks of fever and aching in some cases and persistent bacteremia in soldiers and homeless people. Microbiology
Members of the genus Bartonella are facultative intracellular bacteria, alpha 2 subgroup Pseudomonadota. The genus comprises:
Pathophysiology
In mammals, each Bartonella species is highly adapted to its reservoir host as the result of intracellular parasitism and can persist in the bloodstream of the host. Intraerythrocytic parasitism is only observed in the acute phase of Carrions disease. Bartonella species also have a tropism for endothelial cells, observed in the chronic phase of Carrions disease (also known as verruga Peruana) and bacillary angiomatosis. Pathological response can vary with the immune status of the host. Infection with B. henselae can result in a focal suppurative reaction (CSD in immunocompetent patients), a multifocal angioproliferative response (bacillary angiomatosis in immunocompromised patients), endocarditis, or meningitis. Diagnosis
There are several methods used for diagnosing Bartonella infection including microscopy, serology, and PCR. Microscopy of blood smears is used to diagnose Carrións disease (B. bacilliformis), however for other Bartonella species, microscopy and silver staining are insensitive, not highly specific, and cannot differentiate species. The CDC does not recommend lymph node aspiration for diagnostic purposes. | Bartonellosis is an infectious disease produced by bacteria of the genus Bartonella.Bartonella species cause diseases such as Carrións disease, trench fever, cat-scratch disease, bacillary angiomatosis, peliosis hepatis, chronic bacteremia, endocarditis, chronic lymphadenopathy, and neurological disorders. Presentation
Carrións disease
Patients can develop two clinical phases: an acute septic phase and a chronic eruptive phase associated with skin lesions. In the acute phase (also known as Oroya fever or fiebre de la Oroya), B. bacilliformis infection is a sudden, potentially life-threatening infection associated with high fever and decreased levels of circulating red blood cells (i.e., hemolytic anemia) and transient immunosuppression. B. bacilliformis is considered the most deadly species to date, with a death rate of up to 90% during the acute phase, which typically lasts two to four weeks. Peripheral blood smears show anisomacrocytosis with many bacilli adherent to red blood cells. Thrombocytopenia is also seen and can be very severe. Neurologic manifestations (neurobartonellosis) are altered mental status, agitation, or even coma, ataxia, spinal meningitis, or paralysis. It is seen in 20% of patients with acute infection, in which the prognosis is very guarded with an about 50% mortality. The most feared complication is overwhelming infection mainly by Enterobacteriaceae, particularly Salmonella (both S. typhi and S. non-typhi, as well as reactivation of toxoplasmosis and other opportunistic infections .The chronic manifestation consists of a benign skin eruption with raised, reddish-purple nodules (angiomatous tumours). The bacterium can be seen microscopically, if a skin biopsy is silver stained (the Warthin–Starry method). | 11
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Dicheirus is a genus of beetles in the family Carabidae, containing the following species:
Dicheirus dilatatus Dejean, 1829
Dicheirus obtusus LeConte, 1852
Dicheirus piceus Menetries, 1845
Dicheirus pilosus G. Horn, 1880
Dicheirus strenuus G. Horn, 1868
== References == | Drug Information Portal. U.S. National Library of Medicine. | 0-1
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Diagnosis
Bronchiolitis obliterans is often diagnosed based on the symptoms of obstructive lung disease following lung injury. The definitive diagnosis is through biopsy, but due to the variable distribution of lesions, leading to falsely negative tests, and invasive nature of this procedure it is often not performed. Several tests are often needed to diagnose bronchiolitis obliterans, including spirometry, diffusing capacity of the lung tests (DLCO), lung volume tests, chest X-rays, high-resolution CT (HRCT), and lung biopsy. Pulmonary function testing
Spirometry tests usually show an obstructive pattern and is the most common presentation. A slightly reduced to normal forced vital capacity (FVC), and a reduced FEV1 to FVC ratio and forced expiratory volume (FEV) with little to no correction with the use of bronchodialators are common findings. Lung volume tests may show hyperinflation (excessive air in lungs caused by air trapping). Diffusing capacity of the lung (DLCO) tests are usually normal; people with early-stage OB are more likely to have normal DLCO.FEV1 (forced expiratory volume in 1 second) should be above 80% of predicted values to be considered normal. Bronchiolitis obliterans reduces this to between 16% and 21%. Medical imaging
Early in the disease chest radiography is typically normal but may show hyperinflation. As the disease progresses a reticular pattern with thickening of airway walls may be present. HRCT can also show air trapping when the person being scanned breathes out completely; it can also show thickening in the airway and haziness in the lungs. | These symptoms represent an obstructive pattern that is non-reversible with bronchodilator therapy, and need to be related to various lung insults. These insults include inhalation damage, post transplant auto-immune injury, post-infectious disease, drug reactions, and several auto-immune diseases. Cause
Bronchiolitis obliterans has many possible causes, including collagen vascular disease, transplant rejection in organ transplant patients, viral infection (adenovirus, respiratory syncytial virus, influenza, HIV, cytomegalovirus), Stevens–Johnson syndrome, Pneumocystis pneumonia, drug reaction, aspiration and complications of prematurity (bronchopulmonary dysplasia), and exposure to toxic fumes. Toxins implicated in the condition include diacetyl, sulfur dioxide, nitrogen dioxide, ammonia, chlorine, thionyl chloride, methyl isocyanate, hydrogen fluoride, hydrogen bromide, hydrogen chloride, hydrogen sulfide, phosgene, polyamide-amine dyes, mustard gas and ozone. It can also be present in patients with IBD, systemic lupus erythematosus, juvenile idiopathic arthritis, rheumatoid arthritis, GERD, IgA nephropathy, and ataxia telangiectasia. Activated charcoal has been known to cause it when aspirated. The ingestion of large doses of papaverine in the vegetable Sauropus androgynus has caused it. Additionally, the disorder may be idiopathic (without known cause). Lung transplant
Bronchiolitis obliterans is a common complication in lung transplants because transplanted lungs are at greater risk of alloimmunization as compared to healthy lungs. The disease is often termed bronchiolitis obliterans syndrome (BOS) in the setting of post lung transplantation and hematopoietic stem cell transplant (HSCT). Patients who develop BOS post lung transplant vary in disease latency and severity. Patients often initially have normal lung function on pulmonary function testing and have normal chest radiographs. | 11
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Rocket fuel
Ethanol was commonly used as fuel in early bipropellant rocket (liquid-propelled) vehicles, in conjunction with an oxidizer such as liquid oxygen. The German A-4 ballistic rocket of World War II, better known by its propaganda name V-2, which is credited as having begun the space age, used ethanol as the main constituent of B-Stoff. Under such nomenclature, the ethanol was mixed with 25% water to reduce the combustion chamber temperature. The V-2s design team helped develop US rockets following World War II, including the ethanol-fueled Redstone rocket which launched the first US satellite. Alcohols fell into general disuse as more energy-dense rocket fuels were developed, although ethanol is currently used in lightweight rocket-powered racing aircraft. Fuel cells
Commercial fuel cells operate on reformed natural gas, hydrogen or methanol. Ethanol is an attractive alternative due to its wide availability, low cost, high purity and low toxicity. There is a wide range of fuel cell concepts that have entered trials including direct-ethanol fuel cells, auto-thermal reforming systems and thermally integrated systems. The majority of work is being conducted at a research level although there are a number of organizations at the beginning of the commercialization of ethanol fuel cells. Household heating and cooking
Ethanol fireplaces can be used for home heating or for decoration. Ethanol can also be used as stove fuel for cooking. Feedstock
Ethanol is an important industrial ingredient. It has widespread use as a precursor for other organic compounds such as ethyl halides, ethyl esters, diethyl ether, acetic acid, and ethyl amines. | Paroxetine is also effective for children with obsessive-compulsive disorder.Paroxetine is approved for treatment of PTSD in the United States, Japan and Europe. In the United States it is approved for short-term use.Paroxetine is also FDA-approved for generalized anxiety disorder. Menopausal hot flashes
In 2013, low-dose paroxetine was approved in the US for the treatment of moderate-to-severe vasomotor symptoms such as hot flashes and night sweats associated with menopause. At the low dose used for menopausal hot flashes, side effects are similar to placebo and dose tapering is not required for discontinuation. Fibromyalgia
Studies have also shown paroxetine "appears to be well-tolerated and improve the overall symptomatology in patients with fibromyalgia" but is less robust in helping with the pain involved. Adverse effects
Common side effects include drowsiness, dry mouth, loss of appetite, sweating, trouble sleeping, and sexual dysfunction. Serious side effects may include suicide in those under the age of 25, serotonin syndrome, and mania. While the rate of side effects appears similar compared to other SSRIs and SNRIs, antidepressant discontinuation syndromes may occur more often. | 0-1
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History
The first documented case of LQTS was described in Leipzig by Meissner in 1856, when a deaf girl died after her teacher yelled at her. Soon after being notified, the girls parents reported that her older brother, also deaf, had previously died after a terrible fright. This was several decades before the ECG was invented, but is likely the first described case of Jervell and Lange-Nielsen syndrome. In 1957, the first case documented by ECG was described by Anton Jervell and Fred Lange-Nielsen, working in Tønsberg, Norway. Italian pediatrician Cesarino Romano, in 1963, and Irish pediatrician Owen Conor Ward, in 1964, separately described the more common variant of LQTS with normal hearing, later called Romano-Ward syndrome. The establishment of the International Long-QT Syndrome Registry in 1979 allowed numerous pedigrees to be evaluated in a comprehensive manner. This helped in detecting many of the numerous genes involved. Transgenic animal models of the LQTS helped define the roles of various genes and hormones involved, and recently experimental pharmacological therapies to normalize the abnormal repolarization in animals were published. References
NotesGoldman L (2011). Goldmans Cecil Medicine (24th ed.). Philadelphia: Elsevier Saunders. p. 1196. ISBN 978-1437727883. | Histology
No irregularities in the dentin below invagination
Strains of vital tissue or fine canals that communicates with the pulp could be found
Enamel lining irregularly structured
External and internal enamel have different structures
Management
Preventative treatment - e.g. oral hygiene instructions, fissure sealant
Intentional replantation
Root canal treatment with mineral trioxde aggregate
Periapical surgery with retrograde filling
Extraction
References
== External links == | 0-1
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This allows for the microfilariae that would have been in the tissue to migrate to the liquid phase of the specimen. Additionally, to differentiate the skin-dwelling filariae M. streptocerca and Onchocerca volvulus, a nested polymerase chain reaction (PCR) assay was developed using small amounts of parasite material present in skin biopsies. Prevention
Prevention can be partially achieved through limiting contact with vectors through the use of DEET and other repellents, but due to the predominantly relatively mild symptoms and the infection being generally asymptomatic, little has formally been done to control the disease. Treatment
There is no consensus on optimal therapeutic approach. The most commonly used drug is diethylcarbamazine (DEC), but it is, however, often ineffective. Although other drugs have been tried such as praziquantel, ivermectin, and albendozole, none has proven to be reliably and rapidly effective. Mebendazole appeared more active than DEC in eliminating the infection, and had comparable overall responses. Thiabendazole evidenced a small, but significant activity against the infection. A combination of treatments, DEC plus mebendazole, was much more effective than single drug doses. Epidemiology
Mansonelliasis is found in Latin America from the Yucatán peninsula to northern Argentina, in the Caribbean, and in Africa from Senegal to Kenya and south to Angola and Zimbabwe. M. ozzardi is found only in the New World, M. steptocerca is found only in the Congo Basin, and M. perstans is found in both the previously described areas of Africa and Latin America. | U.S. National Library of Medicine. "Enasidenib mesylate". NCI Dictionary of Cancer Terms. National Cancer Institute. "Enasidenib mesylate". National Cancer Institute. | 0-1
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The pain is usually relieved by sitting up or bending forward, and worsened by lying down (both recumbent and supine positions) or by inspiration (taking a breath in). The pain may resemble that of angina but differs in that pericarditis pain changes with body position, where heart attack pain is generally constant and pressure-like. Other symptoms of pericarditis may include dry cough, fever, fatigue, and anxiety.Due to its similarity to the pain of myocardial infarction (heart attack), pericarditis can be misdiagnosed as a heart attack. Acute myocardial infarction can also cause pericarditis, but the presenting symptoms often differ enough to warrant diagnosis. The following table organizes the clinical presentation of pericarditis differential to myocardial infarction:
Physical examinations
The classic sign of pericarditis is a friction rub heard with a stethoscope on the cardiovascular examination, usually on the lower left sternal border. Other physical signs include a person in distress, positional chest pain, diaphoresis (excessive sweating); possibility of heart failure in form of pericardial tamponade causing pulsus paradoxus, and the Becks triad of low blood pressure (due to decreased cardiac output), distant (muffled) heart sounds, and distension of the jugular vein (JVD). Complications
Pericarditis can progress to pericardial effusion and eventually cardiac tamponade. | Colchicine may be added to the above as it decreases the risk of further episodes of pericarditis.Severe cases may require one or more of the following:
antibiotics to treat tuberculosis or other bacterial causes
steroids are used in acute pericarditis but are not favored because they increase the chance of recurrent pericarditis
pericardiocentesis to treat a large pericardial effusion causing tamponadeRecurrent pericarditis resistant to colchicine and anti-inflammatory steroids may benefit from a number of medicines that affect the action of interleukin 1; they cannot be taken in tablet form. These are anakinra, canakinumab and rilonacept. Rilonacept has been specifically approved as an orphan drug for use in this situation. Azathioprine has also been used.Surgical removal of the pericardium, pericardiectomy, may be used in severe cases and where the pericarditis is causing constriction, impairing cardiac function. It is less effective if the pericarditis is a consequence of trauma, in elderly patients, and if the procedure is done incompletely. It carries a risk of death between 5 and 10%. Epidemiology
About 30% of people with viral pericarditis or pericarditis of an unknown cause have one or several recurrent episodes. See also
Myopericarditis
Viral cardiomyopathy
References
External links
Pericarditis — National Library of Medicine
Pericarditis — National Heart Lung Blood Institute | 11
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Idiopathic unilateral circumscribed hyperhidrosis
Reported association with:
Blue rubber bleb nevus
Glomus tumor
POEMS syndrome
Burning feet syndrome (Gopalans)
Trench foot
Causalgia
Pachydermoperiostosis
Pretibial myxedema
Gustatory sweating associated with:
Encephalitis
Syringomyelia
Diabetic neuropathies
Herpes zoster (shingles)
Parotitis
Parotid abscesses
Thoracic sympathectomy
Auriculotemporal or Freys syndrome
Miscellaneous
Lacrimal sweating (due to postganglionic sympathetic deficit, often seen in Raeders syndrome)
Harlequin syndrome
Emotional hyperhidrosis
Cancer
A variety of cancers have been associated with the development of secondary hyperhidrosis including lymphoma, pheochromocytoma, carcinoid tumors (resulting in carcinoid syndrome), and tumors within the thoracic cavity. Endocrine
Certain endocrine conditions are also known to cause secondary hyperhidrosis including diabetes mellitus (especially when blood sugars are low), acromegaly, hyperpituitarism, pheochromocytoma (tumor of the adrenal glands, present in 71% of patients) and various forms of thyroid disease. Medications
Use of selective serotonin reuptake inhibitors (e.g., sertraline) is a common cause of medication-induced secondary hyperhidrosis. Other medications associated with secondary hyperhidrosis include tricyclic antidepressants, stimulants, opioids, nonsteroidal anti-inflammatory drugs (NSAIDs), glyburide, insulin, anxiolytic agents, adrenergic agonists, and cholinergic agonists. Miscellaneous
In people with a history of spinal cord injuries
Autonomic dysreflexia
Orthostatic hypotension
Posttraumatic syringomyelia
Associated with peripheral neuropathies
Familial dysautonomia (Riley-Day syndrome)
Congenital autonomic dysfunction with universal pain loss
Exposure to cold, notably associated with cold-induced sweating syndrome
Associated with probable brain lesions
Episodic with hypothermia (Hines and Bannick syndrome)
Episodic without hypothermia
Olfactory
Associated with systemic medical problems
Parkinsons disease
Fibromyalgia
Congestive heart failure
Anxiety
Obesity
Menopausal state
Night sweats
Compensatory
Infantile acrodynia induced by chronic low-dose mercury exposure, leading to elevated catecholamine accumulation and resulting in a clinical picture resembling pheochromocytoma. Febrile diseases
Vigorous exercise
A hot, humid environment
Diagnosis
Symmetry of excessive sweating in hyperhidrosis is most consistent with primary hyperhidrosis. To diagnose this condition, a dermatologist gives the patient a physical exam. | Computed tomography or ultrasound may be used instead for imaging.Urine odor in cystinuria has a smell of rotten eggs due to the increase in cystine. Genetics
Cystinuria is an autosomal recessive disease, which means that the defective gene responsible for the disease is located on an autosome, and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disease. The parents of an individual with an autosomal recessive disease both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disease. Although signs and symptoms are rare, there are some directly and indirectly associated with cystinuria. These sign and symptoms consist of 1) hematuria- blood in the urine, 2) flank pain – pain in the side due to kidney pain, 3) renal colic – intense, cramping pain due to stones in the urinary tract, 4) obstructive uropathy- urinary tract disease due to obstruction, and 5) urinary tract infections. Cause
Cystinuria is caused by mutations in the SLC3A1 and SLC7A9 genes. These defects prevent proper reabsorption of basic, or positively charged, amino acids: cystine, lysine, ornithine, arginine. Under normal circumstances, this protein allows certain amino acids, including cystine, to be reabsorbed into the blood from the filtered fluid that will become urine. Mutations in either of these genes disrupt the ability of this transporter protein to reabsorb these amino acids, allowing them to become concentrated in the urine. | 0-1
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Chloroform, or trichloromethane, is an organic compound with formula CHCl3 and is a common organic solvent. It is a colorless, strong-smelling, dense liquid produced on a large scale as a precursor to PTFE. It is also a precursor to various refrigerants. It is one of the four chloromethanes and a trihalomethane. It is a powerful anesthetic, euphoriant, anxiolytic, and sedative when inhaled or ingested. Structure
The molecule adopts a tetrahedral molecular geometry with C3v symmetry. Natural occurrence
The total global flux of chloroform through the environment is approximately 660000 tonnes per year, and about 90% of emissions are natural in origin. Many kinds of seaweed produce chloroform, and fungi are believed to produce chloroform in soil. Abiotic processes are also believed to contribute to natural chloroform productions in soils although the mechanism is still unclear.Chloroform volatilizes readily from soil and surface water and undergoes degradation in air to produce phosgene, dichloromethane, formyl chloride, carbon monoxide, carbon dioxide, and hydrogen chloride. Its half-life in air ranges from 55 to 620 days. Biodegradation in water and soil is slow. Chloroform does not significantly bioaccumulate in aquatic organisms. History
Chloroform was synthesized independently by several investigators circa 1831:
Moldenhawer, a German pharmacist from Frankfurt an der Oder, appears to have produced chloroform in 1830 by mixing chlorinated lime with ethanol; he mistook it for Chloräther (chloric ether, 1,2-dichloroethane), however. | losing consciousness instantaneously, using chloroform. Safety
Exposure
Chloroform is known to form as a by-product of water chlorination along with a range of other disinfection by-products and as such is commonly present in municipal tap water and swimming pools. Reported ranges vary considerably but are generally below the current health standard for total trihalomethanes of 100μg/L. Nonetheless, the presence of chloroform in drinking water at any concentration is considered controversial by some.Historically, chloroform exposure may well have been higher due to its common use as an anesthetic, as an ingredient in cough syrups, and as a constituent of tobacco smoke where DDT had previously been used as a fumigant. Pharmacology
It is well absorbed, metabolized, and eliminated rapidly by mammals after oral, inhalation, or dermal exposure. Accidental splashing into the eyes has caused irritation. Prolonged dermal exposure can result in the development of sores as a result of defatting. Elimination is primarily through the lungs in the form of chloroform and carbon dioxide; less than 1% is excreted in the urine.Chloroform is metabolized in the liver by the cytochrome P-450 enzymes, by oxidation to chloromethanol and by reduction to the dichloromethyl free radical. Other metabolites of chloroform include hydrochloric acid and digluathionyl dithiocarbonate, with carbon dioxide as the predominant end product of metabolism.Like most other general anesthetics and sedative-hypnotic drugs, chloroform is a positive allosteric modulator for the GABAA receptor. Chloroform causes depression of the central nervous system (CNS), ultimately producing deep coma and respiratory center depression. When ingested, chloroform caused symptoms similar to those seen following inhalation. | 11
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Axicabtagene ciloleucel, sold under the brand name Yescarta, is a medication used for the treatment for large B-cell lymphoma that has failed conventional treatment. T cells are removed from a person with lymphoma and genetically engineered to produce a specific T-cell receptor. The resulting chimeric antigen receptor T cells (CAR-Ts) that react to the cancer are then given back to the person to populate the bone marrow. Axicabtagene treatment carries a risk for cytokine release syndrome (CRS) and neurological toxicities.Due to CD19 being a pan-B cell marker, the T-cells that are engineered to target CD19 receptors on the cancerous B cells also influence normal B cells, except some plasma cells. Side effects
Because treatment with axicabtagene carries a risk of cytokine release syndrome and neurological toxicities, the FDA has mandated that hospitals be certified for its use prior to treatment of any patients. History
It was developed by California-based Kite Pharma.Axicabtagene ciloleucel was awarded U.S. Food and Drug Administration (FDA) breakthrough therapy designation on 18 October 2017, for diffuse large B-cell lymphoma, transformed follicular lymphoma, and primary mediastinal B-cell lymphoma. It also received priority review and orphan drug designation.Based on the ZUMA-1 trial, Kite submitted a biologics license application for axicabtagene in March 2017, for the treatment of non-Hodgkin lymphoma.The FDA granted approval on 18 October 2017, for the second-line treatment of diffuse large B-cell lymphoma.On 1 April 2022, the FDA approved axicabtagene ciloleucel for adults with large B-cell lymphoma (LBCL) that is refractory to first-line chemoimmunotherapy or relapses within twelve months of first-line chemoimmunotherapy. | It is not indicated for the treatment of patients with primary central nervous system lymphoma.Approval was based on ZUMA-7, a randomized, open-label, multicenter trial in adults with primary refractory LBCL or relapse within twelve months following completion of first-line therapy. Participants had not yet received treatment for relapsed or refractory lymphoma and were potential candidates for autologous hematopoietic stem cell transplantation (HSCT). A total of 359 participants were randomized 1:1 to receive a single infusion of axicabtagene ciloleucel following fludarabine and cyclophosphamide lymphodepleting chemotherapy or to receive second-line standard therapy, consisting of two or three cycles of chemoimmunotherapy followed by high-dose therapy and autologous HSCT in participants who attained complete remission or partial remission. References
External links
"Axicabtagene ciloleucel". Drug Information Portal. U.S. National Library of Medicine. "Axicabtagene Ciloleucel". National Cancer Institute. 20 October 2017. "Axicabtagene Ciloleucel". NCI Drug Dictionary. National Cancer Institute. | 11
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Epidemiology
As of 2012, the rate of hyphemas in the United States are about 20 cases per 100,000 people annually. The majority of people with a traumatic hyphema are children and young adults. 60% of traumatic hyphemas are sports-related, and there are more cases in males compared to females. See also
Hypopyon
2-D from Gorillaz
Uveitis–Glaucoma–Hyphema syndrome
References
External links
Hyphema - Handbook of Ocular Disease Management | Ventricular flutter is an arrhythmia, more specifically a tachycardia affecting the ventricles with a rate over 250-350 beats/min, and one of the most indiscernible. It is characterized on the ECG by a sinusoidal waveform without clear definition of the QRS and T waves. It has been considered as a possible transition stage between ventricular tachycardia and fibrillation, and is a critically unstable arrhythmia that can result in sudden cardiac death.It can occur in infancy, youth, or as an adult. It can be induced by programmed electrical stimulation. References
External links
http://www.medscape.com/viewarticle/409172_3 | 0-1
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Although nausea and vomiting have been reported to be the most common side effects of EMP, gynecomastia (male breast development) has been found to occur in as many as 83% of men treated with EMP, and the incidence of erectile dysfunction is possibly similar to or slightly less than the risk of gynecomastia. As a rule, feminization, a gynoid fat distribution, demasculinization, and impotence are said to occur in virtually or nearly 100% of men treated with high-dose estrogen therapy. Decreased sexual activity has also been reported in men treated with EMP. These side effects are due to high estrogen levels and low testosterone levels. Prophylactic irradiation of the breasts can be used to decrease the incidence and severity of gynecomastia with estrogens.Severe adverse effects of EMP are thromboembolic and cardiovascular complications including pulmonary embolism, deep vein thrombosis, stroke, thrombophlebitis, coronary artery disease (ischemic heart disease; e.g., myocardial infarction), thrombophlebitis, and congestive heart failure with fluid retention. EMP produces cardiovascular toxicity similarly to diethylstilbestrol, but to a lesser extent in comparison at low doses (e.g., 280 mg/day oral EMP vs. 1 mg/day oral diethylstilbestrol). The prostate cancer disease state also increases the risk of thromboembolism, and combination with docetaxel may exacerbate the risk of thromboembolism as well. Meta-analyses of clinical trials have found that the overall risk of thromboembolism with EMP is 4 to 7%, relative to 0.4% for chemotherapy regimens without EMP. Thromboembolism is the major toxicity-related cause of discontinuation of EMP. | This is especially true in Western countries today. As a result, and also due to the scarce side effects of gonadotropin-releasing hormone modulators (GnRH modulators) like leuprorelin, EMP was almost abandoned. However, encouraging clinical research findings resulted in renewed interest of EMP for the treatment of prostate cancer.EMP has been used at doses of 140 to 1,400 mg/day orally in the treatment of prostate cancer. However, oral EMP is most commonly used at a dose of 560 to 640 mg/day (280–320 mg twice daily). The recommended dosage of oral EMP in the Food and Drug Administration (FDA) label for Emcyt is 14 mg per kg of body weight (i.e., one 140 mg oral capsule for each 10 kg or 22 lbs of body weight) given in 3 or 4 divided doses per day. The label states that most patients in studies of oral EMP in the United States have received 10 to 16 mg per kg per day. This would be about 900 to 1,440 mg/day for a 90-kg or 200-lb man. Lower doses of oral EMP, such as 280 mg/day, have been found to have comparable effectiveness as higher doses but with improved tolerability and reduced toxicity. Doses of 140 mg/day have been described as a very low dosage. EMP has been used at doses of 240 to 450 mg/day intravenously.EMP and other estrogens such as polyestradiol phosphate and ethinylestradiol are far less costly than newer therapies such as GnRH modulators, abiraterone acetate, and enzalutamide. | 11
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Fever
poor appetite
anterior fontanelle bulging
seizures
jitteriness
dyspnea
irritability
anorexia
vomiting
diarrhea
abdominal distention (increase in abdominal size)
neck rigidity
cyanosis
jaundice
sunset eyes (downward gaze of the eyes)
abnormal body temperature (hypo-or hyperthermia)
change of activity (lethargy or irritability)These symptoms are unspecific and may point to many different conditions. Complications
Neuroimaging (X-ray imaging of the brain) is recommended to detect the complications of meningitis. Complications should be suspected when the clinical course is characterized by shock, respiratory failure, focal neurological deficits, a positive cerebrospinal fluid culture after 48 to 72 hours of appropriate antibiotic therapy, or infection with certain organisms, such as Citrobacter koseri and Cronobacter sakazakii for example. Ultrasounds are useful for early imaging to determine ventricular size and hemorrhaging. CT scans later in the therapy should be used to dictate prolonged treatment.If intracranial abscesses (collection of pus in the brain) are found, treatment consisting of a combination of surgical drainage of the abscess and antimicrobial therapy for 4 to 6 weeks is recommended. More imaging should be completed after the end of antibiotic treatment because abscesses have been found after weeks from start of treatment.Relapses have also occurred after appropriate treatment when infected by Gram-negative enteric bacilli. Hearing Loss
Meningitis is one of the leading causes of acquired deafness. Nearly 8% of those with Meningitis will have a permanent sensorineural hearing loss. The longer meningitis is left untreated, the greater the risk of seizures and permanent neurological damage such as hearing loss, memory difficulty, learning disabilities, brain damage, gait problems, kidney failure, shock, and even death. | For higher age groups the benefit to risk ratio increased.Also on 7 April 2021, an interim statement from the WHO said its advisory body, GACVS, found any "causal relationship" between the rare blood clot cases and AZD1222 to be "plausible but is not confirmed".On 20 April 2021, the safety committee of the EMA (PRAC) found a "possible link to very rare cases of unusual blood clots with low blood platelets" for the Johnson & Johnson Janssen vaccine; and required that these rare events, similar to those noted for AZD1222, should be listed as a very rare side effect. The EMA states the overall risk-benefit for the Janssen vaccine remains positive.On 16 December 2021, the US Centers for Disease Control and Prevention (CDC) recommended the Moderna and Pfizer-BioNTech vaccines should be preferred over the Janssen vaccine, following growing concerns about rare blood clots. Janssen should still be offered to people who specifically request it. History
Organizations
Global vaccine safety comes under the remit of the World Health Organization (WHO), and in particular its Global Advisory Committee on Vaccine Safety (GAVCS). Other drug regulatory agencies significantly involved include:
European Medicines Agency (EMA), the regional regulatory authority for the EU. Medicines and Healthcare products Regulatory Agency (MHRA), the medical authority for the United Kingdom. Paul Ehrlich Institute (PEI), a German federal agency supervised by the Federal Ministry of Health with expertise in vaccines and biomedicines. It is a WHO collaborating centre. | 0-1
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Further countering the monoamine hypothesis is the fact that rats with lesions of the dorsal raphe are not more depressive than controls, the finding of increased jugular 5-HIAA in people who are depressed that normalized with selective serotonin reuptake inhibitor (SSRI) treatment, and the preference for carbohydrates in people who are depressed. Already limited, the monoamine hypothesis has been further oversimplified when presented to the general public. A 2022 review found no consistent evidence supporting the serotonin hypothesis, linking serotonin levels and depression.Immune system abnormalities have been observed, including increased levels of cytokines involved in generating sickness behavior (which shares overlap with depression). The effectiveness of nonsteroidal anti-inflammatory drugs (NSAIDs) and cytokine inhibitors in treating depression, and normalization of cytokine levels after successful treatment further suggest immune system abnormalities in depression.HPA-axis abnormalities have been suggested in depression given the association of CRHR1 with depression and the increased frequency of dexamethasone test non-suppression in people who are depressed. However, this abnormality is not adequate as a diagnosis tool, because its sensitivity is only 44%. These stress-related abnormalities are thought to be the cause of hippocampal volume reductions seen in people who are depressed. Furthermore, a meta-analysis yielded decreased dexamethasone suppression, and increased response to psychological stressors. Further abnormal results have been obscured with the cortisol awakening response, with increased response being associated with depression.Theories unifying neuroimaging findings have been proposed. The first model proposed is the limbic-cortical model, which involves hyperactivity of the ventral paralimbic regions and hypoactivity of frontal regulatory regions in emotional processing. | TMS was approved by the FDA for treatment-resistant major depressive disorder (trMDD) in 2008 and as of 2014 evidence supports that it is probably effective. The American Psychiatric Association, the Canadian Network for Mood and Anxiety Disorders, and the Royal Australia and New Zealand College of Psychiatrists have endorsed TMS for trMDD. Transcranial direct current stimulation (tDCS) is another noninvasive method used to stimulate small regions of the brain with a weak electric current. Several meta-analyses have concluded that active tDCS was useful for treating depression.There is a small amount of evidence that sleep deprivation may improve depressive symptoms in some individuals, with the effects usually showing up within a day. This effect is usually temporary. Besides sleepiness, this method can cause a side effect of mania or hypomania. There is insufficient evidence for Reiki and dance movement therapy in depression. Cannabis is specifically not recommended as a treatment. Prognosis
Studies have shown that 80% of those with a first major depressive episode will have at least one more during their life, with a lifetime average of four episodes. Other general population studies indicate that around half those who have an episode recover (whether treated or not) and remain well, while the other half will have at least one more, and around 15% of those experience chronic recurrence. Studies recruiting from selective inpatient sources suggest lower recovery and higher chronicity, while studies of mostly outpatients show that nearly all recover, with a median episode duration of 11 months. | 11
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These drugs include the typical antipsychotics: phenothiazines such as chlorpromazine (Thorazine), and butyrophenones such as haloperidol (Haldol); atypical antipsychotics such as risperidone (Risperdal) and paliperidone (Invega); gastroprokinetic drugs used to treat gastro-esophageal reflux and medication-induced nausea (such as that from chemotherapy): metoclopramide (Reglan) and domperidone; less often, alpha-methyldopa and reserpine, used to control hypertension; and TRH. The use of estrogen-containing oral contraceptives are also known to increase prolactin levels when taken in high doses >35 μg. The sleep drug ramelteon (Rozerem) also increases the risk of hyperprolactinaemia. Particularly, the dopamine antagonists metoclopramide and domperidone are both powerful prolactin stimulators and have been used to stimulate breast milk secretion for decades. However, since prolactin is antagonized by dopamine and the body depends on the two being in balance, the risk of prolactin stimulation is generally present with all drugs that deplete dopamine, either directly or as a rebound effect. Specific diseases
Prolactinoma or other tumors arising in or near the pituitary — such as those that cause acromegaly may block the flow of dopamine from the brain to the prolactin-secreting cells, likewise, division of the pituitary stalk or hypothalamic disease. Other causes include chronic kidney failure, hypothyroidism, bronchogenic carcinoma and sarcoidosis. Some women with polycystic ovary syndrome may have mildly-elevated prolactin levels. | Dihydropteridine reductase deficiency (DHPRD) is a genetic disorder affecting the tetrahydrobiopterin (BH4) synthesis pathway, inherited in the autosomal recessive pattern. It is one of the six known disorders causing tetrahydrobiopterin deficiency, and occurs in patients with mutations of the QDPR gene. The disease presents with such symptoms as elevated levels of phenylalanine (hyperphenylalaninemia), microcephaly, hypotonus, mental retardation and epileptic seizures. Diagnostics
Besides the traditional analysis of symptoms and investigation of phenylalanine concentrations, patients suspected for DHPRD undergo the assessment of enzymatic activity using the dried blood spot method - this permits to distinguish DHPR deficiency from the other forms of BH4 deficiency. Treatment
Patients are prescribed a phenylalanine-reduced diet, with regular monitoring of phenylalanine levels in the blood. Besides the diet, a patient may be prescribed sapropterin, a synthetic analogue of tetrahydrobiopterin. In order to restore dopamine levels in the central nervous system, patients are given L-dopa in conjunction with an inhibitor of aromatic amino acid decarboxylase that acts outside the nervous system, so as to promote the transformation of L-dopa into dopamine inside the central nervous system, and thus to improve the efficiency of the treatment. Since the insufficient levels of BH4 inhibit the transformation of tryptophan into 5-hydroxytryptophan in a reaction in which BH4 serves as a cofactor of the enzyme tryptophane hydroxylase 2, patients suffer from a lack of serotonin in their CNS. In order to correct this deficiency, they are given 5-hydroxytryptophan. In patients with DHPR deficiency, a pronounced lack of 5-methyltetrahydrofolate (5-MTHF) is observed in the central nervous system. | 0-1
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Gynecologists often see it as a gynecological problem, with the ovaries being the primary organ affected. However, recent insights show a multisystem disorder, with the primary problem lying in hormonal regulation in the hypothalamus, with the involvement of many organs. The term PCOS is used due to the fact that there is a wide spectrum of symptoms possible. It is common to have polycystic ovaries without having PCOS; approximately 20% of European women have polcystic ovaries, but most of those women do not have PCOS. Environment
PCOS may be related to or worsened by exposures during the prenatal period, epigenetic factors, environmental impacts (especially industrial endocrine disruptors, such as bisphenol A and certain drugs) and the increasing rates of obesity.Endocrine disruptors are defined as chemicals that can interfere with the endocrine system by mimicking hormones such as estrogen. However, additional research is needed to assess the role that endocrine disruptors may play in disrupting reproductive health in women and possibly triggering or exacerbating PCOS and its related symptoms. | Patisiran, sold under the brand name Onpattro, is a medication used for the treatment of polyneuropathy in people with hereditary transthyretin-mediated amyloidosis, a fatal rare disease that is estimated to affect 50,000 people worldwide.It is the first small interfering RNA-based drug approved by the U.S. Food and Drug Administration (FDA) and the first drug approved by the FDA to treat this condition. It is a gene silencing drug that interferes with the production of an abnormal form of transthyretin. Patisiran utilizes a novel approach to target and reduce production of the TTR protein in the liver via the RNAi pathway.Patisiran was developed and is marketed by Alnylam. The FDA considers it to be a first-in-class medication. History
Patisiran was granted orphan drug status, fast track designation, priority review and breakthrough therapy designation due to its novel mechanism and the rarity of the condition it treats. It was approved for medical use in the United States and in the European Union in August 2018. The per-patient cost is between US$451,430 and US$677,145 per year, depending on the number of vials needed. Formulation
The siRNA active component of Patisiran is formulated into lipid nanoparticles, which protect the RNA and facilitate its delivery to target tissues. The lipid nanoparticle formulation includes buffer components, as well as the lipid components DLin-MC3-DMA, Distearoylphosphatidylcholine, cholesterol, and the PEGylated lipid DMG-PEG 2000. Society and culture
Economics
As of 2020, there were 1050 people globally receiving patisiran, generating $65.5M in net-revenues for Alnylam Pharmaceuticals. References
External links
"Patisiran". Drug Information Portal. U.S. National Library of Medicine. | 0-1
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The condition is named after surgeon Norman Barrett (1903–1979) even though the condition was originally described by Philip Rowland Allison in 1946. Signs and symptoms
The change from normal to premalignant cells indicate Barretts esophagus does not cause any particular symptoms. Barretts esophagus, however, is associated with these symptoms:
frequent and longstanding heartburn
trouble swallowing (dysphagia)
vomiting blood (hematemesis)
pain under the sternum where the esophagus meets the stomach
pain when swallowing (odynophagia), which can lead to unintentional weight lossThe risk of developing Barretts esophagus is increased by central obesity (vs. peripheral obesity). The exact mechanism is unclear. The difference in distribution of fat among men (more central) and women (more peripheral) may explain the increased risk in males. Pathophysiology
Barretts esophagus occurs due to chronic inflammation. The principal cause of chronic inflammation is gastroesophageal reflux disease, GERD (UK: GORD). In this disease, acidic stomach, bile, and small intestine and pancreatic contents cause damage to the cells of the lower esophagus. In turn, this provokes an advantage for cells more resistant to these noxious stimuli in particular HOXA13-expressing stem cells that are characterised by distal (intestinal) characteristics and outcompete the normal squamous cells.This mechanism also explains the selection of HER2/neu (also called ERBB2) and the overexpressing (lineage-addicted) cancer cells during the process of carcinogenesis, and the efficacy of targeted therapy against the Her-2 receptor with trastuzumab (Herceptin) in the treatment of adenocarcinomas at the gastroesophageal junction. Researchers are unable to predict who with heartburn will develop Barretts esophagus. | Coarse facial features or coarse facies describes a constellation of facial features that are present in many inborn errors of metabolism. Features include:
large, bulging head
prominent scalp veins
"saddle-like, flat bridged nose with broad, fleshy tip"
large lips and tongue
small, widely spaced and/or malformed teeth
hypertrophic alveolar ridges and/or gumsHeads tend to be longer than normal from front to back, with a bulging forehead. This is because of the earlier than normal or premature fusion of skull bones in an affected individual. Causes
Several conditions are associated with coarse facial features. Acromegaly
Alpha-mannosidosis type II
Aspartylglycosaminuria
Battaglia Neri syndrome
Borjeson Syndrome
Chromosome 6q deletion syndrome
Coarse face - hypotonia - constipation
Congenital hypothyroidism
Dandy-Walker malformation (with mental retardation basal ganglia disease and seizures)
Dyggve-Melchior-Clausen Syndrome
Fucosidosis type 1
Fucosidosis type II
Gangliosidosis generalized GM1 (type 1)
Gangliosidosis GM1 (type 3)
GM1 gangliosidosis
Goldberg syndrome
Hyde-Forster-Mccarthy-Berry syndrome
Hyper IgE
Hypomelanosis of Ito
I cell disease
Immunodeficiency due to defect in MAPBP-interacting protein
Infantile sialic acid storage disorder
Job syndrome
Mannosidosis (alpha B lysosomal)
McCune-Albright Syndrome
Mental retardation (X-linked - epilepsy - progressive joint contractures - typical face)
Mental retardation (X-linked Raynaud type)
Mieschers syndrome
Morquio syndrome
Morquio syndrome type A
Morquio syndrome type B
MPS 3 C
MPS 3 D
Mucolipidosis III
Mucopolysaccharidosis type 2 Hunter syndrome- mild form
Mucopolysaccharidosis type 2 Hunter syndrome- severe form
Mucopolysaccharidosis type 3
Mucopolysaccharidosis type 6
Mucopolysaccharidosis type 7 Sly syndrome
Mucopolysaccharidosis type I Hurler syndrome
Mucopolysaccharidosis type I Hurler/Scheie syndrome
Mucopolysaccharidosis type I Scheie syndrome
Multiple endocrine abnormalities - adenylyl cyclase dysfunction
Multiple endocrine neoplasia type 2b
Neuraminidase deficiency (type II juvenile form)
Nodulosis-arthropathy-osteolysis syndrome
Nonkeratan-sulfate-excreting Morquio syndrome
Pituitary tumors (adult)
Sialidosis type II (congenital)
Sialidosis type II (infantile)
Sialuria syndrome
Simpson-Golabi-Behmel syndrome
Simpson-Golabi-Behmel syndrome - type 1 (SGBS1)
Skeletal dysplasia - coarse facies - mental retardation
Spondyloepimetaphyseal dysplasia (genevieve type)
Sulfatidosis juvenile (Austin type)
Winchester syndrome
See also
Facies (medical)
References
External links
https://web.archive.org/web/20090106211640/http://www.mps1disease.com/patient/about/mps_pt_symptom_coarse_facial_features.asp | 0-1
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Oral and maxillofacial pathology refers to the diseases of the mouth ("oral cavity" or "stoma"), jaws ("maxillae" or "gnath") and related structures such as salivary glands, temporomandibular joints, facial muscles and perioral skin (the skin around the mouth). The mouth is an important organ with many different functions. It is also prone to a variety of medical and dental disorders.The specialty oral and maxillofacial pathology is concerned with diagnosis and study of the causes and effects of diseases affecting the oral and maxillofacial region. It is sometimes considered to be a specialty of dentistry and pathology. Sometimes the term head and neck pathology is used instead, which may indicate that the pathologist deals with otorhinolaryngologic disorders (i.e. ear, nose and throat) in addition to maxillofacial disorders. In this role there is some overlap between the expertise of head and neck pathologists and that of endocrine pathologists. Diagnosis
The key to any diagnosis is thorough medical, dental, social and psychological history as well as assessing certain lifestyle risk factors that may be involved in disease processes. This is followed by a thorough clinical investigation including extra-oral and intra-oral hard and soft tissues.It is sometimes the case that a diagnosis and treatment regime are possible to determine from history and examination, however it is good practice to compile a list of differential diagnoses. | Bacterial toxins and the bodys natural defenses start to break down the bone and connective tissues. The tooth may eventually become loose and have to be removed. Scarlet fever is caused by a particular streptococci species, Streptococci Pyogenes, and is classified be a severe form of bacterial sore throat. The condition involves the release of pyrogenic and erythrogenic endotoxins from the immune system. It starts as tonsilitis and pharyngitis before involving the soft palate and the tongue. It usually occurs in children where a fever occurs and an erythematous rash develops on the face and spreads to most part of the body. If not treated, late stages of this condition may include a furred, raw, red tongue. Treatment options include penicillin and the prognosis is generally excellent.Viral
Herpes simplex (infection with herpes simplex virus, or HSV) is very common in the mouth and lips. This virus can cause blisters and sores around the mouth (herpetic gingivostomatitis) and lips (herpes labialis). HSV infections tend to recur periodically. Although many people get infected with the virus, only 10% actually develop the sores. The sores may last anywhere from 3–10 days and are very infectious. Some people have recurrences either in the same location or at a nearby site. Unless the individual has an impaired immune system, e.g., owing to HIV or cancer-related immune suppression, recurrent infections tend to be mild in nature and may be brought on by stress, sun, menstrual periods, trauma or physical stress. Mumps of the salivary glands is a viral infection of the parotid glands. | 11
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Lastly, Isatuximab reveals direct killing activity when a larger increase in apoptosis is detected in CD38 expressing cancer cells. Furthermore, isatuximab demonstrated a dose dependent inhibition of CD38 enzymatic activity. However, daratumumab with the same experimental conditions shows a more limited inhibition without a dose response. Reactions
Isatuximab binds uniquely to an epitope on the CD38 receptor and is the only CD38 antibody which can start apoptosis directly. Isatuximab binds to a different CD38 epitope amino-acid sequence than does the anti-CD38 monoclonal antibody daratumumab. The binding with the CD38 receptor is mainly via the gamma heavy chains and are more potent than other CD38 antibodies such as daratumumab which can inhibit the enzymatic activity of CD38. Moreover, isatuximab inhibits the hydrolase activity of CD38.The antibodies show signs of improving antitumor immunity by eliminating regulatory T cells, B cells and myeloid-derived suppressor cells. The difference in binding between isatuximab and daratumumab is in the recognition of the different amino acid groups. Isatuximab identifies 23 amino acids of CD38 to the contrary with daratumumab who has 27. The residue of Glu233 has a flexible sidechain and faces the N-terminal of Asp1 residue in the isatuximab light chain. The latter light chain of isatuximab is also flexible which makes the interaction between CD38/Glu233 and the Asp1 weaker than the other interactions between CD38 and isatuximab. The caspase-dependent apoptotic pathway and the lysosomal mediated cell death pathway in MM cells is induced by isatuximab. The MM cell death follows the downstream reactions of the lysosomal activation. | Instead, there are usually uniformly dilated acini with thin alveolar septa and little or no interstitial fibrosis. It develops most commonly in the first 4 weeks after birth. Diagnosis
Earlier criteria
The classic diagnosis of BPD may be assigned at 28 days of life if the following criteria are met:
Positive pressure ventilation during the first 2 weeks of life for a minimum of 3 days. Clinical signs of abnormal respiratory function. Requirements for supplemental oxygen for longer than 28 days of age to maintain PaO2 above 50 mm Hg. Chest radiograph with diffuse abnormal findings characteristic of BPD. | 0-1
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Finally, influential groups can pressure, and sway the interests of the government to their favor. The government and its regulators can become vested in the benefits of the ecotourism industry which they are supposed to regulate, causing restrictive environmental regulations and enforcement to become more lenient. Management of ecotourism sites by private ecotourism companies offers an alternative to the cost of regulation and deficiency of government agencies. It is believed that these companies have a self-interest in limited environmental degradation because tourists will pay more for pristine environments, which translates to higher profit. However, theory indicates that this practice is not economically feasible and will fail to manage the environment. The model of monopolistic competition states that distinctiveness will entail profits, but profits will promote imitation. A company that protects its ecotourism sites is able to charge a premium for the novel experience and pristine environment. But when other companies view the success of this approach, they also enter the market with similar practices, increasing competition and reducing demand. Eventually, the demand will be reduced until the economic profit is zero. A cost-benefit analysis shows that the company bears the cost of environmental protection without receiving the gains. Without economic incentive, the whole premise of self-interest through environmental protection is quashed; instead, ecotourism companies will minimize environment related expenses and maximize tourism demand.The tragedy of the commons offers another model for economic unsustainability from environmental protection, in ecotourism sites utilized by many companies. | In 2008 the Global Sustainable Tourism Council Criteria was launched at the IUCN World Conservation Congress. The Criteria, managed by the Global Sustainable Tourism Council, created a global standard for sustainable travel and tourism and includes criteria and performance indicators for destinations, tour operators and hotels. The GSTC provides accreditation through a third-party to Certification Bodies to legitimize claims of sustainability.Environmental impact assessments could also be used as a form of accreditation. Feasibility is evaluated from a scientific basis, and recommendations could be made to optimally plan infrastructure, set tourist capacity, and manage the ecology. This form of accreditation is more sensitive to site-specific conditions. Some countries have their own certification programs for ecotourism. Costa Rica, for example, runs the GSTC-Recognized Certification of Sustainable Tourism (CST) program, which is intended to balance the effect that business has on the local environment. The CST program focuses on a companys interaction with natural and cultural resources, the improvement of quality of life within local communities, and the economic contribution to other programs of national development. CST uses a rating system that categorizes a company based upon how sustainable its operations are. CST evaluates the interaction between the company and the surrounding habitat; the management policies and operation systems within the company; how the company encourages its clients to become an active contributor towards sustainable policies; and the interaction between the company and local communities/the overall population. Based upon these criteria, the company is evaluated for the strength of its sustainability. | 11
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In February 2016, Immunomedics announced that sacituzumab govitecan had received an FDA breakthrough therapy designation (a classification designed to expedite the development and review of drugs that are intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition) for the treatment of people with triple-negative breast cancer who have failed at least two other prior therapies for metastatic disease. History
Sacituzumab govitecan was added to the proposed International nonproprietary name (INN) list in 2015, and to the recommended list in 2016.Sacituzumab govitecan-hziy was approved for medical use in the United States in April 2020.Sacituzumab govitecan-hziy was approved based on the results of IMMU-132-01, a multicenter, single-arm clinical trial (NCT01631552) of 108 participants with metastatic triple-negative breast cancer who had received at least two prior treatments for metastatic disease. Of the 108 participants involved within the study, 107 were female and 1 was male. Participants received sacituzumab govitecan-hziy at a dose of 10 milligrams per kilogram of body weight intravenously on days one and eight every 21 days. Treatment with sacituzumab govitecan-hziy was continued until disease progression or unacceptable toxicity. Tumor imaging was obtained every eight weeks. The efficacy of sacituzumab govitecan-hziy was based on the overall response rate (ORR) – which reflects the percentage of participants that had a certain amount of tumor shrinkage. The ORR was 33.3% (95% confidence interval [CI], 24.6 to 43.1). Additionally, with the 33.3% of study participants who achieved a response, 2.8% of participants experienced complete responses. | Clinical significance
Giant osteoclasts can occur in some diseases, including Pagets disease of bone and bisphosphonate toxicity. In cats, abnormal odontoclast activity can cause feline odontoclastic resorptive lesions, necessitating extraction of the affected teeth. History
Osteoclasts were discovered by Kolliker in 1873. See also
List of human cell types derived from the germ layers
References
External links
MedicineNet
Osteoclasts at the US National Library of Medicine Medical Subject Headings (MeSH)
The Life of Osteoclast
Random42: Animation by Random42 Scientific Communication on the role of osteoclasts in bone remodeling | 0-1
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Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. GISTs arise in the smooth muscle pacemaker interstitial cell of Cajal, or similar cells. They are defined as tumors whose behavior is driven by mutations in the KIT gene (85%), PDGFRA gene (10%), or BRAF kinase (rare). 95% of GISTs stain positively for KIT (CD117). Most (66%) occur in the stomach and gastric GISTs have a lower malignant potential than tumors found elsewhere in the GI tract. Classification
GIST was introduced as a diagnostic term in 1983.: 1060 Until the late 1990s, many non-epithelial tumors of the gastrointestinal tract were called "gastrointestinal stromal tumors". Histopathologists were unable to specifically distinguish among types we now know to be dissimilar molecularly. Subsequently, CD34, and later CD117 were identified as markers that could distinguish the various types. Additionally, in the absence of specific therapy, the diagnostic categorization had only a limited influence on prognosis and therapy. The understanding of GIST biology changed significantly with identification of the molecular basis of GIST,: 1065 particularly c-KIT. Historically, literature reviews prior to the molecular definition of GIST, and for a short time thereafter, asserted that 70-80% of GISTs were benign. The identification of a molecular basis for GIST led to the exclusion of many tumors that had been considered as GIST previously, and also the incorporation of a much larger number of tumors that had been labeled as other types of sarcomas and undifferentiated carcinomas. | Imatinib (Glivec/Gleevec), an orally administered drug initially marketed for chronic myelogenous leukemia based on bcr-abl inhibition, also inhibits both c-KIT tyrosine kinase mutations and PDGFRA mutations other than D842V, and is useful in treating GISTs in several situations. Imatinib has been used in selected neoadjuvant settings. : 23 In the adjuvant treatment setting, the majority of GIST tumors are cured by surgery, and do not need adjuvant therapy. An exception to this is where the anatomical position of the tumour means that surgery is technically difficult or complex. For example, rectal GIST often requires radical surgery to achieve complete resection, involving abdominoperineal resection and permanent stoma. In these situations, the use of neoadjuvant imatinib can significantly decrease both tumour size and mitotic activity, and permit less radical sphincter-preserving surgery.A substantial proportion of GIST tumors have a high risk of recurrence as estimated by a number of validated risk stratification schemes, and can be considered for adjuvant therapy. The selection criteria underpinning the decision for possible use of imatinib in these settings, including a risk assessment based on pathological factors such as tumor size, mitotic rate and location, can be used to predict the risk of recurrence in GIST patients. Tumors <2 cm with a mitotic rate of <5/50 HPF have been shown to have lower risk of recurrence than larger or more aggressive tumors. Following surgical resection of GISTs, adjuvant treatment with imatinib reduces the risk of disease recurrence in higher risk groups. | 11
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The biosynthetic precursors to riboflavin are ribulose 5-phosphate and guanosine triphosphate. The former is converted to L-3,4-dihydroxy-2-butanone-4-phosphate while the latter is transformed in a series of reactions that lead to 5-amino-6-(D-ribitylamino)uracil. These two compounds are then the substrates for the penultimate step in the pathway, catalysed by the enzyme lumazine synthase in reaction EC 2.5.1.78. In the final step of the biosynthesis, two molecules of 6,7-dimethyl-8-ribityllumazine are combined by the enzyme riboflavin synthase in a dismutation reaction. This generates one molecule of riboflavin and one of 5-amino-6-(D-ribitylamino) uracil. The latter is recycled to the previous reaction in the sequence. Conversions of riboflavin to the cofactors FMN and FAD are carried out by the enzymes riboflavin kinase and FAD synthetase acting sequentially. Industrial synthesis
The industrial-scale production of riboflavin uses various microorganisms, including filamentous fungi such as Ashbya gossypii, Candida famata and Candida flaveri, as well as the bacteria Corynebacterium ammoniagenes and Bacillus subtilis. B. subtilis that has been genetically modified to both increase the production of riboflavin and to introduce an antibiotic (ampicillin) resistance marker, is employed at a commercial scale to produce riboflavin for feed and food fortification. By 2012, over 4,000 tonnes per annum were produced by such fermentation processes.In the presence of high concentrations of hydrocarbons or aromatic compounds, some bacteria overproduce riboflavin, possibly as a protective mechanism. | Talimogene laherparepvec, sold under the brand name Imlygic, is a biopharmaceutical medication used to treat melanoma that cannot be operated on; it is injected directly into a subset of lesions which generates a systemic immune response against the recipients cancer. The final four year analysis from the pivotal phase 3 study upon which TVEC was approved by the FDA showed a 31.5% response rate with a 16.9% complete response (CR) rate. There was also a substantial and statistically significant survival benefit in patients with earlier metastatic disease (stages IIIb-IVM1a) and in patients who hadnt received prior systemic treatment for melanoma. The earlier stage group had a reduction in the risk of death of approximately 50% with one in four patients appearing to have met, or be close to be reaching, the medical definition of cure. Real world use of talimogene laherparepvec have shown response rates of up to 88.5% with CR rates of up to 61.5%.Around half of people treated with talimogene laherparepvec in clinical trials experienced fatigue and chills; around 40% had fever, around 35% had nausea, and around 30% had flu-like symptoms as well as pain at the injection site. The reactions were mild to moderate in severity; 2% of people had severe reactions and these were generally cellulitis.Talimogene laherparepvec is a genetically engineered herpes virus (an oncolytic herpes virus). Two genes were removed – one that shuts down an individual cells defenses, and another that helps the virus evade the immune system – and a gene for human GM-CSF was added. | 0-1
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Archived from the original on October 19, 2021. | Atovaquone, sold under the brand name Mepron, is a quinone antimicrobial medication for the prevention and treatment of Pneumocystis jirovecii pneumonia (PCP).Atovaquone is a chemical compound that belongs to the class of naphthoquinones. Atovaquone is a hydroxy-1,4-naphthoquinone, an analog of both ubiquinone and lawsone, with antipneumocystic activity. Medical uses
Atovaquone is a medication used to treat or prevent:
For pneumocystis pneumonia (PCP), it is used in mild cases, although it is not approved for treatment of severe cases. For toxoplasmosis, the medication has antiparasitic and therapeutic effects. For malaria, it is one of the two components (along with proguanil) in the drug Malarone. Malarone has fewer side effects and is more expensive than mefloquine. Resistance has been observed. For babesia, it is often used in conjunction with oral azithromycin.Trimethoprim/sulfamethoxazole (TMP-SMX, Bactrim) is generally considered first-line therapy for PCP (not to be confused with sulfadiazine and pyrimethamine, which is first line for toxoplasmosis). However, atovaquone may be used in patients who cannot tolerate, or are allergic to, sulfonamide medications such as TMP-SMX. In addition, atovaquone has the advantage of not causing myelosuppression, which is an important issue in patients who have undergone bone marrow transplantation. Atovaquone is given prophylactically to kidney transplant patients to prevent PCP in cases where Bactrim is contraindicated for the patient. Malaria
Atovaquone, as a combination preparation with proguanil, has been commercially available from GlaxoSmithKline since 2000 as Malarone for the treatment and prevention of malaria. Research
COVID-19
Preliminary research found that atovaquone could inhibit the replication of SARS-CoV-2 in vitro. | 0-1
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There are two subtypes of hydatidiform mole: complete hydatidiform mole, and partial hydatidiform mole. The four malignant tumours
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumour
Epithelioid trophoblastic tumourAll five closely related tumours develop in the placenta. All five tumours arise from trophoblast cells that form the outer layer of the blastocyst in the early development of the fetus. In a normal pregnancy, trophoblasts aid the implantation of the fertilised egg into the uterine wall. But in GTD, they develop into tumour cells. Cause
Two main risk factors increase the likelihood for the development of GTD: 1) The woman being under 20 years of age, or over 35 years of age, and 2) previous GTD. Although molar pregnancies affect women of all ages, women under 16 and over 45 years of age have an increased risk of developing a molar pregnancy. Being from Asia/of Asian ethnicity is an important risk factor.Hydatidiform moles are abnormal conceptions with excessive placental development. Conception takes place, but placental tissue grows very fast, rather than supporting the growth of a fetus.Complete hydatidiform moles have no fetal tissue and no maternal DNA, as a result of a maternal ovum with no functional DNA. Most commonly, a single spermatozoon duplicates and fertilises an empty ovum. Less commonly, two separate spermatozoa fertilise an empty ovum (dispermic fertilisation). Partial hydatidiform moles have a fetus or fetal cells. They are triploid in origin, containing one set of maternal haploid genes and two sets of paternal haploid genes. They almost always occur following dispermic fertilisation of a normal ovum. | 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. | 0-1
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An antibiotic may be prescribed by a physician to help prevent bacterial infection of the lesion area. In rare cases, surgical removal of the lesions can be done to help increase rate of healing, and help minimize risk of bacterial or fungal infection. Upon healing, no long term side effects have been reported. History
Paravaccinia virus was first characterized in by Edward Jenner in 1799 with the presence of lesions on humans, later described as Milkers nodule. Jenner associated the lesions found on human who had contact with infected cattle. Since first being characterized in cows, bovine papular stomatitis has been isolated in sheep, goats, and red deer creating new potential sources for human infection. Bolvine papular stomatitis has been reported in the United States of America, Great Britain, Brazil, Switzerland, and Japan
Disease in animals
Pseudocowpox is a worldwide disease of cattle. Symptoms include ring or horseshoe shaped scabs on the teats, which usually heal within six weeks. Lesions may also develop on the muzzles and in the mouths of nursing calves. Spread is by fomites, including hands, calves mouths, and milking machines. Lesions may also appear on the hands of milkers, a clinical presentation known as milkers nodule. This disease in humans is nearly identical to orf. == References == | Commonly used tests include a complete blood count (CBC), bone marrow examination, leukocyte telomere length test (e.g. Flow FISH), pulmonary function test, and genetic testing. Management
The mainstay of treatment in dyskeratosis congenita is hematopoietic stem cell transplantation, best outcome with sibling donor. Short term therapy in initial stages is with anabolic steroids [oxymetholone, danazol] or with erythropoietin-like hormones or with granulocyte-colony stimulating factor [filgrastim) all these therapies are directed to cope with effects of bone marrow failure which manifests as low red and white blood cell counts. These medications help to increase the blood components and make up for the deficiencies caused due to bone marrow failure. Dyskeratosis Congenita in regards to stem cell transplantation have to be very carefully treated with low intensity radiation/chemo to avoid potentially catastrophic effects of Host versus graft disease and toxicity to other organs affected by short telomeres which makes them very sensitive to any radiation especially the lungs, and liver. Prognosis
DC is associated with shorter life expectancy, but many live to at least age 60. Main cause of mortality in these patients are related to bone marrow failure. Nearly 80% of the patients of dyskeratosis congenita develop bone marrow failure. Research
Recent research has used induced pluripotent stem cells to study disease mechanisms in humans, and discovered that the reprogramming of somatic cells restores telomere elongation in dyskeratosis congenita (DKC) cells despite the genetic lesions that affect telomerase. The reprogrammed DKC cells were able to overcome a critical limitation in TERC levels and restored function (telomere maintenance and self-renewal). | 0-1
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Erythema toxicum neonatorum is a common, non-threatening rash in newborns. It appears in 4-70% of newborns within the first week of life, and it typically improves within 1–2 weeks. It only occurs during the newborn period, but may appear slightly later in premature babies. The rash has a variable appearance. It typically includes blotchy red spots, often with overlying firm, yellow-white bumps or pus-filled boils. There may be only a few or many lesions. The lesions can appear almost anywhere on the body, and individual lesions may appear and disappear within hours. There are no other symptoms associated with erythema toxicum neonatorum, and the rash does not have any long-term effects on the skin. Erythema toxicum neonatorum is not harmful and does not require any treatment. Epidemiology
The exact prevalence of erythema toxicum neonatorum is unknown, and studies estimate prevalence as low as 3.7 percent to as high as 72 percent. It is one of the most commonly diagnosed rashes in healthy babies. It is more common among infants born at higher gestational age and is rare among premature infants. Erythema toxicum neonatorum is more likely to develop in infants delivered vaginally. Higher birth weight is an additional risk factor. There may be a slightly increased risk in males, but this association is unclear. There are no known associations with race or ethnicity. Presentation
Erythema toxicum neonatorum usually appears during the first week of life, most often on day two. | This is part of a normal process in which bacteria from the environment start to grow on a babys skin. It is unknown whether the immune response that causes erythema toxicum neonatorum is helpful to the baby. Recent research indicates an association with Demodex mites infestation (demodicosis). Diagnosis
Health professionals can diagnose erythema toxicum neonatorum with a skin exam. Most cases of erythema toxicum neonatorum can be diagnosed without further testing. If more testing is needed to make a diagnosis, the contents of a lesion can be examined under a microscope. A health professional may make a small cut into a pus-filled lesion and collect a swab of pus for testing. Lesions caused by erythema toxicum neonatorum contain eosinophils and other immune cells. These cells can be seen under a microscope when a special stain is applied to the sample.Since the appearance of erythema toxicum neonatorum varies, it may be confused with other newborn rashes. Some newborn infections cause bumps or boils, which may look like erythema toxicum neonatorum. Bacterial infections, including Staphylococcus and Streptococcus infections, almost always cause additional symptoms. These symptoms may be severe, and they are usually not limited to rash. Bacterial rashes can be diagnosed by testing pus from a lesion along with a blood sample. Bacteria can be seen under a microscope with a special stain or may be found on a culture. Fungal infection with Candida may also cause a similar rash in newborns, but it usually causes additional symptoms like thrush. | 11
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Gingivostomatitis is a combination of gingivitis and stomatitis, or an inflammation of the oral mucosa and gingiva. Herpetic gingivostomatitis is often the initial presentation during the first ("primary") herpes simplex infection. It is of greater severity than herpes labialis (cold sores) which is often the subsequent presentations. Primary herpetic gingivostomatitis is the most common viral infection of the mouth.Primary herpetic gingivostomatitis (PHGS) represents the clinically apparent pattern of primary herpes simplex virus (HSV) infection, since the vast majority of other primary infections are symptomless. PHGS is caused predominantly by HSV-1 and affects mainly children. Prodromal symptoms, such as fever, anorexia, irritability, malaise and headache, may occur in advance of disease. The disease presents as numerous pin-head vesicles, which rupture rapidly to form painful irregular ulcerations covered by yellow–grey membranes. Sub-mandibular lymphadenitis, halitosis and refusal to drink are usual concomitant findings. Signs and symptoms
The symptoms can be mild or severe and may include:
Not able to chew or swallow
Sores on the inside of the cheeks or gums
Fever
General discomfort, uneasiness, or ill feeling
Very sore mouth with no desire to eat
Halitosis (bad breath)
Causes
Herpetic gingivostomatitis is an infection caused by the herpes simplex virus (HSV). The HSV is a double-stranded DNA virus categorised into two types; HSV-1 and HSV-2. HSV-1 is predominantly responsible for oral, facial and ocular infections whereas HSV-2 is responsible for most genital and cutaneous lower herpetic lesions. | nurseries and orphanages.Epidemiology: Those living in developing countries are at a higher risk of HSV-1 infection. It has been reported that around a 1/3rd of children living in developing countries are HSV-1 positive by 5 years old and 70-80% of the population are infected by the age of adolescence. In developed countries only 20% of children are infected at the age of 5 and there is no significant increase in disease prevalence until 20–40 years old where the percentage of infected individuals ranges from 40-60% Socio-economic status: Those with a lower income have a higher risk of HSV-1 infection at a younger age.Race: Studies have demonstrated that in the USA 35% of African Americans by the age of 5 have presented with the disease whereas only 18% of White Americans are affected. Pathophysiology
Herpetic gingivostomatitis originates from a primary infection of HSV-1. The series of events that take place during this infection include replication of the herpes simplex virus, cell lysis and finally, destruction of the mucosal tissue.HSV-1 can very easily enter and replicate within epidermal and dermal cells through skin or mucosal surfaces which have abrasions. This results in numerous small vesicles or blisters of up to 1-2mm on the oral mucosa, erosions on the lips, eventual hemorrhagic crusting and even ulceration, covered by a yellowish-grey pseudomembrane, surrounded by an erythematous halo.As the virus continues to replicate and incolulate in great amounts, it can enter autonomic or sensory ganglia, where it travels within axons to reach ganglionic nerve bodies. | 11
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Spectrum of susceptibility
Doxycycline has been used successfully to treat sexually transmitted, respiratory, and ophthalmic infections. Representative pathogenic genera include Chlamydia, Streptococcus, Ureaplasma, Mycoplasma, and others. The following represents MIC susceptibility data for a few medically significant microorganisms. Chlamydia psittaci: 0.03 μg/mL
Mycoplasma pneumoniae: 0.016 μg/mL—2 μg/mL
Streptococcus pneumoniae: 0.06 μg/mL—32 μg/mL
Sclerotherapy
Doxycycline is also used for sclerotherapy in slow-flow vascular malformations, namely venous and lymphatic malformations, as well as post-operative lymphoceles. Others
Subantimicrobial-dose doxycycline (SDD) is widely used as an adjunctive treatment to scaling and root planing for periodontitis. Significant differences were observed for all investigated clinical parameters of periodontitis in favor of the scaling and root planing + SDD group where SDD dosage regimens is 20 mg twice daily for three months in a meta-analysis published in 2011. Contraindications
Pregnancy and lactation
Doxycycline is categorized by the FDA as a class D drug in pregnancy. Doxycycline crosses into breastmilk. Other tetracycline antibiotics are contraindicated in pregnancy and up to eight years of age, due to the potential for disrupting bone and tooth development. They include a class warning about staining of teeth and decreased development of dental enamel in children exposed to tetracyclines in utero, during breastfeeding or during young childhood. However, the FDA has acknowledged that the actual risk of dental staining of primary teeth is undetermined for doxycycline specifically. | By comparison, the tetracycline antibiotic minocycline penetrates significantly better into the CSF and meninges.Doxycycline metabolism is negligible. It is actively excreted into the gut (in part via the gallbladder, in part directly from blood vessels), where some of it is inactivated by forming chelates. About 40% are eliminated via the kidneys, much less in people with end-stage kidney disease. The biological half-life is 18 to 22 hours (16±6 hours according to another source) in healthy people, slightly longer in those with end-stage kidney disease, and significantly longer in those with liver disease. Chemistry
Expired tetracyclines or tetracyclines allowed to stand at a pH less than 2 are reported to be nephrotoxic due to the formation of a degradation product, anhydro-4-epitetracycline causing Fanconi syndrome. In the case of doxycycline, the absence of a hydroxyl group in C-6 prevents the formation of the nephrotoxic compound. Nevertheless, tetracyclines and doxycycline itself have to be taken with caution in patients with kidney injury, as they can worsen azotemia due to catabolic effects. Chemical properties
Doxycycline, doxycycline monohydrate and doxycycline hyclate are yellow, crystalline powders with a bitter taste. | 11
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Anxiety disorders are a cluster of mental disorders characterized by significant and uncontrollable feelings of anxiety and fear such that a persons social, occupational, and personal function are significantly impaired. Anxiety may cause physical and cognitive symptoms, such as restlessness, irritability, easy fatiguability, difficulty concentrating, increased heart rate, chest pain, abdominal pain, and a variety of other symptoms that may vary based on the individual.In casual discourse, the words anxiety and fear are often used interchangeably. In clinical usage, they have distinct meanings: anxiety is defined as an unpleasant emotional state for which the cause is either not readily identified or perceived to be uncontrollable or unavoidable, whereas fear is an emotional and physiological response to a recognized external threat. The umbrella term anxiety disorder refers to a number of specific disorders that include fears (phobias) or anxiety symptoms. There are several types of anxiety disorders, including generalized anxiety disorder, specific phobia, social anxiety disorder, separation anxiety disorder, agoraphobia, panic disorder, and selective mutism. The individual disorder can be diagnosed using the specific and unique symptoms, triggering events, and timing. If a person is diagnosed with an anxiety disorder, a medical professional must have evaluated the person to ensure the anxiety cannot be attributed to another medical illness or mental disorder. It is possible for an individual to have more than one anxiety disorder during their life or at the same time and anxiety disorders are marked by a typical persistent course. | Juvenile hyaline fibromatosis (also known as "Fibromatosis hyalinica multiplex juvenilis," "Murray–Puretic–Drescher syndrome") is a very rare, autosomal recessive disease due to mutations in capillary morphogenesis protein-2 (CMG-2 gene). It occurs from early childhood to adulthood, and presents as slow-growing, pearly white or skin-colored dermal or subcutaneous papules or nodules on the face, scalp, and back, which may be confused clinically with neurofibromatosis. The World Health Organization, 2020, reclassified the papules and nodules that occur in juvenile hyaline firbromatosis as one of the specific benign types of tumors in the category of fibroblastic and myofibroblastic tumors. Presentation
This condition is characterised by abnormal growth of hyalinized fibrous tissue with cutaneous, mucosal, osteoarticular and systemic involvement. Clinical features include extreme pain at minimal handling in a newborn, gingival hypertrophy, subcutaneous nodules, painful joint stiffness and contractures, muscle weakness and hypotonia. Genetics
This condition is due to mutations in the anthrax toxin receptor-2 (ANTXR2) gene. This gene is also known as capillary morphogenesis protein-2. This gene is located on the long arm of chromosome 4 (4q21.21). Management
There is no presently known curative treatment for this condition.Management is supportive
Prognosis
This is very poor with a median age at death of 15 months. Epidemiology
84 cases have been reported as of 2018. See also
List of cutaneous conditions
References
== External links == | 0-1
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Children with the juvenile form are likely to die between the ages 5–15, while the lifespans of those with the adult form will probably not be affected. Epidemiology
Ashkenazi Jews have a high incidence of Tay–Sachs and other lipid storage diseases. In the United States, about 1 in 27 to 1 in 30 Ashkenazi Jews is a recessive carrier. The disease incidence is about 1 in every 3,500 newborn among Ashkenazi Jews. French Canadians and the Cajun community of Louisiana have an occurrence similar to the Ashkenazi Jews. Irish Americans have a 1 in 50 chance of being a carrier. In the general population, the incidence of carriers as heterozygotes is about 1 in 300. The incidence is approximately 1 in 320,000 newborns in the general population in the United States.Three general classes of theories have been proposed to explain the high frequency of Tay–Sachs carriers in the Ashkenazi Jewish population:
Heterozygote advantage. When applied to a particular allele, this theory posits that mutation carriers have a selective advantage, perhaps in a particular environment. Reproductive compensation. Parents who lose a child because of disease tend to "compensate" by having additional children following the loss. This phenomenon may maintain and possibly even increase the incidence of autosomal recessive disease. Founder effect. This hypothesis states that the high incidence of the 1278insTATC chromosomes is the result of an elevated allele frequency that existed by chance in an early founder population.Tay–Sachs disease was one of the first genetic disorders for which epidemiology was studied using molecular data. | The Juvenile Diabetes Research Foundation (JDRF), founded by parents of children with type 1 diabetes, is the worlds largest provider of charity-based funding for type 1 diabetes research. Other charities include the American Diabetes Association, Diabetes UK, Diabetes Research and Wellness Foundation, Diabetes Australia, the Canadian Diabetes Association. A number of approaches have been explored to understand causes and provide treatments for type 1. Prevention
Type 1 diabetes is not currently preventable. Several trials have attempted dietary interventions with the hope of reducing the autoimmunity that leads to type 1 diabetes. Trials that withheld cows milk or gave infants formula free of bovine insulin decreased the development of β-cell-targeted antibodies, but did not prevent the development of type 1 diabetes. Similarly, trials that gave high-risk individuals injected insulin, oral insulin, or nicotinamide did not prevent diabetes development.Other research has focused on treating high-risk individuals with immunosuppressive agents to prevent beta cell destruction. Large trials of cyclosporine treatment suggested that cyclosporine could improve insulin secretion in those recently diagnosed with type 1 diabetes; however, people who stopped taking cyclosporine rapidly stopped making insulin, and cyclosporines kidney toxicity and increased risk of cancer prevented people from using it long-term. Several other immunosuppressive agents – prednisone, azathioprine, anti-thymocyte globulin, mycophenolate, and antibodies against CD20 and IL2 receptor α – have been the subject of research, but none have provided lasting protection from development of type 1 diabetes. | 0-1
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Eletriptan, sold under the brand name Relpax and used in the form of eletriptan hydrobromide, is a second generation triptan medication intended for treatment of migraine headaches. It is used as an abortive medication, blocking a migraine attack which is already in progress. Eletriptan is marketed and manufactured by Pfizer Inc.
Approval and availability
Eletriptan was approved by the US Food and Drug Administration (FDA) on December 26, 2002, for the acute treatment of migraine with or without aura in adults. It is available only by prescription in the United States and Canada. It is not intended for the prophylactic therapy of migraine or for use in the management of hemiplegic or basilar migraine. It is available in 20 mg and 40 mg strengths. Eletriptan was covered by U.S. Patent no. 5545644 and U.S. Patent no. 6110940; both now expired. Mechanism of action
Eletriptan is believed to reduce swelling of the blood vessels surrounding the brain. This swelling is associated with the head pain of a migraine attack. Eletriptan blocks the release of substances from nerve endings that cause more pain and other symptoms like nausea, and sensitivity to light and sound. It is thought that these actions contribute to relief of symptoms by eletriptan. Eletriptan is a serotonin receptor agonist, specifically an agonist of certain 5-HT1 family receptors. Eletriptan binds with high affinity to the 5-HT[1B, 1D, 1F] receptors. It has a modest affinity to the 5-HT[1A, 1E, 2B, 7] receptors, and little to no affinity at the 5-HT[2A, 2C, 3, 4, 5A, 6] receptors. | History
Lumacaftor/ivacaftor was approved by the FDA in July 2015 under breakthrough therapy status and under a priority review. Previously approved for adults and pre-teens, approved on 8-7-18 for children age 2–5. Society and culture
As of March 2016 the combination drug cost $259,000 a year in the United States.In Denmark, it was estimated in August 2015 that if the drug were introduced, the cost would amount to 2 million Danish krones (approximately 270,000 euro) each year per person.The Dutch Minister of Health announced in October 2017 that the drug would not be admitted to the public health insurance package, making it impossible to have treatment with the drug covered by Dutch health insurance. The minister stated that the price for the drug, negotiated to 170,000 euro per patient per year, is "unacceptably high in relation to the relatively modest effect, as determined by the (Dutch) Healthcare Institute". Approximately 750 patients are affected by this decision. On 25 October, the Dutch Minister of Health announced that an agreement had been brokered with Vertex Pharmaceuticals, the company that manufactures the drug, resulting in admittance to the Dutch public health insurance package. Part of the agreement is that the result of the negotiation about the price of the treatment will not be disclosed.Protracted discussions within the United Kingdom were brought to a conclusion in September and October 2019 as NHS Scotland and NHS England both struck deals with Vertex respectively. | 0-1
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It is important to also note that chemicals sometimes have several different names, and do not always appear on labels.The distinction between the various types of contact dermatitis is based on a number of factors. The morphology of the tissues, the histology, and immunologic findings are all used in diagnosis of the form of the condition. However, as suggested previously, there is some confusion in the distinction of the different forms of contact dermatitis. Using histology on its own is insufficient, as these findings have been acknowledged not to distinguish, and even positive patch testing does not rule out the existence of an irritant form of dermatitis as well as an immunological one. Prevention
In an industrial setting the employer has a duty of care to its worker to provide the correct level of safety equipment to mitigate exposure to harmful irritants. This can take the form of protective clothing, gloves, or barrier cream, depending on the working environment. It is impossible to eliminate the complete exposure to harmful irritants but can be avoided using the multidimensional approach. The multidimensional approach includes eight basic elements to follow. They are:
Identification of possible cutaneous irritants and allergens
To avoid skin exposure, use appropriate control measures or chemical substitutes. Personal protection can be achieved by the use of protective clothes or barrier creams. | The mechanism of action varies from toxin to toxin, but is usually due to the production of a photoproduct. Toxins which are associated with PCD include the psoralens. Psoralens are in fact used therapeutically for the treatment of psoriasis, eczema, and vitiligo. Photocontact dermatitis is another condition in which the distinction between forms of contact dermatitis is not clear-cut. Immunological mechanisms can also play a part, causing a response similar to ACD. Diagnosis
Since contact dermatitis relies on an irritant or an allergen to initiate the reaction, it is important for the patient to identify the responsible agent and avoid it. This can be accomplished by having patch tests, one of various methods commonly known as allergy testing. The patch tests were based on the concept of a type IV hypersensitivity reaction where there is exposure of allergens to skin and checking for the development of contact dermatitis in that area. This test involves the application of suspected irritant to a part of the skin and cover it with impermeable material and attached to the skin with the help of adhesive plaster. The top three allergens found in patch tests from 2005 to 2006 were: nickel sulfate (19.0%), Myroxylon pereirae (Balsam of Peru, 11.9%), and fragrance mix I (11.5%).The patient must know where the irritant or allergen is found to be able to avoid it. | 11
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Erythrasma is often mistakenly diagnosed as dermatophytic infection which is a fungal infection and not a bacterial infection. The difference here is that fungi are multicellular and eukaryotes while bacteria are single celled prokaryotes. This is vital to differentiate because of the way they reproduce will indicate how the infection will spread throughout the human body. Mechanism
Corynebacterium minutissimum is the bacterium that causes this infection, often club shaped rods when observed under a microscope following a staining procedure, which is a result of snapping division which makes them look like a picket fence. This bacterium is gram positive, which means it has a very thick cell wall that cannot be easily penetrated. Electron microscopy confirms the bacterial nature of erythrasma, it shows decreased electron density in keratinized cells at the sites of proliferation. This means that the bacterium causes erythrasma by breaking down keratin Fibrils in the skin. Corynebacterium minutissimum consumes carbohydrates such as glucose, dextrose, sucrose, maltose, and mannitol.Erythrasma manifests mostly in slightly webbed spaces between toes (or other body region skin folds like the thighs/groin area) in warm atmospheric regions, and is more prevalent in dark skinned humans. As a person ages, they are more susceptible to this infection. This bacterium is not only found in warm atmospheric regions, but also warm and sweaty parts of the human body. Corynebacterium minutissimum survives the best here due to the encouraged fungal growth in these regions and allows it to replicate. It is more prevalent in African Americans due to their skin pigmentation. | Nathalie syndrome is a rare genetic developmental defect during embryogenesis disorder and is thought to be hereditary.In 1975 a physician described four siblings in a Dutch family with symptoms of the condition; the condition was named after the oldest sibling.According to Orphanet, the condition occurs in 1 in 1 million people.Children with this condition appear younger than their age. Nathalie syndrome can cause disability and death around early or mid adulthood. Sudden death, cardiomyopathy, and heart failure have been reported in some cases. == References == | 0-1
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Autoimmune disease
Mycophenolate is increasingly utilized as a steroid sparing treatment in autoimmune diseases and similar immune-mediated disorders including Behçets disease, pemphigus vulgaris, immunoglobulin A nephropathy, small vessel vasculitides, and psoriasis. It is also used for retroperitoneal fibrosis along with a number of other medications. Specifically it has also be used for psoriasis not treatable by other methods.Its increasing application in treating lupus nephritis has demonstrated more frequent complete response and less frequent complications compared to cyclophosphamide bolus therapy, a regimen with risk of bone marrow suppression, infertility, and malignancy. Further work addressing maintenance therapy demonstrated mycophenolate superior to cyclophosphamide, again in terms of response and side-effects. Walsh proposed that mycophenolate should be considered as a first-line induction therapy for treatment of lupus nephritis in people without kidney dysfunction. Comparison to other agents
Compared with azathioprine it has higher incidence of diarrhea, and no difference in risk of any of the other side effects in transplant patients. Mycophenolic acid is 15 times more expensive than azathioprine. Adverse effects
Common adverse drug reactions (≥ 1% of people) include diarrhea, nausea, vomiting, joint pain; infections, leukopenia, or anemia reflect the immunosuppressive and myelosuppressive nature of the drug. Mycophenolate sodium is also commonly associated with fatigue, headache, cough and/or breathing issues. Intravenous (IV) administration of mycophenolate mofetil is also commonly associated with thrombophlebitis and thrombosis. Infrequent adverse effects (0.1–1% of people) include esophagitis, gastritis, gastrointestinal tract hemorrhage, and/or invasive cytomegalovirus (CMV) infection. | Meningism is a set of symptoms similar to those of meningitis but not caused by meningitis. Whereas meningitis is inflammation of the meninges (membranes that cover the central nervous system), meningism is caused by nonmeningitic irritation of the meninges, usually associated with acute febrile illness, especially in children and adolescents. Meningism involves the triad (3-symptom syndrome) of nuchal rigidity (neck stiffness), photophobia (intolerance of bright light) and headache. It therefore requires differentiating from other CNS problems with similar symptoms, including meningitis and some types of intracranial hemorrhage. Related clinical signs include Kernigs sign and three signs all named Brudzinskis sign. Although nosologic coding systems, such as ICD-10 and MeSH, define meningism/meningismus as meningitis-like but in fact not meningitis, many physicians use the term meningism in a loose sense clinically to refer to any meningitis-like set of symptoms before the cause is definitively known. In this sense, the word implies "suspected meningitis". The words meningeal symptoms can be used instead to avoid ambiguity, thus reserving the term meningism for its strict sense. Signs and symptoms
The main clinical signs that indicate meningism are nuchal rigidity, Kernigs sign and Brudzinskis signs. None of the signs are particularly sensitive; in adults with meningitis, nuchal rigidity was present in 30% and Kernigs or Brudzinskis sign only in 5%. Nuchal rigidity
Nuchal rigidity is the inability to flex the neck forward due to rigidity of the neck muscles; if flexion of the neck is painful but full range of motion is present, nuchal rigidity is absent. | 0-1
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Drug Information Portal. U.S. National Library of Medicine. "Almotriptan malate". Drug Information Portal. U.S. National Library of Medicine. | 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. | 0-1
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Research
The use of a nitric oxide delivery system (glyceryl trinitrate patches) applied over the area of maximal tenderness was found to reduce pain and increase range of motion and strength.A promising therapy involves eccentric loading exercises involving lengthening muscular contractions. Other animals
Bowed tendon is a horsemans term for tendinitis (inflammation) and tendinosis (degeneration), most commonly seen in the superficial digital flexor tendon in the front leg of horses. Mesenchymal stem cells, derived from a horses bone marrow or fat, are currently being used for tendon repair in horses. References
External links
Questions and Answers about Bursitis and Tendinitis - US National Institute of Arthritis and Musculoskeletal and Skin Diseases | Vismodegib (trade name Erivedge ERR-i-vej) is a drug for the treatment of basal-cell carcinoma (BCC). The approval of vismodegib on January 30, 2012, represents the first Hedgehog signaling pathway targeting agent to gain U.S. Food and Drug Administration (FDA) approval. The drug is also undergoing clinical trials for metastatic colorectal cancer, small-cell lung cancer, advanced stomach cancer, pancreatic cancer, medulloblastoma and chondrosarcoma as of June 2011. The drug was developed by the biotechnology/pharmaceutical company Genentech. Indication
Vismodegib is indicated for patients with basal-cell carcinoma (BCC) which has metastasized to other parts of the body, relapsed after surgery, or cannot be treated with surgery or radiation. Mechanism of action
The substance acts as a cyclopamine-competitive antagonist of the smoothened receptor (SMO) which is part of the Hedgehog signaling pathway. SMO inhibition causes the transcription factors GLI1 and GLI2 to remain inactive, which prevents the expression of tumor mediating genes within the hedgehog pathway. This pathway is pathogenetically relevant in more than 90% of basal-cell carcinomas. Side effects
In clinical trials, common side effects included gastrointestinal disorders (nausea, vomiting, diarrhoea, constipation), muscle spasms, fatigue, hair loss, and dysgeusia (distortion of the sense of taste). The effects were mostly mild to moderate. Development
Vismodegib has undergone several promising phase I and phase II clinical trials for its use in treating medulloblastoma. See also
Cyclopamine, a naturally occurring SMO antagonist
References
Further reading
Efficacy and Safety of Vismodegib
External links
"Vismodegib". Drug Information Portal. U.S. National Library of Medicine. Food and Drug Administration (FDA) approved vismodegib | 0-1
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In order to get the best grasp on the issues and begin positive progression, multiple interviews should be held to assess the marital relationship.After completing the assessment, it is best to deliver information about risk with both individuals in the relationship. Due to confidentiality, the patient should give consent for this information to be shared unless there is a risk to another individual and it is serious and immediate. This is the only case in which confidentiality is invalid. The professional should ensure that all necessary steps are taken to guarantee the safety of a potential victim, keeping in mind that it is possible that authorities may have to be alerted regarding the matter. If the professional has reason to believe that there is a high risk of harm to themselves or another person, the individual who is morbidly jealous should be admitted to hospital as soon as possible to prevent any negative outcomes for any parties involved. Management
Morbid jealousy encompasses various psychiatric states and the best way to approach treatment depends on the symptoms that are observed in the individual. Therefore, prognosis and outcomes vary from person to person and depends on the situation and the complexities of the interpersonal relationships being observed. Also, other issues that may exacerbate the negative aspects of the environment created by jealous behavior need to be addressed in order to begin reparations. | Margetuximab, sold under the brand name Margenza, is a chimeric IgG monoclonal antibody medication against HER2 used for the treatment of cancer.The most common adverse drug reactions in combination with chemotherapy are fatigue/asthenia, nausea, diarrhea, vomiting, constipation, headache, pyrexia, alopecia, abdominal pain, peripheral neuropathy, arthralgia/myalgia, cough, decreased appetite, dyspnea, infusion-related reactions, palmar-plantar erythrodysesthesia, and extremity pain.This drug was created by Raven biotechnologies, which was later acquired by MacroGenics. It was engineered to increase affinity for CD16A polymorphisms and decrease affinity for FcγRIIB (CD32B), an inhibitory receptor.It binds to the same target (epitope) as trastuzumab, on the HER2 receptor. Medical uses
Margetuximab is indicated, in combination with chemotherapy, for the treatment of adults with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. History
It is in phase III clinical trials for combination therapy in metastatic breast cancer in collaboration with Merck. Phase II trials are also in progress for gastric cancer and esophageal cancer.In June 2020, it received orphan drug designation from the U.S. Food and Drug Administration (FDA).Efficacy was evaluated in SOPHIA (NCT02492711), a randomized, multicenter, open-label trial of 536 participants with IHC 3+ or ISH-amplified HER2+ metastatic breast cancer who had received prior treatment with other anti-HER2 therapies. Participants were randomized (1:1) to margetuximab plus chemotherapy or trastuzumab plus chemotherapy. | 0-1
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In 2012, B pseudomallei was classified as a "Tier 1 select agent" by the U.S. Centers for Disease Control. In 2014, co-trimoxazole was established as the only oral eradication therapy rather than combination therapy of co-trimoxazole with doxycycline. In 2016, a statistical model was developed to predict the occurrence of global melioidosis per year. Synonyms
Pseudoglanders
Whitmores disease (after Captain Alfred Whitmore, who first described the disease)
Nightcliff gardeners disease (Nightcliff is a suburb of Darwin, Australia where melioidosis is endemic)
Paddy-field disease
Morphia injectors septicaemia
Biological warfare
Interest in melioidosis has been expressed because it has the potential to be developed as a biological weapon. Another similar bacterium, Burkholderia mallei was used by the Germans in World War I to infect livestock shipped to Allied countries. Deliberate infection of human prisoners of war and animals using B. mallei were carried out in Chinas Pingfang District by the Japanese during World War II. The Soviet Union reportedly used B. mallei during the Soviet–Afghan War in 1982 and 1984. B. pseudomallei, like B. mallei, was studied by both the US and Soviet Union as a potential biological warfare agent, but never weaponized. Other countries such as Iran, Iraq, North Korea, and Syria may have investigated the properties of B. pseudomallei for biological weapons. The bacterium is readily available in the environment. It can also be aerosolized and transmitted via inhalation. However, the B. pseudomallei has never been used in biological warfare. The actual risk of the deliberate release of B. pseudomallei or B. mallei is unknown. | In resource-poor settings, the risk of death from the disease is more than 40%.Recurrent melioidosis can occur either due to re-infection or relapse after the completion of eradication therapy. Re-infection is due to a new strain of B. pseudomallei bacteria. Meanwhile, relapse is due to failure to clear infections after the eradication therapy. Recurrent melioidosis is rare since 2014 due to improved antibiotic therapy and prolongation of the intensive phase of therapy as evident in Darwin Prospective Melioidosis Study. On the other hand, recrudescence are those who present with symptoms during the eradication therapy. Recrudescence rates may be improved by ensuring adherence to a full course of eradication therapy e.g. by reducing self-discharge against medical advice.Underlying medical conditions such as diabetes mellitus, chronic kidney disease, and cancer can worsen the long-term survival and disability of those who recover from infection. One of the complications of melioidosis is encephalomyelitis. It can cause quadriparesis (muscle weakness in all the limbs), partial flaccid paraparesis (muscle weakness of both legs), or foot drop. For those with previous melioidosis-associated bone and joint infections, complications such as sinus tract infection, bone and joint deformities with limited range of motion can occur. Epidemiology
Melioidosis is an understudied disease that remains endemic in developing countries. In 2015, the International Melioidosis Society was formed to raise awareness of the disease. In 2016, a statistical model was developed which predicted that the number is 165,000 cases per year with 138,000 of those occurring in East and South Asia and the Pacific. | 11
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Malay perspective
When Malays were asked why they thought that women were more likely to suffer from latah, they responded with the cultural explanation that women have less "semangat" or soul substance. They also said women are simply easier to tease than men, and coupling these two together, latah becomes more readily observable and developed throughout recurrent provocation in women than in men. This also accounts for the higher prevalence of latah in lower status persons, as they are more vulnerable to abuse than others. The Malay also believe women are more susceptible because they lose more blood than men, through menstruation. Some Malay believe that excess tickling of a child will predispose them to latah later in life. In the DSM
Latah was included in Diagnostic and Statistical Manual of Mental Disorders (DSM) IV under the "Dissociative Disorder: Not Otherwise Specified" section as a culture–bound syndrome. DSM IV describes latah as a hypersensitivity to sudden fright, often with echopraxia, echolalia, command obedience, and dissociative or trancelike behavior. It mentions other cultures where latah is found, but the only further information the DSM-IV provides is that in Malaysia, it is more often found in middle–aged women. It has been removed from DSM-5, and rather than the DSM-5 expanding upon the DSM IVs list of culture–bound syndromes, it has instead provided cross-lists for more commonly known disorders that a culture-bound syndrome might be classified as. | Myospherulosis, also known as spherulocytosis, is a foreign body-type granulomatous reaction to lipid-containing material and blood.It may be seen in various settings including:
Fat necrosis. Malignancy, e.g. renal cell carcinoma. Placement of topical tetracycline in a petrolatum base into a surgical site.The resultant histopathologic pattern is most unusual and initially was mistakenly thought to represent a previously undescribed endosporulating fungus. See also
Fat necrosis
== References == | 0-1
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Treatments, depending upon the cause and severity, may include a pharmacological approach (i.e., the use of certain steroids), or surgical intervention, like a cochlear implant.Pulmonary, or pulmonic stenosis is an often congenital narrowing of the pulmonary valve; it can be present in nasodigitoacoustic-affected infants. Treatment of this cardiac abnormality can require surgery, or non-surgical procedures like balloon valvuloplasty (widening the valve with a balloon catheter). History and epidemiology
The syndrome was initially described in 1973 by James A. Keipert and associates. They reported of two brothers with broad distal phalanges, sensorineural hearing loss, and facial features consistent with what would become known as Keipert or "nasodigitoacoustic" syndrome. Although no specific rate of incidence has been determined, the syndrome is considered a rare disease by both the Office of Rare Diseases (ORDR) at the National Institutes of Health, and Orphanet. This suggests, respectively, that nasodigitoacoustic syndrome affects less than 200,000 people in the U.S., or affects no greater than 1 per 2,000 people in Europe. References
Publications
Gorlin, R. J.; Toriello, H. V.; Cohen, M. M. (1995). Hereditary hearing loss and its syndromes. U. S.: Oxford University Press. pp. 208–209. ISBN 9780195065527. Retrieved April 21, 2011. External links
Nasodigitoacoustic syndrome listing at the Office of Rare Diseases website
Keipert syndrome - Orphanet | A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by an enzyme deficiency affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells.GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism (genetically defective enzymes) involved in these processes. In livestock, acquired GSD is caused by intoxication with the alkaloid castanospermine. Types
Remarks:
Some GSDs have different forms, e.g. infantile, juvenile, adult (late-onset). Some GSDs have different subtypes, e.g. GSD1a / GSD1b, GSD9A1 / GSD9A2 / GSD9B / GSD9C / GSD9D. GSD type 0: Although glycogen synthase deficiency does not result in storage of extra glycogen in the liver, it is often classified with the GSDs as type 0 because it is another defect of glycogen storage and can cause similar problems. GSD type VIII (GSD 8): In the past it was considered a distinct condition, however it is now classified with GSD type VI or GSD IXa1; it has been described as X-linked recessive inherited. GSD type XI (GSD 11): Fanconi-Bickel syndrome, hepatorenal glycogenosis with renal Fanconi syndrome, no longer considered a glycogen storage disease. GSD type XIV (GSD 14): Now classed as Congenital disorder of glycosylation type 1 (CDG1T), affects the phosphoglucomutase enzyme (gene PGM1). Lafora disease is considered a complex neurodegenerative disease and also a glycogen metabolism disorder. Diagnosis
Treatment
Treatment is dependent on the type of glycogen storage disease. | 0-1
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This form of inheritance for Nasodigitoacoustic syndrome is not yet absolute, though, as a girl has been reported with the disorder. It is suggested that further analysis is needed for the inheritance to be formally established.The mutations causing this syndrome have been mapped to the glypican 4 (GPC4) gene. This gene is located on the long arm of chromosome X (Xq26.2). Diagnosis
The constellation of anomalies seen with nasodigitoacoustic syndrome result in a distinct diagnosis. The diagnostic criteria for the disorder are broad distal phalanges of the thumbs and big toes, accompanied by a broad and shortened nose, sensorineural hearing loss and developmental delay, with predominant occurrence in males. Classification
Nasodigitoacoustic syndrome is similar to several syndromes that share its features. Brachydactyly of the distal phalanges, sensorineural deafness and pulmonary stenosis are common with Keutel syndrome. In Muenke syndrome, developmental delay, distal brachydactyly and sensorineural hearing loss are reported; features of Teunissen-Cremers syndrome include nasal aberrations and broadness of the thumbs and big toes, also with brachydactyly. Broad thumbs and big toes are primary characteristics of Rubinstein syndrome. Management
A number of features found with nasodigitoacoustic syndrome can be managed or treated. Sensorineural hearing loss in humans may be caused by a loss of hair cells (sensory receptors in the inner ear that are associated with hearing). This can be hereditary and/or within a syndrome, as is the case with nasodigitoacoustic syndrome, or attributed to infections such as viruses. For the management of sensorineural hearing loss, hearing aids have been used. | Treatments, depending upon the cause and severity, may include a pharmacological approach (i.e., the use of certain steroids), or surgical intervention, like a cochlear implant.Pulmonary, or pulmonic stenosis is an often congenital narrowing of the pulmonary valve; it can be present in nasodigitoacoustic-affected infants. Treatment of this cardiac abnormality can require surgery, or non-surgical procedures like balloon valvuloplasty (widening the valve with a balloon catheter). History and epidemiology
The syndrome was initially described in 1973 by James A. Keipert and associates. They reported of two brothers with broad distal phalanges, sensorineural hearing loss, and facial features consistent with what would become known as Keipert or "nasodigitoacoustic" syndrome. Although no specific rate of incidence has been determined, the syndrome is considered a rare disease by both the Office of Rare Diseases (ORDR) at the National Institutes of Health, and Orphanet. This suggests, respectively, that nasodigitoacoustic syndrome affects less than 200,000 people in the U.S., or affects no greater than 1 per 2,000 people in Europe. References
Publications
Gorlin, R. J.; Toriello, H. V.; Cohen, M. M. (1995). Hereditary hearing loss and its syndromes. U. S.: Oxford University Press. pp. 208–209. ISBN 9780195065527. Retrieved April 21, 2011. External links
Nasodigitoacoustic syndrome listing at the Office of Rare Diseases website
Keipert syndrome - Orphanet | 11
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Meningism is a set of symptoms similar to those of meningitis but not caused by meningitis. Whereas meningitis is inflammation of the meninges (membranes that cover the central nervous system), meningism is caused by nonmeningitic irritation of the meninges, usually associated with acute febrile illness, especially in children and adolescents. Meningism involves the triad (3-symptom syndrome) of nuchal rigidity (neck stiffness), photophobia (intolerance of bright light) and headache. It therefore requires differentiating from other CNS problems with similar symptoms, including meningitis and some types of intracranial hemorrhage. Related clinical signs include Kernigs sign and three signs all named Brudzinskis sign. Although nosologic coding systems, such as ICD-10 and MeSH, define meningism/meningismus as meningitis-like but in fact not meningitis, many physicians use the term meningism in a loose sense clinically to refer to any meningitis-like set of symptoms before the cause is definitively known. In this sense, the word implies "suspected meningitis". The words meningeal symptoms can be used instead to avoid ambiguity, thus reserving the term meningism for its strict sense. Signs and symptoms
The main clinical signs that indicate meningism are nuchal rigidity, Kernigs sign and Brudzinskis signs. None of the signs are particularly sensitive; in adults with meningitis, nuchal rigidity was present in 30% and Kernigs or Brudzinskis sign only in 5%. Nuchal rigidity
Nuchal rigidity is the inability to flex the neck forward due to rigidity of the neck muscles; if flexion of the neck is painful but full range of motion is present, nuchal rigidity is absent. | Kernigs sign
Kernigs sign (after Waldemar Kernig (1840–1917), a Russian neurologist) is positive when the thigh is flexed at the hip and knee at 90 degree angles, and subsequent extension in the knee is painful (leading to resistance). This may indicate subarachnoid hemorrhage or meningitis. Patients may also show opisthotonus—spasm of the whole body that leads to legs and head being bent back and body bowed forward. Brudzinskis signs
Jozef Brudzinski (1874–1917), a Polish pediatrician, is credited with several signs in meningitis. The most commonly used sign (Brudzinskis neck sign) is positive when the forced flexion of the neck elicits a reflex flexion of the hips, with the patient lying supine.Other signs attributed to Brudzinski:
The symphyseal sign, in which pressure on the pubic symphysis leads to abduction of the leg and reflexive hip and knee flexion. The cheek sign, in which pressure on the cheek below the zygoma leads to rising and flexion in the forearm. Brudzinskis reflex, in which passive flexion of one knee into the abdomen leads to involuntary flexion in the opposite leg, and stretching of a limb that was flexed leads to contralateral extension. See also
Meningitis
Meningoencephalitis
References
External links
FPnotebook page on meningeal signs
Image of Kernigs sign | 11
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Lymphangiomatosis is a condition where a lymphangioma is not present in a single localised mass, but in a widespread or multifocal manner. It is a rare type of tumor which results from an abnormal development of the lymphatic system.It is thought to be the result of congenital errors of lymphatic development occurring prior to the 20th week of gestation. Lymphangiomatosis is a condition marked by the presence of cysts that result from an increase both in the size and number of thin-walled lymphatic channels that are abnormally interconnected and dilated. 75% of cases involve multiple organs. It typically presents by age 20 and, although it is technically benign, these deranged lymphatics tend to invade surrounding tissues and cause problems due to invasion and/or compression of adjacent structures. The condition is most common in the bones and lungs and shares some characteristics with Gorham’s disease. Up to 75% of patients with lymphangiomatosis have bone involvement, leading some to conclude that lymphangiomatosis and Gorham’s disease should be considered as a spectrum of disease rather than separate diseases. When it occurs in the lungs, lymphangiomatosis has serious consequences and is most aggressive in the youngest children. When the condition extends into the chest it commonly results in the accumulation of chyle in the linings of the heart and/or lungs.Chyle is composed of lymph fluid and fats that are absorbed from the small intestine by specialized lymphatic vessels called lacteals during digestion. | Abdominal
Lymphangiomatosis has been reported in every region of the abdomen, though the most reported sites involve the intestines and peritoneum; spleen, kidneys, and liver. Often there are no symptoms until late in the progression of the disease. When they do occur, symptoms include abdominal pain and/or distension; nausea, vomiting, diarrhea; decreased appetite and malnourishment. When the disease affects the kidneys the symptoms include flank pain, abdominal distension, blood in the urine, and, possibly, elevated blood pressure, which may result in it being confused with other cystic renal disease. When lymphangiomatosis occurs in the liver and/or spleen it may be confused with polycystic liver disease. Symptoms may include abdominal fullness and distension; anemia, disseminated intravascular coagulopathy (DIC), fluid accumulation in the abdomen(ascites), decreased appetite, weight loss, fatigue; late findings include liver failure. Bones
Symptoms of lymphangiomatosis in the skeletal system are the same as those of Gorham’s disease. Frequently asymptomatic, skeletal lymphangiomatosis may be discovered incidentally or when a pathological fracture occurs. Patients may experience pain of varying severity in areas around the effected bone. When the disease occurs in the bones of the spine, neurological symptoms such as numbness and tingling may occur due to spinal nerve compression. Progression of disease in the spine may lead to paralysis. Lymphangiomatosis in conjunction with Chiari I malformation also has been reported. Causes
The cause of lymphangiomatosis is not yet known. As stated earlier, it is generally considered to be the result of congenital errors of lymphatic development occurring prior to the 20th week of gestation. | 11
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The risk of depression and anxiety are also increased in the visually impaired; 32.2% report depressive symptoms (12.01% in general population), and 15.61% report anxiety symptoms (10.69% in general population).The subjects making the most use of rehabilitation instruments, who lived alone, and preserved their own mobility and occupation were the least depressed, with the lowest risk of suicide and the highest level of social integration. Those with worsening sight and the prognosis of eventual blindness are at comparatively high risk of suicide and thus may be in need of supportive services. Many studies have demonstrated how rapid acceptance of the serious visual impairment has led to a better, more productive compliance with rehabilitation programs. Moreover, psychological distress has been reported to be at its highest when sight loss is not complete, but the prognosis is unfavorable. Therefore, early intervention is imperative for enabling successful psychological adjustment. Associated conditions
Blindness can occur in combination with such conditions as intellectual disability, autism spectrum disorders, cerebral palsy, hearing impairments, and epilepsy. Blindness in combination with hearing loss is known as deafblindness. It has been estimated that over half of completely blind people have non-24-hour sleep–wake disorder, a condition in which a persons circadian rhythm, normally slightly longer than 24 hours, is not entrained (synchronized) to the light–dark cycle. | Visual impairment, also known as vision impairment, is a medical definition primarily measured based on an individuals better eye visual acuity; in the absence of treatment such as correctable eyewear, assistive devices, and medical treatment– visual impairment may cause the individual difficulties with normal daily tasks including reading and walking. Low vision is a functional definition of visual impairment that is chronic, uncorrectable with treatment or correctable lenses, and impacts daily living. As such low vision can be used as a disability metric and varies based on an individuals experience, environmental demands, accommodations, and access to services. The American Academy of Ophthalmology defines visual impairment as the best-corrected visual acuity of less than 20/40 in the better eye, and the World Health Organization defines it as a presenting acuity of less than 6/12 in the better eye. The term blindness is used for complete or nearly complete vision loss. In addition to the various permanent conditions, fleeting temporary vision impairment, amaurosis fugax, may occur, and may indicate serious medical problems. The most common causes of visual impairment globally are uncorrected refractive errors (43%), cataracts (33%), and glaucoma (2%). Refractive errors include near-sightedness, far-sightedness, presbyopia, and astigmatism. Cataracts are the most common cause of blindness. Other disorders that may cause visual problems include age-related macular degeneration, diabetic retinopathy, corneal clouding, childhood blindness, and a number of infections. Visual impairment can also be caused by problems in the brain due to stroke, premature birth, or trauma, among others. These cases are known as cortical visual impairment. | 11
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Prognosis
Factors that affect prognosis include:
tumor thickness in millimeters (Breslows depth),
depth related to skin structures (Clark level),
type of melanoma,
presence of ulceration,
presence of lymphatic/perineural invasion,
presence of tumor-infiltrating lymphocytes (if present, prognosis is better),
location of lesion,
presence of satellite lesions, and
presence of regional or distant metastasis.Certain types of melanoma have worse prognoses but this is explained by their thickness. Less invasive melanomas even with lymph node metastases carry a better prognosis than deep melanomas without regional metastasis at time of staging. Local recurrences tend to behave similarly to a primary unless they are at the site of a wide local excision (as opposed to a staged excision or punch/shave excision) since these recurrences tend to indicate lymphatic invasion. When melanomas have spread to the lymph nodes, one of the most important factors is the number of nodes with malignancy. Extent of malignancy within a node is also important; micrometastases in which malignancy is only microscopic have a more favorable prognosis than macrometastases. In some cases micrometastases may only be detected by special staining, and if malignancy is only detectable by a rarely employed test known as the polymerase chain reaction (PCR), the prognosis is better. Macrometastases in which malignancy is clinically apparent (in some cases cancer completely replaces a node) have a far worse prognosis, and if nodes are matted or if there is extracapsular extension, the prognosis is worse still. | TCF4 – In 2007, deletions of or point mutations in this gene, which is located on 18q, were identified as the cause of Pitt-Hopkins disease. This is the first gene that has been definitively shown to directly cause a clinical phenotype when deleted. If a deletion includes the TCF4 gene (located at 52,889,562-52,946,887), features of Pitt-Hopkins may be present, including abnormal corpus callosum; short neck; small penis; accessory and wide-spaced nipples; broad or clubbed fingers; and sacral dimple. Those with deletions inclusive of TCF4 have a significantly more severe cognitive phenotype. TSHZ1 - Point mutations and deletions of this gene, located on 18q, are linked with congenital aural atresia Individuals with deletions inclusive of this gene have a 78% chance of having aural atresia. Critical regions – Recent research has narrowed the critical regions for four features of the distal 18q- phenotype down to a small segment of distal 18q, although the precise genes responsible for those features remain to be identified. Haplolethal Regions - There are two regions on chromosome 18 that has never been found to be deleted. They are located between the centromere and 22,826,284 bp (18q11.2) and between 43,832,732 and 45,297,446 bp (18q21.1). It is hypothesized that there are genes in these regions that are lethal when deleted. Nomenclature
The phrase “ring 18” refers to the shape that the normally linear chromosome assumes when one tip of the chromosome joins the other. A ring-shaped chromosome is the result. | 0-1
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Molsidomine and nitroprusside already contain nitrogen in the right oxidation state (+2) and liberate NO without the aid of enzymes.NO stimulates the soluble form of the enzyme guanylate cyclase in the smooth muscle cells of blood vessels. Guanylate cyclase produces cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP). cGMP in turn activates cyclic nucleotide-dependent protein kinase G, which phosphorylates various proteins that play a role in decreasing intracellular calcium levels, leading to relaxation of the muscle cells and thus to dilation of blood vessels.The most important effect in angina is the widening of veins, which increases their capacity to hold blood ("venous pooling") and reduces the pressure of the blood returning to the heart (the preload). Widening of the large arteries also reduces the pressure against which the heart has to pump, the afterload. Lower preload and afterload result in the heart needing less energy and thus less oxygen. Besides, NO donated by nitrovasodilators can reduce coronary spasms, increasing the hearts oxygen supply.PDE5 inhibitors block deactivation of cGMP by the enzyme phosphodiesterase-5. In combination with the increased cGMP production caused by nitrovasodilators, this leads to high concentrations of cGMP, extensive venous pooling, and potentially life-threatening hypotension. Nitrate tolerance
Nitrates exhibit development of tolerance, or more specifically tachyphylaxis, meaning that repeated application results in a fast decrease of effect, usually within 24 hours. A pause of six to eight hours restores the original effectiveness. This phenomenon was originally thought to be a consequence of depletion of thiol (–SH) groups necessary for the reduction of nitrates. | Hair typically grows back normally and treatment is not indicated. A similar situation occurs in women taking the fertility-stimulating drug clomiphene. Other causes
Autoimmune disease. Alopecia areata is an autoimmune disorder also known as "spot baldness" that can result in hair loss ranging from just one location (Alopecia areata monolocularis) to every hair on the entire body (Alopecia areata universalis). Although thought to be caused by hair follicles becoming dormant, what triggers alopecia areata is not known. In most cases the condition corrects itself, but it can also spread to the entire scalp (alopecia totalis) or to the entire body (alopecia universalis). Skin diseases and cancer. Localized or diffuse hair loss may also occur in cicatricial alopecia (lupus erythematosus, lichen plano pilaris, folliculitis decalvans, central centrifugal cicatricial alopecia, postmenopausal frontal fibrosing alopecia, etc.). Tumours and skin outgrowths also induce localized baldness (sebaceous nevus, basal cell carcinoma, squamous cell carcinoma). Hypothyroidism (an under-active thyroid) and the side effects of its related medications can cause hair loss, typically frontal, which is particularly associated with thinning of the outer third of the eyebrows (also seen with syphilis). Hyperthyroidism (an over-active thyroid) can also cause hair loss, which is parietal rather than frontal. Sebaceous cysts. Temporary loss of hair can occur in areas where sebaceous cysts are present for considerable duration (normally one to several weeks). Congenital triangular alopecia – It is a triangular, or oval in some cases, shaped patch of hair loss in the temple area of the scalp that occurs mostly in young children. | 0-1
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In absence of other viable treatment options, artesunate may be used. Children
Artesunate is safe for use in children. Artesunate + sulfadoxine/pyrimethamine should be avoided in the newborns due to sulfadoxine/pyrmethamine effects on bilirubin. Parenteral artesunate dosing for treatment of severe malaria in children less than 20 kg should be higher than that of adults in order to increase exposure. When artesunate cannot be given orally or intramuscularly due to an individuals weakness or inability to swallow, rectal administration may be given as pre-referral treatment as long as parenteral administration is initiated after transfer to a more advanced facility. Adverse effects
Artesunate may cause serious side effects including hemolytic anemia (a condition in which red blood cells are destroyed), and severe allergic reactions.Artesunate is generally safe and well tolerated. Artesunate-based regimens are less likely to cause vomiting and tinnitus than quinine plus anti-malarial antibiotic therapy. The best recognised adverse effect of the artemisinins is that they lower reticulocyte counts. This is not usually of clinical relevance.With increased use of I.V. artesunate, there have been reports of post-artesunate delayed haemolysis (PADH). Delayed haemolysis (occurring around two weeks after treatment) has been observed in people treated with artesunate for severe malaria. Contraindications
Artesunate is typically a well tolerated medicine. Known contraindications include a previous severe allergic reaction to artesunate.Drugs that should be avoided while on artesunate are the drugs that inhibit the liver enzyme CYP2A6. These drugs include amiodarone, desipramine, isoniazid, ketoconazole, letrozole, methoxsalen and tranylcypromine. Mechanisms of action
The mechanisms of action of artesunate remains unclear and debatable. | Moreover, vedolizumab treatment was shown to achieve higher percentage of clinical remissions (31.3% vs. 22.5%) in patients with ulcerative colitis in comparison to adalimumab treatment. Crohns disease
In one main study in adult patients with moderate to severe active Crohns disease in whom conventional therapy or TNF-alpha antagonists were ineffective or could not be tolerated, vedolizumab was shown to be more effective than placebo: 15% (32 out of 220) of patients receiving vedolizumab showed improved symptoms after 6 weeks of treatment, compared with 7% (10 out of 148) of patients on placebo. The maintenance of the effect up to 52 weeks was more effective with vedolizumab than with placebo. History
The cell line used to develop vedolizumab was created by physician scientists at the Massachusetts General Hospital in Boston as a result of work executed in Dr. Robert Colvins lab. This was part of a program to analyze the molecular basis of lymphocyte activation. An antibody was isolated that reacted with long term activated antigen-specific (tetanus toxoid) T-lymphocytes originally isolated from blood lymphocytes. The cell lines were created in Dr. Jim T. Kurnicks lab. Although the antibody did not block primary activation of T-lymphocytes, it appeared late after activation with a number of lymphocytic stimuli, and was named "Act-1" because it was the first activation marker identified by this group of investigators. | 0-1
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Inadequate ventilatory response to exertion was indicated by the fact that, despite resting values in the normal range,
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rose markedly with exertion even when the divers breathed air at a depth of only a few feet.A variety of reasons exists for carbon dioxide not being expelled completely when the diver exhales:
The diver is exhaling into a vessel that does not allow all the CO2 to escape to the environment, such as a long snorkel, full-face diving mask, or diving helmet, and the diver then reinhales from that vessel, causing increased dead space. | Brown-Séquard syndrome (also known as Brown-Séquards hemiplegia, Brown-Séquards paralysis, hemiparaplegic syndrome, hemiplegia et hemiparaplegia spinalis, or spinal hemiparaplegia) is caused by damage to one half of the spinal cord, i.e. hemisection of the spinal cord resulting in paralysis and loss of proprioception on the same (or ipsilateral) side as the injury or lesion, and loss of pain and temperature sensation on the opposite (or contralateral) side as the lesion. It is named after physiologist Charles-Édouard Brown-Séquard, who first described the condition in 1850. Causes
Brown-Séquard syndrome may be caused by injury to the spinal cord resulting from a spinal cord tumor, trauma [such as a fall or injury from gunshot or puncture to the cervical or thoracic spine], ischemia (obstruction of a blood vessel), or infectious or inflammatory diseases such as tuberculosis, or multiple sclerosis. In its pure form, it is rarely seen. The most common cause is penetrating trauma such as a gunshot wound or stab wound to the spinal cord. Decompression sickness may also be a cause of Brown-Séquard syndrome.The presentation can be progressive and incomplete. It can advance from a typical Brown-Séquard syndrome to complete paralysis. It is not always permanent and progression or resolution depends on the severity of the original spinal cord injury and the underlying pathology that caused it in the first place. | 0-1
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showed promising benefits of short-term (< 6 months) DAPT followed by P2Y12 inhibitors in selected patients, as well as the benefits of extended-term (> 12 months) DAPT in high risk patients. In conclusion, the optimal duration of DAPT after PCIs should be personalized after outweighing each patients risks of ischemic events and risks of bleeding events with consideration of multiple patient-related and procedure-related factors. Moreover, aspirin should be continued indefinitely after DAPT is complete. Cancer prevention
Aspirin may reduce the overall risk of both getting cancer and dying from cancer. There is substantial evidence for lowering the risk of colorectal cancer (CRC), but must be taken for at least 10–20 years to see this benefit. It may also slightly reduce the risk of endometrial cancer, breast cancer, and prostate cancer.Some conclude the benefits are greater than the risks due to bleeding in those at average risk. Others are unclear if the benefits are greater than the risk. Given this uncertainty, the 2007 United States Preventive Services Task Force (USPSTF) guidelines on this topic recommended against the use of aspirin for prevention of CRC in people with average risk. | Hereditary persistence of fetal hemoglobin (HPFH) is a benign condition in which increased fetal hemoglobin (hemoglobin F, HbF) production continues well into adulthood, disregarding the normal shutoff point after which only adult-type hemoglobin should be produced. Presentation
The condition is asymptomatic, and is only noticed when screening for other hemoglobin disorders. Sickle cell disease
In persons with sickle cell disease, high levels of fetal hemoglobin as found in a newborn or as found abnormally in persons with hereditary persistence of fetal hemoglobin, the HbF causes the sickle cell disease to be less severe. In essence the HbF inhibits polymerization of HbS. A similar mechanism occurs with persons who have sickle cell trait. Approximately 40% of the hemoglobin is in the HbS form while the rest is in normal HbA form. The HbA form interferes with HbS polymerization. Causes
HPFH can be caused by mutations in the β globin gene cluster, or the γ gene promoter region. In addition HbF levels are influenced by polymorphisms in the BCL11A gene and in the MYB gene enhancer. In HPFH the percentage of HbF varies from 0.8-1.0% to about 30% of the total hemoglobin, but levels as high as 100% can be seen in homozygotes for delta beta thalassemia. Diagnosis
Epidemiology
About 10% of the population has an HbF level >1.0%. HPFH may alleviate the severity of certain hemoglobinopathies and thalassemias, and is selected for in populations with a high prevalence of these conditions (which in turn are often selected for in areas where malaria is endemic). | 0-1
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SDG2 recognizes that dealing with hunger is not only based on increasing food production but also on proper markets, access to land and technology and increased and efficient incomes for farmers.A report by the International Food Policy Research Institute (IFPRI) of 2013 argued that the emphasis of the SDGs should be on eliminating hunger and under-nutrition, rather than on poverty, and that attempts should be made to do so by 2025 rather than 2030. The argument is based on an analysis of experiences in China, Vietnam, Brazil, and Thailand and the fact that people suffering from severe hunger face extra impediments to improving their lives, whether it be by education or work. Three pathways to achieve this were identified: 1) agriculture-led; 2) social protection- and nutrition- intervention-led; or 3) a combination of both of these approaches. Regional
Much of the worlds regional alliances are located in Africa. For example, the Alliance for Food Sovereignty in Africa or the Alliance for a Green Revolution in Africa.The Food and Agriculture Organization of the UN has created a partnership that will act through the African Unions CAADP framework aiming to end hunger in Africa by 2025. It includes different interventions including support for improved food production, a strengthening of social protection and integration of the right to food into national legislation. National
Examples of hunger relief organisations that operate on the national level include The Trussell Trust in the United Kingdom, the Nalabothu Foundation in India, and Feeding America in the United States. | Cutis laxa may also be seen in association with inherited connective tissue disorders such as Ehlers–Danlos syndromes. Another syndrome associated with cutis laxa is Lenz-Majewski syndrome which is due to a mutation in the phosphatidylserine synthase 1 (PTDSS1) gene.In contrast, acquired cutis laxa often has a triggering event such as urticaria, drugs (such as penicillin) or neoplasms. Acquired cutis laxa may also be immunologically mediated, as it can involve dermal deposit of immunoglobulins and it can occur with autoimmune diseases. Acquired cutis laxa has been associated with granular immunoglobulin A deposits as well as abundant neutrophils. One hypothesis for the cause is excessive elastase release from neutrophils and macrophages. It has also been considered that mutations in elastin (ELN) and fibulin-5 (FBLN5) genes can increase susceptibility of elastic fibres to inflammatory degradation in acquired cutis laxa.Acquired cutis laxa has also been seen in conjunction with a number of conditions including: rheumatoid arthritis, systemic lupus erythematosus, celiac disease, and monoclonal gammopathies. It can also occur as a postinflammatory response after urticaria. Urticarial skin fibroblasts have shown a 2- to 3- fold increase in elastase activity in a patient with acquired cutis laxa. Diagnosis
Treatment
As of 2019, there is no treatment for cutis laxa. Procedures aimed at mitigating symptoms and identifying subsequent conditions are often advised. No pharmacological agent has been able to stop the progression of the disease. However, cosmetic surgeries are potentially an option as cutis laxa does not generally involve vascular fragility. See also
Occipital horn syndrome
List of cutaneous conditions
References
Further reading
External links
Medscape entry on Cutis Laxa | 0-1
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Traditional systematic desensitization involves a person being exposed to the object they are afraid of over time so that the fear and discomfort do not become overwhelming. This controlled exposure to the anxiety-provoking stimulus is key to the effectiveness of exposure therapy in the treatment of specific phobias. It has been shown that humor is an excellent alternative when traditional systematic desensitization is ineffective. Humor systematic desensitization involves a series of treatment activities that elicit humor with the feared object. Previously learned progressive muscle relaxation procedures can be used as the activities become more difficult. Progressive muscle relaxation helps people relax before and during exposure to the feared stimulus. Virtual reality therapy is another technique that helps phobic people confront a feared object. It uses virtual reality to generate scenes that may not have been possible or ethical in the physical world. It is equally as effective as traditional exposure therapy and offers additional advantages. These include controlling the scenes and having the phobic person endure more exposure than they might handle in reality. Medications
Medications are a treatment option often utilized in combination with CBT or if CBT was not tolerated or effective. Medications can help regulate apprehension and fear of a particular fearful object or situation. There are various medication options available for both social anxiety disorder and agoraphobia. The use of medications for specific phobias, besides the limited role of benzodiazepines, do not currently have established guidelines due to minimal supporting evidence. | Riluzole is a medication used to treat amyotrophic lateral sclerosis and other motor neuron diseases. Riluzole delays the onset of ventilator-dependence or tracheostomy in some people and may increase survival by two to three months. Riluzole is available in tablet and liquid form. Medical use
Amyotrophic lateral sclerosis
Riluzole was approved in the United States for the treatment of ALS by the U.S. Food and Drug Administration (FDA) in 1995. A Cochrane Library review states a 9% gain in the probability of surviving one year. Adverse effects
Very common (>10% frequency): nausea; weakness; decreased lung function
Common (1–10% frequency): headache; dizziness; drowsiness; vomiting; abdominal pain; increased aminotransferases
Uncommon (0.1-1% frequency): pancreatitis; interstitial lung disease
Rare (<0.1% frequency): neutropenia; allergic reaction (including angiooedema, anaphylactoid reaction)
Overdose
Symptoms of overdose include: neurological and psychiatric symptoms, acute toxic encephalopathy with stupor, coma and methemoglobinemia. Severe methemoglobinemia may be rapidly reversible after treatment with methylene blue. Contraindications
Contraindications for riluzole include: known prior hypersensitivity to riluzole or any of the excipients inside the preparations, liver disease, pregnancy or lactation. Interactions
CYP1A2 substrates, inhibitors and inducers would probably interact with riluzole, due its dependency on this cytochrome for metabolism. Mechanism of action
Riluzole preferentially blocks TTX-sensitive sodium channels, which are associated with damaged neurons. Riluzole has also been reported to directly inhibit the kainate and NMDA receptors. The drug has also been shown to postsynaptically potentiate GABAA receptors via an allosteric binding site. However, the action of riluzole on glutamate receptors has been controversial, as no binding of the drug to any known sites has been shown for them. | 0-1
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Bexarotene, sold under the brand Targretin, is an antineoplastic (anti-cancer) agent used for the treatment of cutaneous T cell lymphoma (CTCL). It is a third-generation retinoid.It was approved by the U.S. Food and Drug Administration (FDA) in December 1999, and the European Medicines Agency (EMA) in March 2001. It is available as a generic medication. Medical uses
Bexarotene is indicated for the treatment of cutaneous manifestations of cutaneous T-cell lymphoma in people who are refractory to at least one prior systemic therapy (oral) and for the topical treatment of cutaneous lesions in patients with CTCL who have refractory or persistent disease after other therapies or who have not tolerated other therapies (topical).It has been used off-label for non-small cell lung cancer and breast cancer. Contraindications
Known contraindications include:
Adverse effects
Overall the most common adverse effects are skin reactions (mostly itchiness and rashes), leucopenia, headache, weakness, thyroid anomalies (which seem to be mediated by RXR-mediated downregulation of thyroid stimulating hormone) and blood lipid anomalies such as hypercholesterolaemia (high blood cholesterol) and hyperlipidaemia, hypothyroidism. Interactions
Its plasma concentration may be increased by concomitant treatment with CYP3A4 inhibitors such as ketoconazole. It may also induce CYP3A4, and hence CYP3A4 substrates like cyclophosphamide may have their plasma concentrations reduced. Likewise consumption of grapefruit juice might increase bexarotenes plasma concentrations, hence potentially altering its therapeutic effects. Mechanism
Bexarotene is a retinoid that selectively activates retinoid X receptors (RXRs), as opposed to the retinoic acid receptors, the other major target of retinoic acid (the acid form of vitamin A). | However, he or she may close one eye to compensate for the problem. In children, the reason for not seeing double is that the brain may ignore the image it receives from the squinting eye. This shutting down is known as Suppression. Generally, exotropia progresses in frequency and duration. As the disorder progresses, the eyes start to turn out when looking at close objects as well as those in the distance. If left untreated, the eye may turn out continually, causing a loss of binocular vision or stereopsis. In young children with any form of strabismus, the brain may learn to ignore the misaligned eyes image and see only the image from the best-seeing eye. This is called amblyopia, or lazy eye, and results in a loss of binocular vision, impairing depth perception. In adults who develop strabismus, double vision sometimes occurs because the brain has already been trained to receive images from both eyes and cannot ignore the image from the turned eye. Additionally in adults who have had exotropia since childhood, the brain may adapt to using a "blind-spot", whereby it receives images from both eyes, but no full image from the deviating eye, thus avoiding double vision, and in fact, increasing peripheral vision on the side of the deviating eye. According to a study published in the American Journal of Ophthalmology, over 90 percent of children with intermittent exotropia become nearsighted by the time they’re 20. Causes
The causes of exotropia are not fully understood. | 0-1
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The prevalence of PVT in patients with cirrhosis is unclear, with a wide variety of incidence claimed by various researchers (estimated to be 1 in 100 by some while others believe it affects nearly 1 in 4).Thrombophilia (including inherited conditions such as factor V Leiden deficiency, protein C or S deficiency, or antiphospholipid antibody syndrome) is another common cause. Nearly one-third of patients have a myeloproliferative disorder (e.g. polycythemia vera or primary thrombocytosis), most commonly due to a Janus kinase 2 (JAK2) gene mutation. Oral contraceptive use or pregnancy are other non-inherited tendencies for thrombosis.Alternatively, the portal vein may be injured as a result of pancreatitis, diverticulitis, cholangiocarcinoma, hepatocellular carcinoma (HCC), or abdominal surgery/trauma. Red flags for cancerous growth as a cause are elevated alpha fetoprotein levels, portal vein diameter greater than 2.3 cm, pulsatility on Doppler ultrasound imaging, or hyperintense hepatic arterial phase (HAP) on CT scan with contrast.PVT is also a known complication of surgical removal of the spleen. During the last several years, myeloproliferative neoplasms (MPNs) have emerged as a leading systemic cause of splanchnic vein thromboses (which include PVT). Mechanism
The main portal vein is formed by the union of the splenic vein and superior mesenteric vein (SMV). It is responsible for approximately three-fourths of the liver’s blood flow, transported from much of the gastrointestinal system as well as the pancreas, gallbladder, and spleen. Cirrhosis alters bleeding pathways thus patients are simultaneously at risk of uncontrolled bleeding and forming clots. | A long-standing hindrance in flow as in chronic PVT, also known as portal cavernoma, can cause an increase in the hepatic venous pressure gradient (portal hypertension) and increased blood flow through subsidiary veins. This may lead to ascites or bleeding from varices.An infected thrombus may become septic, known as pylephlebitis; if blood cultures are positive for growth at this time, the most common organism is Bacteroides. Diagnosis
The diagnosis of portal vein thrombosis is usually made with imaging confirming a clot in the portal vein; ultrasound is the least invasive method and the addition of Doppler technique shows a filling defect in blood flow. PVT may be classified as either occlusive or nonocclusive based on evidence of blood flow around the clot. An alternative characterization based on site can be made: Type 1 is limited to the main portal vein, Type 2 involves only a portal vein branch (2a, or 2b if both branches are affected), and Type 3 if clot is found throughout both areas. Determination of condition severity may be derived via computed tomography (CT) with contrast, magnetic resonance imaging (MRI), or MR angiography (MRA). Those with chronic PVT may undergo upper endoscopy (esophagogastroduodenoscopy, EGD) to evaluate the presence of concurrent dilated veins (varices) in the stomach or esophagus. Other than perhaps slightly elevated transaminases, laboratory tests to evaluate liver function are typically normal. | 11
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It contains a hydrogenase that can produce energy by oxidizing molecular hydrogen (H2) made by intestinal bacteria. It produces oxidase, catalase, and urease. H. pylori possesses five major outer membrane protein families. The largest family includes known and putative adhesins. The other four families are porins, iron transporters, flagellum-associated proteins, and proteins of unknown function. Like other typical Gram-negative bacteria, the outer membrane of H. pylori consists of phospholipids and lipopolysaccharide (LPS). The O antigen of LPS may be fucosylated and mimic Lewis blood group antigens found on the gastric epithelium. The outer membrane also contains cholesterol glucosides, which are present in few other bacteria. Genome
Helicobacter pylori consists of a large diversity of strains, and hundreds of genomes have been completely sequenced. The genome of the strain "26695" consists of about 1.7 million base pairs, with some 1,576 genes. The pan-genome, that is a combined set of 30 sequenced strains, encodes 2,239 protein families (orthologous groups, OGs). Among them, 1,248 OGs are conserved in all the 30 strains, and represent the universal core. The remaining 991 OGs correspond to the accessory genome in which 277 OGs are unique (i.e., OGs present in only one strain). Transcriptome
In 2010, Sharma et al. presented a comprehensive analysis of transcription at single-nucleotide resolution by differential RNA-seq that confirmed the known acid induction of major virulence loci, such as the urease (ure) operon or the cag pathogenicity island (see below). | Nonetheless, glutamate by itself does not elicit an intense umami taste. The mixing of glutamate with nucleotides inosine-5-monophosphate (IMP) or guanosine-5-monophosphate (GMP) enhances the taste of umami; T1R1 and T1R3 respond primarily to mixtures of glutamate and nucleotides. While research has shown that this synergism occurs in some animal species with other amino acids, studies of human taste receptors show that the same reaction only occurs between glutamate and the selected nucleotides. Moreover, sodium in monosodium glutamate may activate glutamate to produce a stronger umami taste.Two hypotheses for the explanation of umami taste transduction have been introduced: the first posits that the umami taste is transduced by an N-methyl-D-aspartate (NMDA) type glutamate ion channel receptor; the second posits that the taste is transduced by a metabotropic type glutamate receptor (taste-mGluR4). The metabotropic glutamate receptors such as mGluR4 and mGluR1 can be easily activated at glutamate concentration levels found in food. Sources
Natural occurrence
Glutamate is ubiquitous in biological life. It is found naturally in all living cells, primarily in the bound form as a constituent of proteins. Only a fraction of the glutamate in foods is in its "free" form, and only free glutamate produces an umami flavor in foods. The savory flavor of tomatoes, fermented soy products, yeast extracts, certain sharp cheeses, and fermented or hydrolyzed protein products (such as soy sauce and fermented bean paste) is partially due to the presence of free glutamate ions. Asia
Japanese cuisine originally used broth made from kombu (kelp) to produce the umami taste in soups. | 0-1
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Arrhythmia can be hard to spot in people with TSC, other than by performing routine ECG. For example, arrhythmia may cause fainting that is confused with drop seizures, and symptoms of arrhythmia such as palpitations may not be reported in an individual with developmental delay. Skin
Some form of dermatological sign is present in 96% of individuals with TSC. Most cause no problems, but are helpful in diagnosis. Some cases may cause disfigurement, necessitating treatment. The most common skin abnormalities include:
Hypomelanic macules ("ash leaf spots") are present in about 90% of people with TSC. These small white or lighter patches of skin may appear anywhere on the body, and are caused by a lack of melanin. They are usually the only visible sign of TSC at birth. In fair-skinned individuals, a Woods lamp (ultraviolet light) may be required to see them. On the scalp, the effect may be a white patch of hair (poliosis). Patches smaller than 3mm are known as "confetti" skin lesions. Facial angiofibromas are present in about 75% of people with TSC. These are a rash of reddish spots or bumps on the nose and cheeks in a butterfly distribution, which consist of blood vessels and fibrous tissue. This potentially socially embarrassing rash starts to appear during childhood. Ungual fibromas: Also known as Koenens tumors, these are small fleshy tumors that grow around and under the toenails or fingernails. These are rare in childhood, but common by middle age. | The complex appears to interact with RHEB GTPase, thus sequestering it from activating mTOR signalling, part of the growth factor (insulin) signalling pathway. Thus, mutations at the TSC1 and TSC2 loci result in a loss of control of cell growth and cell division, and therefore a predisposition to forming tumors. TSC affects tissues from different germ layers. Cutaneous and visceral lesions may occur, including angiofibroma, cardiac rhabdomyomas, and renal angiomyolipomas. The central nervous system lesions seen in this disorder include hamartomas of the cortex, hamartomas of the ventricular walls, and subependymal giant cell tumors, which typically develop in the vicinity of the foramina of Monro.Molecular genetic studies have defined at least two loci for TSC. In TSC1, the abnormality is localized on chromosome 9q34, but the nature of the gene protein, called hamartin, remains unclear. No missense mutations occur in TSC1. In TSC2, the gene abnormalities are on chromosome 16p13. This gene encodes tuberin, a guanosine triphosphatase–activating protein. The specific function of this protein is unknown. In TSC2, all types of mutations have been reported; new mutations occur frequently. Few differences have yet been observed in the clinical phenotypes of patients with mutation of one gene or the other.Cells from individuals with pathogenic mutations in the TSC2 gene display abnormal accumulation of glycogen that is associated with depletion of lysosomes and autophagic impairment. | 11
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Diagnosis
There are some laboratory tests that may aid in diagnosis of GSD-V. A muscle biopsy will note the absence of myophosphorylase in muscle fibers. In some cases, acid-Schiff stained glycogen can be seen with microscopy.Genetic sequencing of the PYGM gene (which codes for the muscle isoform of glycogen phosphorylase) may be done to determine the presence of gene mutations, determining if McArdles is present. This type of testing is considerably less invasive than a muscle biopsy.The physician can also perform an ischemic forearm exercise test as described above. Some findings suggest a nonischemic test could be performed with similar results. The nonischemic version of this test would involve not cutting off the blood flow to the exercising arm. Findings consistent with McArdles disease would include a failure of lactate to rise in venous blood and exaggerated ammonia levels. These findings would indicate a severe muscle glycolytic block. Serum lactate may fail to rise in part because of increased uptake via the monocarboxylate transporter (MCT1), which is upregulated in skeletal muscle in McArdle disease. Lactate may be used as a fuel source once converted to pyruvate. Ammonia levels may rise given ammonia is a by-product of the adenylate kinase pathway, an alternative pathway for ATP production. In this pathway, two ADP molecules combine to make ATP; AMP is deaminated in this process, producing inosine monophosphate (IMP) and ammonia (NH3).Physicians may also check resting levels of creatine kinase, which are moderately increased in 90% of patients. | The interactions of several amino acids in myophosphorylases structure are known. Ser-14 is modified by phosphorylase kinase during activation of the enzyme. Lys-680 is involved in binding the pyridoxal phosphate, which is the active form of vitamin B6, a cofactor required by myophosphorylase. By similarity, other sites have been estimated: Tyr-76 binds AMP, Cys-109 and Cys-143 are involved in subunit association, and Tyr-156 may be involved in allosteric control. Function
Myophosphorylase is the form of the glycogen phosphorylase found in muscle that catalyses the following reaction:((1→4)-alpha-D-glucosyl) (n) + phosphate = ((1→4)-alpha-D-glucosyl) (n-1) + alpha-D-glucose 1-phosphate
Failure of this enzyme ultimately impairs the operation of ATPases. This is due to the lack of normal pH fall during exercise, which impairs the creatine kinase equilibrium and exaggerates the rise of ADP. Pathophysiology
Myophosphorylase is involved in the breakdown of glycogen to glucose for use in muscle. The enzyme removes 1,4 glycosyl residues from outer branches of glycogen and adds inorganic phosphate to form glucose-1-phosphate. Ordinarily, the removal of 1,4 glycosyl residues by myophosphorylase leads to the formation of glucose-1-phosphate during glycogen breakdown and the polar, phosphorylated glucose cannot leave the cell membrane and so is marked for intracellular catabolism. In McArdles Disease, deficiency of myophosphorylase leads to accumulation of intramuscular glycogen and a lack of glucose-1-phosphate for cellular fuel. Myophosphorylase exists in the active form when phosphorylated. The enzyme phosphorylase kinase plays a role in phosphorylating glycogen phosphorylase to activate it and another enzyme, protein phosphatase-1, inactivates glycogen phosphorylase through dephosphorylation. | 11
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When the full thickness of the epithelium is penetrated (ulceration), the lesion becomes covered with a fibrinous exudate and takes on a yellow-grey color. Because an ulcer is a breach of the normal lining, when seen in cross section, the lesion is a crater. A "halo" may be present, which is a reddening of the surrounding mucosa and is caused by inflammation. There may also be edema (swelling) around the ulcer. Chronic trauma may produce an ulcer with a keratotic (white, thickened mucosa) margin. Malignant lesions may ulcerate either because the tumor infiltrates the mucosa from adjacent tissues, or because the lesion originates within the mucosa itself, and the disorganized growth leads to a break in the normal architecture of the lining tissues. Repeat episodes of mouth ulcers can be indicative of an immunodeficiency, signaling low levels of immunoglobulin in the oral mucous membranes. Chemotherapy, HIV, and mononucleosis are all causes of immunodeficiency/immunosuppression with which oral ulcers may become a common manifestation. Autoimmunity is also a cause of oral ulceration. Mucous membrane pemphigoid, an autoimmune reaction to the epithelial basement membrane, causes desquamation/ulceration of the oral mucosa. Numerous aphthous ulcers could be indicative of an inflammatory autoimmune disease called Behçets disease. This can later involve skin lesions and uveitis in the eyes. Vitamin C deficiency may lead to scurvy which impairs wound healing, which can contribute to ulcer formation. For a detailed discussion of the pathophysiology of aphthous stomatitis, see Aphthous stomatitis#Causes. | The applicant for this medicinal product is Merck Europe B.V. Tepotinib (Tepmetko) was approved for medical use in the European Union in February 2022. References
Further reading
Paik PK, Felip E, Veillon R, Sakai H, Cortot AB, Garassino MC, et al. (September 2020). "Tepotinib in Non-Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations". N Engl J Med. 383 (10): 931–43. doi:10.1056/NEJMoa2004407. PMC 8422679. PMID 32469185. External links
"Tepotinib". Drug Information Portal. U.S. National Library of Medicine. "Tepotinib hydrochloride". Drug Information Portal. U.S. National Library of Medicine. "Tepotinib hydrochloride". NCI Drug Dictionary. National Cancer Institute. Clinical trial number NCT02864992 for "Tepotinib Phase II in Non-small Cell Lung Cancer (NSCLC) Harboring MET Alterations (VISION)" at ClinicalTrials.gov | 0-1
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Fusarium
Parasites: Toxoplasma gondii, Toxocara.A recent systematic review found that the most common source of infectious transmission following cataract surgery was attributed to a contaminated intaocular solution (i.e. irrigation solution, viscoelastic, or diluted antibiotic), although there is a large diversity of exogenous microorganisms that can travel via various routes including the operating room environment, phacoemulsifcation machine, surgical instruments, topical anesthetics, intraocular lens, autoclave solution, and cotton wool swabs.Late-onset endophthalmitis is mostly caused by Cutibacterium acnes.Causative organisms are not present in all cases. Endophthalmitis can emerge by entirely sterile means, e.g. an allergic reaction to a drug administered intravitreally. Diagnosis
Diagnosis:
Microbiology testing. PCR. TASS vs Infectious endophthalmitis. Prevention
A Cochrane Review sought to evaluate the effects of perioperative antibiotic prophylaxis for endophthalmitis following cataract surgery. The review showed high-certainty evidence that antibiotic injections in the eye with cefuroxime at the end of surgery lowers the chance of endophthalmitis. Also, the review showed moderate evidence that antibiotic eye drops (levofloxacin or chloramphenicol) with antibiotic injections (cefuroxime or penicillin) probably lowers the chance of endophthalmitis compared with injections or eye drops alone. Separate studies from the research showed that a periocular injection of penicillin with chloramphenicol-suphadimidine eye drops, and an intracameral cefuroxime injection with topical levofloxacin resulted in a risk reduction of developing endophthalmitis following cataract surgery for subjects. In the case of intravitreal injections, however, antibiotics are not effective. Studies have demonstrated no difference between rates of infection with and without antibiotics when intravitreal injections are performed. | Research
CFTR mutations that are responsive to elexacaftor/tezacaftor/ivacaftor were determined by an in-vitro study of Fischer Rat Thyroid (FRT) cells that expressed mutant CFTR. Elexacaftor/tezacaftor/ivacaftor showed effectiveness with mutations where the CFTR protein was being successfully delivered to the cell surface. References
External links
"Elexacaftor". Drug Information Portal. U.S. National Library of Medicine. "Ivacaftor regimen with Tezacaftor". Drug Information Portal. U.S. National Library of Medicine. | 0-1
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A proposed view is that dissociation has a physiological basis, in that it involves automatically triggered mechanisms such as increased blood pressure and alertness, that would, as Lynn contends, imply its existence as a cross-species disorder. A second area of controversy surrounds the question of whether or not dissociation as a defense versus pathological dissociation are qualitatively or quantitatively different. Experiences and symptoms of dissociation can range from the more mundane to those associated with posttraumatic stress disorder (PTSD) or acute stress disorder (ASD) to dissociative disorders. Mirroring this complexity, the DSM-5 workgroup considered grouping dissociative disorders with other trauma/stress disorders, but instead decided to put them in the following chapter to emphasize the close relationship. The DSM-5 also introduced a dissociative subtype of PTSD.A 2012 review article supports the hypothesis that current or recent trauma may affect an individuals assessment of the more distant past, changing the experience of the past and resulting in dissociative states. However, experimental research in cognitive science continues to challenge claims concerning the validity of the dissociation construct, which is still based on Janetian notions of structural dissociation. Even the claimed etiological link between trauma/abuse and dissociation has been questioned. Links observed between trauma/abuse and DD are largely only present from a Western cultural context. For non-Western cultures dissociation "may constitute a "normal" psychological capacity". An alternative model proposes a perspective on dissociation based on a recently established link between a labile sleep–wake cycle and memory errors, cognitive failures, problems in attentional control, and difficulties in distinguishing fantasy from reality. | This shift may be reflected in higher than normal mean corpuscular volume (MCV) values, an indicator of red blood cell size.This is not a pathological condition but may indicate a propensity toward iron deficiency anemia due to high red blood cell turnover. == References == | 0-1
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Hypertrichosis is an abnormal amount of hair growth over the body. The two distinct types of hypertrichosis are generalized hypertrichosis, which occurs over the entire body, and localized hypertrichosis, which is restricted to a certain area. Hypertrichosis can be either congenital (present at birth) or acquired later in life. The excess growth of hair occurs in areas of the skin with the exception of androgen-dependent hair of the pubic area, face, and axillary regions.Several circus sideshow performers in the 19th and early 20th centuries, such as Julia Pastrana, had hypertrichosis. Many of them worked as freaks and were promoted as having distinct human and animal traits. Classification
Two methods of classification are used for hypertrichosis. One divides them into either generalized versus localized hypertrichosis, while the other divides them into congenital versus acquired. Congenital
Congenital forms of hypertrichosis are caused by genetic mutations, and are extremely rare, unlike acquired forms. Congenital hypertrichosis is always present at birth. Hypertrichosis lanuginosa
Congenital hypertrichosis lanuginosa can be noticed at birth, with the infant completely covered in thin lanugo hair. In normal circumstances, lanugo hair is shed before birth and replaced by vellus hair; however, in a person with congenital hypertrichosis lanuginosa, the lanugo hair remains after birth. The palms of the hands, soles of the feet, and mucous membranes are not affected. As the person ages, the lanugo hair may thin, leaving only limited areas of hypertrichosis. Generalized hypertrichosis
Congenital generalized hypertrichosis causes males to exhibit excessive facial and upper body hair, whereas women exhibit less severe asymmetrical hair distribution. | Epilation methods, such as plucking, electrology, waxing, sugaring, threading remove the entire hair from the root, the results lasting several days to several weeks.Permanent hair removal uses chemicals, energy of various types, or a combination to target the cells that cause hair growth. Laser hair removal is an effective method of hair removal on hairs that have color. Laser cannot treat white hair. The laser targets the melanin color in the lower third of the hair follicle, which is the target zone. Electrolysis (electrology) uses electrical current, and/or localized heating. The U.S. Food and Drug Administration (FDA) allows only electrology to use the term "permanent hair removal" because it has been shown to be able to treat all colors of hair.Medication to reduce production of hair is currently under testing. One medicinal option suppresses testosterone by increasing the sex hormone-binding globulin. Another controls the overproduction of hair through the regulation of a luteinizing hormone. Epidemiology
Congenital forms of hypertrichosis are rare. Only 50 cases of congenital hypertrichosis lanuginosa have been recorded since the Middle Ages, and fewer than 100 cases of congenital generalized hypertrichosis have been documented in scientific publications and by the media. Congenital generalized hypertrichosis is isolated to one family in Mexico. Acquired hypertrichosis and hirsutism are more common. For example, hirsutism occurs in about 10% of women between ages 18 and 45. Society and culture
People with hair often found jobs as circus performers, making the best of their unusual appearance. | 11
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This was the main reason for pig cysticercosis largely being eliminated from the region. This of course is not a quick answer to the problem in developing countries. Pigs
The intervention strategies to eradicate cysticercosis includes surveillance of pigs in foci of transmission and massive chemotherapy treatment of humans. In reality, control of T. solium by a single intervention, for instance, by treating only human population will not work because the existing infected pigs can still carry on the cycle. The proposed strategy for eradication is to do multilateral intervention by treating both human and porcine populations. It is feasible because treating pigs with oxfendazole has been shown to be effective and once treated, pigs are protected from further infections for at least 3 months. Limitations
Even with the concurrent treatment of humans and pigs, complete elimination is hard to achieve. In one study conducted in 12 villages in Peru, both humans and pigs were treated with praziquantel and oxfendazole, with the coverage of more than 75% in humans and 90% in pigs The result shows a decrease in prevalence and incidence in the intervention area; however the effect did not eliminate T. solium. The possible reason includes the incomplete coverage and re-infection. Even though T. solium could be eliminated through mass treatment of human and porcine population, it is not sustainable. Moreover, both tapeworm carriers of humans and pigs tend to spread the disease from endemic to non-endemic areas resulting in periodic outbreaks of cysticercosis or outbreaks in new areas. | Estimates from 2010 were that it contributed to at least 50,000 deaths annually.In US during 1990–2002, 221 cysticercosis deaths were identified. Mortality rates were highest for Latinos and men. The mean age at death was 40.5 years (range 2–88). Most patients, 84.6%, were foreign born, and 62% had emigrated from Mexico. The 33 US-born persons who died of cysticercosis represented 15% of all cysticercosis-related deaths. The cysticercosis mortality rate was highest in California, which accounted for 60% of all cysticercosis deaths. History
The earliest reference to tapeworms were found in the works of ancient Egyptians that date back to almost 2000 BC. The description of measled pork in the History of Animals written by Aristotle (384–322 BC) showed that the infection of pork with tapeworm was known to ancient Greeks at that time. It was also known to Jewish and later to early Muslim physicians and has been proposed as one of the reasons for pork being forbidden by Jewish and Islamic dietary laws. Recent examination of evolutionary histories of hosts and parasites and DNA evidence show that over 10,000 years ago, ancestors of modern humans in Africa became exposed to tapeworm when they scavenged for food or preyed on antelopes and bovids, and later passed the infection on to domestic animals such as pigs.Cysticercosis was described by Johannes Udalric Rumler in 1555; however, the connection between tapeworms and cysticercosis had not been recognized at that time. | 11
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This serves as a useful marker for MDR-TB, because isolated RMP resistance is rare (except when patients have a history of being treated with rifampicin alone). If the results of a gene probe (rpoB) are known to be positive, then it is reasonable to omit RMP and to use SHEZ+MXF+cycloserine. The reason for maintaining the patient on INH is that INH is so potent in treating TB that it is foolish to omit it until there is microbiological proof that it is ineffective (even though isoniazid resistance so commonly occurs with rifampicin resistance). For treatment of RR- and MDT-TB, WHO treatment guidelines are as follows: "a regimen with at least five effective TB medicines during the intensive phase is recommended, including pyrazinamide and four core second-line TB medicines – one chosen from Group A, one from Group B, and at least two from Group C3 (conditional recommendation, very low certainty in the evidence). If the minimum number of effective TB medicines cannot be composed as given above, an agent from Group D2 and other agents from Group D3 may be added to bring the total to five. It is recommended that the regimen be further strengthened with high-dose isoniazid and/or ethambutol (conditional recommendation, very low certainty in the evidence)." | Their efficacy and safety are unknown:
pretomanid (manufactured by Novartis, developed in partnership with TB Alliance), and
delamanid. In cases of extremely resistant disease, surgery to remove infection portions of the lung is, in general, the final option. The center with the largest experience in this is the National Jewish Medical and Research Center in Denver, Colorado. In 17 years of experience, they have performed 180 operations; of these, 98 were lobectomies and 82 were pneumonectomies. There is a 3.3% operative mortality, with an additional 6.8% dying following the operation; 12% experienced significant morbidity (in particular, extreme breathlessness). Of 91 patients who were culture-positive before surgery, only 4 were culture-positive after surgery.The resurgence of tuberculosis in the United States, the advent of HIV-related tuberculosis, and the development of strains of TB resistant to the first-line therapies developed in recent decades—serve to reinforce the thesis that Mycobacterium tuberculosis, the causative organism, makes its own preferential option for the poor. The simple truth is that almost all tuberculosis deaths result from a lack of access to existing effective therapy.Treatment success rates remain unacceptably low globally with variation between regions. 2016 data published by the WHO reported treatment success rates of multidrug-resistant TB globally. For those started on treatment for multidrug-resistant TB 56% successfully completed treatment, either treatment course completion or eradication of disease; 15% of those died while in treatment; 15% were lost to follow-up; 8% had treatment failure and there was no data on the remaining 6%. | 11
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If there is reason to believe that none of the
x
j
{\displaystyle x_{j}}
s is caused by y, then estimates of the coefficients
a
j
{\displaystyle a_{j}}
are obtained. | A subgroup of the process theories is the mechanistic view on causality. It states that that causal relations supervene on mechanisms. While the notion of mechanism is understood differently, the definition put forward by the group of philosophers referred to as the New Mechanists dominate the literature. Fields
Science
For the scientific investigation of efficient causality, the cause and effect are each best conceived of as temporally transient processes. Within the conceptual frame of the scientific method, an investigator sets up several distinct and contrasting temporally transient material processes that have the structure of experiments, and records candidate material responses, normally intending to determine causality in the physical world. For instance, one may want to know whether a high intake of carrots causes humans to develop the bubonic plague. The quantity of carrot intake is a process that is varied from occasion to occasion. The occurrence or non-occurrence of subsequent bubonic plague is recorded. To establish causality, the experiment must fulfill certain criteria, only one example of which is mentioned here. For example, instances of the hypothesized cause must be set up to occur at a time when the hypothesized effect is relatively unlikely in the absence of the hypothesized cause; such unlikelihood is to be established by empirical evidence. A mere observation of a correlation is not nearly adequate to establish causality. In nearly all cases, establishment of causality relies on repetition of experiments and probabilistic reasoning. Hardly ever is causality established more firmly than as more or less probable. | 11
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Ranking the countries by the male-only or female-only rates produces much the same result, but with less meaningfulness, as the score range in the single-sex rankings is much-reduced (4 for women, 3 for men, as compared with 14 for the overall score range), suggesting that the differences between female and male rates, within each country, is what drives the distinctions between the countries.As of 2017, the cross-national lifetime prevalence of PTSD was 3.9%, based on a survey were 5.6% had been exposed to trauma. The primary factor impacting treatment-seeking behavior, which can help to mitigate PTSD development after trauma was income, while being younger, female, and having less social status (less education, lower individual income, and being unemployed) were all factors associated with less treatment-seeking behaviour. United States
The National Comorbidity Survey Replication has estimated that the lifetime prevalence of PTSD among adult Americans is 6.8%, with women (9.7%) more than twice as likely as men (3.6%) to have PTSD at some point in their lives. More than 60% of men and more than 60% of women experience at least one traumatic event in their life. The most frequently reported traumatic events by men are rape, combat, and childhood neglect or physical abuse. Women most frequently report instances of rape, sexual molestation, physical attack, being threatened with a weapon and childhood physical abuse. 88% of men and 79% of women with lifetime PTSD have at least one comorbid psychiatric disorder. | Homatropine (Equipin, Isopto Homatropine) is an anticholinergic medication that is an antagonist at muscarinic acetylcholine receptors and thus the parasympathetic nervous system. It is used in eye drops as a cycloplegic (to temporarily paralyze accommodation), and as a mydriatic (to dilate the pupil). The related chemical compound homatropine methylbromide (methylhomatropine) is a different medication. Homatropine is less potent than atropine and has a shorter duration of action. It is available as the hydrobromide salt. Homatropine is also given as an atropine substitute given to reverse the muscarinic and CNS effects associated with indirect cholinomimetic (anti-AChase) administration. It is on the World Health Organizations List of Essential Medicines. Side effects
Blurred vision
Sensitivity to light
Contraindications
Untreated glaucoma
Myasthenia gravis
Severe heart failure
Thyrotoxicosis
== References == | 0-1
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However, many drug targets that were shown to be effective in the SOD1G93A transgenic mouse failed in clinical trials in humans; other SOD1 models have had similar problems. Most of these drugs were identified as potentially effective based on a single study in a rodent SOD1 model and then failed in clinical trials in patients who primarily had sporadic ALS. It is thought that these clinical trials failed because SOD1 mutations account for only 2% of all ALS cases and because the pathology of SOD1 ALS is thought to be distinct from all other types of ALS; it lacks the abnormal aggregations of TDP-43 protein or FUS protein seen in nearly all other cases of ALS.As of 2018, there are about 20 TARDBP mouse models, a dozen FUS mouse models, and a number of C9orf72, PFN1, and UBQLN2 mouse models. There are also new methods of developing animal models, including viral transgenesis, in which viruses are used to deliver mutant genes to an animal model, and CRISPR/Cas9, which can be used to give an animal model multiple mutated genes. Both of these methods are faster and cheaper than traditional methods of genetically engineering mice; they also allow scientists to study the effects of a mutation in mice of different genetic backgrounds, which better represents the genetic diversity seen in humans.Cellular models used to study ALS include the yeast Saccharomyces cerevisiae and rat or mouse motor neurons in culture. Small-animal models include the fruit fly, the roundworm C. elegans, and the zebrafish. | Attitudes toward invasive ventilation vary from country to country; about 30% of people with ALS in Japan choose invasive ventilation, versus less than 5% in North America and Europe. Therapy
Physical therapy plays a large role in rehabilitation for individuals with ALS. Specifically, physical, occupational, and speech therapists can set goals and promote benefits for individuals with ALS by delaying loss of strength, maintaining endurance, limiting pain, improving speech and swallowing, preventing complications, and promoting functional independence.Occupational therapy and special equipment such as assistive technology can also enhance peoples independence and safety throughout the course of ALS. Gentle, low-impact aerobic exercise such as performing activities of daily living, walking, swimming, and stationary bicycling can strengthen unaffected muscles, improve cardiovascular health, and help people fight fatigue and depression. Range of motion and stretching exercises can help prevent painful spasticity and shortening (contracture) of muscles. Physical and occupational therapists can recommend exercises that provide these benefits without overworking muscles, because muscle exhaustion can lead to worsening of symptoms associated with ALS, rather than providing help to people with ALS. They can suggest devices such as ramps, braces, walkers, bathroom equipment (shower chairs, toilet risers, etc. ), and wheelchairs that help people remain mobile. Occupational therapists can provide or recommend equipment and adaptations to enable ALS people to retain as much safety and independence in activities of daily living as possible. Since respiratory insufficiency is the primary cause of mortality, physical therapists can help improve respiratory outcomes in people with ALS by implementing pulmonary physical therapy. | 11
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Diagnosis
Diagnosis is based on symptoms and upon finding an embedded tick, usually on the scalp. In the absence of a tick, the differential diagnosis includes Guillain–Barré syndrome. Early signs of tick poisoning could be a change of an animals ‘voice’, weakness in the back legs or vomiting. Prevention
No human vaccine is currently available for any tick-borne disease, except for tick-borne encephalitis. Individuals should therefore take precautions when entering tick-infested areas, particularly in the spring and summer months. Preventive measures include avoiding trails that are overgrown with bushy vegetation, wearing light-coloured clothes that allow one to see the ticks more easily, and wearing long pants and closed-toe shoes. Tick repellents containing DEET (N,N, diethyl-m-toluamide) are only marginally effective and can be applied to skin or clothing. Rarely, severe reactions can occur in some people who use DEET-containing products. Young children may be especially vulnerable to these adverse effects. Permethrin, which can only be applied to clothing, is much more effective in preventing tick bites. Permethrin is not a repellent but rather an insecticide; it causes ticks to curl up and fall off the protected clothing. Treatment
Removal of the offending tick usually results in resolution of symptoms within several hours to days. If the tick is not removed, the toxin can be fatal. A 1969 study of children reported mortality rates of 10 – 12 percent, mostly due to respiratory paralysis. The tick is best removed by grasping it as close to the skin as possible and pulling in a firm steady manner. | The most recent updates to these recommendations are based on new information regarding RSV seasonality, palivizumab pharmacokinetics, the incidence of bronchiolitis hospitalizations, the effect of gestational age and other risk factors on RSV hospitalization rates, the mortality of children hospitalized with RSV infection, the effect of prophylaxis on wheezing, and palivizumab-resistant RSV isolates. RSV Prophylaxis
All infants younger than one year who were born at <29 weeks (i.e. ≤28 weeks, 6 days) of gestation are recommended to use palivizumab. Infants younger than one year with bronchopulmonary dysplasia (i.e. who were born at <32 weeks gestation and required supplemental oxygen for the first 28 days after birth) and infants younger than two years with bronchopulmonary dysplasia who require medical therapy (e.g. supplemental oxygen, glucocorticoids, diuretics) within six months of the anticipated RSV season are recommended to use palivizumab as prophylaxis. A Cochrane review shows evidence that palivizumab RSV prophylaxis is effective at reducing the frequency of hospitalization in children with RSV infection.Since the risk of RSV decreases after the first year following birth, the use of palivizumab for children more than 12 months of age is generally not recommended with the exception of premature infants who need supplemental oxygen, bronchodilator therapy, or steroid therapy at the time of their second RSV season. RSV Prophylaxis Target Groups
Infants younger than one year of age with hemodynamically significant congenital heart disease. Infants younger than one year of age with neuromuscular disorders impairing the ability to clear secretions from the upper airways or pulmonary abnormalities. | 0-1
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One historical example of a private organization using this model is LifeSharers, which is free to join and whose members agree to sign a document giving preferred access to their organs. "The proposal [for an organ mutual insurance pool] can be easily summarized: An individual would receive priority for any needed transplant if that individual agrees that his or her organs will be available to other members of the insurance pool in the event of his or her death. … The main purpose [of this proposal] is to increase the supply of transplantable organs in order to save or improve more lives." Technical advances allows the use of donors that were previously rejected. For example, hepatitis C can be knowingly transplanted and treated in the organ recipient.In hospitals, organ network representatives routinely screen patient records to identify potential donors shortly in advance of their deaths. In many cases, organ-procurement representatives will request screening tests (such as blood typing) or organ-preserving drugs (such as blood pressure drugs) to keep potential donors organs viable until their suitability for transplants can be determined and family consent (if needed) can be obtained. This practice increases transplant efficiency, as potential donors who are unsuitable due to infection or other causes are removed from consideration before their deaths, and decreases the avoidable loss of organs. It may also benefit families indirectly, as the families of unsuitable donors are not approached to discuss organ donation. Distribution
The United States has two agencies that govern organ procurement and distribution within the country. | 250 Canadians die on average waiting for transplant organs every year.Each province has different methods and registries for intent to donate organs or tissues as a deceased donor. In some provinces, such as Newfoundland and Labrador and New Brunswick organ donation registration is completed by completing the "Intent to donate" section when applying or renewing ones provincial medical care. In Ontario, one must be 16 years of age to register as an organ and tissue donor and register with ServiceOntario. Alberta requires that a person must be 18 years of age or older and register with the Alberta Organ and Tissue Donation Registry. Opt-out donation in Canada
Nova Scotia, Canada, is the first jurisdiction in North America that will be introducing an automatic organ donation program unless residents opt out; this is known as presumed consent. The Human Organ and Tissue Act was introduced on April 2, 2019. When the new legislation is in effect, all people who have been Nova Scotia residents for a minimum of 12 consecutive months, with appropriate decision-making capacity and are over 19 years of age are considered potential donors and will be automatically referred to donation programs if they are determined to be good candidates. In the case of persons under 19 years of age and people without appropriate decision-making capacity, they will only be considered as organ donors if their parent, guardian or decision-maker opts them into the program. | 11
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Rings --- Also known as Schatzki rings from the discoverer, these rings are usually mucosal rings rather than muscular rings, and are located near the gastroesophageal junction at the squamo-columnar junction. Presence of multiple rings may suggest eosinophilic esophagitis. Rings cause intermittent mechanical dysphagia, meaning patients will usually present with transient discomfort and regurgitation while swallowing solids and then liquids, depending on the constriction of the ring. Webs --- Usually squamous mucosal protrusion into the esophageal lumen, especially anterior cervical esophagus behind the cricoid area. Patients are usually asymptomatic or have intermittent dysphagia. An important association of esophageal webs is to the Plummer–Vinson syndrome in iron deficiency, in which case patients will also have anemia, koilonychia, fatigue, and other symptoms of anemia. Achalasia is an idiopathic motility disorder characterized by failure of lower esophageal sphincter (LES) relaxation as well as loss of peristalsis in the distal esophagus, which is mostly smooth muscle. Both of these features impair the ability of the esophagus to empty contents into the stomach. Patients usually complain of dysphagia to both solids and liquids. Dysphagia to liquids, in particular, is a characteristic of achalasia. Other symptoms of achalasia include regurgitation, night coughing, chest pain, weight loss, and heartburn. The combination of achalasia, adrenal insufficiency, and alacrima (lack of tear production) in children is known as the triple-A (Allgrove) syndrome. In most cases the cause is unknown (idiopathic), but in some regions of the world, achalasia can also be caused by Chagas disease due to infection by Trypanosoma cruzi. | The starting unit is then modified by a series of Claisen condensations with malonyl or methylmalonyl substrates, which are attached to an acyl carrier protein (ACP) and extend the polyketide by two carbons each. After each successive condensation, the growing polyketide is further modified according to enzymatic domains that are present to reduce and dehydrate it, thereby introducing the diversity of functionalities observed in rapamycin (figure 1). Once the linear polyketide is complete, L-pipecolic acid, which is synthesized by a lysine cycloamidase from an L-lysine, is added to the terminal end of the polyketide by an NRPS. Then, the NSPS cyclizes the polyketide, giving prerapamycin, the first enzyme-free product. The macrocyclic core is then customized by a series of post-PKS enzymes through methylations by MTases and oxidations by P-450s to yield rapamycin. Research
Cancer
The antiproliferative effects of sirolimus may have a role in treating cancer. When dosed appropriately, sirolimus can enhance the immune response to tumor targeting or otherwise promote tumor regression in clinical trials. Sirolimus seems to lower the cancer risk in some transplant patients.Sirolimus was shown to inhibit the progression of dermal Kaposis sarcoma in patients with renal transplants. Other mTOR inhibitors, such as temsirolimus (CCI-779) or everolimus (RAD001), are being tested for use in cancers such as glioblastoma multiforme and mantle cell lymphoma. However, these drugs have a higher rate of fatal adverse events in cancer patients than control drugs.A combination therapy of doxorubicin and sirolimus has been shown to drive Akt-positive lymphomas into remission in mice. | 0-1
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Older adults with visual impairment (including glaucoma, age-related macular degeneration, and diabetic retinopathy) have decreased physical activity as measured with self-reports and accelerometers. The US National Health and Nutrition Examination Survey (NHANES) showed that people with corrected visual acuity of less than 20/40 spent significantly less time in moderate to vigorous physical activity. Age-related macular degeneration is also associated with a 50% decrease in physical activity–however physical activity is protective against age-related macular degeneration progression.In terms of mobility, those with visual impairment have a slower gait speed than those without visual impairment; however, the rate of decline remains proportional with increasing age in both groups. Additionally, the visually impaired also have greater difficulty walking a quarter mile (400 m) and walking up stairs, as compared to those with normal vision. Cognitive
Older adults with vision loss are at an increased risk of memory loss, cognitive impairment, and cognitive decline. Social and psychological
Studies demonstrate an association between older adults with visual impairment and a poor mental health; discrimination was identified as one of the causes of this association. Older adults with visual impairment have a 1.5-fold risk of reporting perceived discrimination and of these individuals, there was a 2-fold risk of loneliness and 4-fold risk of reporting a lower quality of life. Among adults with visual impairment, the prevalence of moderate loneliness is 28.7% (18.2% in general population) and prevalence of severe loneliness is 19.7% (2.7% in general population). | Tools such as the white cane with a red tip – the international symbol of blindness – may also be used to improve mobility. A long cane is used to extend the users range of touch sensation. It is usually swung in a low sweeping motion, across the intended path of travel, to detect obstacles. However, techniques for cane travel can vary depending on the user and/or the situation. Some visually impaired persons do not carry these kinds of canes, opting instead for the shorter, lighter identification (ID) cane. Still others require a support cane. The choice depends on the individuals vision, motivation, and other factors. A small number of people employ guide dogs to assist in mobility. These dogs are trained to navigate around various obstacles, and to indicate when it becomes necessary to go up or down a step. However, the helpfulness of guide dogs is limited by the inability of dogs to understand complex directions. The human half of the guide dog team does the directing, based upon skills acquired through previous mobility training. In this sense, the handler might be likened to an aircrafts navigator, who must know how to get from one place to another, and the dog to the pilot, who gets them there safely. GPS devices can also be used as a mobility aid. Such software can assist blind people with orientation and navigation, but it is not a replacement for traditional mobility tools such as white canes and guide dogs. | 11
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